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Open Access Publications from the University of California

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Dermatology Online Journal is an open-access, refereed publication intended to meet reference and education needs of the international dermatology community since 1995. Dermatology Online Journal is supported by the Department of Dermatology UC Davis, and by the Northern California Veterans Administration.

Volume 22, Issue 3, 2016

Review

Antifungal agents for onychomycosis: new treatment strategies to improve safety

Onychomycosis is a common and difficult-to-treat fungal infection of the nail unit that gradually leads to dystrophic changes of the nail plate and nail bed. If untreated, infection progresses and may lead to discomfort, reduced quality of life, and risk of complications in patients with comorbid conditions (eg, diabetes, human immunodeficiency virus, peripheral vascular disease). Onychomycosis treatments are designed to eradicate causative pathogens (most commonly Trichophyton rubrum and Trichophyton mentagrophytes), restore healthy nails, and prevent recurrence or spread of infection. Given the deep-seated nature of most cases of onychomycosis, an effective antifungal agent needs to achieve and maintain sufficient drug concentrations throughout the nail unit for the duration of healthy nail in-growth. Oral antifungal drugs are the most effective available therapy and are generally well tolerated, but may be limited by safety concerns and the potential for drug-drug interactions (DDIs). Thus, treating physicians and pharmacists must be cognizant of a patient’s current medications; indeed, it may not be feasible to treat onychomycosis in patients with diabetes, heart disease, or depression because of the risk for DDIs. Current topical therapy is not associated with risk of DDIs. Tavaborole and efinaconazole, two recently approved topical agents, have demonstrated good nail penetration and high negative culture rates in clinical trials of patients with onychomycosis. This article provides the treating physician and pharmacist with information on the safety and effectiveness of current oral (allylamine, azole) and topical (ciclopirox, efinaconazole, tavaborole) treatment to aid in making informed treatment decisions based on the unique characteristics (medication history, comorbidities, nature of onychomycosis) of each patient.

Original

Reduction in pain scores and improvement in depressive symptoms in patients with hidradenitis suppurativa treated with adalimumab in a phase 2, randomized, placebo-controlled trial

Background: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease with frequent comorbidities of painand depression. Adalimumab treatment for 16 weeks improved HS lesions significantly versus placebo (NCT00918255).Objective: The relationship between pain and depressive symptoms and the effects of adalimumab on each was examined in this post hoc analysis.Methods: Patients with moderate to severe HS (N=154) were randomized 1:1:1 to adalimumab 40 mg weekly (ew), adalimumab 40 mg every other week (eow), or placebo. Skin pain was assessed using a visual analog scale (VAS; 0–100 mm). Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9; score ≥10 indicative of depression).Results: At baseline, overall mean±SD pain VAS was 54.3±26.5 mm and 41.8% of patients had PHQ-9 scores ≥10. At baseline, VAS pain scores (mean±SD) were significantly higher (P<0.001) for patients with PHQ-9 scores ≥10 (63.9±23.3) versus <10 (47.4±26.7). At Week 16, clinically relevant pain reduction was observed for ew-treated patients with baseline PHQ-9 score ≥10 (ew, 45.8%; eow, 29.4%; placebo, 23.8%) and <10 (ew, 50.0%; eow, 37.9%; placebo, 29.6%), but did not reach statistical significance. In patients with high baseline pain (≥median VAS score), adalimumab ew significantly decreased depressivesymptoms versus placebo (PHQ-9 scores, –34.03% vs +2.26%; P<0.01).Conclusion: Patients with moderate to severe HS had a high degree of pain and depressive symptoms at baseline. Adalimumabtherapy was associated with decreased pain and depressive symptoms compared to baseline.

Case Report

Pemphigus foliaceus exacerbated by radiation, in association with myasthenia gravis

Pemphigus foliaceus (PF) is a sporadic autoimmune blistering disease of unknown etiology. The production of immunoglobulin G4 antibodies against desmoglein-1 is responsible for the clinical manifestation of PF. We present a case of a woman with a recent diagnosis of myasthenia gravis (MG), who was also recently treated with radiation therapy for breast cancer. The clinical exam, supported by biopsy and direct immunofluorescence, were consistent with PF. We present this case to increase the awareness of the potential exacerbation or induction of PF with radiation, and of the association of PF and myasthenia gravis. Only five prior cases of radiation-exacerbated or radiation-induced PF have been reported in the literature to date. Furthermore, the co-existence of the autoimmune entities of myasthenia gravis and PF has been reported in the literature in only 9 cases and was also noted in this patient.

Tinea capitis in adults

Background: Tinea capitis is caused by dermatophyte fungi that utilize keratin as a nutrient source.  Scalp erythema, scaling, andcrusting are typical signs of this disease.  Although most commonly seen in prepubescent children, tinea capitis can occur in adults.Results: Endothrix tinea capitis owing to Trichophyton tonsurans commonly produces generalized scaling and localized perifollicular inflammation reminiscent of lichen planopilaris. Ectothrix tinea capitis owing to Microsporum sp. produces well- demarcated erythematous plaques suggestive of psoriasis. H&E stained biopsy specimens, KOH preparations or fungal cultures will confirm the diagnosis.Conclusion: Because of a low index of suspicion for tinea capitis in adults with scaling and alopecia, diagnosis and appropriate treatment are often delayed. Resistance to treatment for seborrheic dermatitis or psoriasis should prompt a KOH, fungal culture orbiopsy to confirm the diagnosis of tinea capitis and initiate systemic antifungal agents.

Molluscum contagiosum of the eyelid: case report in a man receiving methotrexate and literature review of molluscum contagiosum in patients who are immunosuppressed secondary to methotrexate or HIV infection

Background: Molluscum contagiosum is a benign viral infection of the skin. Lesions typically present as dome-shaped, flesh-colored, umbilicated papules that range in size from 1 to 5 millimeters in diameter. They are usually asymptomatic, but can become tender or pruritic. Children and immunocompromised adults, including individuals being treated with immunosuppressive drugs, are most susceptible to infection. Single or multiple lesions most commonly appear on the extremities, face, genitals, and trunk. However, albeit rarely, molluscum contagiosum may also develop at other sites, including the eyelids.Purpose: We describe the clinical and pathologic findings of a man who developed molluscum contagiosum of the eyelid while receiving methotrexate. We also review the characteristics of other patients with molluscum contagiosum acquired either during treatment with methotrexate or associated with human immunodeficiency virus (HIV) infection and summarize the unusual sites of presentation for the viral lesions in these individuals.Materials and methods: The features of a man receiving methotrexate who developed molluscum contagiosum of the eyelid are presented. Using PubMed, the following terms were searched and relevant citations assessed: adalimumab, contagiosum, Enbrel, etanercept, Humira, infliximab, methotrexate, molluscum, Remicade, TNF alpha, and tumor necrosis factor alpha. In addition, the literature on methotrexate treatment and molluscum contagiosum is reviewed.Results:  Several small papules were observed on the eyelid of a 24-year-old man who had been receiving methotrexate and adalimumab (Humira) for the treatment of Crohn disease. The lesions were removed by shave biopsy. Microscopic examination revealed epidermal hyperplasia composed of keratinocytes filled with large eosinophilic intracytoplasmic inclusions. Based on correlation of the clinical presentation and histopathologic findings, a diagnosis of molluscum contagiosum was established. The patient applied mupirocin 2% ointment to the biopsy sites, which subsequently healed without complication or recurrence.Conclusion: Molluscum contagiosum is a benign viral papular eruption that frequently affects children and immunocompromised adults. Patients treated with immunosuppressive agents, such as methotrexate, have a heightened risk of developing molluscum contagiosum lesions. It remains to be determined whether adjunct therapy with a tumor necrosis factor alpha inhibitor increasesthe risk of this viral infection. Diagnosis can usually be established by clinical presentation, although a biopsy is sometimesrequired to exclude other conditions. Molluscum contagiosum is generally self-limiting and often resolves spontaneously within18 months. However, topical (cantharidin) or locally destructive (curettage, cryotherapy, and/or laser) therapy may be indic tedfor patients who are concerned about persistent lesions and for children who are particularly susceptible to autoinoculation.

Severe pediculosis capitus: a case of “crusted lice” with autoeczematization

Pediculosis humanus capitus infestations are common and classically present with intense pruritus of the scalp. Although many treatment options are available, lice are becoming more resistant to conventional therapies and severe clinical presentations are bound to become more prevalent. We present a case of treatment-resistant pediculosis capitus resulting in diffuse autoeczematization of the torso and extremities and severe crusting and scaling of the scalp, which we called “crusted lice.” This eruption differs from the well-described id reaction known as “pediculid” and represents a more dramatic manifestation of rampant infestation. This paper provides an up-to-date review of treatment options available for pediculosis humanus capitus, including newer medications like the ones that eventually led to resolution of our patient’s extreme infestation.

Mercury toxicity presenting as acrodynia and a papulovesicular eruption in a 5-year-old girl

Acrodynia is a reaction that occurs in children who have been exposed to mercury. Mercury toxicity has systemic manifestations as well as cutaneous manifestations, which can appear similar to those found in a number of other diseases. We present a case of acrodynia caused by mercury exposure in a previously healthy 5-year-old girl who developed hypertension, palmoplantar pruritus, and a papulovesicular eruption.

Commentary

Evaluating Dermatology Residency Program Websites

Background: Internet resources play an important role in how medical students access information related to residency programs.Evaluating program websites is necessary in order to provide accurate information for applicants and provide information regarding areas of website improvement for programs. To date, dermatology residency websites (D  WS) have not been evaluated.This paper evaluates dermatology residency websites based on availability of predefined measures.Methods: Using the FREIDA (Fellowship and Residency Electronic Interactive Database) Online database, authors searched forall accredited dermatology program websites. Eligible programs were identified through the FREIDA Online database and had a functioning website. Two authors independently extracted data with consensus or third researcher resolution of differences. This data was accessed and archived from July 15th to July 17th, 2015.Primary outcomes measured were presence of content on education, resident and faculty information, program environment, applicant recruitment, schedule, salary, and website quality evaluated using an online tool (WooRank.com).Results: Out of 117 accredited dermatology residencies, 115 had functioning webpages. Of these, 76.5% (75) had direct links found on the FRIEDA Online database. Most programs contained information on education, faculty, program environment, and applicant recruitment. However, website quality and marketing effectiveness were highly variable; most programs were deemed to need improvements in the functioning of their webpages. Also, additional information on current residents and about potential away rotations were lacking from most websites with only 52.2% (60) and 41.7% (48) of programs providing this content, respectively.Conclusions: A majority of dermatology residency websites contained adequate information on many of the factors we evaluated. However, many were lacking in areas that matter to applicants. We hope this report will encourage dermatology residencyprograms to improve their websites and provide adequate content to attract the top residents for their respective programs.

Vestibular papillomatosis: An important differential diagnosis of vulvar papillomas

Most authors believe that vestibular papillomatosis (VP) is an anatomical variant of the vestibular mucosa. But VP is sometimes misdiagnosed as genital warts and this can lead to aggressive investigations, therapy, and anxiety in patients. We present a patient with VP. Dermoscopy and reflectance confocal microscopy (RCM) were performed to differentiate VP from other papilomatous diseases of the vulva.

Case Presentation

Generalized acquired cutis laxa type 1: a case report and brief review of literature

Cutis laxa, clinically characterized by loose and pendulous skin related to loss of elastic tissue, is a rare heterogeneous condition. It is classified into congenital and acquired types. We report a case of generalized acquired cutis laxa type 1 in a young man following pruritic urticarial plaques. We have done a brief review of literature.

Two small yellowish papules in a 1 year-old boy: cutaneous leishmaniasis

Cutaneous leishma iasis (CL) is zoonosis with a spectrum of cutaneous manifestations caused by protozoan parasites of thegenus Leishmania.Manifestation varies according to the parasite virulence and the host immune response. Pentavalent antimonials (sodium stibogluconate and meglumine antimoniate) have been used as a first-line therapy for the last 70 years around the world.We report a case of a 1-year-old boy with two small yellowish papules mimicking juvenile xantogranuloma diagnosed with cutaneous leishmaniasis after a biopsy. Patient underwent treatment with 2 sessions of intralesional (IL) meglumine antimoniate (Glucantime®) with complete clearance of both lesions.Conclusion: Cutaneous leishmaniasis treatment is difficult to standardize; treatment options in children include wound careand watchful waiting,  intralesional pentavalent antimonials, topical paramomycin, or oral miltefosine.

Isotretinoin therapy for the treatment of acne in patients with cystic fibrosis: a case series and review of the literature

Background: Cystic fibrosis (CF) is the most common severe autosomal recessive disorder in Caucasians. Viscous secretionstypically obstruct the lungs, pancreas, and gastrointestinal tract. As disease management improves, patients will increasingly seek care for conditions such as acne. Isotretinoin therapy for acne in patients with CF is controversial owing to concerns that the medication may exacerbate CF-related hepatic, pulmonary, and ocular complications.Purpose: We describe two patients with CF treated with isotretinoin from our clinic and also provide a literature review of 11 similar cases. We describe patient outcomes, common complications, and the risks for severe adverse effects.Materials and methods: The clinical courses of two patients with CF who were treated with isotretinoin for moderate-severe acne are presented. Using PubMed, we analyzed previous case reports of patients with CF who were prescribed isotretinoin and review complications associated with systemic retinoids.Results: Based on a synthesis of the literature and our own experience, it appears that isotretinoin therapy for CF patients with moderate-severe acne may be an appropriate option when clinically indi ated. If dermatologists monitor lab values and adverseeffects carefully, patients with CF can benefit from isotretinoin therapy.

Correspondence: The association between morphea profunda and monoclonal gammopathy: A case series

It is known that eosinophilic fasciitis can be associated with monoclonal gammopathy. There is clinical similarity between eosinophilic fasciitis and morphea profunda, but it is unclear whether morphea profunda might be associated with monoclonal gammopathy. The temporal quantification of gammopathy in morphea profunda has not been well characterized. We describe four patients with morphea profunda that were associated with monoclonal gammopathy. Three were associated with monoclonal IgG protein and one with IgM. No patients in our series developed myeloma. In conclusion, the association of monoclonal gammopathy is not unique to eosinophilic fasciitis and scleromyxedema. Further studies are necessary to characterize further the relationship between the two conditions.

Lichen planus-like drug reaction associated with recombinant human growth hormone therapy in a child patient with Turner syndrome

Turner syndrome (TS) is a genetic disease with an incidence rate of between 1:2000 and 1:5000 live female births. The treatment of TS differs according to age and Recombinant Human Growth Hormone (RHGH) therapy is usually given for the treatment of short stature in girls with TS in childhood. We describe the first case of a TS patient who presented with a clinical picture compatible with oral and palmoplantar lichen planus-like reaction during RHGH therapy; spontaneous remission occurred after therapy suspension.

Innovative use of chemodenervation in the treatment of postoperative genital hyperhidrosis-like symptoms

Postoperative complications present in many forms and can cause great morbidity and even mortality in patients who experience them. Frey syndrome is an example of a postoperative complication in which aberrant nerve regeneration following parotidectomy leads to hyperhidrosis induced by gustatory stimuli. We present a unique but similar case of aberrant nerve regeneration and resulting hypersecretion that emerged 6-7 months following perineoplasty and labial reduction for lichen sclerosus in a 53-year-old woman. An exhaustive investigation ruled out genitourinary causes of her symptoms. Pads, tampons, and surgical procedures provided no relief. We propose that the mechanism of her excessive watery secretions is similar to that which causes Frey syndrome: iatrogenic damage to nerves that aberrantly regenerate to innervate local structures involved in secretory control. The parallels between our patient’s condition and Frey syndrome are evident in the duration between surgery and onset of symptoms and the response to treatment with onabotulinum toxin, highlighting a shared cholinergic pathway. Onabotulinum injections are well tolerated by patients with localized hyperhidrosis and symptom control typically lasts several months. In this manuscript we present a novel mode of delivery of onabotulinum toxin topically to a mucosal region. With these treatments, the patient's hyperhidrosis-like symptoms remain well controlled for 3-4 months, at which point she returns to clinic for treatment. The patient did not experience symptomatic relief until this unique treatment plan was initiated. Her case illustrates the need for further understanding of recalcitrant postoperative complications involving local structures controlling liquid secretion, such as sweat glands and vascular plexuses.

Adult with morbilliform rash and tattoo bullae

A 34-year-old woman was diagnosed with Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), most likelyrelated to a reaction to allopurinol.The patient presented with a 2-week history of a painful pruritic rash that started on her back and progressed to the rest of her body over a five-day period. The eruption started after several new drugs were started, including allopurinol for hyperuricemia. On physical examination, the patient had a diffuse morbilliform eruption and geometric intact bullae limited to the boundaries of tattoos.Most presentations of DRESS include a morbilliform eruption.  However, DRESS does not commonly present with bullae. There have been no known reported cases of bullae forming in the area of tattoos in cases of DRESS. This unique presentation suggests that a component of the tattoo or tattooing process alters the cutaneous immune response, creating an immunocompromiseddistrict. This alteration may promote a greater localized reaction in the setting of widespread skin involvement in DRESS.

Photo Vignette

Cutaneous metastatic pigmented breast carcinoma

A 66-year-old woman presented with a 3 cm black, ulcerated nodule located on the skin of the upper abdomen, just below the breast. The lesion was painful to the touch, but the patient reported no other associated symptoms and was otherwise healthy. A 4-mm punch biopsy of the affected skin was obtained and the histological diagnosis was cutaneous metastatic pigmented breast carcinoma.

Localized bullous eruption in a patient with anasarca

The diagnosis of bullae can be a challenge. The proper diagnosis and prompt treatment is mandatory because most of these diseases are associated with a significant degree of morbidity. The authors present the case of a 76-year-old woman admitted for treatment of anasarca. She also exhibited a bullous eruption localized to the right upper limb.

Letter

Triangular temporal alopecia: a rare case in adulthood

Triangular temporal alopecia (TTA) is an asymptomatic, circumscribed, non-scarring form of alopecia that affects the temporal scalp. Although TTA is most often seen between ages two and nine, the condition has rarely been described in adults. If unrecognized, adulthood TTA can be misdiagnosed, leading to unnecessary steroid treatment. This case report describes TTA in an adult woman who had no prior history of alopecia. It also reviews the existing TTA literature, describing the diagnosis and management of this condition.

Pressure to publish for residency applicants in dermatology

As it grows increasingly difficult to match into a dermatology residency program each year, there is a widening gap in research accomplishments between those who have and have not matched successfully. Applicants should be aware of the current trends in order to maximize their chances of matching. Such research inequality may subsequently lead to increases in the pressure to publish and the incidence of academic misrepresentation. Academic dermatology programs should be aware of these issues in order to help their students successfully match and exercise caution when reviewing the curricula vitae of applicants. We believe that student mentors in dermatology are in the best position to help applicants navigate these challenges until effective checkpoints can be built-in to the application system.