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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 23, Issue 11, 2017

Original

Psoriasis and wound healing outcomes: A retrospective cohort study examining wound complications and antibiotic use

Little is known about wound healing in psoriasis. We performed a cohort study examining differences in wound healing complications between patients with and without psoriasis. Psoriasis patients with traumatic wounds were matched 1:3 to non-psoriasis patients with traumatic wounds based on age, gender, and body mass index (BMI). We examined theincidence of wound complications including infection, necrosis, and hematoma as well as incident antibiotic use within three months following diagnosis of a traumatic wound. The study included 164 patients with traumatic wounds, comprised of 41 patients with psoriasis matched to 123 patients without psoriasis. No statistically significant differences were detected in the incidence of overall wound complications between wound patients with psoriasis and wound patients without psoriasis (14.6% versus. 13.0%, HR 1.18, CI 0.39-3.56). After adjustment for diabetes, peripheral vascular disease, and smoking, no statistically significant differences were detected in the incidence of overall wound complications between patients with and without psoriasis (HR 1.11, CI 0.34-3.58). Specifically, the adjusted rates of antibiotic use were not significantly different between those with and without psoriasis (HR 0.65, CI 0.29-1.46). The incidence of wound complications following traumatic wounds of the skin was found to be similar between patients with and without psoriasis.

Review

Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders

Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is an autosomal dominant, tumor predisposing disorder usuallycaused by germline mutations in mismatch repair (MMR) genes. A subset of HNPCC, Muir-Torre Syndrome (MTS) also involves MMR gene defects and is generally accepted as a variant of HNPCC. MTS is typicallycharacterized by at least one visceral malignancy and one cutaneous neoplasm of sebaceous differentiation, with or without keratoacanthomas. In either version of the disorder, nonfunctional MMR systems lead tothe loss of genomic integrity, marked commonly by mismatches in repetitive DNA sequences, resulting in microsatellite instabilities. Deleterious nucleotide alterations ultimately drive the process of tumorigenesis in both HNPCC and MTS. The following article reviews the epidemiology, genetics, clinical presentation, and management of HNPCC and its MTS variant.

Sexual side effects of 5-α-reductase inhibitors finasteride and dutasteride: A comprehensive review

The 5-α-reductase inhibitors finasteride and dutasteride are frequently used in the treatment of androgenetic alopecia and benign prostatichyperplasia. These drugs are effective at reducing levels of dihydrotestosterone, the primary androgen responsible for the pathogenesis of both these conditions. However, finasteride and dutasteride have also been shown to produce an increase in the incidence of sexual dysfunction, namely, impotence, decreased libido, and ejaculation disorder. The purpose of this study is to review the existing medical literature with regard to the sexual side effects of 5-α-reductase inhibitor therapy. This review is an extensive look at the sexual effects of 5-α-reductase inhibitors and compares outcomes for finasteride versus dutasteride in addition to comparing sexualside effects for each of the different dosages prescribed of finasteride and dutasteride.

Wilderness dermatology: mountain exposures

Exploring the mountains is a highly rewarding past time; however, certain high-altitude exposures can lead to dermatologic manifestations. In this review article, the authors will describe cold, solar, and severe weather that one may experience when spending time outdoors. Factors such as increased ultraviolet radiation, temperature extremes, and low partial pressure of oxygen, along with human physiologic parameters also contribute to disease severity and presentation. This review article will address the diagnosis, treatment, and prevention of high-altitude dermatology exposures.

Metformin as an adjunct therapy for the treatment of moderate to severe acne vulgaris

The purpose of this literature review is to evaluate the use of metformin as an adjunct therapy in the treatment of moderate-to-severe acne in those not diagnosed with polycystic ovary syndrome (PCOS) or androgen excess. The authors conducted independent literature searches. Results were limited to clinical trials and randomized controlled trials. Studies with participants diagnosed with moderateto-severe acne vulgaris taking metformin versus placebo or other active treatment were included;studies with participants diagnosed with PCOS or androgen excess were excluded. The authors found three studies consistent with the search guidelines that evaluated the effects of metformin as adjunct therapy in moderate to severe acne vulgaris. In eachstudy, metformin was an effective adjunct therapy in the treatment of moderate-to-severe acne vulgaris.

Commentary

Does daily folic acid supplementation reduce methotrexate efficacy?

Methotrexate is a mainstay treatment for autoimmune and inflammatory conditions in the field of Dermatology. However, in some patients, its use is associated with significant side effects and toxicity. Folate supplementation with either folic acid or folinic acid often mitigates side effects and reduces the incidence of systemic toxicity related to methotrexate. Although the value of methotrexate is clear, debate remains about folate supplementation. There is little agreement about the proper dosing or frequency of folate supplementation as many believe that daily folate supplementation can reduce methotrexate efficacy. Although daily use of folic acid does not appear to affect methotrexate efficacy, dosing of folinic acid close to methotrexate administration may hinder methotrexate efficacy. Therefore, folic acid should be used daily with methotrexate to ameliorate side effects, whereas folinic acid should only be used for methotrexate toxicity.

Greater distance to an academic medical center is associated with poorer melanoma prognostic factors: The University of Colorado Experience

Introduction: Numerous studies report a correlation between distance to diagnostic provider in an academic medical center and poorer prognosis ofdisease. Limited research on this topic exists with respect to melanoma.

Methods: This was a retrospective chart review of 1,463 adults (≥18 years) initially diagnosed with melanoma between 2006-2016. Associations between distance traveled and Breslow depth and presence of metastatic disease were assessed via cumulative and binary logistic regression models, adjusting for patient and tumor characteristics.

Results: Subjects traveling ≥50 miles had 58% greater odds of having an increased Breslow depth than those traveling less than that distance (OR: 1.58; 95% CI: 1.24-2.01; p<0.0001), and had four times the odds of presenting with metastatic disease (OR: 4.04; 95% CI: 3.00-5.46; p<0.0001).

Discussion: We highlight the correlation between increased distance to our academic medical center with greater Breslow depths and the presence ofmetastatic disease at presentation.

Conclusion: Future studies assessing other factors and regional differences that limit access to diagnosis might help improve screening efforts to prevent poorer prognosis for patients in these areas.

Modernizing dermatology interest groups in medical school: Certificate programs

This commentary addresses the increasingly competitive nature of applying to dermatology residency programs and how both interest groups in medical schools and their dermatology departments can help to better prepare applicants. As previous literature argued that dermatology has been underemphasized in medical school curricula, we propose five fundamental options that interest groups can implement in order to offer increased exposure to our field in medical training. Furthermore, with therecent trend of many schools conferring certificates in various specialized concentrations, we also discuss interest groups pioneering certificate-grantingprograms in dermatology competency. The pros and cons of having a recognized certificate program in dermatology are presented.

Case Report

Pityriasis lichenoides-like drug reaction: A clinical histopathologic study of 10 cases

Background: Lymphomatoid drug reactions can mimic endogenous T and B cell lymphoproliferative diseases.

Objectives: We present a novel form of cutaneous drug reaction with features of pityriasis lichenoides (PL), a recognized form of T cell dyscrasia. Methods: Ten cases were studied where a cutaneous eruption exhibiting semblance to PL within a few weeks to months after starting a particular drug. Results: The patient cohort comprised 7 females and 3 males with the mean age of 60 years. Widely distributederythematous cutaneous lesions were present in 6 cases whereas a more localized distribution was seen in three cases. The most frequently implicated drugsassociated with the eruption were antidepressants and statins. Histologic examination showed a morphologic picture identical to PL including marked epitheliotropism of mildly atypical lymphocytes, psoriasiform epidermal hyperplasia, dyskeratosis, hemorrhage, and a thick parakeratotic scale. Therewas a significant reduction in the expression of CD7 and CD62L amid the T cells. Regression of the eruption occurred in all cases excluding one. Conclusion: Thefindings conform the categorization of this process as a form of T-cell dyscrasia albeit one that is reversible, dependent on the drug withdrawal. The limitationof our study includes the retrospective design of the study.

Sublamina densa-type linear IgA bullous dermatosis with IgA autoantibodies specific for type VII collagen: a case report and clinicopathological review of 32 cases

Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disorder characterized by linear deposits of IgA at the basement membrane zone(BMZ) and/or by circulating IgA anti-BMZ antibodies. Comparing with other immuno-bullous diseases, LABD represents a heterogeneous disease entitywith diversity of pathogenic IgA autoantibodies to different hemidesmosomal antigens and an association with malignancies and occasional drug use. We herein present an 82-year-old Japanese man with LABD, whose indirect immunofluorescence using 1M NaCl-split skin showed positive staining for IgA at the dermal side alone. Fluorescence overlay antigen mapping using laser scanning confocal microscopy (FOAM-LSCM) was employed to examine the in vivo bound patient’s IgA, which was specific for type VII collagen (COL7), a prominent antigen of the sublamina densa. One year later, he developed malignant lymphoma, suggesting the diagnosis of paraneoplastic LABD. We reviewed 32 cases of sublamina-densa type LABD with anti-COL7 IgA antibodies thus far reported in the literature to compare the clinicopathological characteristics of this rare disease variant and emphasize that COL7 is the main autoantigen in sublamina densa disease.

A diagnostically challenging case of CD8+ primary cutaneous gamma/delta T-cell lymphoma

Primary cutaneous gamma/delta T-cell lymphoma (PCγδTCL) is a rare form of cutaneous lymphoma characterized by abnormal clonal proliferation of mature, activated gamma-delta T cells expressing the γδ heterodimer of the T-cell receptor (TCR). As an entity, PCγδTCL has recently undergone diagnostic revision since its introduction in the 2008 WHO classification of cutaneous lymphomas and confirmedin 2016. Nonetheless, diagnosis remains difficult both clinically and histologically, given its broad range of clinical manifestations and immunohistochemical phenotypes. Herein, we present a rare case of CD8+ PCγδTCL with a discussion highlighting theheterogeneity within this entity.

Case Presentation

Crohn disease-associated neutrophilic urticarial dermatosis: report and literature review of neutrophilic urticarial dermatosis

Neutrophilic urticarial dermatosis (NUD) is a useful diagnostic term for urticarial lesions that are less pruritic and more painful than conventional urticaria. The histopathologic features include neutrophilic infiltrates in the interstitial dermis with a higher density than idiopathic urticaria. NUD has been associated with several systemic conditions, which are predominantly autoimmune and autoinflammatory in nature. A woman with Crohn disease who developed NUD is described. Literature reports of other conditions in which neutrophilic urticarial dermatosis have been observed are also reviewed and summarized. NUD has not only been described in the setting of inflammatory bowel disease, but also in patients who have systemic lupus erythematosus, adult-onset Still disease, and IgA gammopathy. NUD is usually associated with an underlying disease. Therapeutic agents that target neutrophils (such as dapsone and colchicine) and antagonists to interleukin-1 receptor (such as anakinra) may be effective modalities for affected patients. NUD can be added to the list of dermatologic manifestations associated with systemic inflammation, particularly inflammatory bowel disease.

Pediatric pustular psoriasis responsive to cyclosporine bridged to etanercept: A treatment approach

Pustular psoriasis occurs rarely in children but can present with acute toxicity requiring inpatient admission. For the best approach, medical providers should have an evidence based and systematic treatment algorithm in their armamentarium. Toillustrate this point, we describe a 13-year-old girl who was admitted with generalized pustular psoriasis and who responded dramatically to “wet wrap” therapy and cyclosporine bridged to etanercept. Using this case example, we highlight the three most important considerations in any patient with new onset pustularpsoriasis: avoidance of disease complications, acute “rescue” therapy, and maintenance therapy.

A patient case highlighting the myriad of cutaneous adverse effects of prolonged use of hydroxyurea

Background: Hydroxyurea is an antimetabolite primarily used to treat myeloproliferative disorders, and chronic treatment is associated with many cutaneous adverse effects ranging in severity from ichthyosis to aggressive nonmelanoma skin cancer.

Case Presentation: We report a 67-year-oldman with a history of polycythemia vera who was referred for management of progressively worsening dorsal hand lesions. The patient presented withhyperpigmentation, ichthyosis, plantar keratoderma, dermatomyositis-like eruptions, two squamous cell carcinomas, and actinic keratoses. The adversereactions observed were acknowledged to be related to chronic hydroxyurea use. The patient underwent Mohs excision of the squamous cell carcinomas and thehydroxyurea was promptly discontinued; subsequent cutaneous improvement of the dermatomyositislike lesions ensued. Another clinically suspicious aggressive squamous cell carcinoma was suspected and the patient was referred to the plastic surgery department for complete excision because of the size of the lesion. The patient remains on periodic dermatology follow up.

Conclusions: We report a case that exemplifies the cutaneous adverse effects of chronic hydroxyurea therapy. Although many cases improve after drug discontinuation, strict photoprotection and ongoing surveillance are indicated given the recently proposed premalignant potential of dermatomyositis-like eruptions and the aggressive nature of hydroxyurea-induced nonmelanoma skin cancer.

Classic form of eosinophilic pustular folliculitis in an immunocompetent girl: rapid and complete resolution after low-dose oral indomethacin treatment

Eosinophilic pustular folliculitis (EPF) is a rare noninfectious pruritic dermatosis, first described by Ise and Ofuji in 1965. We report the case of a 15-year oldimmunocompetent girl that presented with a widespread papulopustular eruption four days after her arrival in Japan. The clinical diagnosis of the classicform of EPF was confirmed by histological examination of the lesional skin that revealed an intense, mainly eosinophilic, dermal infiltrate within and aroundpilosebaceous units. Oral administration of lowdose indomethacin (25 mg/day) led to a complete resolution of the eruption within 6 weeks without causing any side effects. The patient is presently completing a 15-month follow-up and remains free ofrelapses. To the best of our knowledge, it is the first time that low-dose oral indomethacin is reported to be capable of causing a rapid and complete resolutionof the classic form of EPF.

Flame figures in linear IgA bullous dermatosis: a novel histopathologic finding

Background: Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease usually with a neutrophil rich inflammatory infiltrate, and characterized by linear IgA deposition at the basement membrane zone (BMZ), and neutrophil predominant dermal inflammation. We report a case of LABD with numerous eosinophils and flame figure formation, a unique histopathologic finding not previously reported. A 69-year-old woman presented with a rapidly progressive, intensely pruritic rash over forearms, breasts, axillae, hips, and thighs. Thelesions were comprised of annular vesicles and bullae with hemorrhagic crusts and erosions. The clinical differential diagnosis included bullous pemphigoid(BP), LABD, and epidermolysis bullosa aquisita (EBA).

Results: A biopsy from a bullous plaque on the wrist revealed a subepidermal blister with neutrophils and numerous eosinophils with flame figure formation.Direct immunofluorescent (DIF) microscopy revealed linear deposition of IgA at the BMZ.

Conclusions: Although unusual, the combined findings supported a diagnosis of LABD. Increased eosinophils may be associated with drug-induced LABD and may explain the numerous eosinophils in our case. It is important to be aware of this finding as the pathology may easily be misdiagnosed as BP, or possibly bullousWells syndrome. This case emphasizes that combined clinical, pathologic, and DIF findings are essential in the diagnosis of bullous dermatoses.

Is it just a psoriasiform dermatitis?

Bazex syndrome (BS) is a rare paraneoplastic syndrome most frequently associated with squamous cell carcinomas of the upper aerodigestive tractand other tumours. Characteristically, cutaneous lesions precede the diagnosis of malignancy. We report a 72-year-old patient with 1-year history of acral dermatitis. The diagnosis of BS was based on the presence of psoriasiform acral dermatitis and the evidence of two simultaneous tumors (prostate adenocarcinoma and undifferentiated carcinoma ofthe submandibular gland). It is important to have this syndrome in mind since cutaneous features usually precede an underlying neoplasm.

A case of leukocytoclastic vasculitis caused by novel anticoagulant rivaroxaban

Cutaneous leukocytoclastic vasculitis (LCV) is type of small vessel vasculitis that commonly presents as palpable purpura involving the lower extremities and buttocks. Approximately half of cases are idiopathic, but the disease may be triggered by infection, drug reaction, inflammatory disease, or other causes. We report a case of leukocytoclastic vasculitis secondary to the novel anticoagulant rivaroxaban (Xarelto®).

Cutaneous metastasis to the scalp as the primary presentation of colorectal adenocarcinoma

Eruptaneous metastasis is an uncommon presentation of colorectal adenocarcinoma that can occur years after diagnosis of the primary cancer or manifest as the first sign of malignancy. It is essential to diagnose these metastases immediately, as this late-stage development carries a poor prognosis. The scalp is one of the less common sites for skin metastases and nodules may be mistaken for benign entities. In this case report, we report on the case of a 61-year-old woman with CREST syndrome who presented with a cutaneous metastasis to the scalp as the first sign ofcolorectal adenocarcinoma.

Photo Vignette

Vulvar metastatic Crohn disease: clinical, histopathological and ultrasonographic findings

Metastatic Crohn disease (MCD) is an unusual type of cutaneous Crohn disease characterized by skin lesions separated from the lesions of the gastrointestinal tract. The diagnosis of MCD is essentially histological,showing noncaseating granulomas in the dermis and subcutaneous fat tissue. We report a case of MCD with vulvar involvement and clinical, histopathological, and ultrasonographic findings of this disease.

Lichen amyloidosis of the scalp and forehead

Lichen amyloidosis is a subtype of primary localized cutaneous amyloidosis (PLCA), which presents as discrete, firm, closely-set 1-3mm, dome-shapedbrown papules commonly involving the anterior aspect of shins and extensor surfaces of forearms. We present a case of an otherwise healthy man in his 30s with solitary facial involvement of lichen amyloidosis, which is very uncommon.