Clinical Advisor June 2014

THE CLINICAL ADVISOR • JUNE 2014

A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS

NEWSLINE

■ OSA and bone health ■ Shingles raises stroke risk ■ Supplement use increases ADVISOR FORUM

■ Otitis and penicillin ■ Wound numbing tips ■ Stress fracture “tune-up” LEGAL ADVISOR

When does a mistake turn into medical malpractice?

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■ Dermatology Clinic

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CLINICAL CHALLENGE

NEURO PUZZLE Why would arm position affect neurovascular status?

Editor Delicia Honen Yard, editor@ClinicalAdvisor.com Production editor Kim Daigneau Senior digital content editor Nicole Blazek Digital content editor Brianne M. Aiken Contributing editors Mark P. Brady, PA-C; Philip R. Cohen, MD; Deborah L. Cross, MPH, CRNP, ANP; Sharon Dudley-Brown, PhD, FNP; Abimbola Farinde, PharmD; Laura A. Foster, CRNP, FNP; Abby A. Jacobson, PA; Maria Kidner, DNP, FNP; Joan W. Kiely, MSN, CRNP; Debra August King, PhD, PA; Ann W. Latner, JD; Mary Newberry, CNM, MSN; Claire Babcock O’Connell, MPH, PA; Kathy Pereira, DNP, FNP; Sherril Sego, DNP, FNP; Julee B. Waldrop, DNP, PNP, FNP; Ann Walsh, PA-C, SCT(ASCP); Kim Zuber, PA-C Group art director, Haymarket Medical Jennifer Dvoretz Production director Kathleen Millea Grinder Circulation manager Paul Silver National accounts manager Alison McCauley, 646.638.6098 alison.mccauley @ haymarketmedical.com Publisher Thomas P. Hennessy, 646.638.6085 tom.hennessy @ haymarketmedia.com Editorial director Jeff Forster Senior vice president, digital products and medical magazines Jim Burke, RPh Senior vice president, clinical communications John Pal CEO, Haymarket Media, Inc. Lee Maniscalco All correspondence to: The Clinical Advisor 114 West 26th Street, 4th Floor, New York, NY 10001 For advertising sales, call 646.638.6085.

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CONTENTS JUNE 2014

NEWS AND COMMENT

DEPARTMENTS

20 Newsline ■■Sleep apnea linked to osteoporosis ■■Antibiotics may do in appendicitis ■■Heavy bleeding is common during menopause ■■Dental health tied to CHD ■■Dietary supplement usage up ■■And more

98 Derm Dx Read the clinical descriptions, view the images, and make your diagnosis at ClinicalAdvisor.com.

99 Legal Advisor A case against a clinician raises the question of whether the error constitutes malpractice.

32 Drug Update ■■Long-term COPD maintenance ■■PDE4 inhibitor treats psoriatic arthritis

Sleep apnea now tied to osteoporosis 20

130 Commentary

105 CME/CE Dermatology Clinic n Annular eruption on the lower leg on an otherwise healthy woman

FEATURES

n Scaly plaques some years after ­onychomycosis therapy

52 What to know about home genetic-test kits Do-it-yourself genetic testing requires context from primary-care clinicians.

n Crateriform nodule on the calf of

Basal cell carcinoma reviewed 72

72 The two most common forms of skin cancer The start of the “sun-worshipping season” is a good time to review the basics of basal and squamous cell carcinomas.

MAKING CONTACT

CA0614_TOC.indd 13

Follow us on Twitter @ClinicalAdvisor

an avid cyclist n Enduring eruption of chest papules on a young girl.

114 CME/CE Posttest

84 CME/CE Improving outcomes for infants with NAS Newborns who were exposed to certain substances in utero face unique challenges in the first months of life.

92 CME/CE Posttest

102 Stat Consult Find out the most recent information on the risks and benefits of hormone replacement therapy.

Continues on page 14

Medication error leads to problems 99

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CONTENTS DEPARTMENTS (cont’d)

■ In unruptured brain arteriovenous

malformation, interventional therapy appears to worsen outcomes compared to medical management.

■ And more

117 Clinical Challenge ■ A man tells the orthopedics clinic staff about odd sensations in his hand one week after a car accident.

ADVISOR FORUM

■ A woman suffers cyclic pain after

multiple abdominal and pelvic surgeries.

124 Alternative Meds Update Chia seeds are touted for their high content of healthful oils.

94

Consultations ■ Otitis treatment in a child with suspected penicillin allergy ■ Go gluten-free for psoriasis?

■ The need for vitamin supplements among older patients ■ Numbing a wound on infected skin

96

Clinical Pearls ■ A stress fracture “tune-up” ■ Explaining loss of consciousness ■ And more

Chia: not just for pets anymore 124

126 Evidence-Based Medicine ■ Parent-delivered cognitive-behavioral therapy may improve anxiety in children.

■ Walking appears to reduce the risk of CV events in patients with impaired glucose tolerance at risk of CVD.

HOW TO CONTACT US THE CLINIC AL ADVIS

JUNE 2 014

NEWSLIN

E

■ OSA and bone health ■ Shingles raises stroke risk ■ Supplem ent use incre ases

ADVISOR

• www.ClinicalAdvisor.com/Advisor Forum • Send it by e-mail to letters@ClinicalAdvisor.com • Fax it to 646.638.6117 • Mail it to The Clinical Advisor, 114 W. 26th St., 4th Floor, New York, NY 10001 VOLUM E

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FORUM

■ Otitis and penicillin ■ Wound num ■ Stress fract bing tips ure “tune-up ”

LEGAL ADV

ISO

R When does a mistake turn into medical malpractice?

CLINICAL

| www.Clin icalA

dvisor.com

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NEURO P

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UZZLE Why Caption wouin ld

here arm likeposi so and tionsom affec e-t neurtime ovascula s exte r statu nds to s? two lines like this.

✶ FREE CME/CE COU

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PLAQUES ONYCHO POST MYCO

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MAKING CONTACT

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EXCLUSIVE TO THE WEB AT

ClinicalAdvisor.com/web-only Web Exclusives

Videos

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Cliniad.com/1kiCUPY

Vedolizumab approved to treat ­ulcerative colitis, Crohn disease The FDA has approved vedolizumab (Entyvio) for patients with inadequate response to conventional therapies.

Zinc reduces childhood diarrhea morbidity Supplements have no clear effect on mortality and a slight effect on promoting children’s growth.

Don’t bring work home: needlesticks, body fluids and high-risk exposures Sudave Mendiratta, MD, FACEP, discusses the extra precautions healthcare providers must take when dealing with high-exposure diseases.

Understanding preventive care Beth Grivett, PA-C, explains more about the United States Preventive Services Task Force and preventive care under the new health-care laws.

How likely is a dengue outbreak during the World Cup? Researchers estimate a high chance of outbreak in northeastern regions of Brazil, but a low chance in host cities.

Whole grains for whole body health Glenn Gaesser, PhD, discusses the importance of whole grains in the diet.

Can CVD patients get too much exercise?

Intensive exercise may not benefit patients with existing heart conditions.

The Waiting Room Official Blog of The Clinical Advisor CliniAd.com/VwgfCl

Derm Dx Interact with your peers by viewing the images and offering your diagnosis and comments.

CliniAd.com/1kpPU6l

Sharon M. O’Brien, MPAS, PA-C Consider grief’s role in significant sleep disturbances Patients who receive a diagnosis of complicated grief and sleep disturbance have nearly double the risk of early death.

Robyn Carlisle, MSN, CNM, WHNP Don’t overlook physical abuse Placing resources on intimate-partner violence in strategic areas of the office can help patients who might not otherwise speak out.

A darkening, thickening birthmark A 4-year-old girl presents with her mother with a chief complaint of a birthmark on the right leg that has grown darker and thicker.

MAKING CONTACT

Follow us on Twitter @ClinicalAdvisor

Jim Anderson, MPAS, PA-C, DFAAPA, ATC PAs rock: lessons from WAPA Washington state physician assistants came together to discuss the latest issues affecting the profession.

Like us on Facebook facebook.com/TheClinicalAdvisor

Visit us on the web ClinicalAdvisor.com

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18 THE CLINICAL ADVISOR • JUNE 2014 • www.ClinicalAdvisor.com

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Newsline

Antibiotics rather than surgery for appendicitis page 24

J U N E 2 014

Benzodiazepines linked with worse COPD page 26

CT assesses arterial plaque in diabetes page 31

© THINKSTOCK

Sleep apnea linked to osteoporosis

Persons with OSA were 2.7 times more likely to develop osteoporosis.

blood pressure. The disorder is also associated with hypertension, heart disease, and diabetes.

As described in Journal of Clinical Sleep Medicine, Nathaniel S. Marshall, PhD, and fellow investigators followed 397 adults; 4.6% had moderate to severe OSA and 20.6% had mild OSA. Over the course of two decades, 77 people died and 31 had strokes. There were also 125 cancer events with 39 deaths. Mild sleep apnea was not associated with any significantly increased health risks.

The FDA has approved a new treatment for persons suffering from moderate to severe OSA. Offering an alternative for people who are unable to use continuous positive airway pressure (CPAP) machines, Inspire Upper Airway Stimulation therapy is a fully implanted neurostimulation device.

Estimated number of U.S. emergency department (ED) visits due to injuries from pool chemicals, 2003–2012 Median estimated number of people making such ED visits per year during the period studied was 4,247 (range: 3,151–5,216).

Source: National Electronic Injury Surveillance System, 2003–2012 (MMWR. 2014;63[19]:428)

Estimated no of ED visits

PREVIOUS studies have shown that people with sleep apnea are at greater risk for a number of serious health events and diagnoses. Now added to that list is an increased risk of osteoporosis.

Researchers in Taiwan reviewed the medical records of nearly 1,400 people who received a diagnosis of obstructive sleep apnea (OSA) between 2000 and 2008. Over the next six years, the investigators followed this group until a diagnosis of osteoporosis or death, or the end of 2011.

Compared with more than 20,000 persons without OSA, those with sleep apnea were found to be 2.7 times more likely to develop osteoporosis. The study, reported in The Journal of Clinical Endocrinology & Metabolism by KaiJen Tien, MD, and colleagues, found the highest risk for osteoporosis in women and in older people with sleep apnea.“Ongoing sleep disruptions caused by obstructive sleep apnea can harm many of

the body’s systems, including the skeletal system,” explained Tien in an accompanying statement.

“When sleep apnea periodically deprives the body of oxygen, it can weaken bones and raise the risk of osteoporosis. The progressive condition can lead to bone fractures, increased medical costs, reduced quality of life, and even death.”

In a related report, the results of a 20-year follow-up study revealed a link between moderate to severe OSA and an increased risk of stroke, cancer, and death.

People suffering from OSA were 4.2 times more likely to die, 3.7 times more likely to suffer a stroke, 3.4 times more likely to die from cancer, and 2.5 times more likely to develop cancer than were those without sleep apnea. The findings were adjusted to allow for factors such as body mass index, smoking status, total cholesterol, and

6,000 4,500 3,000 1,500 0

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Year

20 THE CLINICAL ADVISOR • JUNE 2014 • www.ClinicalAdvisor.com

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Newsline WHEN CHILDREN present with uncomplicated acute appendicitis, antibiotics offer a good option over surgery, according to the results of what the reporting investigators describe as the first prospective study on nonoperative management of acute appendicitis in pediatric patients in the United States.

As researchers Peter C. Minneci, MD, MHSc, and colleagues wrote in Journal of the American College of Surgeons, the study involved 77 youths who had received a diagnosis of uncomplicated acute appendicitis from a surgeon in the emergency department at Nationwide Children’s Hospital in Columbus, Ohio. The patients, aged 7 to 17 years, had experienced abdominal pain for 48 hours or less; had a white blood cell count below 18,000; had an ultrasound or computed tomography (CT) scan to establish that

their appendix was 1.1 cm thick or smaller and to rule out rupture; and showed no indication of abscess or fecalith.

Thirty families opted for antibiotics alone and 47 selected surgery.

Children in the nonoperative group were admitted to the hospital, where they received intravenous (IV) antibiotics for at least 24 hours, followed by a 10-day course of oral antibiotics after discharge. Among that group of patients, 93% showed improvement within 24 hours.

When symptoms persisted, three patients eventually underwent an appendectomy. None suffered a ruptured appendix.

“Based on the current study, children with uncomplicated appendicitis are good candidates for nonoperative management,” observed Katherine J. Deans, MD, who co-led the study with Minneci.

© THINKSTOCK

Antibiotics may suffice in appendicitis

Children with uncomplicated appendicitis might avoid surgery.

More than 80,000 children undergo appendectomies each year. Although many do require surgery, a significant number would qualify for treatment with antibiotics alone, Minneci pointed out in an accompanying statement. To further evaluate this option, Deans and Minneci are enrolling 10 other pediatric hospitals in similar trials.

Heavy bleeding is common during menopause While many women approaching menopause think it will spell the end of their menstrual periods, the opposite actually might be true. According to researchers at the University of Michigan, most women experience an increase in both the amount and the duration of bleeding during the menopausal transition.

Providing the first long-term study of bleeding patterns in women of multiple ethnicities going through menopause, the investigators studied more than 1,300 women aged 42 years to 52 years for a decade. They discovered that the majority of women reported prolonged episodes of heavy bleeding and frequent spotting.

The research team found that it is not unusual for women to experience bleeding for 10 or more days, spotting for six or more days, and/or heavy bleeding for three or more days during the transition. In fact, 91% of the women in the study reported one to

three occurrences of bleeding that lasted 10 or more days over a 3-year period. Nearly 88% reported 6 or more days of spotting, and almost 78% recorded 3 or more days of heavy flow. More than 25% of the women studied had as many as three episodes of 10 or more days of bleeding during a 6-month period.

“For most women in their 30s, menstrual periods are highly predictable. With the onset of the menopausal transition in their 40s, women’s menstrual periods can change dramatically.

These dramatic changes can be disconcerting and often provoke questions about whether something is wrong,” commented Sioban Harlow, PhD, lead author of the study, which appears in BJOG: An International Journal of Obstetrics and Gynaecology.

The authors say more research is needed before the information regarding what constitutes “normal” in the menopausal transition should affect diagnostic or therapeutic interventions.

24 THE CLINICAL ADVISOR • JUNE 2014 • www.ClinicalAdvisor.com

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Newsline

DATA APPEARING in European Journal of Preventive Cardiology from Ola Vedin and colleagues speaks to the potential relationship between periodontal disease and cardiovascular disease: When nearly 16,000 individuals with established coronary heart disease (CHD) completed a lifestyle questionnaire—including queries about dental health—the results showed that signs of periodontal disease were widespread among this patient group.

The study participants came from the STABILITY trial, a clinical trial involving people from 39 different countries. All participants had chronic coronary heart disease and at least one additional risk factor for CHD. Of note was a high incidence of tooth loss; 16% of respondents said they had no teeth and 41% had less than 15. More than one-quarter of the study participants reported bleeding gums during tooth-brushing.

In addition to answering the questionnaire, the study group underwent a physical examination and blood tests. Vedin’s group discovered that increased tooth loss was also strongly linked with higher levels of low-density lipoprotein (LDL) cholesterol, fasting glucose levels, and systolic blood pressure as well as larger waist circumference. The incidence of bleeding gums was strongly tied to higher LDL cholesterol levels and systolic blood pressure.

Dietary supplement usage up AMERICAN adults are using more d iet a r y supplement s than the National Health and Nutrition Examination Surveys (NHANES) previously indicated.

That is the conclusion of a review of 5 consecutive years of surveys carried out by the Council for Responsible Nutrition (CRN) between 2007 and 2011 and completed online by about 2,000 U.S. adults annually ( J Am Coll Nutr.

2014;33(2):176-182).

According to Annette Dickinson, PhD, lead author of the review, the NHANES reports only inquired about supplement use within the previous 30 days. The current review included “regular, occasional, and seasonal use throughout the year, which more realistically captures the full scope of dietary supplement utilization.”

Dickinson and her team discovered

Two-thirds of persons surveyed used supplements.

the following information: • The percentage of people who used supplements ranged from 64% to 69%.

• When regular users were asked if they took a variety of supplements or a multivitamin alone, the percentage who said they used a variety rose over the 5-year period from 28% to 36%, while the percentage who took a multivitamin only decreased from 24% to 17%.

• The main reasons given for using dietary supplements were “for overall health and wellness” and “to fill nutrient gaps in the diet.”

The surveys also found that people using dietary supplements are more likely than nonusers to partake in such healthy behaviors as exercising regularly, eating a balanced diet, and having regular medical checkups.

© THINKSTOCK

Dental health tied to CHD

Benzodiazepines linked with worse COPD The use of benzodiazepines is associated with significantly increased risks of adverse respiratory outcomes in older adults with chronic obstructive pulmonary disease (COPD), reports a team of Canadian investigators.

Commonly prescribed for insomnia, anxiety, and breathing issues, benzodiazepines may actually contribute to respiratory problems in older people with COPD. According to Nicholas Vozoris, MD, a respirologist and lead author of the European Respiratory Journal study, these agents may depress breathing ability and lead to pneumonia.

The retrospective population-based cohort study identified adults with COPD who were aged 66 years and older and living in Ontario,

Canada, during 2003-2010. Relative risks of several important respiratory outcomes were examined within 30 days of new benzodiazepine use compared with nonuse.

New users of benzodiazepines were 45% more likely to experience an exacerbation of respiratory symptoms requiring such outpatient treatment as oral corticosteroids or respiratory antibiotics than were nonusers of benzodiazepines. They also were 92% more likely to visit the emergency department for respiratory complaints, including worsening of their COPD symptoms or the development of pneumonia.

The findings were consistent regardless of the severity of the person’s illness.

26 THE CLINICAL ADVISOR • JUNE 2014 • www.ClinicalAdvisor.com

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Newsline PEOPLE experiencing the painful skin rash herpes zoster, better known as shingles, may have a higher risk of stroke—particularly during the first 4 weeks. The good news for sufferers is that oral antiviral drugs may significantly reduce that risk.

Those findings, published in the journal Clinical Infectious Diseases, offer some important new information about the varicella zoster virus, which causes shingles in 1 million adults in the United States each year.

When Sinéad Langan, MD, PhD, and fellow researchers at the London School of Hygiene & Tropical Medicine in the United Kingdom looked at a database of 6,584 stroke patients who also suffered from shingles, they found the stroke rate was 63% higher

within the first 4 weeks of a shingles attack, compared with the patient’s baseline risk. That risk began to taper off over the next 5 months—dropping to 42% in weeks 5 through 12 and then to 23% for up to 6 months later. The picture was somewhat different

The varicella zoster virus can infect the nasociliary nerve.

when the rash formed around one or both of the eyes: In those cases, stroke risk increased threefold, compared with baseline risk.

Treatment with antiviral drugs may reduce that risk, according to Langan. “We found that the risk of stroke was lower in people who were treated with antiviral medications for their shingles, compared with those not treated with antivirals,” she explained in a statement describing her team’s findings.

Indeed, persons with shingles who were not treated with antivirals had nearly twice the risk of stroke compared with those who received medication. In addition to urging greater use of antiviral therapy, the authors called for improved shingles vaccination programs to prevent stroke associated with the virus.

© SPL / SCIENCE SOURCE

Stroke risk rises with shingles attack

WOMEN with diabetes are 14% less likely to undergo routine mammography compared with those without diabetes, found researchers at the Institute for Clinical Evaluation Sciences (ICES) in collaboration with Women’s College Hospital, both in Toronto, Ontario, Canada.

The recent study, by Lorraine Lipscombe, MD, and colleagues, published in Diabetic Medicine, reviewed the mammography rates of 504,288 women aged 50 to 69 years between 1999 and 2010. Of these women, 188,759 had diabetes; 315,529 did not. The investigators

Diabetes tied to higher breast cancer risk.

looked at the likelihood of at least one screening mammogram in the women with diabetes within a 36-month period starting January 1, 1999, their 50th birthday, or 2 years after their diabetes diagnosis—whichever date came last.

They compared the results with those of age-matched women without diabetes, adjusting for socioeconomic status and other factors.

A total of 321,564 (63.8%) women had mammograms.

Women with diabetes had lower mammography rates, even if they were in the highest socioeconomic status quintile. This is

significant because women with diabetes are at an increased risk for breast cancer and have poorer survival rates once diagnosed.

“Managing the demands of a chronic condition such as diabetes is challenging for many women, leaving other preventative actions, like screening for cancer, to fall by the wayside,” pointed out Lipscombe in a statement. “Our study found having diabetes posed a significant barrier to breast cancer screening even after considering a woman’s socioeconomic status, a known contributor to disparities in care among women.”

© THINKSTOCK

Mammography rates lower with diabetes

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Newsline I N DI V I DUA L S who a re phys­ically active at least twice a week in midlife appear to have a lower likelihood than their less active counterparts of developing dementia in old age. That finding comes from the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) Study performed at the University of Eastern Finland.

While the researchers observed this protective effect throughout the study population, it was especially evident among overweight and obese people.

Leisure-time ­physical activity protected against dementia.

Leisure-time physical activity (LTPA) has previously been shown to have a positive impact on health in general and on cardiovascular well-being in particular. However, the link between LTPA and dementia has been less clear-cut.

In this study, which included more than 1,400 participants (average age 50 years at study enrollment), Anna-Maija Tolppanen and associates looked at the impact of LTPA on dementia risk from mid- to late life, and the effect of body mass index

(BMI), sex, and genetics on that risk.

Based on the information gleaned from the 28-year followup, Tolppanen’s group proposed that “the window of opportunity” for physical activity to avert dementia may actually extend from midlife to older ages. They also noted in their report in Alzheimer’s & Dementia that further data are required regarding the type, intensity, and duration of physical activity most useful for battling late-life cognitive decline.

© THINKSTOCK

Midlife activity may stave off dementia

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CT assesses plaque in diabetes Computed tomography (CT) imaging can identify and evaluate arterial plaque in patients with diabetes, according to a new study in Radiology. This represents a potentially significant advance for a population with an increased risk of myocardial infarction and other cardiovascular events.

Calcified, or stable, plaque is less likely to rupture (and potentially cause a fatal heart attack) than noncalcified, or soft, plaque. One possible screening technique to distinguish between the two types is quantitative plaque analysis with

coronary computed tomography angiography (CCTA).

In the multicenter study, João A.C. Lima, MD, a cardiologist at Johns Hopkins University in Baltimore, Maryland, and fellow investigators assessed the relationship between coronary plaque detected by CCTA and cardiovascular risk factors in 224 asymptomatic people with diabetes. They measured coronary artery wall volume and length to determine a coronary plaque volume index (PVI) for each patient. PVI was related to age,

­ oronary C CT angiography was used to distinguish between stable and soft plaque.

gender, body mass index (BMI), and duration of diabetes.

Younger people with a shorter history of diabetes had a greater percentage of soft plaque. Only about one-third of the coronary plaque detected showed calcification.

“These findings represent a very important step in the ability to quantify plaque, particularly noncalcified plaque,” affirmed Lima in a statement describing the study. “People with soft plaque respond better to interventions, particularly medical therapy like statins.” n

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DrugUpdate New drug information from the publishers of MPR

Long-term COPD maintenance Product: Anoro Ellipta Company: GlaxoSmithKline

bronchial smooth muscle and inhibits the release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Pharmacologic class:

Anticholinergic + longacting β2-agonist.

Active ingredients:

Umeclidinium 62.5mcg, vilanterol 25mcg; per inhalation; dry powder for oral inhalation.

Indication: Long-term

maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Limitations of use: not indicated for relief of acute bronchospasm or for treatment of asthma.

Pharmacology: Umeclidinium, a long-acting antimuscarinic agent, inhibits the M3 receptor at the smooth muscle leading to bronchodilation. Vilanterol, a longacting β2-agonist, relaxes

Clinical trials: The efficacy of Anoro Ellipta is based primarily on six dose-ranging trials in 1,908 subjects with COPD or asthma and two placebo-controlled confirmatory trials with additional support from the two active-controlled and two crossover trials in 5,388 subjects with COPD. The umeclidinium dose selection was supported by a 7-day placebo-controlled

crossover trial evaluating 4 doses (15.6 mcg–125 mcg) or placebo in 163 patients with COPD. The 62.5 mcg and 125 mcg doses showed larger improvements in FEV1 over 24 hours vs. the lower doses of 15.6 and 31.25mcg. The vilanterol dose selection was supported by a 28-day, placebocontrolled, parallel-group trial evaluating five doses (3 mcg–50 mcg) or placebo in 602 patients with COPD. Results demonstrated doserelated increases in FEV1 vs. placebo at day 1 and day 28. The results supported the selection of the vilanterol 25 mcg once-daily dose for further evaluation in the confirmatory COPD trials.

A placebo-controlled trial evaluated Anoro Ellipta Continued pg. 41

PDE4 inhibitor treats psoriatic arthritis Product: Otezla Company: Celgene Pharmacologic class: Phosphodiesterase 4 (PDE4) inhibitor Active ingredient:

Apremilast 10mg, 20mg, 30mg; tabs.

Indication: Treatment of

adults with active psoriatic arthritis.

Pharmacology:

Apremilast is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. The specific mechanism(s) by which apremilast exerts its therapeutic action in psoriatic arthritis is not well defined.

Clinical trials: The safety

and efficacy of Otezla was evaluated in three Anoro Ellipta is a long-acting muscarinic agent.

Continued pg. 41

For more products, visit www.eMPR.com

32 THE CLINICAL ADVISOR • JUNE 2014 • www.ClinicalAdvisor.com

CA0614_DrugUpdate.indd 32

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DrugUpdate Anoro Ellipta from pg. 32

Warnings/Precautions:

(umeclidinium/vilanterol 62.5 mcg/25 mcg), umeclidinium 62.5 mcg, vilanterol 25 mcg, and placebo. At day 169, the differences in the least squares mean change from baseline in trough FEV1 for Anoro Ellipta relative to placebo, umeclidinium 62.5 mcg, and vilanterol 25 mcg were 167 mL (95% CI: 128, 207), 52 mL (95% CI: 17, 87), and 95 mL (95% CI: 60, 130), respectively.

For more clinical trial data, see full labeling.

Increased risk of asthmarelated deaths. Do not initiate in rapidly or acutely deteriorating COPD. Not for relief of acute bronchospasm. Prescribe a short-acting, inhaled β2-agonist for acute symptoms; monitor for increased need. Do not exceed recommended dose. Not for use with other long-acting β2-agonists. Discontinue if paradoxical bronchospasm occurs; use alternative therapy. Cardiovascular disease (especially coronary insufficiency, arrhythmias, hypertension). Convulsive disorders. Thyrotoxicosis.

Hyperresponsiveness to sympathomimetics.

Diabetes. Ketoacidosis.

Narrow-angle glaucoma.

Urinary retention. Prostatic

Adults: 1 inhalation once daily.

Children: Not established.

Contraindications:

Severe hypersensitivity to milk proteins.

Otezla from pg. 32

The specific actions by which Otezla works against psoriatic arthritis is not well defined.

multicenter, randomized, double-blind, placebocontrolled trials of similar design (Studies PsA-1, PsA2, and PsA-3). Patients with active psoriatic arthritis (≥3 swollen joints and ≥3 tender joints) despite prior or current treatment with diseasemodifying antirheumatic drugs (DMARDs) were randomized (n=1,493).

Across all studies, patients were randomized to placebo (n=496), Otezla 20

hyperplasia. Bladder-neck obstruction. Risk of hypokalemia or hyperglycemia. Labor and delivery.

Pregnancy (Category C).

Nursing mothers: not recommended.

Interactions: Caution

with concomitant strong CYP3A4 inhibitors (e.g., ketoconazole [Extina, Ketozole, Nizoral, Xolegel], ritonavir [Norvir], clarithromycin [Biaxin], conivaptan [Vaprisol], indinavir [Crixivan], itraconazole [Onmel, Sporanox], lopinavir, nefazodone, nelfinavir [Viracept], saquinavir [Invirase], telithromycin [Ketek], troleandomycin, voriconazole[Vfend]), MAOIs, tricyclic antidepressants, drugs known to prolong the QT interval mg (n=500), or Otezla 30 mg (n=497) twice daily over an initial 5-day titration. Patients were allowed to receive concomitant methotrexate (Rheumatrex, Trexall), sulfasalazine (Azulfidine), leflunomide (Arava), low-dose oral corticosteroids, and/or nonsteroidal anti-inflammatory drugs (NSAIDs) during the trial.

The primary endpoint was the percentage of patients achieving American College of Rheumatology 20

or within two weeks of discontinuing such agents (increased cardiac effects), potassium-depleting diuretics. Antagonized by β-blockers; if needed, consider cardioselective agents.

Additive effects with concomitant other anticholinergic drugs; avoid.

Adverse reactions:

Pharyngitis, sinusitis, lower-respiratory-tract infection, constipation, diarrhea, pain in extremity, muscle spasms, neck and chest pain; risk of asthma-related death.

How supplied: Dry pow-

der inhaler—30 doses ■ For more information call 888.825.5249 or visit www.GSKsource.com.

(ACR20) response at week 16. Placebo nonresponders (<20% improvement at week 16) were re-randomized to Otezla 20 mg twice daily or 30 mg twice daily. At week 24, all remaining placebo patients were re-randomized to Otezla 20 mg twice daily or 30 mg twice daily.

Overall, Otezla 30 mg twice daily ± DMARDs resulted in a greater proportion of patients with an ACR20 response at week 16 compared with placebo

For more products, visit www.eMPR.com

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JUNE 2014 41

DrugUpdate ± DMARDs (PsA-1: 38% vs. 19%; PsA-2: 32% vs.

19%; PsA-3: 41% vs. 18%; P<0.05).

Otezla 30 mg twice daily also improved each ACR component compared with placebo at week 16 in Study PsA-1, including mean change from baseline in the number of tender joints (-7 vs. -2), number of swollen joints (-5 vs. -2), and patient’s pain assessment (-14 vs. - 6).

In Study PsA-1, Otezla 30 mg twice daily also showed greater improvement compared with placebo in mean change from baseline for the Health Assessment Questionnaire Disability Index (HAQDI) score at week 16 (- 0.244 vs. - 0.086; 95%

CI: - 0.26, - 0.06). The proportions of HAQ-DI responders (≥0.3 improvement from baseline) at week 16 for the Otezla 30 mg twice-daily group were 38%, compared with 27% with placebo. Consistent results were seen in Studies PsA-2 and PsA-3.

and evening). Severe renal impairment (creatinine clearance <30mL/min): Reduce to 30 mg once daily; for initial titration, use only morning dose schedule and skip evening doses.

Adults: Swallow whole.

Initially titrate over five days. Starting on day 1: 10 mg in the morning. Day 2: 10 mg in the morning and 10 mg in the evening.

Day 3: 10 mg in morning and 20 mg in the evening. Day 4: 20 mg in the morning and 20 mg in the evening. Day 5: 20 mg in the morning and 30 mg in the evening. Following on Day 6 and thereafter: 30 mg twice daily (morning

Warnings/Precautions:

“It’s an audio guide, sweetheart, not a remote.”

Children: <18 years: not

established.

History of depression and/ or suicidal thoughts or behaviors; monitor for clinical worsening or other mood changes. Monitor weight regularly; evaluate and consider discontinuing if unexplained or significant weight loss occurs. Renal impairment. Pregnancy (Cat. C). Nursing mothers.

Interactions: Concomitant

strong CYP450 inducers

(e.g., rifampin [Rifadin], phenobarbital, carbamazepine, phenytoin [Dilantin, Phenytek]): not recommended.

Adverse reactions:

Diarrhea, nausea, headache, upper-respiratorytract infection, vomiting, nasopharyngitis, upper abdominal pain; weight loss, depression.

Note: Register pregnant

patients exposed to Otezla by calling (877) 311-8972.

How supplied: Tabs

30mg—60; 2-week starter pack—13+14; Carton—2×14 n For more information, call 888.771.0141 or visit www.Otezla.com.

© The New Yorker Collection 2014 from cartoonbank.com. All Rights Reserved.

Otezla from pg. 41

“Are you throwing me a surprise birthday party?”

For more products, visit www.eMPR.com

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JUNE 2014 47

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FEATURE: THERESA CAPRIOTTI, DO, MSN, CRNP, AND MARY KLINE

What to know about home genetic-test kits Consumers becoming more involved in do-it-yourself genetic testing need primary-care clinicians to put the results into context for them.

I

t has been more than 10 years since the Human Genome Project first sequenced and analyzed our DNA (www.genome.gov/10001772).

Now a growing number of companies are offering personal genome-testing kits directly to consumers. These tests provide information about susceptibility to disease, inherited traits, and individual pharmacologic responses.

Primary-care providers (PCPs) are increasingly expected to interpret the results from these genetic-test kits for patients, who often have questions about the validity and predictive ability of such products. Patients are also seeking advice on preventive screening and treatments regarding their genetic susceptibilities. Consequently, PCPs are being called upon to provide education, counseling, and psychosocial support for patients who perform home genetic tests.

© ISTOCK

What are DTC genetic-test kits?

Caption in here like Users of home geneticso and sometimes test kits provide a extends to two lines buccal swab or saliva like this. sample of DNA.

Direct-to-consumer (DTC) home genetic-test kits claim to be able to detect traits and risk of disease, predict responses to drug treatment, and determine ancestry.1 Companies such as 23andMe, Navigenics, deCODE, and Pathway Genomics all offer DTC genetic test kits online for approximately $99.00 and assure confidentiality of results.2 Websites such as 23andMe.com ask consumers to create an account and order the DNA kit from the site’s online store. The kit is shipped directly to the consumer, who then follows the instructions for DNA harvesting by means of buccal swab or saliva sample, and sends the kit back to the company to await results. Once the tests are

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HOME GENETIC-TEST KITS

A complex disease such as cancer or diabetes usually develops based on the interplay between more than one mutation and nongenetic factors. completed, the consumer is notified and given “personalized” recommendations based on the genetic findings.3 On November 22, 2013, the U.S. Food and Drug Administration (FDA) ordered the 23andMe genomics company to cease marketing its Saliva Collection Kit and Personal Genome Service (PGS).4 The FDA asserted that the product is an unapproved and uncleared diagnostic device with questionable validity. Navigenics and deCode have also withdrawn genetic test kits from the market. It remains to be seen if these companies will reintroduce their products.

How DTC genetic-test kits work

DTC genetic tests are based on genome-wide association studies (GWAS). A GWA study scans complete sets of DNA of a population to find genetic variations associated with specific diseases. GWAS focus on markers of genetic variation, single-nucleotide polymorphisms (SNPs) —differences in the amino acids that make up DNA. If one type of SNP is seen more frequently in people with a disease, the SNP is said to be “associated” with the disease.5,6 It is important to understand that SNPs do not directly cause disease; they are commonly found in persons with the given disease. SNPs cannot be solely relied upon for prediction of disease because it is combinations of gene mutations and environmental factors that most often cause disease, rather than an SNP. Four types of tests in a kit

Four different types of tests are included in a DTC genetic-test kit. One test shows single gene mutations that have strong genotype-phenotype correlations. These include common Mendelian disorders such as cystic fibrosis, Huntington disease, and beta thalassemia. Another test can identify particular genetic variants that affect metabolism of certain drugs. An additional test indicates the consumer’s risk for polygenic complex diseases such as cardiovascular disorders, diabetes, cancers, and osteoporosis. Finally, there are genetic tests that can confirm or deny paternity based on DNA test results.1 As our knowledge of the human genome expands, more diseases, conditions, and drug responses are being added to the list of what can be detected through DTC genetic-test kits.

Benefits and drawbacks of DTC genetic-test kits

Proponents of genetic-test kits contend that providing this information directly to consumers could result in improved patient compliance with health screening and preventive

health-care practices. Consumers may become more conscientious about lifestyle changes that reduce their risk of disease development. The tests could also motivate consumers to make proactive decisions regarding preventive treatments.5 For example, BRCA1/BRCA2 gene mutations are a common topic of discussion among patients and primary-care providers. Studies show that providing information regarding inheritance of BRCA1 and BRCA2 mutations increases awareness of ovarian cancer and of breast cancer screening and prevention among patients and their families. Once they learn that they carry these mutations, women often choose to undergo risk-reducing procedures such as bilateral mastectomies and oophorectomies.7-9 Skeptics of DTC test kits, however, are concerned that a false prediction of increased risk of disease and confusing results can cause anxiety for patients and lead to unnecessary tests, procedures, and costs without proper guidance from health-care professionals. Conversely, consumers who receive falsely reassuring results could neglect to obtain needed screening tests or to follow necessary preventive measures.5 According to research, the DTC genetic-test kits are proficient in predicting the risk of some highly inheritable monogenic diseases.6 However, when it comes to such complex diseases as cancer and diabetes, many factors play a role in a person’s risk. A complex disease usually develops based on the interplay between more than one genetic mutation and nongenetic factors such as diet, exercise, smoking status, and alcohol use.10 Because of these variables, experts say that complex diseases cannot be predicted using DTC genetic-test kits. In addition, studies are starting to show that home genetic-test kit results often vary among test-kit manufacturers. This raises questions about the reliability of findings.5 Finally, genetic-test-kit results are based on a Caucasian reference population. When calculating risks, these products do not account for ancestry of consumers who are non-Caucasian.11 PCPs and genetic testing

PCPs have expressed both positive and negative reactions to DTC test kits. In one Web-based study, approximately 40% of PCPs reported that they would tailor the healthcare management of a patient to the results of genetic-test kits.10 For patients showing an increased risk for Alzheimer disease, they would suggest more frequent early screening for dementia; order more computed tomography, magnetic

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HOME GENETIC TEST-KITS

Patients consult primary-care providers more often than they do the counselors recommended on home genetic-test kits regarding the results. resonance imaging, and positron emission tomography scans; and educate these patients regarding disease prevention. For persons whose results showed an increased risk of glaucoma, PCPs said they would recommend eye exams more often.

PCPs made similar statements regarding patients whose tests revealed an increased risk of cardiovascular disease and type 2 diabetes, saying they would place more emphasis on pertinent lifestyle changes for these individuals and perform more frequent screening and laboratory tests.

Although manufacturers of the DTC genetic-test kits do refer consumers to a genetics counselor specified on the label, studies show that less than 10% of customers utilize the kit’s recommended counselor. Instead, pharmacists and PCPs are being consulted most often regarding the results yielded by these products.1 The majority of member-physicians of the American Medical Association do not feel prepared to implement FDA-approved genetic-testing recommendations in their practice: A study of family-practice physicians indicated that more than 75% feel they need more education regarding genetic aspects of patient care.12 Many PCPs underwent their education and training prior to the current upsurge in information regarding genomics, and studies show patients sense that PCPs are unprepared in the area of genetics. A 2011 national survey revealed that only 17% of Americans believed their provider to be up-to-date and knowledgeable about genomics-based medicine.10,13-17 Necessary proficiency of the PCP

The PCP is in an ideal position to evaluate and treat patients for genetic disease because primary care combines treatment of acute illness with disease prevention and anticipatory guidance. Experts contend that PCPs need to incorporate basic genomic competencies into their daily practice, including the following:18-21 Identify individuals who have increased genetic risks. PCPs need to recognize key information in the patient history that indicates risk of a genetic disorder. Every patient warrants a comprehensive family history, and charting a three-generation pedigree on the patient is ideal. A pedigree can identify other at-risk family members who might benefit from genetics counseling or testing. Patients can chart their own family pedigree using a tool from the U.S. Surgeon General, available at My Family Health Portrait (www. familyhistory.hhs.gov).

Distinguish physical features of common genetic conditions. The PCP should have knowledge of specific dysmorphic characteristics that raise suspicion of genetic disorders.

Refer patients with genetic susceptibilities for appropriate screening and diagnostic tests. The identification of certain genetic susceptibilities in a given patient should be followed by appropriate referrals for screening and diagnostic tests.

Monitor the health of individuals with a genetic disorder. PCPs in collaboration with appropriate subspecialists should work to monitor the health of patients with a genetic disorder or those at increased risk of harboring a genetic disorder.

Provide basic genetic information to patients and families. By providing information regarding genetics to patients and families, PCPs are able to help patients make informed decisions.

Tailor patient treatment and management to genetic information. Some patients who receive genetic susceptibility information will opt to obtain preventive treatment.

PCPs need to be well-informed about prophylactic treatments and procedures related to genetic susceptibility and be upto-date in pharmacogenomics—the influence of genetics on medication metabolism and response. Identifying individual gene differences can help customize medication choice and dosing regimen for the best patient response.

Provide collaborative health care. Individuals with complex genetic disorders or susceptibilities need a healthcare team that works together to meet the patient’s needs.

PCPs will have to incorporate the recommendations of other health-care providers into the patient’s plan of care.

Recognize psychosocial aspects of genetic testing and diagnosis. Genetic information can influence the emotional, psychological, and social health of patients. For example, such knowledge can provoke anxiety in some individuals. Genetic information of the patient may also be applicable to family members, making family genetics counseling necessary.

Appropriately refer patients to genetics counselors.

PCPs are in the position to know which patients with genetic health-care needs require referral. Patients with a significant family history of genetic disorders should be referred to genetics counselors and medical specialists. Genetics counselors can discuss the implications of highly penetrant gene mutations. These specialists are also more informed about

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HOME GENETIC-TEST KITS

POLL POSITION

Are home genetic test kits helpful or harmful to patients?

n=80 62%

Yes No helpful – 28 votes n Mostly n Mostly harmful – 27 votes n Not – 25 votes Othersure2% 0

20%

Conclusion

33.75%

TK36%35%

31.25% 40%

60%

regions of the genome that are translated into proteins.

Currently, WGS and WES are used to identify specific gene changes in cancer cells to guide patient therapy, to identify a person’s inherited cancer risk, and to estimate prognosis. These methods of genome testing are unavailable for DTC use due to prohibitive costs, but are predicted to be more affordable and widely available in the near future for more extensive use.23

80%

the limitations of genetic testing, the potential repercussions for other family members, and other implications such as the effect on health-care costs.

Safeguard patient genetic information. The Genetic Information Nondiscrimination Act of 2008 (GINA; information available at www.eeoc.gov/laws/statutes/gina.cfm) underscores the importance of confidentiality of genetic information and that the PCP should not provide patient genomic information to third parties without authorized patient permission.

Broaden knowledge base with continuing education in genomics. Research regarding genetics and genomics is emerging rapidly and patients are becoming increasingly cognizant of how genetics influences their health. PCPs will need to keep pace with this burgeoning field of knowledge.

PCPs are increasingly being called upon to provide genetic information to patients and their families. PCPs need to interpret genetic-test results, assess genetic risk, order preventive screening tests and diagnostic tests, educate patients and their families, and advise patients about preventive treatments and follow-up. It is clear that PCPs need proficiency in genomics for daily practice. For more information on integrating genomics into primary-care practice, refer to the Genetics in Primary Care Institute (www.geneticsinprimarycare.org/ YourPractice/Patient-Management-and-Guidelines/Pages/ Patient-Management-and-Guidelines.aspx#jump-5).20 n Dr. Capriotti is a clinical associate professor at the Villanova University College of Nursing in Villanova, Pa., where Ms. Kline is a BSN honors student.

References 1. Patrinos GP, Baker DJ, Al-Mulla F, et al. Genetic tests obtainable through pharmacies: the good, the bad, and the ugly. Hum Genomics. 2013;7(1):17.

Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3711749/.

2. Bloss CS, Darst BF, Topol EJ, Schork NJ. Direct-to-consumer personalized genomic testing. Hum Mol Genet. 2011;20(R2):R132–141. Available at hmg.oxfordjournals.org/content/early/2011/08/24/hmg.ddr349.full.

3. 23andMe, Inc. Information retrieved September 29, 2013, from www.23andMe.com.

The future of genomics in primary care

4. U.S. Food and Drug Administration. Inspections, Compliance,

Patients are actively seeking knowledge about their unique susceptibilities and will soon be able to incorporate this information into their personal health-care management.6 Although DTC genetic-test kits are being pulled from the market, more reliable versions will soon be available. More accurate methods of genome analysis—whole genome sequencing (WGS) and whole exome sequencing (WES)— are currently used in specialized clinical settings,22 and will become available for wider use.

WGS determines the complete DNA sequence of an organism’s genome at a single time. This entails sequencing all of the organism’s chromosomal DNA as well as DNA contained in the mitochondria. WES selectively deciphers the coding

Enforcement, and Criminal Investigations Warning Letter: 23andMe, Inc. 11/22/13. Available at www.fda.gov/iceci/enforcementactions/warningletters/2013/ucm376296.htm 5. Bloss CS, Schork NJ, Topol EJ. Effect of direct-to-consumer genomewide profiling to assess disease risk. N Engl J Med. 2011;364(6):524-534.

Available at www.nejm.org/doi/full/10.1056/NEJMoa1011893#t=articleTop. 6. Janssens ACJW, van Duijn CM. An epidemiological perspective on the future of direct-to-consumer personal genome testing. Investig Genet.

2010;1(1):10. Available at www.investigativegenetics.com/content/1/1/10.

7. Schwartz MD, Isaacs C, Graves KD, et al. Long-term outcomes of BRCA1/ BRCA2 testing: risk reduction and surveillance. Cancer. 2012;118(2):510-517.

Available at onlinelibrary.wiley.com/doi/10.1002/cncr.26294/pdf.

Continues on page 67

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8. Dohany L, Gustafson S, Ducaine W, Zakalik D. Psychological distress with direct-to-consumer genetic testing: a case report of an unexpected BRCA positive test result. J Genet Couns. 2012;21(3):399-401.

9. Skytte AB, Crüger D, Gerster M, et al. Breast cancer after bilateral riskreducing mastectomy. Clin Genet. 2011;79(5):431-437.

10. Bernhardt, BA, Zayac C, Gordon, ES, et al. Incorporating direct-toconsumer genomic information into patient care: Attitudes and experi-

CLINICAL SLIDESHOW For more information on breast cancer, a focus of genetic testing, view the slideshow at CliniAd.com/1mYmqeB

ences of primary care physicians. Per Med. 2012;9(7):683-692. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684987/.

11. Bloss CS, Topol EJ, Schork NJ. Association of direct-to-consumer genome-wide disease risk estimates and self-reported disease. Genet

18. Loud JT. Direct-to-consumer genetic and genomic testing: pre-

Epidemiol. 2012;36(1):66-70.

paring nurse practitioners for genomic healthcare. J Nurse Pract.

12. Powell KP, Christianson CA, Cogswell WA, et al. Educational needs

2010;6(8):585-594.

of primary care physicians regarding direct-to-consumer genetic testing.

19. Scott J, Trotter T. Primary care and genetics and genomics. Pediatrics.

J Genet Couns. 2012;21(3):469-478.

2013;132(Suppl 3):S231-237. Available at pediatrics.aappublications.org/

13. Cogent Research. Company press release via Business Wire: Americans

content/132/Supplement_3/S231.full.pdf+html.

skeptical of physicians’ knowledge of genomics. January 25, 2011. Available

20. Genetics in Primary Care Institute (GPCI). Available at

at www.businesswire.com/news/home/20110125006349/en.

GeneticsInPrimaryCare.org.

14. Pandey A. A piece of my mind. Preparing for the 21st-century patient.

21. Feero WG, Guttmacher AE, Collins FS. Genomic medicine—an updat-

JAMA. 2013;309(14):1471-1472.

ed primer. N Engl J Med. 2010;362(21):2001-2011. Available at www.nejm.

15. Mainous AG 3rd, Johnson SP, Chirina S, Baker R. Academic family phy-

org/doi/full/10.1056/NEJMra0907175.

sicians’ perception of genetic testing and integration into practice: a CERA

22. Johansen Taber KA, Dickinson BD, Wilson M. The promise and chal-

study. Fam Med. 2013;45(4):257-262.

lenges of next-generation genome sequencing for clinical care. JAMA Intern

16. Goldsmith L, Jackson L, O’Connor A, Skirton H. Direct-to-consumer

Med. 2014;174(2):275-280.

genomic testing from the perspective of the health professional: a system-

23. Korf BR, Rehm HL. New approaches to molecular diagnosis. JAMA.

atic review of the literature. J Community Genet. 2013;4(2):169-180.

2013;309(14):1511-1521.

17. Marshall E. Human genome 10th anniversary: waiting for the revolu-

“Let’s try focusing on your posts that do receive comments.”

All electronic documents accessed May 15, 2014.

© The New Yorker Collection 2014 from cartoonbank.com. All Rights Reserved.

tion. Science. 2011;331(6017):526-529.

“I fear there are only so many bamboo metaphors the average reader can tolerate.” www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JUNE 2014 67

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FEATURE: ABBY A. JACOBSON, MS, PA-C

The two most common forms of skin cancer The start of the “sun-worshipping season” is a good time to review the primary-care basics of basal cell and squamous cell carcinomas.

A

ccording to the American Cancer Society, skin cancer is the most common cancer in the United States.1 While melanoma is the deadliest form of skin cancer, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are much more common. [Editor’s note: Also see Ms. Jacobson’s related article, “Save a life with early detection of melanoma,” in the May 2014 issue of The Clinical Advisor, available at www.clinicaladvisor.com/ save-a-life-with-early-detection-of-melanoma/ article/343079/; accessed May 15, 2014.]

© DERMPICS / SCIENCE SOURCE

BCC overview

Most basal cell ­carcinomas occur on the face, particularly the nose.

BCCs account for approximately 80% of all skin cancers.2 These epithelial tumors develop from basal cells, located in the lower layer of the epidermis. BCCs are slow-growing and rarely metastasize. They are seen most frequently, but not exclusively, in fair-skinned individuals with a history of actinic exposure. The most common sites of BCC are sun-exposed areas such as the face, ears, and chest. The majority of BCCs—70%—occur on the face, particularly on the nose.2 Another 25% of BCCs occur on the trunk or the extremities, and the remaining 5% on the penis, vulva, or perianal skin, suggesting that there is more to the development of BCC than simply actinic exposure, although actinic exposure is carcinogenic and can lead to mutations directly related to the development of BCCs. Clinical appearance. BCCs can have various presentations, with the most common being a

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MOST COMMON SKIN CANCERS

A superficial BCC should be considered in a patient with red, flaky patches, particularly if that patient has a history of significant sun exposure. pearly papule with telangiectases in the lesion and a rolled edge.

These tumors often bleed. Many patients present with a chief complaint of a nonhealing pimple. The pathology of these classically appearing BCCs are reported as “nodular” BCCs on histologic analysis. Infiltrative BCCs often appear clinically the same as nodular BCCs; however, infiltrative BCCs are difficult to read at the margins because they do not have distinct borders under the microscope. This makes treatment more challenging. Micronodular BCCs have a more distinct border both to the naked eye and under the microscope, and appear as classically described but tend not to ulcerate.

Three forms of BCC can have a more variable clinical appearance that makes diagnosis difficult: morpheaform BCC, pigmented BCC, and superficial BCC. • Morpheaform BCC appears yellowish and waxy with a tinge of pink, and is often more sclerotic, lacking any ulcercation. These lesions often feel firm on palpation.

This finding illustrates the point that a skin examination is often tactile as well as visual.

• Pigmented BCC resembles a traditional BCC but has specks of pigment in it, giving it an almost peppered appearance.

• Superficial BCC can be much more subtle and appear as an erythematous patch or plaque with or without scale.

Superficial BCC occurs most commonly on the upper trunk and shoulders. These lesions are easily misdiagnosed or overlooked as being an eczema patch or psoriasis patch.

A superficial BCC should be considered in the differential diagnosis if a patient presents with red, flaky patches, particularly if that patient has a history of significant sun exposure. Any person with a history of significant sun exposure should be a candidate for a complete skin examination with a dermatology professional.

Diagnosis. The diagnosis of a BCC is made by biopsy. A shave, tangential, or saucerization biopsy is adequate to make the diagnosis and treatment plan. A punch biopsy can be performed if a melanoma is in the differential diagnosis.

Treatment. BCCs typically are treated surgically. Surgical options include excision with appropriate margins, electrodesiccation and curettage (ED&C), and Mohs micrographic surgery. ED&C, the most commonly performed treatment, is done only after the lesion has been debulked during biopsy.

This treatment may result in bleeding and scarring; patients are often left with a white or pink annular scar that is larger than the original lesion. Also, because the clinician performing the ED&C cannot discern the margins of the BCC (with

no tissue being sent away for pathology in this procedure, the clinician cannot be sure that all cancerous cells are being cleared), he or she may not go wide or deep enough, or, conversely, may go wider or deeper than is necessary. The depth and width covered by ED&C are operator-dependent but do rely on the different feel and sound of normal tissue versus cancerous tissue during curettage: Cancerous tissue is often softer; the feel of its removal can be likened to the removal of softened butter. In comparison, normal, healthy tissue is resilient and firm.

Despite the procedure’s drawbacks, ED&C is the most cost-effective treatment option for BCC. The recurrence rate of a BCC 5 years after ED&C is 7.7%.2 Skin also may heal more easily following ED&C than following a procedure that requires stitches.

Mohs micrographic surgery should be considered as a treatment option for skin cancers that are located in cosmetically sensitive areas, are close to adjacent structures that could cause anatomical dysfunction (such as lesions that pull down on the lower eyelid, creating chronic eye-moisture issues; or lesions that pull up the lip border), are larger lesions, or are BCC subtypes with a high incidence of recurrence. Named after the physician who invented the technique in the 1930s, Mohs micrographic surgery is a stepwise procedure in which layers of the involved tissue are removed, fixed on-site by a histology technician, and then mapped by a pathologist (often the dermatologist performing the procedure). The margins are read immediately, and a complex repair, such as a flap or a graft, is done on-site by the same physician that day or the next day. Although this procedure can be relatively costly, it is associated with the lowest recurrence rate of all treatment options for BCC. In addition, Mohs micrographic surgery often provides the most elegant cosmetic result, and in some cases is the only good option for maintaining normal function of surrounding structures. The 5-year recurrence rate of BCC following Mohs surgery has been reported to be as low as 1% in some studies.2 Radiation therapy is an option for patients who have large, advanced BCC lesions or who are not candidates for surgery based on location of the tumor or the person’s general health status. Both topical 5-fluorouracil (Carac, Efudex, Fluoroplex) and imiquimod (Aldara, Zyclara) are FDA-approved for the treatment of basal cell skin cancers, and often are used to treat diffuse areas of sun damage in patients who have a history of BCC or who are at high risk

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MOST COMMON SKIN CANCERS

Superficial basal cells are much more responsive to topical therapy than are micronodular BCCs, which tend to be more aggressive and go deeper.

© THINKSTOCK

for BCC or SCC. These agents should be applied only to superficial BCC in low-risk areas, such as the arms and the back, and require close clinical follow-up by a dermatology provider following use.

5-fluorouracil typically is applied twice a day for 3 to 6 weeks. Crusting, erythema, and stinging of the skin are common and expected reactions to 5-fluorouracil.3 Cure rates for the treatment of superficial BCC with 5-fluorouracil vary, but a 90% clearance rate has been reported.4 Imiquimod has various dosing regimens, but a common routine is to apply the cream 5 days a week for 6 to 12 weeks. Inflammation, irritation, and crusting are expected side effects during treatment with imiquimod as with all topical therapies for BCC.4 (When skin does not react this way during such treatment, it is an indication that the area has become cancer-free.) Studies suggest that cure rates with topical imiquimod range from 73% to 82%. Selection of this treatment option should be based on the tumor’s histologic subtype and location, and a careful analysis of risk-to-benefit ratio that requires the clinician to take into account the risk of recurrence of the original lesion. A recurrence of BCC on the back, for example, is less of a concern than a recurring lesion on the ear, where there is very little spare tissue.

In addition, certain subtypes are more vulnerable to topical therapy: Superficial basal cells are much more responsive to topical therapy than are micronodular BCCs, which tend to be more aggressive and go deeper.

Whereas some providers use imiquimod as their first-line

Some sunscreens work by deflecting ultraviolet rays, whereas others contain chemicals that transform the rays into heat.

agent, others prefer 5-fluorouracil, which is less expensive (albeit still costly) and has been observed by some anecdotally to have better clearance.

Vismodegib (Erivedge), an oral therapy, was approved in January 2012 as a once-a-day capsule, representing the first FDA-authorized treatment for advanced forms of BCC. This inhibitor of the Hedgehog signaling pathway is intended for the treatment of adults with metastatic BCC or with locally advanced BCC that has recurred after surgery, and for adults who are not candidates for surgical or radiation therapy.5 Long-term follow-up. Regardless of the type of BCC therapy used, patients need to be educated about proper sun-protective behaviors. Instruct these individuals to apply sunscreen—with a sun-protection factor (SPF) of 30 or higher—20 minutes before sun exposure and to reapply it every two hours, or more often if they have been in the water or are sweating.

Sunscreens generally work in one of two ways, depending on their ingredients: The more traditional formulations, which contain metals such as zinc oxide or titanium dioxide, reflect light. Other sunscreens use different chemicals, such as avobenzone or ecamsule, which actually absorb the UV radiation and disperse the energy as heat. Heat is currently believed to be harmless to cells and certainly less harmful than true UV radiation.

Also advise patients to avoid peak sunlight hours (10 a.m.–2 p.m.), to seek shade when possible, to wear clothing that protects the skin from ultraviolet (UV) light, and to wear hats.

Routine clinical monitoring in the form of complete skin examinations for BCC and other skin cancers is essential.

A person who has had one BCC has as high as a 44% risk of developing another BCC within the first three years following initial diagnosis.6 For persons with a new diagnosis of BCC, a common recommendation is to undergo skin examinations every 6 months for the first 5 years depending on the patient’s history, risk level, and ability to monitor his or her own skin. The most common histologic types of BCCs to recur are micronodular, infiltrative, morpheaform, and superficial carcinomas.2 Tumors that are larger than 2 cm or that have been treated more than once have a higher recurrence rate.2 Recurrence is most common on the nose and elsewhere on the face.2 The following are warning signs of a BCC recurrence: • Breakdown of previously healed scar tissue • Enlargement of the scar tissue • Formation of a papule or nodule within the scar tissue

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SCC often appears on sun-exposed parts of the body as an ulcerate plaque or papule with scaling or crusting, or as a horny wartlike growth.

SCC overview

SCC accounts for 16% of all skin cancers. Compared with BCC, this type of skin cancer can grow faster, is more aggressive, and carries a greater risk for metastasis. Although cutaneous SCC is rarely fatal, these lesions can become large and bleed or ulcerate on a daily basis to the point of causing discomfort and pain. Additionally, cutaneous SCC often develops on the head or neck, so lesion removal can result in disfigurement and can impair local structure functioning.

The most common cause of SCC is UV radiation damage to p53 tumor suppressor gene. Keratinocytes in the skin then undergo rapid and uncontrolled cloning and growth. Further genetic defects are acquired during this process, leading to the invasion of SCC. Many other genetic abnormalities are associated with or are being studied in the development of SCC. Immunosuppression resulting from immunosuppressive therapy following organ transplantation can lead to multiple SCCs. Therefore, all organ recipients should undergo full clinical skin examinations as part of their long-term follow up care. In addition, any form of chronic immunosuppression, such as that caused by human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS), predisposes a person to SCC. Other risk factors for the development of SCC include exposure to not just UV radiation but other forms of radiation as well, exposure to known human carcinogens, and human papillomavirus (HPV) infection.

Clinical appearance. SCC often appears on sun-exposed parts of the body as an ulcerate plaque or papule with scaling or crusting, or as a horny wartlike growth. Symptoms suggestive of nerve involvement include numbness, twitching, and visual changes (if the lesion is on the head or face).8 SCC can be painful even if there is no nerve involvement.

Diagnosis. SCC is diagnosed by skin biopsy. A shave, tangential, or saucerization biopsy is adequate for the diagnosis of a solitary small lesion. A punch biopsy would provide full thickness analysis and depth of invasion. Computed tomography (CT) imaging should be performed to investigate concerns

of local soft-tissue involvement, and magnetic resonance imaging (MRI) should be performed to investigate concerns of nerve involvement. A fine-needle biopsy is required to evaluate nodule or local lymph node involvement.

If the pathology report describes the lesion as poorly differentiated, the level of atypia is most severe and may even make histology diagnosis difficult to differentiate between mesenchymal tumors, melanoma, or lymphoma. Both acantholytic (adenoid) SCC and spindle cell SCC have a more aggressive clinical course, and management should reflect that.8 Other SCC lesions associated with more aggressive behavior include those that involve the lips, ears, anogenital region, or nerves; those that develop within a scar or chronic wound; those larger than 2 cm; those that have invaded the subcutaneous fat; those with poor differentiation; and those representing a recurrent disease.9 SCCs in the following locations are associated with high rates of metastasis: scalp, forehead, temple, eyelid, nose, dorsal surface of the hands, penis, and scrotum.8 Unlike BCC, SCC on an eyelid can invade the ocular nerve or the bone of the orbit, or can metastasize to more distant locations, to become fatal.10 Of clinical importance is squamous cell in situ (Bowen disease), a cancerous malignancy that will progresses to invasive SCC if left untreated. SCC in situ often appears as a pink or mildly scaly plaque, patch, or macule.

An actinic keratosis (AK) is a common skin lesion that can progress to SCC. AKs can be subtle to obvious. They Continues on page 116

© DR. P. MARAZZI / SCIENCE SOURCE

• Development of crusting or scale on the scar tissue • Bleeding or ulceration of the scar tissue.

Any change at the site of a previously treated BCC must be evaluated pathologically. Patients with a history of BCC are at an increased risk of developing cutaneous melanoma.7 making the need for regular skin examinations for these patients even more vital.

Squamous cell carcinomas that develop on the scalp, as shown here, are associated with high rates of metastasis.

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CME CE

■ EDUCATIONAL OBJECTIVES: After completing the activity, the participant should be better able to: • Describe the symptoms and complications of neonatal abstinence syndrome (NAS) • Implement evidence-based nutrition strategies to improve outcomes in infants with NAS ■ COMPLETE THE POSTTEST: Page 92

FEATURED COURSE

■ ADDITIONAL CME/CE CREDIT: Page 106

This activity is supported by an educational grant from Mead Johnson Nutrition and jointly sponsored by Medical Education Resources (MER), Nurse Practitioner Associates for Continuing Education (NPACE), and Haymarket Medical Education (HME).

Faculty Craig L. Jensen, MD Associate Professor of Pediatrics Baylor College of Medicine Attending Physician Texas Children’s Hospital Houston, TX Release Date: June 2014 Expiration Date: June 2015 Estimated time to complete the educational activity: 30 minutes Target Audience: This activity has been designed to meet the educational needs of primary-care physicians, pediatricians, physician assistants, nurse practitioners, and dietitians.

Physician Credit: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of MER and HME. MER is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation: MER designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Dietitian Credit: Medical Education Resources (Provider Number ME110) is a Continuing Professional Education (CPE) Accredited Provider with the Commission on Dietetic Registration (CDR).

Nursing Credit: Nurse Practitioner Associates for Continuing Education (NPACE) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation (ANCC).

Credit Designation: NPACE designates this educational activity for a maximum of 0.5 contact hours of credit. Participants should only claim credit commensurate with the extent of their participation in the activity.

Disclosure Policy—MER MER ensures balance, independence, objectivity, and scientific rigor in all our educational programs. In accordance with this policy, MER identifies conflicts of interest with its instructors, content managers, and other individuals who are in a position to control the content of an activity. Conflicts are resolved by MER to ensure that all scientific research referred to, reported, or used in a CME activity conforms to the generally accepted standards of experimental design, data collection, and analysis. MER is committed to providing its learners with high-quality CME activities that promote improvements or quality in health care and not the business interest of a commercial interest.

Disclosure Policy—NPACE NPACE is committed to ensuring all educational activities are balanced and free from bias. All faculty participating in our programs disclose any relationships they may have with a commercial interest whose products or services are related to the content of the activity. NPACE’s status as an accredited provider

of continuing nursing education does not imply endorsement by NPACE or ANCC of any commercial products discussed in conjunction with this program.

NPACE maintains content integrity and prevents bias in the presence of commercial support through: 1) disclosing relevant relationships of activity planners, authors, and content reviewers with any commercial interest, or lack thereof; 2) disclosing commercial support; 3) removing individuals with conflict of interest from the activity; 4) revising the role of the individual with the conflict so that the relationship is no longer relevant to the activity; 5) not awarding contact hours for a portion or all of the activity; 6) undertaking review of the activity by a content reviewer to evaluate for bias, balance, evidence-based content or other indicators of integrity; 7) monitoring the activity to evaluate for bias; and/or 8) reviewing participant feedback.

Faculty Disclosure Craig L. Jensen, MD, is a consultant to Mead Johnson Nutrition. He is also on the Speakers’ Bureau for Mead Johnson Nutrition.

Staff/Planners’ Disclosures Krista Sierra, Susan Basilico, and Marjorie Hale, all of HME, have no financial relationships to disclose.

MER Content Manager has no financial relationships to disclose.

R. Mimi Secor, MS, MEd, NP, FAANP, of NPACE is a consultant to GenPath Diagnostic Labs and Shionogi, and is on the Speakers’ Bureau for Hologic.

Method of Participation: There are no fees for participating in or receiving CME/CE credit for this activity. During the period June 2014 through June 2015, participants must: 1) read the learning objectives and faculty disclosures; 2) study the educational activity; 3) complete the posttest and submit it online. Physicians may register at www.myCME.com (June 2014) and 4) complete the evaluation form online.

A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better.

Disclaimer: The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of MER, NPACE, or HME. The authors have disclosed if there is any discussion of published and/or investigational uses of agents that are not indicated by the FDA in their presentations. The opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of MER, NPACE, or HME. Before prescribing any medicine, primary references and full prescribing information should be consulted. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The information presented in this activity is not meant to serve as a guideline for patient management.

Jointly sponsored by

Commercial support for this activity was provided through an educational grant from

®

Nurse Practitioner Associates

for Continuing Education

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CRAIG L. JENSEN, MD

Improving outcomes for infants with NAS Newborns who were exposed to certain substances in utero face unique challenges during their first months of life.

M

ichael B. is a 5-week-old infant who was born to a 25-year-old single white mother, gravida 1, para 1. The mother used heroin during most of her pregnancy and enrolled in a methadone maintenance program during week 30 of gestation. Since that time, she has taken 150 mg of methadone daily. She admits to drinking “a few” beers during her pregnancy and also smoked approximately 20 cigarettes per week.

Michael was born at 38 weeks’ gestation via spontaneous vaginal delivery. Apgar scores at birth were 8 and 9. At the time of Michael’s birth, his mother tested negative for opioids, cocaine, and benzodiazepines. However, he exhibited withdrawal symptoms (excitability, irritability, hyperactive reflexes, vomiting, diarrhea) for the first month of his life. Other than being small for gestational age, Michael’s physical exam was normal.

While in the neonatal intensive care unit (NICU), Michael was put on a short-acting opiate preparation that was gradually

discontinued. From birth, he experienced difficulties with feeding and weight gain. To ensure he received adequate nutrition, expressed breast milk was supplemented with high-calorie infant formula; frequent, small feedings were given until he was released from the hospital three weeks after his birth.

Since returning home, Michael’s mother has attempted to breastfeed exclusively but the baby is having difficulty in feeding and is beginning to lose weight. She is upset during her first visit to the baby’s pediatrician; she says she feels a great deal of guilt and remorse regarding her drug use during pregnancy and that she wants to “do the right thing” for her child by continuing to breastfeed. She is frustrated by the persistent feeding difficulties that Michael exhibits and unsure how she can help him.

Most clinicians who manage the care of very young children will eventually encounter an infant with neonatal abstinence syndrome (NAS), a group of problems that occur in a newborn who had been exposed to addictive illegal or prescription drugs while in the mother’s womb.1 The number of infants born with the condition increased threefold between 2000 and 2009.2 In addition to neurologic excitability and gastrointestinal issues, children with this condition often show signs of poor feeding or slow growth and are at increased risk for morbidity and mortality. 3 According to the American Academy of Pediatrics (AAP), these infants usually have greater caloric needs than do healthy babies.3 Because parents look to clinicians when seeking healthcare advice for their children,4,5 it is important that healthcare providers are aware of strategies to improve long-term outcomes of these young patients.

© ISTOCK

The public health issue of babies born addicted

Meeting the higher caloric requirements of infants with NAS is important for development and long-term health.

Drug and substance misuse has become a serious public health issue in the United States, particularly among women of childbearing age.5 Women comprise approximately 30% of the population addicted to illicit drugs, with the majority

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CME CE

IMPROVING OUTCOMES FOR INFANTS WITH NAS

The outcome of the infant exposed to illicit drugs in utero depends, in part, on the quality of care the mother receives during her pregnancy. aged 15 to 44 years.5 According to the National Institute on Drug Abuse, illegal drug use among pregnant women increased from 3% in 2002 to 4.4% in 2010 and was highest among 15- to 17-year-olds (Table 1).4 One serious and concerning consequence of this increase is the growing number of infants who are born addicted and develop the complex disorder known as NAS, a condition that develops in 50% to 95% of newborns exposed prenatally to illicit drugs.5 Although maternal use of benzodiazepines, amphetamines, cocaine, or barbiturates is associated with NAS, the syndrome most commonly occurs in infants exposed to opioids, afflicting as many as 60% to 80% of those exposed to heroin or methadone (Dolophine, Methadose).5,6 The incidence of opiate-associated NAS increased more than threefold between 2000 and 2009, which paralleled the nearly fivefold increase in mothers using or dependent on opioids.6 Not surprisingly, NAS is associated with increased healthcare utilization costs (Table 2). One study cited a 35% increase in neonatal hospital charges between 2000 and 2009, although the mean length of stay (LOS) for NAS remained unchanged.5 Nationally, total hospital charges for NAS more than tripled by 2009.6 That year, an estimated 13,539 newborns in the United States developed the condition, a statistic equivalent to approximately one infant born per hour with signs of drug withdrawal.5 Effects of antenatal drug use on the developing fetus

If used during pregnancy, many drugs produce teratogenic effects (e.g., skeletal and facial abnormalities) and adversely affect fetal growth and/or maturation, the developing

TABLE 1. Illicit drug use reported by women aged 15 to 44 years* in a survey by the National Institute on Drug Abuse, 20104 Age Group

Percentage of Women

15 to 17 years

16.2%

18 to 25 years

7.4%

26 to 44 years

1.9%

*Drug use reported within one month of the survey.

neurologic systems, and brain organization.4,6 Drugs can also indirectly affect the fetus by interfering with the environment within the womb. Some drugs can cause contractions of the womb, decreasing the blood supply to the baby, while others may cause early, delayed, or prolonged labor.

Infants with NAS are more likely to be born prematurely, have lower birth weight (<2,500 g), be small for gestational age, and have smaller head circumference (Table 3).4,6,7 Prenatal drug exposure increases the risk for neonatal mortality, including sudden infant death syndrome, and for medical, developmental, emotional, and behavioral problems (Table 3).4,6 The outcome of the infant exposed to illicit drugs in utero depends, in part, on the quality of care the mother receives during her pregnancy.7 Unfortunately, stigma may prevent some pregnant women from disclosing their drug use and cause them to avoid or delay prenatal care.4,6 On the other hand, pregnancy can be a motivating factor for entry into a treatment program that can improve prenatal care, optimize maternal physical and mental health, and reduce withdrawal symptoms and drug cravings.2,8

TABLE 2. Trends in the incidence of NAS and related health-care utilization and expenditures5 2002

2009

P for trend

NAS rate (per 1,000 hospital births per year)

1.20

3.39

<0.001

Mean hospital charges

$39,400

$53, 400

<0.001

Length of stay

15.8 days

16.4 days

0.06

National total hospital charges

$190 million

$720 million

<0.001

NAS = neonatal abstinence syndrome

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Infants exhibiting poor feeding should be evaluated for causes other than NAS, including sepsis, hypoglycemia, immaturity, bowel obstruction, and pyloric stenosis.

Clinical presentation and assessment of NAS

Many factors influence the clinical presentation of NAS, including the class of drug used during pregnancy, how much of the drug was used, time of most recent use, factors impacting maternal and fetal metabolism, neonatal immaturity or illness, and polydrug use.8 Signs of withdrawal typically appear within 24 to 72 hours after birth and may last two to three days or up to eight weeks or longer.2,4,8 The majority of NAS symptoms manifest in the central nervous system (CNS) and in the gastrointestinal (GI) tract, where opioid receptors are highly concentrated, as well as in the autonomic nervous system.2 Hallmark features of NAS include extreme irritability, excessive and high-pitched crying, reduced quality and duration of sleep after a feeding, an inability to self-soothe, and increased muscle tone, tremors, and seizures.4,8 Signs of autonomic dysregulation include sweating, frequent yawning and sneezing, and respiratory distress.4,8

GI disturbances present as excessive sucking, feeding intolerance, regurgitation or vomiting, and loose or watery stools.4,8 However, the presentation of GI symptoms differs according to the drug used during pregnancy.9 Antenatal use of narcotics (heroin, methadone), or fentanyl (Duragesic) may cause vomiting and diarrhea. Feeding difficulties are associated with marijuana use, and infants exposed to cocaine may show a poor tolerance to oral feedings.9 Infants exhibiting poor feeding should be evaluated for causes other than NAS, including sepsis, hypoglycemia, immaturity, bowel obstruction, and pyloric stenosis.10 The most commonly used rating of the severity of withdrawal is a modified Finnegan Neonatal Abstinence Score, which rates the signs and symptoms of CNS disturbances; metabolic, vasomotor, and respiratory disturbances; and GI disturbances on a 5-point scale, usually at birth and every four hours or after each feeding (Figure 1).2,8,11 All infants should be monitored closely for signs of fever,

TABLE 3. Potential effects of prenatal drug exposure on birth outcomes, central nervous system development, cognitive function, and behavior19

Birth outcomes

Nicotine

Marijuana

Cocaine

Methamphetamine

Heroin/Opioids

Prematurity

No fetal growth effects

Prematurity

Small for gestational age

Prematurity

Decreased birth height, weight, head circumference

No physical abnormalities

Decreased birth height, weight, head circumference

Decreased birth weight

Decreased birth height, weight, head circumference

Sudden infant death syndrome

Intraventricular hemorrhage

Sudden infant death syndrome

Increased infant mortality rate Effects on CNS development, cognitive function, and behavior

Excitability, hypertonia

Mild withdrawal symptoms; poor autonomic control, particularly of state regulation (the ability to adjust one’s level of alertness as required for a task)

Conduct disorder, Executive function reduced IQ, aggression, impairment, reading antisocial behavior, and spelling difficulty impulsivity, ADHD

Early neurobehavioral deficits, poor clarity of infant cues during feeding

Poor movement quality, lower arousal, increased lethargy, increased physiological stress

Neonatal abstinence syndrome, less rhythmic swallowing, strabismus

Delayed information processing, general cognitive delay, attention problems, disruptive behaviors

No mental or motor delay

Possible delay in general cognitive function, anxiety, aggression, disruptive/ inattentive behavior

ADHD = attention deficit/hyperactivity disorder; CNS = central nervous system; IQ = intelligence quotient

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CME CE

IMPROVING OUTCOMES FOR INFANTS WITH NAS

NEONATAL ABSTINENCE SCORING SYSTEM Modified Finnegan Neonatal Abstinence Score Sheet 11

Central Nervous System Disturbances

System

Signs and Symptoms

Score

Excessive high-pitched (or other) cry <5 mins

2

Continuous high-pitched (or other) cry > 5 mins

3

Sleeps < 1 hour after feeding

3

Sleeps <2 hours after feeding

2

Sleeps <3 hours after feeding

1

Hyperactive Moro reflex

2

Markedly hyperactive Moro reflex

3

Mild tremors when disturbed

1

Moderate-severe tremors when disturbed

2

Mild tremors when undisturbed

3

Moderate-severe tremors when undisturbed

4

Increased muscle tone

1

Excoriation (chin, knees, elbow, toes, nose)

1

Myoclonic jerks (twitching/jerking of limbs)

3

Generalized convulsions

5

Gastrointestinal Disturbances

Metabolic/Vasomotor/ Respiratory Disturbances

Sweating

AM

PM

Comments

1 o

Hyperthermia 98.96-100.94 F

1

Hyperthermia >101.12o F

2

Frequent yawning (>3-4 times/scoring interval)

1

Mottling

1

Nasal stuffiness

1

Sneezing (> 3-4 times/scoring interval)

1

Nasal flaring

2

Respiratory rate > 60/min

1

Respiratory rate > 60/min with retractions

2

Excessive sucking

1

Poor feeding (infrequent/uncoordinated suck)

2

Regurgitation (≥ 2 times during/post feeding)

2

Projectile vomiting

3

Loose stools (curds/seedy appearance)

2

Watery stools (water ring on diaper around stool)

3

Total Score Date/Time Initials of Scorer

Adapted from Finnegan LP. In: Nelson N, editor. Current therapy in neonatal-perinatal medicine. 2ed. Ontario: BC Decker;1990.

FIGURE 1. Modified Finnegan Neonatal Abstinence Scoring Tool11

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dehydration, or weight loss.6 The duration of hospitalization depends on an accurate assessment of maternal drug history, the half-life of the drug, and response to pharmacologic treatment, if needed.2,8 Nonpharmacologic management of NAS

Nonpharmacologic management is the standard of care for infants with symptoms of NAS.7 A number of supportive measures address the signs and symptoms of NAS and ensure that infants achieve adequate sleep and nutrition for consistent weight gain and begin to integrate into a social environment.6 However, drug therapy may be indicated to manage moderate-to-severe signs of NAS and prevent such complications as fever, weight loss, and seizures if the infant does not respond to a consistent program of nonpharmacologic supportive care.2 Infants with NAS should be placed in a dark, quiet environment (see Box, page 7).2,12,13 because just a small amount of stimulation can produce a hyperactive or underactive CNS response to the external environment in these infants.2,13 Handling should be slow and gentle, and care should be clustered to promote longer periods of sleep.14 Tight swaddling and positioning of infants on the back or side to mimic the fetal position can prevent hypertonic and erratic movements.14 Applying pressure to the infant’s head and body can have a calming effect.14 Other techniques such as rocking and swaying motions, and rubbing instead of patting when burping, also are comforting.2,14 Nonnutritive sucking with a pacifier promotes self-soothing, decreases stress, and lessens erratic and uncoordinated movements and the risk of excoriations.2,14 Ensuring optimal nutrition for infants with NAS

Infants with NAS have higher caloric requirements due to the energy expenditure associated with increased crying and activity, decreased sleep, and calories lost with regurgitation, vomiting, and/or diarrhea.2,15 The caloric needs of these infants can be as high as 150 to 250 cal/kg per day.

Hyperphagia is one sign of this increased need.15 Infants with NAS should undergo frequent, small feedings (every three to four hours) to minimize hunger and allow for adequate growth.2,15 Feeding with hypercaloric formula (24 calories per ounce) may be required to meet nutritional needs and facilitate weight gain.15 While somewhat controversial for infants with NAS,13 breastfeeding is beneficial for both the mother and the infant and is recommended by the AAP as first-line nutrition. It

enhances maternal-fetal bonding, decreases the mother’s stress response to the infant’s withdrawal symptoms, and improves the infant’s sleep patterns.13,14 Several studies have shown that infants with NAS who were breastfed or fed breast milk had lower Finnegan scores, and fewer babies required pharmacologic therapy.2,16-18 In addition, breastfeeding the infant or feeding the infant breast milk may allow for more aggressive weaning from methadone, resulting in earlier discharge and a shorter length of stay in the hospital.13 Breastfeeding can effectively decrease NAS symptoms because methadone and buprenorphine are transferred to the breast milk.2,14 Maternal contact while breastfeeding also plays a role in ameliorating symptoms.14 Unless otherwise contraindicated, mothers who adhere to a supervised drug-treatment program should be encouraged to breastfeed or to express breast milk, as long as the infant continues to gain weight.2,13 The previous recommendations of the AAP advised against breastfeeding for mothers receiving maintenance doses of methadone of more than 20 mg/24 h.16 However, in an updated position statement, the AAP stated that methadone was compatible with breastfeeding.18 Supplementary feedings with expressed breast milk or hypercaloric formula may be required until an adequate caloric intake is reached.10 Breastfeeding, however, is contraindicated in certain cases, such as if the mother is still using illicit drugs or is HIV-positive.18 In such cases, frequent feedings with highcalorie commercial infant formulas are recommended.10 Post-discharge management and prognosis

Infants with NAS usually are observed in the hospital for four to seven days.2 However, because evidence of withdrawal may be delayed until five to seven days after birth and after hospital discharge, outpatient follow-up should take place early, and parents or caregivers should be advised of the signs of late withdrawal.2,4,8 Whether infants are breastfed or formula-fed, parents should be given appropriate information and support regarding feeding to ensure their ongoing involvement with infant care.10 Parents who formula-feed should be educated about safe practices for the preparation, transportation, and storage of prepared infant formula as well as appropriate methods for heating or reheating reconstituted prepared formula.10 The class of drug used during pregnancy may affect the infant’s CNS development, cognitive function, and behavior as he or she grows (Table 3).19 Antenatal use of tobacco is

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IMPROVING OUTCOMES FOR INFANTS WITH NAS

associated with a lower IQ for the child as well as aggression, antisocial behavior, and attention deficit/hyperactivity disorder (ADHD),19 while the developmental effects of fetal exposure to tetrahydrocannabinol (THC) manifest as impairment of executive function and difficulties with reading and spelling.19 Infants born to mothers who used cocaine may exhibit a general cognitive delay and inhibited information processing; as children, they may be small for their age, have problems with attention, and exhibit disruptive behaviors.19 On the other hand, fetal exposure to methamphetamine does not appear to produce mental or motor delays in infants and toddlers.19 Infants exposed to opiates antenatally may have delays in general cognitive function and may experience anxiety, aggression, and disruptive or inattentive behavior as children.19 Relatively few studies on long-term outcomes in infants with NAS have been performed. Confounding variables that may affect outcomes include unsafe/unhealthy home environment, dysfunctional caregivers, fetal growth restriction, and polydrug exposure.

be monitored closely for weight gain and for the development of other diseases.

Conclusion

As the use of illicit drugs by pregnant women increases, so does the number of infants who develop signs and symptoms of NAS, the prevalence of which is most pronounced in infants exposed to opioids. Nonpharmacologic management with supportive measures to ameliorate the infant’s CNS, GI, and autonomic disturbances are the standard of care, regardless of the need for pharmacologic intervention.

Given the increased medical and developmental risks infants with NAS face, adequate nutrition to meet the increased caloric needs is essential for weight gain and growth. Small, frequent feedings with hypercaloric infant formula given in a low-stimulus environment, alone or as a supplement to breastfeeding, are recommended. n References 1. Jones HE, Kaltenbach K. Neonatal abstinence syndrome. JAMA. 2012;308:762-763.

Nonpharmacologic supportive care for infants with NAS

2. Hudak ML, Tan RC, The Committee on Drugs, The Committee on Fetus

Parents of infants with NAS should be counseled on evidence-based, supportive treatments to implement after hospital discharge (see Box, below). Swaddling techniques may help minimize fussiness and agitation, and may be particularly useful during feedings.

Poor motor control also can contribute to poor feeding.

For example, the infant may turn his or her head from side to side vigorously when the nipple or pacifier is brought close to the mouth. Helping to steady the head will be helpful in these instances.12 Bright lights, excessive noise, and other sensory stimulation should be kept to a minimum. It is essential that the infant

Available at pediatrics.aappublications.org/content/129/2/e540.full.pdf+html.

and Newborn Neonatal Drug Withdrawal. Pediatrics. 2012;129:e540-e560.

3. Allen RE, Myers AL. Nutrition in toddlers. Am Fam Physician. 2006;74: 1527-1532. Available at www.aafp.org/afp/2006/1101/p1527.html.

4. Wendell AD. Overview and epidemiology of substance abuse in pregnancy. Clin Obstet Gynecol. 2013;56:91-96.

5. Patrick SW, Schumacher RE, Benneyworth BD, et al. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009. JAMA. 2012;307:1934-1940. Available at jama. jamanetwork.com/article.aspx?articleid=1151530&resultClick=3.

6. Behnke M, Smith VC, Committee on Substance Abuse, Committee on Fetus and Newborn. Prenatal substance abuse: short- and long-term effects on the exposed fetus. Pediatrics. 2013;131:e1009-e1024. Available at pediatrics.aappublications.org/content/131/3/e1009.full.pdf+html.

Nonpharmacologic supportive care for infants with neonatal abstinence syndrome2,13 • Decrease environmental stimuli.

• Use tight swaddling; position on side or back in "C" curve.

• Apply pressure over infant's head and body for calming effects.

• Cluster infant-care activities with gentle handling.

7. Queensland Maternity and Neonatal Clinical Guidelines Program.

Neonatal abstinence syndrome. 2010; Queensland, Australia. Available at www.health.qld.gov.au/qcg/documents/g_nas5-0.pdf.

8. Logan BA, Brown MS, Hayes MJ. Neonatal abstinence syndrome: treatment and pediatric outcomes. Clin Obstet Gynecol. 2013;56:186-192.

9. March of Dimes. Available at http://www.marchofdimes.com/baby/ neonatal-abstinence-syndrome-%28nas%29.aspx.

• Encourage non-nutritive sucking.

10. University of Iowa. Neonatal abstinence syndrome. Available at

• Use small, frequent feedings, with hypercaloric formula if needed.

www.uiowa.edu/~medtest3/nas/NAS.pdf.

• The baby should be breastfed if possible.

11. Finnegan LP, Connaughton JF Jr, Kron RE, Emich JP. Neonatal abstinence syndrome: assessment and management. Addict Dis. 1975;2:141-158.

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12. Velez ML, Jansson LM, Schroeder J, Williams E. Prenatal methadone

17. Jansson LM, Choo R, Velez ML, et al. Methadone maintenance and

exposure and neonatal neurobehavioral functioning. Pediatr Res.

breastfeeding in the neonatal period. Pediatrics. 2008;121:106-114. Available

2009;66:704-709.

at pediatrics.aappublications.org/content/101/6/1079.full.pdf+html.

13. Sublett J. Neonatal abstinence syndrome: therapeutic interventions.

18. American Academy of Pediatrics Committee on Drugs. The

MCN Am J Matern Child Nurs. 2013;38:102-107.

transfer of drugs and other chemicals into human milk. Pediatrics.

14. Pritham UA. Breastfeeding promotion for management of neonatal

2001;108:776-789. Available at pediatrics.aappublications.org/

abstinence syndrome. J Obstet Gynecol Neonatal Nurs. 2013;42:517-526.

content/108/3/776.full.pdf+html.

15. McQueen KA, Murphy-Oikonen J, Gerlach K, Montelpare W. The

19. Minnes S, Lang A, Singer L. Prenatal tobacco, marijuana, stimulant,

impact of infant feeding method on neonatal abstinence scores of

and opiate exposure: outcomes and practice implications. Addict Sci Clin

methadone-exposed infants. Adv Neonatal Care. 2011;11:282-290.

Pract. 2011;61:57-70. Available at www.ncbi.nlm.nih.gov/pmc/articles/

16. American Academy of Pediatrics Committee on Drugs. Neonatal

PMC3188826/.

drug withdrawal. Pediatrics. 1998;101(6):1079-1088. Available at pediatrics. aappublications.org/content/121/1/106.full.pdf+html.

All electronic documents accessed April 15, 2014.

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POSTTEST Expiration date: June 2015

Credit Designation: MER is accredited by the ACCME to provide continuing medical education for physicians. MER designates this educational activity for a maximum of 0.5 AMA PRA Category l Credit™.

Nurse Practitioner Associates for Continuing Education (NPACE) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. NPACE designates this educational activity for a maximum of 0.5 contact hours of credit.

Dietitian Credit: Medical Education Resources (Provider Number ME110) is a Continuing Professional Education (CPE) Accredited Provider with the Commission on Dietetic Registration (CDR). Registered Dietitians (RDs) and Dietetic Technicians (DTRs) will receive 0.5 continuing professional education unit (CPEU) for completion of this program/material.

Participants should only claim credit commensurate with the extent of their participation in the activity.

A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better. Posttest must be completed and submitted online. Please go to CliniAd.com/1tnVRBU. CREDITS: 0.5

| Improving outcomes for infants with neonatal abstinence syndrome

1. According to the American Academy of Pediatrics (AAP), which of the following statements about infants with neonatal abstinence syndrome (NAS) is true? a. They tend to be smaller than healthy infants until after age 1 year. b. They tend to have a higher incidence of atopic dermatitis than do healthy neonates. c. They usually have greater caloric needs than do healthy babies. d. All of the above 2. The majority of women addicted to illicit drugs: a. Also use alcohol b. Are of childbearing age c. Are infected with HIV or hepatitis d. All of the above 3. NAS most commonly occurs in: a. Infants born to mothers who use opioids b. Infants born to mothers who use cocaine or methamphetamine c. Infants born to mothers who use prescription drugs d. Infants born to mothers who abuse alcohol

6. The caloric needs of infants with NAS can be as high as: a. 100 cal/kg per day b. 150 cal/kg per day c. 200 cal/kg per day d. 250 cal/kg per day 7. One sign of the increased caloric needs of infants with NAS is: a. Near-constant suckling b. Hyperphagia c. Slow growth d. Lethargy 8. Breastfeeding in NAS: a. Is not recommended b. Is contraindicated if the mother is still using illicit drugs or is HIV-positive c. Is contraindicated if the mother is using methadone (Dolophine, Methadose) d. Is contraindicated if the infant was small for gestational age at birth

4. The majority of NAS symptoms manifest in the: a. Central nervous system b. Gastrointestinal (GI) tract c. Autonomic nervous system d. All of the above e. Both A and B

9. Infants with NAS who are not breastfed: a. Should receive frequent feedings with high-calorie commercial infant formulas b. Should receive on-demand feedings with lactose-free infant formula c. Should receive only hydrolyzed infant formula d. None of the above

5. GI disturbances in infants with NAS: a. Are usually similar no matter what drug was used during pregnancy b. Are usually related to hypoglycemia c. Usually manifest in symptoms that include feeding intolerance d. Are relatively uncommon

10. Which of the following drugs or drug classes does not appear to produce mental or motor delays in infants and toddlers? a. Cocaine b. Opioids c. Tobacco d. Methamphetamine

TO TAKE THE POSTTEST please go to CliniAd.com/1tnVRBU

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Advisor Forum These are letters from practitioners around the country who want to share their clinical problems and successes, observations, and pearls with their colleagues. Responding consultants are identified below. We invite you to participate.

Inside the Forum JUNE 2014

Consultations Otitis treatment and penicillin allergy. 94 Go gluten-free for psoriasis?. . . . . . . . 95 Vitamin supplements for the elderly. . 95 Numbing a wound on infected skin. . 95

Clinical Pearls A stress fracture “tune-up”. . . . . . . . . 96 Explaining loss of consciousness. . . . . 96 Lymph node clues to conjunctivitis. . . 96 Self-monitoring for HTN awareness. . 96 A solid plan for written plans . . . . . . . 96

Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001.

You may also fax (646) 638-6117, or contact us by e-mail at letters@ clinicaladvisor.com.

If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter.

No anonymous contributions will be accepted.

Removing objects from the nose . . . . 96

CONSULTATIONS OTITIS TREATMENT IN A CHILD WITH SUSPECTED PENICILLIN ALLERGY A boy, aged 2 years, presented to a pediatric urgent-care clinic and was diagnosed with a serum sickness-like reaction in response to antibiotics prescribed for acute otitis media (AOM). The classic symptoms presented 6 hours after intramuscular injection of ceftriaxone [Rocephin]; however, prior to that injection, the patient had a full 10-day course of high-dose amoxicillin [Amoxil, Larotid, Moxtag] followed by four days of no medications and then 48 hours of high-dose amoxicillin and clavulanic acid (Amoclav, Augmentin, Clavamox).

Given this history, what would you prescribe for a future AOM or other infection that would typically call for a penicillin? Would you tell the family to treat this as a penicillin allergy?—JANIS MANDAC-DY, CPNP, San Francisco The term “serum sickness” refers to an allergic-like reaction to the administration of antibodies or to protein-containing therapies used to treat immune conditions. I suspect that Ms. Mandac-Dy is referring to a systemic allergic reaction that was not anaphylaxis. Symptoms of an allergic reaction to a drug can develop during the course of treatment or, in rare cases, up to a couple of weeks after the drug was administered.

Augmentin lists serum sickness-like reaction as an adverse reaction, and Rocephin lists serum sickness as an adverse reaction. Given the

OUR CONSULTANTS

Philip R. Cohen, MD,

is clinical associate professor of dermatology, University of Texas Medical Center, Houston.

Deborah L. Cross, MPH, CRNP, ANP-BC, is associate program

director, Gerontology NP Program, University of Pennsylvania School of Nursing, Philadelphia.

Abimbola Farinde, PharmD, MS,

is a professor at Columbia Southern University in Orange Beach, Ala.

Abby A. Jacobson, PA-C,

Maria Kidner, DNP, FNP-C,

is a physician assistant at Delaware Valley Dermatology Group in Wilmington, Del.

is a nurse practitioner with Cheyenne Cardiology Associates in Cheyenne, Wyo.

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small chance for cross-reactivity with cephalosporins, the penicillin family should both be avoided until testing can be done to determine a true penicillin allergy (Allergy Asthma Immunol Res. 2012;4:251263; available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3423598/, accessed May 15, 2014). The recommended next line of treatment for AOM is clindamycin (Cleocin) (Pediatrics. 2013;131:e964-e999; available at pediatrics.aappublications.org/content/131/3/e964.full, accessed May 15, 2014).—Julee B. Waldrop, DNP (188-1)

GO GLUTEN-FREE FOR PSORIASIS? Would a gluten-free diet help with such inflammatory diseases as psoriasis?—JAMES SPALL, FNP, Knoxville, Tenn.

In the absence of symptoms of celiac disease, I generally do not recommend that patients go gluten-free as a treatment for inflammatory disease. No research has yet shown that psoriasis can be improved with a gluten-free diet.

Anyone who decides to eliminate gluten from his or her diet should first consult a dietitian for guidance. Gluten can be hidden in unexpected foods, such as lunch meat and salad dressing. A gluten-free diet must be maintained for at least 90 days before improvement can be assessed.—Abby A. Jacobson, PA-C (188-2)

THE NEED FOR VITAMIN SUPPLEMENTS AMONG OLDER PATIENTS I receive a number of recommendations to add multivitamin, vitamin D, vitamin C, and calcium supplements to the diets of elderly patients in long-term-care facilities (even those in hospice care). Given the risk of overdose, why is it that so many dietitians recommend that elderly patients be placed on vitamin supplements?—RHONDA WHITE, FNP, ANP, Gainesville, Fla.

Debra August King, PhD, PA,

is senior physician assistant at New York-Presbyterian Hospital, New York City.

Mary Newberry, CNM, MSN,

provides well-woman gynecologic care as a midwife with Prima Medical Group, Greenbrae, Calif.

As an individual ages, he or she can experience a loss of taste, a lack of appropriate appetite, chewing and swallowing issues, and decreased physical activity that can reduce the normal, healthy intake of food. Without a well-balanced diet that incorporates each of the food groups, elderly patients may need vitamin supplements to avoid missing key nutrients. Vitamin D, vitamin B12, vitamin C, and vitamin A have been shown to be beneficial during the aging process. To prevent hypervitaminosis, patients must be instructed to never take more than the recommended daily allowance of any vitamin or supplement. Elderly patients should provide a list of all prescription and nonprescription medications they are taking as well as all vitamins, herbal, and natural remedies.—Abimbola Farinde, PharmD (188-3)

NUMBING A WOUND ON INFECTED SKIN Incision and drainage procedures on methicillin-resistant Staphylococcus aureus wounds can be painful. Lidocaine does not seem to work very well. What other numbing agents are available?—ALYCE HUNTSINGER, FNP, NNP, Portland, Ore. Incision and drainage on already infected skin structures will always be uncomfortable for the patient. The infection most likely has created inflammation and pressure on surrounding skin, structures, and nerves. Most importantly, all local anesthetics will function poorly in the acidic environment of an acutely infected abscess, no matter what the infective organism is.

I recommend lidocaine with epinephrine for all site-appropriate structures and patients whenever possible. The epinephrine will help control bleeding and further numb the area. Another advantage to using epinephrine is that the patient will be numb for longer post procedure.

Bupivacaine 0.25% (Marcaine) with epinephrine is another option.

Claire O’Connell, MPH, PA-C,

teaches in the PA Program at the New Jersey Medical School and Rutgers University, Piscataway, N.J.

Continues on page 96

Sherril Sego, FNP-C, DNP,

is a primary-care nurse practitioner at the Department of Veterans Affairs Medical Center in Kansas City, Mo.

Julee B.Waldrop, DNP,

is associate professor at the University of Central Florida (UCF), and practices pediatrics at the UCF Health Center.

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Advisor Forum © KALLISTA IMAGES / CUSTOM MEDICAL STOCK PHOTO

of them should be evaluated by a medical professional to determine when he or she can safely return to play.—BARBARA CROSS, PhD, APRN-BC, Hampton, Va. (188-6)

LYMPH NODE CLUES TO CONJUNCTIVITIS When assessing red eyes, feel for pre-auricular lymph node enlargement. The presence of pre-auricular lymphadenopathy is usually indicative of viral conjunctivitis, not bacterial conjunctivitis.—ROBERT MITCHELSON, PA, Maricopa, Ariz. (188-7)

Lidocaine with epinephrine helps numb MRSA abscess for incision.

Make sure you place the local anesthesia and let the patient sit for at least 20 minutes before starting the procedure. This allows the anesthesia to take effect and will help decrease the patient’s discomfort.

I also believe in the power of distraction. Have staff or a family member talk to the patient about anything other than the procedure or pain. Providing rubber balls that the patient can squeeze during the procedure may be helpful as well. Finally, some clinicians believe that stimulating adjacent tissue with movement alleviates pain.— Abby A. Jacobson, PA-C (188-4)

CLINICAL PEARLS A STRESS FRACTURE “TUNE-UP” What is an easy way to distinguish between shin splints and a stress fracture? Use a tuning fork. The vibration will cause bone pain in the presence of a stress fracture.—CHRISTINA KURKOWSKI, MS, RN, ONC, CNOR, ANP-C, ONPC, Wausau, Wis. (188-5) EXPLAINING LOSS OF CONSCIOUSNESS When interviewing parents and adolescents about sports participation, it is important to get a thorough history of possible concussive events. Many parents will report, “Oh, he/she hit her head but didn’t black out.” It’s important to educate them to the signs of concussion: loss of consciousness (LOC); alteration of consciousness (AOC), including dizziness, seeing stars, confusion, or disorientation for any period of time; and post-traumatic amnesia (PTA), in which the person can’t recall events that occurred immediately before or after the hit. These are all signs of a concussion, and the child who experiences any

SELF-MONITORING FOR HTN AWARENESS The prevalence of hypertension is increasing, especially in my home state of Mississippi. One problem with hypertension is the absence of symptoms. Individuals in rural areas experience many difficulties in accessing health-care services, so what I am doing in my practice is prescribing self-monitoring of blood pressure, either with a home device or through a public kiosk, to patients who have hypertension or patients who are at risk of developing hypertension. I have found that once patients see their numbers, this information will motivate change to do what is necessary.—LANEITA DAVIS, DNP, FNP-BC, Tunica, Miss. (188-8) A SOLID PLAN FOR WRITTEN PLANS When providing a written management plan for patients with chronic disease, place the plan in the patient’s hands. It should be in a larger font, with treatment changes or updates bulleted by chronic disease.When you review the plan with the patient, don’t ask, “Do you understand?” Instead, say, “To make sure that I have been clear, can you summarize the plan for me?” With a clear, simply written plan in hand, the patient can review it and ask questions, and not feel put on the spot to remember everything we clinicians tend to say rather quickly toward the end of the visit.—GAIL MARION, PA-C, PhD, Winston-Salem, N.C (188-9) REMOVING OBJECTS FROM THE NOSE To painlessly remove a foreign body from the nose, obtain an infant Foley catheter and apply K-Y Jelly. Insert into the nose beyond the foreign body. Blow up the balloon at the tip and gently pull out. Generally, the balloon will remove the foreign body as the balloon is pulled out.—SALLY KREGER, APRN, Jetmore, Kan. (188-10) n

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Writers’ Guidelines The Clinical Advisor welcomes submissions from its readers. Writing for us is an opportunity to share your knowledge and experience with your colleagues — and to collect a fee in the bargain! We pay an honorarium for every submission we accept.

We’ll be glad to work with you to develop your ideas into compelling articles. As for length, that depends on which kind of article you submit.

CLINICAL FEATURES update our readers on the latest information about conditions seen in everyday practice. Running approximately 2,500 to 5,000 words, including the references, features can be written either as regular narratives or as a series of questions and answers. Topics should be selected with the busy primary-care clinician in mind; specialists should review specialty topics from the primary-care point of view.

If at all possible, articles should be accompanied by clinical photos.

Charts, tables, and algorithms are also encouraged. Please include your title and affiliation.

CLINICAL CHALLENGE is our popular department comprising histories of difficult cases. Each case is presented as a step-by-step, chronological account, revealing the author’s thought processes along the way. It is divided into sections in this order: the patient presentation; the patient history; the twists and turns eventually leading to a diagnosis; the treatment and outcome; and a discussion of the lessons learned or of the condition in general.

The length should be about 1,500 words, and accompanying images are encouraged. Please include your title and affiliation.

DERMATOLOGY CLINIC is a department that presents photos of actual cases and asks readers to identify the condition. Each case opens with one or two color photos and a 75-to-100-word description of the patient presentation, without giving away the diagnosis.

This is followed by a 750-to-1,000-word summary that includes a fuller description of the ailment, an explanation of how the correct diagnosis was reached, a general review of the condition along with a differential diagnosis, and a description of the patient’s treatment and outcome. Topics must be approved by the editor prior to submission. Please include your title and affiliation.

COMMENTARY is our guest editorial page. It gives you the opportunity to sound off on an issue of importance to your colleagues nationwide. A typical Commentary runs about 600 words in length. Please include your title and affiliation.

To discuss your editorial ideas, contact us by phone at 646.638.6078; by e-mail to editor@ClinicalAdvisor.com; or by mail to The Clinical Advisor, 114 West 26th Street, 4th Floor, New York, NY 10001. www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JUNE 2014 97

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Derm Dx

EXCLUSIVE TO THE WEB

INTERACT WITH YOUR PEERS by viewing the images and offering your diagnosis and comments. To post your answer, obtain more clues, or view similar cases, visit CliniAd.com/10KIbCF. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

A darkening, thickening birthmark A patient, aged 4 years, presents with her mother with a chief complaint of a birthmark on the right leg that has darkened and become thicker. The lesion extends from the patient’s proximal medial thigh down to her ankle. The patient has no other abnormal findings.

CAN YOU DIAGNOSE THIS CONDITION?

• Nevus anemicus • Epidermal nevus • Halo nevus • Nevus depigmentosus ● See the full case at CliniAd.com/1kpPU6l

Derm Dx: White patch of skin since infanthood An 8-year-old patient presents for a routine physical exam. His mother notes a white patch of skin that she states has been present since the boy was several weeks old. The patient has an otherwise normal exam.

CAN YOU DIAGNOSE THIS CONDITION?

• Nevus anemicus • Nevus depigmentosus • Epidermal nevus • Halo nevus ● See the full case at CliniAd.com/1h3ZUTD

Have you missed any recent Derm Dx cases? Go to CliniAd.com/10KIbCF for a complete archive of past quizzes as well as additional images of last month’s other cases.

White patch around a mole

Persistent swelling on the elbow

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LEGAL ADVISOR CASE

A mistake or medical malpractice?

BY ANN W. LATNER, JD

Mistakes by health-care practitioners happen every day, despite the best of intentions. But does a mistake always rise to the level of medical malpractice?

This month’s case examines that question.

Ms. P, aged 35 years, was a nurse practitioner employed in the emergency department of a hospital. She had been working there for the past two years and she enjoyed the fast-paced atmosphere. Ms. P’s first job had been in a small family practice, but after about a decade, she found the work to be a bit too repetitive and tedious. She certainly never had that issue in the emergency department. As a rule, Ms. P liked the varied cases and found the work interesting and challenging. Some days, however, were more challenging than others. This particular day was one of them.

Ms. P and her husband, a paramedic, had three children, all younger than age 7 years. On one particular day, two of them were sick with a stomach virus and home from school, and Ms. P was dealing with the logistics of arranging child care until her shift was over. She would have taken the day off, but with three young

© THINKSTOCK

A case against a clinician raises the question of whether the error constitutes malpractice.

Two of the medications were to be given via IV, and the third, epinephrine, was to be given subcutaneously.

children, she had already used the bulk of her leave, and her husband had to work as well.

Ms. P was tempted to feel sorry for herself, but there was never any time for that. Instead, she straightened her spine, asked her mother to watch the children for the rest of the day, and began looking at the charts of the new patients flowing steadily into the emergency department.

One of the patients was 58-year-old Mrs. Z. She had come in suffering from an allergic reaction to acetaminophen with codeine, which had been prescribed by her dentist for pain following a dental procedure. Mrs. Z had already been seen by the emergency department physician, Dr. L. The physician ordered that three medications be administered to the patient—two to be given intravenously, and the third, epinephrine (Adrenaclick, Adrenalin Chloride Solution, EpiPen, Twinject), to be Cases presented are based on actual occurrences.

Names of participants and details have been changed.

Cases are informational only; no specific legal advice is intended. Persons pictured are not the actual individuals mentioned in the article.

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LEGAL ADVISOR given subcutaneously. Ms. P prepared the medications, but accidently put the epinephrine in the IV as well.

The patient sat up immediately, put her hands on her chest, and said her heart was palpitating. She became pale, nauseated, and anxious. Recognizing that the patient was experiencing the side effects of epinephrine much faster than expected, Ms. P felt her heart sink as she realized her mistake. She immediately notified the physician.

“I’m so sorry Dr. L,” said Ms. P. “I made a mistake and put the epinephrine in the patient’s IV rather than administering it subcutaneously. Mrs. Z is having anxiety and palpitations and is nauseous.”

The physician examined the patient and had her transferred to the intensive care unit (ICU). The rest of the day passed as a miserable blur to Ms. P. She spoke candidly to the hospital administrators and risk management team, and filled out all the necessary reports before her shift ended and she went home.

Dr. L spoke to the patient about the erroneous administration of the epinephrine and explained to her that she’d have to stay at the hospital for observation. Hospital administrators and risk managers met with Mrs. Z and her family during her stay and also acknowledged that an error had been made.

The administrators reassured Mrs. Z that everything would be taken care of, that she would be seen by the best physicians they had, and that they were very sorry for her discomfort.

Mrs. Z was discharged from the hospital within a week, but she continued to complain about ongoing symptoms and serious medical conditions allegedly caused by the IV administration of epinephrine. She returned to the hospital’s emergency department six times post-discharge. On the first visit, the attending physician conducted a full assessment but found no physical abnormalities. On the second visit, Mrs. Z underwent a variety of cardiac and neurologic tests, all of which came back negative. After four additional visits to the emergency department, Mrs. Z’s physicians still could not discover any physical problems other than an unrelated kidney infection.

Despite this, Mrs. Z sued the hospital for $5.7 million, alleging anoxic brain damage, cardiac damage, thoracic outlet syndrome, headaches, depression, anxiety, cognitive defects, and pain in the neck, shoulder, and back, all supposedly caused by the intravenous administration of epinephrine by Ms. P. Ms. P was notified of the lawsuit and felt terrible that her error had caused such problems, but the hospital administrators were kind about it and pointed out that until then, her record had been impeccable. The hospital’s lawyers began gearing up for a trial. The discovery process was long and slow, with numerous medical records being subpoenaed and medical experts being retained.

From the beginning, the hospital’s lawyers and administrators agreed that they should admit that the error took place and that Ms. P’s actions had fallen below the standard of care.

The attorneys filed a formal stipulation in court, admitting the error, but clearly stating that the patient had not sustained actual damages. Since liability had already been admitted, the only issue to go to the jury was whether Mrs. Z had injuries, and whether those injuries had been caused by Ms. P’s error.

On the issue of causation, the hospital introduced a parade of experts, including but not limited to a neurologist, a neuropsychologist, and a cardiologist, to testify that the patient had suffered no permanent harm from the administration of the epinephrine. Other evidence introduced by the hospital’s attorneys showed that Mrs. Z had seen physicians for anxiety, chest pain, headaches, and neck and shoulder pain for years before Ms. P’s error occurred. The plaintiff introduced her own experts to try to prove that she had sustained injury.

The judge asked the jury to decide the answer to one simple question before it reached the question of amount of damages: Did the hospital’s breach of the standard of care cause the plaintiff’s injuries? The jury’s response to that question was, “No,” and the jury awarded no damages to Mrs. Z. Legal background

Four essential elements need to be proven for a medical malpractice case to be successful: 1) the existence of a legal duty of care on the part of the health-care provider, 2) a breach of this duty, 3) a causal relationship between the breach of the duty and injury to the patient, and 4) the existence of damages from the injury. Without these four elements, a malpractice case will fail.

In this case, Ms. P had a legal duty to her patient, and she did breach that duty by executing an action that fell below the standard of care required by the profession. However, the plaintiff was unable to prove causation—that is, that Ms. P’s breach caused the injuries in question. The case therefore failed.

Protecting yourself

Mistakes happen, but how one responds to them is very important. Ms. P took responsibility, sought help immediately, and cooperated fully with the risk management team and the hospital’s administrators. One word of caution: Before making any statements to a patient, find out whether your state has an “apology law,” which allows clinicians to apologize or express sympathy to a patient without fear that such actions will be used as evidence in court. n Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

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Stat Consult

A quick review of common conditions, using the best global evidence

FDA-approved indications for estrogen

Hormone replacement therapy (HRT)

• Treatment of moderate to severe vasomotor symptoms (for example, hot flashes) associated with menopause • Treatment of moderate to severe symptoms of vulvar and vaginal atrophy (dryness, irritation) associated with menopause (if only indication, consider topical vaginal products) • Prevention of postmenopausal osteoporosis (if only indication, carefully consider nonestrogen treatments).

BY ALAN DRABKIN, MD

United States Preventive Services Task Force (USPSTF) recommendations

Dr. Drabkin is a clinical editor for DynaMed (www.ebscohost.com/ dynamed), a database of comprehensive updated summaries covering more than 3,200 clinical topics, and assistant clinical professor of population medicine at Harvard Medical School.

• Routine use of combined estrogen and progestin is not recommended for prevention of chronic conditions in postmenopausal women.

• Routine use of estrogen alone is not recommended for prevention of chronic conditions in postmenopausal women who have had a hysterectomy.

© CAROLYN A. MCKEONE / SCIENCE SOURCE

Benefits of HRT

• Estrogen proven to alleviate menopausal symptoms • HRT shown to prevent bone loss (increase bone mineral density) and may prevent osteoporotic fractures ——risks of long-term use may outweigh benefits ——HRT reduced ■■ hip fractures ■■ vertebral fractures ■■ osteoporotic fractures ■■ HRT reduced colorectal cancer risk.

Risks of HRT

The risks of longterm use of HRT may outweigh the benefits.

• No differences in overall mortality or quality of life • Increased risk of ——endometrial cancer (if estrogens used without progestins) ——breast cancer ——venous thromboembolism ——gallstones and gallbladder disease

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• Possible increased risk for ——cardiovascular disease ——ovarian cancer ——worsening of urinary incontinence Key evidence

• Long-term hormone replacement therapy increases risk of coronary events, venous thromboembolism, stroke, breast cancer, and death due to lung cancer in postmenopausal women (Cochrane Database Syst Rev. 2012;7:CD004143; published online July 11, 2012).

• Women’s Health Initiative (WHI) trial ( JAMA. 2002:288[3]:321-333; available at jama.jamanetwork. com/article.aspx?articleid=195120, accessed May 15, 2014) ——long-term use of HRT has more risks than benefits in healthy postmenopausal women ——no clinically meaningful effect on health-related quality of life ——may increase risk of ovarian cancer ——Three years after halt of WHI trial, HRT associated with higher rates of cancer but not cardiovascular disease ——HRT may increase risk of mortality from lung cancer.

——Vasomotor symptoms may worsen after stopping estrogen therapy.

——HRT associated with increased risk of breast cancer at 11 years ——Estrogen with or without progesterone may not have overall benefits at 13 years.

• WISDOM trial (BMJ. 2007;335[7613]:239; available at http://www.bmj.com/content/335/7613/239, accessed May 15, 2014) ——HRT increases risk of cardiovascular disease and venous thromboembolism in older postmenopausal women.

• Heart and Estrogen/Progestin Replacement Study (HERS) trial ( JAMA. 2002;288[1]:49-57; available at ht t ps://ja ma.ja manet work.com /ar t icle. aspx?articleid=195079, accessed May 15, 2014, and JAMA. 2002;288[1]:58-64; available at https://jama.jamanetwork.com/article.aspx?articleid=195080, accessed May 15, 2014) ——HRT only improves quality of life in symptomatic postmenopausal women; otherwise worsens quality of life.

Contraindications

• Unexplained abnormal vaginal bleeding • Active liver disease

• Pregnancy • Estrogen-dependent carcinoma (unless palliative use) • Breast cancer • Precautions include hypertriglyceridemia, cardiovascular disease, hepatic dysfunction, renal insufficiency, asthma, epilepsy, migraine, depression, gallbladder disease, bone disease with hypercalcemia, diabetes, hypertension • Consider waiting 3-12 months if fibroids or endometriosis • Thromboembolic disease ——Relative contraindications include active thrombophlebitis, or history of thrombophlebitis associated with estrogen replacement therapy (ERT).

——Consider discontinuation during immobilization, or at least 4 weeks before surgery.

• Endometrial cancer • Discontinue if hypertension or jaundice occurs.

Side effects

• Vaginal bleeding • Breast tenderness, breast swelling, mastodynia • Nausea, vomiting, abdominal cramps • Fluid retention, edema, bloating • Headache, migraine, dizziness • Depression • Increased size of uterine fibroids • Changes in libido, chloasma, hair loss, hirsutism • No sustained adverse effect on weight • Intolerance to contact lenses • Estrogen use may be associated with Raynaud phenomenon.

HRT and effect on other conditions

• May increase risk of dementia • Estrogen can increase size of uterine fibroids.

• Increased risk of hepatic tumors • Increased risk of systemic lupus erythematosus (SLE) in women • May increase risk of disease flares ——acute intermittent porphyria (AIP) attacks ——dry eye syndrome ——new diagnosis of asthma ——decline in kidney function ——gastroesophageal reflux disease (GERD) ——Postmenopausal estradiol may be associated with increased risk for meningioma.

——effect on cognitive function controversial ——may decrease risk of Alzheimer disease.

• No effect on frequency of urinary tract infections.

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Stat Consult HRT alternatives

• Depending on reasons for HRT, alternatives to HRT may include ——phytoestrogens ——black cohosh ——tibolone ——raloxifene (Evista) ——selective serotonin reuptake inhibitors (SSRIs) • DHEA supplements cannot yet be recommended.

• “Bioidentical hormones” (plant-derived hormones prepared by pharmacist) ——American College of Obstetricians and Gynecologists (ACOG) committee opinion on compounded bioidentical menopausal hormone therapy ■■ conventional hormone therapy preferred over compounded hormone therapy ■■ insufficient evidence to support superiority claims of compounded bioidentical hormones over conventional menopausal hormone therapy »»FDA warns claims of ‘bioidentical hormone replacement therapy’ safety and effectiveness are unsupported by medical evidence and are considered false and misleading.

• Increases bone mineral density, lowers total and lowdensity lipoprotein (LDL) cholesterol • Does not stimulate endometrium • Does not affect cognitive function.

DHEA supplements

• Associated with limited benefit on most postmenopausal symptoms • Appears similar to HRT for increased sexual function and improved menopausal symptoms in postmenopausal women.

• Not associated with adverse endometrial effects or changes in blood lipids or insulin sensitivity.

Effects of discontinuing HRT

• Discontinuation is associated with recurrence or onset of menopausal symptoms.

• Change in quality of life following HRT discontinuation may vary with age.

• Discontinuation after myocardial infarction (MI) does not appear to increase or decrease risk of reinfarction or mortality at 1 year. n

Phytoestrogens

• Consensus opinion from the North American Menopause Society suggests that evidence regarding isoflavones is conflicting and inadequate; women are advised to consume whole foods containing isoflavones for potential cardiovascular benefits.

• Active ingredient unknown • Not a phytoestrogen and may have selective estrogenic action • Most-studied product is isopropanolic extract of black cohosh, known as Remifemin • Widely advocated for treatment of menopausal symptoms ——usual dose of black cohosh 20 mg (1 tablet) twice daily if using Remifemin ——70%-80% response rates reported but insufficient evidence to determine efficacy relative to placebo • Concern for hepatotoxicity • Should not be confused with blue cohosh (a hepatotoxic herb).

Raloxifene

• Does not improve hot flashes or vaginal bleeding • Reduces risk of breast cancer and vertebral fracture, but increases risk of fatal stroke and venous thromboembolism

© The New Yorker Collection 2014 from cartoonbank.com. All Rights Reserved.

Black cohosh

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d

CME CE

n LEARNING OBJECTIVES

For Dermatology Clinic

• To examine various skin pathologies • To apply increased knowledge of dermatologic conditions • To formulate diagnostic procedures and protocols for specific dermatologic conditions n COMPLETE THE POSTTEST: Page 114

DERMATOLOGY COURSES

n ADDITIONAL CME/CE CREDIT: Page 84

This activity is provided by Haymarket Medical Education (HME) in ­collaboration with Medical Education Resources (MER).

Release Date: June 2014 Expiration Date: June 2015 Estimated time to complete the educational activity: 30 minutes Statement of Need: Undertraining in dermatology for primary-care providers is a common phenomenon. Thus, primary-care clinicians need additional educational outlets devoted to the diagnosis and treatment of specific dermatologic conditions. For clinicians out of training, CME becomes the most accessible route.

Target Audience: This activity has been designed to meet the educational needs of primary-care clinicians who treat patients with various dermatologic conditions.

Faculty Kaitlyn Powell, fourth-year medical student Virginia Commonwealth University, Richmond Erin Reese, MD, assistant professor of dermatology Virginia Commonwealth University, Richmond

reported, or used in a CME/CE activity conforms to the generally accepted standards of experimental design, data collection, and analysis. HME is committed to providing its learners with high-quality CME/CE activities that promote improvements in health care and not those of a commercial interest.

Faculty Disclosures The faculty reported the following financial relationships with commercial interests whose products or services may be related to the content of this CME activity:

Name of faculty

Financial Relationship

Kaitlyn Powell

No relevant financial relationships

Erin Reese, MD

No relevant financial relationships

Audrey Chan, MD

No relevant financial relationships

Tiffany L. Shih, MD

No relevant financial relationships

Audrey Chan, MD, third-year dermatology resident Baylor College of Medicine, Houston

Staff/Planners’ Disclosures The planners and managers for this program reported the following financial relationships with commercial interests whose products or services may be related to the content of this CME activity:

Tiffany L. Shih, MD, resident physician University of Minnesota, Minneapolis

HME planners and managers have no relevant financial relationships to disclose.

Accreditation Statements

MER planners and managers, and Veronda Smith, BC-FNP, have no relevant financial relationships to disclose.

Physician Credit: HME is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation: HME designates this educational activity for a maximum of 0.5 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nursing Credit: MER is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

Credit Designation: This CE activity provides 0.5 contact hour of continuing nursing education.

MER is a provider of continuing nursing education by the California Board of Nursing Registered Nursing, Provider #CEP 12299, for 0.5 contact hour.

American Academy of Physician Assistants (AAPA) The AAPA accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME or a recognized state medical society. Physician assistants may receive a maximum of 0.5 hour of Category I credit for completing this program.

Disclosure Policy In accordance with the ACCME Standards for Commercial Support, HME requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest.

HME resolves all conflicts of interest in an effort to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.

Furthermore, HME seeks to verify that all scientific research referred to,

0614_CME derm disclosure page.indd 82

Method of Participation: There are no fees for participating in and receiving CME/CE credit for this activity. During the period of June 2014 through June 2015, participants must: 1) read the learning objectives and faculty disclosures; 2) study the educational activity; 3) complete the posttest and submit it online (clinicians may register at www.myCME.com); and 4) complete the evaluation form online.

A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed posttest with a score of 70% or better.

Disclaimer: The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of HME or MER. The authors have disclosed if there is any discussion of published and/or investigational uses of agents that are not indicated by the FDA in their presentations. The opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of HME or MER. Before prescribing any medicine, primary references and full prescribing information should be consulted. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The information presented in this activity is not meant to serve as a guideline for patient management.

6/6/14 3:15 PM

CME Dermatology Clinic CE CASE #1

Annular eruption on the lower leg KAITLYN POWELL AND ERIN REESE, MD

An otherwise healthy 38-year-old woman presented to the dermatology clinic with a several-month history of a slightly itchy, expanding rash on the lower leg. Treatment with a topical corticosteroid when the rash first appeared helped the itch but seemed to make the rash slightly worse. Treatment with a topical antifungal several weeks before presentation was also unsuccessful. Examination revealed erythematous pustules and few deeper-seated nodules on the left lower leg in an annular configuration.

What is your diagnosis? Turn to page 108.

CASE #2

Scaly plaques after onychomycosis therapy AUDREY CHAN, MD

A Caucasian male, aged 67 years, presented to the dermatology clinic.

Some years earlier, he had used terbinafine for onychomycosis for 3 months; several months later, erythematous annular scaly plaques developed on the sun-exposed scalp, chest, back, and extensor arms.

A review of systems was negative for arthritis, seizures, and psychosis.

Serologies were notable for positive Ro and La antibodies. A skin biopsy was notable for mild vacuolar interface change, a sparse superficial perivascular infiltrate, and dermal mucin. The patient’s previous dermatologist had initiated hydroxychloroquine therapy, with resolution of the skin lesions. The patient asked to continue on hydroxychloroquine for maintenance therapy.

What is your diagnosis? Turn to page 109.

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n LEARNING OBJECTIVES: • To examine various skin pathologies • To apply increased knowledge of dermatologic conditions • To formulate diagnostic procedures and protocols for specific dermatologic conditions.

n COMPLETE THE POSTTEST: Page 114 n ADDITIONAL CME/CE CREDIT: Page 84 Turn to page 105 for additional information on this month’s CME/CE courses.

CASE #3

Crateriform nodule on a cyclist TIFFANY L. SHIH, MD

A 59-year-old Caucasian female presented to clinic with a crateriform nodule on the posterior right calf. She stated that it first appeared as a small, pimple-like lesion and grew rapidly over three weeks. It was currently approximately 1 cm in diameter. The patient reported being an avid biker and spending several hours daily riding in biker shorts with both her calves exposed. She denied any pain, tenderness, or bleeding, but she did note that the lesion had developed a keratotic core at the center.

What is your diagnosis? Turn to page 111.

CASE #4

Enduring eruption of papules on the chest AUDREY CHAN, MD

An 8-year-old African-American female presented to dermatology with an eruption on the chest. The mother reported that it had been present for several years. The patient denied pruritus and a review of systems was negative for fever, chills, and weight loss. Personal and family history was negative for steatocystomas, nail dystrophy, and leukoplakia. Social history was noncontributory. The patient was on no medications. Physical exam was notable for numerous hyperkeratotic, follicularly based papules of 2 mm to 3 mm on the anterior chest. There were no soft, mobile, yellow subcutaneous nodules on the chest. No dystrophic nails or white oral plaques were seen.

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CME CE

CASE #1

Dermatology Clinic

Majocchi granuloma

The patientâ&#x20AC;&#x2122;s diagnosis was con f ir med by per for ming a potassium hydroxide preparation of the affected skin, which revealed fungal hyphae. Of note, if this test had been done while the patient had been using the topical antifungal or shortly thereafter, it may have yielded a false-negative result. Given the clinical appearance with deeper-seated lesions, the presence of fungal elements on the potassium hydroxide preparation, and the lack of response to topical antifungals, the patient was diagnosed with Majocchi granuloma, a cutaneous infection caused by dermatophytosis of the hair follicle.

The condition was first described in 1883 by Domenico Majocchi, who named it granuloma tricofitico to indicate the causative organism at the time, Trichophyton tonsurans, and the granulomatous inflammatory infiltrate seen in association with the hair follicle.1,2 Two forms of Majocchi granuloma exist. The first is a superficial variant consisting of asymptomatic papules and pustules. It is most common in immunocompetent patients, particularly women who frequently shave their legs. The act of hair removal disrupts the follicular anatomy, making it susceptible to infection and subsequent occlusion.2 The second type of Majocchi granuloma is clinically characterized by tender, deeper-seated plaques and nodules. It is most common in immunocompromised patients. As organisms proliferate, follicular rupture may occur, causing introduction of fungal elements into the dermis and occasional abscess formation.3,4 Skin lesions of Majocchi granuloma are generally asymptomatic. The typical appearance is that of erythematous papules, pustules, or nodules, arranged in an annular configuration. If a patient has recently used a topical emollient, steroid, or antifungal, scales may be absent. The lower extremity is the body site most commonly affected

by Majocchi granuloma, but other areas of involvement may include the scalp, face, forearms, inguinal creases, and genitals.5,6 Without treatment, the rash persists and can lead to scarring.2,7 The rash often begins as classic tinea corporis (ringworm), with an annular, erythematous plaque with scale at the border. Over time, if the infection persists or is left untreated,

the fungus may infiltrate more deeply into the hair follicle with a resulting alteration in clinical appearance.

Having a chronic superficial fungal infection of the skin or nails predisposes patients to the development of Majocchi granuloma. If a topical steroid is then applied to this infection, there can be an increase in the number of fungal hyphae on the skin.5,8 In addition, increased heat, moisture, and use of topical preparations can occlude the hair follicle, creating an ideal environment for the fungus to proliferate.2,9 Immunosuppression (either iatrogenic or due to underlying medical conditions) is also a risk factor for development of Majocchi granuloma.3,10,11 The most common dermatophyte cultured from lesions of Majocchi granuloma is Trichophyton rubrum. Other reported causative species include T. mentagrophytes, T. tonsurans, T. verrucosum, Microsporum canis, and Epidermophyton floccosum.

The most common dermatophyte that is cultured from lesions of Majocchi granuloma is Trichophyton rubrum.

Trauma to the skin is usually the inciting event that allows keratin to be introduced into the dermis, thus providing a substrate for dermatophytes.2,5 As the inflammatory reaction to the keratin and the dermatophyte (both of which are seen as foreign material within the dermis) occurs, cellular destruction and amounts of stromal acid mucopolysaccharide increase. The acidic environment then creates a more hospitable medium for hyphae growth.10 Macrophages also play a key role in dermatophyte destruction, but corticosteroids inhibit the ability of the macrophages to perform this role.2 The diagnosis can often be made by scraping the affected skin onto a glass slide, adding potassium hydroxide, gently heating, and examining under a microscope. This simple bedside test will reveal fungal hyphae, but sometimes the hyphae do not appear in their usual forms.10 When this test is inconclusive or negative, obtaining a tissue specimen for biopsy or tissue culture is indicated. Histopathologic examination of an early lesion shows suppurative folliculitis. Over time, later lesions demonstrate perifollicular granulomatous inflammation and dermal abscesses.7 Frequently, there is an infiltrate of eosinophils, histiocytes, keratin, and foreign body giant cells.7,12 Alopecia may also be apparent. Fungal elements are highlighted with Periodic Acid-Schiff (PAS) and Gomori methenamine silver (GMS) staining.2,10,11

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While the appearance of Majocchi granuloma is fairly characteristic, other entities may mimic its clinical presentation. The differential diagnosis is discussed herein: Acne vulgaris tends to preferentially affect the face, and patients will also have comedones. Bacterial folliculitis can present on any hair-bearing surface, and usually consists of follicularbased pustules. Doing a culture of the purulent material is helpful. For the deeper variant of Majocchi granuloma, lesions may look like erythema nodosum, an inflammatory condition of the subcutaneous fat occurring on the anterior shins. Erythema nodosum occurs as a reaction either to a medication or to another systemic condition and consists of tender subcutaneous nodules. Cutaneous sarcoidosis can present in a number of different ways, but lesions are usually smooth, violaceous, sometimes annular plaques that are often seen on the face but can occur anywhere on the body. It is seen more commonly in African-American patients, and the lungs are the most commonly involved extracutaneous site. If the diagnosis is unclear, a biopsy should be done.

Most cases of Majocchi granuloma fail to respond to topical antifungal therapy due to poor penetration into the deeper portions of the follicular unit.6 For this reason, systemic antifungals are usually required for a duration of at least 4 to 8 weeks, with most lesions resolving within 6 weeks.2 In immunocompromised patients, longer treatment courses may be necessary.

Our patient was treated with oral terbinafine for 4 weeks and showed rapid improvement without residual scarring.

The patient had experienced no recurrence after 1 year.

Ms. Powell is a fourth-year medical student at Virginia Commonwealth University in Richmond, Virginia. Dr. Reese is an assistant professor of dermatology at Virginia Commonwealth University.

References 1. Saadat P, Kappel S, Young S, et al. Aspergillus fumigatus Majocchi’s granuloma in a patient with acquired immunodeficiency syndrome. Clin Exp Dermatol. 2008;33(4):450-453.

2. Ilkit M, Durdu M, Karakas M. Majocchi’s granuloma: a symptom complex caused by fungal pathogens. Med Mycol. 2012;50(5):449-457.

3. Gupta S, Kumar B, Radotra BD, Rai R. Majocchi’s granuloma trichophyticum in an immunocompromised patient. Int J Dermatol. 2000;39(2):140-141.

4. Gill M, Sachdeva B, Gill PS, et al. Majocchi’s granuloma of the face in an immunocompetent patient. J Dermatol. 2007;34(10):702-704.

5. Bae BG, Kim HJ, Ryu DJ, et al. Majocchi granuloma caused by Microsporum canis as tinea incognito. Mycoses. 2011;54(4):361-362.

6. Cho HR, Lee MH, Haw CR. Majocchi’s granuloma of the scrotum.

Mycoses. 2007;50(6):520-522.

7. Arenas R, Toussaint S, Isa-Isa R. Kerion and dermatophytic granuloma.

Mycological and histopathological findings in 19 children with inflammatory tinea capitis of the scalp. Int J Dermatol. 2006;45(3):215-219.

8. Elgart ML. Tinea incognito: an update on majocchi granuloma. Dermatol Clin. 1996;14(1):51-55.

9. Hazelrigg DE, Williams TE, Rudolph AH. Nodular granulomatous perifolliculitis. JAMA. 1975;233(3):270-271.

10. Smith KJ, Neafie RC, Skelton HG 3rd, et al. Majocchi’s granuloma.

J Cutan Pathol. 1991;18(1):28-35.

11. Tateishi Y, Sato H, Akiyama M, et al. Severe generalized deep dermatophytosis due to Trichophyton rubrum (trichophytic granuloma) in a patient with atopic dermatitis. Arch Dermatol. 2004;140(5):624-625.

12. Grossman ME, Pappert AS, Garzon MC, Silvers DN. Invasive Trichophyton rubrum infection in the immunocompromised host: report of three cases. J Am Acad Dermatol. 1995;33(2 Pt 1):315-318.

CASE #2

Drug-induced SCLE

Subacute cutaneous lupus erythematosus (SCLE) was f irst described in 1979 by Sontheimer, Thomas, and Gilliam.1 SCLE tends to be less inflammatory and longerlasting than acute cutaneous lupus erythematosus (ACLE).

In contrast, SCLE tends to resolve more quickly than chronic cutaneous lupus (discoid lupus erythematosus [DLE], lupus erythematosus tumidus, lupus panniculitis, and chilblain lupus).2 SCLE most commonly affects Caucasian females, with a peak incidence between the ages of 15 and 40 years.1 Drug-induced SCLE also affects more females than males at a ratio of 6:1.3 The pathogenesis of cutaneous lupus is not well understood, but is likely related to a genetic predisposition triggered by environmental factors including ultraviolet radiation (UVR); medications; and, possibly, viruses.2 Genetic factors increasing risk of SCLE include human leukocyte antigen (HLA)-DR3 positivity and C2 and C4 deficiencies.1,2 Recently, genes previously associated with SLE, such as TYK2, IRF5, and CTLA4, have also been shown to increase the risk of both SCLE and DLE.2

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Common medication causes of SCLE can be remembered by the mnemonic “HoT DANG”: hydrochlorothiazide, terbinafine, diltiazem (and other calcium channel blockers), angiotensin converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and griseofulvin. Of these medications, hydrochlorothiazide is the most frequent cause of drug-induced SCLE.1 Rarely, antihistamines and anticonvulsants have also been reported to cause SCLE.1,2 As of 2008, 27 cases of terbinafine-induced SCLE have been reported.3

It is hard to blame definitively a drug for SCLE unless SCLE resolves when the drug is stopped and recurs upon re-exposure.

Terbinafine, a synthetic oral allylamine, is the first-line treatment for onychomycosis. In general, terbinafine is a safe medication; the most common adverse effects include headache, gastrointestinal symptoms, and dermatologic manifestations. In terbinafine-induced SCLE, skin lesions appeared on average 7 weeks after the start of treatment with the medication.3 Clinically, SCLE can present with one of two morphologies: polycyclic or papulosquamous.1,2 In the polycyclic variant, lesions are annular with raised red borders and central clearing.2 The papulosquamous variant can present with either an eczematous or psoriasiform appearance. Lesions are often pink but can be red or violaceous.1 The lesions are covered with a thin scale that is easily detached.1 Telangiectasias may be noted.1 Because there is no follicular involvement, lesions do not resolve with scar but can leave dyspigmentation, most commonly hypopigmentation or depigmentation.1,2 The most common locations of involvement are the sun-exposed areas including the neck, extensor arms, and upper chest and back. While the sides of the face are often affected, the mid-facial skin is characteristically spared.2 Approximately 50% of patients will report photosensitivity.1 In terms of extracutaneous manifestations, about 75% of patients report arthralgias or arthritis, 20% are noted to have leukopenia, and 10% to 15% of patients will have evidence of systemic lupus erythematosus (SLE).1 In addition, 20% of SCLE patients also may have lesions of DLE.1 SCLE can also be associated with Sjogren syndrome, which is not surprising given the fact that both diseases have antiRo antibodies.2

The diagnoses of SCLE and drug-induced SCLE are made clinically and with the presence of antibodies against Ro/ SSA. A skin biopsy is typically performed, as histopathologic findings can be helpful. Vacuolar interface dermatitis is found in nearly all active skin lesions; however, in older lesions this finding may be subtle.1 Mild hyperkeratosis and parakeratosis may be seen.1 There is usually a relatively sparse, superficial perivascular infiltrate comprised mostly of lymphocytes.2 Direct immunofluorescence (DIF) is positive in only one-third of cases, so when SCLE is highly suspected, skin biopsies are not usually sent for DIF studies. In terbinafine-induced SCLE, antibodies against Ro/ SSA are present in 86% of patients, anti-nuclear antibodies (ANA) in 79%, and antibodies against La/SSB in 39%.3 While most cases of drug-induced SLE are positive for anti-histone antibodies, in drug-induced SCLE only 29% of patients will be positive.3 The differential diagnosis of SCLE includes psoriasis, tinea corporis, photolichenoid drug eruption, dermatitis (atopic, contact, and photocontact), and pemphigus foliaceus.2 The majority of these entities lack the vacuolar interface change on histology. The presence of anti-Ro antibodies is highly suggestive of SCLE. Although a drug can be suspected of causing SCLE, unless the SCLE resolves with discontinuation of therapy and recurs upon re-exposure to the same medication, it is difficult to blame definitively a particular medication for having caused SCLE. However, if a patient receives a diagnosis of SCLE, it is prudent to discuss with the patient’s other providers the possibility of switching medications that are common culprits of drug-induced SCLE to acceptable alternatives.

After the suspected drug is discontinued, the treatment of drug-induced SCLE is the same as for native SCLE. Sun protection, sun avoidance, and topical corticosteroids should be initiated in minimally symptomatic patients and patients with minimal skin involvement. For patients with significant skin involvement, hydroxychloroquine is the gold-standard systemic treatment of SCLE. Typically, patients are started at hydroxychloroquine 200 mg PO twice a day. It can take 2 to 3 months for any improvement to be noted.2 When skin lesions have resolved, decreasing the dose by about 25% every 3 to 6 months is recommended.4 Some patients may relapse after discontinuation of therapy, in which case a weekly dose of hydroxychloroquine 100-200 mg PO may be necessary to maintain clearance.4 All patients require a baseline complete ophthalmologic exam prior to or soon after initiation of hydroxychloroquine; for patients taking

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hydroxychloroquine longer than 5 years, an annual eye exam is recommended while on the medication because of the potential for antimalarial eye toxicity.4 The most common adverse effects of hydroxychloroquine therapy include gastrointestinal symptoms and blue-gray dyschromia that affects the shins, face, palate, and nail beds. Most references recommend that a complete blood cell count and comprehensive metabolic panel be checked every 3 to 6 months. It is imperative to insist that patients who smoke cigarettes see their primary-care provider for smoking-cessation help, as there is evidence to suggest smoking decreases the efficacy of hydroxychloroquine therapy.

Because our patient had been clear for years on hydroxychloroquine 200 mg twice daily, a tapering regimen was initiated several months ago, with no recurrence or flare to date.

Dr. Chan is a third-year dermatology resident at Baylor College of Medicine in Houston.

References

They then enter a stationary phase for another 2 to 6 weeks. Finally, they enter a stage in which they spontaneously involute and form an atrophic, depressed scar. The length of each of these stages can be quite variable, and an estimated 5% of keratoacanthomas do recur.2 There are also documented cases of deeper invasion. Therefore, keratoacanthomas are routinely treated as squamous cell carcinoma and are excised.1,2 Keratoacanthomas are thought to be strongly associated with sun-exposed areas such as the head, neck, and extremities, with or without pain or tenderness. Elderly fair-skinned individuals are most likely to develop these lesions. Dorsal hands in men and lower legs in women are the most common sites. Often, subungual keratoacanthomas do not regress spontaneously and can cause early underlying bone destruction.1,2 Diagnosis can often be made based on clinical presentation, but it is reasonable to perform an excisional biopsy to obtain a histologic diagnosis for confirmation. On histopathology, the lesion will appear quite similar to a

1. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2011:158-160.

2. Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 3rd ed. St. Louis, Mo.: Elsevier-Mosby; 2008:Chap. 41.

3. Lorentz K, Booken N, Goerdt S, Goebeler M. Subacute cutaneous lupus erythematosus induced by terbinafine: case report and review of litera-

Most keratoacanthomas span about 5 mm to 15 mm in diameter, but they can become as large as 25 mm.

ture. J Dtsch Dermatol Ges. 2008;6(10):823-828.

4. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 3rd ed.

Philadelphia, Pa.: Saunders Elsevier; 2012:98-119,241- 251.

CASE #3

Keratoacanthoma

Keratoacanthomas are often considered a variant of squamous cell carcinoma. There are some who consider these lesions benign tumors, or pseudomalignancies.1 They typically present as a solitary, rapidly enlarging papule that erupts into a sharply wellcircumscribed crateriform nodule with a central keratotic core in 3 to 8 weeks. Most keratoacanthomas span about 5 mm to 15 mm in diameter, but can become as large as 25 mm. Interestingly, these lesions exhibit rapid growth for the first 2 to 6 weeks.

low-grade squamous cell carcinoma. The crateriform lesion contains an eosinophilic keratin core flanked by acanthotic epithelium. The keratinocytes in the epidermis frequently have a pink, glassy cytoplasm with often a dense inflammatory infiltrate. Keratoacanthomas characteristically show terminal differentiation where peripheral edges of the tumor lose their infiltrative features, leaving a thin rim of keratinizing cells.2 Differential diagnoses include invasive, more aggressive squamous cell carcinoma; verrucous carcinoma; cutaneous horn; prurigo nodularis; merkel cell carcinoma; and metastatic carcinoma of the skin. These lesions typically do not exhibit the triphasic history as seen in keratoacanthomas.

However, all these diagnoses can present clinically and morphologically similar to a keratoacanthoma, and therefore all suspicious lesions should be biopsied for a definitive diagnosis. Multiple keratoacanthomas or sudden eruption of keratoacanthomas represents cause for concern about the possible presence of such conditions as Muir-Torr Syndrome, keratoacanthoma centrifugum marginatum, Ferguson Smith

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type multiple self-healing keratoacanthomas, or generalized eruptive keratoacanthomas (Grzybowski variant).1,2 Although keratoacanthomas resolve spontaneously, it is difficult to predict how long this would take. These lesions can also cause destruction of surrounding tissue for up to a year. Therefore, it is generally accepted that these lesions be removed surgically. If there are concerns regarding loss of function or cosmetically sensitive areas, nonsurgical treatment can also be considered—for example, intralesional therapies such as 5-fluorouracil solution, bleomycin, or methotrexate.

Low-dose methotrexate has also been offered if multiple lesions are present. Radiation therapy may also be used in cases of giant keratoacanthoma if surgical excision is not feasible.2 This patient was treated with excisional biopsy followed by primary intention closure. The specimen was sent to pathology to ensure that the margins were clear. It is important to exclude the diagnosis of a more aggressive squamous cell carcinoma.

Dr. Shih is a resident physician at the University of Minnesota in Minneapolis.

References 1.Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, Pa.: Saunders Elsevier; 2012:1771, 1781-1784.

2.James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2011:631-633.

CASE #4

Eruptive vellus hair cysts

Eruptive vellus hair cysts, first described by Esterly, Fretzin, and Pinkus in 1977,1 have been reported most commonly in children and young adults.2 The average age of diagnosis is age 24 years, with 90% of cases diagnosed in persons younger than age 35 years.2 Males and females 2 are equally affected. No racial or ethnic predilection has been observed.2 The pathogenesis of eruptive vellus hair cysts is unknown.

Although its occurrence is typically sporadic, familial cases of eruptive vellus hair cysts have been described.2 Familial eruptive vellus hair cysts are inherited in an autosomal

dominant fashion, but no underlying mutation has been identified to date.2 Eruptive vellus hair cysts are characteristically seen in the setting of steatocystoma multiplex and pachyonychia congenita. Steatocystoma multiplex is an autosomal dominant disorder caused by KRT17 mutations encoding keratin 17, expressed in the nail bed, hair follicles, and sebaceous glands.3 Pachyonychia congenita is also an autosomal dominant genodermatosis, historically classified into pachyonychia congenita types 1 and 2. According to this old classification

The most common locations of eruptive vellus hair cysts are the anterior chest and the central abdomen. system, eruptive vellus hair cysts occur more commonly in pachyonychia congenita type 2 with mutations in KRT6B and KRT17, encoding keratin 6B and keratin 17, respectively.

Eruptive vellus hair cysts present with the sudden onset of many small (1 mm to 7 mm) dome-shaped papules of variable color.3 The papules often are skin-colored but also can be darkly pigmented.3 Individual papules are follicularly based.2 Eruptive vellus hair cysts tend to be symmetric and generalized.2 The lesions usually are not grouped.4 The most common locations are the anterior chest and central abdomen.3,4 Less common locations include the upper and lower extremities, face, neck, posterior trunk, and/or buttocks.4 The pinna of the ear may be affected, but this is rare.

Eruptive vellus hair cysts on the face can be hyperpigmented and reportedly have been misdiagnosed as a nevus of Ota.4 Lesions are usually asymptomatic, but may occasionally become inflamed and subsequently pruritic. Rarely, only a solitary lesion may be present. These lesions typically persist indefinitely.3 On rare occasions, some lesions may resolve through transepidermal elimination of the cyst products.3 Cyst contents may be induced by pressure as well.2 Eruptive vellus hair cysts developing in later adulthood have been reported in the setting of chronic renal failure.5 The diagnosis of eruptive vellus hair cysts is often made on clinical grounds alone. However, when the diagnosis is in question, a skin biopsy is diagnostic. Histopathologic examination reveals a small cystic structure in the dermis, lined by stratified squamous epithelium.3 The lining shows epithelial keratinization with a granular layer.2,3 The cyst contents include loose laminated keratin and numerous

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vellus hairs.3 A less commonly used diagnostic technique is the application of a topical anesthetic, followed by a tiny incision at the top of the suspected vellus hair cyst to express the contents. The contents are then microscopically examined for the presence of vellus hairs.4 Syndromes that are associated with eruptive vellus hair cysts include steatocystoma multiplex and pachyonychia congenita type 2. In steatocystoma multiplex, multiple steatocystomas with eruptive vellus hair cysts are the hallmark of this genodermatosis. Steatocystomas present as soft subcutaneous nodules, measuring from a few millimeters to a centimeter in diameter.3 The most common locations are the chest, forearms, axillae, and groin.3 If punctured, the steatocystomas drain an oily fluid.3 Steatocystomas are usually asymptomatic and tend to persist indefinitely.3 Pachyonychia congenita type 2 (PC2) is characterized by distinctive “omega nails” caused by wedge-shaped nail-bed thickening with elevation of the nail plate, nonpremalignant oral leukokeratosis, and variable palmoplantar keratoderma in addition to steatocystomas and eruptive vellus hair cysts. Other clinical features of PC2 include follicular keratoses, natal/prenatal teeth, and pili torti or other hair abnormalities.3

The diagnosis of eruptive vellus hair cysts is often made on clinical grounds alone, but a skin biopsy is diagnostic.

Eruptive vellus hair cysts have rarely been described in the settings of hidrotic ectodermal dysplasia (Clouston syndrome), hypohidrotic ectodermal dysplasia (ChristSiemens-Touraine syndrome), and Lowe syndrome (oculocerebrorenal syndrome).5 Hidrotic ectodermal dysplasia presents with diffuse palmoplantar keratoderma, hypotrichosis, and nail dystrophy. Patients with hypohidrotic ectodermal dysplasia are easily recognized by their facial features (saddle nose, full everted lips, frontal bossing, and periorbital wrinkling), peg-shaped teeth, hypohidrosis, and sparse hair. Lowe syndrome is characterized by renal failure (renal Fanconi syndrome), mental retardation, and eye abnormalities (most commonly, bilateral congenital cataracts). Patients with Lowe syndrome also are noted to have small bone structure, often secondary to hypophosphatemic rickets in the setting of renal failure, and poor dentition. Eruptive vellus hair cysts have been reported

in the literature only once in a 20-year-old patient with Lowe syndrome.6 The differential diagnosis of eruptive vellus hair cysts includes milia, molluscum contagiosum, syringomas, folliculitis, and keratosis pilaris.4 Milia are white, dome-shaped papules most commonly located on the face. Molluscum contagiosum are often grouped and commonly have an umbilicated center, unlike the discrete lesions of eruptive vellus hair cysts that are often hyperkeratotic. Syringomas are firm, skin-colored papules. They are most characteristically seen on the periorbital area, but can be seen on the upper trunk. Syringomas are typically larger than eruptive vellus hair cysts and have no associated hyperkeratosis. Although folliculitis is common on the chest, it is notable for pustules, which are not seen in eruptive vellus hair cysts. Although individual lesions of keratosis pilaris are similar to those of eruptive vellus hair cysts, keratosis pilaris is predominantly located on the lateral proximal upper and lower extremities. A biopsy will definitively differentiate all of these entities from eruptive vellus hair cysts.

If lesions are asymptomatic and not cosmetically bothersome, no treatment is necessary or recommended. For patients desiring treatment, “incision of individual cysts and expression of their contents followed by gentle curettage, light electrodesiccation with expression of contents, therapy with topical vitamin A acid (tretinoin), lactic acid (12% lotion) or laser” have been reported.4 Tazarotene 0.1% cream has also been reported to lead to clinical improvement.5 Our patient was asymptomatic and unconcerned by the appearance of her eruptive vellus hair cysts, so reassurance was provided and no treatment was initiated. n Dr. Chan is a third-year dermatology resident at Baylor College of Medicine in Houston.

References 1. Esterly NB, Fretzin DF, Pinkus H. Eruptive vellus hair cysts. Arch Dermatol. 1977;113(4):500-503.

2. Patel U, Terushkin V, Fischer M, et al. Eruptive vellus hair cysts.

Dermatol Online J. 2012;18(12):7. Available at http://escholarship.org/uc/ item/0dz2b51s; accessed May 15, 2014.

3. Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 3rd ed. St. Louis, Mo.: Elsevier-Mosby; 2008:Chap. 111.

4. Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology. 4th ed.

Philadelphia, Pa.: Saunders Elsevier; 2011:154.

5. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin. 11th ed.

Philadelphia, Pa.: Saunders Elsevier; 2011:671.

6. Nandedkar MA, Minus H, Nandedkar MA. Eruptive vellus hair cysts in a patient with Lowe syndrome. Pediatr Dermatol. 2004;21(1):54-57.

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CME CE

POSTTEST Expiration date: June 2015

Physician Credit: Haymarket Medical Education (HME) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation: HME designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

American Academy of Physician Assistants (AAPA): The AAPA accepts certificates of participation for educational activities certified for AMA PRA Category 1 Credit™ from organizations accredited by ACCME or a recognized state medical society. Physician assistants may receive a maximum of 0.5 hour of Category 1 credit for completing this program.

Nursing Credit: MER is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

Credit Designation: This CE activity provides 0.5 contact hour of continuing nursing education.

MER is a provider of continuing nursing education by the California Board of Nursing Registered Nursing, Provider #CEP 12299, for 0.5 contact hour.

CREDITS: 0.5

Dermatology Clinic page 106

Case #1: Majocchi granuloma

Case #3: Keratoacanthoma

1. What is a risk factor for Majocchi granuloma? a. Exposure to animals b. Peripheral vascular disease c. Immunosuppression d. Stasis dermatitis

5. What is the most common site of keratoacanthoma in women? a. Back b. Head and neck c. Dorsal hands d. Lower legs

2. What systemic medication is used in the treatment of Majocchi granuloma? a. Tetracycline b. Terbinafine c. Prednisone d. Methotrexate Case #2: Drug-induced subacute cutaneous lupus erythematosus (SCLE) 3. Which of the following is the most common extracutaneous manifestation associated with SCLE? a. Arthralgias b. Leukopenia c. Thyroiditis d. Lymphoma

4. What should patients who have SCLE and significant skin involvement receive? a. Cyclophosphamide b. Hydroxychloroquine c. Azathioprine d. Doxycycline

6. What is a treatment for multiple keratoacanthomas? a. Radiation therapy b. Cryotherapy c. Low-dose methotrexate d. Intralesional 5-fluorouracil Case #4: Eruptive vellus hair cysts 7. Eruptive vellus hair cysts present as a. Many small, dome-shaped papules of variable color b. Small, grouped vesicles that coalesce to form plaques c. Flesh-colored, waxy umbilicated papules d. Violaceous papules with fine white lines on the surface 8. In contrast to eruptive vellus hair cysts, the presence of firm, skin-colored papules seen on the periorbital area characterizes a. Milia b. Molluscum contagiosum c. Keratosis pilaris d. Syringoma

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Global Education Group (Global) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education to physicians. Global Education Group designates this live activity for a minimum of 32.0 AMA PRA Category 1 Credit(s) TM. This activity will be approved for continuing pharmacy, psychology, nurse practitioner, nursing and dentistry education. Applications for certification of social work NASW and family physician AAFP hours will be applied for. For more information and complete CME/CE accreditation details, visit our website at www.painweek.org.

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FEATURE: MOST COMMON SKIN CANCERS

Persons who present with early SCC lesions and who receive adequate treatment have a 5-year survival rate of greater than 90%.

Continued from page 83

Summary

are often rough or scaly macules or plaques of pink, tan, or brown color. These lesions often wax and wane but rarely resolve on their own. AKs can be diagnosed clinically and treated, but because a clinical diagnosis can be wrong, patients should be followed for complete resolution of a treated AK. A lesion identified as an AK that does not resolve may in fact be an SCC. A more definitive way to differentiate between an AK and SCC would be to biopsy the lesion.

Once an AK is diagnosed, treatment options include liquid nitrogen cryotherapy, photodynamic therapy, and topical prescription chemotherapy. Patients using topical prescription chemotherapeutic agents such as topical 5-fluorouracil, imiquimod cream, and ingenol mebutate (Picato) can expect to experience irritation, redness, swelling, and scabbing of the skin during cutaneous treatment of AK. However, ingenol mebutate and other new topical agents require as few as 3 days of application, compared with up to 12 weeks of application required by some older medications, and the skin normally returns to baseline (the AK resolves, as does any inflammation or crusting) in 14 to 21 days. Correctly identifying AK is important in terms of preventing SCC, which can have much more devastating treatment and life-expectancy outcomes.

Treatment. Uncomplicated, solitary, small lesions caught early can be treated with ED&C. However, excision or Mohs surgery excision are the more commonly used treatments due to the potentially aggressive nature of SCC. Chemotherapy or radiation therapy may be used adjunctively or for patients who are not surgical candidates.

Persons who present with early SCC lesions and who receive adequate treatment have a 5-year survival rate of greater than 90%. Conversely, patients with advanced SCC tumors with lymph node involvement have a dramatically lower 5-year survival rate, of 25% to 45%.8 Long-term follow-up. Persons with SCC should be counseled similarly to persons with BCC in terms of using sun protection, taking other steps to prevent recurrence, and undergoing skin examinations. Persons with SCC also should undergo regional lymph node examinations.7 Clinicians should be aware that like persons with a history of BCC, persons with a history of SCC are at increased risk for cutaneous melanoma.7 Both groups of patients also should be counseled to avoid the carcinogenic exposure of tanning beds: Utilizing indoor tanning devices more than doubles an individual’s risk of developing SCC.8

Primary-care clinicians are in a unique and critical position of being able to flag patients with risk factors for BCC and/or SCC. These providers also often can identify clinically abnormal lesions that require a biopsy and a subsequent treatment plan. There are two common themes when talking about BCC and SCC: Early detection is key, and prevention is essential. n Ms. Jacobson is a physician assistant practicing in dermatology at Delaware Valley Dermatology Group in Wilmington, Delaware, and at Dermatology and Skin Surgery Center of York in York, Pennsylvania.

References 1. American Cancer Society. Skin cancer. Available at www.cancer.org/ cancer/skincancer/index.

2. Bader RS. Basal cell carcinoma. Medscape. Updated March 27, 2014.

Available at emedicine.medscape.com/article/276624-overview.

3. National Institutes of Health National Library of Medicine. Fluorouracil topical. MedlinePlus website. Available at www.nlm.nih.gov/medlineplus/ druginfo/meds/a605010.html.

4. Love WE, Bernhard JD, Bordeaux JS. Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review. Arch Dermatol. 2009;145(12):1431-1438.

5. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-2179.

Available at www.nejm.org/doi/full/10.1056/NEJMoa1113713#t=articleTop. 6. Levi F, Randimbison L, Maspoli M, et al. High incidence of second basal cell skin cancers. Int J Cancer. 2006;119(6):1505-1507. Available at onlinelibrary.wiley.com/doi/10.1002/ijc.22000/pdf.

7. National Comprehensive Cancer Network, Inc. Guidelines Version 2.2014: Basal Cell and Squamous Cell Skin Cancers. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). 2014; p. MS-3.

8. Monroe MM. Cutaneous squamous cell carcinoma. Medscape.

Updated April 7, 2014. Available at emedicine.medscape.com/ article/1965430-overview.

9. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol.

1992;26(6):976-990.

10. Cook BE Jr, Bartley GB. Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmsted County, Minnesota. Ophthalmology. 1999;106(4):746-750.

All electronic documents accessed May 15, 2014.

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Clinical Challenge Numbness, tingling, weakness, and coolness in a “jammed” hand MATTHEW PRICE, MS, RN, CNP, ONP-C, RNFA

A man tells the orthopedics clinic staff about odd sensations in his hand a week after a car accident.

Raised arm ­interrupts subclavian artery blood flow.

© PHANIE / SCIENCE SOURCE

­

Blood flow is normal when arm is lowered.

Mr. P, aged 31 years, is a right-hand-dominant male who was a restrained driver in a motor-vehicle accident that occurred approximately 1 week prior to his presentation to the orthopedic clinic for follow-up. The patient stated that during the accident he “jammed” his left ring finger and also forcibly jammed his left hand and wrist into the steering wheel. Mr. P denied hitting his head or losing consciousness.

Since the time of the accident Mr. P had experienced nearly constant numbness and tingling in his hand, which was exacerbated by forward elevation of his shoulder (elevation of the arm) to approximately 90 degrees. He also complained of decreased grip strength as well as intermittent coolness and blanching in his left hand.

Mr. P denied Reynaud disease, carpal tunnel syndrome, or any other significant medical or surgical history. He was employed as a local truck driver and denied a history of repetitive motion injury or use of vibratory tools or equipment. His symptoms were not exacerbated by sneezing, coughing, or straining, and he said he had no nausea, headache, or visual disturbances. All other review of systems was unremarkable. Mr. P did have a 10-pack-year history of smoking, and consumed alcohol socially.

He denied illicit drug use.

CASE #1

1. PHYSICAL EXAM, X-RAYS No significant erythema, edema, or ecchymosis was appreciated about the left upper extremity compared with the contralateral side. A superficial abrasion was located centrally on the volar aspect of the left wrist. Grip strength was possibly weaker on the left side than on the right side. The patient demonstrated full active range of motion in all metacarpophalangeal and interphalangeal joints as well as in his wrist, elbow, and shoulder without discomfort—no symptoms of impingement were elicited with active or passive shoulder range of motion. No significant pain was elicited with deep palpation about the hand, wrist, elbow, or shoulder.

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Clinical Challenge Mr. P had a 2+ radial pulse on his left, with sluggish capillary refill in his distal extremity, compared with the contralateral side. Additionally, the left hand was cooler to the touch compared with the contralateral side. The radial, median, ulnar, and axillary nerves had motor function grossly intact. The patient did report numbness and tingling with light palpation, affecting his index through small fingers, with an increase in these symptoms in the ulnar distribution. This finding was exacerbated by forward elevation of the shoulder to 90 degrees and above, particularly throughout the ring and small fingers. Sensation was intact and normal through the thumb. Tinel’s sign of the median nerve was negative, as were Phalen’s test and Spurling’s test.

Radiographs of Mr. P’s left hand and wrist did not reveal any osseous injury. Furthermore, normal alignment of all carpals, metacarpals, and phalanges was appreciated (Figure 1).

No imaging of the proximal extremity was obtained initially.

2. DIAGNOSIS Given the patient’s symptoms, mechanism of injury, and physical-examination findings of an abrasion over the volar wrist, an initial differential diagnosis was acute carpal tunnel syndrome. Any trauma about the wrist can result in swelling, which, in turn, can lead to compression of the median nerve within the flexor retinaculum (carpal tunnel). Carpal tunnel syndrome did not, however, account for the fact that only a portion of the median nerve sensory distribution was affected, or the fact that the patient’s neurologic symptoms were exacerbated by the elevation of his arm at the shoulder. As a result, pathology of more proximal neurological structures needed to be considered.

A clinical diagnosis of thoracic outlet syndrome (TOS) was made based on Mr. P’s symptoms and physical-examination findings. While a multitude of imaging studies and provocative maneuvers can aid in the diagnosis of TOS, many of these have low diagnostic sensitivity and specificity and/or are associated with significant costs. By forming a working diagnosis of TOS based on history and physical-examination findings, we were able to try conservative, low-cost, and noninvasive therapies before moving on to more complex diagnostics and diagnoses.

3. TREATMENT Several types of TOS have been identified and are described in the Discussion section at right. Mr. P had symptoms consistent with neurologic TOS (NTOS), which has been managed conservatively for the 11 months since diagnosis—no invasive

FIGURE 1. Radiograph of patient’s left hand/wrist showed no osseous injury and normal alignment of all carpals, metacarpals, and phalanges.

tests or procedures have been employed to date. The patient is obese (BMI 36) with very broad shoulders and the tendency toward poor posture, often sitting with his shoulders hunched over. He was instructed to work on improving his posture by sitting and standing with his shoulders more rolled back.

Mr. P also was enrolled in an occupational-therapy program to help him improve his posture through stretching exercises and strengthening of the trapezius muscles and neck muscles.

This conservative treatment regimen is intended to open up the area surrounding the brachial plexus in the hopes of subsequently relieving pressure on the nerves and vessels.

If a patient displays continued paresthesia or progressing atrophy of the distal upper extremity, an electromyogram and/or an interscalene block would be indicated to further evaluate any of these long-term deficits and aid in surgical planning (i.e., decompression of the brachial plexus), if needed.1-3

4. DISCUSSION The thoracic outlet is the anatomic space formed by the first rib, the clavicle, and the scalene and pectoralis minor muscles. Major neurovascular structures traverse this space, including the brachial plexus and the subclavian artery and vein.2 TOS results from compression of the brachial plexus and/or subclavian vessels as they pass from the cervical spine, through the thoracic outlet, toward the proximal arm.4,5 This compression can cause a multitude of neurologic and vascular symptoms capable of affecting all levels of the upper extremity.

Three major types of TOS have been described: venous, arterial, and neurologic, with venous and arterial often

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grouped together as “vascular”.6 Vascular TOS often manifests symptoms of pain, pallor, paresthesia, diminished pulses and capillary refill, and swelling of the extremity related to venous congestion. Comparatively, NTOS also may be associated with pain, paresthesia, weakness, and altered sensation, although secondary to compression of proximal neurologic structures.

NTOS has often been qualified as either “true” or “disputed.”

The use of these terms arose as a result of a limitation of tests to diagnose NTOS accurately as well as inconsistent patient presentation in which some, but not all, of the accepted “true” NTOS symptoms/diagnostic criteria were exhibited. Illig et al. have noted that this verbiage has now become passé in the face of a better understanding of NTOS etiology and pathophysiology.7 In general, however, many clinicians—including this author—continue to find the terms “true” and “disputed” useful descriptors of the patient’s condition and diagnosis.

The term “true NTOS” is typically applied when specific examination criteria are met and after electromyography studies and other anatomic evidence have confirmed the diagnosis.

While not the gold standard for diagnosis, some studies support the use of scalene muscle injections to confirm NTOS diagnoses.1,8,9 Conversely, disputed NTOS is an effective and descriptive terminology that allows for understanding of the patient’s disease etiology and related symptoms without the use of expensive and uncomfortable confirmatory tests and other elaborate clinical workups.2 Overall incidence of TOS has been hard to estimate as the condition is often associated with vague patient symptomatology and poor diagnostic and radiographic confirmation. Nevertheless, NTOS is considered the most prevalent variant of TOS, accounting for an estimated 90% to 97% of all cases.2,3,7 Typical etiology of NTOS is hyperextension of the neck, commonly a whiplash-type injury from a motor-vehicle accident. NTOS symptoms can also result from work-related injuries, particularly those involving repetitive movements of the upper extremities.3,7 Other factors that predispose a person to TOS include the presence of cervical ribs, anomalous first ribs, and congenital narrowing of scalene triangles.7 Taken by themselves, provocative maneuvers during the physical examination for TOS typically are not reliable diagnostic tools: Most tests have been shown to have low sensitivity and specificity.2,3 The Adson test is perhaps the oldest and best-known maneuver for eliciting detectable physical-examination findings in NTOS.3 Adson was the first to describe TOS—then called scalene anticus syndrome—as well as his provocative maneuver for eliciting related symptoms.10 In the Adson test the examiner palpates the patient’s radial pulse. The patient’s arm is then externally rotated and

extended, and the neck is rotated and extended toward the test arm while the patient takes a deep breath. This exercise is intended to demonstrate compression of the interscalene space by showing a diminished or absent radial pulse. Other provocative maneuvers are also designed to elicit symptoms through exacerbation of compression about the brachial plexus. Again, because of the poor reliability of these tests, many authors recommend that the findings are considered in conjunction with history, physical examination, and other imaging and diagnostic testing to guide diagnosis.2 Ancillary testing, including radiographic imaging and electrodiagnostic studies, can also be important in the diagnosis of TOS. Historically, despite subjective symptomatology, the diagnosis of “classic” NTOS was made only when objective findings were present, specifically: a) a complete cervical or anomalous first rib; and b) electrodiagnostic changes in ulnar nerve conduction.3 There are now promising new tests for evaluating NTOS, including computed tomography (CT) and magnetic resonance (MR) imaging. While relatively new, studies using MR neurography have also demonstrated clinical significance in the diagnosis of NTOS.11 Treatment for TOS is varied and can range from watchful waiting and conservative measures to interscalene blocks and surgical intervention. For the patient described here, the condition was managed conservatively with occupational therapy and rehabilitative exercises to promote proper posture; as noted in the Treatment section (page 118), this approach had been successful for approximately 11 months to date. For patients who fail conservative therapies, interscalene injections with botulinum toxin type A (Botox) have brought at least temporary relief in some cases of NTOS.12 Surgery continues to be a controversial last option for management of TOS. In cases of acute arterial compromise, emergent surgery is warranted.13 Other options for brachial plexus decompression, particularly in NTOS cases, have shown varying levels of efficacy, but one study did report a 94% success rate with surgical decompression in patients who had previously benefited from interscalene injections.14

5. CONCLUSION Thoracic outlet syndrome can be debilitating for the patient and confusing for the clinician. This is true not just in terms of the physical manifestations of the diagnosis, but also because of the vagueness of the etiology, diagnostic criteria, and treatment options associated with TOS. A thorough history and physical examination are the cornerstones in forming a differential diagnosis. Whereas conservative

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Clinical Challenge measures are often effective in addressing symptoms of acute TOS, surgical intervention may be indicated for chronic and/or limb-threatening issues. n Mr. Price is the manager of Orthopedic Advanced Practice Providers at Riverside Methodist Hospital, Columbus, Ohio.

Unusual use of radiation therapy for pelvic pain

References

PAM ZIMMERMAN, MSN, FNP-C, OCN

1. Benzon HT, Rodes ME, Chekka K, et al. Scalene muscle injec-

A woman suffers cyclic pain after multiple abdominal and pelvic surgeries.

tions for neurogenic thoracic outlet syndrome: case series. Pain Pract.

2012;12(1):66-70.

2. Ozoa G, Alves D, Fish DE. Thoracic outlet syndrome. Phys Med Rehabil Clin N Am. 2011;22(3):473-483.

3. Sanders RJ, Hammond SL, Rao NM. Thoracic outlet syndrome: a review. Neurologist. 2008;14(6):365-373.

4. Huang JH, Zager EL. Thoracic outlet syndrome. Neurosurgery.

2004;55(4):897-903.

5. Sanders RJ, Hammond SL, Rao NM. Diagnosis of thoracic outlet syndrome. J Vasc Surg. 2007;46(3):601-604. Available at www.jvascsurg. org/article/S0741-5214(07)00734-3/pdf.

6. Thompson JF. Thoracic outlet syndrome. Surgery (Oxford).

2013;31(5):256-260.

7. Illig KA, Thompson RW, Freischlag JA, et al., eds. Thoracic Outlet Syndrome. London, United Kingdom: Springer-Verlag; 2013: xi, 26-27.

8. Jordan SE, Ahn SS, Gelabert HA. Combining ultrasonography and electromyography for botulinum chemodenervation treatment of thoracic outlet syndrome: comparison with fluoroscopy and electromyography guidance. Pain Physician. 2007;10(4):541-546. Available at www. painphysicianjournal.com/2007/july/2007;10;541-546.pdf.

9. Torriani M, Gupta R, Donahue DM. Sonographically guided anesthetic injection of anterior scalene muscle for investigation of neurogenic thoracic outlet syndrome. Skeletal Radiol. 2009;38(11):1083-1087.

10. Adson AW. Surgical treatment for symptoms produced by cervical ribs 11. Filler AG, Maravilla KR, Tsuruda JS. MR neurography and muscle MR imaging for image diagnosis of disorders affecting the peripheral nerves and musculature. Neurol Clin. 2004;22(3):643-682.

12. Jordan SE, Ahn SS, Freischlag JA, et al. Selective botulinum chemo­ denervation of the scalene muscles for treatment of neurogenic thoracic outlet syndrome. Ann Vasc Surg. 2000;14(4):365-369.

13. Kenny RA, Traynor GB, Withington D, Keegan DJ. Thoracic outlet syndrome: a useful exercise treatment option. Am J Surg. 1993;165(2):282-284.

14. Jamieson WG, Chinnick B. Thoracic outlet syndrome: fact or fancy?

A review of 409 consecutive patients who underwent operation.

Can J Surg. 1996;39(4):321-326. Available at canjsurg.ca/wp-content/ uploads/2014/03/39-4-321.pdf.

All electronic documents accessed May 15, 2014.

A patient who will be referred to as Ms. L in this case study was 34 years old when she presented to the emergency department in January 2012 with severe pain in the right lower quadrant that radiated to her back. She also reported a feeling of pressure when voiding but no dysuria, urinary frequency, or hematuria. Ms. L denied melena and diarrhea. She also denied fevers, chills, and night sweats. She rated the pain as 10/10 in severity.

On further questioning, the patient described the pain as cyclic in nature, occurring every 4 to 6 weeks over the previous 18 months. Although she was taking oxycodone hydrochloride with acetaminophen 10 mg every 4 hours, the pain persisted, prompting her visit to the emergency department.

CASE #2

© THINKSTOCK

and the scalenus anticus muscle. Surg Gynecol Obstet. 1947;85(6):687-700.

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1. HISTORY Ms. L was gravida 3, para 3. She had a history of multiple abdominal and pelvic surgeries, including Cesarean sections in 2002, 2005, and 2008, and an endometrial ablation and dilation and curettage (D&C) in 2008. She underwent a hysterectomy in 2009 due to abnormal uterine bleeding. A bilateral salpingo-oophorectomy was performed later that year. Ms. L had complications after each of these surgeries, which led to additional surgeries including hernia repair, partial cystectomy, adhesiolysis, and a transureterouretero­ stomy due to ureteral strictures and injury. She had chronic urinary tract infections.

Ms. L reported that she had previously been evaluated for her ongoing pain, but because of her many surgeries and subsequent complications, she was advised that additional surgeries were not in her best interest.

FIGURE 1. A lesion in the right lower quadrant was causing the patient cyclic pain.

2. EXAM AND TESTS Initial examination in the emergency department revealed the following: temperature 36.9°C, pulse 98, respirations 18, blood pressure 131/78, oxygen saturation 96% on room air. General: The patient appeared to be in no acute distress. Head: normocephalic, atraumatic. Pupils: PERRLA (pupils equal, round, reactive to light and accommodation). Lungs: clear to auscultation. Heart: regular rate and rhythm without murmur. Abdomen: obese and soft with mild tenderness in the right lower quadrant. No rebound or guarding. Good bowel sounds. Extremities: no edema, clubbing, or cyanosis. Skin: no rash. Neurologic: alert and oriented x 3. Cranial nerves II-VII grossly intact.

Initial testing included laboratory studies: complete blood count, urinalysis, basic metabolic panel (BMP), and liver function tests (LFTs). The laboratory studies showed a normal white count (8.9), hemoglobin (13), normal BMP, and LFTs within normal limits. Urine was negative.

A computed tomography (CT) scan of the abdomen and pelvis without contrast showed a postoperative ureteral diversion, a 4-mm caliceal stone in the lower pole of the right kidney, severe hepatic steatosis, and a 3-cm right ovarian cyst.

3. EVALUATION Based on the information obtained to this point, differential diagnoses could include, but are not limited to, neoplasia, pelvic inflammatory disease, pelvic adhesions, ovarian

FIGURE 2. A similar lesion was later discovered in the patient’s left lower quadrant as well.

remnant syndrome, and endometriosis.

A gynecologic consultation was ordered for further evaluation of the patient’s pain and the nonspecific right adnexal tissue. Previous pathology showed no evidence of endometriosis. It was suspected that the right-lowerquadrant pain and the cyst seen on imaging were likely due to a right ovarian remnant. To further help identify this right-lower-quadrant lesion as being hormone-related, a 3-month trial of a luteinizing hormone-releasing hormone (LHRH) agonist, leuprolide (Eligard, Lupron), was initiated

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Clinical Challenge to suppress ovarian function. If the pain were to dissipate during the course of therapy, it would be reasonable to attribute the pain to an ovarian remnant.

Leuprolide was to be administered in three 30-mg doses, with each dose delivered 4 weeks apart. After the first 8 weeks of leuprolide therapy, the patient reported that she was no longer experiencing any right-sided abdominal pain.

However, she did experience significant side effects from the leuprolide including hot flashes, nausea, and anxiety.

Therefore, the third injection of leuprolide was not given.

The absence of pain with leuprolide therapy further confirmed the suspicion that the right-lower-quadrant lesion was a functional ovarian remnant (Figure 1).

4. TREATMENT Due to the small but nonetheless valid risk of ovarian remnants containing malignant cells, the surgical approach by laparotomy or laparoscopy is the primary treatment option.1 However, this patient was deemed to be a high-risk surgical candidate as a result of her previous multiple and difficult surgeries. Therefore, a noninvasive approach to treatment was recommended.

Ms. L was referred for a meeting with a radiation oncologist to discuss radiation therapy in this setting. The radiation oncologist recommended that Ms. L receive a course of external beam radiation therapy to the right ovarian remnant, with the goal of therapy being to stop ovarian function.

Ms. L received external beam radiation of 200 centigray (cGy) units in 10 fractions over 10 treatment days, for a total of 2,000 cGy. The radiation was delivered using a threedimensional (3D) conformal technique and was completed in May 2012. The patient experienced no adverse effects from radiation and completed all planned treatments with resolution of her right-lower-abdominal pain.

5. FURTHER SYMPTOMS, TREATMENT Ms. L did well until 6 months later, when she developed pain in the left lower quadrant similar to the previous right-sided pain. She returned for further evaluation, bringing with her copies of a CT scan of the abdomen and pelvis performed with contrast in November 2012. The imaging revealed a diffuse fatty infiltration of the liver, cholecystectomy clips, a small calculus within the lower pole of the right kidney, postoperative changes within the pelvis, and a left ovarian cyst of 2.3 cm. The right ovary was not identified. The patient’s previous hysterectomy

FIGURE 3. The same radiation treatment regimen was used for the left-sided lesion as had been used for the right-sided lesion.

was identified, as were changes to the anterior abdominal wall. The right ureter appeared to cross the midline. The distal ureters were not well seen.

A transvaginal and pelvic ultrasound was performed to help identify the ovarian cyst seen on the CT scan. The ultrasound revealed a hypoechoic solid structure in the left adnexa measuring 4.0 × 1.5 × 2.7 cm. On previous scans, the structure had measured 3.0 × 1.5 × 2.3 cm. There was minimal vascular flow in this lesion, with no clear cystic structures present within it.

Because of the radiographic similarities between this lesion (Figure 2) and the previous lesion identified as being an ovarian remnant, radiation therapy was again initiated. The same treatment regimen was used for this left-sided lesion as had been used for the right-sided lesion (Figure 3). The treatment was completed in April 2013. The patient tolerated the treatment well, experiencing no acute side effects.

6. OUTCOME Since completing radiation treatment for bilateral ovarian remnants, Ms. L has been followed by a urologist for ongoing issues related to chronic urinary tract infections that predated her radiation treatments. She occasionally takes a short-acting opioid, oxycodone (Roxicodone) for pain associated with those infections. However, she has not experienced any further symptoms related to the ovarian remnants and remains pain-free from that standpoint. She experienced no acute side effects during radiation treatment for the ovarian remnants, and has had no ongoing issues related to that treatment.

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7. DISCUSSION

“I see a huge emerging market for undeath insurance, is what I see.”

“Cute is whatever you can get away with.”

Mrs. Zimmerman is a family nurse practitioner as well as an assistant professor of radiation oncology at Mayo Clinic Arizona in Phoenix.

References 1. Kho RM, Abrao MS. Ovarian remnant syndrome: etiology, diagnosis, treatment and impact of endometriosis. Curr Opin Obstet Gynecol. 2012;24(4):210-214.

2. Magtibay PM, Nyholm JL, Hernandez JL, Podratz KC. Ovarian remnant syndrome. Am J Obstet Gynecol. 2005;193(6): 2062-2066.

3. Dereska NH, Cornella J, Hibner M, Magrina JF: Mucinous adeno­ carcinoma in an ovarian remnant. Int J Gynecol Cancer. 2004;4(4): 683-686.

4. Kho RM, Magrina JF, Magtibay PM. Pathologic findings and outcomes of a minimally invasive approach to ovarian remnant syndrome.

Fertil Steril. 2007;87(5):1005-1009.

“Where once there was one sandwich—now there are two!”

© The New Yorker Collection 2014 from cartoonbank.com. All Rights Reserved.

Ovarian remnant syndrome is a rare condition that occurs when ovarian tissue is left behind after a unilateral or bilateral oophorectomy.2 Incomplete removal of ovarian tissue can cause symptoms of pelvic pain, which is often cyclic in nature.

Other symptoms of ovarian remnant syndrome include dyspareunia, dysuria, and/or pain with urination or defecation. Ovarian remnant syndrome can also present as a pelvic mass, with or without pain.3 Symptoms usually begin within the first 5 years after oophorectomy.1 Evaluation of ovarian remnant syndrome should begin with a detailed medical history, including gynecologic history, previous surgeries, and description of symptoms.

Tests can include lab work to measure levels of folliclestimulating hormone (FSH), which should be very high after bilateral oophorectomy, and estradiol, which should be very low. If these are not the results, functioning ovarian tissue may be present.

CT scans, ultrasounds, and magnetic resonance imaging (MRI) can identify abnormal tissue to help determine the diagnosis.

Surgical excision, radiation therapy, and/or medication are all therapeutic options for ovarian remnants, with surgery being the first-line treatment.4 Radiation therapy for this condition can be delivered in a short amount of time with minimal to no side effects, making it a viable treatment option for women with ovarian remnants who are not good surgical candidates. n

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ALTERNATIVE MEDS UPDATE

What you should know about the herbs and supplements patients use

By Sherril Sego, FNP-C, DNP. Ms. Sego is a staff clinician at the VA Hospital in Kansas City, Mo., where she practices adult medicine and women’s health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas.

Chia seeds

© THINKSTOCK

Most of us have had the dubious pleasure of receiving a Chia Pet as a “gift” at one time or another.

These odd-looking clay figurines grew miraculous thick, green, curly “hair” from hundreds of tiny chia seeds when the clay had been moistened for several days. The seeds stayed moist and sprouted quickly, in large part due to their hydrophilic nature: Chia seeds can absorb and retain up to 27 times their weight in water. For the majority of gift recipients, the fun died quickly, as did the Chia Pet’s hair. There seemed to be no point in trying to maintain the green locks beyond a few days. However, an expanding interest in chia seeds just may have us all trying to grow Chia Pets.

Background

Science

Today’s market for the nutritious chia seed would probably come as absolutely no surprise to the ancient peoples of southern Mexico and Central America. Civilizations such as those of the Aztec and Mayan Indians grew chia as a dietary staple.

Unless otherwise specified, the term “chia” usually refers to the chia species Salvia hispanica.1 S. hispanica is a rapidly growing biennial plant well-suited to arid climates and poor, sandy soil.1 Growing to a height of about 36 inches, the plant flowers in long clusters of deep blue and purple.

The tiny seeds measure no more than 2 mm and are usually brown or black.

One chia plant can produce thousands of seeds. These seeds are composed of up to 40% oil, with the remaining structure high in protein and fiber. In today’s use of chia, it is the oil that is of particular interest.

Nutritionally, chia seed oil is more than 60% alpha-linolenic acid (ALA).2 This makes chia oil one of the highest in composition of this rich omega-3 fatty acid among all oil-bearing seeds.

Research involving both chia seeds and chia oil verified that plasma ALA levels increased up to 91% at 2.5 hours postingestion and stayed elevated for nearly 24 hours.3 The role of omega-3 fatty acids in human health has been debated for many years.

Even though the necessity of these compounds for health and well-being has never been disputed, the optimal recommended amount in daily foods and supplements is not as clear.

Unlike some other oil-bearing seeds, chia seeds do not require grinding for their oils to be released.4 This characteristic makes them a more appealing ingredient in healthfood snacks and cereals. A quarter-cup of chia seeds contains approximately 8 mg of iron and 10 g of fiber. Chia seeds are being studied as a weight-modifying food. In one study

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of 62 overweight women (BMI 25 or higher), the participants were randomized to consume either 25 g/day of chia seeds or placebo for a period of 10 weeks.5 Although plasma ALA levels increased significantly in the chia-seed group, these individuals had no statistically significant weight loss or change in body-fat percentage.

In a different trial, some participants were fed muffins made with chia seeds, while other participants ate chia-free muffins.6 When asked to rate their levels of satiety periodically over the next 90 minutes, persons who consumed the chia seed muffins consistently rated their satiety levels higher than did those who ate the regular muffins.

A different group of researchers evaluated specified dietary patterns abundant in chia seeds and the effect on multiple factors comprising the condition of metabolic syndrome.7 At the end of the 2-month, placebo-controlled trial, all participants had reductions in body weight and waist circumference, but only the dietary study group had decreases in serum triglycerides, C-reactive protein, and glucose levels.

Another very common condition—pruritus in end-stage renal disease (ESRD)—was shown to be successfully managed with chia seed oil in a small study.8 As the investigators noted, an estimated 40% to 80% of persons with ESRD suffer from chronically dry and itchy skin, with typical emollient lotions offering slight relief.

The researchers evaluated five healthy individuals with xerotic pruritus and five persons with ESRD who complained of severe itching due to ESRD or diabetes. Participants used a topical formulation containing 4% chia seed oils daily for 8 weeks and rated their symptom relief according to a standardized scale. The ESRD group reported statistically significant improvement in pruritus and dryness at the end of the trial; the healthy volunteers demonstrated similar improvements. None of the participants suffered any adverse events.

Safety, how supplied

Cost, dose The cost of chia seed products is almost as varied as the range of products. In bulk, chia seeds average about $6 per pound. The appropriate dose of chia products depends on the intent of use. There is no standardized recommended dose, but a typical serving of seeds or ground seed is a quarter-cup.

Summary

Chia seeds are a rich source of the omega-3 fatty acid known as ALA.

Persons who ate the chia seed muffins consistently rated their satiety levels higher than did those who ate regular muffins.

Very seldom does a product with very little downside surface. In the case of chia seeds, there seems to be mostly good news, without any bad news. As long as patients are counseled regarding the always present potential for allergy, chia seed compounds represent a healthy and tasty way to boost beneficial fatty acids and fiber. n References 1. Small E. Blossoming treasures of biodiversity. 34. Chia— not just a pet. Biodiversity. 2011;12(1):49-56. Available at www. tandfonline.com/doi/pdf/10.1080/14888386.2011.575104.

2. Mohd Ali N, Yeap SK, Ho WY, et al. The promising future of chia, Salvia hispanica L. J Biomed Biotechnol. 2012;2012:171956.

Available at www.hindawi.com/journals/bmri/2012/171956.

3. Nieman DC, Gillitt ND, Knab AM, et al. Fatty acid bioavailability study of single oral doses of milled chia seed snack clusters or chia seed oil in healthy subjects. The FASEB Journal. 2013;27:125.5 4. Ho H, Lee AS, Jovanovski E, et al. Effect of whole and ground Salba seeds (Salvia Hispanica L.) on postprandial glycemia in healthy volunteers: a randomized controlled, dose-response trial. Eur J Clin Nutr. 2013;67(7):786-788.

5. Nieman DC, Gillitt N, Jin F, et al. Chia seed supplementation and disease risk factors in overweight women: a metabolomics investigation. J Altern Complement Med. 2012;18(7):700-708.

6. Balakrishnan G. Influence of chia seeds on satiety. Thesis (M.S.)—University of Florida; 2012. Available at ufdc.ufl. edu/UFE0044269/00001 and ufdcimages.uflib.ufl.edu/UF/ E0/04/42/69/00001/BALAKRISHNAN_G.pdf.

7. Muñoz LA, Cobos A, Diaz O, Aguilera JM. Chia seed (Salvia hispanica): an ancient grain and a new functional food. Food Reviews International. 2013;29(4):394-408.

8. Jeong SK, Park HJ, Park BD, Kim IH. Effectiveness of topical chia seed oil on pruritus of end-stage renal disease (ESRD) patients and healthy volunteers. Ann Dermatol.

2010;22(2):143-148. Available at pdf.medrang.co.kr/

© THINKSTOCK

Chia seeds are available in a wide variety of forms, including but not limited to whole seeds, oil, “chia snacks,” chia oil, and chia meal. The seeds are on the FDA’S “generally regarded as safe” (GRAS) listing; however, persons with allergic histories should initially consume these products with caution.

Aod/022/Aod022-02-03.pdf.

All electronic documents accessed May 15, 2014.

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Evidence-Based Medicine This department uses the best available scientific findings to offer practice guidance on a wide range of conditions seen in primary care.The author, Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester. DynaMed (www.ebscohost.com/dynamed/) is a database that provides evidence-based infor-­­ mation on more than 3,000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.The most important evidence identified is summarized here.

PARENT-DELIVERED COGNITIVEBEHAVIORAL THERAPY MAY IMPROVE ANXIETY IN CHILDREN Level 2: Mid-level evidence Anxiety disorders are common in children and can have both immediate and life-long consequences. Cognitive behavioral therapy (CBT) has been shown to be effective for childhood and adolescent anxiety disorders (Cochrane Database Syst Rev. 2013;[6]:CD004690), but access to treatment may be limited. A recent randomized trial evaluated a low-intensity CBT intervention delivered by parents (with guidance from therapists) for children with anxiety disorders in the United Kingdom.

A total of 194 children aged 7-12 years with diagnosed anxiety disorders (generalized anxiety disorder, social phobia, separation anxiety disorder, panic disorder/agoraphobia, and specific phobias) were randomized to 1 of 2 parent-delivered CBT interventions vs. waitlist control for 12 weeks. In the full-guidance CBT group, parents received a self-help book and had 4 face-to-face meetings and 4 telephone calls with therapists (one contact weekly for the first 8 weeks, total therapist time < 5.5 hours) to provide anxiety education, develop graded exposure plan, and review progress. Parents in the brief-guidance CBT group received similar training and feedback from therapists but with a total of 4 sessions every other week. Families in the waitlist control group were asked to hold off on any anxiety interventions for 12 weeks.

At the end of treatment, rates of recovery from the primary anxiety diagnosis were 50% in the full-guidance CBT group and 25% in the waitlist control group (p = 0.013, NNT 4). In the full-guidance group, 34% of children recovered from all anxiety diagnoses compared to 11% of

Recovery rates from the ­primary anxiety diagnosis were 50% in the fullguidance CBT group and 25% in the waitlist control group.

controls (p = 0.006, NNT 5). Recovery rates were higher in the brief-guidance group than in controls, but the differences were not statistically significant. Both full and brief guidance were associated with higher rates of “much or very much improved” status on clinical global impression ratings compared to control. In a follow-up analysis of 49 children from the fullguidance group at 6 months, 76% no longer met the diagnostic criteria for their primary diagnosis.

While the lack of a true attention control condition weakens this trial’s validity, it appears that parent-led CBT may be an effective low-cost first-line approach for treating childhood anxiety disorders before seeking more intensive treatment (Br J Psychiatry. 2013;203[6]:436-444).

WALKING APPEARS TO REDUCE RISK OF CV EVENTS IN PATIENTS WITH IMPAIRED GLUCOSE TOLERANCE AT RISK OF CVD Level 2: Mid-level evidence Lifestyle modifications have been shown to reduce the rate of progression to type 2 diabetes in patients with impaired glucose tolerance (BMJ. 2007;334[7588]:299). In fact, the Diabetes Prevention Program trial demonstrated that lifestyle changes can reduce the incidence of diabetes more effectively than can metformin (N Engl J Med. 2002;346[6]:393403), and a secondary analysis showed that such changes are cost-effective for diabetes prevention across all age groups (Ann Intern The quality of the evidence supporting each item is rated from Level 1 (highest) to Level 3 (lowest). Absolute risk reductions are presented as the number needed to treat (NNT) for one patient to benefit. Absolute risk increases are presented as the number needed to harm (NNH).

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© THINKSTOCK

Med. 2005;142(5):323-332). However, the impact of lifestyle changes on cardiovascular outcomes in patients with impaired glucose metabolism has remained unclear.

Now, a cohort analysis of data from a randomized trial evaluates the association between walking and the risk of cardiovascular events in a patient population at risk of developing cardiovascular disease.

A total of 9,018 individuals with impaired glucose tolerance and increased risk of cardiovascular disease who had been participants in the NAVIGATOR trial were included in the analysis. All patients had existing cardiovascular disease if ≥ 50 years old, or had at least one additional cardiovascular risk factor if ≥ 55 years old. Ambulatory activity was assessed using a pedometer at baseline and again at 12 months.

Overall, 531 patients had a cardiovascular event (defined as a composite of cardiovascular mortality, non-fatal stroke, or myocardial infarction) during 45,211 person-years of follow-up. After 12 months follow-up, researchers found that each increase over baseline in activity by 2,000 steps per day (about 20 minutes of walking at a moderate pace) was associated with a decrease in the risk of cardiovascular events, with a hazard ratio of 0.92 (95% CI 0.86-0.99).

Similarly, a higher baseline activity rate was also associated with decreased risk of cardiovascular events, with a hazard ratio of 0.9 (95% CI 0.84-0.96).

These findings were consistent across additional analyses adjusted for all potential confounders evaluated, including treatment group and changes in body mass index. However, it should be noted that an important limitation of this study is the large proportion of patients for whom some data were missing (25% at baseline and 45% at 12 months).

Adding about 2,000 steps per day may lower the risk for CV events.

Previous studies evaluating interventions in patients with prediabetes have focused only on prevention of a diabetes diagnosis. There has been an absence of more patientoriented outcomes.

This study extends the findings of the previous research by evaluating clinical complications among patients with prediabetes, specifically showing decreased cardiovascular events with increased activity levels. Further, it quantifies the relationship between activity and cardiovascular risk in a way that is easy to communicate to patients (Lancet.

2014;383[9922]:1059-1066).

IN ADULTS WITH UNRUPTURED BRAIN ARTERIOVENOUS MALFORMATION, INTERVENTIONAL THERAPY APPEARS TO WORSEN OUTCOMES COMPARED TO MEDICAL MANAGEMENT Level 2: Mid-level evidence With the increased use of noninvasive neuroimaging, there has been an increase in the detection of brain arteriovenous malformations prior to symptomatic bleeding, but there is currently no clear consensus for the management of these lesions. Patients diagnosed with unruptured or asymptomatic arteriovenous malformations may be managed conservatively or, alternatively, they may be offered interventional therapy with the aim of obliterating the origin of the arteriovenous malformation. Several interventional therapies, including neurosurgery, embolization, and stereotactic radiotherapy have been used successfully in these patients, but there is little clinical evidence to guide the choice of interventional therapy, or to demonstrate its superiority over conservative management. A prospective population-based cohort study in Scotland previously showed that patients receiving interventional therapy for arteriovenous malformation had worse outcomes than those who did not (Lancet Neurol. 2008;7[3]:223-230). Now, a randomized trial compares the addition of interventional therapy to medical management vs. medical management alone in adults with unruptured arteriovenous malformation.

A total of 226 adults (mean age 45 years) with unruptured brain arteriovenous malformation were randomized to medical management alone vs. medical management plus interventional therapy. Patients, clinicians, and investigators were aware of treatment assignment. Medical management consisted of pharmacologic therapy for existing medical disorders (such as seizures or headaches) or any coexisting vascular risk factors (such as diabetes or arterial hypertension), as needed. Patients randomized to interventional therapy additionally received neurosurgery, embolization, or stereotactic radiotherapy, either

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alone or in combination, at the discretion of the local trial investigator. Patients with evidence of recent or prior hemorrhage, or who had received previous interventional therapy for brain arteriovenous malformation, were excluded from the trial. The goal of the interventional therapy was complete eradication of the arteriovenous malformation. The primary outcome was a composite of symptomatic stroke or death.

The trial was stopped early by an independent data and safety monitoring board, due to superiority of medical management alone based on a prespecified stopping value for the primary outcome. The interim analysis included 223 patients (99% of those randomized) with a median follow-up of 33 months.

Symptomatic stroke or death occurred in 10% of those receiving medical management alone vs. 31% of those receiving interventional therapy plus medical management (p < 0.05, NNT 5). The incidence of stroke was 11% with medical management alone vs.

39% with interventional therapy plus medical management (p < 0.0001, NNT 4). In addition, neurologic deficits unrelated to stroke occurred in 0.9% of those treated with medical management alone vs. 12% of those treated with interventional therapy plus medical management (p = 0.0008, NNT 9).

The results of this trial extend previous findings from an observational study, and further support the conclusion that current interventional therapies for unruptured arteriovenous malformations do not improve cerebrovascular outcomes.

However, arteriovenous malformations are associated with a long natural history, and the median follow-up of 33 months included in this trial limits the ability to make conclusions about long-term effectiveness. In addition, by not including patients who had received previous interventional therapy for brain arteriovenous malformation, patients with a more aggressive disease course may have been excluded, and this may therefore limit the generalizability of the findings (Lancet. 2014;383[9917]:614-621).

IN ADULTS WITH MODERATE OR SEVERE COPD WITHOUT BRONCHIECTASIS, CONTINUOUS PROPHYLACTIC ANTIBIOTICS REDUCE EXACERBATIONS BUT AZITHROMYCIN MAY INCREASE RISK OF HEARING LOSS Level 1: Likely reliable evidence Many patients with COPD will experience acute exacerbations, which often occur after respiratory infections. These exacerbations may require additional treatments, and can lead to reduced quality of life and increased risk of hospitalization or mortality.

A recent Cochrane review evaluated the efficacy of prophylactic antibiotics in adults with moderate or severe COPD.

© KALLISTA IMAGES / CUSTOM MEDICAL STOCK PHOTO

Evidence-Based Medicine

Vague pulmonary nodules in this COPD patient suggest pneumonia.

The systematic review identified seven randomized trials comparing prophylactic oral antibiotics to placebo for at least 3 months in 3,170 adults with moderate or severe COPD. All patients were at least 40 years old and had presented with 1 or more exacerbations in the previous year. Trials evaluating patients with bronchiectasis, asthma, or genetic diseases such as cystic fibrosis were excluded. The use of antibiotics was continuous in 5 trials and intermittent or pulsed in the other 2 trials. The antibiotics evaluated included erythromycin, azithromycin, clarithromycin, and moxifloxacin. The primary outcomes for the review were the number of exacerbations and quality of life, assessed with the St. George’s Respiratory Questionnaire (0-100 points, with higher scores indicating worse quality of life).

The duration of follow-up was 6 to 12 months in the analysis of exacerbations and 6 to 18 months for the analyses of quality of life and serious adverse events. In a meta-analysis of 4 trials with 2,411 adults, prophylactic antibiotics were associated with reduced risk of exacerbations (odds ratio 0.64, 95% CI 0.45-0.9), with a number needed to treat (NNT) from 5 to 40, assuming an exacerbation rate of 60% with placebo. A sensitivity analysis showed that the reduction in exacerbations was significant only in trials evaluating continuous antibiotics.

Adverse effects were evaluated in two analyses. Prophylactic antibiotics were associated with an increased incidence of gastrointestinal adverse events in a meta-analysis of 4 trials with 2,408 adults (odds ratio 1.58, 95% CI 1.01-2.47).

In addition, one high-quality trial evaluating prophylactic azithromycin in 1,117 adults showed that azithromycin was associated with an increased risk of hearing impairment (p = 0.04, NNH 20). This trial also evaluated antibiotic susceptibility of selected respiratory pathogens in patients who were

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IN ELDERLY PATIENTS WITH ATRIAL FIBRILLATION RECEIVING DIALYSIS, WARFARIN MAY INCREASE RISK OF BLEEDING WITHOUT DECREASING RISK OF STROKE Level 2: Mid-level evidence Warfarin is widely used for thromboembolic prophylaxis in patients with atrial fibrillation, including patients with chronic kidney disease. A recent randomized trial has shown that adjusted-dose warfarin reduces the risk of ischemic stroke or systemic embolism compared to low-dose warfarin or aspirin in patients with moderate kidney disease (Clin J Am Soc Nephrol. 2011;6[11]:2599-2604). However, the role of warfarin in patients with more advanced kidney disease remains unclear. No randomized trials evaluating warfarin for prevention of cardiovascular outcomes in patients receiving dialysis have been conducted, and observational studies in this population have been conflicting. Now, a new cohort study has evaluated the use of warfarin among elderly patients on dialysis who developed atrial fibrillation.

A total of 1,626 patients aged 65 years or older receiving hemodialysis or peritoneal dialysis prior to hospitalization for atrial fibrillation were retrospectively evaluated for an association between warfarin use and risk of bleeding or stroke. Bleeding events included intracerebral, gastrointestinal, or intraocular bleeding, hematuria, or bleeding at an unspecified location. Stroke events included ischemic stroke, transient ischemic attack, or a retinal infarct. About 46% of patients received warfarin within 30 days of hospital discharge. Comparing the baseline risks for patients receiving warfarin vs. those not receiving warfarin, 84% vs. 86% had a high risk of bleeding (HAS-BLED score ≥ 3) and 77% vs.

69% had a high risk of stroke (CHADS2 score ≥ 2), but p values for these differences were not reported.

In an unadjusted analysis, the rate of bleeding was 10.9 per 100 person-years with warfarin vs. 7.3 per 100 person-years with no warfarin (p < 0.001), with no significant difference in the rate of stroke (3.4 per 100 person-years with warfarin vs. 2.9 per 100 person-years with no warfarin). A separate analysis adjusted for propensity to receive warfarin (with propensity scores based on multiple clinical and demographic factors including baseline risk) had results consistent with those of the unadjusted analysis.

Oral anticoagulation in patients with advanced kidney disease has recently been called into question based on results from several observational studies. Indeed, the routine use of oral anticoagulants in patients with chronic kidney disease requiring dialysis is no longer recommended in guidelines from either Kidney Disease: Improving Global Outcomes (Kidney Int. 2011; 80[6]:572-586) or the Canadian Cardiovascular Society (Can J Cardiol. 2012;28[2]:125-136).

The findings from this latest observational study support these updated guidelines, and suggest that warfarin may increase the risk of bleeding with no benefit in primary stroke prevention among patients with atrial fibrillation who require dialysis.

Although this study has attempted to account for potential confounders in their statistical analyses, it is nonetheless limited by its observational design, and a randomized trial evaluating oral anticoagulation for primary prevention of stroke in patients with atrial fibrillation who require dialysis is warranted. In the meantime, use of oral anticoagulants in this patient population should be approached with caution (Shah M., Tsadok MA, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis Circulation. 2014 Jan 22 early online. Available at http://circ.ahajournals.org/content/ early/2014/01/22/CIRCULATIONAHA.113.004777.full. pdf+html, accessed May 15, 2014). n

“Fifth hand. Pale chartreuse.”

© The New Yorker Collection 2014 from cartoonbank.com. All Rights Reserved.

not colonized at enrollment but became colonized during the study, and found that 84% of patients receiving azithromycin harbored macrolide-resistant organisms compared to 41% of patients receiving placebo (p < 0.001).

Another recent systematic review of six randomized trials had consistent findings, showing a 37% relative risk reduction in COPD exacerbations among patients taking macrolides compared to placebo (Respir Med. 2013;107[9]:1385-1392). However, the benefit of reduced exacerbations must be balanced against an increased risk of adverse events. Furthermore, the continuous use of prophylactic antibiotics in this population may have a significant impact on antibiotic resistance in the wider community. (Cochrane Database Syst Rev. 2013;11:CD009764).

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COMMENTARY Alexandra LiVecchi, BSN, is a CRNP graduate student (MSN-FNP) at the Greensburg Campus of Carlow University in Greensburg, Pa.

Help children keep asthma at bay The inability to breathe causes anxiety and can be extremely frightening for children with asthma as well as for their caregivers. Primary-care clinicians can improve the quality of life for these patients with proper guidance and education designed to lessen the severity and symptoms of asthma and reduce exposure to potential triggers.

Early intervention and education for children with asthma and their caregivers can improve the family’s quality of life by reducing trips to the health-care provider’s office, the clinic, or the emergency department as well as by minimizing hospital stays, missed school days, and parents’ loss of

Begin to impart asthma information to young patients and/or their caregivers as early as possible.

income due to staying home with the sick child.

This goal can be accomplished by counseling children with asthma and their caregivers on the avoidance of asthma-related triggers, approaches to daily asthma management and medication use, and actions to take when asthma worsens.

Children are extremely susceptible to environmental triggers that can cause and/or worsen asthma, as Wu and Takaro pointed out in their report for Environmental Health Perspectives (2007;115[6]:971-975). The offending substances and the severity of the asthmatic reactions these elements incite may differ from patient to patient, but health-care providers must become familiar with the long list of potential triggers in order to educate young patients and their caregivers and reduce the likelihood of asthma attacks.

Wu and Takaro named in their article common household risk factors for asthma: tobacco smoke, house dust mites, cockroaches, dog and cat dander, and mold. But the full list of culprits that can bring on an asthma flare is much longer, encompassing such diverse stimulants as inhalation of smoke from burning wood or burning leaves, or inhalation of chemicals; influenza, cold, sinus, and other respiratory infections; acid reflux; physical exercise; certain medications such as aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs); high humidity; cold, dry air; shellfish or certain other foods as well as food additives; perfumes; stress; and many other factors, as

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specified by the American Lung Association (www.lung.org).

Clinicians should begin imparting asthma information to young patients and/or their caregivers as early as possible in the disease course and ensure that these individuals know how to use spirometers, other equipment or devices, and medications. Continuous assessment of the patient’s ability to use such products properly and repeated demonstrations are necessary until the asthma is well-controlled and the child is able to manage the chronic condition. Receiving guidance on how to lessen the severity and frequency of asthma episodes, and knowing the symptoms to watch for, helps the child and/or caregiver remain in control of the disease. Longterm control is achieved through compliance, awareness of the causes of the asthmatic attack, and the use of maintenance medications.

In the office, help the patient and family by developing an action plan that explains how to reduce and control asthma attacks. Encourage immunizations, particularly influenza and pneumonia vaccinations, to decrease respiratory infections in the young patient. Finally, assess at every encounter spirometry and peak meter device usage as well as medication compliance and understanding. Ask about frequency of use of quick-relief inhalers. Anticipatory guidance and continuous reinforcement will help the child and family identify and treat asthma attacks early. n

For advertising information, contact: Tom Hennessy at 646-638-6085 or email: Tom.Hennessy@ClinicalAdvisor.com

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