January 2016 Clinical Advisor by The Clinical Advisor

THE CLINICAL ADVISOR • JANUARY 2016

A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS

NEWSLINE

■ Chronic kidney disease ■ Skin cancer screening ■ Shingles and stroke risk CASE STUDY Obesity

A long-term weight loss plan LEGAL ADVISOR

JANUARY 2016

| www.ClinicalAdvisor.com

PAP SMEAR SCREENING FOR

CERVICAL CANCER Cervical cancer progresses slowly and is preceded by precancerous cell changes.

An undisclosed condition

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HEREDITARY BREAST CANCER RISK PAGE 36

■ Dermatologic Clinic VOLUME 19, NUMBER 1

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Editor Colby Stong, editor@ClinicalAdvisor.com Senior editor Sandhya George Associate digital content editor Hannah Dellabella Assistant editor Lauren Biscaldi

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If a patient has you stumped, write us and we’ll forward your query to one of our consultants and publish the response in Advisor Forum.You can also use this space to contribute a clinical pearl of your own or comment on another letter.

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.

CLINICAL PEARLS

It cannot be beat.—TERRI JORDAN, ARNP, Daytona Beach, Fla. (202-2)

NEUTROPHILS AND LYMPHOCYTES In interpreting a complete blood count with differential, anytime the neutrophils and lymphocytes are numerically close, it is a viral cause; when the neutrophils and lymphocytes are numerically distant, it is a bacterial cause. This is very helpful in determining treatment.—DONNA CARTER, FNP-C, Scottsburg, Ind. (202-1) GENERIC “CAINE” IS EFFECTIVE FOR WOUND CARE For pain relief, most pharmacies offer a “caine” at 2-510%, and basically nothing higher, for between $5 and $30 per tube. I work in wound care and use Walmart’s

INTRA-ARTICULAR INJECTIONS FOR SEVERE OSTEOARTHRITIS Patients with severe osteoarthritis in the knees seem to do better with intra-articular injections if you have them sit up and dangle their legs off the examination table and distract the knee slightly when administering the injection.—ROSEMARY LEDBETTER, PhD, PA, Troy, Ill. (202-3)

YOUR COMMENTS SLIPPED CAPITAL FEMORAL EPIPHYSIS IN OBESE ADOLESCENTS I just read the CME/CE article by Marilou Shreve, DNP, APRN, entitled, “Assessing and treating pediatric obesity” [ June 2015]. I was concerned regarding the oversight of a critical issue in obese adolescents: the increased risk of slipped capital femoral epiphysis (SCFE). This was not addressed in the article. The case study (p. 55) gave incomplete advice regarding the evaluation of an obese adolescent male with knee pain. The most common etiology of the insidious onset of knee pain in children is the hip, due to referred pain from the

Equate brand—vagicaine 20% benzocaine. When using this before debriding a wound, give it three minutes to sedate the nerves, then perform the procedure. I get good results, as patients say. It relieves pain and burning for $1.88.

Advisor F

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 contact us by e-mail at editor@ 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.

orum

These are lette and successe rs from practitioners s, observat around the below. We ions, and country who OUR CONSULTANTS pearls with invite you want to shar to participa their colle e their clinic agues. Resp te. al problems onding cons ultants are identified CON SULTAT IONS

TREATM ENT FOR INFECT URINAR ION SGLT2 REC MALE CHI S IN THE UNC Y TRACT IRCUMCI LD FOR DIA EPTOR BLOCKE If a male SED child conti Deborah L. Cross, MPH, CRNP, Laura A.BET Foster,ES CRNP, FNP, Abby A. Jacobson, PA-C, RS Abimbola Farinde, PhD, PharmD, With the nues toassociate ANP-BC, is practices family medicine is a physician assistant is a professor redevprogram adven t ofPrimary circu SGLT2 recep at Delaware Valley urinaryattract director, Gerontology NP elop Program, mcisi Columbia Southern moda litywith Palmetto on be perfo for type tor infecPhysicians Dermatology University of Pennsylvania School blockersGroup University 2 diabe rmed? regarding inCare as a treatm in Wilmington, Del. in Orange Beach, Ala. useCharleston, S.C. tes, is there ent urology is of Nursing, Philadelphia. any evide NATHAN in patients with to protect the is well advise nce or data type 1 diabe GARDNE d tes mellitus?— R, PA-C, continues to to recommend a circum upper tracts, the kidne CPAAPA, ys. develo cision It p recurr•ent 44 THE ADVISOR AUGUST 2015 •on www.ClinicalAdvisor.com Castleton, severaCLINICAL l consideration urinary tract the male child who As it currently stands N.Y. , SGLT2 s that infections. for glycemic impede the receptor blocke There are control in ability to cleansenter into this decisio rs are FDA adults with n. Poor hygien should the e and quell -approved child have e may appro diet and exercise, but with type 2 diabetes phimosis, simpl infection potential. appropriate the in ved conjun FDA for use in patien Moreover, AdvisorForum_CA0815.indd urine 44 9/29/15ction 2:38 PM e cathet culture can ts with type has stated that they ketoacidosi steroid cream be a challenge. erization to obtain s, or those are not may tempo an FAR with severe 1 diabetes, patients with Having a short tion of the rarily solve renal functi diabetic steroid the trial of informINDE, PhD, Pharm these issues tenden , though after for infection D (See bottom on.—ABIMBOL ation about once again.—C cy redevelops, placin cessaA Dr. Farinde.) of this page Milwaukee g (203-2) for more , Wis. (203- OLEEN ROSEN, the child at risk 1) DNP, FNP -C, CLI Philip R. Cohen, MD,

is clinicaltions associate professor , shou ld of dermatology, University a of Texas Medical Center, The focus of Houston.

NICAL

Send us your letter Advisor Forum, The s with questions New York, and comm Clinical Advisor ents to: , 114 clinicaladvisoNY 10001. You may contacWest 26th Street , please indicatr.com. If you are writing in t us by e-mail at 4th Floor, each item. e so by including response editor@ to a the Letters are policy is edited for number in parent published letter, to heses at length and contribution print the author ’s name with clarity. The Clinicathe end of s will be accepted. l Advisor the letter. No anonym ’s ous

Write us today.

OUR CO

NSULTA

PEARLS

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VAGINA L RESULT DISCHARGE AND ING FRO If a female M TAMPON ODOR patient has USE a ask if she uses tamp history of vaginal disch ons. If she the pelvic arge with says “yes,” exam when cond odor, that you woul , do not enter ucting the rotating of d to take a pap smea vagina in the same the specu way r. Instead, the cervix. lum Most retain from side to side start shallow until reach ed tampons ing are lodge d in the fold

Philip R.

Cohen, MD, is clinical associa te profess of dermat or ology, of Texas MedicaUniversity l Center, Houston.

62 THE CLINI

Deborah L. Cross, MPH, ANP-B

CRNP, C, is associa te program director, Geronto logy NP Program University of Pennsyl vania School , of Nursing , Philadelphia.

CAL ADVI

SOR • SEPTE

SEND TO The Clinical Advisor 114 West 26th Street, 4th floor New York, NY 10001 AdvisorForum_

CA0915

E-MAIL editor@clinicaladvisor.com

4 THE CLINICAL ADVISOR • JANUARY 2016 • www.ClinicalAdvisor.com

MBER 2015

Abimbo la Farinde

, PhD,

is a profess PharmD, or at Columb ia Souther n Univers in Orange ity Beach, Ala.

• www.Clinic

alAdvisor.c

Laura A.

Foster,

practices familyCRNP, FNP, with Palmett medicine o Primary Care Physicia ns in Charles ton, S.C.

Abby A.

Jacobso

is a physicia n, PA-C, n at Delawa assistant re Dermatology Valley in Wilmington,Group Del.

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Screening with HPV-Alone invites more risk into women’s lives than you may think. One out of 5 cases of cervical cancer were missed with HPV-Alone screening in a recent landmark, retrospective study—the largest ever conducted to evaluate the effectiveness of cervical cancer screening strategies in women ages 30-65.1* Additionally, screening with Pap+HPV Together™ (co-testing) identified more than 70% of those missed cancers.1 And it only requires one sample. So is HPV-Alone screening really worth the risk? Screen your patients with Pap+HPV Together. Because every woman deserves the best possible protection from cervical cancer. See more data at PapPlusHPV.com.

* A positive HPV screening result may lead to further evaluation with cytology and/or colposcopy. Reference: 1. Blatt AJ, Kennedy R, Luff RD, Austin RM, Rabin DS. Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices. Cancer Cytopathol. 2015 April (Study included ThinPrep®, SurePath, Hybrid Capture 2 assay). ADS-01325-001 Rev. 001 © 2015 Hologic, Inc. All rights reserved. Hologic, Science of Sure, Pap+HPV Together, ThinPrep and associated logos are trademarks and/or registered trademarks of Hologic, Inc. and/or its subsidiaries in the United States and/or other countries. All other trademarks, registered trademarks, and product names are the property of their respective owners. This information is intended for medical professionals in the U.S. and is not intended as a product solicitation or promotion where such activities are prohibited. Because Hologic materials are distributed through websites, eBroadcasts and tradeshows, it is not always possible to control where such materials appear. For specific information on what products are available for sale in a particular country, please contact your local Hologic representative or write to diagnostic.solutions@hologic.com.

CONTENTS JANUARY 2016

NEWS AND COMMENT 18 Newsline ■■Initiating alpha-blocker therapy linked to higher risk of stroke in men ■■Rheumatoid arthritis patients fare better in NP-, PA-staffed practices ■■Prostate cancer treatment linked to Alzheimer’s risk ■■Ventricle pacing reduces heart failure in chronic kidney disease patients ■■False-positive mammograms may indicate increased risk of developing breast cancer ■■Monitoring advised for adults born preterm ■■Better prenatal care and higher rates of breastfeeding help lower SIDS rate ■■Guidelines for hematologic malignancies during pregnancy ■■Chemotherapy response is lower in black women ■■Shingles increases stroke and myocardial infarction risk in the elderly ■■And more.

36 CME/CE Hereditary breast cancer risk assessment in primary care Clinicians should be proficient at assessing hereditary breast cancer risk in their patients and be aware of the indications for referral to genetic counseling. 43 CME/CE Feature posttest

Alpha-blockers and stroke risk 18

DEPARTMENTS 14 Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com 46 CME/CE Dermatology Clinic n Thickening of skin and plaques on a man’s nipples and areolas n Shiny, skin-colored, pinhead-sized grouped papules on a young boy

Efficacy of visual skin screening uncertain 22

51 CME/CE Dermatologic Look-Alikes Circular rashes

102 Commentary ■■Full practice authority and opiate use

57 CME/CE Dermatology posttest

FEATURES

Continues on page 12

24 Cervical cancer screening: Why less is best ACOG’s recommendations regarding Pap smear testing for cervical cancer may be the best evidence-based practice for patients.

MAKING CONTACT

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Achieving sustained weight loss 65

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CONTENTS DEPARTMENTS, cont’d 58

Legal Advisor Undisclosed condition leads to death. A patient’s widow asserts that the clinician should have checked hospital records taken prior to admission.

Case Study Achieving sustained weight loss in an obese patient

Evidence-Based Medicine ■ Vitamin D supplementation does not improve functional outcomes in postmenopausal women ■ Initiating antiretroviral therapy in HIV patients with CD4 T-cell counts >500 cells/mcL ■ Denosumab may reduce the risk of fracture in women with breast cancer on aromatase inhibitor therapy ■ Palliative chemotherapy may reduce quality of life in some patients with end-stage cancer

OTC treatments for cough and colds 94

Stat Consult Influenza in children

OTC Corner Cold and cough symptom relief

Alternative Meds Update Lactobacillus acidophilus

ADVISOR FORUM 44

Your Comments ■ Pap smears, HPV, and screening for cervical cancer ■ Ethical concerns with IUDs ■ Enlarging brown spots: A misdiagnosed solar lentigo?

Your Questions ■ Laser therapy for onychomycosis of the toenails

Clinical Pearls ■ Pap smear testing in a patient who is obese

Health benefits of L acidophilus 98

HOW TO CONTACT US THE CLINIC RY 2016

n Chronic kidney dise ase n Skin canc er screenin g n Shingles and stroke risk CASE STU

Obesity

A long-term

weight loss plan

LEGAL ADV

An undisclos

ISOR

ed condition

✶ FREE CE COURSE

NERS

JANU ARY

2016

| www.Clin icalA

dvisor.com

PAP SMEA

R SCREEN

CERVICAL ING FOR CANCER Cervical cancer progresse s slowly and is prec eded by precance rous cell chan ges.

• Send it by e-mail to editor@ClinicalAdvisor.com

n Featured

Cour

HEREDITARse CANCER Y BREAST RISK PAGE 36

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EXCLUSIVE TO THE WEB AT

ClinicalAdvisor.com The Waiting Room

Web Exclusives

Official Blog of The Clinical Advisor

ClinicalAdvisor.com/News

ClinicalAdvisor.com/WaitingRoom Sharon M. O’Brien, MPAS, PA-C The other signs and symptoms of obstructive sleep apnea Look for symptoms such as headaches, daytime sleepiness, and forgetfulness when diagnosing OSA. Robyn Carlisle, MSN, CNM The importance of proper names Using the correct names for parts of the reproductive system can lead to better knowledge and care of the body. Jillian Knowles, MMS, PA-C When “you’ll be fine,” isn’t fine Clinicians should communicate thoroughly with patients to ensure their injuries will heal properly based on their lifestyle.

Smoking linked to infertility, early menopause Researchers found an increased risk for infertility and natural menopause before age 50 in women who are either active smokers or regularly exposed to secondhand smoke. Few adults taking necessary cholesterollowering medications A CDC team analyzed national data from 2005 through 2014 and found that 35% of Americans eligible to take cholesterollowering medication were not taking the drugs. FDA approves adjuvant flu vaccine for use in the elderly The FDA has approved Fluad, a trivalent flu vaccine with the adjuvant MF59, for use in patients aged 65 and older.

Multimedia ClinicalAdvisor.com/Multimedia The symptoms and treatment of uterine fibroids A patient discusses the symptoms of uterine fibroids, which can cause pain and bleeding. Watch it here: ClinicalAdvisor.com/UterineFibroidsVid Women with recurrent miscarriages do not benefit from progesterone After more than 60 years of uncertainty, a study has shown that progesterone therapy does not improve outcomes for women with unexplained recurrent

miscarriages. Researchers can now focus their efforts on finding other potentially effective treatments. Watch it here: ClinicalAdvisor.com/ProgesteroneVid New screening recommendations from the American Academy of Pediatrics The American Academy of Pediatrics has released updated screening recommendations for cholesterol, depression, and HIV in children and adolescents. Watch it here: ClinicalAdvisor.com/AAPVid See more on page 17

MAKING CONTACT

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Advisor Dx

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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 ClinicalAdvisor.com/AdvisorDx. Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

Ortho Dx

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Atrophy to the first dorsal web space of the hand A 56-year-old man presents with several months of progressive weakness of the right hand. He works in construction and has had difficulty grasping objects. On examination, atrophy to the first dorsal web space is seen, as shown in the image. WHICH NERVE MAY BE ENTRAPPED?

• Median nerve • Ulnar nerve • Axillary nerve • Radial nerve ● See the full case at ClinicalAdvisor.com/OrthoDx_Jan16

Derm Dx A recurring firm and hyperpigmented nodule A 45-year-old woman who is moderately obese presents with a recurrent lesion on her left leg. The lesion was removed elsewhere by shave excision but re-formed after several months. She was advised that the biopsy was benign. Trauma to the site has resulted in bleeding, but otherwise the lesion has been asymptomatic. CAN YOU DIAGNOSE THE CONDITION?

• Clear cell hidradenoma • Pyogenic granuloma • Nodular melanoma • Kaposi sarcoma ● See the full case at ClinicalAdvisor.com/DermDx_Jan16

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JANUARY 2016 17

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Newsline J A N U A R Y 2 016

False-positive mammograms and cancer risk page 19

Lower SIDS rate linked to better prenatal care page 20

Shingles increases stroke, MI risk in the elderly page 22

MEN WHO have recently begun alpha-blocker therapy, often prescribed for prostate hypertrophy, may have an increased risk of ischemic stroke, according to a report published online ahead of print December 7 in the Canadian Medical Association Journal. The risk was more pronounced among patients who were not taking other antihypertensive agents. “We recommend caution when prescribing alpha-blockers to patients who are not taking other antihypertensive medications,” wrote lead author Chao-Lun Lai, MD, PhD, and colleagues. The study included 7,502 men in Taiwan who were aged 50 years or older; mean age was 71 years at initiation of alpha-blocker treatment.

The investigators found an increased risk of ischemic stroke among all patients within 21 days following initiation of alphablocker therapy and a reduced risk 22 to 60 days after beginning treatment, compared with the risk before exposure to the medication. Among patients who were not taking other antihypertensive agents, there was a twofold increased risk of ischemic stroke during the early initiation period than during the later period. In contrast, men who were already taking other antihypertensives had no increased risk of stroke. “One possible explanation of our findings was that patients without underlying hypertension were vulnerable to the first-dose

Initiating alpha-blocker therapy linked to higher risk of stroke in men Caution is urged when prescribing alpha-blockers to patients who are not taking other antihypertensive medications.

effect of alpha-blockers and contributed to the observed increase in risk of ischemic stroke in the early initiation period of alphablockers in the whole study population,” the authors wrote. “In contrast, patients with underlying hypertension appeared to be tolerant of the first-dose effect of alpha-blockers, benefited from the positive influence of alpha-blockers on cerebral blood f low, and contributed to the observed decrease in risk of ischemic stroke in the late initiation period in the whole study population,” the investigators reported.

Rheumatoid arthritis patients fare better in NP-, PA-staffed practices PATIENTS WITH rheumatoid arthritis (RA) have better outcomes in practices staffed with nurse practitioners (NPs) or physician assistants (PAs), according to research published November 24 online ahead of print in Arthritis Care & Research. Daniel H. Solomon, MD, MPH, and colleagues enrolled 7 rheumatology practices across the United States—4 practices with NPs or PAs and 3 practices without. Medical records of 301 patients were reviewed, representing 1,982 total visits; 77% of patients were female, and the mean age was 61 years. “The Affordable Care Act proposes wider use of NPs and PAs,” said Dr. Solomon, “but little is known about outcomes of care provided by them in medical specialties.”

When the researchers compared care outcomes across both types of practices, their primary analysis indicated that patients who received care in practices staffed with NPs or PAs were more likely to have lower disease activity (odds ratio, 0.32) than were patients receiving care in rheumatologist-only practices. “Patients seen in practices with NPs or PAs had lower RA disease activity over 2 years, compared to those seen in rheumatologist-only practices,” Dr. Solomon concluded. “No differences were observed in the change in disease activity between visits either within or between the different types of provider practice.”

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Prostate cancer Ventricle pacing reduces heart failure treatment linked in chronic kidney disease patients to Alzheimer’s risk USE OF CARDIAC resynchroheartbeats, or CRT-D (n = 9,525), nization therapy with defibrillator (CRT-D) resulted in lower risk of hospitalization for heart failure or death than use of only an implantable cardioverter-defibrillator (ICD) in patients with moderateto-severe chronic kidney disease, according to a study published online ahead of print December 15 in the Journal of the American College of Cardiology. The study findings may be independent of kidney function, however. Lead author Daniel J. Friedman, MD, and fellow investigators studied 10,946 patients with chronic kidney disease (stage 3-5) who were eligible for an ICD (n = 1,421), which is implanted in the chest and provides an electric shock when it detects life-threatening abnormal

Results support the use of CRT, independent of kidney function.

which can pace both ventricles simultaneously in addition to delivering a shock. Of the eligible group, 87% received CRT-D. Researchers found a 15% to 20% reduction in the risk of hospitalization for or death from heart failure in patients who received CRT-D, compared with those who received an ICD. This finding remained even after adjusting for age, sex, severity of chronic kidney disease, and presence of atrial fibrillation or flutter. “Taken in sum, the results from this study support the use of CRT, independent of kidney function. These results, however, should be confirmed by prospective randomized studies,” Dr. Friedman said.

False-positive mammograms and breast cancer risk FALSE-POSITIVE RESULTS on a screening mammogram are associated with a greater risk of developing breast cancer in the 10 years following the result, according to a study published online ahead of print December 2 in Cancer Epidemiology, Biomarkers, & Prevention. Lead author Louise M. Henderson, PhD, and fellow investigators used data from the Breast Cancer Surveillance Consortium collected from 1994 to 2009, including 2.2 million screening mammogram results for 1.3 million women aged 40 to 74 years in their analysis. The researchers found that women with a false-positive finding who were referred for additional imaging had a 39% increased risk of developing

breast cancer in the following decade and women with a false-positive result who were referred for biopsy had a 76% increased risk, when compared with women who received a true-negative result (defined as no cancer in the year following the examination). “Our finding that breast cancer risk remains elevated up to 10 years after the false-positive result suggests that the radiologist observed suspicious findings on mammograms that are a marker of future cancer risk,” Dr. Henderson said. “Given that the initial result is a false-positive, it is possible that the abnormal pattern, while noncancerous, is a radiographic marker associated with subsequent cancer.”

ANDROGEN deprivation therapy, often used in the treatment of prostate cancer, has been associated with a nearly twofold increase in risk for Alzheimer’s disease, according to a study published online ahead of print December 7 in the Journal of Clinical Oncology. Senior author Nigam Shah, MBBS, PhD, and colleagues analyzed the electronic medical records of approximately 5.5 million patients, identifying 16,888 men with nonmetastatic prostate cancer for inclusion in their study. Of these, 2,397 men (14.2%) received androgen deprivation therapy during a median followup of 2.7 years. The researchers found a statistically significant association between use of androgen deprivation therapy and risk for Alzheimer’s disease; patients treated with the therapy had a 1.88-times increased rate of developing Alzheimer’s disease, compared with patients who did not receive the therapy. In addition, the investigators noted a statistically significant increased risk of Alzheimer’s disease with longer periods of treatment; men who were on androgen deprivation therapy for more than 12 months had a 2.12-times higher risk of being diagnosed with Alzheimer’s disease. “The association found in this study should be evaluated in the context of the overall treatment choices available to any specific patient,” Dr. Shah said.

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Newsline Monitoring is advised for adults born preterm

failure, and diabetes, including gestational diabetes. In addition, impaired respiratory function and suboptimal bone mass that can lead to osteoporosis and fractures have also been linked to preterm birth. “By identifying patients who were born prematurely, we can

Guidelines for hematologic malignancies in pregnancy NEW TREATMENT guidelines for the clinical management of hematologic malignancies in pregnant women have been published November 30 online ahead of print in the Journal of Clinical Oncology. The guidelines, developed by an international group of experts, include information on diagnostics, chemotherapy, radiotherapy, perinatal care, maternal care, and pediatric care. During pregnancy, the incidence of hematologic malignancies is 0.02%, a figure that continues to increase as more women become pregnant at later ages. Symptoms of hematologic malignancies can sometimes mimic the physiologic changes that occur during pregnancy. Because early treatment is crucial to favorable outcomes, it is recommended that clinicians use “a high index of suspicion.” “This consensus summary equips healthcare professionals with novel diagnostic and treatment methodologies that aim for optimal treatment of the mother, while protecting fetal and pediatric health,” the authors wrote.

Preterm birth has been associated with premature death and hypertension.

take steps to prevent and manage chronic diseases for which they may be at risk to help prevent early death and allow a patient to live a longer, healthier life,” Dr. Luu said. Dr. Luu and colleagues recommended the following in caring for adults born preterm: • Measure blood pressure regularly to help manage risk of early heart disease, including monitoring pregnant women who were born preterm. • Include pulmonary function testing for those who have long-term respiratory issues. • Encourage calcium-rich diets and weight-bearing exercises to prevent osteoporosis.

Better prenatal care, breastfeeding help lower the rate of SIDS THE SUCCESS OF the public health campaign “Back-to-Sleep,” which encouraged parents to place infants to sleep on their back and avoid potential suffocation hazards such as soft bedding in cribs, is only one factor in lower rates of sudden infant death syndrome (SIDS), according to a report published online ahead of print December 2 in Pediatrics. Lead author Richard Goldstein, MD, and colleagues analyzed data on infant mortality from 1983 to 2012, finding an overall decrease of 71% in deaths attributed to SIDS. Positive trends in other factors, which have been associated with susceptibility to SIDS, may have contributed to the decrease. These include

better prenatal and neonatal care, greater rates of breast feeding, and lower rates of smoking during pregnancy and teen pregnancy. For instance, rates of pregnant women who smoked decreased from 16% in 1987 to 10% in 2011. In addition, the Back-to-Sleep campaign began at the same time as a substantial increase in the use of postnatal steroids, which reduce respiratory distress and are especially a factor for premature babies at higher risk of SIDS. “While we continue to stress safe sleep environments, we should also move forward in improving overall maternal and infant health and in researching the underlying biology that may well also influence SIDS,” Dr. Goldstein said.

CLINICIANS should ask patients about their perinatal history to identify those who were born prematurely, an event that has been associated with a number of adverse health conditions, according to a review published online ahead of print December 7 in the Canadian Medical Association Journal. The survival of infants born before 37 weeks’ gestation has become commonplace in the last 3 to 4 decades due to advances in health care, according to lead author Thuy Mai Luu, MD, MSc. Preterm birth has been associated with an increased risk of premature death, hypertension and heart anomalies associated with heart

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Newsline Chemotherapy Evidence lacking to assess benefits/ response lower harm of visual skin cancer screening in black women EVIDENCE IS insufficient to met their inclusion criteria, highassess the balance of benefits and harms of visual screening for skin cancer in adults, according to the U.S. Preventive Services Task Force (USPSTF). The task force did find that clinicians have modest sensitivity and specificity in detecting melanoma during visual checks; however, evidence also showed that these visual screenings may have negative effects. The evidence did not provide sufficient data to quantify these harms. The team conducted a systemic review of evidence on visual skin cancer screenings in primary care settings, reviewing more than 12,000 studies. The task force noted that very few screening studies

USPSTF releases statement on skin cancer screening.

lighting a need for more research. Specifically, the group believes that future research should evaluate the efficacy of targeted screening for patients at high risk for skin cancer. In 2015, approximately 74,000 people in the United States will develop melanoma, with 9,940 dying from the disease. “The task force is dedicated to helping Americans avoid skin cancer and lead healthy lives,” said Michael P. Pignone, MD, MPH. “Until we have more research to better understand the balance of benefits and harms of a clinical visual skin exam, we encourage patients to talk to their doctor about any concerns they have about their skin.”

Shingles increases stroke, MI risk in elderly THE RISK FOR STROKE may be more than double in the first week following a shingles diagnosis, with myocardial infarction (MI) risk also increasing, according to research published December 15 online ahead of print in PLoS Medicine. Caroline Minassian, PhD, and colleagues analyzed data from 42,954 Medicare recipients who were diagnosed with shingles and a stroke between 2006 and 2011. Also included were 24,237 patients with shingles who experienced an MI in the same time frame. The average patient age was 80 years; about two-thirds were women, and about 90% were white. Stroke and MI occurrence were tracked during five different periods of time in the year following a shingles diagnosis: week 1;

weeks 2 to 4; weeks 5 to 12; weeks 13 to 26; and 6 months. Compared with the risk of stroke prior to a shingles diagnosis, the risk increased for up to 3 months following a shingles diagnosis. The biggest increase, more than twofold, occurred during the first week. That risk decreased after 6 months, the investigators found. An increase in MI risk followed a similar trajectory, with almost a twofold risk occurring during the first week following a shingles diagnosis. The study team said there was no evidence that shingles vaccinations had either prevented or aggravated stroke or MI risk. “However, this finding requires further study due to low vaccine uptake in our study population,” said Dr. Minassian. n

NEOADJUVANT chemotherapy treatment is less likely to be effective in African American women with breast cancer than in women in other racial minority groups, suggests research published December 20 in the Journal of Clinical Oncology. Brigid K. Killelea, MD, of the Yale University School of Medicine, and colleagues used the National Cancer Database to identify women with stage 1 through stage 3 breast cancer who were diagnosed in 2010 or 2011. More than 278,000 patients with known race and identity were analyzed; 46% of those patients received chemotherapy. Within the 46%, chemotherapy timing was known for 121,446 patients, revealing that 27,300 women (23%) received neoadjuvant chemotherapy. “Neoadjuvant chemotherapy in particular was given more frequently to black, Hispanic, and Asian women than to white women,” said Dr Killelea. Of the 17,970 patients with a known outcome, 33% had a pathologic complete response (pCR). African American women in particular had a lower rate of pCR for estrogen receptor/progesterone receptor-negative tumors, human epidermal growth factor receptor 2-positive tumors (43% versus 54%) and triple-negative tumors (37% versus 43%). This difference persisted when adjusted for age, clinical T stage, clinical N stage, histology, and grade comorbidity index, among other factors.

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FEATURE: KENDA HARRISON, MSN, FNP-C

Cervical cancer screening: Why less is best ACOG’s recommendations regarding Pap smear testing for cervical cancer may be the best evidence-based practice for patients.

n 2012, the American Congress of Obstetricians and Gynecologists (ACOG) updated its recommendations regarding the starting age and frequency of Papanicolaou (Pap) smear testing. It is now recommended that the test, an important screening tool for cervical cancer, start later and be performed less frequently for most women. Many healthcare providers have expressed confusion and concern regarding the new guidelines. This article examines the rationale for screening, reviews the recommendations in the latest guidelines, and seeks clarity on the best evidence-based practice.

Disparity between guidelines and practice

Photomicrograph of cells collected using a Pap smear showing cervical dysplasia (mag. x400).

Use of the Pap smear test as a tool for screening for cervical cancer has significantly reduced the incidence of the disease in the United States.1 Before Pap smear testing began to be used in 1945, cervical cancer was the most common cause of cancer deaths in women.2 According to the most recent data available from the National Institutes of Health,3 cervical cancer is now the 14th most frequently diagnosed cancer in American women. In 2009, and again in 2012, the ACOG released updated recommendations lengthening the time between screenings from the traditional yearly Pap smear to every 3 years for most women.4 However, one study found that most healthcare providers still recommend yearly Pap smear tests to patients who qualify for less frequent testing under the current guidelines.5

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Transient human papillomavirus infection

Infection with high-risk types of human papillomavirus (HPV), which is transmitted via sexual contact, has been linked to almost all cases of invasive cervical cancer.6 Other risk factors for cervical cancer include smoking, high parity, young age at first intercourse, and long-term use of oral contraceptives.7 There is a high incidence of HPV infection in women by their early 20s, yet these infections are largely transient and rarely lead to lasting cervical cell changes. Invasive cervical cancer in women younger than age 20 is a statistic rarity, with only 0.05 cases per 100,000 women in the United States.7 Even in the presence of advanced cervical dysplasia, women in this age group typically have regression of the abnormal cells, and they rarely develop cervical carcinoma. In one study, 93% of women aged 16 to 23 years with normal Pap smear test results but who were positive for types 16 and 18 HPV—the most likely subtypes to cause cancerous changes—had cleared the virus in 36 months.7 Another study revealed that more than 90% of women with both positive HPV test results and early abnormal cell changes on Pap smears had cleared the HPV infection 2 years later.7 The transient nature of HPV infection in younger women led the ACOG to recommend in its latest guidelines that in the absence of risk factors, women should begin Pap testing at age 21, regardless of their age of first intercourse.8 Earlier recommendations by the ACOG advised that Pap testing begin 3 years after women became sexually active, or at age 21, whichever came first.9 The current guidelines list certain personal factors that warrant earlier testing, which include positive human immunodeficiency virus status, being in an immunocompromised state, or previous treatment for cervical abnormalities.8

POLL POSITION

Which of the following best describes your opinion of ACOG’s recommendations for Pap smear testing for cervical cancer? n=578

■ They are clinically appropriate ■ They are inadequate ■ Regardless, my recommendations to my patients are not consistent with the guidelines

73.18%

13.32% 13.49%

For more polls, visit ClinicalAdvisor.com/Polls.

of CIN 3 peaks in women in their late 20s, whereas the incidence of cervical carcinoma peaks in women in their 40s, giving support to the indolent nature of cervical cancer.7 The period between appearance of dysplasia and development of cancer allows a lengthy window for treatment of abnormal cells with various methods, such as the loop electrosurgical excision procedure (LEEP); in almost all cases, the prevention of invasive carcinoma is achieved with this procedure. It should be noted that many women, by some estimates nearly 50%, who are diagnosed with cervical carcinoma have never had a Pap smear test prior to the one that leads to the diagnosis of cancer.11 Another study revealed that more than 50% of women diagnosed with cervical cancer had not been screened for cervical cancer within the 3 to 5 years prior to their diagnosis.7 ACOG recommendations

Slow development of cervical cancer

Cervical cancer is a disease that progresses slowly, and it is preceded by a lengthy period of precancerous cell changes prior to the development of the cancer. These precancerous changes often spontaneously regress with no treatment. Data suggest that the presence of the lowest level of change, cervical intraepithelial neoplasia (CIN) 1, does not lead to a significantly increased risk for development of the highest level of dysplasia, CIN 3.7 Up to 43% of patients with CIN 2 and 32% of those with CIN 3 have remission without development of cervical carcinoma.7 When the highest level of dysplasia persists, it typically takes 10 years to result in invasive cervical cancer.10 The incidence

The latest ACOG guidelines recommend a longer span between testing, in contrast to the traditional annual test. In the absence of risk factors such as those previously mentioned, women are advised to be screened every 3 years until age 30, at which point CIN 3 changes are most likely to be found. After age 30, screening may be occur every 3 years by cytology alone, or by coscreening with both cytology and HPV testing every 5 years. The longer period recommended between screening, when both Pap and HPV testing are performed, is due to the link between HPV and nearly all cases of cervical cancer.4 An important exemption to the less frequent screening recommendations is for women who have had CIN 2 or higher levels of dysplasia. These patients need yearly screening

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CERVICAL CANCER SCREENING: WHY LESS IS BEST

Recommendations by women’s healthcare providers are among the strongest influences in convincing women to obtain Pap smear testing. for 20 years following dysplasia treatment or spontaneous regression.8 It is important to note that although Pap testing and HPV screening are invaluable tools in the detection of women at risk for cervical cancer, only a colposcopy procedure can identify the exact topography of cervical lesions.12 Clinicians should educate patients that, although the recommended length of time between Pap tests has been widened, the ACOG does recommend yearly pelvic examinations in women aged 21 years and older to include an external visual, speculum, and bimanual examination.13 However, the ACOG states that clinical evidence of the value of this examination is lacking in healthy, asymptomatic women and that the decision to proceed with yearly pelvic examinations is best made by the healthcare provider and patient.13 In addition, clinical breast examinations are recommended for women age 20 to 39 every 1 to 3 years, and yearly examinations are recommended for women age 40 and older. Healthcare providers must use their clinical judgment to adapt these guidelines to their patients, including risk factors in the patient’s history and behaviors that might warrant testing more frequently. In addition, with longer intervals between screenings, clinicians should educate themselves regarding symptoms of cervical cancer, and they should question patients during visits about the presence of any of these symptoms.

Poor clinician adherence to guidelines

Recommendations by women’s healthcare providers are among the strongest influences in convincing women to obtain Pap smear testing.14 Many clinicians report that guidelines by organizations such as the ACOG were influential in their recommendations to patients.5 However, recommendations to patients regarding intervals between testing and when to begin and end testing remain inconsistent among clinicians.15 One study found that few clinicians’ screening practices were consistent with current recommendations.5 When tested on common patient scenarios to determine if Pap smear testing was warranted, many healthcare providers gave answers that conflicted with current guidelines; almost half of providers in the study indicated that they would recommend Pap smear testing on a teenager who had not yet had sexual intercourse.5 Historically, changes in medical recommendations often take time to be accepted and implemented. This may be especially true when most insurance companies continue to pay for screening beyond the frequency of the recommendations.15 Loss of income due to less frequent testing is cited as a reason for clinicians’ resistance to recommended changes.16 A survey of insurance coverage within my practice revealed coverage for Pap smears that are performed more frequently than current ACOG guidelines recommend. Medicare provides coverage for Pap smears every 2 years for women of nonchildbearing age and at low risk and coverage yearly for women of childbearing age and those considered at high risk.17 TRICARE, a part of the Military Health System that provides insurance for military families, covers Pap smear testing for sexually active patients aged 18 and older, with the frequency to be determined by the clinician.18 Health insurance providers such as Cigna, Blue Cross Blue Shield Association, and Aetna also continue to provide coverage for yearly Pap smears, per their customer service representatives.

Effects of screening on patients

Light micrograph of a vaginal smear showing epithelial squamous cells that are infected with the human papilloma virus.

Other factors should be considered in screening women for cervical cancer more frequently than recommended. Women often report anxiety, embarrassment, and fear when facing Pap smear screening; these feelings are due both to apprehension regarding the test results and the invasive nature of the screening itself.19 In addition, women who have received abnormal Pap smear results report avoiding future visits due to fear.20 Colposcopy with biopsy is the procedure performed to further evaluate abnormal Pap smear results. Being informed

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CERVICAL CANCER SCREENING: WHY LESS IS BEST

The most common treatments in the United States for moderate and severe cervical dysplasia are cold knife conization and LEEP. of abnormal Pap smear results and referred for a colposcopy is a great source of stress and anxiety for many women.21 Aside from the emotional effects, one study found that 39% of women reported pain following colposcopy, 47% reported bleeding, and 34% reported unusual discharge.7 When biopsy results reveal a CIN 2 or higher level of dysplasia, current practice in the United States is to treat these lesions.22 The most common treatments in the United States for moderate and severe cervical dysplasia are coldknife conization and LEEP; however, these treatments are not without risks.7 Cold-knife conization has been linked to higher risk of low-birth-weight babies, preterm premature rupture of membranes during pregnancy, and perinatal mortality.23 Women who have the LEEP, which can weaken the cervix, have twice the risk of giving birth prematurely.23 Patients often state that, along with anxiety, negative effects on their sex life persist long after these procedures.20 The increasing cost of health care is a concern to both patients and clinicians. Pap smear testing is frequently accompanied by HPV testing. The cost of these tests, along with common testing on specimens for infections that are often combined with Pap testing, can reach $1,000.24 In surveying my area by telephone, I found colposcopy costs, with biopsy and pathology, quoted in the range of $1,500 to $2,500. Over

the course of a lifetime, in a low-risk woman, following the recommended guidelines for the length between testing could have a substantial financial effect on both the patient and the healthcare system. Conclusions

Testing of cervical cells obtained via Pap smear screening has lowered the rate of cervical carcinomas. Research has shed light on the role that HPV plays in the development of cervical cancer and on the frequent remission of dysplasia and slow-moving and often predictable progress of the disease. Detection and treatment of cervical dysplasia before the onset of carcinoma is the goal of screening; however, it must be acknowledged that testing and treatment of cervical dysplasia is not without risk and negative effect. Analysis of this information led to changes in screening recommendations for women of all ages, both by raising the age at which screening should begin and by lengthening the interval between screenings for most women. The ACOG’s current recommendations—to begin screening with Pap testing at age 21, to screen every 3 years until age 30, and to screen every 3 years with Pap testing or every 5 years in combination with HPV testing thereafter—is the best evidence-based practice for patients, barring any of the above-mentioned risk factors. n Kenda Harrison, MSN, FNP-C, is a family nurse practitioner in Shelbyville, Tennessee. References 1. Sherris J, Wittet S, Kleine A, et al. Evidence-based, alternative cervical cancer screening approaches in low-resource settings. Int Perspect Sex Reprod Health. 2009;35(3):147-154. 2. Schwaiger C, Aruda M, LaCoursiere S, Rubin R. Current guidelines for cervical cancer screening. J Am Acad Nurse Pract. 2012;24(7):417-424. 3. Cervical cancer. National Institutes of Health Research Portfolio Online Reporting Tools (RePORT) website. http://www.report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=76. Updated March 29, 2013.

4. Cervical cancer screening. American Congress of Obstetricians and Gynecologists website. http://www.acog.org/Patients/FAQs/ Cervical-Cancer-Screening 5. Benard VB, Saraiya M, Greek A, et al. Overview of the CDC Cervical Cancer (Cx3) Study: an educational intervention of HPV testing for cervical cancer screening. J Womens Health (Larchmt). 2014;23(3):197-203.

A colposcopy of the cervix showing moderate (CIN 2) dysplasia. The affected precancerous area is dark red and puffy.

6. Vegunta S, Kransdorf LN, Mayer AP. Why more is not always better: new Pap smear guidelines. J Womens Health (Larchmt). 2014;23(1):105-106.

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CERVICAL CANCER SCREENING: WHY LESS IS BEST

7. Vesco KK, Whitlock EP, Eder M, et al. Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the US preventive services task force. Ann Intern Med. 2011;155(10):698-705. 8. Randel A. ACOG releases guidelines on cervical cancer screening. Am Fam Physician. 2013;88(11):776-777. 9. ACOG Committee on Practice Bulletins. ACOG Practice Bulletin Number 45, August 2003: Committee on Practice Bulletins-Gynecology. Cervical Cytology Screening. Obstet Gynecol. 2003;102(2):417-427. 10. Cox JT. Update on cervical disease. OBG Management website. http:// www.obgmanagement.com/home/article/update-on-cervical-disease/720 e926b6c5df4049d6dc75619088f24.html. Updated March 2012. 11. Morrison R, Moody P, Shelton M. Pap smear rates: predictor of cervical cancer mortality disparity? Online J Rural Nurs Health Care. 2010;10(2)21-27. 12. Petry KU. Management options for cervical intraepithelial neoplasia. Best Pract Res Clin Obstet Gynaecol. 2011;25(5):641-651.

“What are your views on migration?”

13. Well-woman recommendations. American Congress of Obstetricians and Gynecologists website. http://www.acog.org/ About-ACOG/ACOG-Departments/Annual-Womens-Health-Care/ Well-Woman-Recommendations 14. Linton DM. Cervical cancer screening interval. Clin J Oncol Nurs. 2009;13(2):235-237. 15. Almeida CM, Rodriguez MA, Skootsky S, et al. Cervical cancer screening overuse and underuse: patient and physician factors. Am J Manag Care. 2013;19(6):482-489. 16. Saraiya M, Steben M, Watson M, Markowitz L. Evolution of cervical cancer screening and prevention in United States and Canada: implications for public health practitioners and clinicians. Prev Med. 2013;57(5):426-433. 17. Cervical & vaginal cancer screenings. Medicare website. https://www. medicare.gov/coverage/cervical-vaginal-cancer-screenings.html 18. Pelvic exams and Pap smears. TRICARE website. http://www.tricare. mil/CoveredServices/IsItCovered/PelvicExamsPapSmears.aspx. Updated June 5, 2015. screening. Current Women’s Health Reviews. 2011;7(4):353-357. 20. Flanagan SM, Wilson S, Luesley D, et al. Adverse outcomes after colposcopy. BMC Womens Health. 2011;11:2. 21. Kola S, Walsh JC. Determinants of pre-procedural state anxiety and negative affect in first-time colposcopy patients: implications for intervention. Eur J Cancer Care (Engl). 2012;21(4):469-476. 22. Pap and HPV testing. National Cancer Institute website. http:// www.cancer.gov/cancertopics/factsheet/detection/Pap-test. Reviewed September 9, 2014. 23. Davisson L. Rational care or rationing care? Updates and controversies in women’s prevention. W V Med J. 2011;107(1):26-28, 30-32. 24. Bettigole C. The thousand-dollar Pap smear. N Engl J Med. 2013;369(16):1486-1487. All electronic documents accessed December 7, 2015.

“O.K. Where is he?”

19. Oscarsson MG. Psychological adjustment of women in cervical cancer

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CME CE FEATURED COURSE

n LEARNING OBJECTIVES After completing the activity, the participant should be better able to: • Identify patients who have an increased chance of developing a hereditary risk syndrome to reduce the odds of developing breast cancer • Assess for genetic mutations that affect breast cancer • Define management options for patients who have an elevated risk and average risk for breast cancer n COMPLETE THE POSTTEST: Page 43 n ADDITIONAL CME/CE CREDIT: Page 46, 51, 57

This activity is provided by Haymarket Medical Education (HME) for physician credit. This activity is jointly provided by Global Education Group and HME for nursing contact hours. Release Date: January 15, 2016 Expiration Date: January 15, 2017 Estimated time to complete the educational activity: 30 minutes Statement of Need: Primary care clinicians need to know how to properly assess patients who have an increased risk of genetic syndromes, as well as recognize familial disease patterns suggestive of inherited susceptibility to breast cancer. Target Audience: This activity has been designed to meet the educational needs of primary care health care professionals who will treat patients with breast cancer. Faculty Karen Herold, DNP, WHCNP-BC, FNP-BC Hoag Breast Center, Newport Beach, CA Jeanne Homer, MS, CGC Hoag Memorial Hospital, Newport Beach, CA Accreditation Statements 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 enduring material 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: Global Education Group is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s COA. Credit Designation: This educational activity for 0.5 contact hours is provided by Global Education Group. Nurses 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 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, 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.

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

Name of faculty

Reported Financial Relationship

Karen Herold, DNP, FNP-BC

No relevant financial relationships

Jeanne Homer, MS, CGC

No relevant financial relationships

Staff/Planners’ Disclosures The planners, managers, and reviewers 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: HME planners, managers, and reviewers have no relevant financial relationships to disclose. Global Education Group planners: Ashley Marostica, RN, MSN, Amanda Glazar, PhD, and Andrea Funk have nothing to disclose. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. HME and Global Education Group do not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Method of Participation: There are no fees for participating in and receiving CME/CE credit for this activity. During the period of January 15, 2016, through January 15, 2017, 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 Global Education Group. 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.

12/31/15 1:04 PM

CME CE FEATURED COURSE: KAREN HEROLD, DNP, WHCNP-BC, FNP-BC, AND JEANNE HOMER, MS, CGC

Hereditary breast cancer risk assessment in primary care Clinicians should be proficient at assessing hereditary breast cancer risk in their patients and be aware of the indications for referral to genetic counseling.

ecause of early detection and more effective treatment regimens, the number of women living with breast cancer in the United States has increased to approximately 2.8 million.1 Although it does occur in men, breast cancer is the most common cancer in women, irrespective of a woman’s race or ethnicity. Based on current rates of breast cancer incidence, approximately one in every eight women born today will be diagnosed with breast cancer during her lifetime. Treatment of breast cancer has steadily improved in the 21st century. These improvements have been accomplished through advances in breast imaging, recognition and identification of germline mutations, and evidence-based interventions, including risk-reducing medications and lifestyle changes. Primary care clinicians should complete a hereditary cancer risk assessment at each patient visit. Although cancer risk assessment may be unfamiliar to many primary care clinicians, it is incumbent on them to be proficient and thorough in this type of evaluation. These practices should include recognition of familial disease patterns suggestive of inherited susceptibility to breast cancer, risk assessment, referral to genetic counseling and testing, and interpretation of these results into practice.

Breast cancer may be caused by a genetic mutation or a predisposed genetic link in a woman’s DNA.

Evaluating family history

Evaluation of family history is one of the most effective and least expensive tools to identify individuals at increased risk for breast cancer, and yet many providers do not adequately assess their patients’ familial www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JANUARY 2016 37

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CME CE

FEATURED COURSE

and genetic risk of developing breast cancer. All breast cancers are genetic, but not all breast cancers are hereditary; breast cancer can be attributed to sporadic, familial, or genetic causes. Approximately 5% to 10% of breast cancers can be linked to genetic mutations from the maternal or paternal side; a woman’s risk of breast cancer approximately doubles if she has a first-degree relative who has been diagnosed with the disease.2 Sporadic breast cancer can be partly explained by known risk factors such as age at menarche, age at first live birth, age at menopause, history of proliferative breast disease, and lifestyle factors. Hereditary breast and ovarian cancer (HBOC) syndrome, which is caused by a germline mutation in the high-penetrance breast cancer genes BRCA1 or BRCA2, is characterized by an increased risk for breast cancer.3 An increased likelihood of a BRCA1 or BRCA2 mutation can be suspected on the basis of certain personal and family history characteristics and clinical criteria. The lifetime risk for breast cancer in individuals with a mutation in BRCA1 or BRCA2 is estimated to be 40% to 80%.4 The prognosis for patients with BRCA1- or BRCA2-related breast cancer depends on the stage at which the cancer is diagnosed, and early diagnosis may depend on a patient’s awareness of increased familial or genetic risk. Similarly, patients with mutations in other high-penetrance genes such as tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN), serine/threonine kinase 11 (STK11), and cadherin 1, type 1 (CDH1) may develop cancer predisposition syndromes associated with the development of several types of cancer, and they have a higher likelihood of developing breast cancer in their lifetimes. Moderate-penetrance breast cancer susceptibility genes that can increase breast cancer risk during a woman’s lifetime include checkpoint kinase 2 (CHEK2), ataxia telangiectasia mutated serine/threonine kinase (ATM), nibrin (NBN), RAD50 homolog, double strand break repair protein (RAD50), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and partner and localizer of BRCA2 (PALB2).5 In men, 3 classes of genetic susceptibility to breast cancer (high-, moderate-, and low-penetrance) are recognized, but the genes that are involved and their impact do not exactly overlap in female and male breast cancer.6 An increased likelihood of a genetic mutation in moderate- and high-penetrance genes can be suspected on the basis of certain personal and family history characteristics and clinical criteria. Clinicians may then be able to advise patients who carry a genetic mutation or know of their increased risk of management strategies that might mitigate their breast cancer risk.

Even if no hereditary susceptibility is suggested by the family history, individuals having one or more close relatives with breast cancer may benefit from beginning cancer surveillance at a younger age and/or with more intensive screening than those in the general population. National guidelines recommend that individuals with hereditary breast cancer susceptibility be screened earlier and consider more sensitive screening tests, risk-reducing medications, and/or risk-reducing surgery.7 Risk of sporadic, familial, and hereditary breast cancer may be modified by lifestyle and environmental factors, breast imaging, chemoprevention, and/or prophylactic surgery,8 but awareness and knowledge about techniques to reduce breast cancer risk varies tremendously among individuals, providers, and populations nationwide. It has been hypothesized that when individuals are made aware of the level of their breast cancer risk and are given appropriate tools, support, and screenings, they would take proactive steps to mitigate their risk of developing cancer and increase their odds of survival if breast cancer does occur.9 It is also thought that if patients are informed of their elevated risk for breast cancer, their compliance with breast cancer prevention measures is greater.9 Of note, tools to identify women at elevated risk of developing breast cancer have been validated.10 The National Comprehensive Cancer Network (NCCN),11 a not-for-profit alliance of 26 of the world’s leading cancer centers that is devoted to patient care, research, and education, has developed breast cancer risk-reduction guidelines that can be used in clinical practice. Individuals at elevated risk of developing breast cancer can be identified and encouraged to follow these clinical guidelines to reduce their risk. Indications for referral to genetic counseling

It is important for clinicians in primary care to recognize when referral to a genetic counselor is recommended. A cancer risk assessment should be conducted at every primary care visit, and the patient’s family cancer history should be updated as appropriate at every visit. NCCN guidelines7 recommend referral to a cancer genetics professional when there is a history involving either side of the family—maternal or paternal—of any of the following: • A known mutation in a cancer susceptibility gene in the family • A first- or second-degree relative with breast cancer at age 45 or younger (includes ductal carcinoma in situ). First-degree relatives include siblings, parents, and children; second-degree relatives include grandparents, aunts, uncles, half-siblings, nieces, and nephews; third-degree

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relatives include cousins, half-aunts and uncles, great aunts and uncles, great grandparents, and great grandchildren. • A close family member with at least two primary breast cancers. Close blood relatives include first-, second-, and third-degree relatives. • At least two closely related individuals on the same side of the family with breast cancer • At least one woman in the family with invasive ovarian cancer (including fallopian tube and primary peritoneal cancer) • Breast cancer in a male family member

• Three or more individuals on the same side of the family with pancreatic or prostate cancer (Gleason score ≥ 7) • Ashkenazi (Eastern European) Jewish ancestry and breast, ovarian, or pancreatic cancer at any age There are less common hereditary cancer syndromes that confer an increased risk of developing breast cancer. These syndromes may seem a bit more elusive but it is imperative that clinicians assess their patients for their presence because an increased incidence of breast cancer is seen within families that carry these syndromes. Clinicians should be suspicious of these less common hereditary syndromes when three or

Case 1 AB came in for genetic counseling at age 40, due to her concern about her mother’s history of breast cancer at age 44 and her wish to be proactive in surveillance and prevention measures. Her mother’s only sister died at age 60, and her maternal grandmother died at age 86; neither of them had been diagnosed with cancer of any kind. There was also a history of colon cancer in AB’s father at age 62. AB’s family pedigree, which is a chart that enables a genetics professional to visualize the appearance and phenotype of a particular gene, is shown in Figure 1. Family members affected by breast and colorectal cancer are indicated and standard symbols are used to represent women (circles) and men (squares). According to guidelines from the National Comprehensive Cancer Network, AB met the criterion for testing hereditary breast and ovarian cancer (a first- or second-degree relative with breast cancer at age 45 or younger). However, due to significant limitations in the ability to interpret test results in an individual without cancer, it is recommended that in any family, testing begin with the family member with the highest likelihood of a mutation. If a mutation is identified in that individual, then other family members can be tested for that specific mutation. If no mutation is detected, then testing is usually not indicated for other family members. AB’s mother, now age 62, was the ideal candidate for testing, and she agreed to be tested. Analysis revealed a mutation in the BRCA2 gene. It was therefore recommended that she undergo risk-reducing salpingo-oophorectomy and be screened with breast magnetic resonance imaging (MRI) and mammography annually, or consider risk-reducing bilateral mastectomy or other risk-reducing measures. Her initial breast cancer had been treated with lumpectomy followed by radiation therapy.

FIGURE 1. AB’s family pedigree* Maternal: Ireland

Paternal: England, Germany

Diagnosis = Breast cancer (Br) Diagnosis = Colorectal cancer (CRC)

70s

64 CRC 62

62 BR44

*Each row represents one generation. Circles indicate females, and squares indicate males. A diagonal line through a symbol represents a deceased member of the family. Numbers under symbols provide the age if living or age at death, whereas numbers after cancer type are the ages at diagnosis.

For AB, the following information was now clear: the cancer in her mother was hereditary, and the specific mutation had been identified. AB was tested for the mutation found in her mother, and the results showed that AB did not inherit the mutation. These results were interpreted as a “true negative.” Her risk for hereditary breast cancer having been ruled out, she was advised that she was expected to have the same risk for breast and ovarian cancer as a woman at average risk and should be screened accordingly. In addition, due to the history of colon cancer in her father, AB was advised to begin screening via colonoscopy at age 40, rather than at age 50.

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CME CE

FEATURED COURSE

more findings occur in any of the four following groups: • Sarcoma, adrenocortical carcinoma, brain tumor • Endometrial cancer, thyroid cancer, kidney cancer, macrocephaly, skin findings of trichilemmoma, multiple palmoplantar keratosis, multifocal or extensive oral mucosal papillomatosis, multiple cutaneous facial papules • Diffuse gastric cancer • Hamartomatous polyps of the gastrointestinal tract Patients whose family histories suggest a less common hereditary breast cancer syndrome should also be referred to a genetics professional for genetic counseling. Less common hereditary breast syndromes include Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer.

Genetic counseling and testing

Many individuals with typical family histories greatly overestimate their risk for breast cancer and may unnecessarily live with a disproportionate fear of developing the disease. Genetic counselors specializing in hereditary and familial cancer are trained in hereditary cancer risk assessment in individuals at high risk and can provide expert guidance. Genetic counselors are health professionals with specialized graduate degrees and experience in the areas of medical genetics and counseling. Genetic cancer counseling integrates the following components: • Collection and documentation of a detailed family history of cancer • Review of appropriate medical records

Case 2 GG is a 34-year-old woman who has come to the clinic for her annual well woman examination. She has not had a diagnosis of breast cancer, but she is concerned that she is at high risk of developing breast cancer because she has an older sister (GA) who was diagnosed with breast cancer at age 35. She has a younger sister (GB) who was diagnosed with breast cancer at age 31. On the paternal side of her family, she had an aunt who was diagnosed with breast cancer at age 78 and died at age 82. Why is this patient an appropriate candidate for genetic counseling? A. A known mutation in a breast cancer susceptibility gene within the family B. A family history suggestive of a BRCA mutation C. More than one first-degree relative with breast cancer diagnosed at an age younger than 45 D. More than two family members with primary breast cancer The best answers are C and D. This patient is an appropriate candidate for genetic counseling, because she has 1 or more first-degree relatives who have been diagnosed with breast cancer at age 45 or younger and 2 or more individuals with primary breast cancer on the same side of the family. You receive a report from the genetic counselor after GG’s appointment. The genetic counselor appropriately recommended which of the following for GG and her family? A. Genetic testing for GG B. No testing at this time

C. Genetic testing on a family member who has developed breast cancer D. Tumor testing on GA and GB The best answer is C. The genetic counselor recommended genetic testing on an affected member of GG’s family. Subsequently, GG’s older sister GA undergoes genetic testing and is found to have a BRCA1 mutation. The genetic counselor appropriately makes which of the following recommendations for GG and her family? A. No further testing should be done on this family B. Single-site genetic testing for all of GG’s siblings C. Single-site genetic testing for GG and all of her siblings D. Tumor testing for GA to establish risk-reduction recommendations The best answer is C. Single-site genetic testing for GG and her siblings is the most appropriate next step. GG’s genetic test results are negative for the familial BRCA1 mutation. As her clinician, what do you recommend? A. Educate GG about the fact that she is considered to be at average risk and should therefore follow recommendations for an average-risk individual. B. Suggest a complete genetic panel for GG because something may have been missed. C. Recommend annual breast magnetic resonance imaging because GG is now considered at elevated risk. The best answer is A. Education on GG’s status as a woman at average risk should be provided, and guidelines and screening for an average-risk individual should be followed.

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• Pedigree assessment and recognition of cancer susceptibility syndromes (includes all cancer types) • Calculation of hereditary cancer risk using risk assessment models • Explanation of inheritance pattern and implications for family members • Assistance in exploring the medical and psychologic implications of genetic testing • Review of costs, benefits, and limitations of genetic testing • Provision of informed consent, including issues of privacy, confidentiality, and legal protections against genetic discrimination • Assistance in obtaining insurance coverage for testing • Selection of appropriate genetic testing and testing laboratory • Determination of best strategy for testing within the family • Interpretation of genetic test results • Provision of ongoing emotional support and assistance in informing family members • Assistance in developing a plan for cancer screening and risk reduction, when appropriate • Detailed summary letters sent to patients and their physicians • Referrals to research and local and national support organizations, when appropriate Genetic counseling appointments typically last between 45 minutes and an hour. Interested family members are usually welcome to attend. The genetic counselor usually begins the appointment by listening to the patient’s goals, expectations, and concerns to understand how best to meet the patient’s needs. Information about the family history is collected and documented either prior to or during the appointment. The counselor explains the basic principles of genetics and hereditary cancer, including what clues might indicate that the cancer seen within that family could be hereditary. The patient and counselor review and assess the patient’s family history of cancer together. Many genetic counselors provide a numeric estimate of the likelihood that the patient will carry a gene mutation generated by a validated risk assessment tool. Genetic testing is discussed in detail, including whether testing is indicated for a particular patient, the most useful strategy for testing within the family, possible test results for the patient and the family, and insurance coverage. Many options for genetic testing are now available, ranging from analysis of a single gene mutation to testing dozens of genes simultaneously. The counselor reviews appropriate testing options and answers any questions that the patient has. Genetic testing can usually be performed on a blood or saliva specimen, and results are usually available in 1 to 5 weeks. Once

Case 3 HH is a 44-year-old patient who presents to your office after a recent diagnosis of breast cancer. She decided to transfer her care to you because she made a recent move from another state. She reports that she has a sister, age 55, who was diagnosed with breast cancer at age 51. She also has an aunt on her paternal side, now in her 60s, who was diagnosed with breast cancer 1 year earlier. No one in HH’s family has had genetic counseling or testing, and HH does not know what genetic counseling is. What should you do first? A. Recommend genetic testing to HH B. Recommend genetic testing of HH’s sister C. Recommend no genetic testing at this time D. Recommend that HH have genetic counseling The best answer is D. You should recommend that HH have genetic counseling; she is an appropriate genetic testing candidate because she has breast cancer that was diagnosed at an early age. You receive genetic testing results for HH, and you note that no mutations were detected. Given these results, what risk management recommendations should you make for your patient? A. Recommend risk-reducing bilateral salpingooophorectomy. B. Review recommendations for contralateral breast cancer risk, including prophylactic mastectomy and screening. C. Recommend genetic testing of HH’s sister. D. No recommendations should be made because the patient had negative test results and is not at high risk for another breast cancer. The best answer is B. You should review the recommendations for contralateral breast cancer risk, including prophylactic mastectomy and screening. This is an important consideration, as the patient still may have an increased risk of breast cancer due to both her personal and family history, even though she had negative genetic test results. As a clinician, it is important to consider family history when making recommendations for contralateral breast cancer risk. You should also consider whether this is a family that is affected by only breast cancer or whether the family is affected by breast and ovarian cancer, as this may influence your recommendations for screening and prophylactic surgery.

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CME CE

FEATURED COURSE

TABLE 1. Common myths and misperceptions about genetic counseling Myth

Fact

Genetic counseling and testing are expensive.

The cost of genetic counseling and BRCA testing, if appropriate, must be covered by private health insurers for women whose family history is suggestive of hereditary breast or ovarian cancer. The Patient Protection and Affordable Care Act requires insurance plans that began on or after August 1, 2012, to cover these services as a preventive service without cost sharing (ie, copay, coinsurance)

People who carry BRCA mutations are flagged as high risk and will never be able to get health insurance.

The Genetic Information Nondiscrimination Act prohibits health insurers and most employers from discriminating against individuals based on genetic information, including the results of genetic tests and family history information. According to this act, health insurance companies cannot consider genetic information to be a preexisting condition, nor can they use it to make decisions regarding coverage or rates. More information about this act can be found by visiting www.ginahelp.org or contacting a genetic counselor.

Cancer on the father’s side of the family does not count.

Of hereditary cases of breast cancer, 50% are inherited from the father’s side of the family.2

If there is only one person with breast cancer in the family, that means it cannot be hereditary.

If that person is age 45 or younger, is a man, or is of Ashkenazi ancestry, it could still be hereditary. Young age at diagnosis in one individual is more suspicious for hereditary breast cancer than a history of three women at older ages.

Genetic counseling is not necessary; any doctor can order genetic testing.

Genetic counseling for hereditary cancer is a complex, frequently changing field. Many organizations recommend counseling by a cancer genetics professional before and after genetic testing.2,7,12,13 Research has shown that genetic testing ordered by individuals not certified in genetics can result in harm to their patients,14-16 and some health insurers now require genetic counseling before genetic testing will be covered.

If a gene mutation is found, a patient’s only option is to have a bilateral mastectomy.

Surgery is one of many options for carriers of gene mutations that make patients susceptible to breast cancer.

the results of testing are available, the genetic counselor reviews them with the patient, either in person or by telephone. The genetic counselor discloses to the patient whether a gene mutation was found. In addition, the patient’s chance of developing cancer is discussed, and recommendations for screening and risk reduction are reviewed. If a gene mutation is found, the counselor offers assistance on how to discuss this information with family members and provides information about support groups, cancer gene registries, and other resources that may be helpful to the patient. Many myths exist about genetic counseling and can affect use of genetic counseling and testing. It is important to dispel these myths and address them whenever possible with patients and clinicians. Some of the more common myths and misperceptions about genetic counseling are listed in Table 1.

cancer, clinicians are able to manage patients at increased risk of developing breast cancer in a primary care setting. Patients who are suspected of having an inherited syndrome should be referred to genetic counseling and testing, which allows appropriate risk stratification and management in those found to carry a genetic mutation. If a hereditary breast cancer syndrome is identified, early evaluation and additional interventions can substantially decrease the mortality and morbidity associated with breast cancer. n Karen Herold, DNP, WHCNP-BC, FNP-BC, is the High Risk Breast Cancer Nurse Practitioner for the Hoag Breast Center in Newport Beach, and Jeanne Homer, MS, CGC, is a genetic counselor at the Hoag Family Cancer Institute of Hoag Memorial Hospital Presbyterian in Orange County, Calif. References

Conclusions

1. U.S. breast cancer statistics. Breastcancer.org website. http://www.breast-

Primary care clinicians are in a unique position to identify individuals at increased risk for development of hereditary or familial breast cancer. Using a protocol-driven evaluation of personal and family risk factors and genetic testing for breast

cancer.org/symptoms/understand_bc/statistics. Updated October 23, 2015. 2. Genetics of breast and gynecologic cancers–for health professionals (PDQ®). National Cancer Institute website. http://www.cancer.gov/types/ breast/hp/breast-ovarian-genetics-pdq. Updated November 12, 2015.

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3. Petrucelli N, Daly MB, Feldman GL. BRCA1 and BRCA2 hereditary breast and

11. NCCN Clinical Practice Guidelines in Oncology. Breast cancer

ovarian cancer. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. Gene Reviews.

screening and diagnosis. V. 1.2015. National Comprehensive Cancer

National Institutes of Health website. http://www.ncbi.nlm.nih.gov/books/NBK1247

Network website. http://www.nccn.org/professionals/physician_gls/PDF/

4. Rebbeck TR, Domchek SM. Variation in breast cancer risk in BRCA1 and

breast_risk.pdf

BRCA2 mutation carriers. Breast Cancer Res. 2008;10(4):108.

12. BRCA1 and BRCA2: Cancer risk and genetic testing. National Cancer

5. van der Groep P, van der Wall E, van Diest PJ. Pathology of hereditary

Institute website. http://www.cancer.gov/cancertopics/causes-prevention/

breast cancer. Cell Oncol (Dordr). 2011;34(2):71-88.

genetics/brca-fact-sheet

6. Rizzolo P, Silvestri V, Tommasi S, et al. Male breast cancer: genetics,

13. BRCA-related cancer: risk assessment, genetic counseling,

epigenetics, and ethical aspects. Ann Oncol. 2013;24 (Suppl 8):viii75-viii82.

and genetic testing. US Preventive Services Task Force website.

7. NCCN Clinical Practice Guidelines in Oncology. Genetic/familial high-

http://www.uspreventiveservicestaskforce.org/Page/Name/

risk assessment: breast and ovarian. V.1.2015. National Comprehensive

uspstf-a-and-b-recommendations

Cancer Network website. http://www.nccn.org/professionals/physician_

14. Brierley KL, Campfield D, Ducaine W, et al. Errors in delivery

gls/pdf/genetics_screening.pdf

of cancer genetics services: implications for practice. Conn Med.

8. Gronwald J, Byrski T, Huzarski T, et al. Hereditary breast and ovarian

2010;74(7):413-423.

cancer. Cancer Clin Pract. 2008;6(2):88-98.

15. Brierley KL, Blouch E, Cogswell W, et al. Adverse events in cancer

9. Tracy KA, Quillin JM, Wilson DB, et al. The impact of family history of

genetic testing: medical, ethical, legal, and financial implications. Cancer J.

breast cancer and cancer death on women’s mammography practices and

2012;18(4):303-309.

beliefs. Genet Med. 2008;10(8):621-625.

16. Bonadies DC, Brierley KL, Barnett RE, et al. Adverse events in cancer

10. Owens WL, Gallagher TJ, Kincheloe MJ, Ruetten VL. Implementation

genetic testing: the third case series. Cancer J. 2014;20(4):246-253.

in a large health system of a program to identify women at high risk for All electronic documents accessed December 2, 2015.

breast cancer. J Oncol Pract. 2011;7(2):85-88.

CME CE

POSTTEST Expiration date: January 15, 2017

FEATURED COURSE CREDITS: 0.5

For more credit information, please turn to p. 36. 1. Which of the following is the approximately estimated lifetime risk for breast cancer in individuals with a BRCA1 or BRCA2 mutation? a. 40% to 80% b. 35% to 55% c. 40% to 70% d. 30% to 70%

3. Breast cancer risk can be inherited from which of the following? a. The maternal side of the family b. The paternal side of the family c. The maternal or paternal side of the family d. First-, second-, or third-degree relatives from the maternal side of the family

2. Breast cancer can be attributed to which of the following causes? a. Sporadic, familial, or genetic causes b. Genetic mutations c. Environmental factors d. Family history

4. Approximately which of the following percentages of breast cancers can be linked to high-penetrance gene mutations? a. 0% to 5% b. 15% to 20% c. 20% to 25% d. 10% to 40%

TO TAKE THE POSTTEST please go to: myCME.com/Jan16CAfeature

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YOUR COMMENTS PAP SMEARS, HPV, AND SCREENING FOR CERVICAL CANCER As a family nurse practitioner with 30 years experience in women’s health in eastern North Carolina, I truly believe that there is a particularly virulent strain of human papillomavirus in this part of the nation. Just two examples include advanced cervical cancer in a 15-year-old and a 19-year-old without a history of multiple partners or sexual assault. I am concerned that we are putting young women at risk for long-term problems. The 15-year-old was managed at a teaching center with multiple loop electrosurgical excision procedures, followed by a successful pregnancy later. The 19-year-old had such advanced cancer that the only option was radiation. A valiant attempt to spare her ovaries prior to radiation by surgically moving them up in the pelvis was not successful. Thankfully, she has been cancer-free for 5 years. 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 contact us by e-mail at editor@ 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.

Women are confused by the current recommendations/ guidelines. They are just that—not an absolute edict. Each person should be evaluated, as you noted [“Cervical cancer screening: why less is best,” p. 32], based on history and exposure risk. I ask the patients not only how many partners they have had, but how many partners their current and former partners have had. Too many patients are deferring pelvic exams also, as the perception is that the only indication for a pelvic exam is to obtain a Pap smear. I have this discussion with younger physicians in our office regularly. It is fortunate, as a mid-level provider, I am able to continue to be aggressively conservative with those entrusted to my care.—SARA BROWN, FNP, Leland, N.C. (207-1)

ETHICAL CONCERNS WITH IUDs The November feature article on IUDs [“The IUD rumor mill: common misconceptions,” p. 32] was concise and helpful in terms of allaying patients’ fears about insertion, side effects, and contraindications. One area that was not discussed, however, is the ethical issue that some women may have with the hormonal devices that “make changes to the endometrium to prevent implantation.” Many, if not most, pro-life advocates consider life as beginning at conception. For those women, offering the copper IUD might be an acceptable alternative as it works by preventing actual fertilization.—DIANE HICE, RN, Albuquerque, N. M. (207-2)

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, PhD, PharmD,

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

Laura A. Foster, CRNP, FNP,

Abby A. Jacobson, PA-C,

practices family medicine with Palmetto Primary Care Physicians in Charleston, S.C.

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

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ENLARGING BROWN SPOTS: A MISDIAGNOSED SOLAR LENTIGO? I was reviewing the September 2015 issue [Dermatologic Look-Alikes, “Enlarging brown spots,” p. 79, Case #2]. Immediately, I noticed a pinkish spot on the right medial clavicular region, which potentially could be a lichenoid keratosis, an actinic keratosis, a superficial basal cell carcinoma, a squamous cell carcinoma in situ, or the one diagnosis nobody wants to miss and is probably more unlikely, a melanotic melanoma. The point of why I am writing is that the “enlarging brown spot” most definitely appears to be a solar lentigo. I’m not sure if the pinkish lesion was treated, discussed, or potentially overlooked. If the lesion was not addressed, the patient should return to have it re-evaluated to have it possibly treated or biopsied.—JUAN KOJIMA, PA-C, San Diego, Calif. (207-3)

YOUR QUESTIONS LASER THERAPY FOR ONYCHOMYCOSIS OF THE TOENAILS What is the mechanism of action for laser treatment for onychomycosis of the toenails?—ELIZABETH McDONOUGH, PA-C, Naples, Fla. Onychomycosis is a nail infection caused by a fungus, yeast, or mold. Toenail onychomycosis is most commonly caused by dermatophytes, or fungus. Risk factors include age, diabetes, immunodeficient status, swimming, tinea pedis, psoriasis, and living with others who have onychomycosis. The paucity of data on the efficacy and the mechanisms of action of laser therapy for onychomycosis makes it difficult to answer this question. According to the literature, proposed mechanisms of

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.

action for laser therapy for onychomycosis include direct fungicidal effects, inhibition of fungus by laser-induced changes in the tissue environment, and laser-induced immunologic effects, though an in vitro study evaluating the effects of a submillisecond Nd:YAG laser on fungal nail pathogens did not find support for a laser-induced direct fungicidal effect. Further study with randomized trials that compare laser devices with placebo and other onychomycosis treatments, as well as long-term follow-up studies, will be useful for clarifying the efficacy, mechanisms, optimal regimens, and indications for laser therapies.—LAURA FOSTER, CRNP, FNP (See photo at the bottom of page 52 for more information about Ms. Foster.) (207-4)

CLINICAL PEARLS PAP SMEAR TESTING IN A PATIENT WHO IS OBESE When examining an obese patient, to do a proper Pap smear, position the patient at the edge of the examination table. To identify the cervix while doing the Pap test, have the patient place her hands on her knees and pull her legs back toward her. The cervix will then be very nicely in the view of the speculum. If the vaginal rugae are collapsing on the lateral walls of the vagina and are impeding your ability to see, a condom can be placed over the speculum before the examination. Simply cut the tip off the condom, and place the speculum in the vagina. When the speculum opens, the condom will prevent the vaginal walls bilaterally from obstructing your view. This technique can be used during colposcopy procedures as well.—TERRI FULLER, APRN, Lake Hopatcong, N. J. (207-5) n

Claire O’Connell, MPH, PA-C,

Katherine Pereira, DNP, FNP,

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

is assistant professor, Duke University School of Nursing, Durham, N.C.

Sherril Sego, FNP-C, DNP,

is an independent consultant in Kansas City, Mo.

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CME CE DERMATOLOGY COURSES

n LEARNING OBJECTIVES After completing the activity, the participant should be better able to:

For Dermatology Clinic

• Examine the etiology and clinical presentation of nipple hyperkeratosis and lichen nitidus • Formulate diagnostic procedures and treatment protocols for patients presenting with nipple hyperkeratosis and lichen nitidus

For Dermatologic Look-Alikes

• Differentiate between skin manifestations of fixed drug eruption and nummular eczema while considering their underlying cause • Demonstrate proficiency in identifying and treating fixed drug eruption and nummular eczema n COMPLETE THE POSTTEST: Page 57 n ADDITIONAL CME/CE CREDIT: Page 36

This activity is provided by Haymarket Medical Education (HME) for physician credit. This activity is jointly provided by Global Education Group and HME for nursing contact hours. Release Date: January 15, 2016 Expiration Date: January 15, 2017 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 health-care professionals who treat patients with various dermatologic conditions. Faculty Harina Vin, BS, Baylor College of Medicine, Houston Maura Holcomb, MD, Baylor College of Medicine, Houston Eman Bahrani, BA, Baylor College of Medicine, Houston Jennifer S. Ruth, MD, Baylor College of Medicine, Houston Sachin Allahabadi, BS, BA, Baylor College of Medicine, Houston Rana Mays, MD, Baylor College of Medicine, Houston Accreditation Statements 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 enduring material 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: Global Education Group is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Credit Designation: This educational activity for 0.5 contact hours is provided by Global Education Group. Nurses 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 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 to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.

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

Name of faculty

Reported Financial Relationship

Harina Vin, BS

No relevant financial relationships

Maura Holcomb, MD

No relevant financial relationships

Eman Bahrani, BA

No relevant financial relationships

Jennifer S. Ruth, MD

No relevant financial relationships

Sachin Allahabadi, BS, BA

No relevant financial relationships

Rana Mays, MD

No relevant financial relationships

Staff/Planners’ Disclosures The planners, managers, and reviewers 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: HME planners, managers, and reviewers have no relevant financial relationships to disclose. Global Education Group planners, Ashley Marostica, RN, MSN, Amanda Glazar, PhD, and Andrea Funk, have nothing to disclose. Disclosure of Unlabeled Use: This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. HME and Global Education Group do not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Method of Participation: There are no fees for participating in and receiving CME/CE credit for this activity. During the period of January 15, 2016, through January 15, 2017, 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 Global Education Group. 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.

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

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Dermatology Clinic

CME CE DERMATOLOGY COURSES

CASE #1

Thickening of skin and plaques on a man’s nipples and areolas HARINA VIN, BS, AND MAURA HOLCOMB, MD

A 68-year-old white man presents with 4 weeks of progressively worsening thickening of the skin and plaques on the bilateral nipple and areola. He has no personal or family history of warts or epidermal nevi and has not had hormonal therapy. On examination, he has hyperpigmented, verrucous plaques bilaterally, with no associated erythema or lymphadenopathy. Skin biopsy shows hyperkeratosis with papillomatosis. Corticosteroid treatment failed, but there was some minor improvement with calcipotriol after several weeks of use. What is your diagnosis? Turn to page 48.

CASE #2

Shiny, skin-colored, pinhead-sized grouped papules on a young boy EMAN BAHRANI, BA, AND JENNIFER S. RUTH, MD

A 4-year-old white male presents with a 3-month history of an asymptomatic papular rash on his back, abdomen, chest, upper arms, and ankles. His medical and family histories are otherwise unremarkable. On examination, the grouped papules are shiny, monomorphic, skin-colored, and pinhead-sized. The papules exhibit koebnerization but no erythema or tenderness. His nails, hair, oral mucosa, and genitals are normal. What is your diagnosis? Turn to page 49. www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • JANUARY 2016 47

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CME CE

CASE #1

Dermatology Clinic

Nipple hyperkeratosis

Nipple hyperkeratosis is an acantholytic disorder of the skin. The condition most commonly presents as diffuse, hyperpigmented, verrucous plaques.1 Pruritis is the most common symptom associated with nipple hyperkeratosis, although the majority of cases are asymptomatic. Approximately 50 cases of nipple hyperkeratosis have been reported; of these, 80% occurred in women.1,8 The condition mostly occurs in a woman’s second or third decade of life, usually during pregnancy; however, a significant number of cases also occur sporadically. When nipple hyperkeratosis occurs in males, it is usually in those receiving hormone therapy. In more than 50% of cases, both the nipple and areola are involved.2 Nipple-only involvement is seen in 17% of cases.2 Nipple hyperkeratosis may also be a skin sequela of chronic graft versus host disease.3 Nipple hyperkeratosis can be classified into 3 types: type 1 occurs as an extension of an epidermal nevus; type 2 occurs in association with other dermatoses; and type 3 is idiopathic. In type 2 disease, hyperkeratosis of the nipple occurs as a result of another cutaneous disease process such as atopic dermatitis or acanthosis nigricans.3 Type 3 nipple Treatment options for nipple hyperkeratosis Acitretin Ammonium lactate Calcipotriol Carbon dioxide laser Corticosteroids, topical Lactic acid Liquid nitrogen cryotherapy Salicylic acid Surgical removal of the nipple with graft reconstruction Tretinoin, topical Urea

hyperkeratosis has been associated with puberty, pregnancy, and certain medications used in prostate cancer.4 Most type 3 disease is asymptomatic. In pregnancy, unilateral disease may become bilateral or there may be increased pigmentation and hyperkeratosis, which often persist postpartum. In addition, hyperkeratosis that occurs during pregnancy is more likely to be symptomatic, with breast tenderness and/or pruritis. Type 1 nipple hyperkeratosis is usually unilateral and may occur in both men and women. Type 2 disease is bilateral, and type 3 is bilateral and symmetric.5

Approximately 50 cases of nipple hyperkeratosis have been reported; of these, 80% occurred in women. Diagnosis of the condition is clinical, but biopsy can aid in ruling out other hyperkeratoses. Histologically, in addition to hyperkeratosis, there are nonspecific findings such as acanthosis, papillomatosis, keratin plugging, and dermal lymphocytic infiltration. The immunophenotype of nipple hyperkeratosis shares some features of mycosis fungoides, including a CD3 epidermal infiltrate with a predominance of CD4 cells.6 Clinically, nipple hyperkeratosis can be mistaken for acanthosis nigricans, Darier disease, chronic eczema, epidermal nevus, confluent and reticulated papillomatosis, seborrheic keratosis, Paget disease, basal cell carcinoma, dermatophytosis, or Bowen disease.1 Because nipple hyperkeratosis is generally asymptomatic, features such as nipple discharge or retraction should prompt a search for another etiology. Notably, malignant acanthosis nigricans often presents with hyperkeratosis.7 Nevoid hyperkeratosis of the nipple often presents during or is worsened by pregnancy and estrogen therapy, and therefore, an endocrine association has been postulated. During pregnancy, other physiologic changes of the nipple and areola may occur, including enlargement, hyperpigmentation, secondary areolae, and hypertrophied sebaceous glands. Some argue that pregnancy-associated nipple hyperkeratosis is a distinct clinical entity of hyperkeratosis of the nipple and areola.3 Even when nipple hyperkeratosis is not symptomatic, it can be a cosmetic issue, and hyperkeratosis will not remit unless treated. However, medical treatment alone,

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including corticosteroids, topical agents (0.025% tretinoin, 12% ammonium lactate, 12% lactic acid),3 or keratolytic agents (6% salicylic acid, urea) are often insufficient.1 One case of remission with acitretin and topical calcipotriol treatment has been reported.7 In many cases, surgery is considered an appropriate initial treatment, even though there may be aesthetic consequences. Ablation with a carbon dioxide laser may offer cosmetically acceptable treatment.8 More invasive approaches include cryotherapy,3 radiofrequency ablation,9 and surgical removal of the nipple,10 with subsequent graft reconstruction. Patients should have follow-up visits in 3 to 6 months after therapy, with instructions to return earlier if they experience nipple discharge, retraction, or mass. After presentation and discussion of the various treatment options, the patient in our case elected for a trial of 5% salicylic acid. Moderate improvement was noted at 3-month follow-up. Harina Vin, BS, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston. References 1. Yaghoobi R, Feily A. Bilateral nevoid hyperkeratosis of the nipples and areolae. Int J Dermatol. 2015;54(1):e47-e48. 2. Kubota Y, Koga T, Nakayama J, Kiryu H. Naevoid hyperkeratosis of the nipple and areola in a man. Br J Dermatol. 2000;142(2):382-384.

CASE #2

Lichen nitidus

Lichen nitidus is a rare chronic inflammatory rash of multiple small papules that affects individuals of any race or age but is more prevalent in children and young adults.1 It is self-limited and resolves in months to years. The exact cause of lichen nitidus remains unknown, 2 and no infectious agent that precipitates the rash has been identified. There is debate regarding its relationship to lichen planus and whether they represent different immunologic responses to a shared triggering event, given their occasional coexistence on the same patient.1 Clinically, lichen nitidus is a skin eruption characterized by shiny, flat-topped, skin-colored, pinhead-sized papules arranged in groups and found on the chest, abdomen, genitalia, and upper extremities. The lesions also present along lines of trauma as a result of Koebner phenomenon. These lesions are typically asymptomatic, although pruritus sometimes occurs.1-5 Hypopigmented papules are also common, especially in patients with darker skin.1 As the lesions resolve, they are replaced by postinflammatory hyperpigmented macules that also eventually clear.2

3. Higgins HW, Jenkins J, Horn TD, Kroumpouzos G. Pregnancy-associated hyperkeratosis of the nipple: a report of 25 cases. JAMA Dermatol. 2013;149(6):722-726. 4. Levy-Franckel A. Les hyperkeratoses de l’areole et du mamelon. Paris Med. 1938;28:63-66. 5. Mehregan AH, Rahbari H. Hyperkeratosis of nipple and areola. Arch

The exact cause of lichen nitidus remains unknown, and no infectious agent that precipitates the rash has been identified.

Dermatol. 1977;113(12):1691-1692. 6. Roustan G, Yus ES, Simón A. Nevoid hyperkeratosis of the areola with histopathological features mimicking mycosis fungoides. Eur J Dermatol. 2002;12(1):79-81. 7. Kartal Durmazlar SP, Eskioglu F, Bodur Z. Hyperkeratosis of the nipple and areola: 2 years of remission with low-dose acitretin and topical calcipotriol therapy. J Dermatolog Treat. 2008;19(6):337-340. 8. Fenniche S, Badri T. Images in clinical medicine. Nevoid hyperkeratosis of the nipple and areola. N Engl J Med. 2010;362(17):1618. 9. Ozyazgan I, Kontas¸ O, Ferahbas¸ A. Treatment of nevoid hyperkeratosis of the nipple and areola using a radiofrequency surgical unit. Dermatol Surg. 2005;31(6):703-705. 10. Milanovic R, Martic K, Stanec S, Zic R, Vlajcic Z, Stanec Z. Surgical treatment of nevoid hyperkeratosis of the areola by removal of the areola and reconstruction with a skin graft. Ann Plast Surg. 2005;54(6):667-669.

Less frequently, lichen nitidus presents with nail changes,3 mucosal involvement,1,2 or palmoplantar hyperkeratosis.4 It is not associated with any systemic diseases, although some maintain that the rare occurrence of widespread lichen nitidus can be an early sign of inflammatory bowel disease, especially Crohn’s disease. Thus, a detailed review of systems is necessary in the context of a diffuse eruption.5 In the rare event that lichen nitidus presents with oral involvement, minute flat gray-white papules on the buccal mucosa may be seen.2 Onychodystrophy is seen in a minority of cases of lichen nitidus (<5%-10%) and often precedes the skin manifestations. The lack of skin findings may delay diagnosis. Nail changes include thickening, ridging, pitting, or

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CME CE

Dermatology Clinic

detachment.2 The clinician should suspect lichen nitidus with violaceous or pigmentary changes of the nail fold and subtle papules on the affected digits. Patients with lichen nitidus of the nails are more likely to have palmar involvement as well.3,4 In rare cases, nail lesions associated with lichen nitidus can present as a median canaliform dystrophy, which is a treelike split in the nail plate; this presentation is associated with isotretinoin use and nailbed tumors. Lichen nitidus should be suspected as a possibility in any child with onychodystrophy or median canaliform dystrophy without a history of trauma, isotretinoin use, or subungal tumor.3 Lichen planus

The most difficult diagnosis from which to differentiate lichen nitidus is early lichen planus. more commonly presents with nail changes (10%), but the changes are typically more severe than those seen in lichen nitidus and may exhibit anonychia or pterygium formation. Like the skin lesions that occur, the nail findings of lichen nitidus are self-limited.1-3 Palmar lichen nitidus, although rare, can present as dome-shaped, erythematous, hyperkeratotic, purpuric, or pitted eruptions in the context of lichen nitidus occurring at other sites as well. Palmar lesions may resemble dyshidrotic eczema in some cases. If the papules are pitted or large enough to form plaques, the clinician should rule out arsenical keratosis, Darier disease, nevoid basal cell carcinoma syndrome, and porokeratotic eccrine ostial and dermal duct nevus. When the lesions exhibit hyperkeratosis, consider chronic eczema or keratodermas as well. Unlike skin lesions, palmar lichen nitidus exhibits a chronic course in many patients and may remain refractory to treatment with topical steroids alone or with tacrolimus and acitretin. Palmar lichen nitidus may be difficult to distinguish from lichen planus on examination alone.4 In general, the differential diagnosis of lichen nitidus includes lichen planus, lichen striatus, guttate lichen sclerosus, lichen spinulosus, lichen scrofulosorum, verruca plana, papular sarcoidosis, lichenoid secondary syphilis, frictional lichenoid dermatitis (on the elbows and knees), and eczema.1,3-5 Patient history and clinical findings alone can distinguish lichen nitidus in most cases. The most difficult diagnosis from which to differentiate lichen nitidus is early lichen planus, as lesions identical to

lichen nitidus appear on 25% to 30% of patients with lichen planus.1 Features indicating a diagnosis of lichen nitidus include monomorphic, monochromatic papules and absence of Wickham striae.1 If clinical findings are unclear, the unique histologic appearance of lichen nitidus confirms the diagnosis. A focal inflammatory infiltrate closely apposes the epidermis and is surrounded by elongated epidermal rete ridges on the margins, giving the appearance of a claw clutching a ball. The lesion rarely spans more than 2 to 3 dermal papillae.1-6 The infiltrate is composed of lymphocytes, epithelioid cells, and occasional histiocytes.1,2,6 Parakeratotic caps are frequently present in the overlying atrophic epidermis and are helpful in differentiating lichen nitidus from early, small lesions of lichen planus. Furthermore, lichen nitidus lacks deposits of immunoreactants, a feature that may be seen in lichen planus.1 No treatment is required in most cases of lichen nitidus; reassurance of the patient or parent is usually sufficient.1-4 If the patient is symptomatic or if lesions are generalized or disturbing to the patient cosmetically, several treatment modalities are available, all with varying success rates.2 Topical corticosteroids and oral antihistamines can alleviate pruritus. Topical calcineurin inhibitors have been used successfully in some reports of children with lichen nitidus. If topical therapies fail and lichen nitidus recurs or becomes generalized, narrowband ultraviolet B treatment and photochemotherapy are also options.1,2 The mother of the patient in our case was reassured that the lesions would resolve without treatment, and no treatment was prescribed. n Eman Bahrani, BA, is a medical student and Jennifer S. Ruth, MD, is a dermatology resident at Baylor College of Medicine in Houston. References 1. Schwarz T. Immunology. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:198-199. 2. Chu J, Lam JM. Lichen nitidus. CMAJ. 2014;186(18):E688. 3. Tay EY, Ho MS, Chandran NS, Lee JS, Heng YK. Lichen nitidus presenting with nail changes—case report and review of the literature. Pediatr Dermatol. 2015;32(3):386-388. 4. Cakmak SK, Unal E, Gönül M, Yayla D, Ozhamam E. Lichen nitidus with involvement of the palms. Pediatr Dermatol. 2013;30(5):e100-e101. 5. Wanat KA, Elenitsas R, Chachkin S, Lubinski S, Rosenbach M. Extensive lichen nitidus as a clue to underlying Crohn’s disease. J Am Acad Dermatol. 2012;67(5):e218-e220. 6. Liu H, Chen S, Shi Z, Zhang F. In vivo imaging of lichen nitidus with confocal laser scanning microscopy. Arch Dermatol. 2011;147(1):142.

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CME CE DERMATOLOGY COURSES

Circular rashes SACHIN ALLAHABADI, BS, BA, AND RANA MAYS, MD

CASE #1

CASE #2

A 23-year-old African American woman presents for a rash that has recurred on her arms for the last 2 years. The rash is not pruritic or painful. Initially, the rash was very red and became darker with time. The patient states that the rash occurs in the same spot every time. She is otherwise healthy. Her medications include occasional ibuprofen for menstrual pain and a daily multivitamin. She has tried over-the-counter hydrocortisone with minimal improvement of the lesions.

A 19-year-old African American male presents with a 7-month history of a severely pruritic rash on his legs and arms. He is otherwise healthy and takes a daily multivitamin. He admits to taking long hot showers daily. He uses no moisturizer and washes with a deodorant soap. He has not tried any topical medications for the rash. He is currently taking diphenhydramine as needed for the pruritus, but it has not resulted in substantial improvement in the lesions.

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CME CE

CASE #1

Dermatologic Look-Alikes

Fixed drug eruption

Fixed drug eruption is a common cause of inflammatory skin pathology. Cutaneous reactions are the most common form of adverse drug reaction. Fixed drug eruptions are one of the most common types of cutaneous drug eruption, along with morbilliform (maculopapular) drug reactions and urticaria/angioedema.1-4 Fixed drug eruptions are localized cutaneous responses to an offending medication. The adjective “fixed” indicates that the same cutaneous reaction occurs in the same location if the causative agent is ingested again.5 Fixed drug eruptions typically present as well-defined, circular or oval-shaped violaceous plaques with hyperpigmentation and edema. The lesion may be solitary or few in number, and they may be pruritic, burning, or painful; however, systemic complications are rare.2,5-7 Vesicles or bullae may form in an annular pattern, with potential for erosion or blistering in the middle of the lesion.6 The lesions are transient, fading over a few days to weeks, with residual hyperpigmentation indicative of the affected site that may last weeks to months.8 The original lesion or lesions may not leave residual hyperpigmentation, although this is less common.2,5,9 Although the lesions may occur in any location, common sites include the genitalia (especially the glans penis in males), dorsal area of the hands, feet, lips, perioral area of the face, and trunk.5,6,8 These localized skin reactions tend to occur 1 to 2 weeks after exposure to the drug, but subsequent reactions occur more rapidly, typically within a few hours or at least within 24 hours of exposure.2,5,10 Frequent causative agents of fixed drug eruption include sulfonamides (including trimethoprimsulfamethoxazole), nonsteroidal anti-inflammatory drugs, salicylates, barbiturates, tetracyclines, oral contraceptives, quinine, and carbamazepine.5,6 Severe adverse drug reactions may be fatal or life threatening, especially in pediatric populations who have age-related differences in hepatic drug metabolism.11 The pathophysiology of fixed drug eruption is not well described, but it is thought that fixed drug eruption results from activated intraepidermal CD8+ T cells that elicit a stronger and more rapid response to re-exposure with the same drug, resulting in tissue damage in the lower portions of the epidermis involving keratinocytes and melanocytes.5,12 Histologically, fixed drug eruption may have a variety of presentations but is often characterized by vacuolar interface

dermatitis at the dermoepidermal junction, with necrotic keratinocytes and eosinophilic and neutrophilic infiltrates. Lymphocytic infiltrate may be in the upper dermis.3,5 Damage to the basal cells of the epidermis and melanocytes results in melanin leaking into the papillary dermis, where pigment may be engulfed by macrophages.5 In chronic recurrent fixed drug eruption at the same site, significant fibrotic changes may be seen in the papillary dermis and dermal melanophages.3 Clinical diagnosis of fixed drug eruption is often missed because both clinicians and patients may not recognize the localized skin reaction as a typical drug reaction pattern. Fixed drug eruption can usually be distinguished by history and physical examination, but punch biopsy or medication rechallenge can be useful tools when the diagnosis is uncertain.5 In a patient taking multiple medications, confirmation of the causative agent is accomplished by administering drugs individually to see which reproduces a reaction within a few hours at the same site.13 According to a recent study, patch testing may have diagnostic utility in cases of suspected fixed drug eruption caused by contrast medium or antiepileptic medications.14

The same cutaneous reaction occurs in the same location if the causative agent is ingested again. The differential diagnosis of fixed drug eruption is extensive and includes recurrent herpes simplex infection, tinea infections, nummular eczema, post-inflammatory hyperpigmentation, acute urticaria, arthropod bite infections, pityriasis rosea, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and phytophotodermatitis, among others. Recurrent herpes simplex infection, particularly in the genital region, can be differentiated from fixed drug eruption through skin biopsy detecting herpes simplex virus DNA by means of polymerase chain reaction.15,16 Clinically, herpes simplex virus has grouped vesicles on an erythematous base, with more pain than pruritus.5 Histologically, herpes simplex virus involves margination of nuclear chromatin, multinuclear giant cells, ballooning degeneration, and nuclear viral inclusions, none of which are present in fixed drug eruption.5 Tinea infections present as annular lesions, usually with multiple erythematous scaly papules or plaques that may increase in size and spread centrifugally. Furthermore, the typical distribution differs from that of fixed drug eruption,

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involving the trunk and extremities but excluding the groin, palms and soles, and nails.6 Nummular eczema may be differentiated from fixed drug eruption by typical location. Fixed drug eruption lesions are common on the hands, feet, genitalia, lips, and face, and nummular eczema lesions are more common on extensor surface, although location varies by age.1 Lesions of nummular eczema involve intense pruritus and are chronic, relapsing lesions, whereas lesions in fixed drug eruption may not be pruritic and may fade over a few days to weeks, resulting in hyperpigmentation in the area of the lesion.6 Postinflammatory hyperpigmentation may mimic residual hyperpigmentation following the initial lesion in fixed drug eruption but can be differentiated based on an associated prior inflammatory skin infection such as acne vulgaris, atopic dermatitis, or impetigo.17 Acute urticaria from drug exposure develops rapidly and lesions resolve within 1 day; however, lesions in fixed drug eruption may last for a few days and ultimately disappear, with subsequent hyperpigmentation.18,19 The lesions in urticaria are raised, erythematous, pruritic wheals and may be diffuse and not well demarcated like those in fixed drug eruption. Arthropod bite infections may be differentiated from fixed drug eruption by location, as they tend to occur on the extremities and do not resolve with hyperpigmentation.19,20 Pityriasis rosea in initial stages with a herald patch may mimic fixed drug eruption but will be followed by small, salmon-colored raised lesions across the trunk, often in a Christmas-tree type pattern rather than hyperpigmentation.21 Erythema multiforme can also result from drug exposure. However, it presents as a characteristic target lesion with an erythematous center surrounded by a pale inner ring with an additional erythematous outer ring, unlike the sharply demarcated pigmented vesicles or bullae in fixed drug eruption. Stevens-Johnson syndrome and toxic epidermal necrolysis are extreme forms of erythema multiforme and may be differentiated from fixed drug eruption by the presence of a fever and involvement of the oral mucosa in addition to the conjunctiva and genitourinary regions, with erosions and hemorrhagic crusts that are not present in fixed drug eruption.22 Phytophotodermatitis also involves residual hyperpigmentation, with erythematous and edematous bullae and vesicles similar to those seen in fixed drug eruption, but rather than well-demarcated ring-like lesions, phytophotodermatitis is distributed in streak-like or artificial patterns.5 The treatment of fixed drug eruption begins by identifying and discontinuing the offending drug immediately. If treatment of an underlying condition is still necessary, a different

medication should be prescribed. Medium- or high-potency topical steroids may be provided for symptomatic relief in severe cases, and antihistamines may help relieve associated pruritus. For persistent hyperpigmentation, hydroquinone 4% cream may be applied to decrease the pigmented appearance.5 For the patient in our case, biopsy of the lesion was consistent with fixed drug eruption. Ibuprofen was determined to be the likely culprit, and the patient was advised to discontinue that medication. After discontinuing ibuprofen, there was no recurrence of the lesions.

CASE #2

Nummular eczema

Nummular eczema, also known as nummular dermatitis or discoid eczema, is a common morphologic subtype of eczematous dermatitis.22 The prevalence of nummular eczema has been reported at 2 cases per 1000 people.23 The Greek word eczema means “to boil over” and nummular means “coin shaped,” and both of these words accurately describe the lesions of nummular eczema, which are numerous, well-defined, coin-shaped or discoid, erythematous, oozing, and crusted skin plaques that derive from the confluence of papules and papulovesicles.1,22 If the lesions have a bacterial origin such as Staphylococcus, they are more likely to involve honey-crusted vesicles. Scratch marks or excoriations will often be seen in the lesions as a result of the intense pruritus, and the lesions are often lichenified and hyperkeratotic.8,23 The lesions tend to measure one to a few centimeters in diameter.8,24 Nummular eczema has a predilection for extremities, and lesions tend to be located on the lower limbs (thighs and legs) in men and on the forearms and hand dorsa in women. Lesions are not typically seen on the face or scalp.8 Patients often have severe pruritus, a chronic relapsing course, and may have a personal or family history of atopic diseases, such as food allergies, asthma, or allergic rhinitis.3 Nummular eczema affects males more frequently than females, and it tends to present in males at an older age (>50 years, rather than <30 years in females). Although atopic dermatitis is prominent in children, nummular eczema is not common at a young age.8,23,24

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CME CE

Dermatologic Look-Alikes

The etiology of nummular eczema has not been precisely defined, and factors such as nutrition, infection (bacterial colonization), psychiatric/emotional issues, alcohol intake, and dry skin (especially in the elderly) have all been implicated in its pathogenesis.24-26 The course of eczema oscillates, increasing in colder months, likely as a result of increased contact with hot water, soaps, and detergents, and decreasing in summer months.1,26 In older patients, dry skin leads to cracking and fissuring in the stratum corneum, especially in winter months, which in turn leads to worsening pruritus and dryness, which are common features in nummular eczema.24 With an already damaged skin barrier, allergens may enter the skin and exacerbate the eczema.24 In addition to xerosis, nummular dermatitis is also associated with contact dermatitis and venous hypertension.8,24

In addition to xerosis, nummular dermatitis is also associated with contact dermatitis and venous hypertension. The diagnosis of eczema is primarily based on history and physical examination alone, as there are no distinct diagnostic modalities for eczema. Early histologic examination will show epidermal spongiosis and dermal edema with lymphocytic infiltrate and microvesicle formation, whereas later histologic examination will show hyperkeratosis, parakeratosis, and progressive acanthosis with a thickened granular layer.22 Because contact allergy occurs commonly with nummular eczema, patch testing is recommended in those with persistent or recurrent discoid eczema to distinguish allergen-related causes.25 If the lesions are complicated by bacterial infection, swabs for bacterial culture may be taken, and skin scrapings may be performed with a potassium hydroxide preparation to rule out fungal infection. The differential diagnosis of nummular eczema includes tinea infections, contact dermatitis, fixed drug eruption, cutaneous T-cell lymphoma, granuloma annulare, pityriasis rosea, secondary syphilis, lichen simplex chronicus, and plaque psoriasis. Clinically, tinea infections have a central clearing, with a surrounding and advancing red, scaly, elevated border, but not the crusting, scaling, or lack of central clearing seen in nummular eczema.27 Furthermore, patients with tinea infections may not have a history of eczema and may only have 1 or 2 asymptomatic lesions with affected contacts, especially in humid climates.27 Definitive diagnosis of tinea may be

distinguished by skin scrapings with potassium hydroxide preparation demonstrating dermatophytes. Nummular eczema may be distinguished from contact dermatitis by the characteristic coin-shaped morphology in nummular eczema, although this is often associated with contact dermatitis. Patch testing may be useful in persistent cases to rule out contact allergy.25 The annular lesions of fixed drug eruption appear similar to those of nummular eczema, with central vesicles or bullae, but they tend to occur more often on the hands and feet, genitalia, and lips and face. Lesions in fixed drug eruption are not always pruritic and are more transient than the chronic relapsing lesions of nummular eczema, as fixed drug eruption may fade over a few days, resulting in hyperpigmentation in the area of the lesion.6 In cutaneous T-cell lymphoma, neoplastic T cells cause erythematous scaling, but cutaneous T-cell lymphoma may be differentiated by specific biomarkers or biopsy, depending on the stage of disease. The lesions of cutaneous T-cell lymphoma do not follow developmental boundaries and have a predilection for the bathing trunk region, unlike the extremities, as in nummular eczema.28 Granuloma annulare involves erythematous or flesh-colored papules that are not scaly, but there are no associated vesicles or scaling involved as there is in nummular eczema.6 In its early stages with a herald patch, pityriasis rosea may mimic and be indistinguishable from nummular eczema, but a few days to weeks later, pityriasis rosea will present with small salmon-colored raised lesions across the trunk, often in a Christmas-tree pattern.21 If similar lesions occur on the palms and soles, it is important to rule out secondary syphilis with rapid plasma reagin or Venereal Disease Research Laboratory (VDRL) testing. Lichen simplex chronicus results from lichenification caused by repetitive scratching and itching and is more common in patients with anxiety or obsessive-compulsive disorders. Lesions of lichen simplex chronicus may appear anywhere but are more commonly seen on the head and neck in women and on the perineum and scrotum in men, as opposed to the extremities in nummular eczema.8 Plaque psoriasis presents with a larger, thick, and silvery scale that is not present in nummular eczema. Plaque psoriasis is typically found on the extensor surfaces of the knees and elbows, often with additional involvement on the scalp and positive Koebner phenomenon, whereas nummular eczema tends to be seen on the extremities and does not exhibit Koebner phenomenon.8 Topical corticosteroids, such as hydrocortisone cream 1%, are the initial treatment for nummular eczema, and

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TABLE 1. Fixed drug eruption versus nummular eczema Fixed drug eruption

Nummular eczema

Dermatologic presentation

• Well-defined, circular or oval-shaped violaceous plaques with hyperpigmentation and edema • Transient lesions, fading over a few days to weeks, with residual hyperpigmentation that is indicative of the affected site and that may last weeks to months

Well-defined, coin-shaped or discoid, erythematous, oozing, and crusted skin plaques that derive from the confluence of papules and papulovesicles

Associations

• Related to medications • May in some cases be pruritic, burning, or painful; however, systemic complications are rare

• Severe pruritus, a chronic relapsing course • May have a personal or family history of atopic diseases such as food allergies, asthma, or allergic rhinitis • Tends to present in males at an older age (>50 years versus <30 years in females)

Etiology

Sulfonamides (including trimethoprim-sulfamethoxazole), nonsteroidal anti-inflammatory drugs, salicylates, barbiturates, tetracyclines, oral contraceptives, quinine, and carbamazepine

Imprecisely defined; factors such as nutrition, infection (bacterial colonization), psychiatric/emotional issues, alcohol intake, and dry skin (especially in the elderly) may play a role

Characteristic location

Genitalia (especially the glans penis in males), dorsal surface of hands, feet, lips, perioral area of the face, and trunk

• Predilection for extremities: lower limbs (thighs and legs) in men; forearms and hand dorsa in women • Lesions typically spare the face and scalp

Histology

Vacuolar interface dermatitis at the dermoepidermal junction with necrotic keratinocytes and eosinophilic and neutrophilic infiltrate

• Early histology: epidermal spongiosis and dermal edema with lymphocytic infiltrate and microvesicle formation • Later histology: hyperkeratosis, parakeratosis, and progressive acanthosis with a thickened granular layer

Diagnosis

• History and physical examination • Punch biopsy or medication rechallenge may provide additional assistance

History and physical examination

Treatment

• Discontinue offending drug immediately • Treat symptomatically • Administer medium-potency topical steroids for acute symptomatic relief, in addition to antihistamines for pruritus

• Topical corticosteroids, more potent steroids for refractory cases • Antihistamines for pruritus relief • Emollients such as petrolatum help maintain skin moisture • Severe cases: topical immunomodulators (eg, tacrolimus and pimecrolimus) • Pediatric cases: consider methotrexate

more potent steroids may be used in refractory cases.26 Antihistamines may provide symptomatic relief of pruritus.26 Furthermore, emollients like petrolatum help maintain skin moisture, thereby helping prevent excessive dryness and pruritus. In severe cases, topical immunomodulators, such as tacrolimus and pimecrolimus, may be used. Phototherapy may also be used to clear the lesions.8 Recent studies have demonstrated that methotrexate may be used to treat pediatric nummular eczema without significant adverse effects in eczema that is refractory to conventional treatment.29,30 For the patient in our case, biopsy of the lesions was consistent with nummular eczema. Treatment with a topical clobetasol ointment applied twice daily to the lesions was initiated. The patient was advised to use a gentle cleanser,

shorten his showers to less than 10 minutes, and use moisturizer several times a day. After a few weeks of this regimen, the patient had dramatic clearance of many of the lesions. n Sachin Allahabadi, BS, BA, is a medical student and Rana Mays, MD, is a dermatology resident at Baylor College of Medicine in Houston. References 1. Pugliarello S, Cozzi A, Gisondi P, Girolomoni G. Phenotypes of atopic dermatitis. J Dtsch Dermatol Ges. 2011;9(1):12-20. 2. Farshchian M, Ansar A, Zamanian A, Rahmatpour-Rokni G, KimyaiAsadi A, Farshchian M. Drug-induced skin reactions: a 2-year study. Clin Cosmet Investig Dermatol. 2015;8:53-56.

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CME CE

Dermatologic Look-Alikes

3. Weyers W, Metze D. Histopathology of drug eruptions—general crite-

17. Davis EC, Callender VD. Postinflammatory hyperpigmentation: a

ria, common patterns, and differential diagnosis. Dermatol Pract Concept.

review of the epidemiology, clinical features, and treatment options in skin

2011;1(1):33-47.

of color. J Clin Aesthet Dermatol. 2010;3(7):20-31.

4. Akpinar F, Dervis E. Drug eruptions: an 8-year study including

18. Lee A, Thomson J. Drug-induced skin reactions. In: Lee A, ed. Adverse

106 inpatients at a dermatology clinic in Turkey. Indian J Dermatol.

Drug Reactions. 2nd ed. London, UK: Pharmaceutial Press; 2005.

2012;57(3):194-198.

19. Burkhart CN, Morrell DS, Goldsmith LA, et al., eds. VisualDx: Essential

5. Flowers H, Brodell R, Brents M, Wyatt JP. Fixed drug eruptions: presen-

Pediatric Dermatology. Philadelphia, PA: Lippincott Williams & Wilkins; 2010.

tation, diagnosis, and management. South Med J. 2014;107(11):724-727.

20. Juckett G. Arthropod bites. Am Fam Physician. 2013;88(12):841-847.

6. Alarkhia M. Annular papules: making the right diagnosis. UWOMJ.

21. Stulberg DL, Wolfrey J. Pityriasis rosea. Am Fam Physician. 2004;69(1):87-91.

2008;77(1):34-36.

22. Lazar AJF, Murphy GF. The skin. In: Kumar V, Abbas AK, Aster JC.

7. Mahboob A, Haroon TS. Drugs causing fixed eruptions: a study of 450

Robbins & Cotran Pathologic Basis of Disease. 8th ed. Philadelphia, PA:

cases. Int J Dermatol. 1998;37(11):833-838.

Elsevier Saunders; 2010:1165-1204.

8. Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. Philadelphia, PA: Mosby; 2003.

23. Burgin S. Nummular eczema, lichen simplex chronicus, and prurigo

9. Lee AY. Fixed drug eruptions. Incidence, recognition, and avoidance.

nodularis. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ,

Am J Clin Dermatol. 2000;1(5):277-285.

Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine. 8th ed. New

10. Gaiser CA. Sabatino D. Fluconazole-induced fixed drug eruption. J Clin

York, NY: McGraw Medical; 2012.

Aesthet Dermatol. 2013;6(3):44-45.

24. Bobonich M, Nolen M. Dermatology for Advanced Practice Clinicians.

11. Dilek N, Özkol HU, Akbas¸ A, et al. Cutaneous drug reactions in chil-

Philadelphia, PA: Lippincott Williams & Wilkins; 2014.

dren: a multicentric study. Postepy Dermatol Allergol. 2014;31(6):368-371.

25. Bonamonte D, Foti C, Vestita M, Ranieri LD, Angelini G. Nummular ecze-

12. Shiohara T, Mizukawa Y, Teraki Y. Pathophysiology of fixed drug

ma and contact allergy: a retrospective study. Dermatitis. 2012;23(4):153-157.

eruption: the role of skin-resident T cells. Curr Opin Allergy Clin Immunol.

26. Halberg M. Nummular eczema. J Emerg Med. 2012;43(5):e327-e328.

2002;2(4):317-323.

27. Noble SL, Forbes RC, Stamm PL. Diagnosis and management of com-

13. Ashton R, Leppard B. Differential Diagnosis in Dermatology. 3rd ed.

mon tinea infections. Am Fam Physician. 1998;58(1):163-174.

London, UK: Radcliffe Publishing; 2005.

28. Wong HK. Novel biomarkers, dysregulated epigenetics, and therapy in

14. Ohtoshi S, Kitami Y, Sueki H, Nakada T. Utility of patch testing for

cutaneous T-cell lymphoma. Discov Med. 2013;16(87):71-78.

patients with drug eruption. Clin Exp Dermatol. 2014;39(3):279-283.

29. Roberts H, Orchard D. Methotrexate is a safe and effective treatment

15. Gürkan A, Sarikaya E, Oğuz O, et al. The overlap of fixed drug erup-

for paediatric discoid (nummular) eczema: a case series of 25 children.

tion and human herpes virus type II associated erythema multiforme. J Turk

Australas J Dermatol. 2010;51(2):128-130.

Acad Dermatol. 2007;1(1):3.

30. Deo M, Yung A, Hill S, Rademaker M. Methotrexate for treat-

16. Sonnex C. Sorting out genital ulceration. Trends in Urology Gynaecology

ment of atopic dermatitis in children and adolescents. Int J Dermatol.

& Sexual Health. 2007;12(1)25-29.

2014;53(8):1037-1041.

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CME CE

POSTTEST Expiration date: January 15, 2017

DERMATOLOGY COURSES CREDITS: 0.5

For more credit information, please turn to p. 46.

Dermatology Clinic

Dermatologic Look-Alikes

page 47

Case #1: Nipple hyperkeratosis 1. A man, aged 58 years, presents with features that are consistent with nipple hyperkeratosis. Which of the following features would lead you to rule out typical type 1 nipple hyperkeratosis? a. Unilateral lesion b. Secondary to dermatitis c. Extension of an existing nevus d. Not associated with pregnancy 2. Which of the following is a keratolytic agent that has been shown to be effective in treating nipple hyperkeratosis? a. Zinc pyrithione c. Ammonium lactate b. Urea d. Lactic acid Case # 2: Lichen nitidus 3. A 7-year-old African American female presents with a 5-month history of asymptomatic rash and nail changes, with no pain or pruritus. The mother reports the child’s nails on the first through third digits on the left hand first exhibited dryness and white ridges, and 1 month later, a subtle rash erupted on her shoulders and chest. Examination finds nails on both hands exhibit pitting and ridging but no erythema or tenderness. The rash consists of grouped, shiny, flat-topped, hypopigmented minute papules, which also exhibit koebnerization but no tenderness or erythema. Palms, oral mucosa, and genitals are normal. What is the most appropriate next step? a. Prescribe topical corticosteroids. b. Prescribe topical calcineurin inhibitors. c. Biopsy the lesions. d. Reassure the mother that the condition is self-limited. 4. A 22-year-old white man with a 1-year history of generalized lichen nitidus presents after taking prescription topical medications and oral antihistamines for 4 months without resolution of his pruritus associated with his cutaneous lesions. A thorough review of systems remains negative. What other treatment options could the clinician consider? a. Systemic corticosteroids or oral methotrexate b. Narrowband ultraviolet B or photochemotherapy c. Systemic corticosteroids or photochemotherapy d. Oral methotrexate or narrowband ultraviolet B

page 51

Case #1: Fixed drug eruption 1. After taking trimethoprim-sulfamethoxazole for a urinary tract infection for 1 week, a 14-year-old female has a circular erythematous lesion on her lips. The lesion is no longer visible 5 days later when she sees her clinician, but there is an area of hyperpigmentation. On skin biopsy, which of the following findings would confirm fixed drug eruption? a. Dermal edema with perivascular infiltration by lymphocytes and inflammatory cells, followed by epidermal spongiosis and microvesicle formation b. Variable spongiosis in the epidermis with ballooning keratinocytes and superficial inflammation involving lymphocytes and dermal melanophages c. Margination of nuclear chromatin, multinuclear giant cells, ballooning degeneration, and nuclear inclusions d. Vacuolar interface dermatitis at the dermoepidermal junction with epidermal necrotic keratinocytes, dermal melanophages, and dermal fibrosis 2. Which of the following lesions is most concerning for fixed drug eruption? a. Oral mucosal lesion b. Erythematous pruritic wheals c. Violaceous plaque d. Scaly plaque Case #2: Nummular eczema 3. A 52-year-old man with benign prostatic hypertrophy presents with annular, scaly crusting lesions on his legs that appeared 2 days after he began treatment for urinary tract infection (UTI). He was allergic to nuts as a child but is no longer. His mother had similar papulovesicular lesions in the past. He says he cannot stop scratching his legs because they are extremely itchy. What is the most appropriate step at this time? a. Immediately discontinue the drug used for the UTI b. Treat with hydrocortisone cream 1% and emollients c. Treat with immunomodulators (eg, tacrolimus, pimecrolimus) d. Treat with methotrexate 4. A 28-year-old woman with a family history of asthma would most likely present with nummular eczema at which of the following locations? a. Face and scalp c. Thighs and lower legs b. Dorsa of hands and forearms d. Intertriginous regions

TO TAKE THE POSTTEST please go to: myCME.com/Jan16CAderm

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LEGAL ADVISOR CASE

Undisclosed condition leads to death

BY ANN W. LATNER, JD

In her 17 years of employment with a large university hospital, Ms. M, a 58-year-old nurse, had worked various shifts in different departments. For the last 9 months, she had been working the night shift and found that the schedule suited her. Her children were now adults and living on their own and Ms. M was divorced, so the night shift did not negatively affect her family. Professionally, she preferred it. In the quiet of the hospital at night, Ms. M felt more autonomous and more connected with her patients, who were often alone (as it was after visiting hours) and frightened. One night, at approximately 3 a.m., a patient was brought in from the emergency department (ED) in great pain. Ms. M immediately looked at the patient’s records and orders from the ED physician. The patient, Mr. B, was a 48-year-old man who had been brought into the ED that afternoon complaining of severe abdominal pain, with no obvious cause and no other symptoms such as fever or respiratory distress. The pain was hard to manage; notes from the ED indicated that morphine and hydrocodone/ paracetamol had proven ineffective, and the ED

A patient’s widow asserts that the clinician should have checked hospital records taken prior to admission. A court had to decide whether Ms. M had breached the standard of care for treatment by not accessing prior hospital records.

physician had finally ordered hydromorphone. Even so, the patient’s pain remained severe, and the decision was made to admit him to the hospital for further testing the next day to determine the cause of the pain. The ED physician ordered 1 to 2 mg of hydromorphone administered intravenously no more than every two hours for pain and 12.5 mg of promethazine for nausea. The orders also called for supplemental oxygen as necessary, per the hospital’s protocol. Ms. M introduced herself to the patient and began her standard head-to-toe assessment. The assessment would normally include having the patient fill out a database form regarding past medical history, among other information. However, due to Mr. B’s terrible pain, he was only able to fill out a few lines before giving the form back to Ms. M. 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 “Don’t worry about it,” she told him. “We’ll fill this out later.” Ms. M knew that the hospital’s policy was that the patient’s database form should be filled out within the first 24 hours of admission, but clearly the patient’s pain was interfering. Ms. M went over the ED records again and saw that Mr. B had been given 1 mg of hydromorphone two hours earlier in the ED. By 3:35 a.m., Mr. B was rating his pain as 8 out of 10, and Ms. M administered 2 mg of hydromorphone. By 4:15 a.m., the patient’s pain was more tolerable. His oxygen saturation level was 97% with no supplementation, so Ms. M did not administer additional oxygen. She checked on Mr. B repeatedly and found him alert and awake.

There was no evidence to show that Mr. B’s death was caused by anything that Ms. M did, or did not do. What Ms. M did not know and what the patient and his wife had failed to tell anyone in the ED was that Mr. B had been at the hospital’s sleep center 9 years earlier and he had been diagnosed with severe obstructive sleep apnea and prescribed use of a continuous positive airway pressure (CPAP) machine to maintain an open airway when he slept. At 5 a.m., Mr. B complained of nausea, and Ms. M administered the prescribed dose of promethazine and then checked on the patient again at 5:30 a.m., when he rated his pain as a 3. However, shortly after 6 a.m., he reported to Ms. M that “the pain was coming back.” He rated the pain as a 5 but said it was increasing in severity and he was afraid it would become unbearable again. Ms. M repeated the 2-mg dose of hydromorphone. A half hour later, she checked on the patient and found him, for the first time, lying back in his bed. He rated his pain level as a 1 and finally seemed somewhat comfortable. Ms. M was relieved for the patient and encouraged him to rest. When she checked on him 20 minutes later, the patient was unresponsive. A Code Blue was called, but although the emergency team was able to resuscitate the patient, he died several days later. The autopsy report stated that the anatomic cause for the spontaneous cardiopulmonary arrest could not be identified. Many months later, Ms. M was notified that the hospital was being sued by the patient’s wife, who was alleging wrongful death based on the negligence of Ms. M. Among other things, the lawsuit claimed that Ms. M had breached the standard of care by not checking the medical records and determining that Mr. B needed a CPAP machine. In addition, the lawsuit claimed

that Ms. M did not monitor the patient properly, did not take proper vitals, and gave the patient too much hydromorphone. The hospital’s defense attorney met with Ms. M and explained that the case would likely hinge on testimony from medical experts about what the standard of care is and whether Ms. M had met it. During trial, both sides introduced medical experts. The experts, even those hired by the plaintiff, had to agree that a nurse can rely on the ED records and history and the attending physician’s records of patient history. There was no requirement, either by the hospital, or as part of the standard of care, that Ms. M was responsible for looking up old patient records, even if they were from the same hospital. In addition, the experts agreed that Ms. M had properly given the right amount of pain medication to the patient and that she had not breached the standard of care in any way. The case was dismissed. Legal background

In its decision, the court wrote, “In order to establish medical malpractice, a plaintiff must show: (1) the standard of care recognized by the medical community, (2) the failure of the defendant to meet the requisite standard of care, and (3) a direct causal connection between the medically negligent act and the injury sustained.” In this case, several medical experts testified as to the appropriate standard of care, and the court agreed that the testimony proved that Ms. M had met the requisite standard of care. In addition, there was no evidence to show that Mr. B’s death was caused by anything Ms. M did, or did not do, so the third element (a direct causal connection between the act and the injury) could not be met either. Protecting yourself

Ms. M did nothing wrong in this case, yet that, unfortunately, did not protect her from being involved in a lawsuit when the patient had a bad outcome. However, one of the things that protected Ms. M from liability was her detailed notes about the patient, which clearly documented how often she was checking on him, giving him pain medication, and making sure that he was tolerating the medication. Would it have been helpful for Ms. M to check the patient’s old hospital records? Possibly. However, she was not required to do so, nor was there any assumption that she would be investigating old records. Always take notes that are as detailed as possible so it will be clear how often and how carefully the patient was monitored, even if the notes are examined several years later, as happened with this case due to delays. n Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

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After steadily gaining weight for 10 years, an obese patient seeks help in achieving sustained, long-term weight loss. JULIA JURGENSEN, APRN, CNP

Mrs. Smith, aged 55 years, came to the clinic to discuss her weight and options for losing weight. She says that during the last 10 years, she has had a steady weight gain regardless of what she eats or how much she exercises. She is concerned that a medical reason may be causing this weight gain.

she did not believe it was a program that would work long term because she was eating only packaged foods from the company. She has not gained the weight back that she lost with NutriSystem. Pharmacotherapy for weight loss

Weight history

The patient’s lowest adult weight was 120 pounds. About 6 months ago, she was at her highest weight of 210. Her current weight is 201 pounds, with a BMI of 35.6.

She has tried orlistat and Dexatrim (OTC) in the past. She did not like the side effects of either of these medications and did not lose weight while taking them. Current diet

Past medical history

• Dyslipidemia, treated with simvastatin 20 mg • Hypertension, treated with metoprolol succinate 50 mg • Weight-bearing joint pain, specifically bilateral hips • Gastroesophageal reflux, treated with ranitidine 150 mg as needed • Snoring, per family member’s report • Family history of type 2 diabetes • No family history of Cushing’s disease or thyroid dysfunction Past weight loss attempts

Several years ago, the patient tried Weight Watchers for a 6-month period. While she liked the accountability of Weight Watchers, she was unable to maintain the program due to its cost. She lost 15 pounds during the 6 months but regained the weight after stopping the program. She has tried multiple attempts at recording her food intake and exercise without much success. Recently, she tried NutriSystem and lost approximately 10 pounds. However,

The patient consumes 3 to 5 small meals per day. She tries to adhere to a diet of approximately 1,200 calories per day; however, she does not use a calorie-tracking tool. For breakfast, she usually has fruit with milk, oatmeal, an egg, or an English muffin. She has 1 piece of low-fat string cheese midmorning. For lunch, she typically has a salad with grilled chicken or a grilled chicken sandwich. She has an apple during the late afternoon. Her dinner consists of either chicken or fish and vegetables. She denies snacking after dinner. She likes foods that are high in carbohydrates, and in the past, she has likely consumed more carbohydrates than she needs. She does not eat red meat and consumes minimal sweets. She drinks water, diet soda, and diet green tea. She also has two to three 6-ounce glasses of wine per week. She eats outside the home for approximately 3 lunches and 2 dinners per week. The lunches are at a specific restaurant where she is able to specify exactly how she would like something prepared. Dinners are at a variety of different restaurants.

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Case Study Current activity

The patient reports that she often gets frustrated by her lack of weight loss and quits workout routines frequently. In the last month, she started walking on the treadmill at least a few times per week for 30 to 45 minutes per session. Physical exam

• General: Obese, not cushingoid. No acute distress. • Skin: No suspicious lesions, striae, hirsutism, or acne. • Thyroid: Symmetric, not enlarged, no nodules. • Breasts: Not examined. • Heart: Regular rhythm. No murmurs. • Lungs: Clear to auscultation. • Abdomen: Obese, nontender, nondistended, and normal bowel sounds. No masses, hepatosplenomegaly, or hernias. • Rectum: Not examined. • Genitalia: Not examined. • Joints: No crepitus or xanthoma. • Extremities: No edema or lymphedema. • Gait: Able to rise and walk without difficulty. Balance normal. • Mental: Normal orientation, judgment, and mood. • Last TSH: 1.0 mIU/L • Blood pressure: 119/70 mm Hg • Pulse: 65 bpm QUESTION 1: What additional screening should be completed for Mrs. Smith due to her obesity? A. Fasting glucose B. Overnight oximetry C. Aspartate aminotransferase (AST) and alanine transaminase (ALT) D. All of the above Lab work

Mrs. Smith’s lab work returns as follows: • Fasting glucose: 127 mg/dL • HbA1c: 5.7% • Cholesterol: 175 (triglycerides: 147, HDL: 47, LDL: 68, and non–HDL: 84) • Overnight oximetry: no evidence of sleep apnea. • AST: 34 • ALT: 22

QUESTION 2: Based on these findings, can you diagnose the patient with prediabetes? A. Yes B. No C. Unsure Recommendations

Mrs. Smith is motivated to work on her weight. She understands that if she does not change her habits and lose weight, she will likely develop diabetes within the next 10 years. She is given the following recommendations for the next 3 months: 1. Meet with a dietitian to review her diet, and start documenting food on a daily basis using a tool on her smartphone. 2. Continue walking on the treadmill for a minimum of 150 minutes per week. 3. Monitor weight loss on a weekly basis (same time of day, same clothing, and same scale). 4. Start behavior modification classes with local psychologist for additional behavior changes. 5. Strive for a weight loss goal of 1/2 lb per week (a total of about 6 lbs in 3 months). At her next appointment (3 months later), she has lost about 3 pounds. Mrs. Smith reports eating between 1,400 and 1,500 calories daily (although she is not documenting food) and walking on her treadmill for 30 minutes, 5 days per week. She is attending weekly behavior modification classes to help with weight loss. She does not believe that she has lost enough weight and wonders what else she can do. QUESTION 3: What is the next best step to help Mrs. Smith lose more weight? A. Assess resting energy expenditure B. Complete 1 mg overnight dexamethasone suppression test C. This weight loss is reasonable, and she should continue with her efforts D. All of the above Conclusion

Obesity is a struggle for millions of patients in the United States. Healthcare providers have the ability to encourage

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healthy diets and lifestyles for patients, which can lead to modest weight loss. Many patients have unrealistic weight loss expectations when they think about weight loss goals. However, healthcare providers have the chance to educate them about the valuable health-related benefits of even a modest (5% to 7%) weight loss. It is vital to educate patients on realistic expectations for weight loss efforts and to follow up with them as they try to lose weight. Patients want accountability from their healthcare team regarding their weight. Starting conversations about weight loss can help providers fill that role. ■

ANSWERS QUESTION 1 Answer: D. Physical examination for weight management/ obesity should also include: • Blood pressure • Fasting blood glucose or hemoglobin A1c (within 12 months) • Lipid profile (within 12 months) • Overnight oximetry if the patient has any of the following symptoms: excessive daytime sleepiness/fatigue not explained by other factors; habitual, disruptive snoring; witnessed apneas; snorting, gasping, or choking arousals; restless, fragmented, and/or nonrestorative sleep; or morning headaches • AST and ALT (within 12 months). Treatment of obesity-related comorbidities is the first step in successful management of obesity. QUESTION 2 Answer: A. A diagnosis of prediabetes requires the fasting plasma glucose to be 100 to 125 mg/dL with HbA1c <6.5% or a fasting glucose <126 with HbA1c between 5.7 and 6.5. The patient should start intensive lifestyle modifications to decrease the likelihood of progression to type 2 diabetes. The use of pharmacotherapy (such as metformin) is more controversial because the cardiovascular effects are uncertain. Pharmacotherapy does not affect underlying pathophysiology, and weight loss attributable to medication is small. Metformin is more often used in patients younger than 65 years with prediabetes only after intensive lifestyle interventions fail to reduce HbA1c. Specific lifestyle changes that may delay the onset of diabetes include: • Improved diet (calorie intake appropriate for healthy weight: typically, fewer calories, fewer refined carbohydrates, fewer saturated fats, and more fiber)

Julia Jurgensen, APRN, CNP, practices at the Mayo Clinic department of endocrinology in Rochester, Minn., specializing in diabetes management and obesity. References 1. Frankenfield DC, Muth R, Rowe WA. The Harris-Benedict studies of human basal metabolism: history and limitations. J Am Diet Assoc. 1998;98(4):439-445. 2. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129:S102-S138.

• Maintenance of a BMI ≤25; however, even a 5% to 10% loss of body weight is helpful • Increased physical activity (at least 150 minutes per week) • Smoking cessation • Achieving optimal numbers for cardiovascular risk factors (controlled blood pressure, high HDL, low LDL, and low triglycerides) QUESTION 3 Answer: D. An initial weight loss goal of 5% to 7% of body weight is realistic for most individuals after making lifestyle changes. Most patients have a weight loss goal of ≥30% below their current weight, which is often unrealistic. In the first 3 months of changes, the patient lost 1.5% of her body weight. While this is not in the 5% to 7% percent range, she will likely achieve this goal in the near future with continued efforts and added daily calorie tracking. It would not be unreasonable to determine the patient’s resting energy expenditure to assess the actual amount of calories required by her body during a non-active, 24-hour period. Energy expenditure can be estimated by numerous published formulas. One of the most frequently used formulas for predicted energy expenditure is the Harris-Benedict equation. A limitation of formulas such as these is that each individual patient is unique, and if there is a significant enough difference between the actual measured resting energy expenditure and the calculated energy expenditure, it could be the difference between weight loss and weight stabilization. After measuring the resting energy expenditure, the patient should be advised to reduce her daily caloric intake by 200 to 300 calories below her measured resting energy expenditure. However, if her resting energy expenditure is extremely low, then she should focus on maintaining the caloric intake of the resting energy expenditure and gradually increase activity to 30 minutes per day.

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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 information 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.

VITAMIN D SUPPLEMENTATION DOES NOT IMPROVE FUNCTIONAL OUTCOMES IN POSTMENOPAUSAL WOMEN Level 1 (likely reliable) evidence Vitamin D deficiency is associated with musculoskeletal complications including pain and weakness, osteomalacia, osteoporosis, and secondary hyperparathyroidism. Vitamin D deficiency is especially prevalent in postmenopausal women who are already at an increased risk of osteoporosis and osteoporosis-related fractures (Q JM. 2005;98[9]:667-676). Evidence supporting the use of vitamin D supplements for the treatment and prevention of osteoporosis is limited, and recommendations from current guidelines are inconsistent on the use of vitamin D for these purposes (Clinician’s guide to prevention and treatment of osteoporosis, available at http://nof.org/files/ nof/public/content/file/950/upload/523.pdf; Ann Intern Med. 2013;158[9]:691-696). Recent data have suggested that vitamin D supplementation may also reduce the risk of falls in patients with low vitamin D levels (Cochrane Database Syst Rev. 2012;[9]:CD007146). These data have led the American Geriatrics Society and British Geriatrics Society to recommend at least 800 units/day of vitamin D supplements to older persons with proven vitamin D deficiency and to consider supplementation for all older adults at increased risk of falls ( J Am Geriatr Soc. 2011;59[1]:148-157). A recent randomized trial compared highdose vitamin D3, low-dose vitamin D3, and placebo for 1 year in 230 postmenopausal women with vitamin D insufficiency (25-hydroxyvitamin D, 14–27 ng/mL; JAMA Intern Med. 2015;175[10]:1612-1621). The primary outcome

Researchers found no significant difference in the number of falls or in clinical or bone health outcomes among postmenopausal women who took vitamin D3 supplements or a placebo.

was change in calcium absorption, but rate of falls was one of the secondary outcomes investigated. The high-dose regimen included 50,000 units of vitamin D3 twice monthly plus placebo daily, and the low-dose regimen consisted of 800 units of vitamin D3 daily plus placebo twice monthly. The placebo group received placebos both daily and twice monthly to maintain blinding. Participants were also counseled to consume 600 mg to 1,400 mg of calcium daily by diet or supplement, if needed. From days 30 to 365, the mean 25-hydroxyvitamin D level increased to 56 ng/mL with high-dose vitamin D3 and 28 ng/mL with low-dose vitamin D3, compared to 19 ng/mL with placebo. The change in total fractional calcium absorption at 1 year was significantly increased in the high-dose vitamin D3 group, compared with the low-dose vitamin D3 and placebo groups (+1% vs. −2% vs. −1.3%, respectively). This difference did not correlate with any clinical outcomes. There were no significant differences in the number of falls or percent of fallers across groups, with 35 falls in 29.7% of women in the high-dose vitamin D3 group, 36 falls in 32.9% of women in the lowdose vitamin D 3 group, and 33 falls in 30.3% of women in the placebo group. There were also no significant differences in other clinical or bone health outcomes, including fracture, Timed Up and Go Test, Five Sit-to-Stand Test, functional status measures, or physical activity. This study contrasts with 2 previous systematic reviews (Cochrane Database Syst Rev. 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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Evidence-Based Medicine

INITIATING ANTIRETROVIRAL THERAPY IN HIV PATIENTS WITH CD4 T-CELL COUNTS >500 CELLS/MCL Level 2 (mid-level) evidence Recommendations for initiation of antiretroviral therapy (ART) in asymptomatic adults with HIV are generally based on CD4 T-cell counts; the level needed to start therapy has been progressively increased during the last decade and favors earlier treatment (N Engl J Med. 2013;368[10]:886-889). While treatment guidelines in the United States recommend antiretroviral therapy for all patients infected with HIV, the evidence to support this recommendation was strongest for starting therapy when CD4 T-cell counts are less than 500 cells/mcL. To address this evidence gap, two recent randomized trials, the START Trial and the TEMPRANO ANRS 12136 Trial, compared immediate initiation of ART to delaying ART until specific clinical criteria have been met in asymptomatic, treatment-naïve patients with HIV infection (N Engl J Med. 2015;373[9]:795-807; N Engl J Med. 2015;373[9]:808-822). The START trial included 4,685 adults (mean age, 36 years; male, 73%) from 35 countries with CD4 T-cell counts greater than 500 cells/mcL who were randomly assigned to immediate or delayed ART. The protocol for delayed initiation of ART included starting therapy when the patient had a CD4 T-cell count of 350 cells/mcL or less, or the patient developed AIDS or another condition requiring the initiation of ART (such as pregnancy). This trial was terminated early at the recommendation of the data and safety monitoring board after the group receiving immediate ART demonstrated superior outcomes. At a mean follow-up of 3 years, 1.8% of patients in the immediate-therapy group and 4.1% of patients in the delayed-therapy group experienced at least one of the composite outcomes of serious AIDS-related events, serious non-AIDS-related events, or death (number needed to treat [NNT], 44). Serious AIDS-related events, serious

2012;[9]:CD007146; JAMA. 2004;291[16]:1999-2006) that found a decrease in the risk of falls with vitamin D supplementation. The discrepancy may be explained in part by the populations studied, with the systematic reviews including older adults in general compared with the specific population of postmenopausal women with vitamin D deficiency included in the JAMA Intern Med trial. Also, the mean age of the patients analyzed in the systematic reviews was approximately 10 years older than the women included in this trial. Finally, although there were no differences seen in bone health or functional status, this trial may have been too short to adequately assess these outcomes. Colored scanning electron micrograph of HIV particles (red) that are budding from the membrane of a host cell.

non-AIDS-related events, tuberculosis, and Kaposi sarcoma were all significantly reduced in the immediate-initiation group. Of note, the majority of adverse events observed in this trial occurred when the CD4 count was greater than 500 cells/ mcL. There were no significant differences between groups in all-cause mortality, grade 4 adverse events (defined as potentially life-threatening events requiring medical intervention not attributable to AIDS), or unscheduled hospitalizations. The TEMPRANO trial included 2,056 patients (median age, 35 years; female, 75%) from the Ivory Coast in West Africa with CD4 T-cell counts less than 800 cells/mcL and randomly assigned patients to immediate or delayed initiation of ART and preventive therapy with isoniazid for 6 months or no isoniazid preventive therapy. In this trial, delayed ART initiation was defined by the current World Health Organization (WHO) criteria at the time of enrollment, and patients were followed for 30 months. Comparing immediate to delayed initiation of ART, death or severe HIV-related illness occurred in 6.2% vs. 10.9% of study subjects, respectively (NNT, 22). AIDS, tuberculosis, and invasive bacterial disease were all significantly less common in patients immediately treated with ART, compared to those with delayed initiation of treatment. Grade 3 and 4 adverse events were significantly increased in the immediate-ART group, compared with the delayedART group during the first 6 months after randomization. However, this trend was reversed in the 6 to 30 months after randomization and immediate ART was associated with a significantly reduced risk of serious adverse events, compared with delayed ART in this time period. These two randomized trials demonstrate benefits to mortality and morbidity with ART initiation in HIV-infected patients

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Evidence-Based Medicine

DENOSUMAB MAY REDUCE RISK OF FRACTURE IN WOMEN WITH BREAST CANCER ON AROMATASE INHIBITOR THERAPY Level 2 (mid-level) evidence Bisphosphonates are often recommended for postmenopausal women receiving aromatase inhibitor therapy for hormonereceptor-positive breast cancer with evidence of osteoporosis. Denosumab has previously been shown to reduce the risk of fractures and skeletal events in women with breast cancer with bone metastases (Cochrane Database Syst Rev. 2012;[2]:CD003474). However, the efficacy of denosumab in women with early-stage breast cancer is unknown. A recent randomized trial compared 60 mg of denosumab with placebo administered subcutaneously once every 6 months in 3,425 postmenopausal women (median age, 64 years) with early-stage hormone-receptor-positive breast cancer receiving adjuvant aromatase inhibitor therapy. In addition, elemental calcium and vitamin D supplements were recommended for all women (Lancet. 2015;386[9992]:433-443). At baseline, 45% of women had low bone mineral density (BMD) with T scores less than −1.0. During the median 38 months of treatment, women were treated with a median of 7 doses of their respective study drug. Compared to placebo, denosumab was associated with prolonged time to first clinical fracture (hazard ratio for fracture, 0.5; 95% confidence interval [CI], 0.39–0.65). At 36 months, the estimated rate of clinical fractures was 5% with denosumab, compared to 9.6% with placebo (NNT, 22). The difference in clinical fracture rates was even more substantial at 84 months, with a rate of 11.1% in the

denosumab group vs. 26.2% in the placebo group (NNT, 7). Denosumab was also associated with increased BMD at 12, 24, and 36 months. These results were consistent in subgroup analyses by baseline BMD, age, tumor stage, grade, and histology. Although 24% of women prematurely discontinued treatment, there were no significant differences in adverse events, serious adverse events, or withdrawals due to adverse events. Denosumab was effective regardless of baseline total lumbar spine BMD (low or normal), suggesting it may be helpful for preventing as well as treating bone loss related to aromatase inhibitor treatment. In further subgroup analyses, the benefit of denosumab was not limited to any specific treatment population. Overall, these results suggest that denosumab not only increases BMD, but also reduces the risk of fractures in women with early-stage breast cancer receiving treatment with aromatase inhibitors.

PALLIATIVE CHEMOTHERAPY MAY REDUCE QUALITY OF LIFE IN SOME PATIENTS WITH END-STAGE CANCER Level 2 (mid-level) evidence Determining the best treatment for patients with end-stage cancer is difficult, with little clinical evidence to guide decision making. Chemotherapy has been used for palliative purposes in patients with metastatic disease who have had disease progression on previous chemotherapy regimens, but there is significant variation in its use at the end of life. While early palliative care has been shown to improve quality of life and survival in patients with non-small-cell lung cancer (N Engl J Med. 2010;363[8]:733-742), palliative chemotherapy in the last month of life may increase the

with CD4 T-cell counts greater than 500 cells/mcL. Although both trials were not blinded and the event rates were relatively low, they show a clear benefit to early initiation of ART in asymptomatic patients with HIV infection. This benefit was also observed without an increase in the rate of serious adverse events. Together, the results of these trials provide clear evidence that immediate initiation of ART reduces the development of AIDS, AIDS-related complications, and death in HIV-infected patients regardless of CD4 T-cell counts. Based on these results, the US Department of Health and Human Services has now issued a strong recommendation for initiation of ART in all adults with HIV infection, including those with CD4 T-cell counts greater than 500 cells/mcL (Statement by the HHS panel on antiretroviral guidelines for adults and adolescents regarding results from the START and TEMPRANO Trials, https://aidsinfo.nih. gov/news/1592/statement-from-adult-arv-guideline-panel--start-and-temprano-trials).

Palliative chemotherapy may not be beneficial in patients with endstage cancer and an estimated life expectancy of 6 months or less.

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Evidence-Based Medicine

“Hey, Tarzan—no need to yell.”

“Sweetheart, could you maybe include the dog?”

risk of intensive medical treatment and death in an intensive care unit (Ann Oncol. 2011;22[11]:2375-2380; BMJ. 2014;348:g1219). To further investigate some of these issues, a recent prospective cohort study followed 621 patients with end-stage, progressive metastatic cancer after at least 1 chemotherapy regimen. All patients had a life expectancy of 6 months or less, based on physician estimation. The most common cancers in this study were lung, breast, colon, pancreatic, and other gastrointestinal cancers, which together comprised approximately 70% of all cancers. During the study, 384 patients died. The analysis included 312 patients (81.3%) who were not participating in clinical trials and who had complete data. Of these 312 patients, 50.6% received palliative chemotherapy at baseline, and the distribution of Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores included 39.1% with good performance (PS 1), 37.2% with moderate performance (PS 2), and 18.6% with poor performance (PS 3). Patients receiving chemotherapy were significantly younger and had better baseline performance status. The patient’s quality of life during his or her last week of life was assessed through an interview with the caregiver most knowledgeable about the patient’s care at a median of 2.4 weeks after the patient’s death. Comparing chemotherapy use to nonuse, chemotherapy use was associated with a reduction in the quality of life near death for patients with a good baseline performance status (odds ratio, 0.35; 95% CI, 0.17–0.75). There was no association between chemotherapy use and quality of life near death for patients with moderate or low performance status, however. There was also no significant association between chemotherapy use and mortality. For patients with poor ECOG performance, this study found no association between palliative chemotherapy and quality of life, in agreement with previous studies. Surprisingly, for patients with good ECOG performance, palliative chemotherapy was associated with a reduced quality of life near death. This is the population most likely to receive palliative chemotherapy and in whom it is thought chemotherapy may provide the greatest benefit. Palliative chemotherapy was also not associated with improvement in survival, but the study was underpowered to detect differences in this outcome. Overall, the results of this trial suggest that for all patients with end-stage cancer and an estimated life expectancy of 6 months or less, palliative chemotherapy may negatively affect patient quality of life or at best, offer no benefit. n 80 THE CLINICAL ADVISOR • JANUARY 2016• www.ClinicalAdvisor.com

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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. 82 THE CLINICAL ADVISOR • JANUARY 2016 • www.ClinicalAdvisor.com

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Stat Consult

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

Background

Influenza in children BY ALAN DRABKIN, MD

Dr. Drabkin is a senior clinical writer 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.

The typical incubation period of the flu is 1 to 4 days (mean of 2 days) in children.

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• respiratory infection caused by influenza viruses that often has systemic symptoms • influenza viruses (family Orthomyxoviridae) ——groups A, B, and C based on ribonucleoprotein (internal capsid protein) ——classified as type A or B, strain place/year, subtype H#N# ——type C influenza virus relatively rare • usually occurs in epidemics • seasonal incidence varies with latitude ——temperate countries of Northern and Southern hemispheres have peak activities during winter (in United States, annual epidemics typically occur late fall through early spring) ——tropical regions have high background influenza activity throughout the year with epidemics in months between temperate region activity • nonseasonal influenza viruses ——pandemic (H1N1) 2009 ■■ antigenically distinct from other human influenza A (H1N1) viruses circulating since 1977 so was associated with widespread transmission ——highly pathogenic avian influenza A (H5N1) ■■ has been transmitted from birds to humans in Asia, Africa, Europe, and Middle East with limited, nonsustained human-tohuman transmission ——swine influenza A (H1N1), A (H1N2), and A (H3N2) viruses ■■ are endemic among pig populations in United States ■■ sporadically have infected humans • pathogenesis ——transmitted via large particle respiratory droplets ——typical incubation period 1 to 4 days (mean 2 days) ——children may be infectious for > 10 days ——severely immunocompromised persons can shed virus for months

—— mean duration of influenza-like illness 10.4 days

nonexudative pharyngitis rhonchi ■■ scattered rales • diagnosis ——make diagnosis of influenza on the basis of clinical presentation without testing, especially during periods of peak influenza activity ——diagnostic accuracy may be limited due to overlap with symptoms of other illnesses ——confirm influenza by diagnostic testing ■■ testing recommended for patients with clinical signs and symptoms of influenza for whom results will change clinical care ■■ methods include »»rapid antigen testing (nasopharyngeal or nasal specimen) »»serology »»reverse transcriptase-polymerase chain reaction (RT-PCR) ➤➤ reported to be most sensitive and specific test for influenza ➤➤ recommended as test of choice by Infectious Diseases Society of America (IDSA) »»viral culture »»immunofluorescence assays ——consider chest x-ray if respiratory compromise ■■ ■■

Complications

• more frequent in ——children < 5 years old (especially children < 2 years old) ——children with chronic medical conditions • common complications include ——viral pneumonia ——secondary bacterial pneumonia ——otitis media ——tracheobronchitis ——acute sinusitis ——exacerbations of chronic pulmonary or cardiac disease ——febrile seizure • less common complications include ——pyocarditis ——pericarditis ——myositis ——myoglobinuria ——rhabdomyolysis ——neurologic sequelae ——death Clinical presentation and evaluation

• pattern of illness may vary from mild respiratory illness (similar to common cold) to severe prostration with nonspecific signs and symptoms • initial presentation may be abrupt onset of fever (temperature 37.7° to 40° C [100° to 104° F]) and dry cough • symptoms may include ——Fever ——Malaise ——Headache ——Fatigue ——Weakness ——Anorexia ——Myalgia ——Arthralgia ——dry cough ——chest discomfort ——nausea ——vomiting • physical exam ——no specific signs rule in or rule out influenza ——findings may include ■■ conjunctival injection

Differential diagnosis

• upper respiratory infection • pneumonia • acute bronchitis • acute exacerbation of chronic bronchitis • asthma exacerbation • streptococcal pharyngitis • RSV infection • acute sinusitis in children and adolescents • allergic rhinitis • infectious mononucleosis • severe acute respiratory syndrome (SARS) • recent vaccination with live, attenuated influenza vaccine Management

• antiviral treatment ——efficacy (but results may vary with antiviral resistance patterns) ■■ neuraminidase inhibitors may reduce time to symptom resolution by 0.5 to 3 days in children with influenza

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Stat Consult patients at higher risk for influenza complications unvaccinated staff members in institutional settings ——post-exposure prophylaxis ■■ m ay be given for up to 10 days after the last known exposure only if antivirals can be started within 48 hours of exposure. ——pre-exposure prophylaxis for unexposed children ■■ in the community, give based on the duration of influenza activity for »»up to 28 days for zanamivir »»up to 42 days for oseltamivir ■■ in institutional settings, give for ≥ 2 weeks and until about 10 days after onset of illness in last ill child • exclusion from school for at least 24 hours after the last fever ——appropriate for most situations ——not appropriate in healthcare settings and places with significant numbers of high-risk children • vaccination ——annual influenza vaccination are recommended for all persons ≥ 6 months old without contraindications ——begin vaccination efforts as soon as vaccines are available and continue through illness season • hand hygiene ——may prevent influenza transmission in households if initiated within 36 hours of symptom onset. n ■■ ■■

Prevention

• antiviral prophylaxis ——may be considered for ■■ high-risk close contacts

“How she’s able to manage a career and still juggle her family, I’ll never know.”

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oseltamivir may reduce complications and hospitalization in children with influenza and chronic medical conditions ——recommended as soon as possible (before laboratory confirmation) for patients with suspected influenza who ■■ have severe, complicated, or progressive illness ■■ require hospitalization ■■ are at higher risk for influenza complications ——consider for any outpatient with confirmed or suspected influenza if the treatment can be started within 48 hours of illness onset ——drug choice based on ■■ type of virus circulating ■■ antiviral resistance patterns ——give treatment for 5 days with drug dosing based on age and weight ■■ oseltamivir (Tamiflu) is given orally twice daily »»75 mg for adolescents and children > 40 kg (88 lbs) »»60 mg for children 24-40 kg (53 to 88 lbs) »»45 mg for children 15-23 kg (33 to 51 lbs) »»30 mg for children ≤ 15 kg (33 lbs) »»3 mg/kg children < 12 months old ■■ zanamivir (Relenza) »»2 inhalations of 10 mg twice daily in children ≥ 7 years old »»not recommended in patients with airways disease ■■ reduce doses to once daily if renal impairment (creatinine clearance 10 to 30 mL/minute) ■■ adamantanes (amantadine [Symmetrel], rimantadine [Flumadine]) »»active against influenza A only »»NOT recommended for treatment or prophylaxis of currently circulating influenza A due to resistance • antipyretics ——may reduce fever and provide analgesia ——no evidence of any effect on course of illness ——Combined or alternating acetaminophen and ibuprofen regimens may be more effective than either monotherapy for reducing fever in children. ——avoid aspirin due to association with Reye syndrome • complementary medicine—insufficient evidence for treatment or prevention of influenza ■■

Beyond Rx: OTC Corner Cold and cough symptom relief

Treatment for patients with a common cold does not require a prescription. Clinicians should provide evidence-based advice to their patients for the many other options that are available.

KELLEN LAMBEAU, DNP, APRN, CNP

COLD AND COUGH COMBINATIONS

Safe and effective over-the-counter and herbal treatments are available for patients with viral upper respiratory infections.

Treatment of the common cold requires time and patient education.

The fi rst stop at the pharmacy for a patient with a cold is an overwhelming selection of combination medicines for cold and cough. Although antihistamine/decongestant combinations (without an analgesic) produce no measurable difference in nasal congestion or rhinorrhea, a decongestant/analgesic combination (without an antihistamine) can be helpful in relieving nasal obstruction.1 A Cochrane review of 27 randomized controlled trials studying combination cold treatments found that a single administration at bedtime of an oral antihistamine/decongestant/analgesic combination is better than placebo at producing a feeling of general symptom improvement.1 However, cardiovascular and other risks of taking the medication must be weighed against the modest benefit. These medications have no benefit in young children, however, and the US Food and Drug Administration warns against decongestant use in the pediatric population.

NASAL SPRAYS AND TOPICAL PRODUCTS Patients may use nasal sprays either as adjuncts or as alternatives to systemic treatments. Intranasal ipratropium bromide helps rhinorrhea, but it

This article is part of an ongoing series entitled, Beyond Rx: OTC Corner, which will include topics such as OTC medications, dietary supplements, and other health care approaches that will help nurse practitioners and physician assistants provide patients with tools to manage their health. Robert D. Sheeler, MD, is guest editor of the series. He is an associate professor of family medicine, Mayo Clinic, in Rochester, Minn. He is board certified in family medicine, integrative medicine, and holistic medicine.

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can cause epistaxis. Topical nasal decongestants (such as oxymetazoline) provide rapid symptom relief, but continued use past 5 days leads to rhinitis medicamentosa, or rebound nasal congestion, on withdrawal of the medication. Saline nasal irrigation can be helpful, particularly in children. Guidelines, such as those from the Institute for Clinical Sciences Improvement, recommend gargling with warm salt water (¼ tsp of salt per 8-oz glass of water) to treat a sore throat. One over-the-counter treatment that is available only from online retailers that carry European products is carrageenancontaining nasal spray. The seaweed derivative, already used extensively in cosmetics and foods in the United States, is thought to inhibit rhinovirus replication in the human respiratory tract by forming a gel-like envelope around the virus. In a double-blind, randomized controlled trial

involving 211 adults with early cold symptoms, administration of carrageenan-containing nasal spray three times daily reduced both the viral load in nasal secretions and the duration of illness by more than 2 days.2 Topical products containing aromatics such as camphor, eucalyptus, and menthol also provide symptomatic relief of nasal congestion and cough when applied to the chest or neck.

HERBS Echinacea, or purple coneflower, used to be more popular among children and adults, but it has decreased in popularity in recent years. Although there is a lot of heterogeneity in the preparations of echinacea studied in the literature, in general, a preparation of aerial parts of Echinacea purpurea

TABLE 1. Currently available over-the-counter cold and cough treatments Agents