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■ Ovarian cancer screening ■ Contraception counseling ■ Alcohol and diabetes LEGAL ADVISOR

A clinician’s failure to take notes leads to a lawsuit. ALT MEDS UPDATE

Cod liver oil

■ Dermatology Look-Alikes



■ Feature VOLUME 20, NUMBER 9

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HAND-FOOT-ANDMOUTH DISEASE Hand-foot-andmouth disease is a common childhood illness that can occur in adults.

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Newsline ■■Ovarian cancer screening: a USPSTF

recommendation statement ■■Contraception and adolescents:

ACOG releases counseling recommendations for clinicians ■■Alcohol screening and brief intervention: a practice manual for clinicians ■■CVD prevention: New USPSTF guidelines for lifestyle counseling ■■Regular alcohol consumption is associated with lower risk of diabetes ■■Completing the antibiotic course: Is it necessary? ■■Sleep disorders may increase the risk for Alzheimer’s disease

Routine screening for ovarian cancer? 14

Salary Survey A majority of nurse practitioners and physician assistants earned a higher income than they did in 2015-2016, according to results from The Clinical Advisor’s 2017 annual salary survey. About 55% of NPs earned a raise, compared with 54% of PAs.



Web Roundup A summary of our most recent opinion, news, and multimedia content from Dermatology Clinic n An itchy rash on the abdomen n A dark lesion on the finger


Hand-foot-and-mouth disease in adults HFMD can often go undiagnosed in adults because clinicians may be relatively inexperienced in identifying childhood illnesses in adults.


CME/CE HIV prevention in


CME/CE Feature posttest

Derm Clinic: a dark lesion on the finger 41

diverse populations Available HIV interventions are not being used to the best effect. Identifying patients who are likely to benefit from HIV-prevention strategies is crucial.


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Dermatologic Look-Alikes A fever and a pruritic rash


Legal Advisor Importance of good notetaking. Taking good notes is one of the most important steps a clinician can take to reduce the risk of a lawsuit.

Continues on page 8

Alt Meds Update: cod liver oil 59

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CONTENTS DEPARTMENTS cont’d Alternative Meds Update A tablespoon of cod liver oil contains 400% of the USDA’s recommended daily allowance (RDA) of vitamin A and 200% of the RDA for vitamin D, and it may be linked to a lower risk of depression.


Your Comments ■ Fired for falling asleep on the job: our readers weigh in.


Clinical Pearl ■ Putting out the fi re of a fi re ant bite with toothpaste.


My Most Memorable Patient ■ Diagnosing a pulmonary embolism and saving a life.

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Adding oats to a gluten-free diet may not affect patients with celiac disease The addition of oats to a gluten-free diet did not affect the symptoms, histology, immunity, or serologic features in patients with celiac disease. Tips for avoiding pneumonia in patients with COPD The COPD Foundation has released tips for patients with COPD to avoid pneumonia and exacerbations. Sexually risky behavior more common in women with mental disorders than in men Women with mental illness engage in significantly more sexually risky behaviors than men, and personality risk scores are a significant predictor of total sex acts for women but not men. Sugar consumption linked to increased risk of mood disorders Research reveals an adverse effect of sugar intake from sweet foods and beverages on long-term psychological health. Offering rapid HIV testing increases overall testing rate in the emergency department Rapid HIV testing offered in parallel to patient-clinician consultations increases the testing rate in the emergency department. Screening guidelines for pediatric psoriasis comorbidities The guidelines are the first to provide recommendations for comorbidity screening in pediatric psoriasis patients.


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Gene-editing tool repairs mutation that causes hypertrophic cardiomyopathy Researchers used a gene-editing tool called CRISPR-Cas9 to repair the segment of DNA that causes hypertrophic cardiomyopathy in human embryos. The tool could have the potential to treat and prevent other genetic diseases. Watch the video here:

The Waiting Room Official Blog of The Clinical Advisor Tafari Mbadiwe, MD, JD The role of prescription habits in the opioid epidemic Current surgical and prescribing practices may have a hand in exacerbating the nation’s burgeoning opioid epidemic. Sharon O’Brien, MPAS, PA-C What do my dreams mean? We are still not sure why we dream, but many patients are still curious about the significance of dreams. Tafari Mbadiwe, MD, JD The flu vaccine’s influence on public health Improving influenza vaccination rates will require a much greater commitment to preventive public health to change public perception of the importance and efficacy of flu vaccination.

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Advisor Dx


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

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Which grade of arthritis does this patient have? A 63-year-old woman presents with left knee pain that she has had for several months. The pain is worse when going up and down stairs, and she is achy at the end of the day. She denies prior injury. Anteroposterior, lateral, and merchant view X-rays show mild joint space narrowing, subchondral sclerosis in the medial compartment, and significant osteophytes in the patella femoral joint. WHICH GRADE OF ARTHRITIS IS THIS?

• Grade 1 • Grade 2

• Grade 3 • Grade 4

● See the full case at

Derm Dx A rash on the nasolabial folds, eyelashes, and scalp The patient is a 68-year-old male presenting for treatment of a rash affecting his nasolabial folds, eyelashes, forehead, and scalp. He complains that the condition is itchy and unsightly and that it is most severe in the colder months. Medical history is positive for hypertension, cigarette smoking, and moderate alcohol use. Examination reveals erythema and scaling of the affected areas. CAN YOU DIAGNOSE THIS CONDITION?

• Systemic lupus • Discoid lupus

• Seborrheic dermatitis • Tinea faciei

● See the full case at • THE CLINICAL ADVISOR • SEPTEMBER 2017 11

Newsline S E P T E M B E R 2 017

Alcohol screening and intervention page 15

CVD prevention and lifestyle counseling page 15

Is completing an antibiotic course necessary? page 16

SCREENING FOR ovarian cancer in asymptomatic women is not recommended, as the harms outweigh the benefits, according to the US Preventive Services Task Force (USPSTF). These harms include many false-positive results, which can lead to surgical interventions in women who do not have cancer. The recommendation, which was given a Grade D, applies only to asymptomatic women. The USPSTF commissioned an evidence review of screening for ovarian cancer to update its 2012 recommendation and found 3 good-quality studies

evaluating the effect of annual screening in asymptomatic women not known to be at high risk for ovarian cancer. None of the studies found that screening significantly reduced ovarian cancer mortality. The largest and most recent trial evaluated the effects of 2 screening strategies, transvaginal ultrasound or CA-125 testing with the Risk of Ovarian Cancer Algorithm (ROCA). Women randomized to the transvaginal ultrasound arm had annual screening with transvaginal ultrasound, while women randomized to the CA-125 ROCA


Ovarian cancer screening in asymptomatic women: a USPSTF recommendation Harms may include false-positive results and unnecessary surgery.

arm had annual CA-125 testing with ROCA. After a median follow-up of 11.1 years, ovarian cancer mortality was similar in the control and intervention groups (0.35%, 0.32%, and 0.32% in the control, transvaginal ultrasound, and CA-125 ROCA groups, respectively). The primary trial results found no significant difference in mortality (transvaginal ultrasound hazard ratio [HR], 0.91; CA-25 ROCA HR, 0.89).

Contraception and adolescents: ACOG counseling recommendations THE AMERICAN COLLEGE of Obstetricians and Gynecologists (ACOG) has released recommendations to help obstetriciangynecologists counsel adolescents about using contraception. ACOG notes that clinicians should routinely address a patient’s contraceptive needs, expectations, and concerns regardless of her age or previous sexual activity. ACOG’s Committee on Adolescent Health Care recommends that obstetrician-gynecologists work with their office staff to establish office procedures and routines that protect the privacy of adolescent patients whenever possible. “Ideally, the initial reproductive health visit should take place between 13 years and 15 years and should encompass a discussion about contraception and STIs in addition to preventive medicine services such as human papillomavirus vaccination,” the committee notes.

Recommendations include the following: • Routinely address contraceptive needs, expectations, and concerns, regardless of age or previous sexual activity. • Be aware of the statutes on the rights of minors to consent to healthcare services, as these regulations vary by state. • Emergency contraception should be included in discussions about contraception. ACOG recommends that obstetriciangynecologists write advance prescriptions for oral emergency contraception for their patients. • Long-acting reversible contraceptive methods are safe and excellent choices for adolescents, due to their higher efficacy, higher continuation rates, and higher satisfaction rates compared with short-acting contraceptives. • Obstetrician-gynecologists should begin discussions with information on the most effective methods first.


A manual for alcohol screening and brief intervention

The manual is designed to help clinicians prevent morbidity associated with alcohol use.

misuse are extremely prevalent. Our patients don’t have to abuse alcohol to have bad effects.” The manual addresses how to: • Identify clinicians who can promote alcohol screening and brief intervention • Evaluate the office’s current system for alcohol screening and intervention

• Define a new system for screening and intervention • Standardize the new system using electronic health records for coding, implementing risky drinking registries, and creating a feedback mechanism The US Preventive Services Task Force has given a grade B recommendation to alcohol screening and brief intervention. The AAFP’s practice manual provides a systems-change approach for clinicians to implement alcohol screening and brief intervention into their practice. The manual also provides advice on addressing resistance to change in the office and a printable form to use in the implementation process. The manual includes additional resources for alcohol screening and training opportunities.

CVD prevention: Recommendations for lifestyle counseling A RECENT ISSUE of JAMA includes a new recommendation statement by the US Preventive Services Task Force (USPSTF) regarding behavioral lifestyle counseling for the prevention of cardiovascular disease (CVD) in adults without obesity or known CV risk factors such as hypertension, abnormal blood glucose levels or diabetes, and dyslipidemia. The recommendations are an update of the 2012 guideline. In the United States, CVD is the top cause of mortality, with an estimated 2200 CVD-related deaths each day. Noting the reduced rates of CV morbidity and mortality in adults who follow national

guidelines for physical activity and healthy eating, USPSTF reviewed 88 trials of interventions promoting these behaviors in adults (N=121,190) without known risk factors and a body mass index (BMI) of 18.5 kg/m2 to 30 kg/ m2. According to the researchers, each of these interventions “were judged to be either feasible for delivery in a primary care setting or referable from a primary care setting to community resources.” The USPSTF concluded that the benefit of behavioral counseling for CVD prevention in this particular population is positive, albeit small. Although they found no direct evidence

CVD is the leading cause of mortality in the United States.

that counseling led to decreased CVD or mortality rates, they did observe sustained improvements in systolic and diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), BMI, and waist circumference. Healthful behaviors such as increased produce consumption, reduced salt and calorie intake, and increased physical activity also improved. “Individuals who do not have obesity or risk factors for CVD and want to make behavioral changes may be [the] most likely to benefit from behavioral counseling,” task force vice chair Sue Curry, PhD, provost of the University of Iowa. • THE CLINICAL ADVISOR • SEPTEMBER 2017 15


THE AMERICAN Academy of Family Physicians (AAFP) has created an alcohol screening practice manual to help clinicians prevent morbidity and mortality associated with alcohol use. The manual, entitled Addressing Alcohol Use Practice Manual: An Alcohol Screening and Brief Intervention Program, was created in partnership with the Baylor College of Medicine Practice and Implementation Center, with funding from the CDC. It provides a step-by-step guide through the screening and intervention process. “The family medicine office is the ideal place to address this common problem,” stated Roger Zoorob, MD, MPH, AAFP member and chair of the Baylor College of Medicine. “Alcohol use and

Newsline Alzheimer’s Is a full antibiotic course necessary? A shorter treatment course has LITTLE EVIDENCE is availdisease and generally been believed to be inferiable to support the theory that sleep disorders failing to complete a prescribed or. However, there is little evidence antibiotic course contributes to antibiotic resistance, researchers reported in the BMJ. According to Martin Lewelyn, PhD, from the Department of Global Health and Infection at Brighton and Sussex Medical School in the UK and colleagues, the relationship between antibiotic exposure and antibiotic resistance is unambiguous at the population level and within individual patients. Reducing unnecessary antibiotic use is therefore essential to mitigate antibiotic resistance. However, the authors stated, the idea that stopping antibiotic treatment early encourages antibiotic resistance is not supported by evidence, while taking antibiotics for longer than necessary increases the risk of resistance.

A shorter antibiotic course may not lead to resistance.

that currently recommended durations are minimums, below which patients will be at an increased risk of treatment failure. Examples of how shorter duration of treatment has been shown to reduce clinical efficacy can be seen in otitis media, in which 5 days’ treatment is associated with a lower clinical cure rate (66%) than 10 days (84%) in children younger than age 2 years. A major component to the concept of antibiotic course rate is that it ignored the fact that patients may respond differently to the same antibiotic, according to the researchers. This is currently changing in hospital systems; however, outside the hospital patients might be best advised to stop treatment when they feel better.

Regular alcohol consumption and diabetes risk ALCOHOL DRINKING frequency is associated with a risk of diabetes, with consumption on 3 to 4 days per week associated with the lowest risk of diabetes, according to a study published in Diabetologia. Researchers conducted a cohort study to examine the association between alcohol drinking patterns and diabetes risk in men and women from the general Danish population. The authors used data from the Danish Health Examination Survey from 2007 to 2008. Of the 76,484 survey participants, 28,704 men and 41,847 women were eligible for this study and were followed for a median of 4.9 years. Self-reported questionnaires were used to obtain information on alcohol drinking


patterns, such as frequency of alcohol consumption, frequency of binge drinking, and consumption of wine, beer, and spirits. The authors then averaged beverage-specific and overall weekly alcohol intake. Information on incident cases of diabetes was obtained from the Danish National Diabetes Register. During follow-up, a total of 859 men and 887 women developed diabetes. The lowest risk of diabetes was observed at 14 drinks per week in men (hazard ratio [HR], 0.57) and at 9 drinks per week in women (HR, 0.42). Compared with current alcohol drinkers consuming less than 1 day per week, consumption of alcohol 3 to 4 days weekly was associated with a significantly lower risk for diabetes in men (HR, 0.73) and women (HR, 0.68). n


SLEEP-DISORDERED breathing and obstructive sleep apnea (OSA) are associated with biomarkers for Alzheimer’s disease, according to research presented at the Alzheimer’s Association International Conference 2017 in London. Investigators at Wheaton College found that sleep-disordered breathing increased the accumulation rate of brain β-amyloid in cognitively normal persons and in individuals with mild cognitive impairment. Another study found that obstructive sleep apnea (OSA) was associated with increased brain β-amyloid deposition, decreased cerebrospinal fluid (CSF) levels of β-amyloid, and increased tau protein levels. A combined analysis of the cognitively normal and mild cognitive impairment groups, as well as a third group with Alzheimer’s disease (n=325), found: • Associations between OSA and CSF Aβ42 levels in the MCI and Alzheimer’s groups. • Significant OSA associations with brain Aβ42 levels in cognitively normal persons and those with MCI. • OSA patients had a faster increase in brain Aβ42 over time in the cognitively normal and MCI groups. • OSA patients had a faster decrease in CSF Aβ42 and increases in tau and p-tau volumes over time in both the cognitively normal and MCI groups.


Hand-foot-and-mouth disease in adults HFMD can often go undiagnosed in adults because clinicians may be relatively inexperienced in identifying childhood illnesses in adults.


linicians frequently see patients with common communicable illnesses. Adult patients with exposure to children may be particularly vulnerable to acquiring childhood ailments. Therefore, it is important that providers who care for adults also be familiar with common childhood illnesses and understand how they manifest in adults. Handfoot-and-mouth disease (HFMD) is one such common childhood disease. Although HFMD is usually mild and self-limited in both children and adults, it is possible for the presentation to be much more severe and, in rare cases, lead to meningitis. Generally, HFMD presents with the much milder symptoms that are discussed in this review, which can nonetheless be distressing. Included in this exploration of HFMD is a recent case that has been presented to increase clinicians’ ability to recognize and treat HFMD within adult populations.


What is hand-foot-and-mouth disease?

Lesions under the foot of a man with hand-foot-and-mouth disease.

HFMD is a communicable disease caused by enteroviruses—most commonly coxsackievirus (CV) A16 or enterovirus (EV) 71.1 It was first described in 1958 during an outbreak in Toronto, Ontario, Canada,2,3 and most commonly occurs in children. HMFD is transmitted via fecal-oral, oral-oral, and respiratory routes. The virus can be found in the saliva, sputum, nasal mucus, blister fluid, and stool of an infected person. The virus quickly spreads through close personal contact, droplets in the air, contact with feces, or contact with contaminated objects, such as doorknobs • THE CLINICAL ADVISOR • SEPTEMBER 2017 17


Case Jeff was a 55-year-old married white man working as an attorney in a major city on the eastern coast of the United States. He had been healthy, with all immunizations up-todate, and had not recently traveled. In late January 2014, Jeff developed fatigue, an elevated temperature, chills, and a sore throat. He noted multiple vesicles in the back of his throat. After 2 days, a pruritic eruption of small vesicles began on the dorsal and palmar surfaces of his hands. The vesicles increased rapidly and also appeared on the sole of one foot, along with a diffuse, raised rash on his lower trunk and upper buttocks. In addition to the vesicles, mild swelling of his hands developed. Over the next few days, the rash and discomfort dramatically increased to the point of causing severe pain; Jeff was unable to sleep and experienced uncontrolled itching. Because of the pain, he was no longer able to button his clothing or hold utensils to feed himself. The fever and symptoms continued during the week after onset. Jeff recorded a temperature of 100.8° F after taking ibuprofen. At this point—with the distressing symptoms and continued fever—Jeff sought treatment at an urgent care facility in his community (Figures 1 and 2).

about the extent of his discomfort and the severity of the hand rash, stating that it was the “worst case I have ever seen.” The provider attempted to schedule an appointment with an infectious disease specialist for a second opinion and guidance; however, an appointment was not available before 3 weeks. Jeff was sent home with an analgesic (300 mg of acetaminophen with 30 mg of codeine as needed every 6 hours) for pain and an antihistamine (25 mg of hydroxyzine by mouth three times a day) to relieve the itching and help him sleep. Both medications provided some relief. The day following the urgent care appointment, the vesicles continued to grow and enlarged into bullae; some appeared to contain blood or were surrounded by bruising (Figure 3).

Other household members were healthy, without any reported recent illnesses. Jeff did like to visit and play with his 2-year-old grandson, who attended day care and had his usual share of viral illnesses.

What is usually a mildly annoying child’s illness caused 3 weeks of despair for this male adult patient. It resulted in 2 weeks of missed work and the need for more than 1 month of care for his hands as the affected areas healed. His healing hands drew attention, particularly while he was in public and especially when he was expected to shake hands with clients at work. After 3 months, remnants of scars remained on Jeff’s hands.

Based on Jeff’s presentation and his risk for exposure via his grandchild, the provider diagnosed HFMD but was concerned

FIGURE 1. Pruritic eruption of small vesicles on the patient’s palm.

After 1 week, the fever had resolved, the rash on his lower back and buttocks had also faded, and the vesicles were in various stages of healing. Jeff was able to move his hands, the swelling decreased, and he could maintain basic self-care. Other vesicles had opened and drained serosanguinous fluid. These vesicles were reported to be the most painful. After a few more days, the vesicles dried and formed crusts.

FIGURE 2. Diffuse, raised rash on the patient’s lower trunk.


FIGURE 3. Vesicles grow and enlarge into bullae.

and toys. Less commonly, HFMD can be transmitted if someone swallows poorly treated water in a swimming pool that has been contaminated with stool containing the virus.4 Epidemiology

HFMD is known worldwide, with reported outbreaks in multiple countries. For example, Australia has reported large outbreaks of EV 71 HFMD since 1986. The most recent outbreak, in which 119 children required hospitalization after presenting with fever, lethargy, myoclonus, and skin rash due to EV 71, lasted from December 2012 until May 2013.5 In the United States, HFMD is not a reportable condition. Thus, full statistics for the prevalence and incidence are not available. Large outbreaks are rare in the United States but often occur in Asia.5 Statistics are maintained in China, and approximately 1,900,000 cases and four deaths were reported in 2015. The World Health Organization provides reports that are available monthly.6 Transmission

The virus has an incubation period of 4 to 6 days, after which fever, malaise, sore throat with vesicles, and then hand vesicles develop. Viremia occurs as the virus replicates at sites, such as the skin, mucous membranes, central nervous system, and other organs.6,7 Although affected people are most contagious during the first week, they can remain infectious for approximately 4 to 8 weeks after the onset of illness because of residual viral shedding in stool.8 Sometimes, people (especially adults) will not have symptoms but can still transmit the virus. HFMD is not transmitted to or from household pets or other animals.4 Transmission is usually between family members. Outbreaks tend to be seasonal in temperate climates, occurring more frequently in spring and summer.3 Signs and symptoms

In the United States, the typical case of HFMD is caused by CV A16 and occurs during the warmer months in children younger than 10 years of age.9 The median age of infected children is 19 months, and only 24% of children present with typical signs and symptoms of HFMD. The children initially have malaise and possibly fever; these are followed by characteristic mucocutaneous vesicular lesions in the oropharynx and on the hands and feet. Resolution of the symptoms and lesions takes 7 to 10 days. Cases may be more severe and prolonged in children younger than 2 years of age, including infants. In a typical case, bullae are rare10; however, one-third of patients present with a rash on their feet or buttocks,11 which resolves in about 1 week.


Fortunately, complications are uncommon. Fingernail and toenail loss can occur but is temporary, and the nails grow back without treatment.12,13 Rare cases of viral meningitis have been reported that required hospitalization. Even more unusual is encephalitis or paralysis, usually associated with EV 71 infection.14 Coxsackevirus A6 infection

Recently, severe worldwide outbreaks of HFMD have occurred caused by a strain of coxsackievirus that is less common than EV 71 or CV A16. This newly recognized strain, CV A6, affects both children and adults. Hand, foot and mouth disease The CV A6 strain was first identified in Finland in 2008 during a major outbreak of HFMD. Later outbreaks were detected across Asia and Europe.16 One outbreak of CV A6 HFMD occurred in Israel during the winter months16; CV A6 HFMD was diagnosed in five patients between December 2012 and February 2013. The occurrence of this cluster of cases during winter is not typical for HFMD in temperate regions.1 At Boston Children’s Hospital in the winter of 2012, eight children between 4 months and 3 years of age had HFMD caused by CV A6. The illness was additionally characterized by perioral lesions and lesions on the dorsal surfaces of the hands.17 Approach to the patient with suspected HFMD Diagnosis

HFMD is usually diagnosed by history and physical examination. In the presented case, Jeff had frequent contact with his grandchild, who was younger than 4 years of age, so the grandson was the likely source of the illness. The rash usually consists of papules and vesicles, 2 to 6 mm in size, on the gingiva, buccal mucosa, tongue, and pharynx. Lesions may also be found on the skin of the hands, feet, buttocks, and genitalia.11 Of note, the presentation of CV A6 HFMD has some atypical features: lesions on the dorsal surfaces of the hands, areas of eczema, and large purpuric vesicles/bullae.18 Fever and malaise are often present. CV A6 HFMD has been reported to present with more bothersome symptomatology. Cases of HFMD caused by CV A6 may occur seasonally and have the appearance of typical cases caused by other strains; however, clustered cases of CV A6 HFMD in Scotland and the United States were noted between October and February, whereas typical HFMD outbreaks take place in the summer and early autumn. Untimely presentations may cause providers to miss the diagnosis. Four children were admitted to • THE CLINICAL ADVISOR • SEPTEMBER 2017 19


Cases of HFMD disease that are caused by CV A6 may occur seasonally and have the appearance of typical cases caused by other strains. a hospital in Edinburgh, United Kingdom, during winter. Initially, these patients were treated with acyclovir for a feared diagnosis of eczema herpeticum; afterward, however, molecular typing identified CV A6.19 What about the rash on Jeff ’s trunk and buttocks? Some literature emphasizes that HFMD should be recognized as hand-foot-mouth and buttock disease because lesions appear on the buttocks in one-third of cases. Jeff ’s illness occurred in winter.11 As noted, HFMD occurs more commonly in temperate climates during the summer and fall, but outbreaks of CV A6 HFMD can occur in winter. A cluster of cases of CV A6 HFMD was noted in the United States between November 2013 and December 2014.1,19 CV A6 HFMD also tends to have a more severe course that includes erosive lesions that may be purpuric, and it affects the buttocks.15 In late disease, desquamation of the hands and feet may have a clinical presentation similar to that of certain fungal infections.16 A culture specimen can be sent for laboratory analysis, but this is not always readily available and is rarely done. The virus is found and can be cultured from skin or oral lesions or from stool specimens. The best place to swab for a sample is an oral lesion; however, if there are no vesicles, a rectal swab can be performed.20 The culture result may take longer than 2 weeks, at which point the patient should be recovering.21 A culture can be helpful to determine the strain, guide the care of household contacts, and determine whether an outbreak is occurring. Polymerase chain reaction (PCR) and microarray technology can be used to identify the causative virus. Different healthcare settings may have a variety of specific


Which of the following best describes your experience with hand-foot-and-mouth disease? n=793

■ I’ve encountered it in children and adults

19.29% 41.49%

■ I’ve encountered it only in children ■ I rarely encounter it in either children or adults


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assays.20 An infectious disease consult is rarely necessary but is nevertheless recommended in questionable cases or when the patient is known to be immunosuppressed. Differential diagnosis

HFMD can be confused with another vesicular eruption, such as herpes simplex or varicella-zoster virus infection.17 The differential diagnosis in an adult can include a variety of conditions with cutaneous manifestations, including varicellazoster virus infection, drug reaction, eczema herpeticum, secondary syphilis, and bullous impetigo.18, 22, 23 Other viral infections caused by CV strains or versions of the echovirus can present with herpangina but are usually accompanied by a high fever. Aphthous stomatitis may have the appearance of HFMD with oral ulcerations, but the ulcerations are larger than those in HFMD, are not associated with fever, and may be recurrent.20,21 Eczema herpeticum is a serious skin infection that occurs as a secondary herpesvirus infection within preexisting lesions of atopic dermatitis or another erosive dermatosis. It usually occurs in children and young adults with a history of eczema in which the skin has become compromised and is easily invaded by the herpesvirus. The rash spreads and appears as scattered umbilicated lesions. Eczema herpeticum can become a fulminant disease with systemic symptoms and involvement. Those most at risk are children who have atopic dermatitis or who are immunocompromised. It carries a 10% mortality rate.24 A drug reaction typically presents in the form of pruritic skin lesions. Stevens-Johnson syndrome can be due to a drug reaction. The characteristic features of Stevens-Johnson syndrome include a rapidly developing blistering exanthema and target-like lesions accompanied by mucosal involvement and skin detachment.25 In 2010–2012 in Taiwan, 21 cases of CV A6 HFMD were initially treated as suspected severe drug reactions affecting the skin.25 A drug may be responsible for skin reactions and should always be considered, especially in cases with an atypical clinical presentation, such as that of CV A6 HFMD.25 Drug-induced hypersensitivity syndrome (DIHS) is a multiple-organ drug reaction previously known as drug reaction with eosinophilia and systemic symptoms (DRESS). The former term is now used because eosinophilia is not always present. HFMD is usually limited, milder than DIHS, does not involve organs, other than the skin and mucus membranes and does not lead to full-thickness epidermal necrosis.25


As outbreaks occur, it will be essential for primary care providers to be aware of the adult presentation of HFMD and the newer strain of CV A6. Other childhood illnesses can present with a rash and may be included in the differential diagnosis. A 43-year-old patient in Connecticut developed 2- to 9-mm pink-red papules and papulovesicles on the left forearm, dorsal surfaces of the hands, palms, fingers, and one toe. Small vesicles and erosions were also present on the hard palate and soft palate. The provider ordered a complete blood cell count and PCR of serum for parvovirus B19. The blood cell count was normal, and the result of the test for parvovirus B19 was negative. However, the result of reverse transcriptase (RT)-PCR4 of plasma for enterovirus was positive. A test for viral typing sent to the CDC confirmed CV A6 infection.26 Treatment

The treatment of HFMD is supportive and includes consideration of reducing transmission. In Jeff’s case, the primary symptoms were itching and pain from the lesions. He was treated with analgesics and antihistamines for symptom control. He was encouraged to rest, stay away from the workplace with his active lesions and fever, and increase his fluid intake. Cool liquids and the avoidance of acidic and spicy foods are preferred. If lesions in the mouth are severe to the point that they limit intake, intravenous hydration may be necessary.20 To prevent transmission, Jeff should practice frequent handwashing, especially after touching any blisters or using the bathroom and before eating. Although it is assumed that Jeff was exposed to HFMD via his grandchild, he should stay away from children while he is febrile with active lesions. Institutional outbreaks are possible with children, and contact precautions are recommended in healthcare settings. As new cases of CV A6 HFMD appear and affect adults with an atypical presentation, increased vigilance may become necessary to recognize outbreaks.17 At Jeff’s home, contaminated surfaces and items should be washed and disinfected with dilute chlorine bleach. Jeff should avoid close contact with others while infected—refraining from hugging, kissing, and sharing utensils. Contacts should be observed for the development of symptoms.27 At this time, there is no vaccine for the viruses responsible for HFMD3; however, research is ongoing to develop small-animal models for testing possible vaccines.28

the basis of the clinical presentation, deviated from what has been commonly seen in the past. Jeff’s lesions were larger and clinically more symptomatic than those commonly seen in children. Fortunately, with some symptomatic support, Jeff’s lesions healed, and he experienced no sequelae. Perhaps he did have HFMD from CV A6. As outbreaks occur, it will be essential for primary care providers to be aware of the adult presentation of HFMD and the newer strain of CV A6. n Susan Renda, DNP, ANP-BC, CDE, FNAP, is an assistant professor and AGNP primary care track coordinator at the Johns Hopkins University School of Nursing, and Michael Sanchez, DNP, CRNP, NP-C, FNP-BC, AAHIVS, is an assistant professor at the Johns Hopkins University School of Nursing in Baltimore. References 1. Ben-Chetrit E, Wiener-Well Y, Shulman LM, et al. Coxsackievirus A6-related hand foot and mouth disease: skin manifestations in a cluster of adult patients. J Clin Virol. 2014;59:201-203. 2. Robinson CR, Doane FW, Rhodes AJ. Report of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957: isolation of group A Coxsackie virus. Can Med Assoc J. 1958;79:615-621. 3. Nassef C, Ziemer C, Morrell DS. Hand-foot-and-mouth disease: a new look at a classic viral rash. Curr Opin Pediatr. 2015;27:486-491. 4. Centers for Disease Control and Prevention. Hand, foot, and mouth disease. Causes & transmission. Transmission. about/transmission.html. Updated January 6, 2017. Accessed July 2, 2017. 5. Zander A, Britton PN, Navin T, et al. An outbreak of enterovirus 71 in metropolitan Sydney: enhanced surveillance and lessons learned. Med J Aust. 2014;201:663-666. 6. Centers for Disease Control and Prevention. Hand, foot, and mouth disease (HFMD). Updated January 6, 2017. Accessed July 2, 2017. 7. World Health Organization. Hand, foot, and mouth disease situation update number 478. December 29, 2015. Accessed July 2, 2017. 8. Romero JR. Hand, foot, and mouth disease and herpangina: an overview. Up to Date. Updated June 27, 2017. Accessed July 2, 2017. 9. Buttery V, Kenyon C, Grunewald S, Oberste MS, Nix WA. Atypical presentations of hand, foot, and mouth disease caused by coxsackievirus


A6—Minnesota, 2014. MMWR Morb Mortal Wkly Rep. 2015;64:805.

HFMD may often go undiagnosed in adults because the clinicians who treat them are relatively inexperienced in identifying childhood illnesses. This case, diagnosed as HFMD on

10. Ventarola D, Bordone L, Silverberg N. Update on hand-foot-andmouth disease. Clin Dermatol. 2015; 33:340-346. Continues on page 25 • THE CLINICAL ADVISOR • SEPTEMBER 2017 21


11. Matsuzawa M, Ishii A, Demitsu T, Sugawara H. Coxsackie A16 virusassociated atypical hand-foot-and-mouth disease. Intern Med. 2014;53:643-644. 12. Abramovici G, Keoprasom N, Winslow CY, Tosti A. Onycholysis and subungual haemorrhages in a patient with hand, foot and mouth disease. Br J Dermatol. 2014;170:748-749. 13. Cuppari C, Manti S, Arrigo T, Salpietro C. Not only fever and palmoplantar vesicular eruption. Infection. 2014;42:947-948. 14. Centers for Disease Control and Prevention. Hand, foot, and mouth disease (HFMD). Complications. about/complications.html. Updated January 6, 2017. Accessed July 2, 2017. 15. Mathes EF, Oza V, Frieden IJ, et al. “Eczema coxsackium” and unusual cutaneous findings in an enterovirus outbreak. Pediatrics. 2013;132:e149-e157. doi:10.1542/peds.2012-3175. 16. Downing C, Ramirez-Fort MK, Doan HQ, et al. Coxsackievirus A6 associated hand, foot and mouth disease in adults: clinical presentation and

“This is my last year at camp. Next year I plan to spend the summer at the mall.”

review of the literature. J Clin Virol. 2014;60:381-386. 17. Flett K, Youngster I, Huang J, et al. Hand, foot, and mouth disease caused by coxsackievirus A6. Emerg Infect Dis. 2012;18:1702-1704. 18. Feder H, Bennett N, Modlin J. Atypical hand, foot, and mouth disease: a vesiculobullous eruption caused by Coxsackie virus A6. Lancet. 2014;14:83-86. 19. Sinclair C, Gaunt E, Simmonds P, et al. Atypical hand, foot, and mouth disease associated with coxsackievirus A6 infection, Edinburgh, United Kingdom, January to February 2014. Euro Surveill. 2014;19:20745. Medscape. Updated June 16, 2017. Accessed July 2, 2017. 21. Johns Hopkins Medicine Health Library. Hand-foot-and-mouth disease. hand-foot-and-mouth_disease_90,p01857. Accessed April 23, 2016. 22. Baughn RE, Musher DM. Secondary syphilitic lesions. Clin Microbiol Rev. 2005;18:205-216. 23. Kazlouskaya V, Wittmann C, Tsikhanouskaya I. Pustular secondary

“For a better look at the painting, go to our website.”

syphilis: report of three cases and review of the literature. Int J Dermatol. 2014;53:e428-e431. doi: 10.1111/ijd.12337. 24. Blanter M, Vickers J, Russo M, Sarai B. Eczema herpeticum: would you know it if you saw it? Pediatr Emerg Care. 2015;31:586-588. 25. Chung W, Shih S, Chang C, et al. Clinicopathologic analysis of coxsackievirus A6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions. J Infect Dis. 2013;208:1968-1978. 26. Lott JP, Liu K, Landry ML, et al. Atypical hand-foot-and-mouth disease associated with coxsackievirus A6 infection. J Am Acad Dermatol. 2013;69:736-741. 27. World Health Organization. Western Pacific Region. Hand, foot, and mouth disease. fs_10072012_HFMD/en/. July 10, 2012. Accessed July 2, 2017. 28. Caine EA, Fuchs J, Das SC, Partidos CD, Osorio JE. Efficacy of a trivalent hand, foot, and mouth disease vaccine against enterovirus 71 and coxsackie viruses A16 and A6 in mice. Viruses. 2015;7:5919-5932.

“This is where we added high-caffeine cappuccino to our office coffee machines.” • THE CLINICAL ADVISOR • SEPTEMBER 2017 25

Top, bottom: © Harley Schwadron, 2017. Middle: © The New Yorker Collection 2017 from All Rights Reserved.

20. Nervi SJ. Hand-foot-and-mouth disease (HFMD) workup. http://emedicine.


n EDUCATIONAL OBJECTIVES After completing the activity, the participant should be better able to: • Describe the critical need for HIV-prevention practices for individuals at increased risk for infection • Identify individuals who are most likely to benefit from HIV-prevention strategies • Address general barriers to the implementation of HIV-prevention services within their practice • Implement strategies to provide culturally competent education and counseling about HIV-prevention strategies to patients at risk for HIV infection n COMPLETE THE POST-TEST: Page 40

Release Date: June 26, 2017 Expiration Date: June 25, 2018 Estimated Time to Complete: 1 hour Accredited Provider: This program is jointly provided by Morehouse School of Medicine Office of Extended Professional Education and AKH Inc., Advancing Knowledge in Healthcare. Commercial Supporter: This activity is supported by an educational grant from Gilead Sciences, Inc. Program Description: Prevention strategies are critical in halting the spread of HIV infection. Knowledge of HIV status, condom use, avoidance of injectable drugs, limiting the number of sexual partners, and use of pre-exposure prophylaxis (PrEP) are all integral components of effective HIV prevention. Unfortunately, such interventions are currently not being utilized to best effect, as the racial disparities that have been present from the start of the epidemic persist. Identifying patients likely to benefit from HIV-prevention strategies and providing these individuals with access to these interventions is crucial. Intended Audience: Primary care and internal medicine clinicians (MDs/DOs, physician assistants [PAs], nurses [RNs], and nurse practitioners [NPs]) Conflict of Interest Disclosure Policy: Morehouse School of Medicine (MSM) in accordance with the ACCME guidelines requires instructors, planners, managers, and other individuals who are in a position to control the content of this activity to disclose to the audience any real or apparent conflicts of interest they may have as related to the content of this activity. Full disclosure of speaker relationships will be made at the activity. Those expecting to discuss “off-label” drugs must identify that portion of the presentation as being related to “off-label” drugs. All identified conflicts of interest are thoroughly vetted by MSM for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and the appropriateness of patient care recommendations. Faculty Brian Hujdich Executive Director, HealthHIV, National Coalition for LGBT Health, Washington, DC. Mr. Hujdich has no relevant financial relationship to disclose. Jeffrey T. Kirchner, DO, FAAFP, AAHIVS Medical Director, Penn Medicine/LGHP – Comprehensive Care, Lancaster General Hospital, Lancaster, PA. Dr. Kirchner has no relevant financial relationship to disclose. Niva Lubin-Johnson, MD, FACP Past Section Chair, Advocate Health Care AMA Minority Affairs Section, Chicago, IL. Dr. Lubin-Johnson has no relevant financial relationship to disclose. Edith P. Mitchell, MD, FACP Immediate Past President, National Medical Association, Clinical Professor of Medicine and Medical Oncology, Department of Medical Oncology Director, Center to Eliminate Cancer Disparities Associate Director, Diversity Affairs, Sidney Kimmel Cancer Center at Jefferson, Philadelphia, PA. Dr. Mitchell has no relevant financial relationship to disclose. Elena V. Rios, MD, MSPH, FACP President and Chief Executive Officer, National Hispanic Medical Association, Washington, DC. Dr. Rios has no relevant financial relationship to disclose. Carl G. Streed, Jr, MD Chair, Advisory Committee on LGBTQ Issues American Medical Association, Boston, MA. Dr. Streed has no relevant financial relationship to disclose.

CME Activity Directors Mesfin G. Fransua, MD Associate Professor of Medicine Morehouse School of Medicine, Atlanta, GA. Dr. Fransua has no relevant financial relationship to disclose. H. Gene Stringer, MD Associate Professor of Medicine, Morehouse School of Medicine, Atlanta, GA. Dr. Stringer has no relevant financial relationship to disclose. CE Lead Nurse Planner Dorothy Caputo, MA, BSN, RN AKH Inc., Advancing Knowledge in Healthcare, Jacksonville, FL. Ms. Caputo has no relevant financial relationship to disclose. Provider Disclosures: The staff of Morehouse School of Medicine and Dorothy Caputo, MA, BSN, RN, Lead Nurse Planner of AKH Inc., Advancing Knowledge in Healthcare have no relevant financial relationship to disclose. Publishing Staff Disclosures: Priya Wanchoo, MD, and Michael Broder of Haymarket Medical Education have no relevant financial relationship to disclose. Accreditation Statement: The Morehouse School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Designation Statement: The Morehouse School of Medicine designates this enduring activity for a maximum of up to 1.00 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Accreditation Statement: AKH Inc., Advancing Knowledge in Healthcare is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. Designation Statement: This activity is awarded 1.00 contact hours. Disclaimer: CME activities sponsored by Morehouse School of Medicine are offered for continuing education purposes only. Practitioners must continue to exercise their professional judgment when selecting diagnostic tests and therapy specific to the patient’s medical needs. Instructions: There are no fees for participating in and receiving CME/CE credit for this activity. During the period June 26, 2017 through June 25, 2018, participants must: 1) read the learning objectives and faculty disclosures; 2) complete the pre-assessment test; 3) study the educational activity; and 4) 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 If you have any questions relating to the CME accreditation of this activity, please contact MSM at or 404-752-1106. If you have any questions relating to the CE accreditation of this activity, please contact AKH at If you have any questions relating to your certificate or other issues with the activity, please contact


Produced by


HIV prevention in diverse populations Available HIV interventions are not being utilized to best effect. Identifying patients likely to benefit from HIV-prevention strategies is crucial.



Specific groups are at increased risk for HIV infection and are important targets for prevention strategies

his activity was developed as part of a collaborative initiative involving a number of stakeholders: Haymarket Medical Education (HME), the Morehouse School of Medicine– Center of Excellence on Health Disparities (CEHD), the American Medical Association (AMA), the National AHEC (Area Health Education Center) Organization, the National Hispanic Medical Association (NHMA), the National Medical Association (NMA), HealthHIV, the National Coalition for LGBT Health, and Urban Health Plan. This collaborative initiative, IMPACT on Health Disparities in HIV Prevention, includes several sequenced CME/CE activities and seeks to address barriers to the uptake of HIV prevention practices and offer practical strategies for overcoming these obstacles, especially in patients who are at increased risk for infection (Figure 1). A key focus of this monograph is the importance of cultural competency when engaging patients in the discussion of potentially sensitive personal information to establish trust and uncover potential behaviors that may place individuals at high risk for HIV. By considering the urgency of HIV prevention programs for high-risk groups and the critical need for HIV prevention based on the current demographic dynamics of the epidemic,

To learn more, please visit • THE CLINICAL ADVISOR • SEPTEMBER 2017 27



practicing clinicians will be able to implement strategies to provide culturally competent education and counseling about HIV prevention strategies to patients at risk for HIV infection. Barriers to the implementation of these strategies will also be discussed. Finally, whether it may be time for an HIV continuum of prevention, parallel to the HIV continuum of care that now drives policies regarding testing and treatment efforts, will be discussed. The urgency of HIV prevention programs for high-risk groups

HIV prevention efforts over the past 30 years have brought infection rates down among some populations, including African American women, people who inject drugs (PWID), and heterosexual individuals. Rates have stabilized among gay and bisexual men, including black men who have sex with men (MSM).1 Nevertheless, the annual rate of new HIV infections in the United States remains at approximately 40,000 per year, with a range of social and economic factors putting some populations at greater risk.1 Increased risk of HIV is a result of individual behaviors, not identities; in principle, anyone can become infected. Nevertheless, there are specific groups that are at high risk for HIV infection. In the public health arena, these groups are referred to as key populations, and they are the most important targets for HIV prevention strategies.2

The World Health Organization (WHO) guidelines on HIV prevention, diagnosis, and treatment focus on 5 key populations: (1) MSM, (2) PWID, (3) people in prisons and other types of detention centers, (4) sex workers, and (5) transgender persons.2 As the WHO guidelines point out, many high-risk people belong to more than 1 key population.2 The dynamics of HIV infection require us to view affected populations in the United States somewhat differently than in other regions of the world, particularly because of the overlapping epidemics of HIV, racism, and poverty, which in turn impact issues such as homelessness, drug use, and the exchange of sex for money or nonmonetary items.3 The Centers for Disease Control and Prevention (CDC) estimates that some 1.2 million Americans are currently living with HIV; of these individuals, nearly 1 in 8, or 13%, do not know they are infected.1 By transmission category, most new HIV infections in the United States occur among MSM of all races and ethnicities, followed by African American heterosexual women (Figure 2). While the CDC estimates that MSM account for 4% of the male population of the United States, in 2010 they accounted for 78% of new HIV infections among men and 63% of new infections overall.1 African Americans are the most heavily impacted population by race or ethnicity overall, followed by Hispanics/ Latinos.1 In 2015, African Americans accounted for 45% of

FIGURE 1. IMPACT on health disparities in HIV prevention curriculum The Executive Summit Meeting, The Need for HIV Prevention in Diverse Populations: Eliminating Health Disparities March 2, 2017

Five Online Cases: Alaska Native, African American, LGBTQ, Hispanic, and Native American June 2017

Satellite Symposium at SYNC 2017 April 24, 2017

Two Live Workshops: Morehouse School of Medicine and Urban Health Plan July 2017

Satellite Symposium at NHMA 21st Annual Conference May 6, 2017

Three Case-Based Webinars on HIV Prevention for Specific Audiences: NMA, the National LGBTQ Health Clinics, the Area Health Education Centers (AHECs) May-June 2017


Satellite Symposium at AAFP: FMX (Family Medicine Experience) September 14, 2017

Peer-Reviewed Journal Article: The curriculum design and the outcomes

all HIV diagnoses, though they constituted just 12% of the US population.1 Hispanics/Latinos make up approximately 17% of the US population, yet in 2014 they accounted for 24% of all new HIV infections and 21% of people living with HIV.1 Among people who identify as heterosexual, women bear a far heavier burden of HIV infection than men. Though overall HIV diagnoses among women have declined in recent years, women accounted for 19% of all new HIV diagnoses in the United States in 2015; 86% of HIV diagnoses among women are attributed to heterosexual sex and 13% are attributed to injection drug use.1 Black women continue to be significantly more impacted by HIV than women of other races or ethnicities, accounting for 60% of all new infections among women.1 Also at high risk of HIV infection are PWID, who accounted for 6% of all new infections in 2015—although these numbers have declined throughout the years due to needle-exchange and other harm-reduction programs. Of the HIV diagnoses attributed to intravenous drug use (IDU) in 2015, 40% were among white individuals, 38% were among African Americans, and 19% were among Hispanics/Latinos.1 Also heavily impacted by HIV are transgender persons.1 Based on the 2015 US Transgender Survey, which included responses from 27,715 respondents from all 50 states, the

District of Columbia, American Samoa, Guam, Puerto Rico, and US military bases overseas, 1.4% of all transgender respondents were living with HIV—nearly 5 times the rate in the US population (0.3%). HIV rates were higher among transgender women (3.4%), especially transgender women of color.4 The rate among black respondents (6.7%) was substantially higher, and the rate for black transgender women was a staggering 19%.4 Native American (4.6%) and Latina (4.4%) transgender women also reported higher rates.4 Moreover, 50% of transgender individuals diagnosed with HIV in the United States are African American.5 At the intersection of race, gender, and sexuality, we find the most devastating corner of the ongoing HIV epidemic in the United States. Young black MSM continue to bear the heaviest burden of HIV in the United States, accounting for more new infections than any other subgroup by race, ethnicity, age, or sex, followed by young Hispanic/ Latino MSM.1 The critical need for HIV prevention in high-risk groups

Such statistics underscore the critical need for HIV prevention programs and services targeting these high-risk groups. When striving to implement HIV prevention interventions in these individuals, primary care providers are faced with a number of challenges. One is identifying patients who

FIGURE 2. New HIV diagnoses in the United States, 20151

Black MSM

10,315 7,570

White MSM


Hispanic/Latino MSM


Black Heterosexual Women


Black Heterosexual Men Hispanic/Latina Heterosexual Women White Heterosexual Women


Men Women



2,000 4,000 6,000 8,000 10,000 12,000

MSM, men who have sex with men. • THE CLINICAL ADVISOR • SEPTEMBER 2017 29



Language barriers can prevent high-risk individuals from asking about prevention services and clinicians from providing information about these services. are likely to benefit from HIV prevention strategies: whose responsibility is it to initiate that conversation, and what are the best ways to talk about or otherwise raise awareness about HIV prevention with patients who might be at high risk? Another challenge lies in overcoming the barriers to implementing HIV prevention services in daily clinical practice. These barriers fall into a number of distinct but overlapping categories that can be summed up in 2 words: availability and access. Availability refers to whether or not the services exist at all within a given locale—in particular, underserved areas do not have adequate services available to them. However, it is important to be familiar and establish relationships with services that are available through existing programs via clinics funded by the Ryan White HIV/AIDS Program and other community healthcare centers. In strictly medical terms, we now have a number of effective HIV prevention strategies, comprising behaviors (low-risk or no-risk sex and drug practices), barriers (condoms), and pharmacologic interventions. Behaviors and barriers have been in the HIV prevention armamentarium virtually from the beginning of the epidemic. What is new and exciting in the arena of HIV prevention is the range of pharmacologic interventions that have become available more recently. These include treatmentas-prevention (TasP), post-exposure prophylaxis (PEP), and pre-exposure prophylaxis (PrEP). Each of these methods will be covered in greater detail in subsequent sections. Access refers to whether or not people who need available prevention methods can actually obtain them. Barriers to access can take many forms. Many individuals at risk for HIV infection lack health insurance or access to healthcare services. Many lack awareness that services are available or are not knowledgeable about how to access these interventions. It may also be the healthcare provider (HCP) who lacks adequate awareness or knowledge about prevention services and therefore cannot guide patients or prescribe interventions appropriately. Many practices lack the appropriate staff and other resources to permit adequate prevention strategies. Moreover, time to accomplish adequate and required strategies is not uniformly covered by third-party and reimbursement resources. Additionally, patient-intake tools and screening devices vary in information intake and consequently may not effectively identify patients at greatest risk of HIV infection. Some barriers to access are matters of cultural competence among clinicians. Cultural competence refers to a clinician’s

effectiveness in dealing with patients from diverse backgrounds, particularly based on knowledge of diverse cultures and the ways in which cultural differences impact availability of and access to medical care for different communities.6-11 Language barriers, for example, can prevent high-risk individuals from asking about prevention services and/or clinicians from providing information about such services, which can result in a lack of understanding of symptoms, treatment, or diagnosis; patient nonadherence to treatment plans; and, potentially, premature death. A person in a sexually abusive or sexually coercive domestic setting may not be able to talk about their risk safely to an HCP (this applies to people in both same-sex and opposite-sex relationships). The same may be true of people in prison or other detention environments, again, regardless of sex or sexual orientation. Substance-use issues or mental illness may compromise a high-risk person’s ability to seek HIV prevention services even as they increase their HIV risk by impairing their judgment and making them more likely to engage in HIV risk behaviors. Many of these barriers undermine not only the ability of high-risk people to access prevention services, but also to adhere to prevention methods when they do access services. Strategies exist to overcome many of these barriers; however, implementing such strategies may be difficult for individual clinicians, as they are often matters of social and economic infrastructures, falling largely within the purview of public policy and well beyond the control of individual clinicians, practices, clinics, hospitals, or even communities. What individual clinicians can do is take the practical measures available to them and support, to whatever extent they can, the broader infrastructure changes that require action from public health officials, elected officials, the insurance industry, and the pharmaceutical industry. What practicing clinicians can do to reduce health disparities

What and how much one can do in one’s own practice to prevent new HIV infections will vary from clinician to clinician. For example, HCPs may work in a practice setting where it would be helpful to have staff who speak one or more languages other than English, but they cannot afford to hire such personnel. On the other hand, it does not require any special financial resources to make sure patients are asked about issues of sex, drugs, and those economic,


Once clinicians have identified patients at risk for HIV infection, they can discuss risk factors and recommend HIV testing. cultural, social, and psychosocial issues noted above that may impact HIV risk and access to HIV prevention services. The Institute of Medicine, the US government’s Healthy People 2020 strategy, and the Joint Commission on Accreditation of Healthcare Organizations are among many organizations that have recommended asking sexual orientation and gender identity (SOGI) questions in clinical settings and including such data in electronic health records (EHRs). However, many HCPs are unsure of how to phrase such potentially sensitive questions. A sample intake form utilized by Fenway Health that incorporates SOGI questions may be found here: patient-services/FenwayClient_Registration_v11.pdf. In addition, it is important, as clinicians, to combat stigma linked to societal and cultural factors associated with having HIV along with increasing cultural competence and patient health literacy. For example, if time permits, learning basic medical Spanish may help with improving clinician-patient relationships in the Hispanic/Latino community. Tools are available to help with assessing health literacy and to provide outreach to patients in various languages that can help in communicating with patients more effectively. Eliminating health disparities in access to HIV prevention services begins with talking about HIV with your patients, assessing a patient’s risk for HIV, talking about available prevention methods as appropriate, and prescribing or referring as appropriate. Specifically, clinicians can ask patients about use of alcohol, tobacco, and other substances in the recent past and whether use of such substances led to legal or financial trouble; if a friend or relative had expressed concern about their substance use;

Resources for HIV risk assessment • CDC HIV risk reduction tool • Assess your risk for HIV • Assess risk for sexually acquired HIV-1 through an objective conversation • HIV risk assessment and risk reduction

and if they had tried without success to control or curtail their substance use.12 In terms of sexual practices, clinicians can ask patients whether they have had sex within the past 12 months. If so, follow-up questions can include how many partners they had sex with and whether these partners were male, female, or both and what sexual behavior was engaged in (eg, anal intercourse, vaginal intercourse, fellatio, etc). In addition, clinicians can ask whether recent sexual encounters, whether with their main partner or with additional partners, had involved the influence of alcohol; use of drugs to get high before or during sex; or condom use. Lastly, the risk screening asked whether participants had been held in a detention center, jail, or prison for more than 24 hours during the past 12 months.12 Once clinicians have identified patients as being at risk for HIV infection, they can initiate a frank discussion about HIV risk factors and recommend HIV testing. For patients who test negative, there are effective prevention strategies that clinicians can recommend or prescribe, or to which clinicians can refer appropriate patients. According to the CDC, prevention options for adults at risk of HIV infection include condoms, prevention education and counseling programs, substance abuse treatment and access to sterile syringes, screening and treatment for sexually transmitted infections (STIs),13 and biomedical prevention methods reviewed in the following section. Biomedical prevention methods—Using ART to prevent HIV and reduce health disparities

In recent years, medications used to treat HIV have been evaluated in clinical studies for prevention of HIV infection and been proven safe and effective. Treatment as prevention (TasP) for people with HIV By reducing the viral load (VL) in HIV-positive patients to undetectable levels, antiretroviral therapy (ART) greatly reduces the risk of transmission from treated individuals to HIV-negative partners. This strategy is called treatmentas-prevention, or TasP. This strategy also encompasses the notion of reducing the VL of a community.13 Post-exposure prophylaxis (PEP) Prompt initiation of ART within 72 hours after exposure to HIV reduces the risk of infection. This strategy is called post-exposure prophylaxis (PEP). Originally developed to address accidental exposures among healthcare workers (primarily needlesticks), PEP is now offered to HIV-negative • THE CLINICAL ADVISOR • SEPTEMBER 2017 31



people on an emergency basis for non-occupational exposures occurring through unprotected sex or the sharing of needles or syringes during injection drug use.13 People at risk for HIV infection can take 1 pill containing 2 HIV medications (tenofovir and emtricitabine) once a day to lower their risk of acquiring HIV through sexual activity by more than 90% or from injection drug use by more than 70%. This strategy is called pre-exposure prophylaxis (PrEP).13 Each of these biomedical prevention methods will be discussed in the following sections. HIV treatment as prevention—A new paradigm for safer sex among high-risk populations

This section will review how HIV medical experts recognized—and ultimately proved with clinical data—that ART for HIV, in addition to treating HIV-positive individuals, also served as HIV prevention for the HIV-negative partners of HIV-positive people. However, the promise of TasP is limited as long as disparities in access to testing and treatment remain for groups at risk of HIV infection. ART became available in 1996 with the approval of the first protease inhibitors (PIs) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs), allowing for triple combination therapy, which at the time was referred to as highly active antiretroviral therapy (HAART). Over a decade ago, experts acknowledged that HIV incidence worldwide was likely to remain high for the foreseeable future. Current HIV prevention strategies were only partially effective, and prevention methods were greatly underutilized. Efforts to develop a preventive vaccine have not been successful. And ART—while effective at suppressing viral replication, restoring immune function, and reducing morbidity and mortality among treated patients—could not eradicate HIV infection.14 Consequently, researchers turned their attention to the possibility that ART might be effective not only as a treatment strategy, but also for prevention.14,15 A clinical trial called HIV Prevention Trials Network (HPTN) 052 was conducted in serodiscordant couples to evaluate the effect of ART on preventing HIV transmission to uninfected sexual partners.16 A 2011 interim analysis found that early initiation of ART was associated with a 96% reduction in transmission to uninfected sexual partners in the first 18 months of the study.17,18 In the final analysis, early initiation of ART was associated with a 93% reduction in transmission to uninfected sexual partners.17,18 However, HPTN 052 included only 37 male same-sex couples, and 96% of study participants reported condom use 100% of the time.16

To generate more data on TasP in serodiscordant male couples, the PARTNER (Partners of People on ART—A New Evaluation of the Risks)19 study enrolled 1166 HIVserodiscordant couples at 75 sites in 14 European countries. Of the participants, 108 HIV-negative MSM (33%) and 21 heterosexual participants (4%) reported sex without condoms for at least 2 years.19 Eleven of the HIV-negative partners became HIV-positive during the study—including 10 individuals from MSM couples. However, the researchers determined, through anonymized phylogenetic analysis, that none of the transmissions occurred within the couples, giving a rate of within-couple HIV transmission of zero.19 Currently under way is Opposites Attract, an observational cohort study of serodiscordant male couples in Australia, Bangkok, Thailand, and Rio de Janeiro, Brazil, designed to further elucidate the risk of HIV transmission when the HIV-positive partner is virologically suppressed on ART. A planned interim analysis in 2015 found no linked HIV transmissions in such couples, adding to the accumulating evidence that the rate of HIV transmission under these circumstances is extremely low.20 The accumulated evidence for the effectiveness of TasP has led to the development of test-and-treat strategies. Such s­ trategies seek to expand HIV testing among high-risk ­populations and to provide immediate linkage to care and treatment for those who test positive and prevention services for those who test negative. Beginning in 2010, the United States has endorsed a national strategy for HIV/AIDS that that emphasizes a testand-treat approach both to reduce morbidity and mortality among people with HIV and as an HIV prevention strategy.21 In order for test-and-treat strategies to be effective, however, people at risk for HIV infection must access HIV testing, and those who test positive must not only be linked to medical care and treatment but also remain adherent to ART.21 Unfortunately, the same social, economic, and psychosocial factors that are associated with high risk for HIV infection are also associated with decreased retention in care and decreased adherence to treatment for HIV-positive people.21 Thus, a vicious cycle persists in which the structural factors that increase HIV risk also decrease the likelihood of HIV testing, linkage to HIV care for those who test positive, and adherence to treatment for those who initiate ART, which in turn translates to a decreased TasP benefit for the community. A recent study by Hall and colleagues found that the proportion of people with a late HIV diagnosis (defined as a CD4 count of <200 cells/mL or an opportunistic illness within 3 months of HIV diagnosis) decreased in the United States from 2003 to 2012, both overall and in many high-prevalence


areas.22 Nevertheless, even in areas that have recently intensified HIV testing interventions, some 20% of people who tested HIV-positive had advanced disease at the time of diagnosis.22 The study also found disparities in some areas in the rates of late diagnosis by race, ethnicity, and transmission-risk group.22 Thus, while there is evidence that intensification of testing services has led to increases in earlier diagnosis, much work remains to be done if test-and-treat strategies are to be maximally effective. Post-exposure prophylaxis—Going beyond occupational exposures

The US Department of Health and Human Services (HHS) first published recommendations in 2005 for the use of PEP to prevent HIV infection after non-occupational exposures, including those associated with sexual activity or injection drug use.23 Revised guidelines were issued in 2016 to reflect more recent data on clinical experience with PEP, including the use of newer ART regimens.24 The CDC recommends PEP for HIV-negative people who have experienced possible exposure to HIV-infected blood or bodily fluids.25 The highest-risk exposures include needle sharing and receptive anal intercourse without a condom (or while not using PrEP).25 While insertive anal intercourse and vaginal intercourse pose lower risks, these types of exposure may nevertheless warrant PEP depending on the clinical setting.25 Oral sex, whether insertive or receptive, and human bites pose minimal risk of HIV transmission but may still warrant consideration of PEP in special circumstances.25 Current CDC guidelines recommend a 28-day course of a 3-drug ART regimen for PEP.24 The preferred regimen for otherwise-healthy adults and adolescents is tenofovir disoproxil fumarate (TDF) 300 mg with emtricitabine (FTC) 200 mg once daily, plus raltegravir (RAL) 400 mg twice daily or dolutegravir (DTG) 50 mg once daily. An alternative regimen is TDF 300 mg with FTC 200 mg once daily plus darunavir (DRV) 800 mg and ritonavir (RTV) 100 mg once daily.24 In order to be effective, PEP must be initiated as soon as possible after a high-risk exposure, ideally within 72 hours.24,26 It is important, if feasible, to determine the HIV status of the source of potential exposure so that PEP can be discontinued if the source proves to be HIV-negative.26 Even if the source partner is known to be HIV-positive and on ART, PEP is warranted if the level of ART adherence of the HIV-infected source is unknown.26 If HIV rapid tests or other third-generation antibody tests are used, the exposed person on PEP should be retested for HIV at 4 to 6 weeks, 3 months, and 6 months after exposure.26 If a fourth-generation HIV antigen-antibody

Resources for clinicians • Final Recommendation Statement: Human Immunodeficiency Virus (HIV) Infection: Screening U.S. Preventive Services Task Force. Document/RecommendationStatementFinal/humanimmunodeficiency-virus-hiv-infection-screening/ Published December 2016. • AMA Urges More Physician Education on Use of Once-ADay HIV Prevention Chicago, IL: American Medical Association; June 15, 2016 [press release]. • Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2014: A Clinical Practice Guideline US Public Health Service, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. • Updated Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016 Centers for Disease Control and Prevention, U.S. Department of Health and Human Services. • National Hispanic Medical Association (NHMA) • Morehouse School of Medicine–Center of Excellence on Health Disparities (CEHD) institutes/center-of-excellence-on-health-disparities/ • American Medical Association (AMA) • National AHEC (Area Health Education Center) Organization • HealthHIV • National Coalition for LGBT Health • National Medical Association • Urban Health Plan • Centers for Disease Control and Prevention: Act Against AIDS • THE CLINICAL ADVISOR • SEPTEMBER 2017 33



assay is used and the result is negative, no further testing is required after 3 to 4 months post-exposure.26

The other pivotal study, called Partners PrEP, included 4758 serodiscordant heterosexual couples in Kenya and Uganda. In this study, the HIV-negative partners received FTC/TDF, TDF alone, or placebo. Of the HIV-negative partners, a total of 82 became HIV-positive during the study. Compared with placebo, there was a 67% reduction in the incidence of infection among participants who received TDF alone, and a 75% reduction with FTC/TDF. These results were statistically significant (Figure 3).29 In May 2014, the US Public Health Service (USPHS) released a set of clinical practice guidelines for HIV prevention,30 recommending PrEP as one prevention option for sexually active adults who are at risk for HIV infection based on their sexual practices. These recommendations are based on results from iPrEX and Partners PrEP plus a number of others; the TDF2 Study and the Bangkok Tenofovir Study were among the most important of those considered.31 The TDF2 Study evaluated PrEP among 1219 heterosexual individuals in Botswana. The participants (48% women, 52% men) were randomly assigned to receive FTC/TDF or placebo, with monthly follow-up and additional prevention services

Pre-exposure prophylaxis—Giving greater control to high-risk individuals

In 2012, the US Food and Drug Administration (FDA) approved a once-daily fixed-dose combination of FTC and TDF for HIV PrEP. This approval was based on 2 large, randomized, double-blind, placebo-controlled trials.27-29 One of these, the iPrEX study, evaluated PrEP among 2499 HIV-negative MSM and transgender women who have sex with men. After a median follow-up of 1.2 years, 100 participants were found to have become infected with HIV, including 36 in the active prophylaxis group and 64 in the placebo group, amounting to a significant 44% reduction in the incidence of new HIV infections among the participants receiving PrEP.28 In addition to demonstrating the efficacy of PrEP, the study also showed the importance of PrEP adherence, as study participants in the active arm who became infected were found to have low plasma levels of FTC/TDF.28

FIGURE 3. Kaplan–Meier estimates of the primary end point in the modified intention-to-treat analysis, according to study treatment29

Cumulative Probability of HIV-1 Infection

1.0 0.9



0.8 0.03

0.7 0.6

0.02 TDF




















0.2 0.1 0.0

No. at Risk TDF TDF-FTC Placebo







15 18 21 24 Months Since Randomization

1572 1568 1568

1559 1557 1557

1547 1546 1544

1498 1493 1487

1350 1371 1347

1223 1248 1224

1062 1059 1061

FTC, emtricitabine; TDF, tenofovir disoproxil fumarate.


902 901 902

735 743 744





510 525 523

287 291 295

108 114 120

15 16 18

including testing and counseling. Compared with placebo, PrEP reduced the risk of HIV infection by 62%. Again, efficacy correlated strongly with adherence as measured by drug levels.32 The Bangkok Tenofovir Study included 2413 PWID in Thailand, a population that had not previously been studied as candidates for PrEP. Participants were assigned to receive either TDF or placebo along with testing and counseling and were offered condoms and methadone treatment. Compared with placebo, TDF reduced the risk of HIV infection by 49%.33 Once again, efficacy was correlated with adherence: among patients with detectable TDF in their blood, the reduction in risk of HIV infection was 74%.33 According to the USPHS guidelines, other HIV prevention options for adults at risk include condoms, prevention education and counseling programs, substance abuse treatment and access to sterile syringes, and screening and treatment for STIs.13 The guidelines note that the safety and efficacy of PrEP for adolescents has not been fully characterized, so clinicians should weigh the risks and benefits of PrEP in counseling minor patients.30 Barriers to PrEP implementation for people at high risk for HIV infection

Of all the chemoprophylactic strategies now available for HIV prevention—TasP, PEP, and PrEP—PrEP has proven to be the most controversial and challenging in terms of implementation and uptake.30 While PrEP has the potential to revolutionize HIV prevention and help bring an end to the epidemic, its uptake has been lowest among the populations at highest risk.26 To implement PrEP in those most likely to benefit from it, it is necessary to not only overcome the practical and structural barrier of availability and access, but also the misperceptions, misinformation, and other forms of reluctance that persist among potential users of PrEP and potential prescribers alike. Negative stereotypes—Leveling the playing field and reducing health disparities

Harboring negative stereotypes about PrEP and PrEP users is one barrier to PrEP access to high-risk groups.34 Golub and colleagues recently published a study that identified stereotypes about PrEP use among MSM in New York City who might be candidates for PrEP.34 The study also sought to examine the social, demographic, and behavioral correlates of the different types of PrEP use stereotypes identified.34 Among the 160 MSM who were surveyed, negative stereotypes about PrEP use were identified by 80% of the participants.34 Broadly speaking, 2 types of negative stereotypes were identified,

each by more than 40% of those sampled.34 One was the assumption that PrEP users are actually HIV-positive and are lying about their status.34 The other was that PrEP users are promiscuous and do not want to use condoms.34 Prior to the approval of PrEP, many potential users who were surveyed said they felt that taking PrEP might decrease their use of condoms over time.34-37 Some studies have shown an ongoing high incidence of STIs among PrEP users, suggesting ongoing high-risk behavior.38,39 Other trials, however, actually found decreases in risk behavior over time among patients taking PrEP, including increased use of condoms.28,29 However, risk compensation after PrEP implementation has been examined in several trials: to date, use of PrEP has not been associated with increased sexual risk behavior or with the acquisition of other STIs in most of these studies.28,29,32,40-43 In both the iPrex and Partners PrEP studies, decreasing risk behavior (eg, unprotected receptive anal sex) was observed over time.28,29 However, it is important to note that all randomized and open-label trials of PrEP provided and emphasized the use of condoms as well as HIV testing, so this model may not be fully implemented in actual clinical practice. Advocates have called for measures to combat negative stereotypes about PrEP in the United States through social marketing and educational campaigns targeting high-risk groups, but to date there has been little research to document the specific types of stereotypes that are having the greatest impact on PrEP implementation.34 Adherence to PrEP—Removing barriers to a powerful prevention tool

Adherence to PrEP is another important barrier to HIV prevention among high-risk groups, particularly among those at greatest risk, including young MSM in general and young black and Hispanic/Latino MSM. Given the statistics cited earlier, implementation of PrEP for HIV infection among young MSM in the United States is an urgent issue. But it is also controversial: For one thing, young men, and particularly young black and Latino men, were underrepresented in demonstration studies conducted prior to FDA approval of PrEP in 2012.44 Alongside the ample evidence that young people have difficulty adhering to HIV medication regimens, including both ART and PrEP, the lack of data on young people in these influential PrEP studies does nothing to assuage concerns about broadening the implementation of PrEP in young MSM.44 There are also concerns that young MSM will have more risky sex if they are on PrEP, even though, as stated previously, studies to date provide no evidence of this sort of behavioral disinhibition.44 • THE CLINICAL ADVISOR • SEPTEMBER 2017 35



Adherence to PrEP is another important barrier to HIV prevention among high-risk groups, particularly among those with the greatest risk. To explore these concerns, Hosek and colleagues conducted an open-label study of PrEP among 18- to 22-year-old MSM in 12 US cities.44 Enrolling the youngest and most diverse group of MSM of any PrEP study in the United States to date, this study assessed adherence and sexual behavior, gathered safety data, and evaluated the acceptability of PrEP in this population as well as patterns of PrEP use.44 While most participants had protective blood levels of PrEP for the first quarter of the study, adherence waned over time, suggesting the need for interventions to support adherence in this population. Moreover, adherence declined as the time between study visits increased from monthly to quarterly. This connection among frequency of follow-up, levels of adherence, and health outcomes has been seen in other pediatric and adolescent healthcare contexts and suggests that younger MSM may need more-frequent clinic visits to support adherence to PrEP.44 Of greatest concern was the finding that adherence in this study was poorer among black MSM than it was among other racial or ethnic groups. Additional studies are warranted to elucidate potential racial differences in the pharmacokinetics of dried blood spot testing (used to measure PrEP adherence in this study)44 as well as the barriers affecting access and adherence to PrEP among young black MSM.44 Koester and colleagues evaluated concepts of safety and risk among PrEP users via in-depth interviews with 61 male PrEP users who participated in the iPrEx open-label extension study. Overall, participants did not report significant changes in their sexual practices upon initiating PrEP. Instead, they reported feeling a sense of relief from HIV-related stress. This alleviation of fear did not necessarily lead to less condom use, however. Rather, participants said they felt a sense of security and less fear of HIV. The authors argue that living without the threat of HIV is a significant benefit that remains inadequately explored in HIV prevention research.45 Conclusion: Is it time for an HIV continuum of prevention to reduce health disparities and empower people at high risk of HIV infection?

Recent initiatives to end the HIV epidemic on national, regional, and global levels have relied on the concept of an HIV continuum of care or cascade of care. The continuum of care gives public health officials and healthcare policy experts the ability to measure success in maximizing the proportion of high-risk people who are identified as HIV-positive and linked

to care who then start ART, remain in care, remain adherent to treatment, and achieve and maintain viral suppression.46,47 The continuum of care is understood as a tool for designing and implementing effective TasP strategies. Thus, while the HIV care continuum as a tool is aimed at prevention as its ultimate outcome, it views prevention through the lens of treatment and encourages the design and implementation of interventions aimed at expanding treatment. As such, it is a very useful model; it allows us to break down the continuum of care for people with HIV and intervene at strategic points with effective tactics to reduce barriers and increase access. The continuum of care, however, is a unitary model; it moves from lack of awareness of HIV status to HIV testing and from that point concerns itself only with those who test positive, focusing on linkage to care, initiation of ART, adherence to treatment, and achievement of viral suppression. That’s not surprising when you think about the fact that the HIV continuum of care model was developed in response to clinical studies validating TasP and inspiring the notion of test-and-treat strategies as the ultimate prevention strategy. The seminal test-and-treat articles in the literature go back to the mid to late 2000s, and the foundational review article that established the notion of the HIV care continuum appeared in 2011.14,46,48,49 By contrast, as we noted above, the pivotal trials for PrEP were published in 2010 (iPrEX), 2012 (Partners PrEP and TDF2), and 2013 (Bangkok Tenofovir Study).28,29,32,33 Also significant are the IPERGAY and PROUD studies.50,51 Thus, when the HIV continuum of care model was proposed and embraced for guiding test-and-treat tactics as part of a TasP strategy, PrEP was barely on the horizon, let alone in the picture. In fact, one of the motivators of test-and-treat and TasP was the relatively limited efficacy and even the limited applicability of available prevention methods: many people at high risk for HIV infection used condoms inconsistently, sporadically, or not at all; and PEP, useful only as an emergency measure in any event, was often compromised by poor follow-up and completion rates. Only with the advent of PrEP do we have a prevention method that could rival TasP in terms of availability, access, implementation, and effectiveness. To take full advantage of the promise of PrEP, however, as well as to optimize implementation of other HIV prevention methods (including condoms and PEP), we need to have an HIV continuum of prevention, similar to the HIV continuum of care, that can guide our


Providers must continue to find new and ever more effective ways to address the HIV prevention needs of diverse populations. thinking about how high-risk people move from ignorance of their HIV status through testing and linkage to prevention services and, more importantly, can allow us to measure the success of interventions to increase access to HIV prevention. Nunn and colleagues have newly proposed precisely such an HIV continuum of prevention.52 In particular, they describe a PrEP continuum of care, but the concept could be readily expanded to include any HIV prevention method as the end point as well as combination HIV prevention. Their proposed PrEP continuum of care includes: (1) identifying people at high risk for HIV infection; (2) increasing HIVrisk awareness among people at risk; (3) increasing awareness about PrEP; (4) facilitating access to PrEP; (5) linking people at high risk to a care setting that can provide PrEP; (6) prescribing PrEP; (7) initiating PrEP; (8) adhering to PrEP; and (9) retaining PrEP users in PrEP care.52 In addition, they propose 4 categories of PrEP retention in care that include being: (1) indicated for PrEP and retained in PrEP care; (2) indicated for PrEP and not retained in PrEP care; (3) no longer indicated for PrEP; and (4) lost to follow-up after initiation of PrEP.52 According to the authors, this continuum of PrEP care provides a conceptual framework with which researchers and clinicians can measure PrEP awareness, uptake, adherence, and retention.52 One problem with the proposal from Nunn and colleagues is that it does not define what is meant by “no longer indicated for PrEP.” CDC guidelines for PrEP include indications for MSM, heterosexual men and women, and PWID. A high-risk person in each group can lose his/her indication(s) for PrEP for a number of reasons, including but not limited to becoming HIV-positive. What happens, in terms of a more comprehensive prevention and treatment algorithm, to a high-risk person in one or another risk category who no longer has an indication for PrEP? And again, as we noted earlier, Nunn and colleagues have offered a continuum for PrEP only, not for any other methods of HIV prevention or for combination HIV prevention. A more useful HIV continuum of prevention might include tracking high-risk people as they move from unaware of their HIV status to testing negative for HIV, linkage to HIV prevention services, initiation of HIV prevention services, retention in HIV prevention services and, ideally, repeated HIV testing and ongoing HIV-negative status. Ultimately, what might be most useful is a continuum of care based more on the model used by New York Knows.53

New York Knows is a program of the New York City Department of Health, the aim of which is to help New York City residents learn their HIV status and take advantage of local services for either prevention or treatment, depending on whether a person tests HIV-negative or HIV-positive. The program encourages New Yorkers to know their status by getting tested. People who test HIVpositive are linked to care in which they can receive ART, while people who test HIV-negative are linked to care in which they can receive HIV prevention services, including but not limited to PrEP.53 An HIV continuum based on this approach would include points of bifurcation: highrisk people would enter the continuum unaware of their HIV status. Based on HIV testing, they would initially enter either the treatment or prevention branch of the continuum. Presumably, if they enter the treatment branch of the continuum, they would remain there indefinitely or until we develop medical strategies to eradicate HIV infection (cure). If they enter the prevention branch of the continuum, they would stay there unless and until they become HIV-positive, at which point they would enter the treatment branch of the continuum. Such a model of HIV prevention and treatment continuum would allow public health officials and public policy experts to design, implement, and measure the effectiveness of HIV prevention strategies that encompass both prevention and treatment modalities, including condoms and harm-reduction strategies such as clean needles and syringes, and TasP, PEP, and PrEP. Such a model might also allow stakeholders to address the varied needs of different high-risk populations, including MSM overall, MSM of color, PWID, and transgender persons. Such a model might also allow us to address the wide range of barriers to prevention, both practical and structural, on a much more targeted level than is currently possible—targeted, that is, both on the level of the risk group being served and on the point or points of the treatment or prevention continuum being addressed. On local, national, and global levels, ambitious programs are in place to end the epidemic of HIV/AIDS in the current generation. If we are to meet these goals, we must continue finding new and ever more effective ways to address the HIV prevention needs of diverse populations and to eliminate health disparities affecting the most vulnerable key populations at risk for HIV infection. n • THE CLINICAL ADVISOR • SEPTEMBER 2017 37




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32. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral

46. Gardner EM, McLees MP, Steiner JF, et al. The spectrum of engage-

preexposure prophylaxis for heterosexual HIV transmission in Botswana.

ment in HIV care and its relevance to test-and-treat strategies for preven-

N Engl J Med. 2012;367(5):423-434.

tion of HIV infection. Clin Infect Dis. 2011;52(6):793-800.

33. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral

47. Medland NA, McMahon JH, Chow EP, et al. The HIV care cascade: a

prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand

systematic review of data sources, methodology and comparability. J Int

(the Bangkok Tenofovir Study): a randomised, double-blind, placebo-

AIDS Soc. 2015;18:20634. doi:10.7448/IAS.18.1.20634.

controlled phase 3 trial. Lancet. 2013;381(9883):2083-2090.

48. Dieffenbach CW, Fauci AS. Universal voluntary testing and treatment

34. Golub SA, Gamarel KE, Surace A. Demographic differences in

for prevention of HIV transmission. JAMA. 2009;301(22):2380-2382.

PrEP-related stereotypes: implications for implementation. AIDS Behav.

49. Granich RM, Gilks CF, Dye C, et al. Universal voluntary HIV testing


with immediate antiretroviral therapy as a strategy for elimination of HIV

35. Golub SA, Tomassilli JC, Pantalone DW, et al. Prevalence and corre-

transmission: a mathematical model. Lancet. 2009;373(9657):48-57.

lates of sexual behavior and risk management among HIV-positive adults

50. Sagaon-Teyssier L, Suzan-Monti M, Demoulin B, et al. Uptake of PrEP

over 50. Sex Transm Dis. 2010;37(10):615-620.

and condom and sexual risk behavior among MSM during the ANRS

36. Brooks JT, Buchacz K, Gebo KA, Mermin J. HIV infection and

IPERGAY trial. AIDS Care. 2016;28(suppl 1):48-55.

older Americans: the public health perspective. Am J Public Health.

51. Gafos M, Brodnicki E, Desai M, et al. Acceptability of an open-label


wait-listed trial design: experiences from the PROUD PrEP study. PLoS

37. Brooks RA, Landovitz RJ, Kaplan RL, et al. Sexual risk behaviors and

One. 2017;12(4):e0175596. doi:10.1371/journal.pone.0175596.

acceptability of HIV pre-exposure prophylaxis among HIV-negative gay

52. Nunn AS, Brinkley-Rubinstein L, Oldenburg CE, et al. Defining

and bisexual men in serodiscordant relationships: a mixed methods study.

the HIV pre-exposure prophylaxis care continuum. AIDS. 2017;31(5):

AIDS Patient Care STDS. 2012;26(2):87-94.


38. Volk JE, Marcus JL, Phengrasamy T, et al. No new HIV infections with

53. NYC Health. Infectious Diseases: HIV testing initiatives: New York

increasing use of HIV preexposure prophylaxis in a clinical practice setting.


Clin Infect Dis. 2015;61(10):1601-1603. Accessed June 15, 2017. • THE CLINICAL ADVISOR • SEPTEMBER 2017 39


POST-TEST Expiration date: June 25, 2018

Credit Designation: The Morehouse School of Medicine designates this enduring activity for a maximum of up to 1.00 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity is awarded 1.00 contact hours. A statement of credit will be issued only upon receipt of a completed pre-assessment test, activity evaluation form, and post-test with a score of 70% or higher. All components must be completed and submitted online at CREDITS: 1.00 | HIV prevention in diverse populations

1. The annual rate of new HIV infections in the United States is approximately . a. 40,000 per year b. 100,000 per year c. 25,000 per year d. 75,000 per year 2. Effective antiretroviral therapy (ART), also known as triple-combination therapy or highly active antiretroviral therapy (HAART), became available in . a. 1976 c. 1996 b. 1986 d. 2006 3. US Department of Health & Human Services (HHS) recommendations for use of non-occupational postexposure prophylaxis (PEP) address possible HIV exposures associated with . a. Sexual activity b. Deep kissing c. Percutaneous injuries from needles discarded in public settings d. A and C

6. The group that bears the heaviest burden of HIV infection in the United States today is . a. Men who have sex with men (MSM) regardless of race or ethnicity b. White MSM c. People who inject drugs (PWID) regardless of race or ethnicity d. Heterosexual women 7. A 2016 study found that the proportion of people testing HIV-positive who had advanced disease at the time of their diagnosis was . a. 5% c. 15% b. 10% d. 20% 8. Current Centers for Disease Control and Prevention (CDC) guidelines for non-occupational PEP recommend a 3-drug ART regimen for . a. 7 days c. 21 days b. 14 days d. 28 days

4. The US Food and Drug Administration (FDA) approved a once-daily, fixed-dose combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) for HIV pre-exposure prophylaxis (PrEP) in . a. 1982 c. 2002 b. 1992 d. 2012

9. The study of PrEP implementation among young MSM by Hosek and colleagues (2017) found that compared with other racial or ethnic groups, adherence to PrEP dropped off fastest among . a. White MSM b. Black MSM c. Latino MSM d. Asian MSM

5. The HIV continuum-of-care model was designed to help develop, implement, and measure the effectiveness of . a. PEP strategies b. PrEP strategies c. Test-and-treat strategies d. Condom distribution programs

10. The “New York Knows” program encourages people at high risk for HIV to . a. Get tested only if they think they might be HIV-positive b. Get on ART regardless of their HIV status c. Access HIV prevention if they test HIV-negative d. Get on PrEP if they test HIV-positive

TO TAKE THE POST-TEST please go to:


Dermatology Clinic CASE #1

An itchy rash on the abdomen ESTHER STERN, NP

A 72-year-old man presents to the clinic with an intensely itchy rash on his abdomen and chest that appeared 2 months prior. He denies starting any new medications prior to the onset of the eruption and any systemic symptoms. Although he traveled and stayed in hotels recently, he reports that his wife does not exhibit any similar symptoms. Physical examination reveals numerous discrete papules, crusted papules, and papulovesicles on the chest, abdomen, and mid-back. His upper and lower extremities, face, and groin are unaffected. What is your diagnosis? Turn to page 42


A dark lesion on the finger SYDNEY DUNN, BS, CHRISTOPHER RIZK, MD

The patient is a 13-year-old adolescent girl who presents with a 1-month history of a dark lesion on her finger. She states that the lesion does not bother her, but she came to the clinician because her mother was very concerned about the enlarging area of hyperpigmentation. The patient has no past medical history, no relevant family or social history, and is otherwise in good health. On examination, the rash appears to be a 1 x 1 cm circular patch of hyperpigmentation with overlying scale on the middle finger. During the past month, the rash has grown in size but remains asymptomatic. What is your diagnosis? Turn to page 43 • THE CLINICAL ADVISOR • SEPTEMBER 2017 41

Dermatology Clinic CASE #1

Grover disease

Grover disease (GD), also known as transient acantholytic dermatosis, is a common yet challenging condition that occurs predominantly in middle- to older-aged men. Dr Ralph W. Grover first characterized it in the 1970s. Both the names Grover disease and transient acantholytic dermatosis are misnomers, as this condition not a worrisome disease, nor is it typically very transient. GD occurs commonly in middle-aged patients, with an average age of onset at 64 years.1 It affects men almost twice as often as women. In addition, one study found that this condition is biopsied and diagnosed more frequently in the winter.1 GD may last a few months and then resolve spontaneously or it may persist for many years, with the rash waxing and waning. The origin and pathogenesis of GD is unknown. It is nonfamilial and not immune mediated. Several factors appear to be related to disease onset and flare. These include ultraviolet and ionizing radiation, sweating, heat, and xerosis.2 Interestingly, GD often appears or flares during periods of prolonged bedrest and hospitalization.3 GD also appears to be associated with eczema and allergic contact dermatitis.2 GD presents with discrete, usually monomorphic papules, papulovesicles, crusts, and keratotic erosions, ranging in size from 1 to 3 mm. Lesions may resolve with postinflammatory hyper- or hypopigmentation. Common areas of involvement include the abdomen, chest, and back. The face, groin, palms, and soles are typically spared. Pruritus is usually present, and often the extreme intensity of the itch may seem incompatible with the rash severity. The differential diagnoses of GD are vast; therefore, conclusive diagnosis of GD is challenging for many clinicians. Similar-appearing conditions to consider include drug eruptions, scabies, folliculitis, miliaria, insect bites, and vesicular disorders such as bullous pemphigoid and pemphigus vulgaris. Histopathlogically, GD is an acantholytic process with disruption of the intercellular connections between epidermal keratinocytes. Dyskeratosis may or may not be present. In addition, hyperkeratosis and parakeratosis may be seen. In the setting of a background of eczematous skin, a spongiotic pattern of inflammation will be present. The histopathologic differential diagnoses include Darier disease, Hailey- Hailey disease, pemphigus foliaceus, and pemphigus vulgaris.

Therefore, clinical correlation is required to reach the correct diagnosis. In questionable cases, direct immunofluorescence testing is helpful to rule out autoimmune vesicular disorders. Treatment typically includes use of topical cortisone creams to decrease inflammation and itching. Triamcinolone 0.1% cream can be applied twice daily as needed to the trunk. Corticosteroid use is limited to short-term application given the risk of side effects with long-term use. Emollient use should be encouraged to optimize skin integrity. Over-the-counter creams containing menthol or pramoxine often provide temporary, soothing relief. Oral antihistamines may aid in pruritus relief. Nonsedating antihistamines may be used during the day, whereas nonsedating antihistamines, such as hydroxyzine and diphenhydramine, should be reserved for nighttime use.

Treatment for Grover disease typically includes use of topical cortisone creams to decrease inflammation and itching. In addition, behavior modifications may improve the condition; patients should avoid situations that lead to overheating and sweating, such as intense exercise and sunbathing. Wearing cool, loose clothing is beneficial. For stubborn cases, other reported treatment options include the tumor necrosis factor antagonist etanercept,4 oral isotretinoin,5 and psoralen and ultraviolet A radiation photochemotherapy.6 For the patient above, a punch biopsy sample sent for histopathologic examination confirmed the diagnosis of GD. The patient was prescribed triamcinolone 0.1% cream to be used up to a maximum of three times daily as needed for itching. In addition, he was advised to wear loose clothing and avoid situations in which overheating may occur. Three months later, the patient reported the condition was still present but was no longer very bothersome. Esther Stern, NP, is a family nurse practitioner at Advanced Dermatology & Skin Surgery, P.C., in Lakewood, N.J. References 1. Scheinfeld N, Mones J. Seasonal variation of transient acantholytic dyskeratosis (Grover’s disease). J Am Acad Dermatol. 2006;55:263-268. 2. Parsons JM. Transient acantholytic dermatosis (Grover’s disease): a global perspective. J Am Acad Dermatol. 1996;35(5 Pt 1):653-666.


3. James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Saunders-Elsevier; 2011. 4. Norman R. Use of etanercept in treating pruritus and preventing new lesions in Grover’s disease: a case report. J Am Acad Dermatol. 2007;56(suppl 2):AB53. 5. Helfman RJ. Grover’s disease treated with isotretinoin. Report of four cases. J Am Acad Dermatol. 1985;12:981-984. 6. Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I. Treatment of Skin Disease. Comprehensive Therapeutic Strategies. 3rd ed. Philadelphia, PA; Elsevier Saunders: 2010.


Tinea nigra

Tinea nigra is a rare superficial mycosis most commonly caused by the organism Hortaea werneckii.1-8 Less commonly, tinea nigra is caused by the amorphic fungus Stenella araguata.3 Tinea nigra is characterized by a single, asymptomatic, dark, macule located on the palms or soles of the feet.1,4,8 H werneckii (formerly Phaeoannellomyces werneckii) is a black yeast-like fungus that is typically found in humid environments.4,6 This organism is considered an environmental pathogen and is not part of the normal human flora. It is transmitted via direct contact with infested substances, such as soil or sewage.1,2 The fungus is lipophilic and extremely halotolerant in character, which encourages adhesion to human skin, especially in areas such as the palms or soles.2,6 There is no documented human to human transmission of H werneckii.1,4 Because the causative organism thrives in hot, humid environments, tinea nigra is typically seen in tropical climates such as the southeastern United States (especially along the Gulf Coast). Central America, South America, Asia, and Africa are also common locations for infection, due to their tropical or subtropical climates.1-4,7,8 These infections can also be present in more temperate climates, as people travel from endemic regions.2,7 Tinea nigra can infect people of any age, race, or sex. However, it is most common in children and young adults.1,2,4 The most common predisposing factors for infection with H werneckii are hyperhidrosis of the palms or soles, frequent exposure to soil or sewage, and exposure to a high-salinity environment. Because of these factors, farmers frequently contract tinea nigra.2,4

Tinea nigra typically presents as a single, darkly pigmented, well-demarcated macule located on the palm.1,4,8 Because H werneckii yeast cells are highly halotolerant and hydrophobic in nature, they tend to colonize the palms of the hand more often than other locations. Less common sites of infection include the palmar side of the fingers, soles of the feet, and the trunk.2,4 These macules are often brown to black in coloration and sometimes present with hyperpigmentation of the advancing border.1,4 Some patients report a decrease in pigmentation throughout the day, which can be attributed to clearance of the causative agent due to routine activities.2 Tinea nigra lesions vary in texture, ranging from a mild scale to a velvet-like texture. These lesions are usually not associated with any other symptoms (eg, pruritus, erythema) and thus are often not immediately brought to a physician’s attention.1,2,4 Tinea nigra is classically diagnosed based on clinical findings and then confirmed with potassium hydroxide (KOH) examination and/or culture.1,2 Patients may have a history of travel to an area of tropical climate7 or contact with commonly infested materials.2 KOH examination of skin scrapings reveals brown- or gold-pigmented septate hyphae.1,2,4 Occasionally, hyperchromic blastoconidia can be seen under KOH examination.4 After a 10- to 15-day incubation period, cultures of H werneckii grow in a yeast-like manner with glossy black colonies. After 2 weeks of growth, H werneckii cultures take on a mold-like appearance and morph into a filamentous, melanized growth.1,2,4 Biopsies

Tinea nigra is classically diagnosed based on clinical findings and then confirmed with KOH examination and/or culture. are not often performed because clinical impressions and KOH preparations are usually diagnostic.4 The histopathology of tinea nigra shows darkly pigmented hyphae confined to the stratum corneum with minimal to no associated inflammatory processes.1 Polymerase chain reaction testing is available for H werneckii but is rarely utilized in the clinical setting.2,8 Tinea nigra is most commonly mistaken for other melanocytic lesions, such as acral nevi, acral melanoma, junctional nevi, and lentigines.4 Because H werneckii is limited to the stratum corneum, the areas of hyperpigmentation are easily scraped off, as compared with other pigmented lesions.8 Skin scrapings of tinea nigra reveal positive findings under KOH examination, whereas other melanocytic lesions do not. This test performed by scraping the active border of • THE CLINICAL ADVISOR • SEPTEMBER 2017 43

Dermatology Clinic brown-pigmented septate hyphae, confirming the diagnosis. The patient was treated with topical terbinafine for 3 weeks, which led to the resolution of the lesion. n Sydney Dunn, BS, is a medical student, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston. References 1. Bolognia JL, Jorizzo JL, Schaffer J. Dermatology. 3rd ed. London: Saunders; 2012. 2. Bonifaz A, Badali H, de Hoog GS, et al. Tinea nigra by Hortaea Werneckii, a report of 22 cases from Mexico. Stud Mycol. 2008;61:77-82. 3. Perez C, Colella MT, Olaizola C, Hartung de Capriles C, Magaldi S, Mata-Essayag S. Tinea nigra: report of twelve cases in Venezuela. Mycopathologia. 2005;160:235-238. 4. Bonifaz A. Tinea nigra. In Arenas R, Estrada R, eds. Handbook of Tropical Dermatology. Austin, TX: Landes Bioscience; 2001:24-26. 5. Piliouras P, Allison S, Rosendahl C, Buettner PG, Weedon D. Dermoscopy improves diagnosis of tinea nigra: a study of 50 cases. Australas J Dermatol. 2011;52:191-194. 6. Zalar P, de Hoog GS, Gunde-Cimerman N. Ecology of halotolerant dothideaceous yeasts. Stud Mycol. 1999;43:38-48. 7. Rezusta A, Gilaberte Y, Betran A, et al. Tinea nigra: a rare imported infection. J Eur Acad Dermatol Venereol. 2010;24:89-91. 8. James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, PA: Saunders-Elsevier; 2011. 9. Burke WA. Tinea nigra: treatment with topical ketoconazole. Cutis. 1993;52:209-211. 10. Marks JG Jr, King RD, Davis BM. Treatment of tinea nigra palmaris with miconazole. Arch Dermatol. 1980;116:321-322. 11. Shannon PL, Ramos-Caro FA, Cosgrove BF, Flowers FP. Treatment of tinea nigra with terbinafine. Cutis. 1999;64:199-201.


Left: © Harley Schwadron, 2017. Right: © The New Yorker Collection 2017 from All Rights Reserved.

the lesion, then treating the scrapings with 10% KOH and observing them under a light microscope. Under dermoscopy, tinea nigra presents as patches of pigment that are not restricted to the dermatoglyphs of the palms or soles. This contrasts with the dermoscopic examination of acral nevi or acral melanomas, in which the pigmentation is either constrained to the ridges, as in acral nevi, or constrained to the furrows, as in acral melanoma. Both acral nevi and acral melanoma follow a characteristic parallel-like pattern that is not seen in tinea nigra.5 Other possible causes of lesions that are similar to tinea nigra include skin staining with chemicals or dyes, postinflammatory hyperpigmentation, Addison disease, secondary syphilis, and fixed drug eruption.4 All are easily excluded based on the patient’s history, physical findings, or KOH examination or culture results. Patients with tinea nigra are often cured with topical keratolytic agents, such as Whitfield ointment (6% benzoic acid, 3% salicyclic acid), as the superficial layer containing the causative agent is subsequently sloughed off.1,2 Similarly, simple scraping of the skin is often curative. Topical imidazoles and allylamines have also proven to be an effective means of treating tinea nigra.1,2,8 Specific drugs that have been proven effective include ketoconazole, miconazole, and terbinafine.9-11 Both topical keratolytic agents and topical antifungal medications are applied once or twice daily, usually for a duration of approximately 2 weeks, or until the lesion has resolved. Oral antifungal treatment is not recommended, as topical agents are sufficiently effective.1,2 Once treated, most cases of tinea nigra do not recur.2 Those with recurring infections are most likely due to re-exposure rather than recurrence of the initial infection.1 In this clinical case, a KOH scraping was performed in the office, results of which showed the presence of

Dermatologic Look-Alikes A fever and a pruritic rash WARREN CHAN, BS, MS, CONNIE WANG, MD, CHRISTOPHER RIZK, MD



A 38-year-old man presents with a fever and a pruritic pustular rash on his torso. On examination, the patient has widespread erythematous patches that are studded with nonfollicular, sterile, pinhead-sized pustules that coalesce into lakes of pus over the torso. The rash has been developing over the past 72 hours. The patient has had several similar rashes in the past. Aside from the rash, the patient does not have any other medical problems. In addition, the patient does not have any relevant social or family history.

A 44-year-old woman presents with a fever and a pruritic pustular rash on the torso. On examination, the patient has widespread erythematous patches studded with nonfollicular, sterile, pinhead-sized pustules that coalesce into lakes of pus over the torso. The patient has never had a similar rash in the past. She started having a sore throat 5 days prior. Three days prior, she decided to self-medicate by taking some of her daughter’s leftover erythromycin. The rash rapidly developed over the past 36 hours. The patient does not have any relevant social or family history. • THE CLINICAL ADVISOR • SEPTEMBER 2017 45

Dermatologic Look-Alikes CASE #1

Pustular psoriasis

Pustular psoriasis is a subtype of psoriasis that is traditionally classified into generalized and localized forms. The two major clinical variants of generalized pustular psoriasis (GPP) are von Zumbusch psoriasis (acute GPP) and annular pustular psoriasis (subacute GPP). Acute GPP presents with widespread pustulation, erythema, and systemic symptoms, whereas annular pustular psoriasis exhibits annular or figurate erythematous plaques with peripheral pustules.1,2 Acute GPP occurring in pregnancy is known as impetigo herpetiformis.3,4 The major localized forms of pustular psoriasis include palmoplantar pustulosis, a chronic pustular condition confined to the palms and soles, and acrodermatitis continua of Hallopeau (ACH), a pustular eruption of the digits.1,2 The exact prevalence of pustular psoriasis is not known, and there does not appear to be a strong predilection for sex or race.5,6 Incidence is higher in middle-aged adults, most commonly in those between the ages of 40 and 60 years.5 Annular pustular psoriasis is the most common form of pustular psoriasis in children.1,4 The pathophysiology is not well described, but the clinical features are thought to be attributed to enhanced polymorphonuclear leukocyte chemotaxis.7 Mutations in IL36RN, the gene encoding the interleukin-36 receptor antagonist, lead to unregulated proinflammatory pathways that are believed to be the cause of the neutrophil activation and migration associated with pustular psoriasis.8,9 Predisposing factors of GPP include the withdrawal of systemic steroids, cyclosporine, potent topical corticosteroids, and ustekinumab, as well as upper respiratory tract infections and hormonal changes during pregnancy.1,2 In localized GPP, infection or trauma of a digit has been shown to precede ACH, and smoking is associated with the palmoplantar form of pustular psoriasis.10,11 Additional reported risk factors include sunlight exposure, hypocalcemia, terbinafine, acetazolamide, and salicylates.2 Acute GPP is the most severe form of the disease and is characterized by painful, widespread, patchy erythema studded with pustules.1 Onset is abrupt and recurrent, and pustules frequently converge to form larger areas of pustular accumulations, known as lakes of pus, that resolve after several days, leaving scaling and erythema.1,2 Pruritus, intense

burning, and mucous membrane lesions resulting in cheilitis and geographic tongue are common.1,2 Manifestations of systemic illness, including fever, arthralgia, hypocalcemia, jaundice, erythroderma, cachexia, pneumonia, hepatitis, and congestive heart failure, often accompany these symptoms.1,2,5 Acute GPP can be fatal if left untreated.2,5 Annular pustular psoriasis (subacute GPP) presents as annular erythematous plaques expanding centrifugally for a period of hours to days, with peripheral pustular formation and central healing.1,4 As with acute GPP, residual scale remains after pustular resolution. Localized forms of pustular psoriasis are rare.12 ACH presents with pustules studding erythematous plaques that are usually limited to the distal areas of one or two digits, often of the fingers but sometimes the toes.2,11 It is a chronic inflammatory disease that often involves pustular formation inside the nail bed, leading to shedding of nail plates, onychodystrophy, and anonychia.1,11 Transition to GPP can occur, but is uncommon.1 Palmoplantar pustulosis is characterized by clusters of sterile pustules mixed with yellow-brown macules and scaly erythematous plaques localized to the palms and soles. Pruritus, burning pain, and inflammatory bone lesions are often associated.1 Histologically, pustular psoriasis resembles psoriasis vulgaris, exhibiting parakeratosis, elongated rete ridges, neutrophil migration into the epidermis, and mononuclear perivascular infiltrate in the upper dermis.12,13 Spongiform pustules of Kogoj, formed by the aggregation of neutrophils between keratinocytes, are a characteristic histologic feature.13,14 The diagnosis of pustular psoriasis is made using the history, physical examination, histopathology, and laboratory test results. A history of psoriasis, withdrawal or introduction of drugs (especially systemic steroids), and systemic symptoms such as fever and cachexia, suggest acute GPP.1,6 In patients suspected of having GPP, a skin biopsy is usually obtained due to its ability to distinguish between GPP and other pustular eruptions. Serologic test results revealing leukocytosis, lymphopenia, elevated erythrocyte sedimentation rate, hypocalcemia, decreased albumin, and elevated liver enzymes further aid in the diagnosis of acute GPP.1,5 The differential diagnosis of pustular psoriasis includes acute generalized exanthematous pustulosis (AGEP), immunoglobulin A (IgA) pemphigus, secondarily infected dermatitis, and tinea corporis. AGEP presents with fever and multiple nonfollicular pustules on an erythematous background. It can be very difficult to distinguish from acute GPP, particularly in AGEP patients who also have the IL36RN mutation.14 Rapid resolution within 2 weeks of drug discontinuation, no personal or family history of


psoriasis, and the presence of eosinophils and necrotic keratinocytes favors a diagnosis of AGEP. Acanthosis, papillomatosis, and spongiform pustules of Kogoj point to acute GPP.14,15 The annular pustular eruptions of IgA pemphigus, a rare autoimmune disorder, may be confused with the annular form of pustular psoriasis. However, IgA pemphigus primarily affects middle-aged or elderly adults, whereas annular pustular psoriasis is most common in childhood.4,13 Additionally, IgA deposits in the epidermis revealed by direct immunofluorescence differentiate this disorder from annular pustular psoriasis.13 Clinical presentation of tinea corporis resembles that of annular pustular psoriasis, consisting of annular, erythematous, scaling lesions and central clearing.16,17 A positive potassium hydroxide examination result indicates the former. Treatment of pustular psoriasis is aimed at minimizing skin manifestations, controlling systemic illness, and alleviating symptoms. In cases of relatively stable GPP, acitretin is the treatment of choice, with methotrexate as an alternative.2,18 Cyclosporine and infliximab are used for patients with severe acute GPP.18 In patients who are not responding to these first-line therapies, biologic agents such as etanercept and adalimumab can be used.18 Potent topical corticosteroids such as clobetasol and halobetasol are first-line treatments for ACH and palmoplantar pustulosis.19,20 Moisturizers, oatmeal baths, and wet wraps may provide symptomatic relief. The patient in this vignette was diagnosed with acute GPP and admitted to the hospital for severe acute GPP with systemic symptoms. The patient was then started on cyclosporine for stabilization. The patient was slowly weaned off cyclosporine and started on acitretin for maintenance therapy.


Acute generalized exanthematous pustulosis Acute generalized exanthematous pustulosis (AGEP) is a rare, adverse cutaneous reaction, most often caused by drugs or infection.15 The prevalence of AGEP is 1 to 5 cases per million per year.2,21 It can occur at any age, although most patients are adults. Men and women

are equally affected.15 Drugs are the causative factor in 90% of AGEP cases22,23; the most frequent triggers are antibacterial agents,

particularly aminopenicillins and macrolides, antimalarials, antimycotics, calcium channel blockers, carbamazepine, and paracetamol.2,15,24 Viral causes are more common in children with AGEP, and spider bites have also been implicated.23 Research into the pathophysiologic mechanism of AGEP suggests a pattern of immune dysregulation caused by drugspecific T cells resulting in neutrophil activation, migration, and accumulation in the epidermis.25,26 Additionally, IL36RN mutations, found in acute GPP, have also been discovered in a few cases of AGEP, suggesting that the two may share a common genetic basis.13,27 The histologic picture of AGEP shows a subcorneal or superficial intraepidermal pustule, usually with edema of the papillary dermis, necrotic keratinocytes, eosinophils in the pustules or dermis, and perivascular infiltrates with neutrophils.15,26

AGEP usually begins with an abrupt, pruritic or burning edematous erythema in the intertriginous areas or the face. AGEP usually begins with an abrupt, pruritic or burning edematous erythema occurring in the intertriginous areas or the face.2,15 Multiple pinhead sized, nonfollicular sterile pustules (each less than 5 mm in diameter) then appear on top of the erythema, most often in the skin folds.15,28 The pustular eruption occurs within a few days (usually <5) and rapidly becomes widespread, extending to the trunk and limbs.2,23 Confluence of the pustules may occur, as can other skin findings including facial edema, nonspecific purpuric lesions, a positive Nikolsky sign, and blisters.2 Mucous membrane involvement, if any, is usually limited to the lips.2,15 Patients with AGEP often present with fever, leukocytosis with a neutrophil count >7 × 109/L, and mild eosinophilia.15 Skin symptoms usually resolve spontaneously within 4 to 10 days, leaving a characteristic postpustular pinpoint desquamation.15,23 The diagnosis of AGEP can be made based on the morphologic picture, histopathology, and clinical course.2,15,21 Gram staining and culture is helpful to rule out bacterial infection, and patch testing with the suspected agent is useful for identifying the cause of the condition.2 The differential diagnosis of AGEP includes acute GPP (von Zumbusch), bullous impetigo, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson • THE CLINICAL ADVISOR • SEPTEMBER 2017 47

Dermatologic Look-Alikes syndrome/toxic epidermal necrolysis, and subcorneal pustular dermatosis (Sneddon-Wilkinson disease). Acute GPP is characterized by recurrent, abrupt onset of pustules, erythema, and systemic symptoms and can be very difficult to distinguish from AGEP.14,15 Histologically, acanthosis, papillomatosis, and spongiform pustules of Kogoj suggest acute GPP, whereas necrotic keratinocytes, dermal edema, and eosinophilia indicate AGEP.2,14,15 Other clues that favor the diagnosis of acute GPP include a history of psoriasis, absence of drug exposure, longer duration of fever and pustular eruption, and psoriatic arthritis.15 Sometimes patients with DRESS can present with pustules, producing lesions that look similar to those of AGEP.

However, DRESS often has a less pronounced pustular component, multiple systemic symptoms including fever, lymphadenopathy, hepatitis, and nephritis, and is characterized by a longer drug latency period—over 2 weeks.15,29 Subcorneal pustular dermatosis presents with pustules in the trunk and intertriginous areas that are usually larger than those in AGEP, and are flaccid. Onset is less acute, and the eruptions are chronic and relapsing.15,30 Treatment for AGEP involves discontinuation of the offending drug and symptomatic treatment. Moist dressings, topical corticosteroids, and antihistamines can be used to relieve pruritus, and the application of emollients is helpful during the desquamation phase.2 Because AGEP

TABLE 1. Pustular psoriasis versus acute generalized exanthematous pustulosis Pustular psoriasis (acute generalized pustular psoriasis)

Acute generalized exanthematous pustulosis

Dermatologic presentation

• Widespread erythematous patches studded with nonfollicular, sterile, pinhead-sized pustules that frequently coalesce into lakes of pus • Acute onset with recurrent episodes of pustulation • Pustules resolve after several days leaving scaling and erythema

• Diffuse, edematous erythema studded with nonfollicular, sterile pinhead-sized pustules • Shorter duration of pustules with postpustular desquamation • Acute onset with spontaneous resolution of skin symptoms within 4-10 d


• Often has a personal or family history of psoriasis • Often pruritic or burning • Accompanied by fever, chills, malaise, and systemic illness • Arthritis in ~30% of cases • May be accompanied by jaundice, erythroderma, lower extremity edema, pneumonia, and ocular complications

• Occurs within days of administration of an offending drug, with rapid resolution within 2 wk after its discontinuation • May be pruritic or burning • Fever is usually present, although shorter in duration • May be accompanied by facial edema, nonspecific purpural lesions, a positive Nikolsky sign, and blisters


Mostly idiopathic; administration or withdrawal of systemic glucocorticoids, potent topical corticosteroids, cyclosporine, or ustekinumab; upper respiratory tract infections; hypocalcemia; hormonal changes during pregnancy; and mutations in IL36RN are thought to play a role

90% of cases caused by drugs: antibacterials (aminopenicillins and macrolides), antimalarials, antimycotics, calcium channel blockers, carbamazepine, and paracetamol; can also be caused by viral, bacterial, and parasitic infections, as well as spider bites

Characteristic location


Predominance in skin folds, flexural areas, and the face


• Subcorneal or intraepidermal pustule • Acanthosis and papillomatosis • Spongiform pustules of Kogoj

• Subcorneal or intraepidermal pustule • Necrotic keratinocytes • Eosinophils in the pustules or dermis • Absence of tortuous vessels


History, physical examination, histopathology, laboratory tests

• History, physical examination, histopathology, clinical course • Patch testing for identifying the causative agent


• Minimize skin manifestations, control systemic illness, and alleviate symptoms • Treatment of choice: acitretin or methotrexate • Severe cases: cyclosporine or infliximab • Second-line therapies: etanercept, adalimumab, psoralen and ultraviolet A radiation • Moisturizers, oatmeal baths, and wet wraps for symptomatic relief

• Discontinue offending drug immediately • Treat symptomatically • Moist dressings, topical corticosteroids, and antihistamines for pruritus relief • Emollients for postpustular scaling


is a self-limiting condition with an excellent prognosis, use of systemic corticosteroids is discouraged.15,21 The patient in this vignette was diagnosed with AGEP; the likely causative agent was erythromycin. Due to the severity of systemic symptoms, the patient was admitted to the hospital for observation and symptomatic treatment. The patient’s rash and symptoms significantly improved within a week. The patient was advised to avoid self-medicating and macrolide antibiotics in the future. n

13. Gurgen J, Dorton D. Unusual case of pemphigus vulgaris mimicking localized pustular psoriasis of the hands and feet. Cutis. 2010;86:138-140. 14. Kardaun SH, Kuiper H, Fidler V, Jonkman MF. The histopathological spectrum of acute generalized exanthematous pustulosis (AGEP) and its differentiation from generalized pustular psoriasis. J Cutan Pathol. 2010;37:1220-1229. 15. Sidoroff A, Halevy S, Bavinck JN, Valliant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP)--a clinical reaction pattern. J Cutan Pathol. 2001;28:113-119. 16. Cheng S, Edmonds E, Ben-Gashir M, Yu RC. Subcorneal pustular der-

Warren Chan, BS, MS, is a medical student, Connie Wang, MD, is a dermatology resident, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

matosis: 50 years on. Clin Exp Dermatol. 2008;33:229-233. 17. Kawakami Y, Oyama N, Sakai E, Nishiyama K, Suzutani T, Yamamoto T. Childhood tinea incognito caused by Trichophyton mentagrophytes var. interdigitale mimicking pustular psoriasis. Pediatr Dermatol.



1. Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. 2nd ed. Philadelphia, PA:

18. Robinson A, Van Voorhees AS, Hsu S, et al. Treatment of pustular

Mosby Elsevier; 2008.

psoriasis: from the Medical Board of the National Psoriasis Foundation.

2. Arnold HL, Odom RB, James WD, Andrews GC, eds. Andrews’

J Am Acad Dermatol. 2012;67:279-288.

Diseases of the Skin: Clinical Dermatology. 8th ed. Philadelphia, PA: WB

19. Sehgal VN, Verma P, Sharma S, et al. Acrodermatitis continua of

Saunders; 1990.

Hallopeau: evolution of treatment options. Int J Dermatol. 2011;50:1195-1211.

3. Oumeish OY, Parish JL. Impetigo herpetiformis. Clin Dermatol.

20. Adis¸en E, Tekin O, Gülekon A, Gürer MA. A retrospective analysis of


treatment responses of palmoplantar psoriasis in 114 patients. J Eur Acad

4. Liao PB, Rubinson R, Howard R, Sanchez G, Frieden IJ. Annular pustular

Dermatol Venereol. 2009;23:814-819.

psoriasis--most common form of pustular psoriasis in children: report of

21. Pecina JL, Cappel MA. Acute generalized exanthematous pustulosis.

three cases and review of the literature. Pediatr Dermatol. 2002;19:19-25.

Skinmed. 2010;8:210-214.

5. Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF.

22. Roujeau JC, Bioulac-Sage P, Bourseau C, et al. Acute generalized exan-

Clinical profile, morbidity, and outcome of adult-onset generalized pustular

thematous pustulosis. Analysis of 63 cases. Arch Dermatol. 1991;127:1333-1338.

psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia.

23. Sidoroff A. Acute generalized exanthematous pustulosis [in German].

Int J Dermatol. 2014;53:676-684.

Hautarzt. 2014;65:430-435.

6. Zelickson BD, Muller SA. Generalized pustular psoriasis. A review of

24. Sidoroff A, Dunant A, Viboud C, et al. Risk factors for acute general-

63 cases. Arch Dermatol. 1991;127:1339-1345.

ized exanthematous pustulosis (AGEP)-results of a multinational case-

7. Zelickson BD, Pittelkow MR, Muller SA, Johnson CM. Polymorphonuclear

control study (EuroSCAR). Br J Dermatol. 2007;157:989-996.

leukocyte chemotaxis in generalized pustular psoriasis. Acta Derm Venereol.

25. Schmid S, Kuechler PC, Britschgi M, et al. Acute generalized exanthem-


atous pustulosis: role of cytotoxic T cells in pustule formation. Am J Pathol.

8. Mansouri B, Richards L, Menter A. Treatment of two patients with gen-


eralized pustular psoriasis with the interleukin-β inhibitor gevokizumab.

26. Weedon D. Weedon’s Skin Pathology. 3rd ed. London, UK; Churchill

Br J Dermatol. 2015;173:239-241.

Livingstone; 2009.

9. Takahashi T, Fujimoto N, Kabuto M, Nakanishi T, Tanaka T. Mutation

27. Onoufriadis A, Simpson MA, Pink AE, et al. Mutations in IL36RN/IL1F5

analysis of IL36RN gene in Japanese patients with palmoplantar pustulosis.

are associated with the severe episodic inflammatory skin disease known

J Dermatol. 2016;44:80-83.

as generalized pustular psoriasis. Am J Hum Genet. 2011;89:432-437.

10. Hong SB, Kim NI. Generalized pustular psoriasis following withdrawal

28. Speeckaert MM, Speeckaert R, Lambert J, Brochez L. Acute general-

of short-term cyclosporin therapy for psoriatic arthritis. J Eur Acad

ized exanthematous pustulosis: an overview of the clinical, immunological

Dermatol Venereol. 2005;19:522-523.

and diagnostic concepts. Eur J Dermatol. 2010;20:425-433.

11. Sehgal VN, Verma P, Sharma S, et al. Acrodermatitis continua

29. Teo WL, Pang SM, Koh HY. Allopurinol hypersensitivity syndrome with

of Hallopeau: evolution of treatment options. Int J Dermatol. 2011;50:

acute generalized exanthematous pustulosis manifestations. Cutan Ocul


Toxicol. 2011;30:243-244.

12. Lookingbill DP, Marks JG Jr, eds. Principles of Dermatology. 3rd ed.

30. Sneddon IB, Wilkinson DS. Subcorneal pustular dermatosis. Br J

Philadelphia, PA: WB Saunders; 2000.

Dermatol. 1979;100:61-68. • THE CLINICAL ADVISOR • SEPTEMBER 2017 49

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.

YOUR COMMENTS FIRED FOR FALLING ASLEEP ON THE JOB: OUR READERS WEIGH IN I worked 12-hour nights as an Emergency Medical Services dispatcher before becoming a nurse and then 12-hour days and nights in labor and delivery and in an ICU for many years. I also worked four 12-hour shifts in a row every other week. Not once did I fall asleep on the job. If I felt that tired [Legal Advisor, “Fired for falling asleep on the job,” June, p. 51], I would get up and walk the halls, stock rooms, or do something that required activity so that I could stay awake. While I empathize with this nurse, I would think it wiser to skip the meeting and go home to sleep. The meeting may have seemed like it was life-altering, but falling asleep on the road on the way home is more life-altering. As far as the hospital’s policy is concerned, I think she very likely knew that there was a policy against sleeping on breaks. Also, as stated, sleeping staff members in a public 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 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.

area do not fill the public with confidence. She should have simply called the supervisor on duty to inform a manager that she was too tired to remain and had not taken a break. If she had been relieved already, she may have been allowed to just go home. There are many ways that she could have handled the problem, even if she did risk upsetting the new supervisor.—GENIFER JOHNSON, DHA, MSN, RN, West Palm Beach, Fla. (227-1) Cruel! I worked night shift for 12 years, and there are moments when it is impossible to fight Mother Nature. Cruel, cruel, cruel! Better to not only allow, but encourage, power naps during a scheduled break with coverage provided by another nurse. That would go a long way against inadvertently falling asleep at unplanned times and would increase sharpness and acuity that would benefit the patients. I never understood the mentality of those who would prohibit this. Terrible!—BETTY DITILLO, MSN, APN, ANP, BC, NP-C, ACHPN, AOCNP, CCRN, Livingston, N.J. (227-2)

CLINICAL PEARLS PUTTING OUT THE FIRE OF A FIRE ANT BITE WITH TOOTHPASTE If you are bitten by fire ants, apply any toothpaste to the bites and wash off after 10 minutes. No blisters or reaction will


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.

occur. The toothpaste neutralizes the poison completely. The bites will still itch for a few minutes, but you will have no evidence of the attack by the next day. Toothpaste does NOT work for bee and wasp stings.—LINDA DELO, DO, Port Saint Lucie, Fla. (227-3)

MY MOST MEMORABLE PATIENT DIAGNOSING A PULMONARY EMBOLISM AND SAVING A LIFE I worked for a short time in general surgery after years in family medicine and gynecology. One morning, as I was arriving late to work due to a dental appointment, I was quickly informed that a patient 2 weeks post-op gastric bypass surgery had incorrectly arrived a week early for an appointment. Sensing the distress of the office receptionist, I went directly out to the waiting area to talk with the patient. She (Ms P) and a friend were waiting, laughing, and talking. They were both in their early 70s, neatly dressed, and pleasant. I greeted them and asked if they knew that they were a week early. They quickly admitted that they somehow wrote it on the calendar wrong. Ms P’s friend said, “Just this morning we were talking about it, but [Ms P] was so out of breath that she couldn’t talk.” “What?” I quickly questioned. “Yes, she couldn’t get dressed. She was hassling so.” “How were you yesterday?” was the next question that I asked. “Fine, walked to the mailbox fine,” replied Ms P’s friend. “Pain? Chest? Legs?” I asked. All were okay. This lovely woman looked well. She was not cyanotic. She had no tachypnea. Without a second thought, I knew

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 she had a pulmonary embolism. It may have well been written across her face. Our clinic was one-half block from the hospital emergency department. I asked gently, not to alarm her, “Where is your car?” Her friend replied, “I parked it at the curb just outside the door.” Then without thinking, I broke every protocol rule, without hesitation. “I want you to take her straight to the emergency department door (we could see it across the parking lot). I explained that I was concerned and that I wanted her to go there now to be checked out. With a steady gaze at the friend, I said, “Do not stop. Go directly there, now.” The couple did not hesitate, nor were they alarmed. I picked up the emergency department phone and spoke to the charge nurse. “Meet her at the door, she has a pulmonary embolism. Do not let her wait.” The charge nurse called me back in less than 30 minutes. Ms P had a large pulmonary embolism on CT. But the patient was stable, with no distress, and was doing well. “You saved her life,” the nurse said to me. In retrospect, I questioned whether I should have had her checked in for vitals and called the paramedics. But I had no doubt at the time. Time and calmness were critical. After many, many years of experience, I know there is a second sense that cannot be measured—a Divine guidance. Years of stories, sights, smells, and touches take over. Three weeks later, she and her friend came down the hall looking for me with big smiles and hugs. I was only working in this area a short time, but I know it was for this one event, and I am grateful to have been a part.— DEBORAH UNDERWOOD BROWN, FNP-C, Holly Springs, N.C. (227-4) n

Claire O’Connell, MPH, PA-C,

an associate professor at the Rutgers University Physician Assistant Program, Piscataway, N.J.


Katherine Pereira, DNP, FNP,

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

Sherril Sego, FNP-C, DNP,

is an independent consultant in Kansas City, Mo. • THE CLINICAL ADVISOR • SEPTEMBER 2017 51



How does your salary compare with that of your peers? Is now a good time to ask for a raise? According to results from The Clinical Advisor’s 2017 Salary Survey, it may be. About 55% of nurse practitioners (NPs) and 54% of physician assistants (PAs) earned a higher income this past year than they did in 2015-2016. The average salaries in 2016-2017 for NPs and PAs are:





The gender pay gap remains, and the West prevails The wage gap between men and women continues in all lines of work, and the medical field is no exception. A total of 2136 (89.3%) NP survey responders and 518 (62.3%) PA survey responders were women, compared with 216 male NPs and 307 male PAs. However, male NPs earned $123,547, compared with $104,097 for women. Male PAs earned $128,966, compared with $107,957 for women. Similar to last year’s results, the West remains the region with the highest average salaries for NPs

($113,035) and PAs ($123,875). A majority of NP and PA responders practice their profession in the South, where the average salary for NPs is $104,427 and the average salary for PAs is $114,302. The Midwest has the lowest average salary for NPs ($102,571), and the Northeast has the lowest average salary for PAs ($110,702).

How the results were analyzed We asked our readers to provide their current salaries, which included base pay and bonuses, in increments of $5,000. The salaries were then converted to the midpoint within that category (for example, salaries in the $71,000 to $75,000 category were converted to $73,000). Our salary categories begin with the $0 to $5,000 group and follow in $5,000 increments up through and including the $195,000 to $200,000 group. This year's findings are based on the survey responses from 2,393 nurse practitioners and 831 physician assistants. About 89% of NPs who responded are women, and about 62% of PAs who responded are women.


See the complete survey results online at TABLE 1. Average NP salary by practice area

TABLE 2. Average PA salary by practice area

Practice area

Percent response

Average salary

Practice area

Percent response

Average salary

Family Medicine

21.5% (n = 515)


Family Medicine

15.5% (n = 129)



6.8% (n = 162)


Emergency Medicine

7.5% (n = 62)



5.5% (n = 131)


Orthopedic Surgery

6.6% (n = 55)


Geriatric Medicine

4.5% (n = 107)


Urgent Care

5.5% (n = 46)


Primary Care

4.1% (n = 98)



3.1% (n = 26)


Urgent Care

3.8% (n = 91)



1.8% (n = 15)


TABLE 3. Average NP salary by experience level

TABLE 4. Average PA salary by experience level

Years of experience

Percent response

Average salary

Years of experience

Percent response

Average salary


31.3% (n = 750)



20.9% (n = 174)



22.7% (n = 543)



17.9% (n = 149)



12.5% (n = 299)



16.4% (n = 136)



14.3% (n = 343)



17.1% (n = 142)



18.8% (n = 449)



27.3% (n = 227)


FIGURE 1. Average NP salary by geographic region

FIGURE 2. Average PA salary by geographic region







(n = 442) $113,035 average salary

(n = 572) $102,571 average salary

(n = 482) $106,139 average salary

(n = 172) $123,875 average salary

(n = 178) $116,399 average salary

(n = 204) $110,702 average salary



(n = 887) $104,427 average salary

(n = 272) $114,302 average salary • THE CLINICAL ADVISOR • SEPTEMBER 2017 53


TABLE 5. Average NP salary by urban, suburban, or rural location

TABLE 6. Average PA salary by urban, suburban, or rural location

Practice setting

Percent response

Average salary

Practice setting

Percent response

Average salary


23.3% (n = 558)



18.8% (n = 156)



34.6% (n = 827)



40.8% (n = 339)



41.5% (n = 993)



39.6% (n = 329)


TABLE 7. Average NP salary according to gender

TABLE 8. Average PA salary according to gender





(n = 2,136)

(n = 216)

(n = 518)

(n = 307)





TABLE 9. Average NP salary according to practice setting

TABLE 10. Average PA salary according to practice setting

Practice setting

Percent response

Average salary

Practice setting

Percent response

Average salary

Clinic – Hospital

21.1% (n = 505)


Clinic – Hospital

19.9% (n = 165)


Clinic – Stand Alone

18.1% (n = 433)


Clinic – Stand Alone

20.1% (n = 167)


Office Practice

18.4% (n = 440)


Office Practice

19.1% (n = 159)



14.0% (n = 336)



20.6% (n = 171)


Walk-in/ Ambulatory Care

6.1% (n = 146)


Walk-in/ Ambulatory Care

4.6% (n = 38)


Long-term care

2.8% (n = 67)



3.2% (n = 27)



FIGURE 3. Did you earn more money this year (NPs)?

FIGURE 4. Did you earn more money this year (PAs)?












FIGURE 5. Do you expect to earn more money next year (NPs)?



FIGURE 6. Do you expect to earn more money next year (PAs)?











3.5% TABLE 11. Number of patients seen per week (NPs)

TABLE 12. Number of patients seen per week (PAs)


Percent response


Percent response


16.3% (n = 391)


10.5% (n = 87)


30.3% (n = 724)


25.8% (n = 214)


25.0% (n = 598)


25.6% (n = 213)


18.1% (n = 434)


20.8% (n = 173)


5.4% (n = 130)


9.3% (n = 77)


3.2% (n = 76)


6.6% (n = 55)

The Clinical Advisor thanks all who participated in this year’s salary survey. • THE CLINICAL ADVISOR • SEPTEMBER 2017 55


Importance of good notetaking


Mr P, 42, was a nurse practitioner (NP) who worked with a primary care physician, Dr F, 60. Mr P had been working for the physician for the past 3 years, and the clinicians had a good working relationship. Dr F had particularly wanted to have a male NP, because she believed that some male patients were more comfortable talking to, or being examined by, another male, and she wanted to be able to offer that option. Dr F also employed a female NP. Several of Mr P’s patients were referrals from existing patients of Dr F. One such referral was Mr D, a 51-year-old truck driver who had been referred by his wife, a current patient of Dr F’s. Mr D’s wife made an appointment for her husband after he began experiencing bleeding during bowel movements and rectal pain. The patient seemed uncomfortable discussing his problem, but he reported that he had been bleeding intermittently during bowel movements for the past 2 months. When pressed, he told Mr P that the blood was bright red, and that at times it seemed like the toilet was full of blood.


Taking good notes is one of the most important steps a clinician can take to reduce the risk of a lawsuit.

A clinician neglects to note that he had advised a patient to get a colonoscopy and that the patient had refused.


After their discussion, Mr P informed the patient that he would now perform a physical exam, including a digital rectal examination. The digital exam was negative for any tumors or tears, and Mr P diagnosed the patient with bleeding due to internal hemorrhoids. “I would advise you to schedule a colonoscopy to rule out anything else,” said the clinician. “I can give you a referral to a gastroenterologist who is on your plan.” The patient adamantly refused any referral and told the clinician that he was not interested in a colonoscopy. Mr P gave him a prescription for suppositories and a hemorrhoid cream, and then scheduled the patient to return in 3 weeks for a follow-up appointment. After the patient left, Mr P documented the visit, the exam, and the diagnosis, but he neglected Continues on page 58

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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Recommend BAYER Aspirin— First for secondary prevention. CV=cardiovascular; MI=myocardial infarction. *Nonfatal MI. References: 1. Antithrombotic Trialists’ (ATT) Collaboration. Lancet. 2009;373:1849-1860. 2. Garcia Rodríguez LA, Cea Soriano L, Hill C, Johansson S. Increased risk of stroke after discontinuation of acetylsalicylic acid: a UK primary care study. Neurology. 2011;76:740-746. 3. Garcia Rodríguez LA, Cea-Soriano L, Martín-Merino E, Johansson S. Discontinuation of low dose aspirin and risk of myocardial infarction: case-control study in UK primary care. BMJ. 2011;343:d4094. Bayer and the Bayer Cross are registered trademarks of Bayer. © 2017 Bayer December 2016 65986-PP-BAY-PREV-US-0644

82836ha_a.indd 1

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LEGAL ADVISOR to note that he had advised the patient to get a colonoscopy and that the patient had refused. At the follow-up exam, the patient reported that the rectal pain and bleeding had ceased and that he had not noticed any blood in his stools. Mr P did not suggest a colonoscopy again. During the next year and a half, Mr P saw the patient 8 more times for various other complaints and minor illnesses. The patient never relayed any concerns about continued rectal pain and bleeding, and Mr P did not ask, nor did he have any further discussions with the patient, regarding a colonoscopy. The clinician was unaware that approximately 20 months after Mr D’s initial office visit, his wife made an appointment for him to have a colonoscopy due to his continued rectal pain and bleeding. During the procedure, the gastroenterologist found a tumor and the patient was later diagnosed with differentiated metastatic colon adenocarcinoma. Mr D died 1 year after the cancer diagnosis.

Records did not indicate that the clinician had recommended a colonoscopy or that he followed up during later appointments. After a time, Mr D’s wife sought the counsel of a plaintiff’s attorney and asked whether the attorney thought there was a malpractice case against the physician’s practice. The attorney hired several medical experts to read through the records. The experts pointed out that the records did not indicate that Mr P had ever recommended a colonoscopy. They further pointed out that there were no notes indicating that he had followed up with the patient at later appointments to determine if there was still rectal bleeding, or to recommend a colonoscopy. The attorney told Mr D’s wife that he would take the case, and he filed a medical malpractice lawsuit against Mr P and Dr F’s practice. When Mr P was notified about the lawsuit, he contacted his insurance company, which provided a defense attorney. The attorney also hired medical experts to look at the patient files, and the experts all noted the same issue. “Why didn’t you suggest that the patient have a colonoscopy?” asked the attorney. “I’m sure I did,” replied Mr P. “I recall that the patient strongly told me that he wouldn’t consider it and that I shouldn’t bring it up again.” “But that’s not reflected in the medical records,” said the attorney.

The attorney explained that the practice was being sued for failure to properly evaluate and document, failure to perform adequate and appropriate follow-up, failure to order appropriate treatment, and failure to refer a patient to a specialist. “Without any documentation showing that you recommended a colonoscopy, or followed up with the patient, we’re in a weak position to defend this case,” said the attorney. “I suggest we have a settlement discussion.” On the advice of the attorney, Mr P settled the case out of court for the limits of his liability policy. Legal background

Lawyers often use medical experts to help them decide whether to take on a medical malpractice case, how to defend a case, or whether a case is defensible at all. In some states, medical malpractice laws require medical panels to review cases to decide if they merit a lawsuit. The testimony of a medical expert during trial can often make or break a case. While medical experts can, and certainly do, disagree, their knowledge is key and extremely important to a medical malpractice case. In this situation, all the defense’s medical experts noticed that Mr P did not write down the colonoscopy recommendation or any follow-up about it, and the experts believed this to be a significant flaw in the case’s defense. Protecting yourself

Mr P made several errors in both communication and documentation. The medical experts who reviewed the case were critical of his failure to properly document and follow up about the patient’s history of rectal bleeding and pain, thus allowing the colon cancer to metastasize. He should have documented all patient-related discussions, as well as any treatment orders or recommended tests or referrals. He should have clearly noted the patient’s noncompliance to the suggestion of a colonoscopy and his refusal to accept a referral. He should have noted that he warned the patient that not complying with the recommendations could result in a worsening of his symptoms. Although you cannot force a patient to undergo a screening procedure, you can protect yourself from legal risk by noting that you advised it, that the patient refused, and that you warned the patient of the possible risks associated with refusing. Consider informing the patient in writing that noncompliance with treatment advice could result in a poor outcome. n Ms Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.



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.

Cod liver oil


As the name indicates, cod liver oil is derived from the liver of the Atlantic cod fish (Gadus morhua).1 As with many fish oils, cod liver oil is rich in omega-3 fatty acids, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and has high concentrations of vitamins A and D.2 These rich concentrations of vitamins A and D distinguish cod liver oil from other fish oils. A tablespoon of cod liver oil contains 400% of the US Department of Agriculture’s recommended daily allowance (RDA) of vitamin A and 200% of the RDA for vitamin D.3

Background The compounds in cod liver oil are largely considered to be n-3 polyunsaturated fatty acids (n-3 PUFAs).1 PUFAs are also considered to be free fatty acids and have multiple health benefits, including acting as antibacterial, antifungal, and antiviral agents.1 In recent decades, PUFAs have attracted intense interest from researchers for these functions as well as for their anti-inflammatory effects on the cardiovascular and neurologic systems.

Science Cod liver oil first gained wide acclaim in the prevention and treatment of the bony malformation in children known as rickets.2 Through a series of widely disparate studies and publications, scientists were able to connect the issues of poor nutrition and lack of adequate exposure to sunshine as the key elements in the development of rickets and blindness.2

However, it took several hundred years to actually confirm the association of vitamins A and D deficiency, rickets, and xerophthalmia (often called night blindness).2,4 Vitamin A is essential for the process by which light is converted into electrical signals in the rod cells, cone cells, and photosensitive ganglion cells of the retina. By the middle of the 20th century, rickets in the United States was a rapidly disappearing disease. With rickets fading from the mainstream of medicine in developed countries, scientists are currently focusing on the exciting potential of cod liver oil supplementation to control symptoms of mood and depressive disorders as well as dementia. In a large population study conducted in Norway, nearly 22,000 adults were followed for 2 years.5 The study examined a variety of health aspects and outcomes, one of which was the correlation of daily cod liver oil supplementation and the presence and degree of depressive symptoms. Retrospective data showed that patients consuming daily cod liver oil supplements were approximately 30% less likely to have symptoms of depression than those who did not use • THE CLINICAL ADVISOR • SEPTEMBER 2017 59

ALTERNATIVE MEDS UPDATE the supplemental fish oil. Similar studies agree with these findings. A smaller trial randomly assigned people known to have severe depression and a history of repeated suicide attempts to either high supplemental doses of EPA and DHA, both of which are found in high concentrations in cod liver oil, or placebo.6 All patients continued their standard psychiatric care. At the end of 12 weeks, scores on the Beck Depression Index improved by 50% to 70% in the treatment group compared with the placebo group.5 A study in the Netherlands followed more than 200 men age 70 years and older for up to 15 years, testing their cognitive ability every 5 years and retrospectively correlating self-reported fish consumption. After 5 years, intake estimates of 380 mg/day of EPA and DHA was associated with a statistically significant difference in the Mini-Mental State Examination.7 Participants who did not consume fish regularly showed an average decline that was approximately 300% greater than those who did eat fish regularly.

Safety, interactions High doses of cod liver oil have been shown to have antithrombotic action; therefore, taking it with any other medication or supplement that has blood-thinning action is potentially dangerous.8 More research is being done in those taking high doses (in excess of 3 g of omega-3 PUFAs per day) who are in physically dangerous professions.8 Although there is disagreement among studies, there are enough data showing decreased platelet counts and longer bleeding times to warrant caution.

on specific formulation concentrations. Cod liver oil liquid or capsules are relatively inexpensive, costing in the range of $10 to $15 per month.


High doses of cod liver oil have shown evidence of antithrombotic action.

Patients who had consumed cod liver oil supplements were about 30% less likely to have symptoms of depression.

How supplied, dose, cost

There are many supplements that supply the essential compounds found in cod liver oil, and the recommendation of cod liver oil as a supplement should be guided by the specific condition being considered. As noted, the main concern is toxicity, with higher toxicity in higher concentrations of vitamin A. The secondary concern is a possible increased bleeding tendency. Because most Americans do not consume significant quantities of cold water fish, such as cod, recommending a modest amount of cod liver oil supplementation would be a sound practice. n References 1. Loftsson T, Ilievska B, Asgrimsdottir GM, Ormarsson OT, Stefansson E. Fatty acids from marine lipids: biological activity, formulation and stability. J Drug Delivery Sci Tech. 2016;34:71-75. 2. Rajakumar K. Vitamin D, cod liver oil, sunlight, and rickets: a historical perspective. Pediatrics. 2003;112:e132-135. 3. United States Department of Agriculture. https://www. 4. Leskov IB, Klenchin VA, Handy JW, et al. The gain of rod phototransduction: reconciliation of biochemical and electrophysiological measurements. Neuron. 2000;27:525-537. 5. Raeder MB, Steen VM, Vollset SE, Bjelland I. Associations between cod liver oil use and symptoms of depression: the Hordaland Health Study. J Affect Disord. 2007;101:245-249. 6. Hallahan B, Hibben JR, Davis JM, Garland MR. Omega-3 fatty acid supplementation in patients with recurrent selfharm. Single-centre double-blind randomized controlled trial. Br J Psychiatry. 2007;190:118-122. 7. van Gelder BM, Tijhuis M, Kalmijn S, Kromhout D. Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive


decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr. 2007;85(4):1142-1147. 8. Hamazaki T, Colleran H, Hamazaki K, Matsuoka Y, Itomura M, Hibbein J. The safety of fish oils for those whose risk of injury is high. Mil Med. 2014;179:134-137. 9. National Institutes of Health. Vitamin A. https://ods. Updated August 31, 2016. Accessed July 31, 2017.


Cod liver oil as a supplement is available as both a liquid oil and as capsules. Because of its unpleasant taste and consistency, liquid oil is not generally well tolerated. Capsule forms vary in strength, but because of the potential for toxicity, dosing should be guided by the maximum RDA of vitamin A, which is no more than 3000 IU/day.9 Consumers should follow label instructions based

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September 2017 Clinical Advisor  
September 2017 Clinical Advisor