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Dermatology Online Journal

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About

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 26, Issue 7, 2020

Review

Current and emerging treatment options for metastatic melanoma: a focused review

Melanoma is responsible for nearly 9,000 deaths each year in the United States. Until the early 2000s, chemotherapeutic agents were the mainstay of treatment for metastatic disease. Currently approved treatments include therapies that block signal transduction pathways (BRAF inhibition), increase anti-tumor immune responses (CTLA-4 blockade), or stimulate tumor-infiltrating T cells (IL2). In recent years, various new strategies have emerged. Radiation therapy has been widely underutilized, but it can prime tumor cells that are distant from the field of radiation, a phenomenon termed the abscopal effect. Other therapies such as pembrolizumab disrupt the tumor cells' typical mechanisms of T-cell avoidance. Various other treatments involving imiquimod, adoptive T-cell therapy, and vaccines are currently being studied and can play a role in metastatic melanoma treatment in the future. Herein, we review the past treatment modalities, currently approved treatments, and potentially effective options for the future. We also provide strengths of recommendation and level of evidence for each treatment.

Original

NPM1 and FLT3-TKD mutations are enriched in patients with leukemia cutis

Leukemia cutis (LC) is a dermatologic manifestation of leukemia. Its clinical implications for the patient and the biological mechanism behind the manifestation of LC are unknown. The oncology community is increasingly utilizing mutations to classify a number of malignancies to prognosticate outcomes and to choose targeted therapies. A single-center, retrospective analysis of dermatopathology cases with a diagnosis of leukemia cutis was performed. Patients with genetic testing using the Columbia Combined Cancer Panel (a targeted sequencing protocol of 467 genes) or Genoptix (targeted sequencing protocol of 44 genes) were identified. The frequency of the presence of genetic mutations in LC patients was compared to AML patients from the COSMIC (Catalogue of Somatic Mutations in Cancer) database. Twenty nine cases were confirmed to have leukemia cutis, 22 of which had acute myeloid leukemia (AML). Genetic testing was available in 11 patients. Twelve different mutations were observed with particular enrichment for NPM1 and FLT3-TKD. Our original hypothesis was that patients with LC would display a distinct mutation profile. Ultimately, the distribution of mutations observed in our cohort of LC patients largely reflects the mutational profile seen in AML patients in general.

Case Report

Follicular psoriasis: a report of 5 cases and review of the literature, likely an under-recognized yet distinctive variant of psoriasis

Psoriasis is a common autoimmune dermatosis representing an interplay between certain genetic predisposing factors along with clonally restricted Th1 T cells responding to epidermal keratinocyte derived antigen. A unique IL17/IL23 cytokine-rich milieu is pathogenetically significant and conducive to its salient histomorphologic features, such as epidermal hyperplasia and intraepidermal influx of neutrophils. The classic cutaneous manifestation is that of plaque psoriasis also referred to as psoriasis vulgaris with characteristic well-circumscribed erythematous plaques covered by silvery scales. Follicular psoriasis is an uncommon variant manifesting as a scaly folliculocentric hyperkeratotic eruption of the trunk and extremities, irrespective of the presence or absence of conventional lesions of psoriasis vulgaris. In this study we present 5 cases of follicular psoriasis, review the literature, and provide a proposal regarding relevant pathologic findings and potential pathogenetic mechanisms. The incidence of follicular psoriasis is unknown, emphasizing its rarity given the overall incidence of conventional psoriasis in the general population. Owing to the lack of awareness, this clinical presentation is often mistaken for other follicular dermatoses, including bacterial folliculitis, pityriasis rubra pilaris, keratosis pilaris, or follicular eczema.

Terbinafine-induced lichenoid drug eruption: case report and review of terbinafine-associated cutaneous adverse events

Terbinafine is an antifungal agent used in the treatment of hair, nail, and skin dermatophyte infections. Skin side effects to terbinafine are not common. Lichenoid drug eruption is a medication-related adverse cutaneous event; the lesion morphology and pathology mimic lichen planus. A woman with onychomycosis developed a lichenoid drug eruption one week after starting terbinafine. The features of her dermatosis and the characteristics of two additional men who also experienced terbinafine-induced lichenoid drug eruption are discussed. They were receiving a daily terbinafine dosage of either 125mg or 250mg to treat onychomycosis or tinea cruris. The lichenoid drug eruption presented as diffuse or symmetric lesions within one to two weeks after starting terbinafine treatment. The extremities, chest, abdomen, and/or trunk were common sites. Less frequent locations were the lips, nails, palms, soles, and suprapubic region; lesions did not occur on the oral or genital mucosa. The eruption resolved after discontinuation of the medication (with or without treatment using topical corticosteroids, systemic corticosteroids, or both). In addition, more frequently occurring terbinafine-associated cutaneous adverse events (such as urticaria, erythematous eruptions, pruritus, acute generalized exanthematous pustulosis, subacute cutaneous lupus erythematosus, and papulosquamous conditions) are reviewed.

Case Presentation

Erythrodermic Darier disease associated with metastatic lung adenocarcinoma

We present a patient with erythrodermic Darier disease occurring in temporal association with diagnosis of metastatic lung adenocarcinoma. The patient presented with eroded and crusted keratotic papules and plaques over greater than 90% body surface area with extensive secondary impetiginization. Given a longstanding history of pruritic eruption, this presentation represents a paraneoplastic flare of an underlying genodermatosis. Near total resolution was achieved with chemotherapy and topical corticosteroids.

Primary livedoid vasculopathy associated with mononeuritis multiplex

A 40-year-old woman presented with painful ulcerations on the bilateral lower extremities. A biopsy confirmed the diagnosis of livedoid vasculopathy (LV). She was treated initially with aspirin and pentoxifylline, and with the addition of dipyridamole she has had no recurrence of her ulcerations to date. Despite this positive response to treatment she reported numbness and paresthesias in her legs. Nerve conduction studies confirmed a diagnosis of mononeuritis multiplex. This case highlights mononeuritis multiplex as a rarely described complication of LV, and suggests that early recognition of symptoms and a multidisciplinary approach are necessary for optimal management of this condition.

Nail-patella syndrome: "nailing" the diagnosis in three generations

Nail-patella syndrome (NPS) is a hereditary disorder characterized by fingernail changes, elbow dysplasia, hypoplastic patellae, and presence of iliac horns. Clinical presentation can be subtle, and the spectrum of presentation often makes NPS a challenging diagnosis. Herein, we describe three family members with nail-patella syndrome who presented with different features and varying severity. The opportunity to recognize this rare syndrome in three linear generations provided a unique insight into NPS, and a moment to appreciate the random and unpredictable clinical presentation.

Late granuloma formation secondary to hyaluronic acid injection

Hyaluronic acid injection to rejuvenate or to correct defects is a very common practice in aesthetic medicine. Although it is considered highly safe because of biocompatibility and biodegradability, adverse reactions can occur. Herein, we report a patient with foreign body granuloma formation that presented as multiple subcutaneous nodules on both arms, following injections of hyaluronic acid performed about six years earlier. Our case is unique with respect to timing and area of granuloma appearance.

Vulvar and perineal verrucous changes complicating hidradenitis suppurativa after wide excision: a case and literature review

Poorly controlled and long-standing hidradenitis suppurativa (HS) increases the risk of squamous cell carcinoma (SCC). We report a 54-year-old woman with an over 20-year history of HS, who had previously undergone wide perineal excision with secondary intention healing and presented with a painful verrucous vulvar plaque and proximal non-healing perineal wound. The patient had four perineal scouting biopsies performed and excisional biopsy with no evidence of high-grade dysplasia or carcinoma on histology. Chromogenic in situ hybridization was negative for HPV 16 and 18 mRNA; the patient's HIV and HSV PCR were also negative. Our patient was treated with interferon alfa-2b with notable clinical improvement. There is currently no standardized stepwise approach to monitoring verrucous lesions in HS patients with significant risk factors for SCC. Our report highlights a vigilant approach to monitoring. If scouting biopsies are negative, complete testing for high risk HPV strains (HPV 16 and 18) is warranted. If negative, we recommend follow up every 6 months with no further biopsies except if overt clinical changes are observed. We also recommend treatment of verrucous changes to decrease risk of possible malignant conversion. Interferon alfa-2b was effective in decreasing the verrucous lesion burden in our patient and may be considered.

Photo Vignette

A de novo mutation of KRT1 in a baby girl causing epidermolytic ichthyosis with impressive epidermolytic palmoplantar keratoderma

We report a 6-year-old girl showing epidermolytic ichthyosis/epidermolytic hyperkeratosis (EI/EH). Targeted Next Generation Sequencing revealed a de novo, previously unidentified KRT1 mutation. The findings of this study expands the clinical and  spectrum and genotype-phenotype correlation associated with EI/EH.

Hidradenitis suppurativa at the knees

Hidradenitis suppurativa is a poorly understood, destructive disease centered on pilosebaceous units and characterized by inflammatory nodules that progress to abscesses, sinus tracts, and scars. The typical patient is a young woman with involvement of the axillae, breasts, and groin. Presented is a 60-year-old man with poorly controlled diabetes, who initially developed pink-to-yellowish plaques with punched out ulcers on his knees that evolved to scars and draining sinus tracts. Draining sinus tracts were also noted under the left axilla. Histopathology revealed suppurative granulomatous inflammation centered on hair follicles as well as sinus tracts. Special stains for fungus and mycobacterial bacilli were negative. Cultures and PCR for mycobacterial tuberculosis were negative. The patient was diagnosed with hidradenitis suppurativa. A treatment trial of topical corticosteroids and antibiotics was given, but this regimen failed to improve his lesions. The patient was then started on adalimumab, which yielded marked improvement within three months. This case is reported because of the unusual clinical presentation and to highlight the spectrum of atypical hidradenitis suppurativa.

Eccrine mucinous nevus: clinical and histopathological description in an adult Nevus mucinoso ecrino en el adulto: descripción clínicohistológica

Eccrine mucinous nevus is an uncommon hamartoma whose histological diagnosis is simple because of its peculiar morphological features, which include an increase in the number and/or size of the glands and eccrine ducts accompanied by abundant mucin deposits. When it presents with the typical symptom, focal hyperhidrosis, clinical suspicion is possible.

 

El nevus mucinoso ecrino (NME) es un hamartoma escasamente reportado en la literatura cuyo diagnóstico histológico es sencillo debido a sus peculiares rasgos morfológicos, que incluye un aumento del número y/o tamaño de las glándulas ductos ecrinos acompañado de abundante depósito de mucina. Cuando presenta los hallazgos típicos, como la hiperhidrosis focal, es posible su sospecha clínica.

Congenital trichofolliculoma: a very rare presentation

Trichofolliculoma is an uncommon hair follicle hamartoma. It usually appears during adulthood on the face or scalp as a single, asymptomatic, skin-colored papule/nodule with small protruding hairs. Histopathological features are diagnostic. Very rare congenital cases have been reported. Herein, we report a congenital trichofolliculoma in a 15-year-old girl.

Letter

Discrepancies by dermatology resident gender in diagnostic confidence and management of female and male genital lichen sclerosus

Physician gender may impact their exposure to genital dermatoses during residency. The purpose of this study was to survey current dermatology residents regarding their comfort in diagnosing and managing lichen sclerosus. As residents progress through training, confidence improves in diagnosing and managing both male and female lichen sclerosus. However, residents overall feel less comfortable with male genital lichen sclerosus, with female residents displaying the greatest confidence discrepancy. This study highlights gender discrepancies with dermatology resident confidence and practice habits and may serve to further guide curricula to address these disparities.

The ethical implications of utilizing advertising techniques to increase biologic treatment willingness in patients with psoriasis

Certain techniques used in the advertising and marketing setting may enhance patient willingness to initiate and adhere to treatment. Some methods include manipulation, nudging, bandwagon effect, testimonial effect, and framing. While these tools may improve patient adherence to certain medications, and thus overall health-related outcomes, the ethical implications of utilizing advertising techniques in the medical setting should be explored. We suggest physicians can maintain their ethical duty to act in the patient's best interest, while simultaneously maintaining the principles of informed consent and utilizing advertising techniques based on human psychology to present treatment options.

Orchestrating a virtual conference amidst the COVID-19 pandemic

The current Coronavirus Disease 2019 (COVID-19) pandemic has impacted individuals and groups all across the globe as countries and cities face widespread lockdown to limit transmission of the virus. Many have adapted quickly, utilizing virtual platforms for interviews, employment, and academic/social events. Academic conferences, such as the annual Cochrane Skin Conference, faced similar challenges as large gatherings have been banned. The in-person conference was cancelled several days prior to its hosting at the University of Colorado, leading conference organizers to employ a virtual platform to continue the conference as scheduled. In this letter, logistics, troubleshooting, and conversion of an NIH-funded conference from an in-person to a successful virtual conference are discussed. We hope this letter may serve as a guide for future hosting of academic conferences, and to those dedicated to collaboration and the sharing of information during such unprecedented times.

Nicolau syndrome following intramuscular naltrexone injection

There are a variety of possible adverse drug reactions that can have differing presentations. Recognizing these presentations and the temporal relationship between drug intake and reaction is essential in preventing severe and potentially fatal results. We present a patient who had a sudden post-injection inflammatory response consistent with Nicolau syndrome after a 6 month course of repeated intramuscular naltrexone injections.

Conservative treatment of lentigo maligna with topical imiquimod 5% cream: a case report

The use of imiquimod 5% cream, a topical immunomodulator for the treatment of lentigo maligna (LM) was first described in 2000. Subsequent studies have indicated that imiquimod might be an effective nonsurgical treatment in patients who refuse to have, or are ineligible for surgery because of comorbidities, tumor size, or risk of cosmetic disfigurement. Herein, we outline our experience with treating LM on the nose in an 88-year-old skin cancer patient with significant comorbidities. Given our patient's strong preference against surgical intervention, he was treated with topical imiquimod cream applied once daily for a total of 12 weeks. A two-week treatment holiday was required for severe nausea and vomiting, treated effectively with ondansetron wafers. There were no clinical or dermoscopic signs of LM recurrence 12 months posttreatment. Topical imiquimod is an effective alternative to excision in nonsurgical candidates.

Camouflaging vitiligo using a spray tan

Vitiligo is a depigmenting skin disorder that can cause significant patient distress. Treatment of vitiligo is challenging and should address patient's concern for cosmetic treatment. Herein, we report the case of a 60-year-old patient who achieved temporary improvement in pigmentation using a spray tan. Camouflaging vitiligo using a spray-tan is a reasonable, safe, and effective mechanism for management of vitiligo.

Allergenic potential, marketing claims, and pricing of facial moisturizers

Ingredients found in facial moisturizers can impact a myriad of skin conditions, including sensitive skin syndrome and contact dermatitis. There is a paucity of evidence on the allergenic potential and marketing claims of facial moisturizers, posing challenges to clinician recommendation and consumer selection. In this study, we systematically evaluate the 100 top-selling sun protective facial moisturizers that claim to be natural, fragrance free, expert-approved, age preventing, beneficial for sensitive skin, and sun protective. Allergenic potential of these moisturizers is evaluated based on ingredients used and prices and consumer ratings are compared. Accordingly, 75 of 100 marketed at least one additional benefit. "Anti-aging" products had the highest average price ($14.99/oz) and "expert-approved" had the lowest ($5.91/oz). Consumer rating was highest for facial moisturizers that were "fragrance-free" (4.35/5.00) whereas products that were "natural" received the lowest ratings (3.49/5.00). The most prevalent allergens found in these moisturizers were ethylenediamine tetraacetic acid (EDTA), phenoxyethanol, and cetyl alcohol. "Expert-approved" products had the fewest average allergens in their ingredient lists (P=0.033), whereas products advertising "SPF" had significantly more (P<0.001). Marketing claims play a role in product sales and ratings. When recommending products, physicians should balance allergenic risk with affordability and consumer preferences.