August 2016 Clinical Advisor by The Clinical Advisor

THE CLINICAL ADVISOR • AUGUST 2016

A PEER-REVIEWED FORUM FOR NURSE PRACTITIONERS

NEWSLINE

■ Colorectal cancer ■ Aspergillosis guidelines ■ Opioids/mortality risk FEATURE LGBT Healthcare Issues

What clinicians should know

AUGUST 2016

| www.ClinicalAdvisor.com

MANAGING PATIENTS WITH

URTICARIA A step-care approach is recommended for patients with chronic urticaria.

LEGAL ADVISOR

Unchecked MRI results ALT MEDS UPDATE

Gold therapy

n Dermatology Clinic

RETIFORM PURPURA WITH BULLAE PAGE 63

VOLUME 19, NUMBER 8

n Dermatologic Look-Alikes

PATCHY HAIR LOSS ON THE SCALP PAGE 67

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Editor Colby Stong, editor@ClinicalAdvisor.com Senior editor Sandhya George Associate digital content editor Hannah Dellabella Assistant editor Lauren Biscaldi Contributing editors Mark P. Brady, PA-C; Philip R. Cohen, MD; Deborah L. Cross, MPH, CRNP, ANP; Sharon Dudley-Brown, PhD, FNP; Abimbola Farinde, PharmD; Laura A. Foster, CRNP, FNP; Abby A. Jacobson, PA; Maria Kidner, DNP, FNP; Joan W. Kiely, MSN, CRNP; Debra August King, PhD, PA; Ann W. Latner, JD; Mary Newberry, CNM, MSN; Claire Babcock O’Connell, MPH, PA; Kathy Pereira, DNP, FNP; Sherril Sego, DNP, FNP; Ann Walsh, PA-C, SCT(ASCP); Kim Zuber, PA-C Production editor Kim Daigneau

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CONTENTS AUGUST 2016

NEWS AND COMMENT 14 Newsline ■■USPSTF recommends screening for colorectal cancer in all patients aged 50 to 75 years. ■■Reduced antibiotic prescribing may lead to an increase in respiratory tract infections. ■■Managing aspergillosis: updated guidelines from the IDSA ■■Revised guidelines for safe sedation of pediatric patients ■■Non-vitamin K antagonist oral anticoagulants may be a safe alternative to warfarin for atrial fibrillation. ■■Exercise during pregnancy does not increase preterm birth risk. ■■State restrictions are not associated with reduced opioid misuse among disabled adults. ■■USPSTF finds insufficient evidence to recommend screening for obstructive sleep apnea in asymptomatic adults. ■■Long-acting opioid therapy is linked to increased mortality risk.

48 CME A 34-year-old man with a 1-year history of itchy hives Many patients with chronic urticaria experience symptoms despite standard treatment. Recent developments have enhanced therapy. 54 CME Feature posttest

Screening advised for colorectal cancer 14

Health care for the LGBT community 22

67 Dermatologic Look-Alikes Patchy hair loss on the scalp 72 Legal Advisor Unchecked MRI results

Continues on page 6

22 Healthcare issues in the LGBT community A greater understanding of the health care issues specific to the lesbian, gay, bisexual, and transgender community may improve the quality of care in this population.

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Web Roundup A summary of our most recent opinion, news, and multimedia content from ClinicalAdvisor.com

63 Dermatology Clinic n Retiform purpura with necrosis and bullae n Pink patches on the hip and buttock

FEATURES

MAKING CONTACT

DEPARTMENTS

The anti-inflammatory actions of gold 74

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CONTENTS DEPARTMENTS cont’d Alternative Meds Update Gold. The metal has been extremely useful in many areas of dentistry and medicine. Its anti-inflammatory and antimicrobial actions have been widely recognized.

ADVISOR FORUM 56

Consultations ■ Zika virus: a primary care response

Clinical Pearls ■ Alternative treatment options for chronic pain ■ Thyroid antibodies ■ A tip for encouraging exercise Case Files ■ A case of G6PD deficiency. A 43-year-old man of Mediterranean descent presents with mild splenomegaly and tenderness.

“I can’t make you look younger, but I can make you look like you’ve had a lot of expensive plastic surgery.”

“Head for the carrousel! It’s our only chance!”

HOW TO CONTACT US THE CLINIC AL

TO SUBMIT A CLINICAL QUESTION FOR PUBLICATION: • www.ClinicalAdvisor.com/AdvisorForum

FEATUR E

LGBT

Healthca re Issues What clinic ians should know

LEGAL ADV

Unchecked

ISOR

NERS

AUG UST

2016

| www.Clin icalA

dvisor.com

MANAGI

NG PATI

ENTS W ITH URTIC ARIA A step -care is recomme approach nded for patients with chronic urticaria.

MRI results

ALT MED

S UPDATE

Gold therapy

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

■ Dermatolo gy Clinic

RETIFORM WITH BUL PURPURA LAE PAGE 63

ER 8

• Mail it to The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001

19, NUMB

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IEWE D FORU M FOR NUR SE PRAC TITIO

NEWSLIN

■ Colorect al cancer ■ Aspergil losis ■ Opioids/mo guidelines rtality risk

VOLUM E

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EXCLUSIVE TO THE WEB AT

ClinicalAdvisor.com Web Exclusives

The Waiting Room

ClinicalAdvisor.com/News

Official Blog of The Clinical Advisor ClinicalAdvisor.com/WaitingRoom

Common medications can cause or worsen heart failure, cautions AHA The American Heart Association has published a scientific statement that outlines which medications cause or exacerbate heart failure.

Sharon M. O’Brien, MPAS, PA-C Summertime blues Sunburn, mosquito bites, and fireworks all present dangerous hazards during the summer months.

Consuming fiber from bread, cereal, and fruit may improve aging process Consuming dietary fiber from bread, cereal, and fruit may increase the likelihood of successful aging over 10 years.

Jillian Knowles, MMS, PA-C Helping patients save at the pharmacy Hyperarousal is linked to an increased likelihood of a patient using prescription sleep aids.

New opioid use is common post-hospital discharge among Medicare beneficiaries After an acute hospitalization, many Medicare beneficiaries submit pharmacy claims for opioid prescriptions.

Jim Anderson, MPAS, PA-C, DFAAPA Advances for PAs practicing addiction medicine PAs and NPs who practice addiction medicine have seen progress made in 2016 to increase practice authority.

Cartoon Archive

Multimedia

The Clinical Advisor’s monthly cartoons are also available online.

ClinicalAdvisor.com/Multimedia

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AANP President Cindy Cooke on the 2016 annual meeting Cindy Cooke, DNP, FNP-C, FAANP, President of the Board of Directors of the American Association of Nurse Practitioners (AANP), provides highlights of the AANP 2016 National Conference. Watch it here: ClinicalAdvisor.com/CookeAANP16Video Wendy Wright on arthritis diagnosis and treatment Wendy Wright, MS, RN, APRN, FNP, FAANP, FAAN, discusses the diagnosis and treatment of arthritis at the AANP 2016 National Conference. Watch it here: ClinicalAdvisor.com/WrightAANP16Video Audrey Stevenson on managing frailty in the elderly Audrey Stevenson, PhD, MPH, MSN, FNP-BC, discusses frailty in the elderly at the AANP 2016 National Conference. Watch it here:

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Advisor Dx

EXCLUSIVE TO THE WEB

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

Ortho Dx

In partnership with

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Journal of Orthopedics for Physician Assistants

Valgus-impacted femoral neck fracture A 76-year-old woman presents with severe left hip pain after a fall at home. During examination, the patient has severe pain with passive motion of the left hip. There is no shortening or deformity of the left lower extremity. A valgus-impacted femoral neck fracture is noted on both anteroposterior and lateral x-rays. WHICH TREATMENT IS RECOMMENDED?

• Hemiarthroplasty • Cannulated screw fixation • Total hip arthroplasty • Observation, non-weight bearing ● See the full case at ClinicalAdvisor.com/OrthoDx_Aug16

Derm Dx A nodule on the forearm A 70-year-old man requests treatment for a lesion of his left forearm. The growth has been present for at least 2 years and has been slowly increasing in size. He gives a history of hypertension and hyperlipidemia. Examination reveals a 3-cm nodule that is not fixed to underlying tissue. Pressure elicits minimal tenderness. CAN YOU DIAGNOSE THE CONDITION?

• Epidermoid cyst • Pilar cyst • Angiolipoma • Ganglion ● See the full case at ClinicalAdvisor.com/DermDx_Aug16

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • AUGUST 2016 9

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Newsline A U G U S T 2 016

Guidelines for managing aspergillosis page 15

Exercise, pregnancy, and preterm births page 16

Long-acting opioids and mortality risk page 17

USPSTF recommends screening for colorectal cancer from age 50 to 75 THE U.S. Preventive Services Task Force (USPSTF) recommends screening all patients for colorectal cancer starting at age 50 and continuing to age 75, according to an updated recommendation statement published in JAMA. For patients aged 76 to 85 years, the USPSTF recommends an individualized approach to decide whether to screen for colorectal cancer, taking the patient’s overall health and prior screening history into account. Several available strategies can be used to screen for colorectal cancer. Each has unique advantages and limitations that should

be considered, though no empirical data are available to show that any of the strategies has a greater net benefit. The USPSTF does not offer any ranking or preferred order for the screening tests, focusing instead on using any type of screening to maximize the number of people who undergo screening. About one-third of eligible adults in the United States have never been screened for colorectal cancer, and offering a choice of tests may help increase this number. The USPSTF found “convincing evidence” that screening for colorectal cancer among

A 3D computed tomography scan of the colon, showing a small polyp.

adults aged 50 to 75 years can reduce colorectal cancer morta l it y. However, the benef it of early detection and intervention declines after age 75 years — patients aged 76 to 85 years who have been screened for colorectal cancer previously have, at best, a moderate benefit if screening continues. Adults aged 76 to 85 years who have never been screened for colorectal cancer are more likely to benefit.

PRESCRIBING FEWER antibiotics for self-limiting respiratory tract infections may be associated with a slight increase in the incidence of treatable pneumonia and peritonsillar abscess, according to a study published in BMJ. However, even after antibiotic prescriptions were substantially reduced, the incidence of pneumonia and peritonsillar abscess increased by only a small amount. The study, led by Martin C. Gulliford, FFPH, MA, King’s College London, included registered patients from 610 general practices in the United Kingdom for a total of 45.5 million person years of follow-up. The researchers calculated the standardized proportion of respiratory tract infection consultations in which antibiotics were prescribed for each practice; they also determined the rate of antibiotic prescriptions for respiratory tract infections per 1,000 registered patients. The primary outcomes were incidence

of pneumonia, peritonsillar abscess, mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre’s syndrome. From 2005 to 2014, the proportion of respiratory tract infection consultations with antibiotics prescribed decreased from 53.9% to 50.5% in men and from 54.5% to 51.5% in women. New cases of meningitis decreased annually by 5.3%, cases of mastoiditis decreased annually by 4.6%, and cases of peritonsillar abscess decreased annually by 1.0%. New cases of pneumonia increased annually by 0.4%. The practices in the lowest quarter of antibiotic prescribing rates had higher rates of pneumonia and peritonsillar abscess when compared with practices in the highest quarter. The researchers determined that a 10% reduction in antibiotics prescribed resulted in an adjusted relative risk increase of 12.8% for pneumonia and 9.9% for peritonsillar abscess.

Reduced antibiotic prescribing may lead to increase in RTIs

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Managing aspergillosis: updated guidelines from IDSA THE INFECTIOUS Diseases Society of America (IDSA) has released updated practice guidelines for the diagnosis and management of aspergillosis, published in Clinical Infectious Diseases. The guidelines, which emphasize early diagnosis, focus on the 3 major forms of aspergillosis: invasive aspergillosis (IA), chronic (and saprophytic) forms of aspergillosis, and allergic forms of aspergillosis. Particularly, the guidelines focus on IA and its different manifestations, including invasive pulmonary aspergillosis (IPA), Aspergillus sinusitis, disseminated aspergillosis, and single-organ IA. A few key recommendations are summarized as follows. • The at-risk population for aspergillosis includes patients with prolonged neutropenia, allogeneic hematopoietic stem

cell transplant (HSCT), solid organ transplant (SOT), inherited/acquired immunodeficiencies, and corticosteroid use. • Patients who are hospitalized and are highly immunocompromised should be placed in protected environments to reduce mold exposure. If no protected environment is available, patients should be admitted to a private room with no

Light micrograph showing pulmonary aspergillosis.

connection to construction sites and no plants or cut flowers. • To identify Aspergillus, tissue and f luid specimens should be submitted for simultaneous histopathologic/cytologic and culture examination. For isolates with atypical growth or resistance concerns, identify the species by molecular methods. • If there is a clinical suspicion for IPA, perform a chest CT scan and a bronchoscopy with bronchoalveolar lavage (BAL). • Amphotericin B (AmB) deoxycholate and its lipid derivatives are appropriate for initial and salvage therapy of Aspergillus infections when voriconazole cannot be administered. The complete guidelines are available in Clinical Infectious Diseases and are an update to the 2008 guidelines for Aspergillus.

THE AMERICAN Academy of Pediatrics (AAP) and the American Academy of Pediatric Dentistry (AAPD) have updated their guidelines for safely sedating pediatric patients, as published in Pediatrics. The goals of pediatric sedation are defined as follows: 1. To guard the patient’s safety and welfare 2. To minimize physical discomfort and pain 3. To control anxiety, minimize psychological trauma, and maximize the potential for amnesia 4. To modify behavior and/or movement so as to allow the safe completion of the procedure

Guidelines seek to minimize physical discomfort and pain.

5. To return the patient to a state in which discharge from medical/dental supervision is safe, as determined by recognized criteria The guidelines recommend that clinicians use the lowest dose of drug with the highest therapeutic index for the procedure. Pediatric patients who are in the American Society of Anesthesiologists (ASA) class I or II are considered candidates for minimal, moderate, or deep sedation. Children in ASA class III or IV, children with special needs, and children with anatomic airway abnormalities or moderate to severe

tonsillar hypertrophy should be considered on an individual basis. If pediatric patients are going to be sedated, they must be accompanied to and from the treatment facility by a parent, legal guardian, or other responsible party. If a practitioner is going to use sedation, he or she must have immediately available facilities, personnel, and equipment to manage emergency situations that may arise, including airway obstruction, hypoventilation, laryngospasm, hypoxemia, and apnea. There should also be a protocol for immediate access to back-up emergency services.

IMAGE: TOP: © SCOTT CAMAZINE / SCIENCE SOURCE, BOTTOM: © THINKSTOCK

Revised guidelines for safe sedation of pediatric patients

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Newsline EXERCISE DURING pregnancy does not increase a woman’s risk of preterm birth, according to research published in the American Journal of Obstetrics and Gynecology. Vicenzo Berghel la, M D, Department of Medicine, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sydney Kimmel Medical College at Thomas Jefferson University, Philadelphia, and colleagues conducted a metaanalysis of 9 previously conducted randomized clinical trials of pregnant women who before 23 weeks had been randomized to either an aerobic exercise regimen or a control group. Participants were of normal weight and had uncomplicated, singleton pregnancies without obstetric contraindication to physical activity.

The aerobic exercise group participated in exercise for 35 to 90 minutes, 3 to 4 times per week, for 10 weeks or until their delivery. Nearly 2060 women were included in the meta-analysis; 49.6% were randomized to the exercise group and 50.4% to the control group. In a comparison of both groups, the researchers noted that incidences of preterm birth of <37 weeks and mean gestational age at delivery were similar, although women in the exercise group exhibited signif icantly higher rates of vaginal delivery (73.6% versus 67.5%) and lower rates of gestational diabetes mellitus and hypertensive disorders (2.4% versus 5.9% and 1.9% versus 5.1%, respectively). Incidences of operative vaginal delivery were the similar in both groups.

Exercise in pregnancy does not increase preterm birth risk

Exercise during pregnancy is not linked to preterm birth risk.

“The results of this analysis support current guidelines from the American Congress of Obstetricians and Gynecologists, which sets the recommendations for our field,” stated Dr Berghella. “This paper reinforces that exercise is good for the mom and the baby and does not hold any increased risk in preterm birth.”

NON-VITAMIN K antagonist oral anticoagulants (novel oral anticoagulants [NOACs] dabigatran, rivaroxaban, and apixaban) are safe and effective alternatives to warfarin for anticoagulant-naïve patients with atrial fibrillation, according to a study published in BMJ. No significant difference in ischemic stroke was observed between the NOACs and warfarin. Apixaban and dabigatran had significantly lower risks of death, any bleeding, and major bleeding compared with warfarin. The study included 61,678 patients with non-valvular atrial fibrillation who were naïve to

NOACs may be an effective alternative to warfarin for atrial fibrillation.

oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The researchers confined their cohort to patients on warfarin (n=35,436; 57%), or those receiving standard dosages of NOACs: dabigatran 150 mg (n=12,701; 21%), rivaroxaban 20 mg (n=7,192; 12%), and apixaban 5 mg (n=6,349, 10%). The weighted rate for ischemic stroke or systemic embolism ranged from 2.9 to 3.9 per 100 person years for the NOACs and 3.3 for warfarin, representing no significant difference.

During 1 year of follow-up, rivaroxaban was associated with lower rates of ischemic stroke or systemic embolism compared with warfarin (hazard ratio, 0.83). Apixaban and dabigatran had significantly lower risks of death (5.3% and 2.7%, respectively) compared with warfarin (8.5%). The risk of death for rivaroxaban was 7.7%. The annual rate of any bleeding was 3.3% for apixaban and 2.4% for dabigatran compared with 5.0% for warfarin and 5.3% for rivaroxaban. “All NOACs are generally safe and effective alternatives to warfarin in a clinical care setting,” concluded the researchers.

A safe alternative to warfarin for atrial fibrillation?

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CONTROLLED substance laws are not associated with reductions in hazardous opioid use or overdose among disabled Medicare beneficiaries, according to research published in the New England Journal of Medicine. Ellen Meara, PhD, Dartmouth Institute for Health Policy and Clinical Practice, New Hampshire, and colleagues, analyzed the associations between prescription-opioid receipt and state-level controlled-substance laws. Data were collected for disabled Medicare beneficiaries, ages 21 to 64, who were alive between 2006 and 2012 (8.7 million person-years). The researchers examined the annual prevalence of beneficiaries with 4 or more opioid prescribers, prescriptions yielding a daily morphine-equivalent dose (MED) greater than 120 mg, and treatment for nonfatal prescription opioid overdose, and estimated how opioid outcomes differed based on 8 types of state-level laws. Between 2006 and 2012, states added 81 controlled substance laws. In 2012, 47% of Medicare beneficiaries filled opioid prescriptions, 8% had 4 or more opioid prescribers, 5% had a daily MED greater than 120 mg, and 0.3% were treated for nonfatal prescription opioid overdose. “We observed no significant associations between opioid outcomes and specific types of laws or the number of types enacted,” concluded Dr Meara.

USPSTF finds insufficient evidence for obstructive sleep apnea screening THE USPSTF has found insufficient evidence to assess the balance of benefits and harms of screening for obstructive sleep apnea (OSA) in asymptomatic adults. The estimated prevalence of mild OSA is 10% and 3.8% to 6.5% for moderate to severe OSA, and although OSA is linked to increased all-cause mortality, the exact role that OSA plays in this is unclear. The USPSTF identified existing evidence on the use of screening questionnaires in asymptomatic adults to potentially identify who may benefit from OSA testing to be inadequate. Additionally, according to its draft recommendation statement, the USPSTF found no studies that evaluated the effect of OSA screening on health outcomes. Adequate evidence was found

Screening for OSA not advised in adults without symptoms.

that indicates treatment with a continuous positive airway pressure (CPAP) machine or a mandibular advancement device (MAD) may improve intermediate outcomes, and inadequate evidence was found to suggest that CPAP or MAD treatment can improve other health outcomes such as cognitive impairment or cardiovascular or cerebrovascular events. Inadequate evidence exists to assess any potential harms of OSA screening. “Overall, the USPSTF found insufficient evidence on screening for OSA in … adults with unrecognized symptoms. No studies directly evaluated the benefits or harms of screening for OSA. Few studies evaluated the accuracy of specific screening tool,” the report concluded.

Long-acting opioid therapy and mortality risk PRESCRIPTION of long-acting opioid medications for chronic, noncancer pain is associated with an increased risk of all-cause mortality when compared to alternative medications, according to research published in JAMA. Wayne A. Ray, PhD, Vanderbilt University School of Medicine, Nashville, and colleagues conducted a retrospective cohort study of Tennessee Medicaid patients with chronic, noncancer pain between 1999 and 2012. Patients had received either long-acting opioid therapy or comparable therapy with either an analgesic anticonvulsant or low-dose cyclic antidepressant. Patients had not received palliative or end-of-life care.

The researchers found 22,912 new episodes of prescribed therapy for both longacting opioids and control medications; 185 deaths were recorded in the long-acting opioid group, compared to 87 deaths recorded in the control group. Data analysis showed that patients who were prescribed longacting opioid therapy had a 1.6 times greater risk of all-cause mortality and a 1.9 times greater risk of out-of-hospital death. “More than two-thirds of the excess deaths were due to causes other than unintentional overdose; of these, more than one-half were cardiovascular deaths,” noted Dr Ray. “These findings should be considered when evaluating harms and benefits of treatment.” n

State laws have no effect on opioid misuse

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FEATURE: THERESA CAPRIOTTI, DO, MSN, CRNP, RN; ALEXANDRA GILLESPIE

Healthcare issues in the LGBT community A greater understanding of the healthcare issues specific to the lesbian, gay, bisexual, and transgender community may improve quality of care.

heterosexual bias in healthcare delivery is pervasive, and it may not be perceived by the primary care clinician. However, it can be blatantly clear to the lesbian, gay, bisexual, or transgender (LGBT) patient as early as the initial interaction within the clinical setting. LGBT patients often cannot complete the most basic informational questions that appear as check boxes on initial visit intake forms, such as sex (male or female) or marital status. Although the healthcare provider may be unbiased and openminded, prejudice is well-ingrained in the healthcare system in subtle and overt ways.1-4 Policies and practices in health care that assume and/or favor heterosexuality may leave LGBT patients feeling judged and demeaned, and LGBT patients receive suboptimal health care as a result.5-7

Terminology

LGBT persons frequently receive suboptimal health care.

Sexuality is a human dimension that can only be described on a continuum and often cannot be defined by a specific category. In health care, terms used to define a person’s sexuality include lesbian (L), gay (G), bisexual (B), and transgender (T).8 In the medical literature, lesbians are often referred to as women who have sex with women (WSW). Gay men are often referred to as men who have sex with men (MSM).9 The terms lesbian and gay are used to refer to people who are attracted to members of the same sex, and the term bisexual describes people who are attracted to members of either sex.10,11 The term transgender is used to describe people who do not identify with their biologically

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assigned sex at birth. Transsexual refers to transgender persons who have undergone sex reassignment surgical procedures.8 At times, the acronym LGBT includes the letter Q (LGBTQ). Q denotes the term queer, which is an umbrella category that some have used to refer to the entire LGBT community. The term may be used to describe those who are on a continuum of gender, gender presentation, or sexuality that may not fit within societal “norms.” Q also denotes the term questioning, which indicates a person is in the process of understanding his or her sexual orientation.9,12 It should be taken into consideration that not all LGBT persons identify as queer, and the term may also be used by some as a political or activist identifier. Other terms to understand include intersex and gender dysphoria. The term intersex refers to a person whose reproductive organs and/or chromosomes do not fit into usual patterns (eg, those with Klinefelter syndrome).13 Gender dysphoria is distress associated with one’s sex that was assigned at birth because it is inconsistent with the individual’s perceived and preferred gender identity.14 It is important to recognize that gender dysphoria is not a mental illness but considered gender nonconformity. The World Professional Association of Transgender Health stresses that gender nonconformity is a matter of diversity not pathology.15 Sexual orientation and health

According to the Centers for Disease Control and Prevention (CDC) National Health Statistics Report: Sexual Orientation and Health Among US Adults, 96% of adults aged between 19 and 64 years identify themselves as heterosexual, 1.6% identify as gay or lesbian, 0.7% identify as a bisexual, and 1.1 % indicate “something else” or gave no answer.16 However in 2011, a CDC report from a survey of 13,495 men and women between the years 2006 and 2008 revealed that 12% of women aged between 25 and 44 years had sexual contact with another woman, and 6% of men revealed they had sexual contact with another man.17 These numbers indicate sexual orientation is more accurately described as fluid rather than a set of discrete categories.

Suicide is more common in LGBT individuals than in heterosexuals. LGB individuals are two times more likely than their heterosexual peers to make suicide attempts.22 The risk for depression and anxiety disorders and alcohol and substance abuse is 1.5 times higher in LGBT individuals.23,24 LGBT individuals also suffer incidents of violence against them more than the general population. LGBT youth are often involved in physical fighting, threatened or injured, and bullied on school property.25 Sexual assessment

A detailed sexual history is important in order to assess risk of health problems for LGBT patients. Primary care clinicians need to be sensitive to a patient’s potential discomfort in discussing sexual history, sex partners, or sexual practices. It is important to ensure confidentiality and not make assumptions about sexual orientation. In order to assess risk of STD, it is necessary to ask the patient about the sex and number of their sex partners. The clinician should ask about the length of relationship with sex partners and if the patient practices safe sex. Clinicians should ask specifically how the patient practices safe sex. Also, the clinician needs to ask the patient about the human immunodeficiency virus (HIV) status and drug use of their sex partners.26 Questions need to be specific in order to identify the anatomic sites from which to collect specimens for STD testing. It is necessary to ask about genital, oral, and anal sexual practices and if condoms or dental dams are used. Receptive anal sex increases susceptibility to HIV compared with insertive anal sex.27 Past history of STDs and questions about desire to have children are necessary. Females need to be asked about their menstrual periods and history of pregnancy (Table 1).26 Health issues of MSM

MSM have a uniquely high risk for HIV infection, human papilloma virus (HPV) infection, viral hepatitis, anal cancer, and other disorders contracted by sexual activity. (Table 2). TABLE 1.The five Ps of sexual assessment26

Disparities in health care

The LGBT community, also referred to as sexual minorities, represents a growing and medically underserved population in the United States.18 Lesbian and bisexual women are more likely to have poor physical and mental health, compared with heterosexual women, and they are less likely to use preventive health services. Gay and bisexual men are at higher risk for sexually transmitted diseases (STDs) and poor mental health, compared with heterosexual men.19-21

In sexual assessment, the Centers for Disease Control and Prevention recommends asking about the five Ps: • Partners • Practices • Prevention of sexually transmitted diseases • Past history of sexually transmitted diseases • Prevention of pregnancy

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HEALTHCARE ISSUES IN THE LGBT COMMUNITY

TABLE 2. Most common health-related problems in MSM • HIV infection • Viral hepatitis A, B, C • HPV infection (genital, rectal, or oropharyngeal) • Anal cancer (HPV) • Neisseria gonorrhea infection (genital, rectal, or oropharyngeal) • Chlamydia trachomatis infection (genital, rectal, or oropharyngeal) • Syphilis (genital, rectal, anal, or oropharyngeal)

• Herpes (genital, anal, or oropharyngeal) • Shigella infection* • Meningococcal meningitis* • Depression and suicide • General anxiety disorder • Substance abuse • Smoking • Violence

*Sporadic outbreaks have been reported. Adapted from http://www.cdc.gov/lgbthealth; and Wilkin T. Primary care for men who have sex with men. N Engl J Med. 2015;373(9):854-862.

TABLE 3. Preventive care for MSM Advise condom use and nonpetroleum-based lubricants HIV testing annually (every 6 months in high-risk individuals) Pre-exposure prophylaxis for HIV in those with specific risk Post-exposure prophylaxis for HIV in those with specific risk Hepatitis B vaccine Hepatitis A vaccine HPV vaccine Meningococcal vaccine (in high-risk individuals) Obtain urinary, rectal, oropharyngeal samples for gonorrhea, chlamydia, syphilis, HCV Screening for anal cancer (anal Pap test, DRE) Adapted from Wilkin T. Primary care for men who have sex with men. N Engl J Med. 2015;373(9):854-862.

HIV infection. A 2012 CDC report revealed that, although the MSM population represents approximately 4% of the male population in the United States, MSM accounted for 78% of new HIV infections among men and 63% of all new HIV infections.28 MSM accounted for 54% of all persons who were living with HIV.28 Black MSM were disproportionately affected by HIV, as they accounted for 30% of MSM with HIV and 40% of new HIV diagnoses.28 It is important for the primary care clinician to test MSM for HIV annually. A recent study from the CDC showed that 33% of MSM who did not know their HIV status had not been tested for HIV in the past 12 months.29 Patient

education is vital to increasing the practice of preventive measures to protect MSM from contracting HIV (Table 3). Healthcare professionals should teach MSM the importance of practicing safe sex: using condoms and non–petroleumbased lubricants.29 Preventive primary care for MSM includes pre-exposure prophylaxis (PrEP), which is a prescription pill taken daily by those who do not have HIV but are at high risk for HIV infection. PrEP is particularly needed by patients whose partners are HIV positive. A postexposure strategy is also available that involves the use of antiretroviral medications (eg, tenofovir disoproxil fumarate and raltegravir). The medication is taken after an isolated incident of high-risk exposure (within 72 h and preferably within 24 h) in conjunction with HIV testing. Treatment is continued for 28 days.30 High-risk individuals should be tested for HIV and STDs every 6 months, and they should receive immunizations for the health problems associated with HIV. Testing should also be done periodically for tuberculosis, HPV, and hepatitis A, B, and C .31 HPV infection and anal cancer. A prominent health issue in the MSM community is HPV, which can cause anal papilloma and/or anal cancer. Studies have found HPV infection of the anal canal in up to 60% of MSM, compared with 15% in heterosexual men.32-34 Notably, prevalence of HPV anal infection has been found in almost 100% of HIVseropositive MSM.35,36 HIV-infected MSM also have an increased risk of anal cancer, compared with men without HIV.37 Oncogenic, high-risk HPV infection (eg, HPV types 16 and 18) causes most cervical, penile, vulvar, vaginal, anal, and oropharyngeal cancers and precancers.38 HPV infection causes genital warts, also called condyloma acuminata. These are small or large papular lesions, raised or flat, or shaped like a cauliflower. Signs and symptoms of HPV-related anal cancer include rectal bleeding, mass at the anal opening, pain or feeling of fullness in the anal area, changes in bowel movements, abnormal anal discharge, and swollen lymph nodes of the anal and perineal region.39 Screening for HPV requires a digital rectal examination and anal Papanicolau (Pap) test. Anal condyloma can be cosmetically removed using podofilox or imiquimod. Alternatively, trichloroacetic acid or bichloroacetic acid, intralesional interferon, or fluorouracil can be used. Condyloma can also be removed via cautery or laser treatment. Condyloma can be treated; however, HPV infection often recurs and spreads easily between sexual partners. Preventive measures for MSM should include HPV vaccine.30

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Condyloma acuminata caused by the human papillomavirus on the anus.

Viral hepatitis. MSM are at high risk for contracting hepatitis A, B, and C. Hepatitis A virus (HAV) is spread primarily through the fecal-oral route, either from person to person or through exposure to contaminated food or water. Most acute infections (85%) are asymptomatic.40 In all types of hepatitis, the patient may present with low-grade fever, anorexia, gastrointestinal symptoms, abdominal pain in the upper right quadrant, fatigue, pale stools, dark urine, and jaundice. HAV causes a self-limited infection of less than 2 months duration and confers immunity when resolved. A vaccine is available for HAV and should be recommended to MSM.41 Hepatitis B virus (HBV) is transmitted via blood or mucosal exposure to body fluids of an infected person. In the United States, the most common mode of transmission is by sexual contact and injection drug use.8,42 HBV can lead to chronic hepatitis, hepatitis fibrosis, cirrhosis, or liver cancer. According to the CDC, an estimated 20% of new HBV infections occur in MSM. Immunization against HBV is recommended for all MSM.41,43 Hepatitis B immunoglobulin (HBIg) can also be administered to impart temporary immunity to those exposed to HBV. Primary care clinicians should educate patients regarding safe sex, the necessity of three doses of HBV vaccine, and the availability of postexposure HBIg that can reduce the risk in close contacts.30 Hepatitis C virus (HCV) is transmitted by exposure to infected blood, most commonly through injection drug use. Sexual transmission occurs in rare cases; however, in both MSM and heterosexuals, the likelihood of sexual transmission rises with increase in number of sex partners and when sex partners are infected with HIV.44

Acute HCV infection progresses to chronic liver disease in 75% to 85% of cases.45 Infection commonly causes no symptoms, and the incubation period lasts several months to years. Mild to moderate liver disease may produce vague symptoms, such as chronic fatigue, for years. Due to an immune complex component of HCV infection, extrahepatic manifestations are possible. These include arthralgias, purpura, glomerular dysfunction, peripheral neuropathy, central nervous system vasculitis, and reduced complement levels.46 Chronic HCV infection is the leading cause of liver-related death and hepatocellular carcinoma in the Western world.47,48 It is estimated that only 50% of those chronically infected persons have been diagnosed. Also, fewer than 38% of those with an HCV diagnosis are referred to care and fewer than 11% who are referred for care are treated.49 Because this infection is often asymptomatic until advanced liver disease occurs, the primary care clinician should maintain a high level of suspicion. Spontaneous resolution of HCV infection can occur in some patients; it is unknown why some have natural clearance of the virus. Treatment of HCV consists of a combination of antiviral agents that are successful in greater than 95% of cases.50 Other STDs. MSM are at high risk for STDs. Primary care clinicians should ask patients about symptoms of STDs in the rectum, urethra, and pharynx, and order appropriate diagnostic tests. It is important to ask the patient about rectal pain and anal discharge, which occur in proctitis. The presence of these symptoms should prompt testing for syphilis, Neisseria gonorrhoeae, and Chlamydia trachomatis, which requires a rectal swab for nucleic acid amplification testing.30 Certain strains of Chlamydia can cause lymphogranuloma venereum (LGV), which causes bloody discharge and ulcerative anal lesions. LGV is strongly associated with HIV infection. Antibiotic treatment is necessary.51 Even in the absence of symptoms, screening for STDs— including serologic testing for HIV and syphilis, and oral, rectal, and urinary testing for N gonorrhoeae and C trachomatis—is recommended for MSM once a year or, for those at high risk, twice a year. Unlike urethral infection, rectal gonorrhea and chlamydial infections are often asymptomatic.52 Shigella infection. MSM are at high risk for Shigella infection, also known as shigellosis or gay bowel syndrome.53 Shigella is transmitted via the fecal-oral route or from contaminated food or water. One to 2 days after exposure, Shigella infection causes fever, diarrhea, abdominal pain, and tenesmus. Immunosuppression increases risk of Shigella, and there is a high prevalence in HIV-positive MSM.54 Shigella infection can resolve after 5 to 7 days; severe cases may require antibiotic treatment. Some strains of Shigella are resistant to antibiotics.55,56

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HEALTHCARE ISSUES IN THE LGBT COMMUNITY

Meningococcal meningitis. Outbreaks of meningococcal meningitis have been reported among MSM. This population is reported to have an increased prevalence of oropharyngeal colonization with N meningitides as compared with the general population.57,58 Current guidelines from the Advisory Committee on Immunization Practices (ACIP) do not include MSM as a group that is at high risk for meningococcal meningitis and do not recommend routine vaccination.43 However, outbreaks of meningococcal meningitis are increasingly being reported. It is prudent for MSM, who are living in areas of outbreaks, to obtain meningitis vaccine.59 Mental health disorders and violence. According to a study by Bostwick and colleagues,60 approximately 42% of men who identified as gay or bisexual, or who were unsure of their sexual identity, had higher rates of mood and anxiety disorders. MSM report a higher prevalence of major depression, dysthymia, panic disorder, and general anxiety disorder. Also, intimate partner violence is more prevalent among MSM. According to Stults and colleagues,61 44% of MSM report lifetime intimate partner violence; 39% report victimization and 30 % report perpetration. Those who experience intimate partner violence also report increased substance use, compared with heterosexual men. Substances include alcohol, marijuana, and stimulants. There is also a more prevalent use of inhaled nitrites among MSM.62 According to Buller and colleagues,63 MSM who are victims of intimate partner violence are more likely to engage in substance use, suffer from depressive symptoms, test positive for HIV, and engage in unprotected anal sex. Health issues of WSW

Sexual identity is not necessarily in concordance with sexual behaviors and the sex of sexual partners. Some women who have sex with women consider themselves heterosexual despite having sex with women. Many do not claim bisexuality in research studies or surveys.10,64 It cannot be presumed that women who self-identify as lesbian do not have or have not had male partners. The majority of women (up to 87%) who report same-sex behavior have had male partners in the past and may continue to do so (6% to 23%).65,66 Women are frequently not asked about the sex of their sexual partners by primary care clinicians.63 Clinicians often presume heterosexuality when taking a sexual history of a woman. Also, many WSW report they feel uncomfortable reporting lesbian behavior.66-68 Consequently, many WSW are not screened for the specific health problems that are known to affect lesbians (Table 4).69 Women are also infrequently advised about how to engage in safe sexual activity with other women.70

TABLE 4. Most common health-related problems in WSW and bisexual women • HPV infection (genital, rectal, or oropharyngeal) • Genital herpes • Bacterial vaginosis • Chlamydia trachomatis infection • Neisseria gonorrhea infection • Trichomoniasis • HIV • Lack of regular Pap tests; increases risk of cervical cancer

• Lack of regular mammograms; increases risk of breast cancer • Violence • Depression and suicide • Anxiety • Substance abuse • Smoking* • Overweight/obesity*

*Increase risk of heart disease Adapted from http://www.cdc.gov/lgbthealth; and http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-onHealth-Care-for-Underserved-Women/Health-Care-for-Lesbians-and-Bisexual-Women.

TABLE 5. How can STDs be transmitted in WSW ? Skin-to-skin contact Mucous membrane contact Vaginal fluids Menstrual blood Sex toys Semen from male donor for pregnancy Adapted from http://www.cdc.gov/lgbthealth; and http://www.acog.org/Resources-AndPublications/Committee-Opinions/Committee-on-Health-Care-for-Underserved-Women/ Health-Care-for-Lesbians-and-Bisexual-Women.

STDs. There is an unfounded belief that WSW have a lesser chance of acquiring STDs.70-72 WSW are at risk of acquiring STDs from current and prior partners, both men and women (Table 5). According to Mravcak and associates,67 it is important to dispel the commonly held belief that the transmission of STDs between women is negligible. Notably, HPV, an STD that can cause cervical cancer, is sexually transmitted between female partners. HPV-associated squamous intraepithelial lesions have occurred in lesbians who have never had sex with men. Marrazzo and associates71 note that 13% to 30% of women who report having sex with women test positive for HPV infection. Many WSW, particularly those with a history of having only female partners, believe they have less need for Pap smear and cervical cancer screening. The majority of surveys report that only 44% to 56% of lesbians have regular Pap smears.73-76

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Recommendations for cervical cancer and HPV screening in lesbians and bisexual women, regardless of their sexual history with men, should not differ from screening recommendations for women in general. According to Massad and colleagues,77 risks for abnormal Pap test results and HPV infection are modestly lower in WSW than in women who have sex with men (WSM), but both are common in HIVseropositive women regardless of sexual preference. Both WSW and WSM should be screened similarly. Genital herpes caused by herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) is common in WSW and bisexual women.78 It is important to educate women that HSV can be transmitted by skin-to-skin and mouth-to-genital contact. HSV infection is often asymptomatic and subclinical infection is highly contagious. Shedding of the virus among those who are asymptomatic is exceedingly common, accounting for the majority of transmission events. In a study by Xu and colleagues,78 among women who ever had sex with women, the prevalence of HSV-2 was 45.6% in women who deemed themselves heterosexuals, 35.9% in bisexuals, and 8.2% in lesbians. In comparison, in women who reported no same-sex partners, the prevalence of HSV-2 was 23.8%. Bacterial vaginosis (BV) is particularly prevalent in WSW, with an estimated prevalence of 25% to 52%.79-81 Having a history of female sex partners confers a twofold increased risk of BV.82 Exchange of vaginal fluid among female partners contributes to the initiation of BV. Susceptibility to BV increases with high lifetime number of female sexual partners, a history of receptive oral-anal sex, and not always cleaning an insertive sex toy between uses.79,80 C trachomatis and N gonorrhoeae are the two most common bacterial STDs in the general population.83 Both of these STDs are reported to be less common in women who have sex exclusively with women. However, it is important to note that these STDs are higher in prevalence among bisexual women than the general population.84,85 Tao86 found similar higher prevalence results for viral STDs among bisexual women aged 15 to 44 years. Therefore, it is prudent to screen for C trachomatis and N gonorrhoeae in WSW. According to Mravcak,67 trichomoniasis is also common among WSW. When screening a woman for chlamydia or gonorrhea, the same sample can be used to test for trichomoniasis with the same laboratory-based techniques.87 Untreated chlamydia and gonorrhea can lead to pelvic inflammatory disease, tubal infertility, and chronic pelvic pain. Gonorrhea usually presents with vaginal discharge; however, chlamydia infections are commonly asymptomatic and do not usually cause visible signs of cervicitis. The CDC and the US Preventive Services Task Force recommend

screening for C trachomatis at least annually for all women aged 24 years and younger.88 Syphilis, hepatitis A, hepatitis B, and HIV are uncommon STDs in WSW.67,89-91 In a study by Fishman and Andersen,72 53% of WSW reported that they were at low risk for HIV because of their knowledge of barrier methods and abstinence from sexual activity during menstruation. However, in a study by Koh and colleagues,92 WSW who engage in high-risk behaviors are susceptible to HIV. These behaviors include unprotected sex with men, unprotected sharing of sex toys with women, and injection drug use. WSW are also uniquely at risk for HIV through the use of unscreened semen donation from sources other than a sperm bank. Violence. Lesbians and bisexual women are commonly victims of prejudice and hate crimes, and often fear for their safety. Also, intimate partner violence may occur between women in same-sex relationships; however, these incidents are poorly reported.93 The National Violence Against Women survey of 8000 American women found that 35% of women who live with women had experienced physical abuse in their lifetimes.94 This is in contrast to a 20% rate of domestic violence for women with a history of only opposite-sex cohabitation. In the same survey, more than 11% of women in same-sex relationships reported having been raped, physically assaulted, or stalked by a female partner.94 According to Lhomond and SaurelCubiziolles,95 WSW report more physical violence than WSM. Most aspects of domestic violence in the LGBT community mirror those of the heterosexual population. The power dynamics, the cyclical nature of abuse, and the increase of abuse over time are similar between LGBT and heterosexual relationships.96 However, there are some aspects of domestic violence that are unique to the LGBT experience. According to Kulkin and colleagues,96 “outing” acts as both a tool of abuse and a barrier to seeking help. LGBT individuals often hide outward expressions of their sexual orientation or gender identity for fear of stigma and discrimination; abusive partners may exploit this fear through the threat of forced outing. Even if batterers do not use outing as an abuse tactic, victims are often reluctant to out themselves to obtain help. Outing and associated negative feelings can inhibit them from turning to family, friends, or the police for support, further isolating them in abusive relationships. Mental health. In a study by Reisner and colleagues,97 WSW were more than three times as likely to have a clinical mental health diagnosis relative to the WSM. Many research studies report WSW are disproportionately affected by depression and anxiety.22,98-102

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LGBT adolescents have higher rates of depression, suicidal ideation, substance abuse, and more risky sexual behaviors than heterosexual adolescents. According to Cochran and Mays,103 WSW are at greater risk for suicide than heterosexual women. WSW are also more likely to have a history of past suicide attempts22,104 and increased utilization of mental health services (eg, inpatient psychiatric/mental health treatment).102,105 Prior research suggests that stressors associated with being a WSW, such as leading a marginalized life, hiding one’s sexuality, facing verbal, emotional, or physical abuse, or stigma, may contribute to increased rates of mental health diagnoses among this population.68,106,107 In comparison with heterosexual adolescents, LGBT adolescents have higher rates of depression and suicidal ideation, higher rates of substance abuse, and more risky sexual behaviors.108 In interviews of men and women aged 26 years, women who have had same-sex attraction were significantly more likely to have engaged in deliberate self-harm or to have had suicidal ideation, compared with women who have not had same-sex attraction.109,110 Rates of depression in lesbians were found to be lower among women with social support, those involved in a satisfying relationship, and those more open about their sexual orientation.98,111 Primary care clinicians should identify life stressors and screen lesbians and bisexual women for depression and suicidal ideation. Referral to mental health professionals who have experience with LGBT patients is important. Cancer. WSW are 10 times more likely to not have received timely Pap tests and 10 times more likely to not have received timely mammograms compared with WSM,

even after accounting for measures of healthcare access, sexual identity, and other potentially confounding factors.112 Findings from the National Health Interview Survey revealed that women in same-sex relationships experience greater odds of breast cancer mortality compared with married women. According to Cochran and Mays,103 nulliparity, more common in WSW, is a likely reason for increased risk of breast cancer. Approximately 70% of women aged more than 18 years reported having a pap smear within the past 3 years.113This is in contrast to the available data for WSW. The majority of surveys report that only 44% to 56% of WSW have regular Pap smears to screen for cervical cancer.73-76,114 Despite the efficacy of the Pap test, WSW continue to be at elevated risk of cervical cancer as a result of underuse of screening services and lack of knowledge about risk factors for cervical cancer and appropriate methods of prevention.115 Studies of WSW indicate that negative experiences with the healthcare system and misinformation about disease risk contribute to underuse of medical services in general73,116,117 and routine cervical cancer screening in particular.74,118 A study by Price and coworkers showed that lesbians have a misperception that they are less susceptible to cervical cancer than heterosexual women.119 Additional barriers to participation in routine cervical cancer screening may include lack of healthcare providers’ knowledge of disease risk in this population, providers’ failure to obtain a complete sexual history from WSW, and lack of willingness of WSW to disclose sexual orientation to care providers.67,73,120 Smoking is more common among sexual minorities, both men and women, than among their heterosexual counterparts.121-123 Also, women in this population are more likely than heterosexual women to drink alcohol123-125 and to be overweight or obese.101,124,126 Health issues among transgender individuals

A transgender individual is someone who expresses themselves as a sex different from that assigned at birth. A transsexual individual is someone who has undergone a permanent, surgical sex change. A transman is an individual born female who has undergone hormonal and/or surgical treatment for sex reassignment as a male (FtM). A transwoman is an individual born male who has undergone hormonal and/or surgical treatment for sex reassignment as a female (MtF). It Cervical smear showing cervical dysplasia.

Continues on page 30

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HEALTHCARE ISSUES IN THE LGBT COMMUNITY

Transgender patients can have extreme discomfort with their bodies, and they may find some elements of a physical examination traumatic. is important to note that prior to sex reassignment surgery, an individual must live as a member of the opposite sex for a certain period of time.10,15,64 The prevalence of adult transgenderism and transsexualism is difficult to estimate. A commonly quoted estimate puts the US adult transgender population at about 700,000, or 0.3% of the population.127 Hormonal treatment. Transitioning can include hormone therapy, psychologic therapy, and surgery. Transgender patients can have extreme discomfort with their bodies, and they may find some elements of a physical examination traumatic. It is recommended that provider/patient trust be established before examining sensitive areas (eg, genital, rectal, and vaginal), unless there is an immediate, urgent need to proceed.128,129 The aim of hormonal treatment is to stimulate the development of the secondary sex characteristics of the new sex and to diminish those of the natal sex.130,131 The clinician must provide care for the anatomy that is present, but also recognize that there will be some health needs due to the remaining anatomic features from birth.131 For example, although a transgender MtF patient may have had gender-confirming surgery, she may still need to have prostate-specific antigen levels checked as she ages. MtF transsexuals. For MtF transition, androgenic hormones need to be counteracted by estrogen. Estrogen hormone therapy is prescribed to induce breast formation, atrophy of the testicles, and female distribution of fat, and reduce male-pattern hair growth. The primary care clinician needs to ask about the details of the sexual reassignment surgery in order to consider the anatomy of the patient. For example, the patient should be asked if orchiectomy had been performed. If not, testicular cancer may be a risk.131 The prostate gland is usually left in place and can develop benign hyperplasia or cancer. The enlarged breast tissue can develop cancer and mammography is necessary. If the patient has the BRCA1 or BRCA2 gene mutation, which increases risk of breast cancer, prophylactic mastectomy may be advised. In surgical shortening of the urethra, stenosis of the neomeatus can occur.132 Vaginoplasty usually involves sigmoid colon epithelium; however, no reports of cancer in neovaginal tissue have been reported.133 Hormonal treatment with ethinyl estradiol, although efficacious, should be avoided. When taken at the dosages required for sex reassignment, there is increased risk of deep

venous thrombosis and death from cardiovascular causes as compared with 17ß-estradiol. Smoking should be discouraged as this increases risk of thrombus formation in estrogen therapy.10,134-136 Studies assessing the metabolic effects of androgen deprivation and estrogen therapy in MtF transsexuals have shown that increases in visceral fat are associated with increases in triglyceride levels, insulin resistance, and blood pressure.137,138 Also, estrogen treatment can cause metabolic syndrome.137-140 Therefore, lipid and serum glucose levels should be periodically checked. FtM transsexuals. Treatment in FtM transsexuals is intended to virilize the individual with testosterone administration. Changes due to testosterone include male-pattern hair growth, degeneration of ovaries and uterus, enlargement of the clitoris, and the cessation of uterine bleeding. Depending on the sex reassignment surgery, a hysterectomy and oophorectomy may be involved, or the ovaries may be left in place.132 Because androgens are partially metabolized into estradiols, there may be estrogenic stimulation of the remaining breast tissue, which increases risk of cancer. FtM transsexuals are particularly at risk if they have the BRCA1 or BRCA2 genetic mutation.141,142 FtM transsexuals who have not had oophorectomy can develop polycystic ovaries or cancer. FtM transsexuals who have not had a hysterectomy can develop proliferation of the endometrium, and cervical tissue can undergo cancerous changes. Therefore, a periodic Pap smear is necessary.130,132,135 The patient’s new phallic tissue is derived from skin of the forearm, which is loose tissue. Urethral complications occur in more than 30% of FtM patients, and surgical revision is necessary.143,144 The clinician needs to completely understand the anatomy of the FtM patient in order to make clinical decisions about screening and treating disease. Long-term treatment. After sex-reassignment surgery, including gonadectomy, hormonal therapy must be continued.130,145 Some MtF individuals continue to have male-pattern hair growth; continued administration of antiandrogens, typically at approximately half the preoperative dose, reduces male-pattern hair growth.135 Continued administration of estradiol is required to avoid symptoms and signs of hormone deficiency, such as vasomotor symptoms and osteoporosis in MtF transsexuals. Observational studies have shown that bone mass is generally maintained

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Transsexual individuals have a higher rate of HIV diagnosis than other high-risk populations, including MSM or partners of persons infected with HIV. prevalence rate.156 According to Loverro and colleagues,157 there is a high rate of oncogenic-type HPV infection among transsexual persons that puts them at high risk for anogenital cancer. Cervical and anal Pap smears and HPV vaccination are advised. According to a study by Fernandes and associates, the prevalence rate of syphilis among transgender women was 35% in Central Brazil.158 Among transgender women, being aged 30 years or older, having more than 10 male sexual partners in the past week, and being infected with HIV were associated with syphilis. Mental health issues. Transgender individuals can experience social isolation, prejudice, harassment, and violence from others. Screening for violence should be conducted and patients who have experienced trauma should be evaluated for symptoms of post-traumatic stress disorder. Substance abuse can occur in transgender individuals coping with gender dysphoria or stressful environments. Referral for psychiatric illness and substance abuse treatment should be to a mental health provider with an understanding of transgender care issues.128 Transsexual individuals have high rates of depression, selfharm, substance abuse, and suicide.9,100,159,160 Stigma due to nonconformity, sexual experiences at an early age, a history of physical or sexual abuse, and lack of important social support increase risk for suicidality in this population.161 Grant and colleagues reported that 41% of transsexuals in the United

with estrogen alone in MtF individuals and with testosterone alone in FtM individuals when prescribed at the doses typically used to treat hypogonadism.146 Cancer. Long-term administration of cross-sex hormones may increase risk of hormone-dependent cancer. In both MtF and FtM transsexuals, estrogen-dependent cancers can develop because in MtF people, estrogen is administered, and in FtM people, testosterone is partially converted into estradiol.135 However, according to Mueller and Gooren,147 there are rare case reports of prolactinomas, breast cancers, and prostate carcinomas in MtF patients and rare reports of ovarian carcinoma, breast cancer, and vaginal cancer in FtM patients. There are also infrequent cases of hormonedependent tumors in organs other than the reproductive organs due to estrogen.140 However, the available data are from studies that involved relatively short-term exposure. Risks may become more apparent as subjects age and the duration of hormone exposure increases. STDs. Transgender patients may have sex with men, women, or both. Because of the diverse nature of sexual partners among transgender persons, providers must recognize symptoms of common STDs and screen for asymptomatic STDs on the basis of individual sexual practices.148 Transsexual individuals have high rates of HIV and AIDS.149,150 Herbst and colleagues, in a meta-analysis of four studies, found approximately 28% of transsexuals were HIV-positive.150 Highest rates (56%) were among AfricanAmerican MtF transsexuals. Within an STD clinic in Los Angeles, California, Edwards and coworkers found that transsexuals had a 35% prevalence rate of HIV infection.151 Grant and associates surveyed 6450 transsexual individuals and found the rate of HIV infection was more than four times the national average, with highest rates among MtF persons.152 Transsexual individuals have a higher rate of HIV diagnosis than other high-risk populations, including MSM or partners of persons infected with HIV.153 Transsexual individuals who were unemployed or who had engaged in sex work had particularly high rates of HIV. Early sexual experiences, having multiple partners, needle sharing, and random sexual contacts increase the risk for HIV/AIDS, especially for MtFs.97,151,154 According to a study by Carobene and colleagues,155 HBV and HCV coinfection is common in transsexual sex workers. HPV is particularly prevalent in transsexual sex workers. A study of transsexual sex workers in Argentina showed a 97%

Transgender persons can experience social isolation, prejudice, harassment, and violence from others.

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POLL POSITION

Which of the following best describes your experience with LGBT patients during the past 5 years? n=371

■ Their healthcare issues have increased in number or severity, and I have been able to provide better care for them. ■ Their healthcare issues are unchanged, and I provide the same level of care as before.

11.59% 19.41% 69%

■ More open dialogue about LGBT patients’ sexuality has led to better care for them.

For more polls, visit ClinicalAdvisor.com/Polls.

States have attempted suicide.152 This is in contrast to the less than 2% of persons who attempt suicide in the general population.162

from which to collect specimens for STD testing and cancer screening. Clinicians need to be sensitive that patients may not be comfortable talking about their sexual history, sex partners, or sexual practices until trust is developed. Specific issues should be taken into consideration for MSM, WSW, and transgender persons. MSM are at particularly high risk for many STDs, HIV infection, and anal cancer. It is important to dispel the commonly held belief that the transmission of STDs in WSW is negligible. Women are infrequently advised about how to engage in safe sexual activity with other women. Also, WSW erroneously believe they do not need cervical cancer screening and Pap tests. Transgender individuals have a higher rate of STDs and HIV, compared with the general population. For transsexual individuals, clinicians need to be aware of the specific types of surgical procedures that have been performed. It is important to screen transsexual individuals according to their unchanged anatomy as well as their reconfigured anatomy. Within the whole LGBT community, mental health issues are common, often due to the prejudice these individuals face at the hands of others. ■

American College of Physicians statement

In April 2015, the American College of Physicians (ACP) publicly recognized that there are disparities in health care experienced by the LGBT community and made a series of recommendations to achieve equity for LGBT patients in the healthcare system.163 The nine-point position paper recommended that medical schools, hospitals, and all medical facilities adopt gender identity as part of nondiscrimination policies. It urged comprehensive transgender healthcare inclusion in public and private health insurance plans. They advocated that the definition of family should be inclusive of all those of the patient’s choice, regardless of biological relationship. The ACP also announced its support for civil marriages of same-sex couples, more research into health disorders of LGBT patients, and recruitment of LGBT medical students, residents, and practicing physicians. In addition, the ACP announced its opposition to the conversion, reorientation, or reparative therapy of individuals with LGBT identity.

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141. Burcombe RJ, Makris A, Pittam M, Finer N. Breast cancer after bilat-

women. Drug Alcohol Depend. 2005;77(1):61-70.

eral subcutaneous mastectomy in a female-to-male trans-sexual. Breast.

124. Cochran SD, Mays VM, Bowen D, et al. Cancer-related risk indicators

2003;12(4):290-293.

and preventive screening behaviors among lesbians and bisexual women.

142. Grynberg M, Fanchin R, Dubost G, et al. Histology of genital tract and

Am J Public Health. 2001;91(4):591-597.

breast tissue after long-term testosterone administration in a female-to-

125. Drabble L, Trocki KF, Hughes TL, et al. Sexual orientation differences in

male transsexual population. Reprod Biomed Online. 2010;20(4):553-558.

the relationship between victimization and hazardous drinking among women

143. Hoebeke P, Selvaggi G, Ceulemans P, et al. Impact of sex reassignment

in the national alcohol survey. Psychol Addict Behav. 2013;27(3):639-648.

surgery on lower urinary tract function. Eur Urol. 2005;47(3):398-402.

126. Boehmer U, Bowen DJ. Examining factors linked to overweight and obe-

144. Lumen N, Monstrey S, Goessaert AS, et al. Urethroplasty for stric-

sity in women of different sexual orientations. Prev Med. 2009;48(4):357-361.

tures after phallic reconstruction: a single-institution experience. Eur Urol.

127. Gates GJ. How many people are lesbian, gay, bisexual, and

2011;60(1):150-158.

transgender? The Williams Institute website. http://williamsinstitute.

145. Gooren LJ, Giltay EJ, Bunck MC. Long-term treatment of transsexuals

law.ucla.edu/research/census-lgbt-demographics-studies/

with cross-sex hormones: extensive personal experience. J Clin Endocrinol

how-many-people- are-lesbian-gay-bisexual-and-transgender.

Metab. 2008;93(1):19-25.

128. Halloran L. Caring for transgender patients. J Nurse Pract.

146. van Kesteren P, Lips P, Gooren LJ, et al. Long-term follow-up of bone

2015;11(9):915-916.

mineral density and bone metabolism in transsexuals treated with cross-

129. Primary care protocol for transgender patient care. Center of

sex hormones. Clin Endocrinol (Oxf). 1998;48(3):347-354.

Excellence for Transgender Health website. http://transhealth.ucsf.edu/

147. Mueller A, Gooren L. Hormone-related tumors in transsexuals receiving

trans?page=protocol-00-00.

treatment with cross-sex hormones. Eur J Endocrinol. 2008;159(3):197-202.

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148. 2015 sexually transmitted diseases treatment guidelines. Centers for Disease Control and Prevention website. http://www.cdc.gov/std/tg2015/default.htm. 149. Giami A, Le Bail J. HIV infection and STI in the trans population: a critical review. Rev Epidemiol Sante Publique. 2011;59(4):259-268. 150. Herbst JH, Jacobs ED, Finlayson TJ, et al; HIV/AIDS Prevention Research Synthesis Team. Estimating HIV prevalence and risk behaviors of transgender persons in the United States: a systematic review. AIDS Behav. 2008;12(1):1-17. 151. Edwards JW, Fisher DG, Reynolds GL. Male-to-female transgender and transsexual clients of HIV service programs in Los Angeles County, California. Am J Public Health. 2007;97(6):1030-1033. 152. Grant JM, Mottet LA, Tanis J. National Transgender Discrimination Survey Report on Health and Health Care. Washington, DC: National Center for Transgender Equality; National Gay and Lesbian Task Force; 2010. 153. California tobacco control update 2006. California Department of

“Twinkie! You haven’t changed a bit! What’s your secret?”

Health Services website. https://www.cdph.ca.gov/programs/tobacco/ Documents/Archived%20Files/CTCPUpdate2006.pdf. 154. Lindley LL, Nicholson TJ, Kerby MB, Lu N. HIV/STI-associated risk behaviors among self-identified lesbian, gay, bisexual, and transgender college students in the United States. AIDS Educ Prev. 2003;15(5):413-429. 155. Carobene M, Bolcic F, Farías MS, et al. HIV, HBV, and HCV molecular epidemiology among trans (transvestites, transsexuals, and transgender) sex workers in Argentina. J Med Virol. 2014;86(1):64-70. 156. Dos Ramos Farías MS, Garcia MN, Reynaga E, et al. First report on sexually transmitted infections among trans (male-to-female transvestites, transsexuals, or transgender) and male sex workers in Argentina: high HIV, HPV, HBV, and syphilis prevalence. Int J Infect Dis. 2011;15(9):e635-e640. 157. Loverro G, Di Naro E, Caringella AM, et al. Prevalence of human papillomavirus infection in a clinic sample of transsexuals in Italy. Sex Transm Infect. 2016;92(1):67-69. 158. Fernandes FR, Zanini PB, Rezende GR, et al. Syphilis infection, sexual practices, and bisexual behaviour among men who have sex with men and transgen-

“He’s good with directions, but that’s about it.”

der women: a cross-sectional study. Sex Transm Infect. 2015;91(2):142-149. transgender man. J Midwifery Womens Health. 2008;53(4):331-337. 160. Scourfield J, Roen K, McDermott L. Lesbian, gay, bisexual, and transgender young people’s experiences of distress: resilience, ambivalence and self-destructive behaviour. Health Soc Care Community. 2008;16(3):329-336. 161. Lee R. Health care problems of lesbian, gay, bisexual, and transgender patients. West J Med. 2000;172(6):403-408. 162. Roller CG, Sedlak C, Draucker CB. Navigating the system: how transgender individuals engage in health care services. J Nurs Scholarsh. 2015;47(5):417-424. 163. Daniel H, Butkus R; Health and Public Policy Committee of American College of Physicians. Lesbian, gay, bisexual, and transgender health disparities: executive summary of a policy position paper from the American College of Physicians. Ann Intern Med. 2015;163(2):135-137. All electronic documents accessed June 29, 2016.

“Oh, but it’s fine for you to grade papers?”

159. Dutton L, Koenig K, Fennie K. Gynecologic care of the female-to-male

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CME FEATURED COURSE

n EDUCATIONAL OBJECTIVES At the conclusion of this activity, participants should be better able to: • Effectively evaluate and diagnose chronic urticaria subtypes • Implement appropriate evidence-based recommendations for first- and second-line treatment of patients with chronic urticaria • Analyze third-line treatments for chronic spontaneous urticaria and the evidence and considerations on the selection and use of new immunobiologic therapies • Utilize standardized tools to assess disease severity and response to treatment in patients with urticaria n COMPLETE THE POST-TEST: Page 54

Release Date: January 28, 2016 Expiration Date: January 28, 2017 Estimated Time to Complete: 30 minutes Accredited Provider: This educational activity is provided by Haymarket Medical Education. Commercial Supporter: This activity is supported by an educational grant from Novartis Pharmaceuticals Corporation. Program Description: This case is part of a series entitled “Advancing the Management of Chronic Urticaria With State-of-theArt Diagnostic Tools and Treatment Strategies.” Urticaria is a common condition that affects about 20% of people at some time during their lives and can be triggered by many substances or situations. Unfortunately, many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) have persistent symptoms despite treatment with H1-antihistamines, even at high doses. This case investigates the challenges faced when diagnosing and treating a diabetic patient suffering from itchy hives with episodic angioedema for more than 1 year. Intended Audience: Allergists/immunologists, dermatologists, primary care physicians, and other healthcare providers who diagnose and manage patients with chronic urticaria Conflict of Interest 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. Faculty Allen Kaplan, MD Clinical Professor of Medicine Medical University of South Carolina Charleston, SC

Accreditation Statement: Haymarket Medical Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Designation Statement: Haymarket Medical Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 CreditTM. Physicians should claim only those credits commensurate with the extent of their participation in the activity. Disclosure of Unlabeled Use: This educational activity may contain discussion of approved and/or investigational uses of agents that are not indicated by the FDA. Novartis and Haymarket Medical Education do not recommend the use of any agent outside of the labeled indications. Disclaimer: The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of Novartis and Haymarket Medical Education. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. If you have any questions relating to the accreditation of this activity, please contact cmequestions@haymarketmedical.com. Instructions: There are no fees for participating in and receiving CME credit for this activity. During the period January 28, 2016 through January 28, 2017, participants must: 1) read the learning objectives and faculty disclosures; 2) complete the pre-assessment test; 3) study the educational activity; 4) complete all polling questions; 5) complete the post-test and submit it online. A statement of credit will be issued only upon receipt of the above elements and a post-test score of 70% or higher. All components must be completed and submitted online at myCME.com/Aug16CAfeature.

Faculty Dislosure: Dr. Kaplan serves on the speakers’ bureaus for Genentech, Novartis, and Shire (payment is made through the Robert Michael Educational Institute). Accredited Provider Disclosure: The staff of Haymarket Medical Education have no disclosures to report with any commercial interests relative to this CME activity.

Provided by

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CME

FEATURED COURSE: ALLEN KAPLAN, MD

A 34-year-old man with a 1-year history of itchy hives Many patients with chronic urticaria experience symptoms despite standard treatment. Recent developments have enhanced therapy.

An acute urticarial rash with multiple welts and hives

rticaria comprises a heterogeneous group of diseases involving the onset of pruritic wheals (ie, hives), angioedema, or both.1,2 The various types of urticaria are classified based on acuity and etiology: urticaria presenting for less than 6 weeks is considered acute, whereas chronic urticaria (CU) persists for 6 weeks or more.2-4 These are divided into chronic inducible urticaria, in which symptoms are triggered by physical stimuli, and chronic spontaneous/ idiopathic urticaria (CSU) where no exogenous cause is evident. While allergic triggers are often considered in cases of acute urticaria, there is not an allergic cause for the chronic condition.3 The prevalence of CSU in the general population has been estimated to range from 0.5% to 1%, with chronic autoimmune urticaria (ie, CSU associated with other autoimmune disorders or autoantibodies) accounting for 30% to 50% of such cases.4 Types of chronic inducible urticaria are differentiated by physical triggers such as exposure to cold, pressure, exercise, ultraviolet light, heat, vibration, or water. If no trigger can be identified, the disease is classified as CSU. A patient may also have several subtypes of CU at once (Table 1).2 Although cases of CSU can resolve spontaneously, more serious cases tend to be persistent. In fact, in one study, 30% of moderate and severe cases were still present after 5 years.3 Unfortunately, many patients with CU experience persistent symptoms despite standard treatment with H1-antihistamines, even at high doses (sometimes

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TABLE 1. Chronic urticaria subtypes2 Chronic inducible urticaria

Chronic spontaneous urticaria

• Symptomatic dermographism (urticaria factitia) • Cold urticaria • Delayed pressure urticaria • Solar urticaria • Heat urticaria • Vibratory angioedema • Cholinergic urticaria • Contact urticaria • Aquagenic urticaria

• Spontaneous appearance of wheals, angioedema, or both for ≥6 weeks due to known or unknown causes

up to 4 times the approved dose).5,6 Recent developments, however, have increased our understanding of the pathophysiology behind CSU and have resulted in enhanced treatment strategies, including the possible addition of H2-antihistamines, leukotriene pathway inhibitors, cyclosporine, or the antiimmunoglobulin (Ig) E antibody, omalizumab.1,2 Because CSU can significantly decrease quality of life (QoL)—specifically in diminished social functioning, emotional distress, and a high prevalence of mental health disorders7,8 —the aim is to provide rapid and sustained symptomatic relief. Therefore, clinicians need to be able to accurately diagnose CU/CSU and explain all available therapeutic options to their patients in order to implement a treatment strategy that is safe, effective, and in line with patient expectations and preferences. Introducing Robert

Robert is a 34-year-old male who has been experiencing itchy hives with episodic angioedema over the past year. His first episode of urticaria occurred after eating shellfish; he had hives on his face, neck, and chest and his lips were swollen. Robert’s symptoms persisted for about 4 hours before he sought treatment at an outpatient urgent care clinic, where he was prescribed a standard dose of oral hydroxyzine. His pruritus abated in 1 to 2 hours and his urticaria subsided in 4 hours. His appearance returned to normal by the following morning. He was told to avoid shellfish due to a likely allergy. Despite avoiding shellfish, Robert continued to experience episodes of itchy urticaria (without angioedema), which typically lasted about 8 to 12 hours if left untreated. As a result, his primary care physician (PCP) recommended that Robert take over-the-counter loratadine once a day, which suppressed his symptoms until 3 months ago. Robert now experiences urticaria attacks almost daily, which are

not responsive to loratadine, and he has noticed that his hives become exacerbated when he jogs. Seeking relief, Robert visited his PCP, who referred him to an allergist for proper diagnosis and treatment. Robert’s medical history indicates that he was diagnosed with type 1 diabetes mellitus at the age of 12. Since his diagnosis, Robert has been treated with intensive insulin therapy, and his diabetes has been relatively well controlled. He has no other comorbid conditions and takes no medications besides insulin and loratadine. Because of his diabetes, Robert has always tried to lead a healthy lifestyle, and he especially enjoys running and training for marathons. Robert works full-time as a lawyer and often has to defend cases in court and meet with clients. Upon questioning, Robert admits to his allergist that he has become increasingly self-conscious of his hives and that he has even cancelled a couple of meetings because of spontaneous outbreaks. Robert also announces that he is currently engaged to be married, but he wants to get his condition under control before he sets a date for the wedding. He fears that his hives will ruin the happy occasion, not to mention the wedding photos. Diagnostic considerations

In some individuals, ingesting foods such as shellfish may trigger a direct histamine release from mast cells and lead to episodes of acute urticaria.9 Robert’s clinical presentation of hives, however, is more consistent with CSU. A distinguishing feature of inducible urticarias (except pressure urticaria) is that individual lesions subside within 2 hours. The individual lesions of acute urticaria or CSU typically resolve within 24 hours.1,2,10 This also provides reassurance that the diagnosis is unlikely to be urticarial vasculitis, in which hives typically take up to 2 to 3 days to resolve.10 Robert’s concomitant occurrence of angioedema further supports a diagnosis of CSU, as angioedema can be present alongside hives in approximately 30% to 40% of cases.6 Chronic spontaneous urticaria, which has no discernible external cause, comprises the majority of cases of CU.1 Over half of all cases of CSU are associated with an autoimmune mechanism, primarily autoantibodies against the highaffinity IgE receptor.11 Supporting this hypothesis, a strong association has been found between CU and additional autoimmune diseases, such as type 1 diabetes.12 Currently, the available tests to screen for autoantibodies against the IgE receptor are the autologous serum skin test (ASST) and the basophil histamine-release test, which evaluate the presence of serum histamine-releasing factors of any type. Nevertheless, these tests are negative in approximately half

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of CSU cases,1-2 suggesting that other factors are involved in the pathogenesis of the urticaria. Physical urticaria, for example, constitutes 20% to 30% of all cases of CU, and a few patients have multiple types of physical urticaria simultaneously.13,14 Cholinergic urticaria, which is precipitated by an increase in core body temperature, constitutes 5% of all cases of CU; common triggers include exercise, emotional stress, and bathing in hot water.13 Current guidelines recommend that if an eliciting factor is suspected, provocation tests should be performed to determine whether it is indeed an eliciting factor.1,2 If no symptom-inducing factor can be identified, blood tests (differential blood count, CRP, ESR, liver enzymes, and thyroid-stimulating hormone [TSH]) are recommended; however, routine skin testing for allergy is not necessary.1,2 In summary, the heterogeneity of urticaria symptoms and the lack of specificity provided by currently available laboratory tests can result in delayed diagnoses and inappropriate treatments for patients with CSU. As such, the guidelines emphasize the importance of taking a detailed and relevant clinical history to diagnose and distinguish among subtypes of CU (Table 1).1,2 Robert’s clinical assessment and diagnosis

Upon physical examination, Robert shows signs of small, pinpoint-sized hives, which he says last for 30 to 90 minutes each day, as well as hives 1 to 3 inches in diameter that can last all day. This presentation lends itself to a number of possible types of urticaria, including symptomatic dermographism, cold urticaria, and cholinergic urticaria.10 Moreover, Robert’s history of type 1 diabetes indicates an ongoing autoimmune process, which might be associated with CSU.12 Robert’s laboratory test results indicate a negative ASST; he has an elevated ESR (35 mm/hr), but his CRP, TSH, and liver enzyme levels are normal. Robert thinks that exercise may provoke his hives. Indeed, cholinergic urticaria is typically characterized by numerous punctate wheals (1-3 mm) surrounded by large flares (Figure 1).14 Upon further questioning, however, Robert explains that his hives never appear immediately following exercise; rather, the hives become itchier. After performing a thorough clinical history and physical examination, Robert’s allergist makes a diagnosis of CSU. Treatment strategies for CSU

The cornerstone of treatment for urticaria is eliminating underlying causes and avoiding any known triggers.1,2 The next widely recommended and utilized treatment

FIGURE 1. Patient with cholinergic urticaria exhibiting 1- to 5-mm wheals after exercising. Source: Image used with permission from D@nderm. http://www.danderm-pdv.is.kkh.dk/atlas/3-63-5.html?zoom_highlight=urticaria.

step for both acute and chronic urticaria is symptomatic treatment with pharmacotherapy—typically first-line, nonsedating second-generation H1-antihistamines (eg, loratadine, cetirizine). While most patients respond well to this class of antihistamines, many may require higher doses of H1-antihistamines alone or in combination with other classes of medications. Current guidelines recommend increasing the dosage of the first-line H1-antihistamine up to 4-fold if the standard dose is not effective after a maximum of 2 weeks (Figure 2).1,2 A recent systematic review of 73 studies with 9759 participants concluded that several antihistamines at standard doses are effective and safe compared with placebo.15 No serious adverse events or death events were reported in study participants taking standard-dose H1-antihistamines. Side effects of H1-antihistamines included headache, somnolence, fatigue, and dry mouth, but these are minimized when employing the newer “nonsedating” choices. Robert’s treatment plan

Since Robert was already being treated with a standard dose of the H1-antihistamine loratadine (as instructed by his PCP), the severity and frequency of his CSU and inadequate response over the past 3 months justifies second-line treatment. According to the guidelines, Robert’s H1-antihistamine treatment should therefore be increased. After discussing the potential side effects associated with this new regimen, Robert and his allergist decide to increase his dose of loratadine to 4 times a day. Robert is instructed to return in 1 month to assess the effect of the 4-fold dose increase on his disease severity.

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Despite treatment, individuals with chronic urticaria have significant decrements in QoL and increased mental health concerns. Robert’s disease course

A month later, Robert returns for a follow-up visit with his allergist. Although Robert reports that he has experienced some improvement in his disease activity, experiencing a lower frequency of attacks (2-3 times a week), he expresses that he is still unhappy. Robert’s allergist informs Robert that his Urticaria Activity Score (UAS), a validated tool used to assess disease activity,2 indicates that he is currently experiencing moderate disease. Moreover, Robert feels that the spontaneity of the hives along with the itchiness have taken a toll on his QoL. He is especially concerned because his fiancée would like to schedule their wedding for sometime in the next 6 months. Second- and third-line treatment options for CSU

Chronic urticaria primarily influences the patient’s QoL negatively because of the swelling, itching, and pain as

well as feelings of fatigue. A recent nationwide survey of nearly 200,000 adults in the United States confirmed that individuals with CU—despite current prescription treatment—suffer with significant decrements in QoL, increased prevalence of mental health concerns, impairment in work productivity, and greatly increased use of healthcare.16 These findings suggest a need for treatment plans beyond the current standard of care. In one study, approximately one-third of CSU patients remain antihistamine-resistant, even at high doses, and other observations suggest resistance may be as high as 50%.17 In the step-care approach recommended by both the American and European guidelines (Figure 2),1,2 treatment is initiated based on the patient’s urticaria severity. Third-line treatment options (eg, cyclosporine, leukotriene receptor antagonists, and omalizumab) should be added to the antihistamine treatment only when the patient does not respond to a 4-fold dosage increase of an H1-antihistamine. Short-term

• Modern second-generation antihistamines First Line

Second Line

Third Line

Rescue Therapy

• If symptoms persist after 2 weeks: – 4-fold dosage of modern second-generation antihistamines

• If symptoms persist after 4 weeks: – Add a leukotriene receptor antagonist, cyclosorine A, or omalizumab (in no particular order)

• Corticosteroids may be used for a maximum of 10 days

FIGURE 2. Guideline-recommended step-care approach to the treatment of chronic urticaria.1,2 52 THE CLINICAL ADVISOR • AUGUST 2016 • www.ClinicalAdvisor.com

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Although supported by clinical guidelines and some studies, no second- or third-line options— except omalizumab—are FDA-approved. corticosteroids may also be prescribed for exacerbations or refractory cases.1,2 Alternative treatments, which have been reported but not tested in randomized controlled trials, include dapsone, hydroxychloroquine, sulfasalazine, and methotrexate.1,2 Although supported by clinical guidelines and some clinical studies, no second- or third-line options, with the exception of omalizumab, are US Food and Drug Administration (FDA)-approved for CSU.18 It is important to note that the 2 sets of guidelines differ in the use of H2-antihistamines (eg, ranitidine) as a third-line option: their use has been eliminated as a recommended practice in Europe but not in the United States; yet their use remains controversial in the United States since the supporting evidence is low.1,2 The European guidelines also discourage the formerly propagated use of sedating antihistamines at night, as they change REM sleep patterns and learning curves.2 It is also clear that leukotriene antagonists rarely stop symptoms if high-dose H1 antagonists fail, and that supportive data are not comparable to those reported for cyclosporine19 or omalizumab.18,20

severity in patients with CSU should be assessed in terms of physical symptoms as well as QoL. ■ References 1. Bernstein JA, Lang DM, Khan DA, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133:1270-1277. 2. Zuberbier T, Aberer W, Asero R, et al; European Academy of Allergy and Clinical Immunology; Global Allergy and Asthma European Network; European Dermatology Forum; World Allergy Organization. The EAACI/GA(2) LEN/ EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69(7):868-887. 3. Toubi E, Kessel A, Avshovich N, et al. Clinical and laboratory parameters in predicting chronic urticaria duration: a prospective study of 139 patients. Allergy. 2004;59(8):869-873. 4. Powell RJ, Du Toit GL, Siddique N, et al. BSACI guidelines for the management of chronic urticaria and angio-oedema. Clin Exp Allergy. 2007;37(5):631-650. 5. Staevska M, Popov TA, Kralimarkova T, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol. 2010;125:676-682.

Next steps

6. Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in

After reviewing all the guideline-recommended third-line treatment options for CSU and discussing the potential safety and tolerability issues with each drug, Robert and his allergist together decide to next add an oral leukotriene receptor antagonist to his regimen. Robert is counseled on the importance of treatment adherence and asked to return in 1 month for follow-up. If he is not satisfied with the effects of his new treatment regimen at that time, he and his allergist plan to discuss the option of a subcutaneous injection therapy with omalizumab.

chronic spontaneous urticaria. A GA(2) LEN task force report. Allergy. 2011;66:317-330. 7. Staubach P, Eckhardt-Henn A, Dechene M, et al. Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity. Br J Dermatol. 2006;154(2):294-298. 8. Staubach P, Dechen M, Metz M, et al. High prevalence of mental disorders and emotional distress in patients with chronic spontaneous urticaria. Acta Derm Venereol. 2011;91(5):557-561. 9. Deacock S. An approach to the patient with urticaria. Clin Exp Immunol. 2008;153(2):151-161. 10. Toubi E, Grattan C, Zuberbier T. Diagnostic dilemmas in chronic urticaria.

Summary

J Eur Acad Dermatol Venereol. 2015;29(suppl 3):12-15.

In order to provide patients with proper care and treatment, clinicians need to be able to confirm urticaria and distinguish among different subtypes. According to current guidelines, a thorough clinical history and physical examination with limited laboratory testing are sufficient methods to establish a proper diagnosis.1,2 Since effective treatment of CSU can be challenging, as many patients have a only partial or an unsatisfactory response to standard therapy, guidelinerecommended treatment options should be followed. The safety and tolerability of these agents must also be considered and discussed with individual patients. Finally, disease

11. Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol. 2004;114(3):465-474. 12. Fraser K, Robertson L. Chronic urticaria and autoimmunity. Skin Therapy Lett. 2013;18(7):5-9. 13. Wolf R, Feuerman EJ. Identification of a new physically induced urticaria: cold-induced cholinergic urticaria. J Allergy Clin Immunol. 1982;70:314-315. 14. Cheon HW, Han SJ, Yeo SJ, et al. A case of combined cholinergic and cold urticaria. Korean J Intern Med. 2012;27(4):478-479. 15. Sharma M, Bennett C, Carter B, Cohen SN. H1-antihistamines for chronic spontaneous urticaria: an abridged Cochrane Systematic Review. J Am Acad Dermatol. 2015;73(4):710-716.

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FEATURED COURSE

16. Vietri J, Turner SJ, Tian H, et al. Effect of chronic urticaria on US patients:

of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368(10):

analysis of the National Health and Wellness Survey. Ann Allergy Asthma

924-935.

Immunol. 2015;115(4):306-311.

19. Kessel A, Toubi E. Cyclosporine-A in severe chronic urticaria: the option

17. Weller K, Viehmann K, Bräutigam M, et al. Management of chronic sponta-

for long term therapy. Allergy. 2010;65:1478-1482.

neous urticaria in real life–in accordance with the guidelines? A cross-sectional

20. Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symp-

physician-based survey study. J Eur Acad Dermatol Venereol. 2013;27(1):43-50.

tomatic chronic idiopathic/spontaneous urticaria despite standard combina-

18. Maurer M, Rosen K, Hsieh HJ, et al. Omalizumab for the treatment

tion therapy. J Allergy Clin Immunol. 2013;132:101-109.

CME

POST-TEST Expiration date: January 28, 2017

Credit Designation: Haymarket Medical Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. A statement of credit will be issued only upon receipt of a completed pre-assessment test, polling questions, activity evaluation form, and post-test with a score of 70% or better. All components must be completed and submitted online at myCME.com/Aug16CAfeature. CREDITS: 0.50

| A 34-year-old man presenting with a 1-year history of itchy hives

1. Vicki is a 32-year-old woman who has been experiencing daily episodes of itchy hives that last 2 to 3 hours for the past 2 months. Which of the following diagnostic indicators suggests she may have cholinergic urticaria? a. Her hives appear after she touches something cold b. Her hives appear after she runs on a treadmill c. Her hives are typically 1 to 3 inches in diameter d. She has a positive autologous serum skin test (ASST) 2. Current guidelines recommend the following diagnostic tests for patients with chronic urticaria except for: a. Complete blood cell count (CBC) with differential b. Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) level c. Skin testing for allergies d. Thyroid-stimulating hormone (TSH) test

4. Which of the following standardized tools would best assess Vicki’s disease severity and response to treatment? a. ASST b. Laboratory tests (CBC, ESR, CRP) c. Physical examination d. Urticaria Activity Score (UAS) 5. If a 4-fold dose of second-line H1-antihistamine treatment for CSU is not effective after a maximum of 4 weeks, current guidelines recommend adding any of the following third-line medications to the patient’s treatment regimen except for: a. A leukotriene receptor antagonist b. Cyclosporine c. Hydroxychloroquine d. Omalizumab

3. Vicki’s medical history, physical examination, and laboratory test confirm a diagnosis of chronic spontaneous urticaria (CSU). Which of the following medications would be considered an appropriate first-line treatment? a. A standard dose of an H1-antihistamine b. A double dose of an H1-antihistamine c. A standard dose of an H2-antihistamine d. A standard dose of a leukotriene receptor antagonist TO TAKE THE POST-TEST please go to: myCME.com/Aug16CAfeature

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

CONSULTATIONS ZIKA VIRUS: A PRIMARY CARE RESPONSE What is the response of healthcare providers to Zika virus in a highly endemic population in primary care?—TENA JORDAN, FNP, Houston Healthcare professionals should be educated about the hallmark signs and symptoms of Zika virus and advise their patients about precautions to take. The most common symptoms are fever, rash, joint pain, and conjunctivitis and can also include muscle pain and headache. Pregnant women should protect themselves from mosquitoes and avoid traveling to regions where the Zika virus is present. In addition, men who travel to areas where the Zika virus is present or who have pregnant sexual partners should either abstain from sex or use condoms during sex. The use of EPA-registered insect repellents can help prevent mosquito bites. The CDC has released clinical guidelines for the evaluation, clinical manifestation, diagnosis, and treatment algorithm of the Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 275 7th Avenue, 10th 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.

zika virus for healthcare professionals. As it currently stands, there is no vaccine or prophylactic treatment that is available, but the first vaccine is in the pipeline. Clinicians should educate their patients on infection control, personal protection, and prevention against contracting the illness. These simple precautions may help prevent patients from contracting the illness as well as the potential birth defects that could result. Valuable resources include the following: CDC. Zika virus. Retrieved from https://www.cdc.gov/zika/ hc-providers/index.html (Accessed July 18, 2016). World Health Organization. Zika virus fact sheet. Retrieved from http://www.who.int/mediacentre/factsheets/zika/en/ (Accessed July 18, 2016) —ABIMBOLA FARINDE, PhD, PharmD (See photo at bottom of this page for more information about Dr. Farinde.) (214-1)

CLINICAL PEARLS ALTERNATIVE TREATMENT OPTIONS FOR CHRONIC PAIN The following are alternative treatment options for chronic pain that I discuss with my patients: 1. Use of heat or ice, whichever works best for them. 2. Use of OTC creams. Keep trying different ones until they find the one that works best for them.

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, MS, PA-C,

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

is an assistant professor at Thomas Jefferson University and a dermatology PA at Family Dermatology of Reading, Pa.

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3. Use the cream that works best BEFORE engaging in an activity that they know aggravates the pain to help decrease or delay the pain. 4. If ice works best, keep the cream that helps them in the refrigerator to get a dual benefit. 5. I recently had a patient with chronic pain who had 4 back surgeries and swears that using 1 or 2 drops of peppermint oil rubbed on the area of the pain helps tremendously. 6. If patients must do their own chores due to a lack of help, they should pace themselves and find ways to help lessen the pain. For example, I tell them that if they must sweep the floor, they should do it similar to the way they mow the lawn, as the back and forth motion usually is a culprit in aggravating back pain. —BONNIE LORENZETTI, CRNP, Nicholson, Pa. (214-2)

THYROID ANTIBODIES Look at thyroid antibodies even in the presence of normal thyroid function tests when symptoms of thyroid disease are present (infertility, polycystic ovary syndrome, depression, anxiety, hair loss, weight difficulties, anxiety, fatigue, muscle aches, neurologic complaints, recurrent upper respiratory infections, allergies, etc.), especially in women during puberty and menopause. Newer research supports treatment with synthroid of positive antibodies with normal thyroid function tests. —REBEKAH MIZE, APRN, FNP, Clarksville, AR (214-3) A TIP FOR ENCOURAGING EXERCISE Often, overweight and/or patients with diabetes inquire about how often they ought to exercise as part of their treatment regimen. A fun response to use for these patients is, “Try and participate in some type of exercise every day

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.

that ends in the letter Y.” Once the patient understands that all days of the week end in the letter Y and a daily exercise regimen is being encouraged, they usually leave the office with a smile.—DEANA GOLDIN, DNP, ARNP, FNPBC, Miami (214-4)

CASE FILES A CASE OF G6PD DEFICIENCY Contributed by Sherril Sego, FNP-C, DNP (See photo at bottom of this page for more information about Dr. Sego.) A 43-year-old man of Mediterranean descent presented to his primary care provider for a routine visit. During the examination, the provider noted some mild splenomegaly and tenderness. On closer examination, some scleral icterus was noted. Subsequent labs showed marginally elevated LDH (lactate dehydrogenase), bilirubin, and slight anemia. G6PD, or glucose-6-phosphate dehydrogenase deficiency, is a genetic condition that makes carriers more susceptible to hemolysis and resultant jaundice. Symptoms usually only appear after a triggering event or intake of a certain food or medication. It is particularly common in people of Mediterranean and African origin and in men more often than in women. The main caution in these patients is to avoid triggers of oxidative stress, which, in extreme cases, can lead to hemolytic anemia, acute renal failure, and death. This patient was questioned regarding recent food intakes or other stressors and was found to have been drinking “several cans of beer” every night. His examination and lab values returned to normal limits, and he abstained from alcohol intake. He was also given information on other foods and medication that he should avoid. (214-5) 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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Dermatology Clinic CASE #1

Retiform purpura with areas of necrosis and bullae MELINDA LIU, BA, AND MAURA HOLCOMB, MD

A 50-year-old woman presents with a 5-day history of progressive, painful rash on her face, trunk, extremities, nasal tip, and ears, as well as fever and arthralgia. She has a history of polysubstance use, and her last use was a week prior to symptom onset. Examination reveals retiform purpura with areas of necrosis and bullae formation. Urine toxicology screening is positive for cocaine, and laboratory findings include leukopenia and an elevated erythrocyte sedimentation rate (70 mm/h). What is your diagnosis? Turn to page 64.

CASE #2

Pink patches on the hip and buttock VERNON FORRESTER, BS, AND JULIA R. NUNLEY, MD

A 43-year-old elementary school teacher presents with a rash that began on his left thigh approximately 4 months earlier; the rash has since spread. It is mildly itchy but has no associated pain or bleeding. His past medical history is significant for allergic rhinitis and atopic dermatitis. Suspecting eczema, he has been applying an over-thecounter hydrocortisone 1% cream as well as a moisturizer, which transiently alleviates the itch. He has not changed laundry or hygiene products. On physical examination, there are slightly erythematous, minimally scaly patches scattered over his left hip and buttock. What is your diagnosis? Turn to page 65. www.clinicaladvisor.com • THE CLINICAL ADVISOR • AUGUST 2016 63

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Dermatology Clinic CASE #1

Levamisole-induced antineutrophil cytoplasmic antibody vasculitis

Levamisole-induced vasculitis (LIV) is due to abuse of cocaine adulterated with levamisole; it is a significant public health issue that results in classic cutaneous, laboratory, and histologic findings. An imidazothiazole derivative previously used as an immunomodulatory drug to treat cancer and collagen vascular disease, levamisole was banned by the US Food and Drug Administration in 1998 due to severe adverse effects, including agranulocytosis and reversible cutaneous vasculitis, but it remains available as a veterinary anthelmintic agent.1-3 Due to its physical similarity to cocaine and its ability to enhance neurostimulatory effects, levamisole has been used as a cutting agent in cocaine.2-4 The US Drug Enforcement Agency recently estimated that 69% of cocaine reaching the United States is adulterated with levamisole and more than three-quarters of cocaine users tested positive for levamisole.3 The increasing rate of levamisole adulteration is associated with growing numbers of antineutrophil cytoplasmic antibody (ANCA) vasculitis.4,5 LIV occurs more commonly in women, with a mean age of presentation of 44 years, and is more common in people with the human leukocyte antigen B27 subtype and preexisting rheumatic disease.5,6 Classic cutaneous findings include a tender retiform purpuric rash involving the ears, extremities, trunk, nasal tip, and skin overlying the zygomatic arch.4,5,7 Hemorrhagic bullae are accompanied by subsequent skin sloughing. Lesions of the ear and digits can self-amputate.3,5 Cutaneous lesions resolve spontaneously within a few weeks of drug cessation but can recur upon subsequent exposures.3 Constitutional symptoms include arthralgia, fever, fatigue, night sweats, and weight loss.4,7 Although the pathogenesis of LIV remains unclear, it is thought to be immune-mediated because several immunoglobulins and C3 complexes are seen in immunofluorescence studies of skin lesions.3,5 LIV is a diagnosis of exclusion and relies on a combination of clinical, laboratory, and histologic findings. Patients are screened for cocaine use through urine enzyme immunoassays detecting cocaine metabolites.5 Levamisole can be detected in the serum or urine through the use of gas or liquid chromatographyâ&#x20AC;&#x201C;tandem mass spectrometry; however, this

is often impractical due to its short plasma half-life and the fact that the technique is often inaccessible.4 Therefore, other biomarkers have been proposed as alternatives to support the diagnosis. Unlike other vasculitides, LIV is associated with elevation of multiple ANCA, including both cytoplasmic ANCA (c-ANCA) and perinuclear ANCA (p-ANCA) and antibodies to antihuman neutrophil elastase (anti-HNE), lactoferrin, and cathepsin G.3-5,7 Elevation of antinuclear antibodies, proteinase 3, double-stranded DNA, and lupus anticoagulant are also common, and these elevations resolve following drug withdrawal.2,3,7 Characteristic hematologic changes, including

Levamisole-induced vasculitis occurs more commonly in women, with a mean age of presentation of 44 years. leukopenia, agranulocytosis, and neutropenia, also help differentiate LIV from drug-induced ANCA-associated vasculitis and pure cocaine-linked rheumatologic disease.3,5,7 Biopsy of skin lesions classically reveals microvascular fibrin thrombi and leukocytoclastic vasculitis involving the small vessels of the superficial and deep dermis.3,5,7 Fibrinoid necrosis of the vessel wall often extends into adjacent perivascular connective tissue and is accompanied by extravasated erythrocytes, leukocytoclastic debris, and angiocentric inflammation.5,7 As the use of levamisole-adulterated cocaine continues to increase, LIV should be considered in patients presenting with a combination of retiform purpura, arthritic symptoms, leukopenia, ANCA positivity, and a history of cocaine use. However, LIV remains a diagnosis of exclusion and requires ruling out infections and other idiopathic vasculitides. The differential diagnosis includes ANCA-associated vasculitides (granulomatosis with polyangiitis, microscopic polyangiitis, Churg-Strauss syndrome), which are only associated with elevation of one ANCA; disseminated intravascular coagulation, which is associated with diffuse bleeding and high levels of fibrin degradation products; warfarin-induced skin necrosis, which occurs due to an acquired protein C deficiency following treatment with an anti-vitamin K anticoagulant; thrombocytopenic disorders (heparin-induced thrombocytopenia, idiopathic thrombocytopenic purpura), which are associated with low platelet counts; and tick-borne diseases, including Lyme disease, which is associated with migrating targetoid lesions.3-5,8 Treatment of LIV includes supportive care and counseling for cocaine cessation.4 Although the use of systemic corticosteroids

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Take-away points for levamisole-induced vasculitis Clinical presentation

Differential diagnosis

Diagnosis

Management

• Retiform, tender purpura involving ears, extremities, trunk, nasal tip, and cheeks; associated with arthralgia, flu-like symptoms, fever, night sweats, weight loss • Stellate lesions tend to have bright erythematous borders with or without necrotic centers • Cutaneous lesions resolve spontaneously within a few weeks of drug cessation but can recur upon subsequent exposures ANCA-associated vasculitides (granulomatosis with polyangiitis, microscopic polyangiitis, Churg-Strauss syndrome), warfarin-induced skin necrosis, heparin-induced thrombocytopenia, septic vasculitis, cryoglobulinemia, reactive arthritis, disseminated gonococcal infection, tick-borne diseases (tick-borne typhus, Lyme disease), idiopathic thrombocytopenic purpura, DIC • Diagnosis of exclusion based on clinical, laboratory, and histologic findings • Screening for cocaine use through urine enzyme immunoassay • Multiple ANCA differentiate LIV from other vasculitides • Hematologic changes: agranulocytosis and neutropenia, leukopenia, elevated ESR • Biopsy of skin lesions with microvascular fibrin thrombi and leukocytoclastic vasculitis involving small vessels of superficial and deep dermis • Supportive care and counseling on cocaine cessation • No firm evidence of efficacy of systemic corticosteroids

ANCA, antineutrophil cytoplasmic antibody; DIC, disseminated intravascular coagulation; ESR, erythrocyte sedimentation rate; LIV, levamisole-induced vasculitis.

has been reported, lack of firm evidence of the efficacy of corticosteroid administration and the fact that administration may cause dangerous side effects leads some clinicians to reserve systemic corticosteroids for the management of persistent cases not responding to supportive therapies alone.1,3,8 In patients who demonstrate evidence of infection, granulocyte colonystimulating factor is used to treat agranulocytosis.8 In this case, the patient was transferred to the burn unit where she received surgical debridement of the necrotic tissue, skin grafting, and appropriate supportive therapy. She recovered well over the next few weeks and was counseled on abstaining from cocaine use. n Melinda Liu, BA, is a medical student and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston. References 1. Hahn E, Bogoch II. Levamisole-induced vasculitis in a cocaine user. J Rheumatol. 2015;42(10):1924-1925. 2. Garg L, Gupta S, Swami A, Zhang P. Levamisole/cocaine-induced systemic vasculitis and immune complex glomerulonephritis. Case Rep Nephrol. 2015;2015:372413.

3. Patnaik S, Balderia P, Vanchhawng L, et al. Is levamisole-induced vasculitis a relegated diagnostic possibility? A case report and review of literature. Am J Case Rep. 2015;16:658-662. 4. Baptiste GG, Alexopoulos AS, Masud T, Bonsall JM. Systemic levamisoleinduced vasculitis in a cocaine user without cutaneous findings: a consideration in diagnosis. Case Rep Med. 2015;2015:547023. 5. Roberts JA, Chévez-Barrios P. Levamisole-induced vasculitis: a characteristic cutaneous vasculitis associated with levamisole-adulterated cocaine. Arch Pathol Lab Med. 2015;139(8):1058-1061. 6. Gaertner EM, Switlyk SA. Dermatologic complications from levamisolecontaminated cocaine: a case report and review of the literature. Cutis. 2014;93(2):102-106. 7. Nolan AL, Jen KY. Pathologic manifestations of levamisole-adulterated cocaine exposure. Diagn Pathol. 2015;10:48. 8. Lawrence LA, Jiron JL, Lin HS, Folbe AJ. Levamisole-adulterated cocaine-induced skin necrosis of nose, ears, and extremities: case report. Allergy Rhinol (Providence). 2014;5(3):132-136.

CASE #2

Tinea incognito

Tinea incognito is a cutaneous dermatophyte infection, the appearance of which has been altered by the chronic use of topical or systemic immunosuppressive agents. Because itch is commonly associated, patients often use, or are prescribed, overthe-counter or prescriptionstrength topical steroids, respectively. Dermatophytes metabolize keratin in the stratum corneum via keratolytic enzymes. The host’s normal response to the fungus and to these keratolytic enzymes results in the characteristic symptoms and clinical appearance of ringworm. By blunting the host’s normal immune response, immune suppressants change the clinical appearance of the cutaneous reaction and the host’s sense of pruritus. Unfortunately, immune suppression also increases morbidity by enhancing fungal growth. The term tinea incognito (TI), first coined in 1968 by Ive and Marks in the British Medical Journal, was used to describe 14 cases of cutaneous ringworm with unusual clinical presentations resulting from local application of corticosteroids.1 In their case series, the notably unusual presentations resembled various other dermatologic disorders, including papular rosacea,

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Dermatology Clinic leprosy, and poikiloderma; the fungi Epidermophyton floccosum and Trichophyton rubrum were the most common causes.2 More recently, large-scale trials outside the United States have shown TI to be linked to more than 12 different species of fungi, with T rubrum and T verrucosum being among the most common.2-4 TI commonly affects middle-aged people (mean age, 32-44 years), with an approximately equal incidence between men and women.4-6 The largest and most recent epidemiologic survey of patients with TI showed that 23% had coexisting nondermatologic disorders such as diabetes, hypertension, and malignancy, but only 5.7% had coexisting dermatologic diseases.6 Finally, although TI was initially linked to topical and systemic corticosteroid use, it has more recently been recorded in individuals using topical calcineurin inhibitors as well.5,6 As previously mentioned, there are multiple clinical presentations for TI. Although the majority of TI cases occur on the face and trunk, any area, including the groin, extremities, and scalp, can be affected.2,4,5 Compared with dermatophyte infections not treated with immune suppressants, TI lesions tend to have less scale and minimally raised borders. However, they can have erythema, edema, and pustules3; they are often expansive and can mimic other skin diseases. Eczema, either intrinsic (atopic dermatitis) or extrinsic (contact dermatitis), is the most common eruption that is imitated.2,4,5,7 Other primary cutaneous disorders frequently impersonated by TI include psoriasis, lupus erythematosus, rosacea, pyoderma, and granuloma annulare.2-5 Because TI mimics other dermatologic disorders, it must be differentiated from these primary dermatoses. Most eczemas respond readily to topical steroids and emollients; therefore, worsening of supposed “eczema” with the use of topical immune suppressants is unusual. In this setting, the possibility of TI should be suspected. Psoriasis usually has a classic distribution that helps to differentiate it, as does granuloma annulare. Cutaneous lupus is similarly responsive to steroids or has a characteristic diagnostic appearance. Facial pustules are common in rosacea, but rosacea is mostly a symmetrical disorder. Asymmetrical facial papules and pustules in the setting of steroid use should raise the question of possible TI. Confirming the presence of fungus by culture is the gold standard for the diagnosis of any dermatophyte infection; however, the time required before results are available delays the ultimate diagnosis and potential therapy.8 Microscopic examination of a potassium hydroxide preparation performed on skin scrapings is the most commonly used bedside test to identify a fungal infection. Skin biopsy with special stains is similarly diagnostic, but is more invasive and usually not necessary unless one is investigating the presence of another underlying dermatosis.3 For those experienced with handheld

reflectance confocal microscopy—an emerging diagnostic tool—the diagnosis of TI may also be made readily at the bedside, but expertise in this technology is currently limited.8 Treatment of TI depends on the location and extent of the infection, but starts with cessation of immunosuppressive agents, if possible. For patients with limited skin involvement, topical azoles or allylamines can be effective. Combination steroid/antifungal products are largely ineffective because of the high potency of the incorporated steroid. More extensive infections, and those that fail topical therapy, require systemic treatment.3 Oral therapy with terbinafine, fluconazole, or itraconazole for 2 to 4 weeks is usually effective for cutaneous disease.3,9 Of note, prolonged use of systemic antifungal agents requires monitoring the liver and consideration of relevant drug interactions. Ultimately, the choice and duration of therapy depends upon an individual’s other medical conditions and clinical response to therapy. In our case, the patient discontinued the topical steroid and was placed on oral terbinafine, at 250 mg daily, for 2 weeks. The eruption was fully resolved at his follow-up visit 3 weeks later. n Vernon Forrester, BS, is a medical student and Julia R. Nunley, MD, is a professor of dermatology and program director of dermatology at the Medical College of Virginia Hospitals of Virginia Commonwealth University in Richmond. References 1. Ive FA, Marks R. Tinea incognito. Br Med J. 1968;3(5611):149-152. 2. Ansar A, Farshchian M, Nazeri H, Ghiasian SA. Clinico-epidemiological and mycological aspects of tinea incognito in Iran: a 16-year study. Med Mycol J. 2011;52(1):25-32. 3. Romano C, Maritati E, Gianni C. Tinea incognito in Italy: a 15-year survey. Mycoses. 2006;49(5):383-387. 4. Kim WJ, Kim TW, Mun JH, et al. Tinea incognito in Korea and its risk factors: nine-year multicenter survey. J Korean Med Sci. 2013;28(1):145-151. 5. Crawford KM, Bostrom P, Russ B, Boyd J. Pimecrolimus-induced tinea incognito. Skinmed. 2004;3(6):352-353. 6. Siddaiah N, Erickson Q, Miller G, Elston DM. Tacrolimus-induced tinea incognito. Cutis. 2004;73(4):237-238. 7. Thomsen SF. Atopic dermatitis: natural history, diagnosis, and treatment. ISRN Allergy. 2014;2014:354250. 8. Navarrete-Dechent C, Bajaj S, Marghoob AA, Marchetti MA. Rapid diagnosis of tinea incognito using handheld reflectance confocal microscopy: a paradigm shift in dermatology? Mycoses. 2015;58(6):383-386. 9. Faergemann J, Mörk NJ, Haglund A, Odegård T. A multicentre (doubleblind) comparative study to assess the safety and efficacy of fluconazole and griseofulvin in the treatment of tinea corporis and tinea cruris. Br J Dermatol. 1997;136(4):575-577.

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Dermatologic Look-Alikes Patchy hair loss on the scalp KELLY WILMAS, BS, AND MAURA HOLCOMB, MD

CASE #1

CASE #2

A 46-year-old woman presents with patchy hair loss around the circumference of her head in the frontal, temporal, and occipital regions for the previous 3 months. General and systemic examinations reveal no other abnormalities. The patient has a history of atopic dermatitis. Results of a complete blood count, thyroid panel, renal function tests, and liver function tests are within normal limits; the antinuclear antibody test result is positive at a 1:160 titer. Results of further rheumatic laboratory testing, such as double-stranded DNA antibodies, are negative. Cutaneous examination finds nonscarring, circumferential scalp alopecia.

A 40-year-old man presents with patchy hair loss of the scalp, which began 6 months earlier on the frontal scalp and later involved more temporal areas. His wife also states that she noticed recurrent hair-pulling behavior by the patient as stressful situations at his job increased in frequency. Review of symptoms and physical examination reveal no other abnormalities. Results of a complete blood count, thyroid panel, renal function tests, and liver function tests are within standard range. Dermatologic examination reveals patchy, nonscarring hair loss of the scalp with hairs of variable length distributed along the borders of the alopecia.

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Dermatologic Look-Alikes CASE #1

Alopecia areata

Alopecia areata (AA) is a cellmediated autoimmune disease that targets hair follicles and is commonly seen by dermatologists, constituting 0.7% to 3.8% of all dermatologic visits.1 It typically presents as patchy, nonscarring hair loss in single, well-defined patches or multiple patches, known as patchy AA.1-3 However, it can become a more progressive form, such as alopecia totalis, in which the entire scalp is involved, or alopecia universalis, in which there is a complete loss of hair on the scalp and body.2,3 More rare forms of AA include reticular patches of hair loss, band-like hair loss in the parietal, temporal, and occipital areas (ophiasis type), or a band-like hair loss in the frontal, parietal, and temporal scalp (ophiasis inversus).1 The exact cause of AA is still largely unknown, but it is thought to be a complex, multifactorial disease. With numerous studies, observations, and the formation of patient registries such as the National Alopecia Areata Registry (NAAR), genetics has increasingly been found to play a strong role in the pathogenesis of AA.3 For example, studies indicate a high incidence rate of AA, at 10% to 42%, among first-degree relatives of affected individuals.3 An earlier onset was correlated with an even greater incidence.3 One study showed that 7% of affected individuals had an affected parent, 3% had an affected sibling, and 2% had children with the disease; thus, an autosomal dominant inheritance pattern is suspected.3 Additionally, twin studies have shown a 55% concordance rate of AA in monozygotic twins, suggesting that possible genetic and environmental factors play a role in pathogenesis.3 Evidence also reveals that familial AA progresses more rapidly than sporadic cases, with more relapses and greater resistance to treatments.3 The human leukocyte antigen (HLA) class II alleles DQB1*03 and DRB1*1104 have been indicators of vulnerability to AA, and HLA-DR11 and HLA-DQ7 show possible susceptibility for alopecia totalis and universalis.1 Additionally, 139 single nucleotide polymorphisms are significantly associated with AA.1 Furthermore, studies have shown that emotional stress may play a role in AA pathogenesis due to alteration in the components of the hypothalamicpituitary-adrenal axis, causing a diminished corticosterone response to acute physiologic stress.1 Patients with a history of atopic or autoimmune diseases have an increased risk of developing progressive types of AA.3 A significant association

has also been noted between AA and developing vitiligo, systemic lupus erythematosus, psoriasis, atopic dermatitis, allergic rhinitis, and autoimmune thyroid diseases.3 On histologic examination, AA characteristically shows an accumulation of mononuclear cells surrounding the bulb of the affected hair follicles.1 The disease affects approximately 2% of the US population, with women and men being equally affected.1,4 The majority of affected individuals will achieve total remission within 1 year, with or without treatment, whereas typically 5% of these individuals will progress to chronic, more severe forms of AA.4 In AA, the most common trichoscopic findings are yellow dots, found in 63% to 94% of patients, exclamation-mark hairs that are thicker distally and thinner proximally, tapered hairs, broken hairs, and vellus hairs.5 Less commonly, trichorrhexis nodosa, monilethrix-like hairs, and Pohl-Pinkus constrictions are seen.5 In active AA, uniform black dots, broken hairs, and exclamation-mark hairs can indicate disease activity, whereas yellow dots and vellus hair indicate inactive AA.5 Trichoscopy can also be used to evaluate treatment progress, with pigmented, upright hairs and pigtail hairs demonstrating hair regrowth.5 The differential diagnosis of AA includes tinea capitis and trichotillomania. The lack of skin changes in AA differentiate it from tinea capitis. The patches of hair loss in AA are round compared to the geometric shape seen in trichotillomania. Pathology samples show peribulbar lymphocytic infiltrate around anagen hair follicles when CD4+ and CD8+ T cells become reactive to hair bulb autoantigens, inducing an inflammatory autoimmune response and causing hair loss.4

First-line treatment for alopecia areata includes corticosteroid injections such as triamcinolone acetonide injections. Treatment should be determined by disease severity and age of the patient.1 Most therapies are generally more successful in patchy AA than in alopecia totalis or universalis.1 First-line treatment includes corticosteroid injections such as triamcinolone acetonide injections into the deep dermis or upper subcutis, generally resulting in 71% of patients with subtotal alopecia showing hair regrowth.2 In addition, triamcinolone acetonide, at 2.5 to 10 mg/mL, can be used; 5 mg/mL is the preferred dosage for facial or scalp AA and is given in 4- to 6-week intervals.2 Topical corticosteroids, such as betamethasone valerate foam, can also be prescribed

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but are less effective against alopecia totalis or universalis, compared with injections.2 Second-line therapies include sulfasalazine, photochemotherapy, excimer laser, and fractional photothermolysis laser.2 Third-line therapies used are usually systemic corticosteroids and biologic agents.2 Treatment can also include psychologic support because patient self-esteem and body image may be altered due to the effects of the disease.2 In our case, the patient was diagnosed with AA and was prescribed injections of triamcinolone acetonide at 5 mg/mL each month. The patient began to see improvement in hair growth, texture, and density within 4 weeks of treatment, with full regrowth in 5 months.

CASE #2

Trichotillomania

Trichotillomania is a selfinf licted skin disease that involves pulling out hair and is often associated with psychopathologic impulse control impairment.6 It commonly presents as solitary or multiple, patchy, irregularly bordered areas of alopecia of the scalp with varying lengths of the remaining hair.6 In more severe cases, a rare, extensive tonsure-pattern trichotillomania, in which hair is pulled from the vertex area of the scalp, may occur.7 The disorder typically begins during childhood or adolescence and can continue into adulthood, with girls and women being more affected than boys and men.8 Clinical presentation often consists of acute-onset hair loss, portions of scalp hair that are unaffected, and chaotic regrowth of hair in areas of alopecia.6 Eyebrows, eyelashes, and other body hair are usually not involved.6 Trichotillomania results in clinically significant social and occupational impairment, and patients usually feel embarrassed or ashamed of their pulling behavior.9 The pathogenesis of trichotillomania is complex and composed of many factors. Affected individuals may pull hair to cope with stress, anxiety, sadness, or other difficult emotions.7 Hormonal changes during pregnancy can improve or worsen trichotillomania by causing mood fluctuations.7 Patients feel a sense of relief after the hair is pulled and often do it during isolated time such as while in the bathroom, while driving, or before falling asleep.8 Most patients pull their hair without self-awareness, whereas others mindfully

focus on pulling their hair.8,9 Many patients have psychiatric comorbidity; 65% have a mood disorder throughout their lifetimes, 57% have anxiety disorders, 22% have substance use disorders, and 20% have eating disorders.8 Not only can trichotillomania lead to psychiatric comorbidities, but it can also result in skin irritation and infection.8 Trichoscopic findings can vary depending on the frequency, force, and method of hair pulling. Generally, the examinations reveal numerous, disordered hair shaft deformities with no significant changes in the perifollicular area.7 The hair shafts often show broken hairs of differing lengths, short hairs with trichoptilosis, coiled hairs, exclamation-mark hairs, and black dots indicating hair shaft residues.7 Yellow dots that are characteristic of AA are usually not seen in trichotillomania, although they can occur infrequently.7 A very specific sign of trichotillomania are flame hairs, which occur in about a quarter of affected individuals.10 When more than two hairs emerge from a single follicular unit and are pulled out and break at the same length, a V-sign is created and also indicates trichotillomania.10 Diagonally broken hair shafts that result in dark, short hairs with flower-shaped ends are called tulip hairs, which can also help a clinician identify the condition in a patient.10 Hair shafts that have been continually damaged by the mechanical trauma of hair pulling may cause only hair residues to remain observable.10

A differential diagnosis of trichotillomania includes the followingâ&#x20AC;&#x201D;alopecia areata, androgenic alopecia, and tinea capitis. The differential diagnosis of trichotillomania includes alopecia areata, androgenic alopecia, and tinea capitis.6 The geometric shape and irregular borders of trichotillomania differentiate it from other types of alopecia. Treatment for trichotillomania can be psychologic or pharmacologic but will often only lessen existing symptoms without entirely eliminating the problem.9 The goal for some patients is complete self-restraint from hair pulling, whereas others strive for less frequent hair pulling.9 Selective serotonin reuptake inhibitors are commonly prescribed for the condition, but there is no evidence that these drugs perform better than placebo at improving the disease, according to a meta-analysis of pharmacologic treatment studies.9 However, there is strong empiric support that the amino acid N-acetylcysteine shows strong effectiveness over placebo.9

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Dermatologic Look-Alikes TABLE 1. A comparison of alopecia areata and trichotillomania1-10 Alopecia areata

Trichotillomania

Medical history

Autoimmune diseases, atopic status, family history of AA

Impulse control impairment, mood disorders, anxiety

Clinical presentation

Acute onset, patches of alopecia with well-defined borders

Gradual onset, asymmetrical, patchy alopecia

Findings

Numerous yellow dots, black dots, exclamationmark hairs, broken hairs, vellus hairs, perifollicular mononuclear cell infiltrate

Few or absent yellow dots, black dots, exclamationmark hairs, broken hairs, vellus hairs, coiled hairs, flame hairs,V-sign, no significant perifollicular changes

Treatment

Prognosis

Corticosteroid injections, Habit reversal training, topical corticosteroids, stimulus control, SSRIs, sulfasalazine, photochemo NAC therapy, excimer laser, fractional photothermolysis laser, systemic corticosteroids Majority of cases selfresolve within 1 year if localized

Varies with patient; psychological therapy more successful than pharmacologic

AA, alopecia areata; NAC, N-acetylcysteine; SSRI, selective serotonin reuptake inhibitor.

identifying situations that trigger hair pulling.9 The patient can learn to abolish or limit exposure to these situations.9 A combination of stimulus control and habit reversal training has proven to be very effective against trichotillomania.9 In this case, the patient was diagnosed with trichotillomania and referred to a psychiatrist for operationalized psychodynamic diagnosis and further cognitive behavioral management.7 n Kelly Wilmas, BS, is a medical student at McGovern Medical School of the University of Texas and Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston. References 1. Ito T. Recent advances in the pathogenesis of autoimmune hair loss disease alopecia areata. Clin Dev Immunol. 2013;2013:348546. 2. Alsantali A. Alopecia areata: a new treatment plan. Clin Cosmet Investig Dermatol. 2011;4:107-115. 3. Biran R, Zlotogorski A, Ramot Y. The genetics of alopecia areata: new approaches, new findings, new treatments. J Dermatol Sci. 2015;78(1):11-20. 4. Gorcey L, Spratt E, Leger MC. Alopecia universalis successfully treated with adalimumab. JAMA Dermatol. 2014;150(12):1341-1344. 5. Mubki T, Rudnicka L, Olszewska M, Shapiro J. Evaluation and diagnosis of the hair loss patient: part II. Trichoscopic and laboratory evaluations. J Am Acad Dermatol. 2014;71(3):431.e1-431.e11. 6. Harth W, Blume-Peytavi U. Psychotrichology: psychosomatic aspects of hair diseases. J Dtsch Dermatol Ges. 2013;11(2):125-135. 7. Thakur BK, Verma S, Raphael V, Khonglah Y. Extensive tonsure pattern trichotillomania-trichoscopy and histopathology aid to the diagnosis. Int J Trichology. 2013;5(4):196-198. 8. Franklin ME, Tolin DF. Treating Trichotillomania: Cognitive-behavioral Therapy for Hairpulling and Related Problems. New York, NY: Springer-Verlag; 2007. 9. Woods DW, Houghton DC. Diagnosis, evaluation, and management of trichotillomania. Psychiatr Clin North Am. 2014;37(3):301-317. 10. Yorulmaz A, Artuz F, Erden O. A case of trichotillomania with recently defined trichoscopic findings. Int J Trichology. 2014;6(2):77-79.

Nonpharmacologic treatments include habit reversal training: patients must become conscious of their hair pulling through awareness training.9 They also must acknowledge when their hands move toward the area of hair pulling through a process called competing response training.9 Social support is also important in order to keep the patient encouraged and motivated to eliminate the disease.9 Stimulus control can also be used as a treatment; this involves

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LEGAL ADVISOR CASE

Unchecked MRI results

A clinician sends an 18-year-old patient for a same-day MRI but forgets to review the results with the same urgency.

ANN W. LATNER, JD

Mr F, aged 45 years, was a nurse practitioner (NP) working in the office of a family practice physician, Dr D. Mr F and Dr D had been practicing together for the last 7 years and had a comfortable working relationship. Dr D had a satellite office from which she worked one day per week, on Wednesdays. On those days, Mr F would see the patients in the main office. The system generally worked, and patients who just wanted to see Mr F would often schedule appointments on Wednesday specifically. Wednesdays could often be challenging for Mr F, who had to deal with his own appointments in addition to squeezing people in who needed to be seen immediately. One Wednesday, around noon, Ms P, aged 18 years, came in with her mother. They had called that morning and asked to be seen as soon as possible because Ms P was experiencing some strange symptoms. After Mr F ushered them into an examination room, Ms P described her symptoms. “I’ve had this bad headache since yesterday,” she said, “and my right arm is tingly.”

Communication issues among clinicians and patients are one of the leading causes of errors and malpractice lawsuits.

She went on to describe her tongue as feeling like it was “asleep,” and a numb right leg. A physical examination revealed nothing unusual, but Mr F was somewhat concerned about the symptoms. “I’m going to order an MRI, just to be safe,” he told the patient. “I want you to go to the MRI facility right away. At your age, it’s probably nothing, but let’s make sure.” Ms P and her mother left for the MRI facility, and Mr. F went back to his waiting room full of patients. After the MRI was performed, Ms P and her mother waited at the MRI facility, hoping to be notified about the results, but they were told to call their family physician. Meanwhile, the radiologist noted that Ms P had an acute stroke and sent the report to Mr F’s office. Mr F, busy with patients, did not have a chance to look at the report by the time Ms P called, so 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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he instructed the receptionist to schedule an appointment for Ms P for first thing the next morning to go over the results. The receptionist told Ms P that Mr F would see her the next day to discuss the MRI results. Mr F fully intended to look at the MRI report before he went home, but the afternoon proved busier than expected, and by the time he was done with the waiting room full of patients, he had forgotten about the MRI results, and they sat unopened on his desk. The following morning, as Ms P was preparing for her doctor’s appointment, she had a catastrophic stroke. She was rushed to the hospital, where she required a decompressive craniectomy and cranioplasty, and she was in intensive care for a week and hospitalized for a month. Ms P lost the majority of her right-side vision and had right-side paralysis. She required two years of outpatient rehabilitation but was still left unable to read, write, or speak without difficulty. Ms P’s parents sought the counsel of a plaintiff’s attorney on their daughter’s behalf. The attorney reviewed the medical records and discussed them with the parents. “I see that the NP referred your daughter for an MRI, and the results were conveyed to the practice that same day, yet the NP never called you?” the attorney asked. “No,” Ms P’s mother said, “we were told at the radiology place to call our doctor, which we did, but the receptionist told us to come in the next morning to go over the results. So we thought everything must be fine. I mean, if it were an emergency, they would have told us to go to the hospital, right?” “Yes,” the attorney said. “That’s exactly what they should have told you to do.” The attorney agreed to take on the case, and he filed a medical malpractice lawsuit against Mr F and the medical practice. Mr F felt terrible about what had happened to Ms P. In hindsight, he knew he should have looked at the MRI results as soon as they came in, if only to make sure that nothing was amiss. He spoke to the attorney assigned to him from the practice’s medical malpractice policy. The attorney advised him to just wait out the lawsuit. “Most cases are settled out of court,” the attorney said. “It’s unlikely this will actually go to trial.” However, the case did go to trial, and when called to the stand, Mr F was forced to admit that although he had recognized that Ms P should have an immediate MRI, he had forgotten to look at the results on the same day. After a short deliberation, the jury returned with a $3.5 million verdict against Mr F and the practice.

Legal background

The $3.5 million verdict was subsequently reduced to $2 million because the state where this action took place had a cap on non-economic damages. In general, damages come in two types: economic and non-economic. Examples of economic damages include the cost of past and future medical treatment (which in Ms P’s case was substantial) and reimbursement for lost income or lost/reduced earning potential. Non-economic damages refer to awards for pain and suffering, meant to compensate for pain, stress, scarring, and disfigurement, among others. More than half of the states in the nation have enacted laws putting caps on non-economic damages in medical malpractice cases as part of attempts at medical malpractice reform. Protecting yourself

Recognizing an emergency is an essential skill for a clinician. Knowing when to direct a patient to the hospital emergency department can be crucial to that patient’s outcome. Communication issues—whether between clinicians and patients or between clinicians and other clinicians—are one of the major causes of errors and malpractice lawsuits. In this

Knowing when to direct a patient to the hospital emergency department can be crucial to his or her outcome. case, Mr F recognized that Ms P might have had a stroke—the right-side numbness and tingling, combined with a headache and a numb tongue were clues, which Mr F noticed, to send the patient for an MRI immediately. (A safer option would have been to send Ms P to the emergency department as soon as Mr F even suspected the condition could possibly be a stroke.) However, Mr F failed by not following up on the test results that he sent his patient to receive. If you send your patient for a diagnostic test, follow up on the results. If it is essential enough to send the patient right away, then check on the results right away. Too often, clinicians order tests and assume that someone else will notify them if the results are urgent. If you ordered the test, remember that it is also your responsibility to follow up with the results. n Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

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ALTERNATIVE MEDS UPDATE

What you should know about the herbs and supplements patients use By Sherril Sego, FNP-C, DNP Ms. Sego is an independent consultant in Kansas City, Mo.

Gold

Prized for its luster, purity, and value, gold may be the first metal used by humans. In its raw form, it appears more like a dark yellow rock. The first known health-related use of gold was recorded by the ancient Egyptians approximately 4500 years ago.1 Gold dental work has been found in archeologic sites, indicating that the Egyptians mined, extracted, and shaped the mineral for a wide variety of uses in their civilization. Modern use of gold in medicine began in the early 1900s and was referred to as aurotherapy or chrysotherapy.2

Background Gold is classified as a metal, with the elemental designation of Au. It has a density of nearly 20 g/cm3 and does not melt until it reaches an amazing 1948 degrees Fahrenheit.3 Because of its purity, gold is an inert element when used in the human body. This biocompatibility has made it extremely useful in many areas of dentistry and medicine. Anti-inflammatory and antimicrobial actions have since been widely recognized.

Science The anti-inflammatory mechanism of gold compounds is still one of speculation, but mounting evidence indicates that gold is taken into intracellular organelles and stored in lysosomes. There, it both inhibits the processing of antigenic agents and blocks the reactive processes that produce and release inflammatory cytokines.4,5

Research that was originally directed at the use of gold in rheumatoid arthritis evolved to show potential uses in antimicrobial therapy as well as antiviral therapy. Ongoing studies exploring the use of gold in the treatment of conditions such as cancer and human immunodeficiency virus show promising potential. Even though the use of gold products to treat rheumatoid arthritis has declined since the development of newer anti-inflammatory agents and biologic disease-modifying antirheumatic drugs (DMARDs), its efficacy still appeals to many. In a systematic review of the gold drug auranofin versus placebo for the treatment of rheumatoid arthritis, the gold compound was more efficacious when patient outcomes were scored on the presence of tender joints, pain, and erythrocyte sedimentation rate.6 In a 48-week randomized, placebo-controlled trial, researchers examined the results of using both oral methotrexate and intramuscular gold therapy in patients with

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rheumatoid arthritis whose disease was not sufficiently controlled on methotrexate alone. The study authors reported significant clinical improvement after adding intramuscular gold therapy to methotrexate.7 Adverse events were minimal, and IM gold-related adverse events led to discontinuation in 11% of the gold group over 48 weeks. The same mechanisms of action are currently being explored by researchers for possible anticancer and antimicrobial actions. Gold microparticles in a cancer cell appear to accelerate cell death as well as upregulate tumorsuppressing signals.8 Gold has also been shown to both inhibit cell growth of certain infectious microbes and make these cells more susceptible to oxidative stress and death.9 Laboratory researchers have demonstrated that relatively low intracellular concentrations of gold microparticles exhibit definite inhibitory action against cultures of methicillin-resistant Staphylococcus aureus.10

Safety, interactions, side effects The use of gold therapy is centuries old. However, there are significant side effects associated with the long-term use of parenteral gold products, and the list of organ systems subject to damage by gold therapy is lengthy. Nephropathy, lung damage, and liver injury are well-established adverse effects of long-term gold therapy.11

How supplied, dose

antibiotics has added energy to medical science’s ever-expanding search for antibacterial and antiviral therapies. In addition, the use of gold therapy as an anticancer agent appears promising, as does its more common use as a DMARD. n References 1. Purest Colloids. A Brief History of the Health Support Uses of Gold. https://www.purestcolloids.com/historygold.php. 2. Shaw CF III. Gold-based therapeutic agents. Chem Rev. 1999;99(9):2589-2600.

Gold may have potential for treating patients with rheumatoid arthritis.

The use of gold therapy as an anticancer agent appears promising, as does its more common use as a DMARD.

3. Royal Society of Chemistry. Periodic Table. Gold. http:// www.rsc.org/periodic-table/element/79/gold. 4. Seifert O, Matussek A, Sjögren F, Geffers R, Anderson CD. Gene expression profiling of macrophages: implications for an immunosuppressive effect of dissolucytotic gold ions. J Inflamm (Lond). 2012;9(1):43. 5. Rigobello MP, Folda A, Baldoin MC, Scutari G, Bindoli A. Effect of auranofin on the mitochondrial generation of hydrogen peroxide: role of thioredoxin reductase. Free Radic Res. 2005;39(7):687-695. 6. Suarez-Almazor ME, Spooner CH, Belseck E, Shea B. Auranofin versus placebo in rheumatoid arthritis. Cochrane Database Syst Rev. 2000;(2):CD002048. 7. Lehman AJ, Esdaile JM, Klinkhoff AV, Grant E, Fitzgerald A, Canvin J. A 48-week, randomized, double-blind, doubleobserver, placebo-controlled multicenter trial of combination methotrexate and intramuscular gold therapy in rheumatoid arthritis: results of the METGO study. Arthritis Rheum. 2005;52(5):1360-1370. 8. Park SH, Lee JH, Berek JS, Hu MC. Auranofin displays anticancer activity against ovarian cancer cells through FOXO3 activation independent of p53. Int J Oncol. 2014;45(4):1691-1698. 9. Harbut MB, Vilchèze C, Luo X, et al. Auranofin exerts broad-spectrum bactericidal activities by targeting thiol-

Summary

redox homeostasis. Proceedings Natl Acad Sci U.S.A. 2015;112(14):4453-4458. 10. Hokai Y, Jurkowicz B, Fernández-Gallardo J, et al. Auranofin and related heterometallic gold(I)–thiolates as potent inhibitors of methicillin-resistant Staphylococcus aureus bacterial strains. J Inorg Biochem. 2014;138:81-88. 11. Klinkhoff A. Major side effects of gold therapy. UpToDate. http://www.uptodate.com/contents/major-

The reassessment of an old therapy is not new in medicine, and the future of gold therapy looks bright. Increasing bacterial resistance to

side-effects-of-gold-therapy. Updated March 22, 2016. All electronic documents accessed July 14, 2016

Gold therapy should never be used without ongoing monitoring by a healthcare professional who is experienced in the use of gold products. Currently, oral and intramuscular gold therapy are available by prescription.

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