February 2018 Clinical Advisor by The Clinical Advisor

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■■MCI clinical guideline ■■Calcium and fracture risk ■■Bronchodilators and CVD FEATURE

Long-acting reversible contraceptives: a review LEGAL ADVISOR

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UTIs IN WOMEN Acute urinary tract infections are common in postmenopausal women.

Editor Colby Stong editor@clinicaladvisor.com Associate editor Madeline Morr Assistant editor Rita Aghjayan

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2 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

CONTENTS FEBRUARY 2018

NEWS AND COMMENT 8

3 Long-acting reversible 2 contraceptives Because of the effectiveness of LARCs, they should be considered as a first-line contraceptive option for most women.

Newsline ■■Mild cognitive impairment:

a practice guideline update. New recommendations for clinicians regarding assessing and managing patients with MCI. ■■The American Academy of Family Physicians (AAFP) does not endorse the 2017 hypertension guideline released by the American Heart Association (AHA) and American College of Cardiology (ACC). ■■Ibuprofen use may compromise reproductive health in men, according to a small study published in the Proceedings of the National Academy of Sciences. ■■Vitamin D and calcium supplements do not reduce fracture risk in older adults, according to a study published in JAMA. ■■New long-acting bronchodilator use is linked to an increased risk for cardiovascular events, according to a study published in JAMA Internal Medicine.

New bronchodilator use and CV risk 10

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

Dermatology Clinic n Severe acne on the face and chest n Spots on a woman’s torso and arms

Long-acting reversible contraceptives 23

Continues on page 4

Managing acute UTIs in postmenopausal women Urinary tract infections present clinically as dysuria, with symptoms of frequent and urgent urination secondary to irritation of the urethral and bladder mucosa.

MAKING CONTACT

CME Feature posttest

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28 CME Rosacea: assessment and management strategies Facial symptoms can be bothersome, and visible manifestations can negatively affect patients who have the disorder. Fortunately, various treatments can help.

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Stat Consult Head lice

Dermatologic Look-Alikes Growing, dyspigmented lesions

Legal Advisor Sexual harassment at work ends with a criminal conviction against a clinician.

My Most Memorable Patient ■ Neck and chest pain in a student

Clinical Pearl ■ Relief for orthostatic hypotension

Case Files ■ A man with sneezing fits ■ Wilms tumor in a child

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“In my day, we used to fritter our lives away, not twitter our lives away.”

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UTIs IN W OMEN Acute urin ary tract infections are common postmen opausal wom in en.

EATING

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The AGA recommends PEG laxatives (like MiraLAX) as a first-line constipation treatment1

✔ 96% patient satisfaction rate* ✔ #1 GI-recommended laxative for over 10 years Start with MiraLAX for proven relief of occasional constipation. *Survey of 300 consumers, 2017. Use as directed on product labeling or as directed by your doctor. Reference: 1. Clinical decision support tools. American Gastroenterological Association website. http://campaigns.gastro.org/algorithms/constipation/index.html. Accessed May 12, 2017. Bayer, the Bayer Cross, and MiraLAX are trademarks of Bayer. © 2017 Bayer May 2017 68522-PP-MLX-BASE-US-0328

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FDA proposes new enforcement approach for homeopathic drugs The new approach to homeopathic drugs would update the FDA’s existing policy to better address homeopathic treatments that are being marketed for serious diseases and/or conditions in which there is no evidence of clinical benefit.

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Mechanically expanded TAVR may be beneficial for high-risk aortic stenosis patients Mechanically expanded transcatheter aortic valve replacements may be just as effective as self-expanding aortic valve replacements for patients with aortic stenosis.

The Waiting Room Official Blog of The Clinical Advisor ClinicalAdvisor.com/WaitingRoom Tafari Mbadiwe, MD, JD Examining the effects of wearable fitness trackers Clinicians should not view wearable fitness devices as some sort of universal panacea for health, but as one of many tools in their tool belt.

Maternal folic acid, multivitamin use linked to reduced autism risk Researchers found that compared with mothers who were not exposed to folic acid or multivitamins, mothers taking these supplements had a statistically significant decrease in risk for ASD in offspring. FDA approves shock wave device to treat diabetic foot ulcers The Dermapace System is intended to be used for treatment of chronic, full-thickness diabetic foot ulcers with wound areas that extend through the epidermis, dermis, tendon, or capsule, but without bone exposure. Higher education may help reduce Alzheimer’s disease risk Genetic predictions resulted in decreased odds of Alzheimer’s disease in those with higher attained educations per year of education completed.

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Predicting the top 10 medical innovations for 2018 Each year the Cleveland Clinic announces what its panel of physicians and scientists believe to be the most important medical innovations that will have the greatest impact in the upcoming year.

Case Study in Urgent Care ClinicalAdvisor.com/CaseStudy Brady Pregerson, MD Sore throat and bruises A 32-year-old woman presents to an urgent care clinic with a sore throat, subjective fever, and abnormal bruising. Read the full case at: ClinicalAdvisor.com/CaseSoreThroat Foot pain after jogging A 64-year-old woman presents to an urgent care clinic with 24 hours of left foot pain. She states that she tweaked it while jogging. The pain is localized to the lateral portion of her foot. Read the full case at: ClinicalAdvisor.com/CaseFootPain

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

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Back pain that is aggravated by cold weather A 66-year-old man presents to the office with “years” of on and off lower back pain and stiffness. His stiffness is worse in the morning and seems to be aggravated by cold weather. His pain is predominately located across his mid to lower back. WHAT IS THE MOST LIKELY DIAGNOSIS?

• Ankylosing spondylitis • Diffuse idiopathic skeletal hyperostosis • Degenerative spondylosis • Rheumatoid arthritis ● See the full case at ClinicalAdvisor.com/OrthoDx_Feb18

Derm Dx A papular rash on the scalp A 31-year-old man presents to a homeless clinic complaining of a papular rash on the occipital region of his scalp. The rash began several years earlier but improved without the use of any particular treatment. His lesions are increasing in number and are mildly pruritic. He has had exposure to a variety of new shampoos and laundry detergents since arriving at the homeless shelter. WHAT IS YOUR DIAGNOSIS?

• Acne keloidalis nuchae • Pseudofolliculitis barbae • Molluscum contagiosum • Acne mechanica ● See the full case at ClinicalAdvisor.com/DermDx_Feb18

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Newsline F E B R U A RY 2 018

Calcium and fractures in older adults page 10

Ibuprofen may increase infertility risk in men page 10

Bronchodilator use and CV risk in COPD patients page 10

EXERCISING TWICE a week may improve thinking ability and memory in patients with mild cognitive impairment (MCI), according to a practice guideline update released by the American Academy of Neurology and published in Neurology. Recommendations for assessing mild cognitive impairment include the following: • For patients (or a close contact of patients) who voice concern about memory or impaired cognition, clinicians should assess for MCI and not assume the concerns are related to normal aging. (Level B) • When performing a Medicare Annual Wellness Visit, clinicians should not rely on historical report of subjective memory concerns alone

when assessing for cognitive impairment. (Level B) • For patients for whom screening or assessing for MCI is appropriate, clinicians should use validated assessment tools to assess for cognitive impairment. (Level B) • For patients who test positive for MCI, clinicians should perform a more formal clinical assessment for diagnosis of MCI. (Level B) • For patients with MCI, clinicians should assess for the presence of functional impairment related to cognition before giving a diagnosis of dementia. (Level B) Recommendations for the management of mild cognitive impairment include the following: • For patients diagnosed with MCI, clinicians should wean patients from medications that

Mild cognitive impairment: a practice guideline update

Exercising twice a week may improve thinking ability and memory in patients with mild cognitive impairment.

can contribute to cognitive impairment (where feasible and medically appropriate) and treat modifiable risk factors that may be contributing. (Level B) • For patients diagnosed with MCI, clinicians should counsel the patients and families that there are no pharmacologic or dietary agents currently shown to have symptomatic cognitive benefit in MCI and that no medications are FDA-approved for this purpose. (Level B) • For patients diagnosed with MCI, clinicians may choose not to offer cholinesterase inhibitors. (Level B)

AAFP does not endorse new AHA/ACC hypertension guideline THE AMERICAN Academy of Family Physicians (AAFP) has not endorsed the 2017 hypertension guideline released by the American Heart Association (AHA) and American College of Cardiology (ACC). The AAFP will continue to endorse the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Eighth Joint National Committee (JNC8), according to an AAFP press release. The AAFP, which was not involved in generating the new AHA/ACC hypertension guideline, used the same review process for both the AHA/ACC and JNC8 blood pressure guidelines and found that there was more robust scientific evidence to support the 2014 guidelines, a major factor in the AAFP’s decision.

David O’Gurek, MD, chair of the Commission on Health of the Public and Science for AAFP, noted that the JNC8 guideline “provided strong recommendations to family physicians and patients on appropriate treatment of hypertension.” While the 2017 AHA/ACC guideline used a system to grade the quality of evidence, background resources were not fully assessed and certain trials were heavily weighted while others were not, he added. The two major contributing factors to the decision were the absence of a formatted review process and the lack of quality review for each study by the AHA/ACC. According to the AAFP review process, some parts of the new guidelines did not meet the organization’s criteria.

8 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

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Newsline

ROUTINE VITAMIN D and calcium supplementation is not effective for lowering the incidence of osteoporosis-related fractures in older adults, according to a study in JAMA. Researchers searched databases to identify randomized clinical trials comparing calcium, vitamin D, or combined supplements with placebo or no treatment for fracture incidence in community-dwelling adults older than age 50 years. Thirty-three randomized trials (n = 51,145) met the inclusion criteria. The primary outcome was risk of hip fracture; secondary outcomes included nonvertebral fracture, vertebral fracture, and total fracture. The results showed no significant association of calcium (RR 1.53) or vitamin D (RR 1.21) with risk of hip fracture vs placebo or no treatment. In addition, combined calcium and vitamin D supplementation was not significantly associated with hip fracture vs placebo or no treatment (RR, 1.09). “No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures,” concluded the researchers. “These findings were also consistent in subgroup analyses regardless of supplement dose, gender, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration.

Ibuprofen linked to infertility in men IBUPROFEN INDUCES compensated hypogonadism, compromising the endocrine system through selective transcriptional repression in testes, according to a small study published in Proceedings of the National Academy of Sciences. Thirty-one white males (aged 18 to 35) in a placebo-controlled trial were randomly administered either ibuprofen or a placebo for 2 weeks before and 30 days following one exercise session. Average plasma ibuprofen concentrations varied between 25 and 35 μg/mL with the highest measured concentration at 100 μg/mL (600-mg administration). Total testosterone and its immediate downstream metabolic

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism.

product, 17β-estradiol, levels were analyzed using sex-hormone binding globulin (SHBG). The researchers found that neither free testosterone nor SHBG levels were influenced by ibuprofen immediately, but testosterone concentration was significantly inhibited by ibuprofen based on dosage. After 24 and 48 hours, there was a ‒40% amplification (β = ‒0.405 at 24 h and β = ‒0.664 at 48 h). All steroids from pregnenolone to testosterone and 17β-estradiol were inhibited. “Ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis,” stated the authors.

New bronchodilator use and CV risk PATIENTS WITH chronic obstructive pulmonary disease (COPD) who newly take longacting β2 -agonists (LABAs) or long-acting antimuscarinic antagonists (LAMAs) have an increased risk for cardiovascular events, according to a study published in JAMA Internal Medicine. Researchers included 284,000 patients with COPD who had never received LABA or LAMA therapies, were administered LABA or LAMA, and were monitored for any cardiovascular events. Patients older than age 40 (mean age, 71.1 years) who had either 1 inpatient visit or 2 outpatient visits in 1 year for COPD were eligible for investigation (68.9% of patients were male). Patients had an average follow-up

Patients who are new users of long-acting bronchodilators have an increased risk of having a cardiovascular event.

10 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

of 2 years for any indications of cardiovascular disease (CVD). Of the cohort, 37,719 patients were diagnosed with severe CVD (6.6 per 100 person-years) with 146,139 associated controls (70.1% men). New LABA and LAMA use in COPD patients was linked to a 1.50-fold (LABA) and 1.52-fold (LAMA) increase in cardiovascular risks in the first 30 days of treatment. In prevalent LABA or LAMA use, there was either no risk or reduced risk (9% and 12%, respectively). No significant differences were observed between new LABA and new LAMA use when compared with CVD risks. For every 406 newly treated LABA patients, there was 1 severe event of CVD, and 1 in 391 for newly treated LAMA patients. n

Vitamin D and calcium in older adults

FEATURE: ANNA LEAH POSNER, FNP-BC

Managing acute UTIs in postmenopausal women UTIs present clinically as dysuria, with symptoms of frequent and urgent urination secondary to irritation of the urethral and bladder mucosa.

Colored SEM of epithelial cells and RBCs present in a patient with a UTI.

cute urinary tract infection (UTI) accounts for approximately 3.6 million office visits annually by US women aged 18 to 75 years.1 Bladder problems reportedly cost an estimated $16 billion a year in health-related expenses.1 Although nonbacterial forms of UTI exist, bacterial infections are far more common. UTIs often manifest in an uncomplicated form, which can be successfully treated empirically. They are more common in women than in men as a result of differences in anatomy and hormones.1 UTIs are the second most common types of bacterial infections seen by healthcare providers.1 Eight million people are diagnosed with a UTI annually, and approximately 10% of postmenopausal women will report having had a UTI within the past year.2 With advancing age, the UTI rate increases likely because of the hypoestrogenic state and vaginal epithelium atrophy and stress incontinence. The purpose of this article is to demonstrate UTI as a clinical problem affecting postmenopausal women. The pathophysiology and applicable age changes will be discussed, along with relevant medical and nursing interventions. Lastly, an algorithm will be included to help guide clinicians in the evaluation and treatment of postmenopausal UTI. Only acute UTIs in an ambulatory setting will be discussed, as recurrent UTIs, though frequent among this population, often require referral to a specialist. Continues on page 19

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 11

MANAGING ACUTE UTIs IN POSTMENOPAUSAL WOMEN

PATHOPHYSIOLOGY

UTI may occur in the postmenopausal woman due to the aforementioned physiologic changes of the body. In the following section, the various etiologies will be explained as they have been studied as predisposing risk factors in the elderly female population. Vaginal atrophy and hypoestrogenic state Vaginal atrophy is the thinning and inflammation of the vaginal walls due to a decline in estrogen.1 Vaginal atrophy occurs most often after menopause, but it can also develop during breastfeeding or at any other time estrogen production declines in the body. This puts the elderly woman at risk for frequent UTIs since genital function is closely intertwined with healthy urinary system function. With vaginal atrophy, the risk of vaginal infections increases since atrophy leads to a change in the acidic environment of the vagina, making the elderly woman more susceptible to infection with bacteria, yeast, or other organisms.3 Stress incontinence Incontinence refers to the involuntarily loss of urine from the body.4 Although not a normal consequence of aging, more than 40% of menopausal women have urinary incontinence.4 It occurs commonly in advanced age women due to the weakening of the muscles of the pelvic floor that occur under the rectum and bladder. The weakened pelvic floor contributes to mobility and displacement of the urethra during exertion.4 If pelvic muscles are not properly strengthened, incontinence prevails. Additionally, decreasing amounts of estrogen after menopause also contribute to stress incontinence. Estrogen is responsible for keeping the urethra, vaginal, and pelvic floors healthy.1 It also stimulates blood flow to the pelvic region, increasing strength in the pelvic muscles. Therefore, as estrogen decreases, muscles are simply weaker than they were before.4 This leads to a lack of strength to hold the opening to the bladder closed.5 UTI risk can also be increased with urinary incontinence due to prolonged use of soiled absorbent pads, which can provide an environment for bacterial growth.5 Additional causes Diabetes is associated with a higher risk of acute symptomatic UTI in postmenopausal women.6 Diabetes results in several deviations of the host defense system that might result in a higher risk of certain infections.6 These abnormalities include immunologic impairments, such as impaired migration and phagocytosis from diabetic patients, and local complications

related to neuropathy, such as impaired bladder emptying.5 Also, higher glucose concentration in urine may serve as a culture medium for pathogenic microorganisms.5 CLINICAL PRESENTATION

In general, UTI present clinically as dysuria, with symptoms of frequent and urgent urination secondary to irritation of the urethral and bladder mucosa.4 Older women with UTI may be asymptomatic, presenting with urosepsis or septic shock (severe hypotension, fever, tachycardia, tachypnea), have symptoms only of urinary incontinence, or have any combination of these symptoms.2 In addition, symptoms of UTI that may occur in postmenopausal women but not in younger females may include mental changes or confusion, nausea or vomiting, abdominal pain, or cough and shortness of breath.7 An observational study of women aged 18 to 87 years within a primary healthcare setting revealed that a generalized sense of “feeling out of sorts” was frequent in adult women with acute uncomplicated lower UTI.1 History of present illness When a patient presents with symptoms of UTI, the clinician should elicit a full history of present illness (HPI). The HPI should include specifics regarding when the condition started, as the clinician should ask how many days/weeks the symptoms have been present. The typical features of UTI should next be examined: urinary urgency, frequency, dysuria, hesitancy, and low back pain.1 Because postmenopausal women may not present to the clinician with “typical” UTI symptoms, it is important to investigate for atypical UTI presentations.4 Symptoms of increasing mental confusion, incontinence, unexplained falls, loss of appetite, and nocturia are atypical clinical manifestations that may occur in the older postmenopausal female.4 PHYSICAL EXAMINATION

Initially, it is necessary to assess vital signs to help rule out sepsis. Before the physical assessment is performed, the patient is asked to void so that the urine can be examined and the bladder emptied prior to palpation.8 The abdominal examination should begin with inspection of the lower abdomen and palpation of the urinary bladder. Distention after voiding indicates incomplete emptying and can contribute to probability of contracting a UTI.7 Next, using standard precautions, the perineal examination should be performed in a supine or lithotomy position.8 The clinician inspects the area noting inflammation and any skin lesions around the urethral meatus and vaginal introitus.7 Often patients report “burning with urination” when

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 19

MANAGING ACUTE UTIs IN POSTMENOPAUSAL WOMEN

Antibiotic therapy is the usual prescription in the patient with a UTI. In postmenopausal women, drug therapy is influenced by numerous factors. normal, acidic urine touches labial tissues that are inflamed and ulcerated by vaginal infections.1 LABORATORY ASSESSMENT

Laboratory evaluation for a UTI in this population is similar to the younger female, consisting of a urinalysis with a microscopic count of bacteria, white blood cells (WBCs), and red blood cells (RBCs). Bacteriuria is diagnosed using a clean-voided midstream sample. For a routine analysis, 10 mL of urine is required; smaller quantities are sufficient for culture.9 Traditionally, the presence of 100,000 pure colonies/mL indicates an infection.7 Urine dipstick testing for leukocyte esterase and nitrite is a fast and inexpensive diagnostic method.10 It is a good screening test, with a sensitivity of 75% and specificity of 82%.2 However, urine culture confirms the type of microorganism and the number of colonies.11 Urine culture is expensive and takes approximately 48 hours to obtain results.10 It is indicated when the UTI is complicated or not responsive to usual therapy or if the diagnosis is uncertain.10

OTHER DIAGNOSTIC ASSESSMENT

The clinician usually bases the diagnosis of UTI on the history, physical examination, and laboratory data.2 If urinary retention and obstruction to urinary outflow are suspected, urography, abdominal sonography, or computed tomography (CT) may be needed to determine the site of obstruction or the presence of calculi.9 Voiding cystourethrography is used for the diagnosis of suspected cases of vesicoureteral reflux.9 Lastly, cystoscopy is often performed when there is a history of recurrent UTIs (more than 3 or 4 per year).1 Cystoscopy can identify abnormalities that may have contributed to the development of cystitis such as urethral strictures and bladder calculi.12 It remains the only accurate means of diagnosing interstitial cystitis.12 MEDICAL AND NURSING INTERVENTIONS

Drug therapy Antibiotic therapy is the usual prescription in the patient with a UTI.2 In postmenopausal women, drug therapy is influenced by numerous factors. The organisms causing UTIs in this population differ from the contributing sources in younger

TABLE 1. An algorithm for managing urinary tract infections in postmenopausal women

Three cardinal features

Additional symptoms

• Dysuria • Urinary frequency • Urinary urgency

• Fever, headache, malaise, mental confusion • Suprapubic tenderness, low back pain • Incontinence, loss of appetite, nocturia

Physical exam components

Abnormal findings

• Vital signs • Abdominal • Perineum

• Fever, hypotension, tachycardia • Tenderness, distention • Skin lesions, inflammation, ulceration

Diagnostics

Pertinent findings

• Urinalysis • Urine dipstick • Abdominal sonography, Urography, CT • Cystoscopy

• +Bacteriuria or >100,000 colonies/mL • +Leukocyte esterase and nitrite • +Obstruction or calculi • +Interstitial cystitis, urethral strictures, calculi

Antibiotics • 1st line: Trimethoprim-sulfamethoxazole: 1 tablet BID for 3 d • Trimethoprim 100 mg BID for 3 d • Ciprofloxacin 250 mg BID for 3 d

• Levofloxacin 250 mg daily for 3 d • Norfloxacin 400 mg BID for 3 d • Gatifloxacin 200 mg daily for 3 d

Symptomatic treatment and nonpharmacologic options • Cranberry products • Methenamine salts • Pyridium • Exogenous estrogen

• Sitz bath • Proper perineum care • Cooling of the feet • Increase water intake

20 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

A warm sitz bath taken 2 or 3 times a day for 20 minutes may provide comfort and some relief of local symptoms of a urinary tract infection. women.2 Staphylococcus is rarely isolated, whereas gramnegative bacteria and enterococci are frequent (E coli remains the most common causative organism).13 Pharmacokinetic and pharmacodynamic changes also control medication options to limit drug toxicity and interactions.13 Studies have revealed that a 3-day antibiotic regimen is equally effective and better tolerated than a 7-day course among postmenopausal patients.12 Use of trimethoprim/ sulfamethoxazole is preferred therapy according to national guidelines, with a 94% bacterial eradication rate.14 Other drug therapy options that have shown equivalency include ciprofloxacin, levofloxacin, and gatifloxacine.14 Studies have shown that the use of sulfonamides, ampicillin, and amoxicillin is less effective than the use of trimethoprim/ sulfamethoxazole and the fluoroquinolones and should not be considered as first-line therapy.2 It is important to note that while nitrofurantoin is frequently used in pregnancy, it has not been studied among the postmenopausal population.2 Diet therapy Unless medically contraindicated, fluid intake needs to be at least 2 to 3 L/day for adequate flushing of urine through the system.12 Drinking cranberry juice has been shown to decrease symptomatic UTIs because of the proanthocyanidininhibiting attachment of urinary pathogens to the urinary tract of epithelial cells.2 According to recent data, cranberry juice must be consumed for 3 to 4 weeks to be effective.8 Exogenous estrogen It has been hypothesized that exogenous estrogen can prevent recurrent cystitis by reversing genitourinary mucosal atrophy and restoring a more normal milieu in the vagina.2 Estrogen therapy increases vaginal pH and reverses the microbiologic changes that occur in the vagina after menopause.15 In one randomized, open-label study, the use of an estrogen-impregnated ring or topical estriol cream was associated with a significant reduction in recurrent infections, but the researchers concluded that further studies with larger sample sizes are needed.15 Although small studies have suggested a benefit associated with oral estrogen replacement therapy, there is currently no rationale for prescribing oral estrogens to treat or prevent recurrent cystitis.15 Methenamine salts Methenamine salts have long been used as an alternative strategy for the prevention of UTI. They generate the

production of formaldehyde in acid urine, which, in turn, acts as a bacteriostatic agent.9 As an oral agent, methenamine salts are well tolerated, and adverse effects are generally mild and include abdominal cramps, anorexia, and rash.9 Other pain relief measures To relieve the burning pain and urgent need to urinate, phenazopyridine hydrochloride (phenazopyridine) can be recommended. Not an antibiotic and available without a prescription, phenazopyridine is a bladder analgesic agent that provides pain relief to the lower part of the urinary tract.16 The decline in renal function that can be associated with advanced age should be kept in mind prior to recommending this drug. Several studies have shown that pyridium can cause drug-induced renal failure when not taken properly or taken at excessive doses.16 Non-pharmacologic methods are also useful. A warm sitz bath taken 2 or 3 times a day for 20 minutes may provide comfort and some relief of local symptoms.8 Proper perineum cleansing, wiping front to back to prevent contaminating the urethra with bacteria from the anal area, has been shown to reduce UTI prevalence.8 Cooling of the feet has been shown to promote pain control in an acute UTI.1 Surgical management Surgical interventions for patients with UTI treat the conditions that predispose to recurrent UTIs, such as the removal of obstructions and treatment of calculi.8 Procedures may include cystoscopy to identify and remove calculi or obstructions.9 CONCLUSIONS UTI is a common medical problem for women throughout their lifetime. The physiologic changes that women experience as they age have been shown to be markers of increased risk for UTI. Estrogens especially have an important physiologic effect on the female urinary tract causing symptomatic and functional changes. Vaginal atrophy, a manifestation of estrogen withdrawal after menopause, is often accompanied by urinary symptoms. Clinicians must be cognizant of the differing pathogens of UTI that commonly affect the older female patient for antibiotic treatment. In addition, it is reasonable to use cranberry juice, methenamine salts, and estrogen cream in postmenopausal women as a way of minimizing antibiotic exposure. n Continues on page 22

www.ClinicalAdvisor.com â&#x20AC;˘ THE CLINICAL ADVISOR â&#x20AC;˘ FEBRUARY 2018 21

MANAGING ACUTE UTIs IN POSTMENOPAUSAL WOMEN

Anna Posner, FNP-BC, is a certified family nurse practitioner, Female Pelvic Medicine and Reconstructive Surgery, Penn State Hershey Milton S. Medical Center, in Hershey, Penn. References 1. Bakey W. Predicting UTI in symptomatic postmenopausal women: A review of literature. JAAPA. 2006;19:48-54. 2. Grover M, Bracamonte J, Kanodia A, Edwards E, Weaver, A. Urinary tract infection in women over 65: is age alone a maker of complication. J Am Board Fam Med. 2009;22:266-271. 3. Romanzi L, Chaikin D, Blaivas J. The effect of genital prolapse on voiding. J Urol. 1999;161:581-586. 4. Moore E, Jackson S, Boyko E, Scholes D, Fihn S. Urinary incontinence and urinary tract infection: Temporal relationships in postmenopausal women. Obstet Gynecol. 2008;111:317-323. 5. Kirton C. Assessing for bladder distention. Nursing. 1997;27:64-72.

“Thank you for being a wonderful audience during my cellphone conversation.”

6. Boyko E, Fihn S, Scholes D, Chen C, Normand E, Yarbro P. Diabetes and the risk of acute urinary tract infection in postmenopausal women. Diabetes Care. 2002;25:1778-1783. 7. Scholes D, Hooton T, Roberts P, Gupta K, Stapleton A, Stamm W. Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med. 2005;142:20-27. Retrieved from: http://www.annals.org/ content/142/1/20.full.pdf+html Thinking for Collaborative Care. 4th ed. Saunders: Philadelphia; 2002. 9. Mohsin R, Siddiqui M. Recurrent urinary tract infections in females. J Pakistan Med Assoc. 2010;60:55-59. 10. Patel H, Livsey S, Swann R, Bukhari S. Can urine dipstick testing for urinary tract infection at point of care reduce laboratory work? J Clin Pathol. 2005;58:951-954. 11. Sultana R, Zalstein S, Cameron P, Campbell D. Dipstick urinalysis and the accuracy of the clinical diagnosis of urinary tract infection. J Emer Med. 2001;20:13-19. 12. Metts J. Interstitial cystitis: Urgency and frequency syndrome. Am Fam Phys. 2001;64:1199-1207. 13. Kuklinski D, Koduri S. Predicting urinary tract infections in a urogynecology population. Urol Nurs. 2008;28:56-68. Retrieved from: http://www. biomedsearch.com/nih/Predicting-urinary-tract-infections-in/18335699.html 14. Grabe M, Bishop M, Bjerklunk-Johansen T, et al. Uncomplicated urinary tract infections in adult: Guidelines on urological infections. Euro Assoc Urol. 2010;3:11-38. Retrieved from: http://www.uroweb.org/gls/pdf/ Urological%20Infections%202010.pdf 15. Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol. 1999;180:1072-1079. 16. Parazella M. Drug induced renal failure: Update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci. 2003;325:349-362.

22 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

“Not one crummy valentine.”

8. Ignatavicius D, Workman L (Eds.). Medical Surgical Nursing: Critical

FEATURE: TRACY GEORGE, DNP, APRN-BC, CNE

Long-acting reversible contraceptives Because of the effectiveness of LARCs, they should be considered as a first-line contraceptive option for most women.

An implant is inserted under the skin as long-term birth control for women.

early half of all pregnancies in the United States are unintended.1 Although the teen pregnancy rate has decreased since the 1990s, it is still higher than the rates in other developed countries. Long-acting reversible contraceptives (LARCs) are excellent choices for women at increased risk for unintended pregnancies.1 LARCs include intrauterine devices (IUDs) and implants. LARC methods are highly effective, and there are no issues with patient adherence.2 With oral contraceptives, patients must remember to take their pills daily. With contraceptive injections, patients must obtain their injections regularly. Even though the upfront costs are higher, LARCs are among the most cost-effective methods available because of their low failure rate.1 However, the rate of LARC use is low in the United States, at less than 10%.3 In the past, some providers discouraged adolescents and nulliparous women from using LARCs. The purpose of this article is to provide information on the available LARCs, discuss the 2016 US Medical Eligibility Criteria for Contraceptive Use (US MEC), and describe effective counseling strategies for patients wishing to use LARCs. In addition to the high level of effectiveness of LARCs, the continuation rates for LARCs exceed those for non-LARC methods.4 The continuation rate at 12 months for the levonorgestrel IUD was 88%; similarly, 85% of women continued to use the nonhormonal copper IUD at 1 year.5 In comparison, the continuation rate for non-LARC methods was 57%. The

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 23

LONG-ACTING REVERSIBLE CONTRACEPTIVES

In addition to the high level of effectiveness of LARCs, the continuation rates for LARCs exceed those for non-LARC methods. satisfaction rate for the was 86% at 1 year and was 81% for the nonhormonal copper IUD. In contrast, 53% of women were satisfied with their chosen non-LARC method.5 An important aspect of LARC continuation and satisfaction rates is effective counseling. It is important to assist women in choosing contraceptive methods that meet their reproductive needs.1 Intrauterine devices

The two classes of IUDs are the nonhormonal and hormonal IUDs (Table 1). The nonhormonal IUD is the copper IUD, Paragard, which is 32 by 36 mm in size. It has been approved for 10 years of use.6 The nonhormonal copper IUD is more than 99% effective. Some women have longer menstrual periods and heavier bleeding with this type of IUD, but the side effect may decrease after the first year of use.7 Currently, four hormonal IUDs are available. The Mirena IUD contains 52 mg of levonorgestrel, is 32 by 32 mm in size, and is approved for 5 years of use.6 Like the nonhormonal copper IUD, it is more than 99% effective. In addition, the Mirena IUD has been approved for the treatment of heavy menstrual bleeding, and approximately 20% of women have amenorrhea after 1 year of use.8 The Liletta IUD also contains 52 mg of levonorgestrel, is 32 by 32 mm in size, and is approved for 3 years of use. The Liletta IUD is more than 99% effective. It is now available with a single-handed insertion device to facilitate insertion.9 The Skyla IUD contains 13.5 mg of levonorgestrel,6 is 28 by 30 mm in size, and is more than 99% effective. The Skyla IUD is approved for 3 years of use. Nulliparous women were included in the clinical trials for Skyla, so it is approved for use in women regardless of their childbearing status. Fewer TABLE 1. Comparison of IUDs IUD

Duration of use (years)

Levonorgestrel dose (mg)

Size (mm)

Skyla

13.5

28 × 30

Kyleena

19.5

28 × 30

Liletta

32 × 32

Mirena

32 × 32

Copper

None

32 × 36

IUD = intrauterine device.

women have amenorrhea with the Skyla IUD because of the lower dose of levonorgestrel.8 The newest IUD is the Kyleena IUD, which became available in October 2016. The Kyleena IUD contains 19.5 mg of levonorgestrel and is 28 by 30 mm in size. It is more than 98.5% effective at preventing pregnancy, The Kyleena IUD is approved for 5 years of use. With the Kyleena IUD, irregular bleeding and spotting may occur for 3 to 6 months. However, with time, periods may be shorter and lighter, or even stop entirely.6 Implant

Currently, one contraceptive implant, Nexplanon, is approved in the United States. It contains 68 mg of etonogestrel and is approved for 3 years of use. The implant is inserted subdermally on the inner aspect of the upper, nondominant arm. Before inserting contraceptive implants, healthcare providers must attend a clinical training program sponsored by the manufacturer. The size of the implant is 4 cm (length) by 2 cm (diameter). The contraceptive implant is more than 99% effective at preventing pregnancies. The implant is radiopaque and can be visualized with several modalities: radiography, ultrasonography, computed tomography, and magnetic resonance imaging.10 The most common side effects of the implant are menstrual changes, especially irregular bleeding. However, irregular bleeding with the implant decreases in half of women during the first 3 months of use.11 Weight gain, another concern of patients using contraceptive methods, occurs in 6% to 12% of women using the implant.11 However, most women do not have the implant removed because of weight gain. US medical eligibility criteria

It is important to prescribe contraceptive methods to patients according to the latest evidence. The US Medical Eligibility Criteria (US MEC) were updated in 2016. They provide evidence-based recommendations for healthcare providers to follow when determining which patients can safely use a method of contraception.12 The 2016 US Selected Practice Recommendations for Contraceptive Use (US SPR) offer guidance on how contraceptive methods can be used and on how the obstacles that patients encounter when trying to obtain and use contraceptive methods can be overcome.13 The US MEC and US SPR are available as free applications (apps) for iPhone and Android platforms and online at the Centers for Disease Control and Prevention website. In

24 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

Most women can safely use the hormonal and nonhormonal IUDs, including adolescents who are at risk for unintended pregnancy. addition, the US MEC are available as a chart that can be laminated for ease of use in the clinical setting. The US MEC comprise four categories. The methods in category 1 can be used without restriction regardless of a woman’s health condition or status. Placement in category 2 means that the advantages of the method in a woman with a specific health condition generally outweigh the risks. Placement in category 3 means that the risks of the method outweigh the benefits for a woman with a specific health condition. Methods in category 4 should not be used because they pose an unacceptable health risk. The health conditions addressed in the US MEC (https://www.cdc.gov/reproductivehealth/ contraception/pdf/summary-chart-us-medical-eligibilitycriteria_508tagged.pdf) include hypertension, diabetes, epilepsy, migraine headaches, and cystic fibrosis, among others. Breastfeeding status and smoking status are also considered.12

inserted less than 10 minutes after delivery of the placenta; this insertion is considered to be category 2.12 According to the ACOG, “Immediate postpartum LARC should be offered as an effective option for postpartum contraception; there are few contraindications to postpartum intrauterine devices and implants.”16 However, the expulsion rates for IUDs inserted immediately postpartum can be as high as 10% to 27%, which are higher than the expulsion rates for other IUD insertions.16 Because 40% to 57% of women have sexual intercourse before the 6-week postpartum visit, the higher expulsion rates may be offset by improved protection against pregnancy during the postpartum period.16 A repeat pregnancy may occur as early as 12 to 18 months after delivery if a woman does not start a contraceptive method.15 Therefore, postpartum LARCs may be a way to decrease the rates of unintended pregnancy in postpartum women.

LARC in postpartum and adolescent patients

Contraceptive counseling

Most women can safely use the hormonal and nonhormonal IUDs, including adolescents and postpartum patients who are at high risk for unintended pregnancy. The American College of Obstetricians and Gynecologists (ACOG) Committee Opinion dated 2012 and reaffirmed in 201614 states that IUDs and implants can be safely used in teens, and IUDs can be inserted in nulliparous women. Furthermore, the ACOG recommends that providers consider LARCs as a first-line contraceptive option for most patients.4 Therefore, healthcare providers should counsel patients about LARCs and make these options available to them. According to the US MEC, the age between menarche and 20 years is a category 2 condition, whereas age 20 or older is category 1. Nulliparity is category 2, and parity is category 1.12 The postpartum period is considered to be either category 1 or category 2 for IUDs, depending on the type of IUD and the breastfeeding status of the patient.12 Similarly, there are few restrictions on the use of the implant in adolescents and postpartum patients according to the US MEC.12 Nulliparity and age between menarche and 18 years are considered category 1. For women who are not breastfeeding, the implant is category 1. If a postpartum woman is breastfeeding, the implant is category 2 until postpartum day 42, after which it is category 1.12 According to Rodriguez et al,15 LARCs can be offered safely to most women who are immediately postpartum. The US MEC state that nonhormonal and hormonal IUDs can be

Counseling about contraception is a crucial part of providing reproductive health care to patients. Charts can be used to demonstrate the most effective and least effective methods.17 It is important to discuss how contraceptive methods are used, and providers also need to counsel patients about possible side effects. Many patients are concerned about the effect that a contraceptive method will have on their menstrual cycle, so it is important to counsel them regarding any bleeding that may occur.18 The nonhormonal IUD is often associated with an increase in the amount and duration of bleeding,

POLL POSITION

Which of the following is the greatest barrier to increasing use of long-acting reversible contraceptives?

■ High up-front costs

5.25% 28.45%

■ Overall limited awareness of these options ■ Overcoming misconceptions about their use

20.17% 46.13%

■ Other

For more polls, visit ClinicalAdvisor.com/Polls.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 25

LONG-ACTING REVERSIBLE CONTRACEPTIVES

TABLE 2. Common side effects of the nonhormonal IUD causing discontinuation of use Side effect

Woman experiencing side effect at 1 year (%)

Woman experiencing side effect at 10 years (%)

Bleeding/pain

11.9

3.7

Expulsion

5.7

0.4

Pregnancy

0.7

IUD, intrauterine device. From Teva Women's Health.19

TABLE 3. Common side effects of the Mirena IUD Side effect

Women experiencing side effect at 1 year (%)

Irregular uterine bleeding

31.9

Decreased uterine bleeding

23.4

Increased regular uterine bleeding

11.9

Amenorrhea

18.4

Vaginal discharge

14.9

Vulvovaginitis

10.5

Breast pain

8.5

Benign ovarian cyst

7.5

Dysmenorrhea

6.4

IUD, intrauterine device. From Bayer HealthCare Pharmaceuticals.21

TABLE 4. Common side effects of the Skyla IUD Side effect

Women experiencing side effect at 1 year (%)

Vulvovaginitis

20.2

Ovarian cysts

13.2

Breast pain and discomfort

8.8

Dysmenorrhea

8.6

Increased bleeding

7.8

Abdominal and pelvic pain

18.9

Acne

13.6

Headache

12.4

Nausea

5.5

IUD, intrauterine device. From Bayer HealthCare Pharmaceuticals.22

which may diminish over the first year. Menstrual bleeding and pain were the most common reasons that women chose to discontinue the nonhormonal IUD. Although 11.9% of women experienced bleeding and pain during the first year of use, this percentage decreased to 3.7% at year 10 (Table 2).19 With the levonorgestrel IUDs, patients may expect to have irregular bleeding and spotting, especially during the first 3 to 6 months. With some hormonal IUDs, patients may experience reduced bleeding or even amenorrhea after 1 year of use.18 The amount of levonorgestrel affects the side effect profile of the hormonal IUDs. In Tables 3 and 4, the side effects of Mirena, which contains 52 mg of levonorgestrel, and of Skyla, which has 13.5 mg of levonorgestrel, are provided. With Skyla, 6% of women stop having menstrual cycles after 1 year.10 With Mirena, 20% of women have amenorrhea after using the device for 1 year.10 Common side effects of the implant include headaches, weight gain, vaginitis, acne, abdominal pain, and breast pain.10 Irregular bleeding is also a common side effect of the implant, which can be concerning to patients. Patients should be advised of this possible occurrence before placement of the device.17 Irregular bleeding is the most common reason why women request removal of the implant (Table 5).10 Common side effects of LARCs should be discussed, including headaches, nausea, depression, and breast tenderness. With IUDs, there is a small possibility of expulsion (5%) or perforation of the uterus (1 per 1000 insertions), and an increased risk for pelvic inflammatory disease during the first 3 weeks (1%). Additionally, if pregnancy occurs with an IUD or the implant, there is a slightly increased risk for an ectopic pregnancy.17 The provider should also ensure that patients understand what is being discussed. The teach-back method should be used in the counseling process. Healthcare providers should use written materials at the appropriate literacy level and in the correct language.17 In one study, shared decision aids for low-literacy patients resulted in an increase in the rate of LARC use when they were combined with a shared decision-making approach.20 Smartphone or tablet apps may be another way to enhance counseling, and in one study, patients’ knowledge of and interest in the implant improved after the use of apps.3 It is important to answer all questions and allow patients to hold models or devices if possible. In a shared decision-making approach, it is important always to allow patients to make their own contraceptive choice without coercion.17 Because of the high number of unintended pregnancies in the United States and the effectiveness of LARCs, they

26 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

TABLE 5. Common side effects of the implant Side effect

Woman experiencing side effect (%)

Headache

24.9

Vaginitis

14.5

Weight gain

13.7

Acne

13.5

Breast pain

12.8

Irregular menses

11.1

Abdominal pain

10.9

6. LARC options expand with new intrauterine device. Contracept Technol Update. 2016;37:121-124. 7. Use effective counseling skills when counseling on choosing LARC methods. Contracept Technol Update. 2016;37:101-103. 8. Raphaelides L. New addition to long-acting reversible contraception. J Nurse Pract. 2015;11:377-378. 9. Allergan. Liletta. Important safety information. https://www.lilettahcp. com/about/liletta?slide=2. © 2017. Accessed December 14, 2017. 10. Merck Connect. Nexplanon. https://www.merckconnect.com/nexplanon/overview.html. Accessed December 15, 2017. 11. Update on contraceptive implant ¬– what family planners need to know. Contracept Technol Update. 2016;37:76-77. 12. Curtis KM, Tepper MK, Jatlaoui TC, et al. U.S. medical eligibility criteria

From Merck Connect.10

for contraceptive use, 2016. MMWR Recomm Rep. 2016:65(No. RR-3):1-104. https://www.cdc.gov/mmwr/volumes/65/rr/rr6503a1.htm?s_cid=rr6503a1_w.

should be considered as a first-line contraceptive option for most women. It is important to use the US MEC, which are evidence-based, when contraceptive methods are being considered. Counseling is an important aspect of providing contraceptive methods, including LARCs, and should be offered in a shared decision-making approach to promote patients’ satisfaction and continuation of their chosen method. n

Updated September 21, 2017. Accessed December 14, 2017. 13. Curtis KM, Jatlaoui TC, Tepper MK, et al. U.S. selected practice recommendations for contraceptive use. MMWR Recomm Rep. 2016:65(No. RR-4):1-66. https://www.cdc.gov/mmwr/volumes/65/rr/rr6504a1.htm?s_ cid=rr6504a1_w. Updated June 16, 2017. Accessed December 14, 2017. 14. Committee on Adolescent Health Care Long-Acting Reversible Contraception Working Group. The American College of Obstetricians and Gynecologists. Committee opinion no. 539: adolescents and longacting reversible contraception: implants and intrauterine devices. Obstet

Tracy P. George, DNP, APRN-BC, CNE, is an assistant professor of nursing and coordinator of the Bachelor of General Studies Program, Francis Marion University, in Florence, South Carolina.

Gynecol. 2012;120:983-988 (reaffirmed 2016). 15. Rodriguez MI, EvansM, Espey E. Advocating for immediate postpartum LARC: increasing access, improving outcomes, and decreasing cost. Contraception. 2014;90:468-471. doi:10.1016/j.contraception.2014.07.001

References

16. American College of Obstetricians and Gynecologists’ Committee on

1. Parks C, Peipert JF. Eliminating health disparities in unintended pregnan-

Obstetric Practice. Committee opinion no. 670: immediate postpartum

cy with long-acting reversible contraception (LARC). Am J Obstet Gynecol.

long-acting reversible contraception. Obstet Gynecol. 2016;128:e32-e37.

2016;214:681-688. doi:10.1016/j.ajog.2016.02.017

17. Association of Reproductive Health Professionals. Clinical Minute transcript:

2. Trussell J, Henry N, Hassan F, Prezioso A, Law A, Filonenko A. Burden

counseling young women about long-acting reversible methods. https://www.

of unintended pregnancy in the United States: potential savings with

arhp.org/uploadDocs/IUC-Clinical-Minute.pdf. Accessed December 14, 2017.

increased use of long-acting reversible contraception. Contraception.

18. Short-term bleeding and cramping with LARC method satisfaction

2013;87:154-161. doi:10.1016/j.contraception.2012.07.016

eyed. Contracept Technol Update. 2014;35:121-123.

3. Gilliam ML, Martins SL, Bartlett E, Mistretta SQ, Holl JL. Development

19. Teva Women’s Health. ParaGard prescribing information. http://hcp.

and testing of an iOS waiting room “app” for contraceptive counseling in

paragard.com/Pdf/ParaGard-PI.pdf. Updated September 2014. Accessed

a Title X family planning clinic. Am J Obstet Gynecol. 2014;211:481.e1-e8.

December 15, 2017.

doi:10.1016/j.ajog.2014.05.034

20. George TP, DeCristofaro C, Dumas BP, Murphy PF. Shared decision

4. Committee on Gynecologic Practice Long-Acting Reversible

aids: increasing patient acceptance of long-acting reversible contraception.

Contraception Working Group. Committee opinion no. 642: increasing

Healthcare (Basel). 2015;3:205-218.

access to contraceptive implants and intrauterine devices to reduce unin-

21. Bayer HealthCare Pharmaceuticals. Mirena prescribing information.

tended pregnancy. Obstet Gynecol. 2015;126, e44-e48.

https://labeling.bayerhealthcare.com/html/products/pi/Mirena_PI.pdf.

5. Levine L. The IUD rumor mill: common misconceptions. Clinical Advisor.

Updated June 2017. Accessed December 14, 2017.

http://www.clinicaladvisor.com/features/iud-intrauterine-device-contra-

22. Bayer HealthCare Pharmaceuticals. Skyla prescribing information.

ception-smisconceptions/article/444722/. Published October 13. 2015.

http://labeling.bayerhealthcare.com/html/products/pi/Skyla_PI.pdf.

Accessed December 15, 2017.

Updated March 2017. Accessed December 14, 2017.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 27

■ EDUCATIONAL OBJECTIVES

CME

At the conclusion of this activity, participants should be better able to: • Describe current theories regarding the pathophysiology of rosacea • Identify the spectrum of clinical signs and symptoms of rosacea, including its characteristic persistent facial erythema • Assess the risks, benefi ts, safety profile, and limitations of current and emerging treatments for rosacea • Individualize rosacea treatment plans according to specific manifestations, symptom severity, and other patient characteristics

FEATURED COURSE

• Counsel and educate patients with rosacea to ensure correct and consistent adherence to treatment recommendations ■ COMPLETE THE POSTTEST: Page 38

Release Date: May 5, 2017 Expiration Date: February 28, 2019 Estimated Time to Complete: 1 hour Accredited Provider: This activity is provided by Haymarket Medical Education. Commercial Supporter: This activity is supported by an educational grant from Allergan. Partner: This activity is provided in partnership with the National Rosacea Society. Program Description: Rosacea encompasses a wide variety of clinical manifestations that vary in presentation and magnitude among different patients and at different points in time over the course of the disease. As this Clinical Case demonstrates, facial symptoms such as stinging or burning sensations can be physically bothersome, but it is the visible manifestations of rosacea that often have a profound negative impact on patients. A variety of treatments can help ameliorate signs and symptoms of rosacea. This Case Clinic, which focuses on the management of a patient with worsening rosacea, is part of a series illustrating different clinical challenges in rosacea management that together fulfill the educational objectives outlined below. Intended Audience: Dermatologists and other healthcare professionals who provide care for patients with rosacea. Conflict of Interest Disclosure Policy: In accordance with the ACCME Standards for Commercial Support, HME requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any commercial interest. HME resolves all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs. Faculty ACTIVITY CHAIR James Q. Del Rosso, DO, FAOCD Adjunct Clinical Professor (Dermatology) Touro University Nevada Henderson, NV Research Director / Clinical Dermatology JDR Dermatology Research /Thomas Dermatology Las Vegas, NV Dr. Del Rosso discloses the receipt of consulting, speakers’ bureau and/or contracted research fees from the following: Allergan, Aqua/ Almirall, Bayer, BiopharmX, Celgene, Cutanea, Dermira, Ferndale Pharma Group, Foamix, Galderma, Genentech, LEO Pharma, Novan, Novartis, Pfizer, Promius, Sebacia, Sun Pharma, Unilever, and Valeant.

Accredited Provider Disclosure: Haymarket Medical Education staff involved in the planning and content review of this activity have no relevant financial relationships to disclose. Accreditation Statement: Haymarket Medical Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Designation Statement: Haymarket Medical Education designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Disclosure of Unlabeled Use: This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options for a specific patient’s medical condition. Disclaimer: The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of Haymarket Medical Education, the National Rosacea Society, and Allergan. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Instructions: There are no fees for participating in and receiving CME credit for this activity. During the period May 5, 2017, through February 28, 2019, participants must: 1) read the learning objectives and faculty disclosures; 2) complete the pre-assessment test; 3) study the educational activity; and 4) complete the post-test and evaluation form and submit it online. A statement of credit will be issued only upon receipt of the above elements and a posttest score of 70% or higher. All components must be completed and submitted online at ClinicalAdvisor.com/ Feb18feature. If you have any questions relating to the accreditation of this activity, please contact cmequestions@haymarketmedical.com. If you have any questions relating to your certificate or other issues with the activity, please contact myCME.Support@ haymarketmedical.com.

Provided by

In partnership with

CME

FEATURED COURSE: JAMES Q. DEL ROSSO, DO, FAOCD

Rosacea: Assessment and management strategies Facial symptoms can be bothersome, and visible manifestations can negatively affect patients. Fortunately, various treatments can help.

A variety of treatments can help relieve the signs and symptoms of rosacea.

osacea is a chronic cutaneous disorder primarily affecting the central face: inner cheeks, chin, nose, and central forehead. The condition is characterized by chronicity with remissions and exacerbations. It encompasses a wide variety of clinical manifestations that vary in presentation and magnitude among different patients and at different points in time over the course of the disease.1 Rosacea can present to the clinician primarily due to flushing, facial erythema, telangiectasias, facial edema, papulopustular lesions, ocular signs and/or symptoms, and/or phymatous changes (usually rhinophyma) —although, generally, only some of these features are manifested in any given patient.2,3 The most common presentation is diffuse centrofacial erythema (DCE), either with or without papulopustular lesions.4-6 As this Clinical Case demonstrates, facial symptoms such as stinging or burning sensations can be physically bothersome, but it is the visible manifestations of rosacea that often have a profound negative impact on patients. A variety of treatments can help ameliorate the signs and symptoms of rosacea. However, there is no cure, as affected patients innately exhibit rosacea-prone skin.1,6 Rosacea self-care requires sustained vigilance and commitment to adherence with therapy. Encouraging patients to use recommended skincare and medications correctly and consistently and to minimize exposure to trigger factors can improve outcomes.7,8

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TABLE 1. NRS rosacea classification system Presence of at least 1 primary feature

May include 1 or more secondary feature

• Flushing (transient erythema) • Nontransient erythema • Papules and pustules • Telangiectasia

• Burning or stinging • Plaque • Dry appearance • Edema • Ocular manifestations • Peripheral location • Phymatous changes

NRS, National Rosacea Society. Source: Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Clin Acad Dermatol. 2002;46(4):584-587.

MANIFESTATIONS OF ROSACEA

In 2002, the National Rosacea Society (NRS) introduced a system that classifies rosacea into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.10 This subtype classification can serve as a useful tool for categorizing presentations, especially in the research setting. However, this classification system does not account for the chronicity of rosacea or the fact that individual clinical features, especially those that become persistent between flares, may vary in the timing of their emergence over the course of the disease. Thus, it is now recommended by the American Acne and Rosacea Society (AARS), and other global expert consensus groups, to assess and categorize

rosacea based on the clinical manifestations that are currently observed in the individual patient.6,11,12 Although the core clinical features of rosacea include transient erythema (ie, “flushing” of rosacea); persistent (nontransient) papules, pustules, and telangiectasias; and phymatous changes,13,14 almost all individuals with rosacea exhibit persistent (nontransient) DCE, either with or without inflammatory lesions.1,6,10-12 The characteristic DCE of rosacea increases in intensity during flares due to acute vasodilation and persists as nontransient erythema between flares at a lesser degree of intensity due to fixed dilation and enlargement of superficial facial vasculature.6,15,16 The presence or absence of flushing can be determined through patient history, noting its frequency, duration, extent, and severity.4 The primary and secondary features of rosacea identified by the NRS are summarized in Table 1; however, persistent (nontransient) DCE is considered by many to be a necessary diagnostic feature of rosacea.6,10,15 Differential diagnosis

Among conditions that share some similar features with rosacea are acne vulgaris, seborrheic dermatitis, lupus erythematosus, and polymorphous light eruption (PMLE).17,18 Table 2 summarizes key differences between rosacea and conditions with which it may be confused.18,19 The clinical differentiation of rosacea from chronic photodamage can sometimes be challenging, as persistent erythema and telangiectasias are common in both. In chronic

TABLE 2. Distinguishing features of common disorders mimicking rosacea Condition

Distinctions from rosacea

Acne vulgaris

• Noninflammatory; open or closed comedones • Affects the areas with the highest density of sebaceous follicles (eg, face, upper aspect of the chest, and back) • Usually does not have predominant centrofacial distribution • Less erythema, drying, burning, stinging, or itching

Seborrheic dermatitis

• Pink erythema with fine scaling at different sites of predilection than rosacea; affects scalp, periauricular area, perinasal folds, central chest • Absence of papulopustular lesions

Systemic lupus erythematosus (SLE)

• Protean clinical manifestations; follows a relapsing and remitting course with systemic symptomatology (fever, malaise, polyarthralgias/arthritis of small peripheral joints [ie, fingers]) • Affected skin generally feels warm and appears slightly edematous • Color of the skin has a violaceous quality and may show a more abrupt cutoff, especially at its most lateral margins

Polymorphous light eruption (PMLE)

• The face, neck, outer aspects of the arms, and dorsal surfaces of the hands are most commonly affected; not predominantly centrofacial • Intermittent and recurrent; not chronic • Abrupt onset of erythema, often with papules separated by normal-appearing skin, after sun exposure and subsiding usually within 1 to 7 days

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photodamage, cutaneous involvement tends to be more diffuse and constant, also affecting the lateral face, neck, and ear helices. In contrast, erythema associated with rosacea tends to exhibit centrofacial predominance, with intermittent flares characterized by increased intensity of erythema due to vasodilation (flushing). Of course, many patients with rosacea also may have concurrent skin changes resulting from chronic photodamage, as facial skin is frequently exposed to sunlight over time.6 This is often the case among people who have spent substantial amounts of time outdoors either because of their occupation (as with Gerard) or because of their recreational activities. Comorbidities of rosacea

Associations that may be clinically relevant have been observed between rosacea and certain other disease states, although the pathophysiological connections that may underlie these associations remain unclear. In a large, populationbased, case-control study (6759 patients with rosacea matched with 33,795 controls), women with rosacea were at increased risk for autoimmune diseases including type 1 diabetes mellitus, celiac disease, multiple sclerosis, and rheumatoid arthritis; in men, only rheumatoid arthritis reached statistical significance.20 Moderate to severe (but not mild) rosacea has been reported to be associated with gastroesophageal reflux disease as well as hyperlipidemia, hypertension, and metabolic and cardiovascular (CV) diseases,21 suggesting that it may be prudent to consider assessment of rosacea patients for CV risk factors, although more data are needed before definitive recommendations can be made.21,22

Patient perspectives

Gerard is not unique in his concern that his worsening persistent facial erythema, episodes of flushing, and bouts of papulopustular lesions due to rosacea may be undermining his professional image with his colleagues and clients. It is a common misperception that erythema and, in particular, rhinophyma associated with rosacea are related to excessive alcohol consumption.23 Facial erythema, inflammatory papules and pustules, flushing, burning, and stinging may cause physical and/or psychosocial discomfort,24,25 but for many patients, the emotional impact of the disorder represents a heavier burden. Multiple studies confirm that the effect of rosacea on physical appearance can negatively influence patients’ emotional health, contributing to low self-esteem and confidence, social phobias, anxiety, embarrassment, negative body image, and depression.2,26 Patients report that the primary domains affected are social life and work life. Furthermore, the severity of disease is correlated with the degree of health-related quality-of-life impairment as determined by validated methodologies used in clinical studies—patients who describe themselves as having severe erythema have worse Dermatology Life Quality Index (DLQI) scores than those who rate their erythema as moderate.2 Pathophysiology of rosacea

The pathophysiology of rosacea is not fully understood, but it is multifactorial.27 Genetics play an important role, as do extrinsic triggers. In a twin study (N=550, with 233 pairs of identical twins and 42 pairs of fraternal twins), about

PATIENT CASE: A 54-year-old man with recurrent flares and worsening of centrofacial erythema Gerard B, who works as a construction engineer, presents with erythema of the central face, accompanied by small papules and pustules on the inner cheeks, nose, chin, and central forehead. He reports that the rash developed about 10 days earlier and has progressively worsened. Gerard is fair-skinned (Fitzpatrick skin phototype 1)9 and has apparent photoaging skin damage due to his job-related need to work outdoors. He was first diagnosed with rosacea about 10 years ago. Since then, he has experienced periodic episodes of flaring approximately once or twice a year. The flares are unpredictable, although he reports that his symptoms seem to worsen when the weather is warmer.

He experiences mild stinging and burning, but not itching, of the facial skin. Gerard has been treated in the past with topical metronidazole and oral minocycline, which have helped temporarily, but periodic flares still occur. When the flare resolves, his facial skin remains red. Gerard is seeking treatment for this flare, which he reports is worse than those he has experienced in the past. He is particularly concerned that the appearance of his face is eliciting negative reactions from his clients and colleagues. He admits that he feels very self-conscious and embarrassed by the persistent “bright red” color of his face and also by the “pimples” when they are present.

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half of the risk for developing rosacea was attributed to genetic susceptibility, and half was attributed to environmental factors (eg, exposure to ultraviolet [UV] radiation or extreme heat or cold).14 Dysregulation of the innate and adaptive immune systems with aberrant local inflammatory responses to multiple extrinsic factors (eg, UV exposure, heat exposure, Demodex proliferation, spices); neurovascular dysregulation leading to vasodilation and perivascular inflammation; and physical alterations in arterial, venous, and lymphoid vessels have all been implicated collectively in the development of rosacea.7,27-29 Pathogenic mechanisms can be divided into augmented immune detection and responses and neurovascular dysregulation. “Crosstalk” between augmented immune detection and neurogenic inflammation, along with angiogenesis and contributions from increased numbers of perivascular mast cells, work together both early and later in the course of rosacea to elicit many of its clinical features.1,6,13,15,29-32 Augmented immune response and neurovascular dysregulation

An exacerbated innate immune response induces abnormal cathelicidins, antimicrobial peptides that are present normally within skin to protect against infection by microbial organisms. Cathelicidin (LL-37) is often upregulated in rosacea, producing increased facial inflammation during rosacea flares and hypervascularity (increased density and size of superficial skin vasculature), which increases over time through several downstream signaling pathways.1,13,29-31 In addition, toll-like receptor 2, a pattern-recognition receptor (“alarmin”) that serves as a first line of innate immune defense, is increased in rosacea.33 Expression of TABLE 3. Summary of vascular changes in rosacea Alterations of vascular response and blood flow

• Easier and more prolonged flushing response to heat • Oral-thermal flushing • Increased blood flow in affected skin vs nonaffected skin

Physiochemical stimulation of vasodilation and/ or angiogenesis

• Increase in VEGF in rosacea (nonphymatous skin) and via stimulation by UV exposure • Endothelial nitric oxide leading to vasodilation • Cathelicidins catabolism to LL-37 and other peptides that stimulate angiogenesis and neovascularization

Progressive chronic • Larger cutaneous vessels vasodilation and • Dilated cutaneous vessels angiogenesis • Telangiectasias UV, ultraviolet; VEGF, vascular endothelial growth factor.

interleukin-8, a cytokine responsible for chemoattraction of neutrophils and supporting angiogenesis, is also elevated.1,13 Reactive oxygen species (ROS) levels are elevated in rosacea lesional skin compared with skin in healthy controls. ROS, which appears to be from infiltrated leukocytes, mediates cytokine induction in human keratinocytes and chemokine production in monocytes. Increased ROS activity enhances inflammatory reactions and degenerates dermal collagen and matrix.29 Changes in cutaneous vasculature

Persistent facial erythema results from fixed changes in superficial cutaneous vasculature that develop over time in rosacea.1,5,16 Enlargement of vasculature, hyperpermeability, and fluid extravasation are hallmarks of tissue inflammation, with angiogenesis, lymphangiogenesis, vascular endothelial growth factor (VEGF)-A, and other markers for blood vessels (CD31) and lymphatics (D2-40) that are increased in rosacea. Dilation of cutaneous vasculature and lymphatics has been reported, and Doppler perfusion imaging shows increased cutaneous blood flow in affected skin compared with nonaffected skin.1,15 In many patients, facial skin shows a heightened vasodilatory response to stimuli that include exposure to ambient heat, hot drinks, spicy foods, exercise, or ingestion of vasodilating medications or alcohol. This augmented vascular responsiveness, considered to have a neurogenic inflammatory origin, is associated with neuropeptide release from sensory nerve endings.31 The result is localized hyperemia, edema, erythema, and recruitment of neutrophils. Neuropeptide-induced release of mast-cell mediators contribute to inflammation and to such symptoms as a burning sensation or pruritus.1,6 The vascular changes observed in the skin of patients with rosacea are summarized in Table 3. Ultimately, progressive chronic vasodilation and angiogenesis underlie the development of persistent DCE due to fixed changes in the facial vasculature. Correlation with clinical manifestations

Many clinical manifestations associated with rosacea appear to correlate with specific pathophysiologic pathways and respond at least partially to therapies that modulate and/ or inhibit those pathways.6 Two major pathophysiologic mechanisms may be operative in rosacea-prone skin: neurovascular dysregulation and augmented immune detection and response. Symptoms may be associated with augmented expression of specific cell-surface receptors that elicit proinflammatory neurogenic effects, including dysesthesias.13,34 DCE is the common denominator present in essentially all cases of rosacea (Figure 1). Typically persistent between flares

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FIGURE 1. Pathogenic mechanisms associated with diffuse and persistent facial erythema

AUGMENTED INNATE IMMUNE RESPONSE • Increase in TLR-2 • Increased cathelicidin • Increased serine protease (KLK-5)

ANGIOGENESIS • Increased VEGF • Increased mast cells • Increased cathelicidin-derived peptides (ie, LL-37) • Increased MMP-9

ROSACEA DERMATITIS • SC dysfunction • Increase in “jump-start” cytokines

DIFFUSE FACIAL ERYTHEMA Central face Macular +/- Edema during flare and persistent after therapy

ALTERED VASCULAR RESPONSE • Neurovascular dysregulation • Increased nitric oxide dilation • Increased blood flow

DERMAL MATRIX DEGRADATION • Increase in ROS • Decreased antioxidant reserve • Increased MMPs

INCREASED CATHELICIDIN-DERIVED PEPTIDES (ie, long-form LL-37) • Inflammatory cascade induction • Angiogenesis KLK, kallikrein-related peptidase; MMP, matrix metalloproteinase; ROS, reactive oxygen species; SC, stratum corneum; TLR, toll-like receptor; VEGF, vascular endothelial growth factor. Source: Del Rosso JQ. Advances in understanding and managing rosacea, part 2: the central role, evaluation, and management of diffuse and persistent facial erythema of rosacea. J Clin Aesthet Dermatol. 2012;5:26-36.

(nontransient), DCE is distinct from lesional and perilesional erythema, which occurs only in association with papulopustular lesions. DCE results from fixed enlargement and increased density of superficial facial vasculature accentuated by dysregulation of cutaneous vasomotor response.16 Alpha-adrenoreceptors in the smooth-muscle layer of the vessel wall of superficial cutaneous blood vessels physiologically modulate vascular tone of the vasculature of superficial and deep plexuses: activation of these alpha-adrenoreceptors induces vasoconstriction.35 Facial erythema alone Rosacea can present with facial erythema alone, with sustained vasodilation without inflammatory lesions, and often with symptoms of skin sensitivity (eg, stinging, burning). Facial erythema is induced by a variety of causes, including impairment of the permeability barrier and acute-subacute vasodilation of centrofacial skin vasculature. Vasodilation and the associated increased blood flow correlate with greater intensity of erythema during flares.1 The signals that induce vasodilation of facial vasculature are inflammation secondary to an augmented innate immune response and neuroimmune/neurovascular dysregulation. Inflammation and skin sensitivity are further accentuated by stratum corneum permeability barrier impairment, resulting

in increased central facial transepidermal water loss and skin sensitivity. It is important to differentiate these factors from a clinical perspective, as each is responsive to certain therapeutic approaches but may not be as responsive to others.1 DCE during a flare is induced by neurovascular and acute inflammatory pathways being triggered. DCE that persists between flares is due to the presence of enlarged and chronically dilated superficial cutaneous vasculature and telangiectasias that have developed over time.5 Concurrent with the increase in facial erythema, soft centrofacial edema may occur secondary to extravascular fluid leakage with associated perivascular inflammation and lymphedema caused by engorgement of lymphatic vessels.

PATIENT CASE: Assessment of severity In Gerard’s case, the clinician’s global assessment at the time of presentation indicates severe rosacea, based on the intensity of nontransient erythema along with approximately 25 papulopustular lesions and the patient’s report of moderate to severe transient flushing and mild to moderate symptoms of stinging and burning.

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Facial erythema with inflammatory lesions Rosacea that presents with facial erythema and inflammatory lesions is often multifactorial.15 All the factors contributing to facial erythema alone, as described previously, contribute to DCE in patients who also exhibit papulopustular lesions. When present, these lesions contribute additionally to the overall DCE that a given rosacea patient exhibits by producing lesional and perilesional erythema. The contributions to DCE may include the following: • Erythema directly associated with the inflammatory lesions • Perilesional and lesional erythema • Erythema secondary to inflammatory cascades that are augmented during a flare • Acute vasodilation and chronic vasodilation, the latter secondary to fixed vascular changes that persist between flares TREATMENT APPROACHES

Although classification of rosacea by subtype can be useful in recognition and differential diagnosis, treatment should be guided by the specific visible manifestations in a given patient at the time of presentation.6 A variety of recommendations for treatment of rosacea have been published, including a 5-part consensus series developed by AARS,6,15,35-37 as well as the global ROSacea COnsensus (ROSCO) panel recommendations,8,12 which outline approaches to management of specific features of rosacea. Matching treatment to manifestations

Medical therapy including topical formulations, oral agents, and proper skincare, along with light or laser procedures, are the mainstay of therapy for rosacea. Treatment selection for DCE and telangiectasia is also influenced by how

much the visible signs and associated symptoms bother the patient physically and psychosocially. 34,35 Multiple cutaneous features of rosacea can be treated with more than one agent simultaneously. Table 4 summarizes the topical treatment classes approved by the US Food and Drug Administration (FDA).38 Papulopustular lesions Agents approved in the United States for treatment of inflammatory lesions include topical metronidazole (0.75% gel, cream, lotion; 1% gel, cream), topical azelaic acid (15% gel, foam), ivermectin (1% cream), and doxycycline 40-mg modified-release capsule once daily (subantibiotic dose).35,39 These agents can reduce inflammatory lesions and perilesional/lesional erythema, but they have little to no effect on persistent facial erythema.6,40 Antibiotics, such as doxycycline administered orally at subantibiotic doses, have an anti-inflammatory effect that decreases matrix metalloproteinase expression, downregulating inflammatory cytokines, reducing ROS levels, and inhibiting nitric oxide–mediated vasodilation. 38 Other antimicrobials (eg, tetracycline, minocycline) and macrolides (eg, azithromycin, clarithromycin) are used off-label. Diffuse centrofacial erythema Topical alpha-agonists such as brimonidine (approved in 2013)41 or oxymetazoline (approved in January 2017)42 reduce the persistent DCE of rosacea through vasoconstriction of the superficial vasculature of the face.43 After cutaneous application, they stimulate alpha-adrenergic receptors, inducing reversible vasoconstriction that abates once the drug-receptor interaction dissipates. Used once daily in the

TABLE 4.Topical agents approved for the treatment of rosacea Medication

Level of evidence

Proposed mechanism(s) of action

Sodium sulfacetamide/sulfur

Unknown but likely anti-inflammatory

Metronidazole

Decreased ROS generation; anti-inflammatory

Azelaic acid

Decreased expression of KLKs and cathelicidin; decreased ROS generation

Alpha-adrenergic agents

Vasoconstriction of smooth muscle surrounding vessels of the superficial and deep dermal plexuses

Ivermectin

Antiparasitic and anti-inflammatory properties

KLK, kallikrein-related peptidases; ROS, reactive oxygen species. Level of evidence: IA evidence includes evidence from meta-analyses of randomized controlled trials; IB evidence includes evidence from at least 1 randomized controlled trial; IIA evidence includes evidence from at least 1 controlled study without randomization. Source: Two AM, Wu W, Gallo RL, et al. Rosacea: part II. Topical and systemic therapies in the treatment of rosacea. J Am Acad Dermatol. 2015;72(5):761-770.

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morning, erythema is generally visibly reduced within 30 to 60 minutes to a few hours, with peak effect evident after approximately 3 to 4 hours. Duration of maximal effect is 6 to 8 hours, with return to near-baseline by approximately 12 hours. The alpha-agonists, brimonidine 0.33% gel and oxymetazoline 1% cream, specifically affect vasculature within the superficial and deep dermal plexuses that contain a complete, concentric, smooth muscular layer; they do not seem to exert any beneficial or adverse effects on inflammatory lesions or on capillaries and telangiectasias, which lack a smooth-muscle layer.5,6,29 Brimonidine exerts its effect predominantly through stimulation of alpha 2 adrenoreceptors, while oxymetazoline is primarily an alpha1A adrenoreceptor agonist. Follow-up with the patient at 2 to 4 weeks is recommended to assess response to the alpha-agonist treatment. During follow-up, review instructions for use and ask about tolerability or aggravation of facial erythema, as cases of rebound or paradoxical erythema have been reported with brimonidine in approximately 15% to 20% of treated patients.29,44,45 Sporadic cases of allergic contact dermatitis induced by topical brimonidine have been reported.46 Clinically relevant rebound or paradoxical erythema with oxymetazoline 1% cream was not reported in the pivotal and long-term (52-week) studies to date.42,47 Telangiectasia Persistent areas of telangiectasia can be addressed with physical modalities, such as the use of light and laser devices. Laser technologies include frequency-doubled potassium titanyl phosphate (KTP) laser, neodymium-doped yttrium aluminum garnet laser (Nd:YAG), and pulsed dye laser (PDL). They use wavelengths in a range that is absorbed by hemoglobin, leading to vessel destruction.34,48 Self-care and counseling For all patients with rosacea, self-care is crucial. Optimally, clinicians and patients collaborate on identifying a treatment plan that the patient can follow to achieve long-term control of rosacea symptoms. Elements of such a plan include an appropriate skincare regimen, trigger avoidance, medical therapies, and physical modalities. Many triggers of rosacea f lares have been identified. Sensitivity to triggers varies from person to person, but examples of triggers include extremes of ambient temperature, spicy foods, alcoholic beverages, overly hot foods or beverages, cosmetic and skincare products with potentially irritating

PATIENT CASE: Outcome Gerard expressed that he was interested in controlling the rosacea flares and decreasing the facial redness that persists between flares. He also wanted to keep the regimen as simple as possible. He was educated in proper skincare with emphasis on product selection. He was also informed about consistent photoprotection and sunscreen use. After a discussion of treatment options, it was decided to initiate treatment with oxymetazoline 1% cream once daily in the morning and oral doxycycline 40-mg modified-release capsule once daily. Gerard preferred using only one topical agent, and he felt he would not adhere consistently with use of more than that. He also liked stopping the oral minocycline, as his wife expressed concern to him about long-term antibiotic use, and he was happy to use an oral agent that is not associated with antibiotic selection pressure but that could reduce the frequency and intensity of papulopustular flares. Gerard also expressed interest in future treatment for some of the more visible telangiectasias on his face, although he wanted to hold off until he sees how he responds to the initial treatment regimen.

ingredients, and various kinds of physical or psychological stress.7,8 Patients may benefit by tracking their responses to identify which triggers affect them personally, then applying that knowledge to implement strategies to limit exposures. Adequate early follow-up after developing a treatment plan helps maximize patient adherence.49,50 Adherence tends to be higher for oral medication than for topical medication. Oral therapy is quick and convenient, with no messiness, odor, or other characteristics that patients sometimes cite as disadvantages of topical therapies.49 Patient counseling is an important part of the clinicianpatient partnership in managing rosacea.51 General recommendations include the following: • Set expectations; rosacea is chronic and cannot be cured, but it can be managed • Remind patients about consistent correct medication use and follow up regularly to monitor their progress • Ensure that patients allow enough time to see results of treatment; it may take several weeks before the optimal effects of medical therapy are noticeable • Educate patients that they must continue treatment even after they see improvement, to help ensure that their condition stays under control

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• Encourage gentle facial skincare and photoprotection with sunscreen use every day • Educate patients on identifying their environmental and lifestyle triggers and implementing strategies to minimize exposure to them • Address the psychological and social impact of rosacea • Counsel patients on the need for consistent adherence to treatment—pharmacologic and nonpharmacologic recommendations

3. Woo YR, Lim JH, Cho DH, Park HJ. Rosacea: molecular mechanisms and management of a chronic cutaneous inflammatory condition. Int J Mol Sci. 2016;1562:1-23. 4. Wilkin J, Dahl M, Detmar M, et al; National Rosacea Society Expert Committee. Standard grading system for for rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Am Acad Dermatol. 2004:50(6):907-912. 5. Del Rosso JQ. Advances in understanding and managing rosacea: part 2: the central role, evaluation, and medical management of diffuse and persistent facial erythema of rosacea. J Clin Aesthet Dermatol. 2012;5(3):26-36.

Summary

6. Del Rosso JQ, Thiboutot D, Gallo R, et al. Consensus recommenda-

Optimal management of rosacea requires careful assessment of the clinical features that are present in the individual patient with integration of therapies that adequately treat the presenting signs and symptoms. Proper skincare and photoprotection are important components of the management plan. Many currently available therapies address the papulopustular lesions of rosacea and perilesional/lesional erythema. Topical alpha-agonists, however, are the only agents that specifically target the characteristic DCE of rosacea. These agents induce vasoconstriction of superficial cutaneous vessels, which reduces background erythema over several hours after daily application. When used properly, physical modalities such as laser treatment can be helpful in treating telangiectasia and DCE caused by dilated superficial vasculature. Consideration of the relationship between the specific clinical manifestations in a particular patient is crucial to proper selection of treatment, including combination therapy, with adjustments of the regimen implemented over time when clinically applicable. In summary, differentiating underlying persistent (nontransient) erythema from lesional or perilesional erythema is critical in management decision-making. Lesional and perilesional erythema resolve with use of therapeutic agents that reduce papulopustular lesions. Physical modalities can be used for treatment of telangiectasias. For treatment of persistent DCE, topical alpha-adrenergic receptor agonist therapy is indicated. n

tions from the American Acne & Rosacea Society on the management of rosacea, part 1: a status report on the disease state, general measures, and adjunctive skin care. Cutis. 2013;92(5):234-240. 7. Schwab VD, Sulk M, Seeliger S, et al. Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15(1):53-62. 8. Schaller M, Schöfer H, Homey B, et al. Rosacea management: update on general measures and topical treatment options. J Dtsch Dermatol Ges. 2016;14(suppl 6):17-27. 9. Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol. 1988;124(6):869-871. 10. Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea. J Clin Acad Dermatol. 2002;46(4):584-587. 11. Del Rosso JQ, Gallo RL, Tanghetti E, et al. An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis. 2013;91(3 suppl):1-7. 12. Tan J, Almeida L, Bewley A, et al. Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel. Br J Dermatol. 2017;176(2):431-438. 13. Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Invest Dermatol Symp Proc. 2011;15(1):2-11. 14. Aldrich N, Gerstenblith M, Fu P, et al. Genetic vs environmental factors that correlate with rosacea: a cohort-based survey of twins. JAMA Dermatol. 2015;151(11):1213-1219. 15. Del Rosso JQ, Thiboutot D, Gallo R, et al. Consensus recommendations from the American Acne & Rosacea Society on the man-

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recommendations from the global ROSacea COnsensus (ROSCO) panel.

Acad Dermatol. 2015;73(2):249-254.

Br J Dermatol. 2017;176(2):465-471.

23. Augustynowicz A, Maranda EL, Zullo J, et al. The bard’s blunder—

40. Two AM, Del Rosso JQ. Kallikrein 5-mediated inflammation in rosacea:

debunking the myth around rhinophyma. JAMA Dermatol. 2016;152(4):379.

clinically relevant correlations with acute and chronic manifestations in

24. Huynh TT. Burden of disease: the psychosocial impact of rosacea on a

rosacea and how individual treatments may provide therapeutic benefit.

patient’s quality of life. Am Health Drug Benefits. 2013;6(6):348-354.

J Clin Aesthet Dermatol. 2014;7(1):20-25.

25. van der Linden MM, Van Rappard DC, Daams JG, et al. Health-related

41. Mirvaso [package insert]. Fort Worth, TX: Galderma Laboratories;

quality of life in patients with cutaneous rosacea: a systematic review. Acta

July 2016.

Derm Venereol. 2015;95(4):395-400.

42. Rhofade [package insert]. Irvine, CA: Allergan Pharmaceuticals; 2017.

26. Dirschka T, Micali G, Papadopoulos L, et al. Perceptions on the psycho-

43. Del Rosso JQ. Management of facial erythema of rosacea: what is the

logical impact of facial erythema associated with rosacea: results of inter-

role of topical α-adrenergic receptor agonist therapy? J Am Acad Dermatol.

national survey. Dermatol Ther (Heidelb). 2015;5(2):117-127.

2013;69(6 suppl 1):S44-S56.

27. Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol

44. Docherty JR, Steinhoff M, Lorton D, et al. Multidisciplinary consider-

Sci. 2009;55(2):77-81.

ation of potential pathophysiologic mechanisms of paradoxical erythema

28. Cribier B. Pathophysiology of rosacea: redness, telangiectasia, and

with topical brimonidine therapy. Adv Ther. 2016;33(11):1885-1895.

rosacea. Ann Dermatol Venereol. 2011;138(suppl 3):S184-S191.

45. Tanghetti EA, Jackson JM, Belasco KT, et al. Optimizing the use of topi-

29. Wollina U. Recent advances in the understanding and management of

cal brimonidine in rosacea management: panel recommendations. J Drugs

rosacea. F1000Prime Rep. 2014;6:50.

Dermatol. 2015;14(1):33-40.

30. Two AM, Wu W, Gallo RL, Hata TR. Rosacea: part 1. Introduction, cat-

46. Bangsgaard N, Fischer LA, Zachariae C. Sensitization to and allergic

egorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol.

contact dermatitis caused by Mirvaso(®) (brimonidine tartrate) for treat-

2015;72(5):749-760.

ment of rosacea—2 cases. Contact Dermatitis. 2016;74(6):378-379.

31. Steinhoff M, Schmelz M, Schauber J. Facial erythema of rosacea –

47. Stein-Gold L, Kircik LH, Draelos ZD, et al. Efficacy and safety of topical

aetiology, different pathophysiologies and treatment options. Acta Derm

oxymetazoline cream 1.0% for treatment of facial erythema associated

Venereol. 2016;96(5):579-586.

with rosacea: findings from two phase 3, pivotal trials. Presented at: 75th

32. Aroni K, Tsagroni E, Kavantzas N, et al. A study of the pathogenesis

Annual Meeting of the American Academy of Dermatology (AAD); March

of rosacea: how angiogenesis and mast cells may participate in a complex

3, 2017; Orlando, FL.

multifactorial process. Arch Dermatol Res. 2008;300(3):125-131.

48. Hofmann MA, Lehmann P. Physical modalities for the treatment of

33. Yamasaki K, Kanada K, Macleod DT, et al. TLR2 expression is increased

rosacea. J Dtsch Dermatol Ges. 2016;14(suppl 6):38-43.

in rosacea and stimulates enhanced serine protease production by kerati-

49. Kuo S, Huang KE, Davis SA, Feldman SR. The rosacea patient jour-

nocytes. J Invest Dermatol. 2011;131(3):688-697.

ney: a novel approach to conceptualizing patient experiences. Cutis.

34. Del Rosso JQ. Management of cutaneous rosacea: emphasis on new

2015;95(1):37-43.

medical therapies. Expert Opin Pharmacother. 2014;15(14):2029-2038.

50. Jackson JM, Knuckles M, Minni JP, et al. The role of brimonidine

35. Del Rosso JQ, Thiboutot D, Gallo R, et al. Consensus recommen-

tartrate gel in the treatment of rosacea. Clin Cosmet Investig Dermatol.

dations from the American Acne & Rosacea Society on the manage-

2015;8:529-538.

ment of rosacea, part 5: a guide on the management of rosacea. Cutis.

51. National Rosacea Society. What to do now. https://www.rosacea.org/

2014;93(3):134-138.

patients/whattodonow. Accessed April 25, 2017.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 37

CME

POSTTEST Expiration date: February 28, 2019

A statement of credit will be issued only upon receipt of a completed preassessment test, activity evaluation form, and posttest with a score of 70% or higher. All components must be completed and submitted online at ClinicalAdvisor.com/Feb18feature. CREDITS: 1.00 | Rosacea: Assessment and management strategies

1. Which of the following is the most common presentation of rosacea? a. Persistent telangiectasias with papulopustular lesions and rhinophyma b. Transient flushing and/or facial erythema, either with or without with telangiectasias c. Transient flushing and/or facial erythema with papulopustular lesions d. Persistent diffuse centrofacial erythema (DCE), either with or without papulopustular lesions 2. Which of the following statements regarding the 4 subtypes of rosacea (erythematotelangiectatic, papulopustular, phymatous, and ocular) is true? a. There is little variation or overlap among presentations of the 4 subtypes of rosacea. b. Subtype classification is now widely regarded as clinically irrelevant and misleading. c. Many experts consider persistent (nontransient) DCE a necessary diagnostic feature of rosacea, regardless of subtype. d. Treatment selection should be directed by the patient’s subtype classification. 3. Patients typically find which aspect of rosacea most burdensome? a. Facial stinging and burning sensations b. Lack of effective treatments c. Difficulty adhering to oral treatment regimens d. Psychosocial effects associated with visible manifestations 4. A 35-year-old fair-skinned, red-headed woman with a history of adolescent acne presents with facial erythema and an outbreak of papulopustular lesions affecting her nose and cheeks that developed about 2 months ago, a few weeks after she discontinued oral contraceptives. She tried to treat her “pimples” with the same over-the-counter benzoyl peroxide cleanser she used as a teenager, but discontinued it when she started to experience redness, sensitivity, and stinging of her face, which persist 2 weeks later. The most likely diagnosis is: a. Rosacea c. Seborrheic dermatitis b. Contact dermatitis d. Acne vulgaris

5. Which of the following statements regarding the pathophysiology of rosacea is true? a. Genetics play a more important role than do extrinsic triggers. b. Extrinsic triggers play a more important role than do genetics. c. Pathogenic mechanisms include augmented immune responses and neurovascular dysregulation. d. Rhinophyma develops primarily in response to vasodilating medications or alcohol. 6. Which of the following is not a causative factor in rosacea that presents as persistent DCE alone, without inflammatory lesions? a. Impairment of the permeability barrier b. Acute and/or subacute vasodilation of centrofacial skin vasculature c. Fixed vascular changes and telangiectasias d. Demodex colonization 7. Which of the following treatments has been proven effective in the management of DCE in rosacea? a. Topical alpha-agonists d. Topical ivermectin b. Topical metronidazole e. Oral doxycycline c. Topical azelaic acid (sub-antibiotic dose) 8. What is the presumed mechanism of action of metronidazole in rosacea? a. Vasoconstriction of the smooth muscle surrounding vessels of the superficial and deep dermal plexuses b. Decreased expression of kallikrein-related peptidase (KLK) and cathelicidin plus decreased reactive oxygen species (ROS) generation c. Antiparasitic and anti-inflammatory properties d. Decreased ROS generation and anti-inflammatory effects 9. Patients with rosacea using topical alpha-agonists to treat DCE should be counseled to: a. Expect to see results within 7 to 10 days b. Discontinue treatment after they see adequate improvement in their symptoms c. Use an exfoliating face wash and sunscreen every day d. Identify their environmental and lifestyle triggers and implement strategies to minimize or avoid exposure to them

TO TAKE THE POSTTEST please go to: ClinicalAdvisor.com/Feb18feature

38 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

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

MY MOST MEMORABLE PATIENT NECK AND CHEST PAIN IN A STUDENT My patient was a pre-med student in his early 20s who came in complaining of left-sided neck pain. He wasn’t sure how it started, maybe after playing golf or after staring down for hours while writing a paper. Going to the chiropractor had not helped, nor did a course of steroids and NSAIDs. He is “never sick,” and his mom is a nurse and wanted him to come to the ER and get checked out. When I went through the review of systems, he seemed to say “yes” to everything. He had cold-like symptoms and may have had a few pounds of weight loss but thought it could be stress from school or a few low-grade fevers, etc. Knowing that when I was a student in the medical field I would tend to overexaggerate when I was feeling sick, I just listened and nodded, and in the back of my mind thought everything is probably fine. I started my exam. First his neck, then his heart and lungs. Send us your letters with questions and comments to: Advisor Forum, The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001.You may contact us by e-mail at editor@clinicaladvisor.com. If you are writing in response to a published letter, please indicate so by including the number in parentheses at the end of each item. Letters are edited for length and clarity. The Clinical Advisor’s policy is to print the author’s name with the letter. No anonymous contributions will be accepted.

“When I take a deep breath, it kinda hurts here,” he said, pointing to the left side of his chest. After I finished the rest of my physical exam and got a little more information, we started our workup and decided to do imaging of his neck, and because he happened to mention pain with inspiration, his chest. While all other studies were normal, the chest X-ray seemed suspicious and the radiologist suggested a CT. We waited for the results, and finally the report came back. The pre-med student, who came in complaining of neck pain, had a 12-cm mass in the left side of his chest. I immediately felt awful, as I initially thought he was exaggerating. In PA school you hear about horrible things, and when you sneeze you think, “Oh no, I have cancer.” However, in his case he actually might. We went in to tell him the news. His wife and parents came in, and we went over our findings with them. They fought through tears to ask questions and understand how a seemingly healthy person could have something so dangerous. We couldn’t answer many of their questions at the time and reassured him that now he could get the help he needed. Rather than starting his next semester at school he was referred to oncology to have the mass removed and begin treatment. Is it rare to have a patient with neck pain end up having a 12-cm mass? Absolutely. But on this day I learned to listen and not let my bias take over. I learned that sometimes your gut and initial ideas could be wrong. And I learned that it

OUR CONSULTANTS

Philip R. Cohen, MD,

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

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

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

Abimbola Farinde, PhD, PharmD,

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

40 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

Laura A. Foster, CRNP, FNP,

Abby A. Jacobson, MS, PA-C,

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

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

can be a simple answer or exam finding that can lead you down a completely different path. I won’t forget this patient, his case, or the lessons I have learned. In the future, I will keep my thoughts as thoughts and not allow myself to rush into judgment. My patients will know their bodies better than anyone else. I will never forget to listen.—NICOLLE GALE, PA-C, West Palm Beach, Fla. (232-1)

CLINICAL PEARLS RELIEF FOR ORTHOSTATIC HYPOTENSION Patients on particular medications, or with certain underlying medical conditions, may experience orthostatic hypotension when arising from bed or a chair. If the patient has stepped far enough away from the bed or chair to return safely, suggest that he or she quickly find either a blank part of the nearest wall or the nearest door frame. Then put your back to the wall or door frame, and slide down onto your rump. Even if you pass out on the way down, you are very unlikely to land on your face or risk a broken bone from a fall.—DENNISE RICHARDSON, PhD, PA-C (ret), Seven Points, Texas (232-2)

CASE FILES A MAN WITH SNEEZING FITS Contributed by Sherril Sego, FNP-C, DNP Joe asked his primary care provider why he had fits of sneezing, often mounting into double digits. There was no warning, he had no allergies, and they were not associated

Debra August King, PhD, PA,

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

Mary Newberry, CNM, MSN,

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

with any cold symptoms or other conditions. This condition had been present for as long as Joe could remember. He sought care because after a recent dental procedure that required anesthetizing of the mandibular branch of CN V, he did not sneeze for several days. It is generally accepted that the “sneeze center” is in the medullary area of the brainstem, and specifically associated with the fifth cranial nerve, the trigeminal. With the three branches of this, the largest of the cranial nerves, the majority of facial sensory messages are sent and received. Experimentally, researchers have noted that the association of irritation of the trigeminal nerve root (at approximately C 1-2-3) gives rise to sneezing. After extensive examination and history, it was found that Joe had significant cervical spine impingement of these levels due to notable scoliosis. Since the sneezing fits did not represent a serious condition, Joe was reassured that his condition was benign. (232-3)

WILMS TUMOR IN A CHILD Contributed by Sherril Sego, FNP-C, DNP A 2-year-old boy was having worsening daily episodes of explosive diarrhea. He had no fevers, and his appetite and diet were unchanged. When his mother took him to the pediatrician, an abdominal examination detected a palpable mass in the left flank. Further imaging confirmed a mass on the left kidney. Based on presenting symptoms and imaging, the tentative diagnosis of Wilms’ tumor was made. Biopsy is not typically done due to the risk of fragmentation of this delicate tumor. Surgical excision is the treatment of choice when possible, based on the staging of the tumor, its size, and involvement of associated structures. This child’s tumor was successfully resected. In such cases, the 5-year survival rate is greater than 90%. (232-4) n

Claire O’Connell, MPH, PA-C,

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

Katherine Pereira, DNP, FNP,

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

Sherril Sego, FNP-C, DNP,

is an independent consultant in Kansas City, Mo.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 41

Writers’ Guidelines The Clinical Advisor welcomes submissions from its readers. Writing for us is an opportunity to share your knowledge and experience with your colleagues — and to collect a fee in the bargain! We pay an honorarium for every submission we accept. We’ll be glad to work with you to develop your ideas into compelling articles. As for length, that depends on which kind of article you submit. CLINICAL FEATURES update our readers on the latest information about conditions seen in everyday practice. Running approximately 2,500 to 5,000 words, including the references, features can be written either as regular narratives or as a series of questions and answers. Topics should be selected with the busy primary-care clinician in mind; specialists should review specialty topics from the primary-care point of view. If at all possible, articles should be accompanied by clinical photos. Charts, tables, and algorithms are also encouraged. Please include your title and affiliation. CLINICAL CHALLENGE is our popular department comprising histories of difficult cases. Each case is presented as a step-by-step, chronological account, revealing the author’s thought processes along the way. It is divided into sections in this order: the patient presentation; the patient history; the twists and turns eventually leading to a diagnosis; the treatment and outcome; and a discussion of the lessons learned or of the condition in general. The length should be about 1,500 words, and accompanying images are encouraged. Please include your title and affiliation. Dermatology Clinic CASE #1

Fingernail dystrophy in a young child SIMO HUANG, BS, CHRISTOPHER RIZK, MD

The patient is a 12-year-old Hispanic girl who presents with a 6-month history of nail dystrophy involving all of her fingernails. On examination, all 10 of her fingernails exhibit longitudinal ridging, pitting, fragility, thinning, and distal notching. The patient’s mother is very concerned about the cosmesis of her daughter’s nails. The patient has no systemic symptoms. On review of systems, the patient’s mother noted that her daughter has started to develop circular patches of hair loss that appear to resolve on their own. The patient has no relevant social or family history and does not take any medications. What is your diagnosis? Turn to page 54

CASE #2

Headache, malaise, and a rash ZACHARY SOLOMON, BS, DAVID RIZK, BA, CONNIE WANG, MD

A 42-year-old man presents with a four-day history of experiencing headache, malaise, and stabbing right-sided headache. Two days after his initial symptoms appeared, he developed a rash over the area of pain. He reports that he went hiking through the Texas hill country prior to becoming ill. The patient is otherwise in good health and has an unremarkable medical history. Physical examination reveals unilateral erythematous, thin, raised plaques over the right forehead. In addition, he has no relevant social or family history. What is your diagnosis? Turn to page 55 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • DECEMBER 2017 53

DERMATOLOGY CLINIC is a department that presents photos of actual cases and asks readers to identify the condition. Each case opens with one or two color photos and a 75-to-100-word description of the patient presentation, without giving away the diagnosis. This is followed by a 750-to-1,000-word summary that includes a fuller description of the ailment, an explanation of how the correct diagnosis was reached, a general review of the condition along with a differential diagnosis, and a description of the patient’s treatment and outcome. Topics must be approved by the editor prior to submission. Please include your title and affiliation. COMMENTARY is our guest editorial page. It gives you the opportunity to sound off on an issue of importance to your colleagues nationwide. A typical Commentary runs about 600 words in length. Please include your title and affiliation. To discuss your editorial ideas, contact us by phone at 646.638.6078; by e-mail to editor@ClinicalAdvisor.com; or by mail to The Clinical Advisor, 275 7th Avenue, 10th Floor, New York, NY 10001.

42 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

Dermatology Clinic CASE #1

Severe acne on the face and chest LOGAN DEBORD, BS, DAVID RIZK, BA, CONNIE WANG, MD

The patient is a 21-year-old male who presents for continued acne therapy. He has had severe acne on his face, chest, and back for years. He is happy with his current acne regimen of topical tretinoin, topical clindamycin, and oral minocycline. He has been on the regimen for years. On examination, you notice significant blue-black discoloration confined to sites of previous acne scars. The patient has no other medical problems and no relevant social or family history. What is your diagnosis? Turn to page 44

CASE #2

Spots on a woman’s torso and arms MARGARET BARTON, JULIA R. NUNLEY, MD

A 38-year-old African American woman was referred to dermatology because of spots on her torso and arms. The lesions were asymptomatic, but their development, cause, and cosmesis were of concern. No benefit was seen with the use of OTC remedies such as hydroxycortisone 1% cream or vitamin E oil. Her medical history was significant for systemic lupus erythematosus, well controlled on hydroxychloroquine. Physical examination revealed numerous, well-circumscribed, 0.5- to 2-cm, hypopigmented, round-to-oval macules of wrinkled skin on her anterior chest wall, back, abdomen, and bilateral upper arms. Invagination of the lesions was noted with palpation. A punch biopsy was performed. What is your diagnosis? Turn to page 45 www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 43

Dermatology Clinic CASE #1

Minocycline-induced hyperpigmentation

Minocycline is a broad-spectrum tetracycline antibiotic commonly prescribed for acne vulgaris. Aside from its antimicrobial uses, minocycline has both neuroprotective and anti-inf lammatory activity and thus may be beneficial for autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease, and rosacea.1 Although its most commonly experienced adverse effects are gastrointestinal distress and vertigo, minocycline-induced hyperpigmentation (MIHP) is a common and well-documented adverse effect occurring more frequently, compared with other tetracyclines (possibly due to extended duration of treatment).1,2

The most commonly experienced adverse effects in patients with MIHP are gastrointestinal distress and vertigo. Minocycline may induce either circumscribed or diffuse skin hyperpigmentation. The most common causes of druginduced circumscribed hyperpigmentation are minocycline and certain antimalarials.3 MIHP can be classified into three distinct types: Type I is a blue-black discoloration confined to sites of previous inflammation such as acne or surgical scars; it is likely the most common. Type II consists of circumscribed blue-gray macules ranging from 1 mm to 10 cm in size that appear most commonly on the shins (in a similar distribution to antimalarial-induced hyperpigmentation) and may be mistaken for ecchymoses; however, type II lacks subsequent green and yellow color changes and does not fade quickly. Type III is a diffuse, muddy brown hyperpigmentation most prominent in sun-exposed areas and is the least common type.3,4 Types I and II tend to resolve slowly over time when involving the skin, whereas type III persists indefinitely.5 Types I and II hyperpigmentation may additionally involve mucous membranes, bone (especially within the oral cavity), sclera, nails, teeth, and thyroid. Gray or gray-green discoloration of the teeth may appear in isolation and remain for years after cessation of therapy.4,6 Staining of permanent teeth occurs in 3% to 6% of patients taking at least 100 mg/day of

minocycline, and onset may occur from one month to several years after beginning therapy.6 While the clinical effects of MIHP are mostly cosmetic, case reports have documented thyroid dysfunction secondary to pigmentation in vitro, as well as a possible association with papillary thyroid carcinoma in a patient who developed thyroid pigmentation.7,8 Type I hyperpigmentation appears unrelated to the daily dose of minocycline therapy; the drug’s lipophilicity allows it to distribute widely in adipose tissue and renders clinical effects possible even at low dose.4,6 However, incidence of types II and III MIHP increases with total exposure, with up to 40% of patients treated for at least one year affected. Types I and II typically onset following 3 months to several years of minocycline therapy.4 A higher risk for dermal hyperpigmentation exists for those on minocycline therapy that exceeds either 100 mg/day or a cumulative dose of 70 g.9 The incidence of MIHP in patients undergoing long-term treatment for acne vulgaris ranges from 2.4 to 14.8%.10 The condition has also been found to occur in 54% of patients on daily, long-term suppression for orthopedic infections, with a mean duration of therapy of 1.5 years and mean follow-up of 4.8 years. In this specific cohort of 291 patients, hyperpigmentation continued to persist in 24% following discontinuation.11 Because hyperpigmentation is a well-known side effect of minocycline, the key to diagnosis is establishing ingestion of the drug in the patient history.3 Patients with immunobullous disease may have more significant skin hyperpigmentation, and other possible risk factors include vitamin D deficiency, non-cirrhotic liver pathology, and use of a concurrent medication known to cause hyperpigmentation.11 Minocycline is likely incorporated into tissue after chelating divalent metal cations (eg, iron) and forming insoluble complexes.12 Pigment usually consists of a minocycline metabolite-cation complex stored within macrophage lysosomes (or less commonly, an insoluble drug metabolitemelanin complex).9 Pigmentation in sites other than the skin and oral mucosa is the product of an oxidation reaction and may be permanent.6 Histologically, types I and II MIHP feature pigment granules within macrophages in the dermis and occasionally the subcutaneous fat. Confirmation is made by staining granules positively for melanin/iron (iron in type 1, and melanin and iron in type 2). Increased melanin (in both the epidermis and dermis) is found histologically in type III MIHP, possibly secondary to a low-grade photosensitivity reaction.4 Prevention and treatment of hyperpigmentation includes sun protection, early recognition of the disorder, and discontinuation of minocycline if it occurs.5 While photosensitivity

44 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

reactions are a risk of tetracycline therapy and unlikely to be prevented by sunscreen, they are less common with minocycline as compared with other drugs in its class.6 Multiple case reports have documented complete resolution of MIHP after treatment with Q-switched lasers and fractional photothermolysis, both separately and in combination.4,13 Types I and II are likely more responsive to treatment than type III. The mechanism by which laser therapy removes pigment may be via fragmentation and drainage through lymphatics.14 The patient in this case was diagnosed with type 1 minocycline-induced hyperpigmentation. He was advised to use sun protection and immediately discontinue minocycline. He was offered referral for laser therapy but declined since the discoloration did not bother him. n Logan DeBord, BS, is a medical student at the Baylor College of Medicine, David Rizk, BA, is a medical student at the University of South Alabama, and Connie Wang, MD, is a dermatology resident at the Baylor College of Medicine in Houston. References 1. Garrido-Mesa N, Zarzuelo A, Gálvez J. Minocycline: far beyond an antibiotic. Br J Pharmacol. 2013;169:337–352. 2. Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther. 2005;27:1329–1342. 3. Bolognia JL, Schaffer JV, Duncan, Karynne O, Ko, Christine J. Dermatology Essentials. Philadelphia: Elsevier, Inc; 2014. 4. James WD, Berger TG, Elston DM, Neuhaus IM, Micheletti RG, Andrews GC. Andrews’ Diseases of the Skin: Clinical Dermatology. 12th ed. Philadelphia: Elsevier, Inc; 2016. 5. Geria AN, Tajirian AL, Kihiczak G, Schwartz RA. Minocycline-induced skin pigmentation: an update. Acta Dermatovenerol Croat ADC. 2009;17:123–126. 6. Aronson JK. Meyler’s side effects of drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. 15th ed, vol 4. Amsterdam: Elsevier Science; 2006. 7. Taurog A, Dorris ML, Doerge DR. Minocycline and the thyroid: antithyroid effects of the drug, and the role of thyroid peroxidase in minocycline-induced black pigmentation of the gland. Thyroid Off J Am Thyroid Assoc. 1996;6:211–219. 8. Bruins NA, Oswald JE, Morreau H, Kievit J, Pavel S, Smelt AHM. Papillary thyroid carcinoma in a patient with sarcoidosis treated with minocycline. Neth J Med. 2007;65:185–187. 9. Star P, Choy C, Parsi K. Black veins: a case of minocycline-induced pigmentation post-sclerotherapy and a review of literature. J Cutan Pathol. 2017;44:83–92. 10. Mouton RW, Jordaan HF, Schneider JW. A new type of minocyclineinduced cutaneous hyperpigmentation. Clin Exp Dermatol. 2004;29:8–14. 11. Hanada Y, Berbari EF, Steckelberg JM. Minocycline-induced cutaneous hyperpigmentation in an orthopedic patient population. Open Forum Infect Dis. 2016;3:ofv107.

12. Griffin MO, Fricovsky E, Ceballos G, Villarreal F. Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010;299:C539-548. 13. Riemenschneider K, Powers JG. Successful treatment of minocyclineinduced pigmentation with combined use of Q-switched and pulsed dye lasers. Photodermatol Photoimmunol Photomed. 2017;33:117-119. 14. Nisar MS, Iyer K, Brodell RT, Lloyd JR, Shin TM, Ahmad A. Minocyclineinduced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects. Clin Cosmet Investig Dermatol. 2013;6:159–162.

CASE #2

Anetoderma associated with SLE

Histologic findings from a punch biopsy demonstrated a perivascular and periadnexal lymphohistiocytic infiltrate with normal collagen and no microthrombi; special stains revealed a marked loss of elastic fibers within the dermis, making the diagnosis of anetoderma. Anetoderma, an elastolytic disorder characterized by focal areas of loose skin, is categorized as primary or secondary based on a preexisting inflammatory process. The term anetoderma is derived from the Greek word “anetos,” meaning “slack.”1 Sometimes anetoderma is referred to as macular atrophy due to its clinical findings.2 Anetoderma presents as well-circumscribed areas of wrinkled skin that feel atrophic on palpation and can either herniate inward or bulge outward as sac-like protrusions.2 Most lesions are discrete, round-to-oval in shape, and range in diameter from 0.5 to 2 cm; however, some lesions can coalesce into larger patches.3 Areas are typically skin-colored, though they may be erythematous or hypopigmented. Lesions are most commonly localized to the trunk, thighs, and upper arms. Involvement of the face and neck is rare, while the scalp, palms, and soles are distinctively spared.6 The number of lesions varies greatly, from fewer than 5 to more than 100.3 Lesions may develop individually, or in crops, and enlarge throughout the course of 2 to 3 weeks; new lesions may continue to develop over years. Once present, they persist indefinitely. Fortunately, most are asymptomatic, although pruritus can occur. 3 The classification of anetoderma as primary or secondary is determined by the absence (primary) or presence (secondary) Continues on page 47

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Dermatology Clinic of a pre-existing inflammatory process. Curiously, at times both types can be seen in one individual and both can occur in the presence of a systemic disease.2 Familial anetoderma has been described but is exceedingly rare. Similarly rare is anetoderma in infancy. Initially, primary anetoderma was considered to be an idiopathic disorder; however, substantive evidence indicates an association with various immunologic processes, most commonly the presence of antiphospholipid antibodies, with or without the antiphospholipid syndrome.4 A variety of serologic tests may be abnormal in those with anetoderma, including complement levels and lupus anticoagulant, as well as anticardiolipin, anti-nuclear, and anti-beta-2 glycoprotein antibodies, with or without meeting the criteria for a specific connective tissue disease.4 That said, the association between anetoderma and systemic lupus erythematosus (SLE) is well accepted.5-7 However, because other systemic conditions such as syphilis, Sjogren syndrome, and systemic-sclerosis have also been linked to anetoderma, each patient should be thoroughly evaluated. Secondary anetoderma develops after an inflammatory, infiltrative, or iatrogenic process. Inflammation due to acne, urticarial pigmentosa, syphilis, varicella, lyme disease, leprosy, angular cheilitis, post-hepatitis B vaccination, granuloma annulare, Takayasu arteritis, and juvenile xanthogranuloma may all result in anetoderma. Neoplastic processes such as pilomatrixomas, schwannomas, B-cell lymphomas, mycosis fungoides, hamartomatous congenital melanocytic nevi, myxofibrosarcoma, and dermatofibromas have each been reported in association with anetoderma as well.2,8 Anetoderma may also be iatrogenic, most commonly seen following penicillamine use7 or in association with premature birth.9 Penicillamine-induced anetoderma has been reported in patients with Wilson disease.3 Theoretically, penicillamine may directly alter elastic tissue, or, perhaps, modify lysyl oxidase activity, a copper-dependent enzyme that plays a role in cross-linking elastin.3 Iatrogenic anetoderma of prematurity develops in infants, born between 24 to 32 weeks of gestation, within areas of trauma due to monitoring leads or electrodes or where adhesive tape was placed during their time in the intensive care units.10 Although most neonatal cases of anetoderma are iatrogenic, rarely will anetoderma present in a premature newborn who has not had perinatal monitoring; most congenital cases are associated with very low birth weight (<5th centile).9 The differential diagnosis of localized areas of loose skin is extensive. Conditions to be considered include a variety of other elastic tissue disorders such as cutis laxa, mid-dermal elastolysis, post-inflammatory elastolysis, papular acne scars,

acrodermatitis chronica atrophicans, Atrophoderma of Pasini and Pierini, corticosteroid-induced atrophy, lichen sclerosus, discoid lupus erythematous, perifollicular atrophoderma, perifollicular macular atrophy, neurofibromas, acrodermatitis chronica atrophicans, granulomatous slack skin (a variant of mycosis fungoides), and acrodermatitis chronica atrophicans.2 It is important to use the entire constellation of history, physical examination, and histologic findings to make the diagnosis of anetoderma. Lesion morphology and distribution are uniquely distinct from those of cutis laxa, mid-dermal elastolysis, and postinflammatory elastolysis, which tend to be more diffuse and widespread, compared with the wellcircumscribed lesions of anetoderma.2 When in doubt, histologic examination with special stains will demonstrate the classic loss of elastic fibers of anetoderma.11

Anetoderma presents in patients as wellcircumscribed areas of wrinkled skin that feel atrophic on palpation. The exact pathogenesis of anetoderma remains speculative. Proposed mechanisms include alterations in elastolytic enzyme activity, tissue ischemia, and phagocytosis of elastic fibers, as well as a variety of autoimmune and inflammatory processes.12 Jeong et al postulated that microthrombosis within dermal vessels induced local ischemia and elastic tissue degeneration in lupus-associated anetoderma, especially when associated with antiphospholipid antibodies.5 In the rare cases of familial or congenital anetoderma, theories revolve around the possibility of decreased production of elastic tissue, or increased destruction due to an altered balance of matrix metalloproteases.9 There is no approved treatment for anetoderma; lesions are generally everlasting.2 Reassurance should be provided that anetoderma is a benign, and usually asymptomatic, condition.3 When identified, causes of secondary anetoderma should be appropriately treated to reduce the risk of new lesions.8 Anecdotal reports suggest that topical corticosteroids and vitamin E, as well as oral penicillin G, niacin, aspirin, phenytoin, dapsone may be somewhat helpful. Although not FDA approved, or currently standard of care, surgical techniques such as cryotherapy7 or laser therapy may show some benefit.13,14 Complete surgical excision will result in lesion removal, but the cosmetic result may not be a good alternative.

www.ClinicalAdvisor.com â&#x20AC;˘ THE CLINICAL ADVISOR â&#x20AC;˘ FEBRUARY 2018 47

Dermatology Clinic Complete evaluation for our patient showed no additional laboratory abnormalities, specifically, no antiphospholipid antibodies. It was determined that her systemic lupus erythematosus was the associated systemic condition. She opted not to pursue any other treatment option for the isolated lesions. n Margaret Barton is a fourth-year medical student, and Julia Nunley is a professor of medicine at the Virginia Commonwealth University School of Medicine in Richmond, Va. References 1. Hodak E, David M. Primary anetoderma and antiphospholipid antibodies—review of the literature. Clin Rev Allergy Immunol. 2007;32:162. 2. Lewis KG, Bercovitch L, Dill SW, Robinson-Bostom L. Acquired disor-

“Sorry I’m late—I was getting dressed.”

ders of elastic tissue: part II. decreased elastic tissue. J Am Acad Dermatol. 2004;51:165-185. 3. Venencie PY, Winkelmann RK, Moore BA. Anetoderma. Clinical findings, associations, and long-term follow-up evaluations. Arch Dermatol. 1984;120:1032-1039. 4. Romaní J, Pérez F, Llobet M, et al. Anetoderma associated with antiphospholipid antibodies: case report and review of the literature. J Eur Acad Dermatol Venereol. 2001;15:175-178. derma in a patient with systemic lupus erythematosus. Ann Dermatol. 2014;26:621-623. 6. Funabiki M, Tanioka M, Miyachi Y, Utani A. Anetoderma accompanying microscopic panniculitis in a patient with antiphospholipid syndrome and systemic lupus erythematosus. Clin Exp Dermatol. 2009;34:259-261. 7. Aghaei S, Sodaifi M, Aslani FS, Mazharinia N. An unusual presentation of anetoderma: a case report. BMC Dermatol. 2004;4:9. 8. Kineston DP, Xia Y, Turiansky GM. Anetoderma: a case report and review of the literature. Cutis. 2008;81:501-506. 9. Wain EM, Mellerio JE, Robson A, Atherton DJ. Congenital anetoderma in a preterm infant. Pediatr Dermatol. 2008;25:626-629. 10. Maffeis L, Pugni L, Pietrasanta C, et al. Iatrogenic anetoderma of prematurity: a case report and review of the literature. Case Rep Dermatol Med. 2014;2014:781493. 11. Venencie PY, Winkelmann RK. Monoclonal antibody studies in the skin lesions of patients with anetoderma. Arch Dermatol. 1985;121:747-749. 12. Ishida Y, Koizumi N, Shinkai H, Miyachi Y, Utani, A. Primary anetoderma: a case report and its modified classification. J Dermatol. 2005;32:982–986. 13. Cho S, Jung JY, Lee JH. Treatment of anetoderma occurring after resolution of Stevens-Johnson syndrome using an ablative 10,600-nm carbon dioxide fractional laser. Dermatol Surg. 2012;38:677-679. 14. Lee SM, Kim YJ, Chang SE. Pinhole carbon dioxide laser treatment of secondary anetoderma associated with juvenile xanthogranuloma. Dermatol Surg. 2012;38:1741-1743.

48 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

“He’s at the ‘awkward stage’ in converting to paperless, so he carries both a laptop and a briefcase.”

5. Jeong NJ, Park SB, Im M, Seo YJ, Lee JH, Lee Y. Eruptive aneto-

Stat Consult

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

Description

• common pediatric ectoparasite infestation

Head lice

Also called

• pediculosis capitis Who is most affected

ALAN DRABKIN, MD

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

• healthy children aged 3-12 years regardless of hygiene • girls > boys • household contacts of infested children • adults with poor personal hygiene • less common in African Americans Incidence/prevalence

• common, estimated 6-12 million cases in United States per year • reported prevalence 3.4%-35% Likely risk factors

• head-to-head contact, especially in schools, child care centers, or “sleepover” camps • household contacts • overcrowded living conditions Possible risk factors

• hair traits Factors not associated with increased risk

• • • •

hygiene (in children) length of hair frequency of brushing or shampooing socioeconomic class

Associated conditions

• other louse infestation or scabies (especially in indigent, homeless, or refugee populations) Causes Effective treatments for head lice include topical pediculicides and occlusive agents.

• head louse Pediculus humanus var capitis Pathogenesis

• life cycle repeats every 3 weeks — female louse lives 3-4 weeks, lays up to 10 eggs (nits) daily www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 49

Stat Consult ——eggs initially translucent, attached to base of hair shaft by glue-like substance from louse ——empty egg casings are white, viable nits pigmented ——eggs incubate (need heat of scalp) and hatch in 7-12 days ——female nymphs grow for about 9-12 days, then mate and lay eggs • no transmission of other disease agents to humans History

• Chief concern (CC) ——scalp pruritus (due to injected louse saliva) ——“something crawling on my head” ——often asymptomatic • Social history (SH) ——ask if any cases of head lice at child’s school or day care • Physical ——HEENT ■■ primary findings are nits or adult lice (may require magnifying lens) »»nits at proximal ends of hair shafts »»viable nits most easily seen at nape of neck or behind ears at hairline »»height of nits above scalp due to hair growth indicates duration of infestation (1 cm/month) »»number of lice found may vary by cultural hair grooming practices ■■ secondary skin reactions to lice or scratching »»excoriation »»secondary bacterial infections ——Neck ■■ posterior cervical local adenopathy if secondary skin infection Making the diagnosis

• presence of live adult louse, nymphs, or viable-appearing eggs (nits) on head • nits appear viable if found <1 cm of scalp, firmly attached to hair, and have microscopic “eye spot” Differential diagnosis

• other causes of scalp pruritus ——irritation from hairstyling products ——allergic contact dermatitis ——seborrheic dermatitis • dead eggs or empty egg cases • “pseudo-nits”—nodules resembling nits (can be easily separated from hair) ——dandruff

——dried hairspray ——dirt, lint, sand ——white piedra—fungi (Trichosporon beigelii) ——hair casts—desquamated cylindrical epithelial cell plug that encircles hair, easily movable Testing overview

• inspection ——wet and comb hair, remove tangles ——examine under strong light and with magnifying glass ——use fine-toothed comb (teeth 0.2-0.3 mm apart) ——insert comb near crown at scalp ——comb entire head systematically at least twice ——examine comb after each stroke Treatment overview

• topical pediculicides ——optimal pediculicide dependent on local resistance patterns ——universal retreatment recommended in 7-10 days if live lice seen ——permethrin 1% applied to towel-dried hair, leave for 10 minutes then rinse ■■ F DA approved in adults and children ≥2 months old ■■ recommended by AAP as treatment of choice for head lice ——malathion 0.5% lotion applied to dry hair, then after 8-12 hours washed off with shampoo ■■ FDA approved in adults and children ≥6 years old ■■ recommended when permethrin resistance suspected ——benzyl alcohol lotion 5% lotion applied for 10 minutes ■■ FDA approved in patients ≥6 months old ——ivermectin 0.5% lotion applied to dry hair for 10 minutes ■■ FDA approved in patients >6 months old ——other topical treatments ■■ dimethicone 4% lotion ■■ spinosad 0.9% topical suspension (FDA approved in patients ≥4 years old) ■■ pyrethrins with piperonyl butoxide applied to dry hair for 10 minutes ■■ lindane no longer recommended for use as pediculicide • occlusive agents may be effective including ——melaleuca plus lavender oil ——coconut plus anise oil ——petroleum jelly • nit removal ——evidence limited and inconsistent

50 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

— nit-removal combs do not appear to be effective adjunct to topical pediculicide — “no nit” policies for return to school ■ discouraged by AAP and APHA ■ may be required for reentry to school or day care based on local regulations • oral medications — not approved by FDA for treatment of head lice — options may include ■ trimethoprim-sulfamethoxazole 5 mg/kg twice daily ■ oral ivermectin 400 mcg/kg twice 7 days apart ■ pediculicide considered effective if lice dead or slowly moving 8-12 hours after treatment

• live eggs not removed • acquired resistance to pediculicide • treatments to consider if proven resistance or active infestation documented include — benzyl alcohol 5% if age >6 months — malathion 0.5% if age >24 months — manual removal via wet combing or occlusive method (such as petrolatum jelly or suffocation product) for younger patients, with 2-4 treatment cycles Complications

• secondary bacterial skin infection due to scratching (rare) Prognosis

• physical nit removal (evidence for effectiveness limited and inconsistent) • nit-removal combs do not appear to be effective adjunct to topical pediculicide

• pruritus may persist 7-10 days after effective treatment • current resistance rates unknown • most children with nits but no active lice do not develop active lice • re-infestation may be common

Desiccation

Contacts of index cases

• blowing hot air through custom-built hair dryer for 30 minutes reported effective • desiccation with regular blow-dryer not recommended (due to potential spread)

• screen all household members • treat if live lice or nits identified within 1 cm of scalp • consider treating family members who share a bed with index case even if no live lice found

Treatments not recommended

School attendance

• head shaving (effective but distressing) • flammable or toxic substances such as gasoline or kerosene products • nit-loosening agents (such as vinegar, vinegar-based products, acetone, bleach, vodka, and WD-40) • topical spray (dyes nits bright pink)

• do not restrict children from school due to lice, due to low risk of contagion within classrooms ■

Other management

Follow-up

• confirm treatment success 1-2 days after final application of pediculicide — if moving lice of all sizes present, resistance — if only 1 adult-size louse present, re-infestation • re-treat with different pediculicide if re-infestation occurs within 1 month Causes of treatment failure

• • • • •

misunderstanding/noncompliance instructions inappropriate instructions from product/clinician misdiagnosis inappropriate product used failure to re-treat at recommended interval

Case Study Library Check out all of our case studies in obesity, diabetes, and other important topics in primary care — along with our clinical challenges — by visiting us at: ClinicalAdvisor.com/Case-Study

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Dermatologic Look-Alikes Growing, dyspigmented lesions LINDSEY LIMBAUGH, BA, EMMA WEISS, BA, CHRISTOPHER RIZK, MD

CASE #1

CASE #2

A 54-year-old African American woman presents with large dyspigmented patches on her shins bilaterally. She states that the lesions started as small dots that have progressed to large patches during the last several years. She denies pain, itching, or any type of discomfort associated with the lesions. On examination, the patient has large, waxy, atrophic, yellow-colored plaques on both her shins. The patient has a past medical history of renal failure and type 2 diabetes.

A 26-year-old Indian patient presents with several dyspigmented lesions in his forehead. The patient states that the lesions have been growing and increasing in number for several months. The lesions are not pruritic or painful. On examination, the patient has multiple gray-colored patches, surrounded by faint rings of erythema on his forehead. The patient is very bothered by the cosmetic appearance of the lesions and is presenting for possible treatment options. The patient has no other medical problems.

www.ClinicalAdvisor.com â&#x20AC;˘ THE CLINICAL ADVISOR â&#x20AC;˘ FEBRUARY 2018 53

Dermatologic Look-Alikes CASE #1

Necrobiosis lipoidica

Necrobiosis lipoidica (NL) is a rare granulomatous skin disease historically associated with diabetes mellitus. Although originally named necrobiosis lipoidica diabeticorum by Urbach in 1932, necrobiosis lipoidica more accurately reflects the nature of the disease as it may occur independently of diabetes mellitus.1,2 While historically associated with diabetes mellitus, the incidence of necrobiosis lipoidica among diabetic patients is reported as 0.3%, and the prevalence of diabetes mellitus among patients with NL ranges from 11% to 65%, according to various studies.3,4 NL tends to occur more frequently in women than in men.3 Although NL can occur at any age, the average age of onset of necrobiosis lipoidica in diabetic patients is 30 compared with 41 for non-diabetic patients.3 There are many theories on the pathogenesis of necrobiosis lipoidica, but the exact underlying etiology remains unclear. The most popular theory proposes that glycoprotein deposition in the vasculature produces secondary microangiopathy and the formation of the characteristic skin findings. Alternative studies suggest that the skin findings are secondary to tissue hypoxia, although this is less widely accepted.5 Other theories include the deposition of immunoglobulins in blood vessels, abnormal collagen crosslinking, and neutrophil migration and macrophage proliferation caused by trauma, inflammation, or metabolic changes.6 Because the literature on necrobiosis lipoidica primarily consists of case reports of small patient sample sizes, risk factors for developing the condition are not well defined and are subject to debate. While the relationship between necrobiosis lipoidica and diabetes mellitus remains controversial, diabetes mellitus has been found to be the most prevalent comorbidity of necrobiosis lipoidica. Other potential risk factors include hypertension, obesity, and dyslipidemia.7 Among diabetics, there is evidence that higher HbA1c levels, longer diabetes duration, and a higher daily insulin requirement correlate with necrobiosis lipoidica.8 Necrobiosis lipoidica usually presents as a single papule to few erythematous papules with an enlarging, active border. It is most commonly found on extensor surfaces of the lower extremities; however, it can also affect the face, scalp, trunk, groin, and upper extremity.3,5 Early lesions

initially have a brownish-red center that later progresses to more yellowish-brown in color with an atrophic and waxy center.5,7,9 Eventually, the lesions slowly develop into irregular, well-demarcated violaceous plaques with overlying telangiectasias, which is thought to result from collagen degeneration.5,10 Most lesions are asymptomatic, but as many as 30% of patients may experience exquisite pain if the lesions become ulcerated.7 In rare cases, squamous cell carcinoma may develop in older, ulcerated lesions.5,7,10 A diagnosis of necrobiosis lipoidica can usually be made clinically, but a biopsy may be performed in case of equivocal findings and to rule out squamous cell carcinoma.7,8 Histologically, NL has two characteristic patterns: palisading and pseudotuberculoid, and lesions may contain features of both patterns.11,12 Palisading granulomatous lesions are characterized by linear tiers of hyalinized and necrobiotic

A diagnosis of necrobiosis lipoidica can be made clinically, but a biopsy may be performed in case of equivocal findings. collagen aggregates in the lower dermis surrounded by a rim of inflammatory cells and occur more frequently in diabetic patients.2 The pseudotuberculoid pattern consists principally of epithelioid histiocytes with an increased number of lymphocytes, plasma cells, and giant cells. In contrast to the palisading pattern, necrobiotic collagen is not usually present, although some collagen may be hyalinized and occurs more frequently in nondiabetic or pre-diabetic patients.11 The differential diagnosis of necrobiosis lipoidica includes erythema dyschromicum perstans, granuloma annulare (GA), necrobiotic xanthogranuloma, rheumatoid nodules, and sarcoidosis. Although early forms of each disease may be nearly indistinguishable, granuloma annulare can be distinguished by its failure to develop the epidermal atrophy and characteristic yellow color of necrobiosis lipoidica.1 Necrobiotic xanogranuloma can be distinguished from necrobiosis lipoidica clinically because of its association with paraproteinemia and histologically by the presence of cholesterol clefts.1,13 Rheumatoid nodules present in the context of severe arthritis and tend to arise near joints, especially the elbow, while necrobiosis lipoidica lesions tend to arise on the shins.11,14 Sarcoidosis typically involves other organ systems and does not demonstrate the necrobiosis, hyalinization, and lipid depositions that are distinctive of necrobiosis lipoidica.1,6

54 THE CLINICAL ADVISOR â&#x20AC;˘ FEBRUARY 2018 â&#x20AC;˘ www.ClinicalAdvisor.com

Necrobiosis lipoidica can be difficult to treat, and there are no large randomized placebo-controlled studies that dictate a specific treatment regimen. The most commonly used treatment includes topical, intralesional, and systemic corticosteroids to reduce inflammation and halt disease progression.5,14 Steroid use, however, may cause glucose dysregulation in diabetic patients, so it is recommended to avoid their longterm use and use mostly at the lesion’s active borders.5 The effect of glucose control on necrobiosis lipoidica remains unclear.14 A combination of aspirin and dipyridamole to inhibit platelet aggregation has been proposed to treat necrobiosis lipoidica, although its efficacy has not yet been established.2 Pentoxifylline, tretinoin, mycophenolate, mofetil, cyclosporine A, thalidomide, and topical tacrolimus have been reported as effective treatment modalities; however, further research is needed on their safety and efficacy. Antimalarial and immunosuppressive therapies such as methotrexate have also been proposed as treatment options.14 Various forms of phototherapy have been shown to be successful and may be used as a second-line treatment.9 Trauma should be avoided to reduce the risk of ulcer formation.2,5 The patient in this vignette was biopsied and diagnosed with NL. She was started on topical clobetasol 0.05% ointment and told to apply it to the active borders of her lesions. She noticed a significant slowing in the rate of growth of her lesions.

CASE #2

Erythema dyschromicum perstans

Erythema dyschromicum perstans (EDP) is an asymptomatic, uncommon dermatosis characterized by a persistent ashy-gray discoloration of the skin.15-17 The condition is commonly referred to as “ashy dermatosis” and was first described by Ramirez in 1957.18 Erythema dyschromicum perstans is more prevalent in Latin American populations, although it has been reported in patients from a variety of ethnic backgrounds.16,19 There is no clearly established sexual predilection.16,20 EDP more commonly presents in adulthood but may also be found in children and adolescents. One study found that although adults with erythema dyschromicum perstans are usually of Hispanic origin, children with EDP tend to be Caucasian.16

The etiology of erythema dyschromicum perstans is unknown. It has been associated with ingestion of ammonium nitrate, exposure to environmental contaminants, treatment of a parasitic infestation, HIV infection, atopy, hypothyroidism, and chronic hepatitis C.16,17,21,22 It is thought to be caused by an abnormal immune response to antigens— particularly through the expression of cell adhesion and activation molecules that downstream damage melanocytes and keratinocytes in the basal layer of the epidermis.17,23,24 EDP presents as oval to round ash-gray macules that slowly expand and coalesce to form irregular or polycyclic patches.20 The lesions may be surrounded by an erythematous, slightly elevated border that eventually disappears

EDP presents as oval to round ash-gray macules that slowly expand and coalesce to form irregular or polycyclic patches. within several months.23,25 Although usually asymptomatic, some lesions may be mildly pruritic.26 The most commonly affected regions are the trunk and proximal extremities, followed by the face and neck, without preference for exposed or unexposed areas.15,16,20 Lesion distribution tends to be symmetric, although in very rare cases, erythema dyschromicum perstans may present unilaterally.15 Older lesions of hyperpigmentation may be surrounded by a rim of hypopigmentation and leave a permanent discoloration.19 The active phase erythematous border of erythema dyschromicum perstans exhibits different histologic features from the late-stage or central ashy area of the lesion. The inflammatory borders exhibit vacuolization of the basal cell layer, edematous dermal papillae, occasional colloid bodies, and a mild to moderate perivascular infiltrate consisting of small round cells, histiocytes, and melanophages.15,20,23 Exocytosis of lymphocytes may also be visualized, with a slight predominance of CD8+ over CD4+ lymphocytes.17 Immunofluorescence often shows the deposition of fibrinogen at the dermo-epidermal junction.19 Late-stage lesions and the inactive central regions of lesions exhibit epidermal atrophy with discrete follicular hyperkeratosis.16,19,25 The infiltrates may diminish over time, leaving only vacuolar alteration of basal cells, which may later resolve.16,26 The characteristic ashy color of EDP is due to the accumulation of melanin granules within macrophages in the upper dermis.16,19,20,23 The resulting pigmentary incontinence may be the only microscopic finding in older lesions.20,26

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 55

Dermatologic Look-Alikes The differential diagnosis of erythema dyschromicum perstans includes necrobiosis lipoidica, lichen planus, idiopathic eruptive macular pigmentation, incontinentia pigmenti, postinflammatory hyperpigmentation, and fixed drug eruption, among others. Differentiating between erythema dyschromicum perstans and lichen planus is a subject of controversy. Some researchers consider EDP a variant of lichen planus and suggest calling the condition lichen planus pigmentosus.24,26,27 Others believe that while late-stage erythema dyschromicum perstans may resemble lichen planus pigmentosus, the characteristic active erythematous border distinguishes the former condition from the latter.16,20,22,28 Idiopathic eruptive macular hyperpigmentation may be differentiated by the lack of both initial border erythema and ash-gray color.16,28,29,30 Although late-stage lesions of both EDP and incontinentia pigmenti may resemble each other, lesions of the former present initially as slowly spreading ash-gray macules, and lesions of the latter appear vesicular at first and progress to hyperpigmentation.20,31 Unlike those

with erythema dyschromicum perstans, patients with postinflammatory hyperpigmentation tend to have a history of a preceding cutaneous insult such as drug or phototoxic reactions, infections, physical injury, allergic reactions, or inflammatory diseases.15 Fixed drug eruption may mimic erythema dyschromicum perstans as it presents with a broad spectrum of clinical manifestations but may be distinguished from EDP by the patient’s history, as fixed drug eruptions are induced by a drug or other causative agent.20,32 Although many treatments have been previously tested, most remain ineffective due to persistent residual pigmentation of the lesions. Treatment with antibiotics, topical corticosteroids, keratinolytic agents, isoniazid, chloroquine, and psychotherapy have all had disappointing results.16,25 Other therapeutic agents, such as dapsone,21 clofazimine,23 and isotretinoin,33 have shown initial success but more research is needed. One study showed that without treatment, 50% of children affected by erythema dyschromicum perstans experienced improvement of their lesions within

TABLE 1. Necrobiosis lipoidica versus erythema dyschromicum perstans Necrobiosis lipoidica

Erythema dyschromicum perstans

Dermatologic presentation

• 1 to 3 asymptomatic papules/macules with active erythematous borders that slowly develop into irregular, well-demarcated plaques • Central areas brownish-red to yellowish-brown papules to plaques overlying atrophic and waxy skin • Painful if ulcerated

• Slowly expanding ash-gray macules that are oval, round, or irregular in shape • Lesions may become confluent, presenting as irregular or polycyclic patches • +/- erythematous, slightly raised border that eventually disappears

Associations

• Debated association with diabetes mellitus, especially type 1 • More prevalent in women than in men

• More prevalent in Latin American populations and adults • Usually asymptomatic, though some lesions may be mildly pruritic

Etiology

• Unknown • Linked to aberrant glycoprotein vascular microangiopathy

• Unknown • Thought to be secondary to abnormal immune response to antigens • Increased risk after ingestion of ammonium nitrate, exposure to environmental contaminants, or treatment of a parasitic infestation

Characteristic location

• Typically localized to the shins • May be present on the face, scalp, trunk, groin, and upper extremities

• Predilection for the trunk and proximal extremities, followed by the face and neck • Any area of the body may be involved

Histology

• Palisading granulomatous (diabetic patients): linear tiers of hyalinized and necrobiotic collagen aggregates in the lower dermis surrounded by a rim of inflammatory cells • Pseudotuberuloid granulomatous (nondiabetic patients): epithelioid histiocytes with an increased number of lymphocytes, plasma cells, and giant cells

• Early findings: vacuolization of the basal cell layer, edematous dermal papillae, colloid bodies, and a mild to moderate perivascular lymphocytic infiltrate • Late findings: epidermal atrophy with discrete follicular hyperkeratosis; accumulation of melanin granules within macrophages in the upper dermis

Diagnosis

• History and physical examination

• History and physical examination • Skin biopsy if no erythematous border present

Treatment

• Difficult to treat • Avoid trauma to reduce risk of ulcer formation • Corticosteroids to prevent further expansion • Phototherapy is second-line

• Often ineffective as the hyperpigmentation is permanent • Limited success with dapsone, clofazimine, and isotretinoin

56 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

1 to 5 years.16 Many physicians choose not to recommend any specific treatment for the condition due to its benign nature and lack effective treatment options. The patient in this case study was diagnosed with erythema dyschromicum perstans. The patient requested a biopsy, which confirmed the diagnosis. After being presented with the various treatment options, the patient declined treatment. n

15. Chun JS, Hong SK, Seo JK, Lee D, Sung HS, Hwang SW. A case of unilateral Ashy dermatosis. Ann Dermatol. 2009;21:432-434. 16. Torrelo A, Zaballos P, Colmenero I, Mediero IG, De Prada I, Zambrano A. Erythema dyschromicum perstans in children: a report of 14 cases. J Eur Acad Dermatology Venereol. 2005;19:422-426. 17. Vásquez-Ochoa LA, Isaza-Guzmán DM, Orozco-Mora B, RestrepoMolina R, Trujillo-Perez J, Tapia FJ. Immunopathologic study of erythema dyschromicum perstans (ashy dermatosis). Int J Dermatol. 2006;45:937-941.

Lindsey Limbaugh, BA, is a medical student, Emma Weiss, BA, is a medical student, and Christopher Rizk, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

18. Ramirez CO. Los Cenicientos: Problema Clinico. Report of the First Central American Congress of Dermatology, San Salvador, December 5-8, 1957. 1957;1:122-130. 19. Tschen JA, Tschen EA, McGavran MH. Erythema dyschromicum perstans.

References

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1. Lowitt MH, Dover JS. Necrobiosis lipoidica. J Am Acad Dermatol.

20. Knox JM, Dodge BG, Freeman RG. Erythema dyschromicum perstans.

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Arch Dermatology. 1968;97:262-272.

2. Yen P-S, Wang K-H, Chen W-Y, Yang Y-W, Ho W-T. The many faces

21. Bahadir S, Çobanoglu Ü, Çimsit G, Yayli S, Alpay K. Erythema dyschromi-

of necrobiosis lipoidica: a report of three cases with histologic variations.

cum perstans: Response to dapsone therapy. Int J Dermatol. 2004;43:220-222.

Dermatologica Sin. 2011;29:67-71.

22. Schwartz RA. Erythema dyschromicum perstans: The continuing enig-

3. Muller S, Winkelmann R. Necrobiosis lipoidica diabeticorum: A clinical

ma of Cinderella or ashy dermatosis. Int J Dermatol. 2004;43:230-232.

and pathological investigation of 171 cases. Arch Dermatol. 1966;93:272-281.

23. Baranda L, Torres-Alvarez B, Cortes-Franco R, Moncada B, Portales-

4. O’Toole EA, Kennedy U, Nolan JJ, Young MM, Rogers S, Barnes L.

Perez DP, Gonzalez-Amaro R. Involvement of cell adhesion and activation

Necrobiosis lipoidica: only a minority of patients have diabetes mellitus. Br

molecules in the pathogenesis of erythema dyschromicum perstans (ashy der-

J Dermatol. 1999;140:283-286.

matitis). The effect of clofazimine therapy. Arch Dermatol. 1997;133:325-329.

5. Reid SD, Ladizinski B, Lee K, Baibergenova A, Alavi A. Update on necro-

24. Pinkus H. Lichenoid tissue reactions: A speculative review of the clinical

biosis lipoidica: A review of etiology, diagnosis, and treatment options. J Am

spectrum of epidermal basal cell damage with special reference to ery-

Acad Dermatol. 2013;69:783-791.

thema dyschromicum perstans. Arch Dermatol. 1973;107:840-846.

6. Kota SK, Jammula S, Kota SK, Meher LK, Modi KD. Necrobiosis lipoidica

25. Falabella R. Pigmentary Disorders in Latin America. Dermatol Clin.

diabeticorum: A case-based review of literature. Indian J Endocrinol Metab.

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26. Berger RS, Hayes TJ, Dixon SL. Erythema dyschromicum perstans and

7. Jockenhofer F, Kroger K, Klode J, Renner R, Erfurt-Berge C, Dissemond

lichen planus: Are they related? J Am Acad Dermatol. 1989;21:438-442.

J. Cofactors and comorbidities of necrobiosis lipoidica: analysis of the

27. Naidorf KF, Cohen SR. Erythema dyschromicum perstans and lichen

German DRG data from 2012. J Dtsch Dermatol Ges. 2016;14:277-284.

planus. Arch Dermatol. 1982;118:683-685.

8. Hammer E, Lilienthal E, Hofer SE, Schulz S, Bollow E, Holl RW. Risk

28. Zaynoun S, Rubeiz N, Kibbi AG. Ashy dermatoses—A critical review

factors for necrobiosis lipoidica in type 1 diabetes mellitus. Diabet Med.

of the literature and a proposed simplified clinical classification. Int J

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Dermatol. 2008;47:542-544.

9. Peckruhn M, Tittelbach J, Elsner P. Update: Treatment of necrobiosis

29. Jang KA, Choi JH, Sung KJ, Moon KC, Koh JK. Idiopathic eruptive macu-

lipoidica. JDDG J der Dtsch Dermatologischen Gesellschaft. 2017;15:151-157.

lar pigmentation: Report of 10 cases. J Am Acad Dermatol. 2001;44:351-353.

10. Dissemond J. Necrobiosis lipoidica diabeticorum. N Engl J Med.

30. Volz A, Metze D, Böhm M, Bruckner-Tuderman L, Nashan D.

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Idiopathic eruptive macular pigmentation in a 7-year-old girl: Case report

11. Lynch JM, Barrett TL. Collagenolytic (necrobiotic) granulomas: part II -

and discussion of differences from erythema dyschromicum perstans. Br J

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Dermatol. 2007;157:839-840.

12. Muller S, Winkelmann R. Necrobiosis lipoidica diabeticorum:

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www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 57

LEGAL ADVISOR CASE

Sexual harassment at work

BY ANN W. LATNER, JD

Ms F, 26, was a nurse working in a Veteran’s Administration (VA) facility. She began working there starting the November after her graduation. Getting through school had been challenging, as Ms F was a single mother and had a 4-year-old child at home, but she was determined to succeed. Her first 6 months on the job were fine. She enjoyed the work, and the feedback she received was positive. But then she was assigned to work with Mr G, and everything changed. Mr G, a physician assistant, was in his 30s and had been with the VA for several years. He was immediately attracted to Ms F and made that attraction quite obvious. It started with compliments on her looks and progressed to asking her out. Ms F always politely declined and just tried to laugh off the situation. As time went by, however, Mr G became increasingly persistent—moving on from suggestions of dates to suggestions of sexual encounters. Ms F rebuffed him each time, but that only seemed to encourage him. “Stop fighting it,” he told her, “You’ll say ‘yes’ one of these days, and we will be together. I know how to make you smile.”

A nurse in a VA facility files a complaint against a clinician, which ends with a criminal conviction.

The police investigation of the defendent ended with his criminal conviction, which then resulted in his being fired from the VA.

58 THE CLINICAL ADVISOR • FEBRUARY 2018 • www.ClinicalAdvisor.com

As the months went by, the unwanted attention only increased. When Ms F found herself alone with Mr G, he began touching her and trying to kiss her despite her clearly telling him “no.” Ms F did not know whom to talk to. She was afraid that if she complained to the administration about Mr G’s actions, she might face backlash, perhaps even jeopardizing her own job. With a child at home dependent on her salary, she was afraid to risk that. Her solution was to try to avoid ever being alone with Mr G, but that was not easy. The more Ms F tried to avoid Mr G, the more it seemed to egg him on. He would sneak up on her when she was in a storage room, or make suggestive sounds when she walked by. He also told her that he had a concealed carry permit and sometimes kept a weapon in his car. Her anxiety increased, and she began to dread the job she had once loved. 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.

Finally, after almost 10 months of harassment, things came to a head when Mr G cornered Ms F in an empty bathroom and tried to force himself on her. She fled the room but realized she could not go on like this anymore. She reported Mr G to her supervisor. The supervisor contacted the VA’s law enforcement officials, and Ms F filed a report with them, and with the civilian police. Mr G was transferred to another facility and placed on suspension, and Ms F was given a week of authorized absence. After the week, Ms F requested to be transferred from that particular VA facility. Instead, she was granted 12 weeks of Family and Medical Leave, and 10 days’ worth of advanced sick leave. The police investigation of Mr G ended in his criminal conviction, which then resulted in Mr G being fired from the VA. During her leave, Ms F was diagnosed with post-traumatic stress disorder (PTSD) from the incident. She submitted medical documentation of her diagnosis of PTSD from the assault and requested a transfer to a different unit of the facility or to a different facility. However, the VA replied that based on other medical documentation Ms F was fit to return to duty, and it was the facility’s policy in sexual harassment cases to transfer the perpetrator, not the victim. When her medical leave ran out, Ms F was fired for not returning to her former job in the original location. Ms F sought the counsel of an attorney. After hearing her story, the attorney agreed that she had a case, and he filed a lawsuit against the VA, alleging numerous offenses including sexual harassment/hostile work environment, and disability discrimination based on her diagnosis of PTSD. The VA responded by filing a motion to dismiss all the claims against it. A federal district court had to decide whether the case should proceed. Legal background

In making its decision, the court looked at the two main claims involved in this case: sexual harassment, and whether Ms F’s PTSD constituted a disability that would require a reasonable accommodation (such as Ms F’s request for a transfer). The court agreed with the VA facility that it had properly responded (legally) to the report of sexual harassment made by Ms F. “The hospital did not know about the harassment until the nurse reported it,” wrote the court in its decision. “Once she reported it, the hospital fulfilled all its legal duties as to sexual harassment.”

Law enforcement was immediately notified of the situation, an investigation was begun, Mr G was suspended and moved to another facility, and Ms F was given leave. The court could not fault the facility for its handling of a situation that it was not aware of. Therefore, the court dismissed that part of the lawsuit, holding that the VA had satisfied its legal duties to Ms F. However, the court upheld Ms F’s right to sue for disability discrimination. Ms F notified her employer about her disability, provided a physician’s diagnosis confirming that she had PTSD, and requested a reasonable accommodation (being moved to a different area of the hospital or to

Had the hospital not immediately reacted to Ms F’s report of the situation, she would have had a claim against it. another facility). The federal regulations specifically mention PTSD as a disability. Thus, the court agreed that Ms F could pursue that claim, and the case has been remanded for a future trial. Protecting yourself

As the court pointed out, the hospital was unaware of the situation until Ms F reported it. The facility could not be expected to do something about a situation of which it was unaware. Unfortunately, harassment in the workplace happens. And with greater frequency than we would wish. If you find yourself in that position, you must report it—not just for your own sake, but for the sake of your other coworkers who may also be harassed by that person at some point. Reporting it is the only way to get any legal and practical protection from the harasser. Had the hospital not immediately reacted to Ms F’s report, she would have had a claim against it. However, the hospital acted appropriately and immediately took action once notified. It is the “once notified” that is the issue. If you ever find yourself in the unfortunate situation of being harassed at work, notify your supervisor or your HR department. n Ms Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

www.ClinicalAdvisor.com • THE CLINICAL ADVISOR • FEBRUARY 2018 59