Clinical Advisor March/April, 2021

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Nurse Sues Over Sexual Harassment FEATURE

Erectile Dysfunction: Harbinger of Early Cardiovascular Disease

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MARCH/APRIL 2021

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OSTEOPOROSIS AND OBESITY

The Impact of Obesity on Knee OA Symptoms and Surgical Outcomes Obesity is a modifiable risk factor for osteoarthritis.

CLINICAL CHALLENGE

Bruising, Bleeding Gums, Nosebleeds in Young College Athlete

DERMATOLOGY CLINIC

Inflammation and Redness of the Fingernail Folds

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As much as I don’t like to admit it, I have gained weight over the past year. Blame it on the stress of living through a global pandemic, lockdown, or working from home, but this past year has not been kind to my waistline. It began early during the lockdown when I started baking.

I love to bake, but I really started baking — a lot. Normally, these baked goods would have been distributed to office mates, friends, and family, but with only 3 of us at home, they were consumed by me, myself, and I. I am not alone. There are lots of anecdotal reports of people putting on the “COVID 15” — that is, 15 pounds. As more and more Americans become vaccinated and begin to emerge from isolation, we are going to need help getting back in shape and losing weight.

Unfortunately, the global pandemic coincided with an obesity crisis already wellestablished in the United States. According to the Centers for Disease Control and Prevention (CDC), the adult obesity prevalence has been increasing yearly from 30.5% in 2017-2018 to 42.4% in 2019-2020; the prevalence of severe obesity has increased from 4.7% to 9.2% during these periods.

The CDC’s 2019 Adult Obesity Prevalence Maps show that 12 states have an adult obesity prevalence at or above 35%: Alabama, Arkansas, Indiana, Kansas, Kentucky, Louisiana, Michigan, Mississippi, Oklahoma, South Carolina, Tennessee, and West Virginia. The maps also break down adult obesity prevalence by race and ethnicity: 34 states and the District of Columbia had an obesity prevalence ≥35% among nonHispanic Black adults; 15 states had an obesity prevalence ≥35% among Hispanic adults; and 6 states had an obesity prevalence ≥35% among non-Hispanic White adults.

According to the CDC, these disparities underscore the need to remove barriers to healthy living and ensure that communities support a well-balanced, active lifestyle for all. Even a small amount of weight loss can have a significant impact on one’s health and help prevent or manage chronic diseases that worsen outcomes from COVID-19. As we emerge from our self-isolation, let’s encourage patients to make small changes in their lives to improve their health.

Nikki Kean, Director The Clinical Advisor www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 1

© FREETRANSFORM / GETTY IMAGES

Weight Gain in the United States

Assistant editor Michelle Lampariello

CONTENTS MARCH/APRIL 2021

FEATURES 5

12 Erectile dysfunction: early sign of CVD

Clinical Challenge: Bruising, Bleeding Gums, Nosebleeds in Young College Athlete Immune thrombocytopenia is a common autoimmune disease.

2 Erectile Dysfunction: Harbinger of Early 1 Cardiovascular Disease Comanagement of cardiovascular disease risk factors through exercise and weight loss can improve erectile function.

16 The Impact of Obesity on Knee OA Symptoms and Surgical Outcomes Weight loss is associated with reduced pain, improved function, and better quality of life in patients with knee OA.

DEPARTMENTS 1

From the Director Weight Gain in the United States

4

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

21 Hepatitis C virus-associated skin lesions

21

Dermatology Clinic ■ Inflammation and Redness of the Fingernail Folds ■ Flat-Topped Papule With Wickham Line

25

Dermatologic Look-Alikes Blisters on the Hands

31

Legal Advisor Nurse Sues Over Sexual Harassment

25 Hand, foot, and mouth disease

31 Protection against harassment

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CLINICAL CHALLENGE ClinicalAdvisor.com/CaseStudy

Inappropriate Antibiotic Prescribing Common for Women With UTIs

Brady Pregerson, MD Case Study: Is It More Than Just a Migraine?

A 42-year-old woman with a history of chronic migraines presents for evaluation of a new headache that is different from the migraines she typically experiences. The pain onset is more rapid with vomiting occurring earlier in the headache course. The location of the pain is atypical for her: it is both frontal and occipital as opposed to being primarily frontal. See the full case at: ClinicalAdvisor.com/CaseMarch_April21

A considerable proportion of women with uncomplicated urinary tract infections (UTIs) have inappropriate antibiotic prescribing; women living in rural areas also receive longer duration of therapy.

Coffee: A Cup a Day Keeps Heart Failure Away According to an analysis of 3 large epidemiologic studies, increased coffee intake was linked to a reduced risk of developing heart failure later in life.

Black Infant Mortality Gap Decreases When Black Physicians Provide Care Excess Black infant mortality rate is halved when Black newborns are cared for by a Black physician vs a White physician.

Fezolinetant Reduces Vasomotor Symptoms Associated With Menopause Fezolinetant showed positive results in phase 3 clinical trials with significant reductions found in the frequency and severity of vasomotor symptoms associated with menopause.

THE WAITING ROOM

Official Blog of The Clinical Advisor ClinicalAdvisor.com/WaitingRoom Jim Anderson, MPAS, PA-C, DFAAPA Why Word Choice Matters In recent years, there has been a gradual movement away from the word noncompliant in favor of the word nonadherent to describe patients who do not listen to medical advice or follow clinicians’ recommendations.

MY PRACTICE ClinicalAdvisor.com/MyPractice

COVID-19 Convalescent Plasma Shows Trend Toward Early Survival Benefit Patients who received convalescent plasma had a longer hospital stay compared with hospitalized patients who received standard therapy but a decreased risk for death at 7 and 14 days.

4 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

Kristin Della Volpe NP and PA Experts Discuss Controversy Over USDA-HHS Dietary Guidelines Experts debate the USDA-HHS’ decisions on sugar and alcohol intake limits in the updated Dietary Guidelines for Americans, 2020-2025.

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EXCLUSIVE TO THE WEB AT

FEATURE: ELIZABETH HOUSER, CRNP

Clinical Challenge: Bruising, Bleeding Gums, Nosebleeds in Young College Athlete Immune thrombocytopenia is a common autoimmune disease characterized by low platelet count (<100×109/L) and an increased risk for bleeding.

© JOHN DURHAM / SCIENCE SOURCE

A

Bruising and bleeding can be indicative of many conditions.

21-year-old woman presents to a college health clinic with complaints of bruising easily. Reporting that the bruising began 3 weeks ago, the patient says she first noticed it on her distal arms after playing volleyball. She reports that the bruising never occurred before, although she played 8 years of volleyball including at college.

A review of systems is positive for bleeding gums, frequent nosebleeds, heavy periods, spotting between menstrual cycles, and a petechial rash on both legs. The patient reports that the rash developed after she was running. She also reports that running has become difficult and complains of a progressive decrease in exercise tolerance.

She denies fever, night sweats, weight loss, headaches, abdominal pain, fainting, dizziness, lightheadedness, chest pain, shortness of breath, blood in her stool or urine, and recent illness. Her last menstrual period was 2 weeks ago, and she denies any chance of pregnancy. She denies use of illicit drugs or any new prescription or over-the-counter medications and has no known drug allergies.

The patient is taking a contraceptive containing norgestimate and ethinyl estradiol. She has a medical history of iron-deficiency anemia but is not taking iron supplements. Her family history is significant for lymphomatoid granulomatosis (a rare lymphoma) in her paternal grandfather and leukemia in a maternal first cousin.

On presentation, the student appears well and is alert and oriented.Vital signs are normal (Table 1).

Physical examination reveals ecchymosis on the

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 5

HEMATOLOGY: UNUSUAL CASE OF BLEEDING

FIGURE 1. Ecchymosis on the left wrist.

FIGURE 2. Petechiae of the left lower leg.

distal dorsal arms and the proximal medial legs bilaterally (Figure 1). Petechial spotting is noted on both lower extremities, as well as orally along the gum line (Figure 2). Heart sounds show a normal rate and rhythm without murmur, and lungs are clear to auscultation. She has no lymphadenopathy, abdominal tenderness, or palpable hepatosplenomegaly.

Outpatient laboratory testing is conducted immediately and shows a critically low platelet count and low hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and ferritin (Table 2). Trace hemoglobin is detected in the urinalysis. Peripheral blood smear reveals severe thrombocytopenia and mild microcytic anemia, with no morphologic abnormalities.

The patient’s white blood cell count, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein level, tickborne disease panel, prothrombin time/international normalized ratio, antinuclear antibody test, human chorionic gonadotropin test, and vitamin D, vitamin B12, and folate levels are normal.

Conditions considered in the differential diagnosis include trauma, anemia, infections such as mononucleosis or meningitis, Henoch-Schönlein purpura, drug-induced thrombocytopenia, immune thrombocytopenia (ITP), vasculitis, coagulopathies, myelodysplastic syndromes, and leukemia.

The patient’s medical history, examination findings, and test results suggest a diagnosis of ITP (previously known as idiopathic thrombocytopenic purpura), which is a common autoimmune disease characterized by low platelet count (<100×109/L) and an increased risk for bleeding.1,2 It may present as an isolated thrombocytopenia or occur in the setting of additional autoimmune cytopenias (Evans syndrome), as a manifestation of a primary immunodeficiency, or secondary to an autoimmune condition or infection.2 Although the pathophysiology of ITP is unclear, several mechanisms have been proposed such as autoantibodies and

TABLE 1. Patient’s Vital Signs

TABLE 2. Laboratory Results

Temperature, °F

97.6

Heart rate, bpm

72

Blood pressure, mm Hg

128/78

Respiratory rate per minute

16

Pulse oximetry, % bpm, beats per minute

99 (on room air)

Discussion

Test

Result

Normal Reference Range in Womena

Ferritin, ng/mL

5

6-137

Hemoglobin, g/dL

11

12-16

Hematocrit, %

34.4

36-46

Mean corpuscular hemoglobin, pg/cell

24.9

26-34

Mean corpuscular volume, fL

77.8

80-100

Platelet count/L

1×109

140-440×109

a Normal reference ranges are based on laboratory used by author

6 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

cytotoxic T cells that target platelets and/or megakaryocytes.1 Immune thrombocytopenia affects people of both sexes and all ages, with a peak in childhood and a second and third peak in young adults and the elderly.3 In the United States, the incidence of ITP is approximately 2 to 5 per 100,000 patients per year.2 Platelets are critical to the maintenance of vascular integrity; thus, patients with ITP are at increased risk for bruising and spontaneous bleeding events.1 Patients with a platelet count of <30×109/L are at increased risk for severe bleeding (eg, intracranial hemorrhage, mucocutaneous bleeding, lower gastrointestinal bleeding, other internal bleeding, and menorrhagia).4 Patients with a platelet count of <10×109/L are at risk for life-threatening bleeding.

Deaths associated with ITP are rare and associated most frequently with spontaneous or trauma-induced intracranial hemorrhage.4 Intracranial hemorrhage reportedly occurs in 1.4% of adults and 0.4% of children with ITP, most of whom have chronic ITP.5 If severe bleeding occurs, rapid intervention with platelet transfusions in conjunction with continuous infusion of intravenous immunoglobulin G (IgG) therapy or emergent splenectomy may be lifesaving.6 The signs and symptoms of ITP are highly variable, and onequarter of patients are asymptomatic and diagnosed through routine blood tests.4 Symptoms primarily are related to bleeding in the skin or mucous membranes presenting as petechiae or purpura.6 Patients with platelet counts of ≥30×109/L usually do not require any treatment and can be managed with observation (Table 3).2 If adult patients require intervention, American Society of Hematology (ASH) guidelines recommend treatment with corticosteroids, which prevent the destruction of platelets by macrophages within the spleen.2 The ASH guidelines also include treatment recommendations for children.2 The prognosis of ITP is variable and appears to depend on age, with 1-year spontaneous remission rates in pediatric patients ranging from 74% in children younger than 1 year to 62% in patients aged 10 to 20 years.2 Spontaneous remission rates in adults range from 20% to 45% at 6 months.2

TABLE 3. Selected American Society of Hematology Guidelines on Immune Thrombocytopenia in Adults2 Variable

Recommendation

Adults with newly diagnosed ITP ×109/L and a platelet count of ≥30× who are asymptomatic or have minor mucocutaneous bleeding

• Manage with observation • Corticosteroid treatment typically is not recommended

Adults with newly diagnosed ITP and a platelet count of <30× ×109/L who are asymptomatic or have minor mucocutaneous bleeding

• Corticosteroid treatment is recommended over observation: — Prednisone (0.5-2.0 mg/kg/d for ≤6 weeks) — Dexamethasone (40 mg/d for 4 days) — If rapid response is important, dexamethasone may be preferred over prednisone — Monitor for side effects

Adults with newly diagnosed ITP and a platelet count of <20× ×109/L who are asymptomatic or have minor mucocutaneous bleeding

• Admit to the hospital

total of 2 IgG treatments with good response, and there were no future treatments planned at that time. She moved back home, and no further updates were made. ■ Elizabeth Houser, CRNP, is a nurse practitioner at Indiana University of Pennsylvania, in Indiana, PA. She holds a MS in Nursing from Carlow University. Houser has been practicing in college health for 8 years and has an additional 5 years of emergency nursing experience.

References 1. Arnold DM. Bleeding complications in immune thrombocytopenia.

Hematology. 2015:237-242. doi:10.1182/asheducation-2015.1.237 2. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):

Conclusion

3829-3866. doi:10.1182/bloodadvances.2019000966

The patient in this case study was referred to the emergency department in response to her critical low platelet count.

There the patient received a blood transfusion and high-dose steroids and was admitted to the hospital. The platelet count responded to therapy and began to rise. She was discharged with a platelet count of 38×109/L and diagnosed with ITP. She was sent home on oral steroids and advised to follow up with hematology. At her follow-up appointment with the hematologist, repeat laboratory studies revealed a decline in the platelet count to 3×109/L. This resulted in a second admission to the hospital. She received IgG therapy and, subsequently, the platelet count rose to 93×109/L. She received a

3. Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017;129(21):2829-2835. doi:10.1182/blood-2017-03-754119 4. European Group for Blood and Marrow Transplantation. Immune thrombocytopenia: a practical guide for nurses and other allied healthcare professionals. 2011. Accessed March 22, 2021. https://www.ebmt.org/ practical-guides-immune-thrombocytopenia.

5. Neunert C, Noroozi N, Norman G, et al. Severe bleeding events in adults and children with primary immune thrombocytopenia: a systematic review.

J Thromb Haemost. 2015;13(3):457-464. doi:10.1111/jth.12813 6. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guidelines for thrombocytopenia.

Blood. 2011;117 (16): 4190-4207. doi:10.1182/blood-2010-08-302984

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 7

FEATURE: MELISSA LONG, PA-C; E. RACHEL FINK, MPA, PA-C

Erectile Dysfunction: Harbinger of Early Cardiovascular Disease Comanagement of cardiovascular disease risk factors through exercise and weight loss can improve erectile function.

© DNA ILLUSTRATIONS / SCIENCE SOURCE

Erectile dysfunction may be one of the first physical manifesta­tions of atherosclerosis in men.

E

rectile dysfunction is a common disorder defined as “the persistent inability to achieve and then maintain an erection to permit satisfactory sexual intercourse.”1 An estimated 18 million men in the United States (18%) have ED.2 In a cross-sectional analysis, the prevalence of ED differed markedly by age, ranging from 5.1% in men aged 20 to 39 years to 70.2% in men older than 70 years of age.2 However, a recent study found that the incidence of ED in younger men is increasing, estimating the prevalence of ED in younger men (<40 years) to be as high as 30%.3 Although it can be distressing for patients to discuss ED, proper evaluation and treatment of the condition can significantly improve quality of life.4 The growing acknowledgement that ED is a harbinger of cardiovascular disease (CVD), for example, has made the early diagnosis of ED associated with vascular risk factors a priority for many primary care clinicians. Proper evaluation and treatment of ED has been shown to decrease the risk for CVD morbidity.1,5-9 Causes of Erectile Dysfunction

Erectile dysfunction is caused by a variety of factors such as vascular, endocrinologic, neurologic, psychogenic, and anatomic abnormalities. It also can be caused by a combination of factors, which can make determining the cause of ED more difficult. Psychogenic etiologies of ED include depression, anxiety, and interpersonal partner-related 12 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

conflicts.3 Men with ED related to psychogenic factors tend to experience a sudden onset of symptoms, decreased libido and normal androgen status, nocturnal or self-stimulated erections, and normal findings on penile duplex Doppler ultrasonography.3,10 Patients with ED related to vascular, endocrinologic, or neurologic factors usually experience a gradual onset of symptoms and a low to normal libido, weak noncoital erections, inconsistent early morning erections, and abnormal Doppler ultrasound findings.11,12 Cardiovascular Health and Erectile Dysfunction

Erectile dysfunction may be one of the first physical manifestations of atherosclerosis in men. Patients with ED of vascular etiology are at a higher risk for coronary artery disease (CAD) and should be screened for CVD and educated about lifestyle management options. Similarly, men with known risk factors for CVD — smoking, hyperlipidemia, hypertension, and diabetes — should be screened for ED.6 The coexistence of these diseases often is overlooked by providers and can lead to adverse health effects as both conditions worsen.8 There is a clear link between increasing severity of ED and poor cardiovascular health. Sufficient blood flow and nitric oxide levels are required for successful erections.13 Interference with blood flow greatly affects the ability to maintain an erection.13,14 When more than 50% of the lumen of the deep penile (cavernosal) and common penile arteries are narrowed, ED will occur.13 It also is important to evaluate the elasticity of the endothelium in patients with CVD and those with ED. PohjantähtiMaaroos et al reported that men with ED had a significantly lower arterial elasticity index than those without ED after adjustment for age, diabetes, family history of CVD, smoking, physical activity, use of statins or β-blockers, waist circumference, blood pressure, and lipids.15 This study confirms that atherosclerotic damage physiologically affects the systemic elasticity of arteries, including the penile artery.

Dzenkeviciute et al evaluated subclinical vascular disease in relation to ED severity and found that men with ED had significantly higher CVD risk than controls.7 The severity of ED also was associated with left ventricular hypertrophy, left ventricular diastolic dysfunction, and impaired renal function.

The changes they found in the endothelium were the same changes that occur in patients with chronic kidney disease and chronic myocardial injury.

Inman et al found new-onset CAD in more than 10% of men with ED during a 10-year follow-up period.6 Banks et al found that men with worsening ED and CVD have increasing hospitalizations related to myocardial infarction, ischemic heart disease, and heart failure.Vascular ED also is associated with increased overall mortality.9

Patients without CAD who have ED symptoms likely are experiencing mild endothelial changes beginning in arteries such as the penile artery and should be counseled about measures to prevent CAD.6 Evaluation and Screening

Having an understanding of the relationship between ED and CVD may lead more men to openly discuss their sexual history, allowing providers to address both conditions and possibly prevent the worsening of CVD. Men with better overall cardiovascular health will have a better long-term prognosis related to sexual function.9 Erectile dysfunction often presents as a mix of both psychogenic and vascular etiologies; therefore, it is important to determine the specific cause or causes of ED.11 Evaluation of vascular ED should begin with a thorough history, including medical and sexual history. It is important to approach the topic sensitively and educate the patient about the prevalence of ED. The stigma related to ED is what prevents many men from admitting difficulty in their sexual life.14 A thorough history of the patient’s smoking status, diet, and exercise routines should be included in the patient interview.5 It also is important to ask the patient about major symptoms associated with cardiac disease, such as chest pain, edema, palpitations, syncope, fatigue, and dyspnea. Patients who smoke or have diabetes, hypertension, dyslipidemia, obesity, or metabolic syndrome should be counseled that these diseases not only increase risk for adverse outcomes such as myocardial infarction and stroke but also affect the ability to maintain an erection.16 In general, when discussing a patient’s ability to obtain an erection, there are specific aspects of the history that suggest the problem is vascular. A gradual onset of ED is indicative of vascular etiology. Weak noncoital erections and inconsistent early morning erections suggest abnormal vascular functioning.11 The patient’s sexual partner should be included in the interview and can help explain the patient’s difficulty in obtaining or maintaining an erection, along with sexual technique and any other sexual problems the couple may be facing.17 Physical Examination

The physical examination should start with an assessment of the vital signs. If the patient has tachycardia (pulse >100 beats per minute), hypertension (blood pressure ≥130/80 mm Hg), or tachypnea (respiratory rate >20 breaths per minute), then a more detailed cardiovascular examination should be performed.18 The patient’s waist circumference and BMI should be assessed. All of the peripheral pulses should be palpated and documented for signs of vascular disease. Cardiac auscultation along with auscultation for carotid, aortic, renal, and iliac bruits should be performed.19

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 13

CARDIOVASCULAR HEALTH: ERECTILE DYSFUNCTION

Having an understanding of the relationship between ED and CVD may lead more men to openly discuss their sexual history.

A full urologic examination should be performed, including inspection of the testes and penis for any anatomical abnormalities. Assessment of the bulbocavernosus reflex and anal sphincter tone is important for evaluating the sacral neural outflow.17 A detailed physical examination and thorough history of present illness are key in determining a vascular etiology of ED. The workup for a patient with ED often includes assessment of potential hormonal and psychologic etiologies, but many primary care providers and urologists overlook vascular etiology. A standard cardiovascular assessment should include blood work, including fasting glucose, glycated hemoglobin A1c, lipid panel, creatinine, and serum testosterone, as well as an electrocardiogram.20 The severity of ED is measured using the International Index of Erectile Function (IIEF) or the simplified International Index of Erectile Function (IIEF-5). The IIEF is a validated selfadministered questionnaire that is a highly specific and sensitive measurement of ED severity.21 Questions in the IIEF assess confidence, penetration ability, maintenance of erection, and satisfaction after sexual intercourse.The responses are calculated, with the ED classified as mild, mild-moderate, moderate, or severe.22 Color Doppler ultrasonography is another diagnostic tool that allows for visualization of arterial insufficiency or other vascular etiology of ED.10 This assessment is performed by giving the patient a pharmaceutical agent that causes an erection, followed by ultrasonography of the left and right cavernosal arteries. Many providers use ultrasonography to determine cavernosal artery flow velocities to accurately characterize arterial integrity.12 This allows for identification of hemodynamic instability causing ED. Doppler ultrasound showed a high sensitivity (100%) and specificity (78%) in diagnosing vascular ED in a prospective study.12 Ultrasound findings also can detect the severity of atherosclerotic activity within the penile artery, which may be an indicator of systemic CVD.12 Penile vasculature is small, making it a particularly sensitive marker of systemic vascular disease; smaller arteries often are affected earlier than larger arteries in vascular disease. The diameter of penile arteries is usually 1 to 2 mm compared with 3 to 4 mm for coronary arteries and 5 to 7 mm for carotid arteries. Vessel size theory suggests that an atherosclerotic plaque should occlude and affect the penile artery earlier than a carotid or coronary artery.6 Treatment of Erectile Dysfunction

A variety of medical and nonmedical options can be used to treat vascular ED. Lifestyle changes, such as weight loss,

exercise, dietary changes, cessation of smoking, and reduced alcohol consumption, help treat ED and prevent the development of CVD. These modifiable behaviors should be the first interventions addressed with patients to improve their ED and their cardiovascular health.23 A longitudinal study found that men who initiated physical activity for the first time in midlife had a reduced risk for ED compared with those who remained sedentary (odds ratio, 0.3; 95% CI, 0.1-0.6). One-third of men with ED at baseline were able to improve sexual function through lifestyle changes alone.24 Younger men with vascular ED, in particular, should be counseled on their increased risk for atherosclerosis and educated about lifestyle changes that can lower the risk for CVD and mortality and improve quality of life. For example, the risk for death from CVD declines by half after 5 years of stopping smoking. Thus, smoking cessation should be encouraged in the younger population.25 Phosphodiesterase type 5 (PDE5) inhibitors have been proven to be effective in improving ED in patients with cardiovascular risk factors or CVD.These medications allow for corporeal vascular relaxation and penile erection during sexual stimulation.26 This class of medications also has been shown to improve cardiovascular functioning by increasing the ischemic threshold.27 Three PDE5 inhibitors have been approved by the US Food and Drug Administration: sildenafil, tadalafil, and vardenafil. The drugs are the mainstay of the pharmacologic treatment for ED and have been shown to improve hypertension and endothelial changes in patients with CVD.19 These drugs do not increase the risk for cardiovascular events, such as ischemia, myocardial infarction, and myocardial hypertrophy, and can be safely coadministered with antihypertensive medications, statins, and most other medications.

However, patients should avoid taking nitrates while taking PDE5 inhibitors because a severe drop in blood pressure may occur if these agents are used together.28 Aspirin, a medication known for its antiplatelet activity, also has been studied in patients with ED. In a study comparing aspirin and tadalafil, both medications were proven effective in the treatment of vascular ED; however, a combination of tadalafil and aspirin showed greater efficacy compared with aspirin or tadalafil alone.29 In addition, the analgesic and anti-inflammatory effects of aspirin decrease side effects of tadalafil, such as headache, back pain, extremity pain, flushing, and myalgia. Aspirin also may delay the onset of penile atherosclerosis by inhibiting platelet activity, reducing

14 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

Patients with any sexual dysfunction should be screened for cardiovascular disease and educated promptly about lifestyle management. proinflammatory mediators, and decreasing vascular smooth muscle cell proliferation.29 Low intensity shock-wave therapy (LISWT) is a more invasive treatment option for men with vascular ED. While the mechanism of action of LISWT is unclear, it is believed that the compression and negative pressures created by this therapy lead to shear stress on cell membranes, causing an increased expression of vascular endothelial growth factor and resulting in neovascularization of penile arteries.30 For patients taking β-blockers for heart failure or hypertension who experience ED, practitioners should consider nebivolol, a β-blocker that is less likely to cause difficulty with obtaining and maintain an erection.19

7. Dzenkeviciute V, Petrulioniene Z, Rinkuniene E, Sapoka V, Petrylaite M, Badariene J. Cardiorenal determinants of erectile dysfunction in primary prevention: a cross-sectional study. Med Princ Pract. 2018;27(1):73-79. doi:10.1159/000484949 8. Shah NP, Cainzos-Achirica M, Feldman DI, et al. Cardiovascular disease prevention in men with vascular erectile dysfunction: the view of the preventive cardiologist. Am J Med. 2016;129(3):251-259 doi:10.1016/j. amjmed.2015.08.038 9. Banks E, Joshy G, Abhayaratna WP, et al. Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalisation and all-cause mortality: a prospective cohort study. PLoS Med. 2013;10(1): e1001372. doi:10.1371/ journal.pmed.1001372 10. Deveci S, O’Brien K, Ahmed A, Parker M, Guhring P, Mulhall JP. Can the International Index of Erectile Function distinguish between

Conclusion

organic and psychogenic erectile function? BJU Int. 2008;102(3):354-356.

Healthcare providers should discuss cardiovascular risk factors in all patients with ED. Men with any sexual dysfunction should be screened for CVD and educated promptly about lifestyle management. Early detection and comanagement of CVD risk factors in men with ED is beneficial to promote sexual well-being and prevent CVD.5 ■

doi:10.1111/j.1464-410X.2008.07610.x 11. Same RV, Miner MM, Blaha MJ, Feldman DI, Billups KL. Erectile dysfunction: an early sign of cardiovascular disease. Curr Cardiovasc Risk Rep. 2015;9(49). doi.10.1007/s12170-015-0477-y 12. Yildirim D, Bozkurt IH, Gurses B, Cirakoglu A. A new parameter in the diagnosis of vascular erectile dysfunction with penile Doppler ultrasound : cavernous artery ondulation index. Eur Rev Med Pharmacol Sci.

Melissa Long, PA-C, is a recently graduated physician assistant currently working at Doctors Urology and Pelvic Health Specialists in Augusta, Georgia. E. Rachel Fink, MPA, PA-C, is a physician assistant at Augusta Urology Associates and an assistant professor in the Physician Assistant Program at Augusta University.

2013;17(10):1382-1388.

13. Ponholzer A, Temml C, Rauchenwald M, Madersbacher S. Vascular risk factors and erectile dysfunction in healthy men. Int J Impot Res. 2006;18(5):489-493. doi:10.1038/sj.ijir.3901468 14. Solomon H, Man JW, Jackson G. Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator.

References

Heart. 2003;89(3):251-253. doi:10.1136/heart.89.3.251

1. Jackson G, Boon N, Eardley I, et al. Erectile dysfunction and coronary artery

15. Pohjantähti-Maaroos H, Palomäki A. Comparison of metabolic

disease prediction: evidence-based guidance and consensus. Int J Clin Pract.

syndrome subjects with and without erectile dysfunction—levels of

2010;64(7):848-857. doi:10.1111/j.1742-1241.2010.02410.x

circulating oxidised LDL and arterial elasticity. Int J Clin Pract. 2011;65(3):

2. Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile

274-280. doi:10.1111/j.1742-1241.2010.02595.x

dysfunction in the US. Am J Med. 2007;120(2):151-157. doi:10.1016/j.

16. Swap CJ, Nagurney JT. Value and limitations of chest pain history in the

amjmed.2006.06.010

evaluation of patients with suspected acute coronary syndromes. JAMA.

3. Nguyen HMT, Gabrielson AT, Hellstrom WJG. Erectile dysfunction in

2005;294(20):2623-2629. doi:10.1001/jama.294.20.2623

young men—a review of the prevalence and risk factors. Sex Med Rev.

17. Irwin GM. Erectile dysfunction. Prim Care. 2019;46(2):249-255.

2017;5(4):508-520. doi:10.1016/j.sxmr.2017.05.004

doi:10.1016/j.pop.2019.02.006

4. Pastuszak AW. Current diagnosis and management of erectile dysfunction.

18. Schwartz BG, Kloner RA. How to save a life during a clinic visit for

Curr Sex Health Rep. 2014;6:164-176. doi.10.1007/s11930-014-0023-9

erectile dysfunction by modifying cardiovascular risk factors. Int J Impot Res.

5. Walczak MK, Lokhandwala N, Hodge MB, Guay AT. Prevalence of

2009;21(6):327-335. doi:10.1038/ijir.2009.38

cardiovascular risk factors in erectile dysfunction. J Gend Specif Med.

19. Nehra A, Jackson G, Miner M,,et al. The Princeton III Consensus

2002;5(6):19-24.

recommendations for the management of erectile dysfunction and

6. Inman BA, Sauver JL, Jacobson DJ, et al. A population-based, longitudinal

cardio­vascular disease. Mayo Clin Proc. 2012;87(8):766-778. doi:10.1016/j.

study of erectile dysfunction and future coronary artery disease. Mayo Clin

mayocp.2012.06.015

Proc. 2009;84(2):108-113. doi:10.4065/84.2.108

Continues on page 20

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 15

FEATURE: NATALIE REED, PA-C; KELLY S. REED, PharmD, MPA, PA-C

The Impact of Obesity on Knee OA Symptoms and Surgical Outcomes Weight loss is associated with reduced pain, improved function, and better quality of life in patients with knee OA who are overweight or obese.

O

steoarthritis (OA), or degenerative joint disease, is the most common form of arthritis, affecting more than 32.5 million adults in the United States.1 Osteoarthritis results from damage to or breakdown of cartilage between bones, with the knee being the most common lower-limb joint affected by OA. The prevalence of OA significantly increases with age.1

© ZEPHYR / SCIENCE SOURCE

Risk Factors for Knee OA

The knee is the most common lower-limb joint affected by OA.

Knee OA is a multifactorial disease, with many risk factors playing a role in symptomatic findings and disease progression. Risk factors for knee OA include obesity, physical stress at work, previous trauma or injury to the knee, genetics, and gender (occurs more commonly in women than men).1,2 Common knee surgeries, such as anterior cruciate ligament (ACL) repair and arthroscopic meniscal surgery, may increase a patient’s risk of developing OA,3 in part because of alterations in gait after surgery. Evidence also suggests that varus malalignment increases the risk of developing OA in the medial tibiofemoral aspect of the knee.4 In patients who are obese, increased compressive load on the medial compartment during weight-bearing activities can result in medial tibiofemoral OA.4 It is important for primary care providers to educate their patients about modifiable risk factors for knee OA, such as obesity, so that patients can incorporate changes into their daily routine to improve symptoms of knee pain.

16 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

Symptoms and Diagnosis of Knee OA

Chief complaints from patients with knee OA may include, but are not limited to, knee pain (including at night), loss of function, stiffness, swelling, decreased range of motion, limitations in activities of daily living, and disability.1 A thorough evaluation of a patient’s history can help identify risk factors or potential causes of knee OA. Clinical and physical examination findings also should be considered when diagnosing knee OA.1 Radiographs of the knee in patients with OA show cartilage loss and the resultant narrowing of the joint space and bone spurs around the joint (Figure).5 However, symptom severity in knee OA does not always correspond with radiologic findings.5 Pain is a subjective finding, making it difficult to determine why some people with OA are more symptomatic than others.

Once a diagnosis is made, it is important to identify the best treatment option for each patient.

Treatment Options for Knee OA

Osteoarthritis is a chronic, progressive disease, and treatment goals are targeted toward managing symptoms and slowing disease progression. A wide variety of conservative treatment options are available for knee OA.6-8 First-line pharmacologic treatment options for knee OA include topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroid injections.8 However, these options may be limited by adverse effects and are not recommended for long-term use.8 Other recommended treatments include acetaminophen, duloxetine, topical capsaicin, and tramadol.8 Nonpharmacologic options such as lifestyle recommendations — exercise (walking, strength training, neuromuscular training, and aquatic exercise), tai chi, tibiofemoral knee braces, canes, and weight loss — are strongly recommended for people with knee OA. Alternative therapies that may reduce OA pain complaints include acupuncture, cognitive behavioral therapy, kinesiotaping, patellofemoral braces, radiofrequency ablation, thermal interventions, and yoga.8 The therapeutic effectiveness of these alternative therapies, however, has not been confirmed.7,8 When knee OA becomes refractory to conservative treatment measures and a patient’s quality of life is affected, surgical options should be considered. Several surgical options are considered curative treatments for knee OA. Common surgeries to treat knee OA include total knee replacement (TKR), unicompartmental knee replacement, osteotomy, arthroscopy, and cartilage repair.6 Multiple variables must be considered when determining which treatment option or surgical procedure is most

appropriate for a patient. Weight management interventions are an important step, regardless of whether a patient undergoes conservative or surgical treatment for knee OA. The Role of Weight Loss in OA Management

Obesity is a serious health problem that increases a patient’s risk for many chronic diseases, including joint pain and knee OA. In 2018, the prevalence of obesity in the United States was 42.4%.8 Patients with a BMI ≥30 have a 7-fold increased risk of developing knee OA.2 Weight loss is a healthy way to manage symptoms associated with knee OA. Research shows that weight loss is associated with reduced pain, improved function, and better quality of life in patients with knee OA who are overweight or obese.9,10 There is a strong, consistent relationship between obesity and the development of severe OA knee pain; clinicians can use this information to educate patients about the importance of weight loss to modify the disease course.11 Clinicians should educate patients about how much weight they may need to lose to see an improvement in knee OA symptoms.

Messier et al found that for every 1 pound lost, 4 pounds of stress are unloaded off the knees.12 A body weight reduction of 1% has been associated with a 2.8% improvement in function, pain, and stiffness, as measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scale.10 Thus, overweight or obese patients with knee OA who reduce their weight by 10% could see a 28% decline in knee OA pain and symptoms.10 It is important for patients to understand that weight loss will not reverse the disease process but can alter the severity of their symptoms by reducing the load on the knees.

Daugaard showed that patients with obesity who lost a substantial amount of weight (mean, 12 kg) reduced their pain

Articular Cartilage

Bone Spurs

Meniscus

Cartilage Loss

Normal Joint Space

Joint Space Narrowing

Reproduced with permission from OrthoInfo. © American Academy of Orthopaedic Surgeons. https://orthoinfo.org/

FIGURE. The physiologic changes between a normal knee (left) and a knee with osteoarthritis (right). 5

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 17

OSTEOARTHRITIS AND OBESITY

First-line treatments for knee OA include topical or oral nonsteroidal anti-inflammatory drugs and corticosteroid injections. level.13 However, the inflammation seen on dynamic contrastenhanced magnetic resonance imaging was unchanged from the start of the study.

Weight loss also can help prevent the progression of mild knee pain to severe, debilitating knee pain. Jinks et al found that 19% of new cases of severe knee pain that developed over the 3-year study period in patients who were overweight or obese could have been avoided by a shift downward in BMI category.11 This demonstrates that weight loss is an effective treatment option to improve quality of life and delay surgical intervention. Early intervention by clinical providers focused on educating patients about the benefits of weight loss can help those with knee OA maintain the ability to continue their normal daily activities without disabling pain.

Obesity and Surgical Outcomes

When daily functioning is affected by severe OA pain that is refractory to conservative approaches, surgical intervention becomes a viable option.Total knee replacement is an invasive procedure, and providers and patients must evaluate the risks and benefits of this surgery. For patients who eventually need surgical intervention for knee OA, weight loss also leads to improved outcomes after TKR surgery.

Patients with obesity are at increased risk for surgical revision.14,15 Surgical revisions can be required after loosening or wear of 1 or more components of the prosthetic joint.14 Higher revision rates in patients with obesity have been attributed to increased compressive forces on the joint due to excess weight. Surgical revision of a TKR also may be needed after complications from an infected prosthetic joint.14 Such infections after TKR are more common in patients with obesity compared with patients without obesity.14,15 This is, in part, because obesity is associated with reduced subcutaneous tissue oxygenation, which is associated with higher rates of wound infection.16 The severity of potential postoperative infections can range from a superficial wound infection to deep infection of the prosthetic joint. Studies have shown that patients with obesity who undergo TKR are at increased risk for both deep infections and TKR revisions.15 Despite the possibility of complications, TKR has been proven to improve functional outcomes in patients with and without obesity.

How to Help Patients Lose Weight

When addressing weight loss with patients, it is important to provide them with feasible weight-loss options that can help

them achieve their goals. Clinicians must assess each patient’s needs and access to resources to help them achieve optimal outcomes when they are attempting to lose weight.

Initial weight-loss recommendations should include information on how patients can increase physical activity while also modifying their diet to reduce caloric intake. An open discussion about obstacles to achieving weight loss will allow patients and providers to come up with feasible lifestyle modifications patients can incorporate into their daily routines.

Patients have reported that lack of time and lack of accessibility to an exercise facility are 2 of the most common barriers preventing them from losing weight.17 For patients without access to a gym, clinicians can provide home exercises that require little equipment. For patients who do have access to exercise facilities, aquatic therapy has proven to be an effective option for individuals with knee OA.8 Patients who have concerns about how they will achieve exercise or who experience low physical self-esteem may benefit from group exercise programs or a personal trainer.

For patients to achieve weight loss, they must address diet as well as exercise habits. Information about healthy eating and cost-efficient healthy recipes can provide patients with the skills and resources needed to incorporate healthy eating habits into their daily routines. In a survey conducted at an orthopedic clinic, 61% of participants with obesity reported that they would be most interested in information about

POLL POSITION Which of the following statements is not true about knee OA? ■ Weight loss slows progression of OA

18.95%

■ Obesity increases risk for postoperative infection ■ Patients with BMI ≥30 have 10-fold risk for OA ■ A 10% loss of weight equals 28% decline in pain

31.93% 20.35% 28.77%

For more polls, visit ClinicalAdvisor.com/Polls.

18 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

When addressing weight loss with patients, it is important to provide them with feasible options that can help them achieve their goals. healthy eating when receiving information from a healthcare professional about weight loss.18 Teaching patients how to moderate portions and eliminate unhealthy foods from their diet also is positively associated with successful weight loss. Some patients may benefit from a referral to a registered dietitian when starting their weightloss journey. Reducing caloric intake by decreasing sugar consumption, increasing fruit and vegetable intake, controlling portions, and increasing physical activity provides patients with the greatest chance of achieving weight loss.19 Pharmacotherapy is an option for patients with a high BMI and weight-related comorbidities who have tried and failed to lose weight with exercise and diet alone. A recent meta-analysis of randomized controlled trials found that the following antiobesity medications indicated for long-term use are associated with a significant reduction in body weight: liraglutide, lorcaserin, naltrexone/bupropion, orlistat, and phentermine/extended-release topiramate.20 Primary care providers should discuss these options with their patients to determine whether these options are appropriate.

When conservative treatment options have failed, referral to a bariatric surgeon may be warranted.

Weight-loss methods should be determined based on what is best for the patient and what is most feasible in a given timeframe. Primary care providers can help guide patient education about weight loss and treatment options for patients with knee OA considering TKR surgery. ■ Natalie Reed, PA-C, is a recent graduate of the Physician Assistant Program at Augusta University in Augusta, Georgia, and is currently working in orthopedics in Atlanta. Kelly S. Reed, PharmD, MPA, PA-C, is an assistant professor in the Physician Assistant Program at Augusta University.

References 1. Centers for Disease Control and Prevention. Osteoarthritis (OA).

Updated July 27, 2020. Accessed February 5, 2021. https://www.cdc.gov/ arthritis/basics/osteoarthritis.htm 2. Toivanen AT, Heliövaara M, Impivaara O, et al. Obesity, physically demanding work and traumatic knee injury are major risk factors for knee osteo­arthritis—a population-based study with a follow-up of 22 years.

Rheumatology. 2010;49(2):308-314. doi:10.1093/rheumatology/kep388 3. Capin JJ, Khandha A, Zarzycki, Manal K, Buchanan TS, Synder-Mackler L. Gait mechanics after ACL reconstruction differ according to medial meniscal treatment. J Bone Joint Surg Am. 2018;100(14):1209-1216.

Conclusion

doi:10.2106/JBJS.17.01014

Weight loss can be a beneficial and conservative approach to treating patients who are overweight or obese and have knee OA.Weight loss can improve knee pain, overall function, and quality of life. It is important for clinicians to address weight loss at all encounters with their patients and help set realistic goals. Discussion about patient goals and perceived barriers to weight loss can help providers offer patients resources they need to best meet their individual goals. Most studies show that at least a 10% weight reduction is needed to improve knee pain in OA.9,10,21 If a 10% loss is achieved, encouraging patients to continue their weight-loss journey can help further reduce the load on their knees.

In patients who undergo surgery, obesity is associated with an increased risk for postoperative infection as well as failure of the prosthesis requiring revision surgery.14,15 Thus, for patients undergoing TKR, clinicians may require weight loss before surgery, particularly if patients are morbidly obese. Although it can be challenging for providers and patients to discuss weight loss, it is in the best interest of patients and will contribute to optimal surgical outcomes. Patients who receive weight-loss counseling are 4 times more likely to achieve success after surgery compared with those who do not receive counseling.22

4. Wei J, Gross D, Lane NE, et al. Risk factor for heterogeneity for medial and lateral compartment knee osteoarthritis: analysis of two prospective cohorts. Osteoarthritis Cartilage. 2019;27(4):603-610. doi:10.1016/j. joca.2018.12.013 5. Arthritis of the knee. Orthoinfo. Updated June 2014. Accessed February 5, 2021. https://orthoinfo.aaos.org/en/diseases--conditions/ arthritis-of-the-knee/.

6. Bedson J, Croft PR. The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature. BMC Musculoskelet Disord. 2008;9:116. doi:10.1186/1471-2474-9-116 7. Brown GA. AAOS clinical practice guideline: treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. J Am Acad Orthop Surg.

2013;21(9):577-579. doi:10.5435/JAAOS-21-09-577 8. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 2020;72(2): 149-162. doi:10.1002/acr.24131 9. Messier SP, Mihalko SL, Legault C, et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA. 2013;310(12):1263-1273. doi:10.1001/ jama.2013.277669

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 19

OSTEOARTHRITIS AND OBESITY

10. Christensen R, Astrup A, Bliddal H. Weight loss: the treatment of

16. Kabon B, Nagele A, Reddy D, et al. Obesity decreases perioperative

choice for knee osteoarthritis? A randomized trial. Osteoarthritis Cartilage.

tissue oxygenation. Anesthesiology. 2004;100(2):274-280. doi:10.1097/

2005;13(1):20-27. doi:10.1016/j.joca.2004.10.008

00000542-200402000-00015

11. Jinks C, Jordan K, Croft P. Disabling knee pain—another consequence

17. Wilcox S, Der Ananian C, Abbott J, et al. Perceived exercise barriers,

of obesity: results from a prospective cohort study. BMC Public Health.

enablers, and benefits among exercising and nonexercising adults with

2006;6:258. doi:10.1186/1471-2458-6-258

arthritis: results from a qualitative study. Arthritis Rheum. 2006;55(4):

12. Messier SP, Gutekunst DJ, Davis C, DeVita P. Weight loss

616-627. doi:10.1002/art.22098

reduces knee-joint loads in overweight and obese older adults with

18. Howarth D, Inman D, Lingard E, McCaskie A, Gerrand C. Barriers to

knee osteoarthritis. Arthritis Rheum. 2005;52(7):2026-2032. doi:10.1002/

weight loss in obese patients with knee osteoarthritis. Ann R Coll Surg Engl.

art.21139

2010;92(4):338-340. doi:10.1308/003588410X12628812458653

13. Daugaard CL, Henriksen M, Riis RGC, et al. The impact of a signifi-

19. Varkevisser RDM, van Stralen MM, Kroeze W, Ket JCF, Steenhuis IHM.

cant weight loss on inflammation assessed on DCE-MRI and static MRI

Determinants of weight loss maintenance: a systematic review. Obes Rev.

in knee osteoarthritis: a prospective cohort study. Osteoarthritis Cartilage.

2019;20(2):171-211. doi:10.1111/obr.12772

2020;28(6):766-773. doi:10.1016/j.joca.2020.02.837

20. Singh AK, Singh R. Pharmacotherapy in obesity: a systematic review

14. Boyce L, Prasad A, Barrett M, et al. The outcomes of total knee

and meta-analysis of randomized controlled trials of anti-obesity drugs.

arthroplasty in morbidly obese patients: a systematic review of the

Expert Rev Clin Pharmacol. 2020;13(1):53-64. doi:10.1080/17512433.

literature. Arch Orthop Trauma Surg. 2019;139(4):553-560. doi:10.1007/

2020.1698291

s00402-019-03127-5

21. Atukorala I, Makovey J, Lawler L, et al. Is there a dose-response relationship

15. Kerkhoffs GMMJ, Servien E, Dunn W, Dahm D, Bramer JA,

between weight loss and symptom improvement in persons with knee osteo-

Haverkamp D. The influence of obesity on the complication rate

arthritis? Arthritis Care Res. 2016;68(8):1106-1114. doi:10.1002/acr.22805

and outcome of total knee arthroplasty: a meta-analysis and systematic

22. Centers for Disease Control and Prevention. Weight loss for adults with

literature review. J Bone Joint Surg. 2012;94(20):1839-1844. doi:10.2106/

arthritis.. Updated September 9, 2020. Accessed February 5, 2021. https://

JBJS.K.00820

www.cdc.gov/arthritis/communications/features/arthritis-weight-loss.html

Erectile Dysfunction

25. Prabhat J. The hazards of smoking and the benefits of cessation: a critical

Continued from page 15

summation of the epidemiological evidence in high-income countries. eLife.

2020;9:e49979. doi:10.7554/eLife.49979

20. Schroeder S, Enderle MD, Ossen R, et al. Noninvasive determination

26. Gazzaruso C, Solerte SB, Pujia A, et al. Erectile dysfunction as a

of endothelium-mediated vasodilation as a screening test for coronary

predictor of cardiovascular events and death in diabetic patients with

artery disease: pilot study to assess the predictive value in compari-

angiographically proven asymptomatic coronary artery disease: a potential

son with angina pectoris, exercise electrocardiography, and myocardial

protective role for statins and 5-phosphodiesterase inhibitors. J Am Coll

perfusion imaging. Am Heart J. 1999;138(4 Pt 1):731-739. doi:10.1016/

Cardiol. 2008;51(21):2040-2044. doi:10.1016/j.jacc.2007.10.069

s0002-8703(99)70189-4

27. Thadani U, Smith W, Nash S, et al. The effect of vardenafil, a potent and

21. Tang Z, Li D, Zhang X, et al. Comparison of the simplified

highly selective phosphodiesterase-5 inhibitor for the treatment of erectile

International Index of Erectile Function (IIEF-5) in patients of erectile

dysfunction, on the cardiovascular response to exercise in patients with

dysfunction with different pathophysiologies. BMC Urol. 2014;14:52.

coronary artery disease. J Am Coll Cardiol. 2002;40(11):2006-2012.

doi:10.1186/1471-2490-14-52

doi:10.1016/s0735-1097(02)02563-9

22. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peñ BM. Development and

28. Vlachopoulos C, Ioakeimidis N, Rokkas K, Stefanadis C. Cardiovascular

evaluation of an abridged, 5-item version of the International Index of Erectile

effects of phosphodiesterase type 5 inhibitors. J Sex Med. 2009;6(3):658-674.

Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res.

doi:10.1111/j.1743-6109.2008.01107.x

1999;11(6):319-326. doi:10.1038/sj.ijir.3900472

29. Bayraktar Z, Albayrak S. Efficacy and safety of combination of tadalafil

23. Esposito K, Giugliano F, Maiorino MI, Giugliano D. Dietary factors,

and aspirin versus tadalafil or aspirin alone in patients with vascular erectile

Mediterranean diet and erectile dysfunction. J Sex Med. 2010;7(7):2338-2345.

dysfunction: a comparative randomized prospective study. Int Urol Nephrol.

doi:10.1111/j.1743-6109.2010.01842.x

2019;51(9):1491-1499. doi:10.1007/s11255-019-02211-4

24. Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB,

30. Brunckhorst O, Wells L, Teeling F, Muir G, Muneer A, Ahmed K.

McKinlay JB. Modifiable risk factors and erectile dysfunction: can life-

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style changes modify risk? Urology. 2000;56(2):302-306. doi:10.1016/

therapy for vasculogenic erectile dysfunction. Int Urol Nephrol [Internet].

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2019;51(5):773-781. doi:10.1007/s11255-019-02127-z

20 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

Dermatology Clinic CASE #1

Inflammation and Redness of the Fingernail Folds DINA ZAMIL, BS; TARA L. BRAUN, MD; CHRISTOPHER RIZK, MD

A 35-year-old woman presents to the dermatology clinic with inflammation of her fingernails that first appeared 5 months ago and recently worsened. She reports wearing acrylic nails for the last year, removing them just before the clinic visit.

On examination, the patient has erythema and swelling of the lateral nail folds and hyperpigmentation of the proximal nail folds of all fingers on her right hand. Examination also reveals nail dystrophy, onycholysis, and an absence of cuticles.

She has not tried any treatments for this condition.

What is your diagnosis? Turn to page 22

CASE #2

Flat-Topped Papule With Wickham Line DINA ZAMIL, BS; TARA L. BRAUN, MD; CHRISTOPHER RIZK, MD

A 32-year-old woman presents with an itchy rash that began 3 months ago. She has a history of anxiety but otherwise no known medical conditions. She has tried over-the-counter hydrocortisone cream to treat the rash, finding some relief from the itchiness, but the rash continues to spread. She has no known allergies and has not changed her skin care products or medications. On examination, the patient has dark purple and gray flat-topped papules with fine gray-white streaks on her flexural wrists, dorsal hands, elbows, ankles, and dorsal feet.

What is your diagnosis? Turn to page 23 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 21

Dermatology Clinic CASE #1

Chronic Paronychia

Chronic paronychia is an inflammatory condition of the nail folds lasting longer than 6 weeks.1 Descriptions of paronychia in the medical literature date back to 1891.2 Chronic paronychia primarily results from environmental exposures, irritants, and allergens.1,3,4 More common in women, chronic paronychia typically affects multiple digits, especially the second and third digits of the dominant hand.4,5 The condition commonly occurs in patients aged 40 to 49 years, with a mean age at diagnosis of 43 years.6,7 Etiology and Risk Factors

Chronic paronychia results from inflammation of the perionychium of the nail. It is usually caused by damage to the cuticle that disrupts the barrier between the nail plate and the skin, allowing invasion of fungus or bacteria. Generally, any activity that subjects the nail bed to trauma increases the risk for paronychia. For example, frequent manicures and wearing artificial nails, nail biting, hangnail manipulation, and ingrown nails are risk factors for chronic paronychia.1 Chronic paronychia also is associated with continuous exposure to environmental irritants and, thus, is thought to be a form of hand dermatitis.3,5 Chefs, nurses, swimmers, house cleaners, dishwashers, and barbers are more likely to develop chronic paronychia due to repeated exposure to chemicals, acids, or alkalis.1,3,5,6 People who handle food may develop chronic paronychia due to food hypersensitivity reactions.3 Other populations predisposed to chronic paronychia include patients with diabetes, patients on antiretroviral therapy for HIV, and patients who are immunosuppressed.3,5 Less common causes of chronic paronychia include Raynaud disease, papulosquamous disorders, cancers, and drug toxicity.3 Candida albicans commonly is implicated in the etiology of chronic paronychia and is found in 40% to 95% of fungal cultures of patients with chronic paronychia.5 However, research suggests that topical steroids are more effective than systemic antifungal therapy at treating chronic paronychia.3,5,8 It is thought that Candida albicans infects the nail bed secondary to an existing inflammatory condition.3,5 Diagnosis of Chronic Paronychia

Clinically, chronic paronychia presents with cuticle damage, pain, and swelling and erythema of the nail fold. The condition often

affects multiple digits.1,5 Nails often are thick and discolored.

Damage to the nail matrix can lead to nail plate abnormalities, such as pitting, onychomadesis, longitudinal ridging, and Beau lines, whereas damage to the nail bed can lead to onycholysis.

Lateral margins of the nail plate may even become green, suggesting secondary infection with Pseudomonas aeruginosa.3 The differential diagnosis for chronic paronychia includes several cancers that should be considered when the symptoms affect a single digit, the condition does not respond to treatment, or patients have a history of cancer.1,3,5 The following cancers may cause nail damage: malignant melanoma, squamous cell carcinoma, Kaposi sarcoma, bronchogenic carcinoma, leukemia cutis, subungual keratoacanthoma, myeloma-associated systemic amyloidosis, and digital papillary adenocarcinoma.5 Other conditions that may mimic chronic paronychia include herpetic whitlow, psoriasis, eczema, granuloma annulare, Reiter syndrome, dermatomyositis, pyogenic granuloma, hematoma from pulse oximetry, and, rarely, pemphigus vulgaris and food hypersensitivity.1 Treatment of Chronic Paronychia

Chronic paronychia is diagnosed based on clinical findings and patient history, which generally reveal exposure to irritants or other risk factors.1,5 Clinical history also may reveal episodic worsening of symptoms of paronychia after exposure to moisture.5 If the practitioner suspects malignancy, a nail biopsy may be needed.5 When infection is suspected, a culture for bacteria, fungi, and atypical mycobacteria may be indicated.5 Acute paronychia differs from chronic paronychia because it persists for less than 6 weeks, typically affects a single digit, and results in greater swelling and erythema.1,5 Chronic paronychia can be managed surgically or nonsurgically.1,3,5 It is essential to counsel the patient about avoidance of environmental triggers, including irritants, allergens, chemicals, nail manipulation, and moisture.3,5 Patients also may be advised, when appropriate, to use rubber gloves, keep nails short, and wear comfortable footwear to avoid toenail damage.3 Patients with diabetes should maintain proper glycemic control.3 Topical corticosteroids are used as first-line treatment and topical antifungals may be added; oral antifungals are not indicated.3,5 Tacrolimus ointment (1%) also can be used as an alternative to topical steroid therapy.3,9 Antibiotics (topical or systemic) may be necessary in the presence of secondary infections.3 Overall, response to therapy is slow, and chronic paronychia can take months to resolve, but patients should be advised to continue to avoid triggers and persist with treatment.3 In patients whose condition is unresponsive to nonsurgical measures, surgery is indicated to remove the inflamed tissue or a portion of the eponychium.3,5

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The patient in this case was counseled to avoid acrylic nails and was prescribed clobetasol ointment twice daily for 2 weeks and ketoconazole cream twice daily for 4 weeks.This treatment helped improve the inflammation around her nails, although the nail dystrophy still was present at her 3-month follow-up visit.

References 1. Leggit JC. Acute and chronic paronychia. Am Fam Physician. 2017;96(1):44-51.

2. Diseases of the fingers : B-paronychia. Hospital (Lond 1886). 1891;10(254):226.

3. Relhan V, Goel K, Bansal S, Garg VK. Management of chronic paronychia.

Indian J Dermatol. 2014;59(1):15-20. doi:10.4103/0019-5154.123482 4. Atış G, Göktay F, Altan Ferhatoğlu Z, et al. A proposal for a new severity index for the evaluation of chronic paronychia. Skin Appendage Disord.

2018;5(1):32-37. doi:10.1159/000489024 5. Shafritz AB, Coppage JM. Acute and chronic paronychia of the hand. J Am Acad Orthop Surg. 2014;22(3):165-174. doi:10.5435/JAAOS-22-03-165 6. Bahunuthula RK, Thappa DM, Kumari R, Singh R, Munisamy M, Parija SC. Evaluation of role of Candida in patients with chronic paronychia. Indian J Dermatol Venereol Leprol. 2015;81(5):485-490. doi:10.4103/0378-6323.158635 7. Chow E, Goh CL. Epidemiology of chronic paronychia in a skin hospital in Singapore. Int J Dermatol. 1991;30(11):795-798. doi:10.1111/j.1365-4362.1991.tb04789.x 8.Tosti A, Piraccini BM, Ghetti E, Colombo MD.Topical steroids versus systemic antifungals in the treatment of chronic paronychia: an open, randomized double-blind and double dummy study. J Am Acad Dermatol. 2002;47(1):73-76. doi:10.1067/mjd.2002.122191 9. Rigopoulos D, Gregoriou S, Belyayeva E, Larios G, Kontochristopoulos G, Katsambas A. Efficacy and safety of tacrolimus ointment 0.1% vs. betamethasone 17-valerate 0.1% in the treatment of chronic paronychia: an unblinded randomized study. Br J Dermatol. 2009;160(4):858-860. doi:10.1111/j.1365-2133.2008.08988.x.

CASE #2

Lichen Planus

Lichen planus (LP) is a relatively common inflammatory dermatosis first discovered in 1869

by Erasmus Wilson,1 although the condition previously was reported as “lichen ruber” by Hebra.1-3 The Greek word leichen refers to tree moss and the Latin word planus means planar, referring to the condition’s characteristic flat-topped appearance.1,3 LP was described further clinically in 1892 and 1895, and its histopathology was first described by Darier in 1909.1

Although LP occurs in people of any ethnic background and both sexes, it is slightly more prevalent in women and is much more common in adults than children.2-5 The incidence of LP is estimated to be less than 1%, and it accounts for up to 1.2% of dermatology referrals.3 However, a form of cutaneous LP, actinic LP, is highly prevalent in tropical regions, such as the Middle East, East Africa, and India.3 Mucosal involvement is present in up to 65% of cases of cutaneous LP and can be the only clinical manifestation in 15% to 35% of patients.2 The etiology of LP is thought to be primarily immunemediated.2-4 Cytotoxic CD8+ T cells attack basal keratinocytes and CD4+ helper T cells recruit cytokines,2,3 leading to increased levels of interleukin (IL)-1α, IL-6, and IL-8.6 Other inflammatory cytokines involved include tumor necrosis factor-α and interferon-γ.6 In the dermis and epidermis, there are increased numbers of dendritic cells expressing FXIIIa and S-100-positive Langerhans cells.2,7 The skin’s basement membrane is damaged by the CD8+ cell-mediated destruction of basal keratinocytes, which then allows more CD8+ cells to infiltrate and continuously attack basal keratinocytes.This cycle is hypothesized to explain the chronic nature of LP.3 LP is associated with a number of viruses such as hepatitis B virus, human herpesviruses 6 and 7, and varicella zoster.3 LP is linked most widely to hepatitis C virus (HCV) infection.3-5 A meta-analysis has shown that patients with LP are 5 times more likely to test positive for HCV than controls.5 In addition, interferon therapy for HCV is linked to LP; some patients experience improvement of LP lesions while on this treatment and others have disease flares.3,4,8 Several familial cases of LP have been reported, suggesting a genetic predisposition.3,5 Other risk factors include certain medications, such as antimalarial drugs, β-blockers, thiazides, angiotensin-converting enzyme inhibitors, and nonsteroidal anti-inflammatory drugs, all of which can trigger lichenoid eruptions.3,4 Anxiety, depression, and stress also are associated with LP.3 Additional conditions linked to LP include thymomas, primary biliary cirrhosis, multiple sclerosis, primary sclerosing cholangitis, diabetes mellitus, ulcerative colitis, and Laugier–Hunziker syndrome.3,6 Classically, LP lesions are characterized by violaceous, flattopped papules. The surfaces of these lesions contain fine, white, reticulated lines referred to as Wickham striae. LP commonly appears on the dorsal hands, flexural aspect of wrists and forearms, shins, and presacral area. LP also may be generalized, although this occurs rarely.

A tool used to identify clinical characteristics of cutaneous LP is the 6 Ps: purple, polygonal, planar, pruritic, papules, and

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Dermatology Clinic plaques.3,4,8 Lesions are often itchy and commonly lead to postinflammatory hyperpigmentation.5 Lesions may display Koebner phenomenon, in which lesions arise on the skin at sites of prior traumatic injury.5 Other clinical variants of LP include actinic, annular, atrophic, bullous, hypertrophic, inverse, linear, and ulcerative LP.2-4,8 Histology of LP characteristically shows compact hyperkeratosis without parakeratosis, wedge-shaped hypergranulosis, basal cell liquefaction, colloid bodies, dense “band-like” inflammatory infiltrate (lymphocytes and histiocytes) in the papillary dermis at the dermoepidermal junction, irregular acanthosis with saw-tooth rete ridges, and pigment incontinence.2,5,6

Cutaneous lichen planus is characterized by the 6 Ps: purple, polygonal, planar, pruritic, papules, and plaques.

Lichenoid drug eruptions potentially can be differentiated from idiopathic LP by the presence of eosinophils and/or plasma cells in the infiltrate, focal parakeratosis, focal interruption of the granular layer, and a deep perivascular infiltrate.2 There are no serum or laboratory tests that can be used to diagnose LP. The condition is diagnosed clinically, and, if needed, diagnosis can be confirmed with a punch biopsy.4-6 When LP is suspected, dermoscopy may be used to look for Wickham striae on the surface of the lesions.2 Clinicians also should examine areas commonly affected by LP, including the nails, scalp, genitalia, and oral mucosa.5 Given its strong association with HCV, serum testing for HCV should be considered in patients diagnosed with LP.5 Several conditions must be considered in the differential diagnosis of LP, such as discoid lupus, erythema dyschromicum perstans, pityriasis rosea, psoriasis, secondary syphilis, and other lichenoid dermatoses.4,8 Unlike LP, lichen nitidus tends to appear in younger patients, rarely involves the oral mucosa, and lacks Wickham striae.1,4,5,8 Lichen striatus primarily occurs in younger patients, and the lesions are generally lighter than those of LP, appearing pink, skin colored, or tan, and often occur as a single linear streak of lesions on an extremity.8 Lichenoid drug eruptions are most difficult to differentiate from cutaneous LP because the conditions may appear identical clinically and histologically. Lichenoid drug eruptions potentially may be distinguished from idiopathic LP by the following: generalized and symmetric distribution, photo distribution, lack of Wickham striae, and greater psoriasiform or eczematous morphology.3 Chronic graft-vs-host

disease (GVHD) after stem cell transplantation also can result in lesions identical to idiopathic LP.5,8 In cases of suspected drug eruption or GVHD, medication history and medical history, respectively, could help distinguish these conditions from LP.3 Cutaneous LP can resolve on its own after 1 year, but treatment may help lesions resolve more quickly.4,5 Drug-induced LP must be considered in all cases and suspected offending medications should be withdrawn. The first-line therapy for cutaneous LP is potent topical glucocorticoids such as clobetasol. Additional well-described therapies include intralesional and systemic corticosteroids, oral retinoids such as acitretin, phototherapy, topical calcineurin inhibitors, antimalarial agents, and in treatment-resistant cases, oral immunosuppressive agents (eg, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine).2,4,5,8 The condition of the patient in this case was confirmed via punch biopsy, and she was prescribed topical clobetasol ointment. At her 3-month follow-up visit, the active lesions were resolved for the most part, with some residual postinflammatory hyperpigmentation. ■ Dina Zamil, BS, is a medical student at Baylor College of Medicine, Tara L. Braun, MD, is a resident in the Department of Dermatology at Baylor College of Medicine, and Christopher Rizk, MD, is a dermatologist affiliated with Baylor College of Medicine in Houston,Texas.

References 1. Gupta S, Jawanda MK. Oral lichen planus: an update on etiology, pathogenesis, clinical presentation, diagnosis and management. Indian J Dermatol. 2015;60(3):222-229. doi:10.4103/0019-5154.156315 2. Marshman G. Lichen planus. Australas J Dermatol. 1998;39(1):1-11; quiz 12-13. doi:10.1111/j.1440-0960.1998.tb01233.x 3. Tziotzios C, Lee JYW, Brier T, et al. Lichen planus and lichenoid dermatoses: clinical overview and molecular basis. J Am Acad Dermatol. 2018;79(5):789804. doi:10.1016/j.jaad.2018.02.010 4. Katta R. Lichen planus. Am Fam Physician. 2000;61(11):3319-3324, 3327-3328.

5. Le Cleach L, Chosidow O. Clinical practice. Lichen planus. N Engl J Med. 2012;366(8):723-732. doi:10.1056/NEJMcp1103641 6. Lehman JS, Tollefson MM, Gibson LE. Lichen planus. Int J Dermatol.

2009;48(7):682-694. doi:10.1111/j.1365-4632.2009.04062.x 7. Akasu R, From L, Kahn HJ. Lymphocyte and macrophage subsets in active and inactive lesions of lichen planus. Am J Dermatopathol. 1993;15(3):217-223. doi:10.1097/00000372-199306000-00004 8. Shiohara T, Mizukawa Y. Lichen planus and lichenoid dermatoses.

In: Bolognia JL, Schaffer JV, Cerroni L, eds. Dermatology, 4th ed. Elsevier; 2018;11:188-207.

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Dermatologic Look-Alikes Blisters on the Hands DINA ZAMIL, BS;TARA L. BRAUN, MD; CHRISTOPHER RIZK, MD

CASE #1

CASE #2

A 65-year-old man with hypertension presents to the dermatology clinic with a 3-day history of a rash on his arms and trunk.The patient reports having a similar rash 1 year ago that started 2 weeks after he had a tender blister on his lip. On examination, the patient has numerous scattered, target-like lesions with central vesicles on his palms, dorsal hands, forearms, back, and chest. The rash does not involve the mucosa, and the patient has no systemic symptoms. The patient has no food allergies and has no history of any other medical conditions.The rest of the examination is normal.

A 5-year-old girl presents with a 1-day history of fever, sore throat, and rash that started on her hands and feet and has spread to her legs. She has not been able to eat or drink for 24 hours because of throat pain. She attends day care and has 2 older siblings. On examination, the patient has scattered erythematous macules and vesicles with an erythematous base on her palms, lower legs, and soles of the feet. She also has erosions on her buccal mucosa and posterior oral cavity. The child’s parents report that the child has no food allergies or other chronic conditions.

The rest of the physical examination is normal.

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Dermatologic Look-Alikes CASE #1

Erythema Multiforme

Erythema multiforme (EM) is an acute, immune-mediated, hypersensitivity reaction affecting the skin and/or mucosa.1-3 EM, which can be episodic, recurrent, or seasonal, is known classically for its characteristic target-like lesions.1-4 There are 2 types of EM: EM minor, which affects the skin and not the mucosa; and EM major, which involves the mucosa.1,3 Case reports of EM date back to 1884.5 Although EM originally was considered to be closely related to Stevens-Johnson syndrome and toxic epidermal necrolysis, it now is recognized as a separate disease.1-3 The prevalence of EM is unknown but is estimated to be between 0.01% and 1% of the population.1 EM occurs more commonly in young adults aged 20 to 40 years and women and has no racial predilection.1,2 However, a predisposition among certain Asian ethnic groups has been reported.3,6 In 37% of cases, recurrence of EM has been reported; in children, recurrent EM is more common in boys than girls.1-3,7 EM is caused by an immune response targeting small blood vessels in the mucosa and skin.2,3 Approximately 90% of EM cases are linked to infection, most commonly herpes simplex virus (HSV) type 1 and less often HSV type 2.1-3 The second most common infectious agent is Mycoplasma pneumoniae, particularly in children.1 Other viral infections associated with EM include Epstein-Barr virus, influenza virus, hepatitis C virus, cytomegalovirus, enteroviruses, and adenoviruses.2,3 Bacterial infections associated with EM include salmonella, pneumococcus, Mycobacterium leprae, hemolytic streptococcus, Corynebacterium diphtheriae, and Legionella pneumophila.3 Drug-associated EM is reported in less than 10% of cases.1 Medications most commonly associated with EM include antibiotics, antiepileptics, and nonsteroidal anti-inflammatory drugs. Allopurinol, barbiturates, phenothiazines, statins, and tumor necrosis factor-α inhibitors also have been linked to EM.2 Other causative factors include vaccines, autoimmune diseases, cancers, chemicals, and food additives.2,3 EM commonly is found on sunburned or injured skin.1,2 Patients with EM may present with prodromal symptoms of nausea, fever, malaise, cough, and headache 1 to 2 weeks before the development of skin lesions. Systemic symptoms do not occur in most cases of EM minor and may occur in cases of EM major.1-3 Early cutaneous EM lesions typically appear as pink or red papules surrounded by blanching and

may look similar to papular urticaria or insect bites with a symmetrical distribution.1,2 Over time, these papules develop into target-like lesions with a central bulla or crust. Although skin lesions are frequently asymptomatic, mucosal lesions can be extremely painful.2 The upper extremities, especially the forearms and dorsal hands, are the most commonly affected areas.The trunk, palms of the hands, soles of the feet, neck, and face also may be affected.1-3 Patients with EM major may present with edematous, painful lesions in the oral, ocular, or genital mucosa that develop into bullae before becoming shallow erosions.2 Most episodes of EM resolve within 1 to 4 weeks without scarring, though hypo- or hyperpigmentation may be present.2,3 The histology of EM demonstrates apoptotic keratinocytes, superficial dermal edema, vacuolar degeneration of the basal layer, and perivascular inflammatory infiltrates.3,4 Immunofluorescence findings are nonspecific and may show immunoglobulin M (IgM), fibrin, and C3 deposited along blood vessels and fibrin and C3 deposited along the basement membrane.4

Erythema multiforme is the result of an immune response targeting small blood vessels in the mucosa and skin.

The diagnosis of EM is clinical and based on the patient’s history and physical examination.4 Clinicians should pay attention to potential symptoms of prior infection or a history of medication use that may be linked to EM.2,3 Although laboratory findings will not diagnose EM definitively, biopsy, serology, and direct immunofluorescence can be used to rule out other diseases, such as autoimmune blistering diseases and malignancies.2-4 Other conditions in the differential diagnosis include bullous pemphigoid, primary herpetic gingivostomatitis, pemphigus vulgaris, paraneoplastic pemphigus, fixed drug eruptions, hypersensitivity reactions, and pityriasis rosea. Bullous pemphigoid can be differentiated from EM using immunofluorescence and histology. Primary herpetic gingivostomatitis occurs more frequently in young children without a rash.3 Pemphigus vulgaris presents chronically, while EM is acute, and patients with paraneoplastic pemphigus typically have underlying malignancies. Fixed drug eruptions show temporal trends in medication history, and polymorphous drug eruptions result in plaques in sun-exposed areas. Hypersensitivity reactions commonly are localized to the face; urticarial lesions tend not

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Dermatologic Look-Alikes to last more than 24 hours; and pityriasis rosea presents with scaly, erythematous plaques.2,3 The general approach to treating EM is to provide symptomatic therapy and address the underlying cause, if possible.1-3,8 In cases of EM induced by drugs or infection, the offending medication should be discontinued or the infection treated.1,2,8 Topical steroids, oral antiseptics, and antihistamines can be used for acute EM.2 More severe EM cases may require intravenous fluid administration or systemic corticosteroids.2,3 In patients with recurrent EM caused by HSV, antiviral therapy with famciclovir, valacyclovir, or acyclovir for 6 months can help prevent EM recurrence.3 The patient in this case was diagnosed with recurrent EM secondary to HSV infection. Because his lesions were asymptomatic, the episode was treated with supportive care, and the lesions resolved after 2 weeks. He was started on acyclovir for prevention of future episodes of EM.

CASE #2

Hand, Foot, and Mouth Disease

Hand, foot, and mouth disease (HFMD) is a highly contagious, primarily pediatric, viral infection caused by enteroviruses.9-11 Transmitted by respiratory, fecal, and oral droplets, the illness commonly results in oral lesions and vesicular eruptions affecting the palms, soles, and, occasionally, the buttocks and genitals.9,10 First described in the 1950s in Canada and New Zealand,12,13 HFMD initially was reported as a mild, self-limiting infection that resolved spontaneously.9,14,15 HFMD often occurs in outbreaks in the summer and fall or at summer camps and day care centers.9,10,15 Recently, HFMD has received more attention because of the discovery of unusual manifestations, such as dangerous cardiorespiratory and neurologic symptoms.15 HFMD occurs most commonly in children younger than 10 years of age, with the largest concentration in children younger than 4 years of age, and less commonly in adults.9,10,14 HFMD affects the sexes equally.9,10 In some countries, such as China, health professionals continuously monitor for HFMD. However, the true incidence of HFMD is underreported in most countries because cases with atypical manifestations are not diagnosed accurately.15 Although the disease is rarely fatal in the United States, complications of HFMD in China have

resulted in higher fatality rates. Outbreaks and HFMD-related deaths also are more frequent in India, Malaysia,Vietnam, and Cambodia because of a lack of access to clean water.14 More than 90% of HFMD cases are caused by enterovirus A.15 Although coxsackievirus A16 is implicated most often, coxsackievirus A6 has been associated with more recent outbreaks worldwide and is associated with HFMD in adults.10,11,15 Since 2010, coxsackievirus A10 has played a greater role in HFMD outbreaks in Europe, Asia, and North America.14,15 Enteroviruses causing HFMD incubate for 3 to 6 days, and, although individuals with HFMD are most contagious in the first week of illness, the virus can remain in the stool for 4 to 8 weeks.9 The most severe cases of HFMD are caused by the enterovirus A71.9 Risk factors for developing severe HFMD include male sex, persistent high fever, young age, a lack of skin and oral lesions, increased neutrophil count, and steroid use.15 Additional risk factors for severe HFMD include living in a temperate climate and living in high-income countries, perhaps because of greater testing.16 Patients with HFMD commonly present with throat or mouth pain because of an eruption that affects the posterior oral cavity, buccal mucosa, or tongue. Malaise, low-grade fever, and reduced appetite may be present, along with a papulovesicular or maculopapular rash on the hands or feet.9,10 The

Hand, foot, and mouth disease is a highly contagious, primarily pediatric, viral infection caused by enteroviruses. cutaneous lesions, which start as erythematous macules with a diameter of 2 to 6 mm, later develop into oval vesicles on an erythematous base and resolve after 7 to 10 days.9 Unusual cutaneous features can arise, such as pustules and bullae, desquamation of the palms and soles, eczema coxsackium, and hemorrhagic lesions.9 HFMD also may be accompanied by an exanthem on the buttocks, arms, and legs.10 Finally, severe complications including acute flaccid paralysis, encephalomyelitis, acute transverse myelitis, acute cerebellar ataxia, polio-like syndrome, and cardiorespiratory and pulmonary complications, are possible.9,10 Histopathology of HFMD demonstrates spongiosis and epidermal necrosis or ballooning degeneration of individual keratinocytes. Superficial perivascular inflammation and papillary dermal edema also are found. No multinucleated keratinocytes or inclusion bodies are found.17

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TABLE. Erythema Multiforme vs Hand, Foot, and Mouth Disease Erythema Multiforme1-8

Hand, Foot, and Mouth Disease9-18

Dermatologic presentation

• Target-like, asymptomatic lesions • Patients may present with oral, ocular, or genital mucosal lesions and prodromal symptoms

• 2- to 6-mm erythematous macules that develop into oval vesicles on an erythematous base

Epidemiology

• More common in adults aged 20-40 years • More common in women

• More common in children aged 5-10 years

Potential risk factors

• Exposure to etiologic agents such as drugs and infections

• Healthcare practitioners and individuals exposed to others with HFMD

Etiology

• Infection in 90% of cases, commonly by HSV type 1 and Mycoplasma pneumoniae • Exposure to certain drugs, vaccines, autoimmune diseases, cancers, chemicals, and food additives

• Most commonly caused by coxsackievirus A16, A6, and A10 • Severe cases more likely caused by enterovirus A71

Characteristic location

• Face, trunk, palms of hands, soles of feet, arms, and legs

• Throat and mouth pain; lesions on palms of hands, soles of feet, buttocks, arms, and legs

Histology

• Apoptotic keratinocytes, superficial dermal edema, vacuolar degeneration of the basal layer, perivascular inflammatory infiltrates • Deposits of IgM, fibrin, and C3 along blood vessels and basement membrane

• Spongiosis, epidermal necrosis or ballooning degeneration of individual keratinocytes • No multinucleated keratinocytes or inclusion bodies • Superficial perivascular inflammation and papillary dermal edema

Diagnosis

• Clinical diagnosis with history and physical examination • Biopsies, serology, and direct immunofluorescence to exclude other diagnoses

• Clinical diagnosis with history and physical examination • Polymerase chain reaction and serology to confirm the diagnosis

Treatment

• Symptomatic with topical steroids, oral antiseptics, and antihistamines in acute cases • Address underlying etiologic cause • IV fluids and prednisone in severe cases • Antivirals in recurrent cases of HSV infection

• Symptomatic with acetaminophen, ibuprofen, hydration

HFMD, hand, foot, mouth disease; HSV, herpes simplex virus; IgM, immunoglobulin M; IV, intravenous

Diagnosis of HFMD is based on the clinical presentation of symptoms. Polymerase chain reaction and serology can be used to confirm the diagnosis.9,10 Serology also may be helpful in differentiating the cause of the infection — coxsackievirus vs enterovirus 71 — and measuring IgG levels during recovery.10 A variety of diseases may mimic HFMD, including herpangina, which is caused by the same viruses as HFMD but can be differentiated by a lack of skin involvement because it is limited to the mouth.9,18 Similarly, aphthous ulcers and herpetic gingivostomatitis do not feature the widespread skin involvement seen with HFMD.9 Herpes simplex virus and

varicella-zoster virus also invoke characteristic rashes and can be differentiated from HFMD via biopsy.9,10 Behçet syndrome and pemphigus vulgaris also present with oral involvement; suspected cases warrant further investigation.9 Atopic dermatitis can be recognized based on its recurrent nature; scabies is pruritic; bullous impetigo frequently involves the trunk; and erythema multiforme characteristically features target lesions on the upper extremities.9 Other conditions to consider in the differential diagnosis include Kawasaki disease, viral pharyngitis, toxic epidermal necrolysis, and, if the patient has other risk factors, HIV.9,10

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Dermatologic Look-Alikes Mild cases of HFMD typically resolve spontaneously within 7 to 10 days; thus, symptomatic treatment with acetaminophen or ibuprofen is recommended.9,10,15 Hydration is essential because dehydration can lead to hospitalization.9 Immunoglobulins and antivirals have been used in severe cases, but more evidence is needed to support use of these treatments.9,10,15 In this case, the patient was treated with supportive care including intravenous fluids and ibuprofen. Her rash resolved after approximately 1 week. ■

7. Heinze A, Tollefson M, Holland KE, Chiu YE. Characteristics of pediatric recurrent erythema multiforme. Pediatr Dermatol. 2018;35(1):97-103. doi:10.1111/pde.13357 8. Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. Current perspectives on erythema multiforme. Clin Rev Allergy Immunol. 2018;54(1):177-184. doi:10.1007/s12016-017-8667-7 9. Saguil A, Kane SF, Lauters R, Mercado MG. Hand-foot-and-mouth disease: rapid evidence review. Am Fam Physician. 2019;100(7):408-414.

10. Guerra AM, Orille E, Waseem M. Hand foot and mouth disease.

In: StatPearls. StatPearls Publishing; 2020. Accessed February 12, 2021.

Dina Zamil, BS, is a medical student at Baylor College of Medicine, Tara L. Braun, MD, is a resident in the Department of Dermatology at Baylor College of Medicine, and Christopher Rizk, MD, is a dermatologist affiliated with Baylor College of Medicine in Houston,Texas.

http://www.ncbi.nlm.nih.gov/books/NBK431082/ 11. Kimmis BD, Downing C, Tyring S. Hand-foot-and-mouth disease caused by coxsackievirus A6 on the rise. Cutis. 2018;102(5):353-356.

12. 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(8):615-621.

References

13. Seddon JH, Duff MF. Hand-foot-and-mouth disease: coxsackie virus types

1. Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of

A 5, A10, and A16 infections. N Z Med J. 1971;74(475):368-373.

erythema multiforme: a review for the practicing dermatologist. Int J Dermatol.

14. Aswathyraj S, Arunkumar G, Alidjinou EK, Hober D. Hand, foot and mouth

2012;51(8):889-902. doi:10.1111/j.1365-4632.2011.05348.x

disease (HFMD): emerging epidemiology and the need for a vaccine strategy.

2. Trayes KP, Love G, Studdiford JS. Erythema multiforme: recognition and

Med Microbiol Immunol. 2016;205(5):397-407. doi:10.1007/s00430-016-0465-y

management. Am Fam Physician. 2019;100(2):82-88.

15. Esposito S, Principi N. Hand, foot and mouth disease: current knowledge

3. Samim F, Auluck A, Zed C, Williams PM. Erythema multiforme: a review of

on clinical manifestations, epidemiology, aetiology and prevention. Eur J Clin

epidemiology, pathogenesis, clinical features, and treatment. Dent Clin North

Microbiol Infect Dis. 2018;37(3):391-398. doi:10.1007/s10096-018-3206-x

Am. 2013;57(4):583-596. doi:10.1016/j.cden.2013.07.001

16. Liu Z, Meng Y, Xiang H, Lu Y, Liu S. Association of short-term exposure to

4. Al-Johani KA, Fedele S, Porter SR. Erythema multiforme and related disor-

meteorological factors and risk of hand, foot, and mouth disease: a systematic

ders. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(5):642-654.

review and meta-analysis. Int J Environ Res Public Health. 2020;17(21):8017.

doi:10.1016/j.tripleo.2006.12.008

doi:10.3390/ijerph17218017

5. Spencer HE. Notes of a case of erythema multiforme. Br Med J.

17. Rapini RP. Viral, rickettsial, and chlamydial diseases. In: Practical

1884;2(1236):465. doi:10.1136/bmj.2.1236.465

Dermatopathology. 2nd ed. Saunders; 2012;14:207-217.

6. Lonjou C, Thomas L, Borot N, et al. A marker for Stevens-Johnson

18. Muzumdar S, Rothe MJ, Grant-Kels JM. The rash with maculopapules

syndrome ...: ethnicity matters. Pharmacogenomics J. 2006;6(4):265-268.

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30 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

LEGAL ADVISOR CASE

Nurse Sues Over Sexual Harassment © AJ_WATT / GETTY IMAGES

Nurse in surgical unit quits after years of sexual harassment by a supervisor.

BY ANN W. LATNER, JD

When Ms B was hired to work as a nurse in a surgical center, she had been out of school for a short time and the surgical center was the perfect place to gain experience and grow. The surgical center was under the direction of Dr K, who was a contract employee. He had 2 separate contracts with the surgical center: 1) to provide anesthesia services and 2) to serve as the surgical center’s medical director.

Dr K took a great interest in the new employee, as he did with many of the younger nurses — often joking around with her, sometimes inappropriately.

For a time, Ms B tried to overlook this behavior, but the doctor’s actions increasingly made her feel uncomfortable. He shared with her his previous sexual conquests and how he enjoyed being the dominant man with a submissive woman.

He insinuated that she should engage in a submissive relationship with him and that she should get a tattoo signifying his “ownership” of her. He would write a “sex word of the week” on Ms B’s calendar. He also passed around an unflattering picture of Ms B on her hands and knees, while making inappropriate comments.

After her resignation, Ms B sued Dr K for battery and emotional distress as well as the surgical center for a hostile work environment and constructive discharge.

The behavior was upsetting and confusing to Ms B, especially because Dr K was sometimes kind and helpful and acted appropriately. Then there were instances where he would hug her against her will, pull her hair, push her into a corner, or try to kiss her. The surgical center had a mechanism in place for making complaints, both anonymous and formal, but Ms B was afraid that reporting Dr K would have negative consequences for her career.

After working at the surgical center for more than 2 years, Ms B finally filed an anonymous complaint against Dr K. Afterward, his behavior improved for a few months, but soon he was back to making inappropriate remarks to Ms B. Ms B eventually filed an official complaint well over 3 years after the harassment began.

The surgical center’s management conducted an investigation and its medical executive committee 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.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • MARCH/APRIL 2021 31

LEGAL ADVISOR met 2 months later. At that meeting, the committee terminated the medical director services contract with Dr K and requested that he self-report to a physician health program and take an 8-week leave of absence. The committee did not cancel Dr K’s anesthesia services contract, however.

Ms B took on additional responsibilities at the surgical center as the safety officer after Dr. K left. Her working conditions improved until Dr K returned 2 months later to resume providing anesthesia services. Although Dr K was no longer harassing her, Ms B felt that he was a threat to her safety and her nursing license. She worked for another 10 months but ultimately decided that she had to resign.

Ms B’s working conditions improved until Dr K returned 2 months later to resume providing anesthesia services.

After her resignation, she spoke to a plaintiff ’s attorney who suggested that she sue Dr K for battery and emotional distress and that she sue the surgical center for a hostile work environment and constructive discharge (essentially forcing her to leave the job by making it so intolerable).

Legal Background

Ms B sued both the doctor and the surgical center. Prior to the trial, the court dismissed her constructive discharge claim against the surgical center. The case went to a jury trial. The jury found the surgical center liable for the hostile work environment (as evidenced by other nurses who worked there) and Dr K liable for battery and emotional distress.

The jury awarded Ms B compensatory and punitive damages.

After the trial, Dr K asked for a whole new trial, which the court denied. Then he appealed the emotional distress award. Ms B renewed her claim for constructive discharge against the surgical center.

The appeals court first addressed Ms B’s constructive discharge claim and noted that such claims are appropriate when an employer discriminates against an employee to the point that the working conditions become so “intolerable that a reasonable person in the employee’s position would have felt compelled to resign.”

The court noted that once Ms B made a nonanonymous complaint, it was acted on by management and that Ms B’s requests to never be alone with Dr K had been respected.

The court noted that the criterion for constructive discharge is that the conditions are “intolerable,” which is a higher

criterion than a hostile work environment. The appeals court concluded that “the facts here do not rise to the level of a sufficiently intolerable work environment to constitute constructive discharge.” The court also noted that Ms B had worked at the surgical center for years before filing a complaint, despite being aware of that being an option.

The court looked at the emotional distress claim that Dr K was challenging and noted there are 3 elements required: “that the defendant’s conduct must be 1) intentional/reckless, 2) extreme and outrageous, and 3) cause emotional distress so severe that no reasonable person could be expected to endure it.” The court noted that previous courts have generally required something more than the plaintiff ’s testimony about feeling upset, uncomfortable, or afraid — usually, an outward manifestation of distress is required.

In this case, Ms B did not need medical attention and did not experience weight fluctuation or sleep deprivation, the court pointed out. It concluded that while Ms. B was “subjected to repugnant conduct, she is not able to demonstrate unendurable and severe emotional distress due to that conduct.”

Protecting Yourself

If you are being subjected to harassment at work there are protections you can take but only if there is a record of you complaining about the harassment. It is fair to give your employer a chance to react and rectify the situation, when possible.

When Ms B filed a formal complaint, her employer launched an investigation and took at least some action against Dr K. He was stripped of the medical director contract and made to attend a recovery program. He could not return to work for 2 months, and once he did, management agreed to Ms B’s request that she never be left alone with him.

If you complain about harassment and your employer doesn’t act to protect you and things become so intolerable that you have no viable choice but to leave the job, then there is the potential for a constructive discharge lawsuit. But if you don’t alert your employer to the issue, they cannot be held liable for not acting on it.

If you are subject to harassment, take notes and keep documentation about when, where, and how the harassment happened and use the proper channels to report the abuse.

Also, document any treatment you have needed as a result of the harassement, such as psychopharmaceutical therapy and counseling. ■ Ann W. Latner, JD, a former criminal defense attorney, is a freelance medical writer in Port Washington, New York.

32 THE CLINICAL ADVISOR • MARCH/APRIL 2021 • www.ClinicalAdvisor.com

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