Diagnosis and management of pemphigus: Recommendations of an international panel of experts.

BACKGROUND: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. METHODS: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. RESULTS: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. LIMITATIONS: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. CONCLUSIONS: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Cryptococcal cellulitis: A rare entity histologically mimicking a neutrophilic dermatosis.

Cutaneous Cryptococcus infection presents classically with granulomatous and gelatinous reactive patterns. Cases mimicking neutrophilic dermatoses have not been described. Conversely, neutrophilic dermatoses with degrading cells mimicking cryptococcal organisms have been reported. We report a case of cryptococcal cellulitis in an immunocompromised male with a robust neutrophilic infiltrate raising histologic consideration for a neutrophilic dermatosis.

Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts.

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.

Two decades of using the combination of tetracycline derivatives and niacinamide as steroid-sparing agents in the management of pemphigus: defining a niche for these low toxicity agents.

BACKGROUND: The twin goals of long-term disease control and minimizing toxicities related to immunosuppression necessitate efforts to find effective steroid-sparing agents in the management of patients with autoimmune bullous diseases. Pemphigus especially requires a long view, because the disease can persist throughout a patient's lifetime, yet few clinical trial reports exist to guide the practitioner. OBJECTIVES: We review the response of pemphigus patients to tetracycline, doxycycline, or minocycline plus niacinamide (TCN/NAM) as steroid-sparing therapy and to determine the effects of TCN/NAM on autoantibody levels during the long-term treatment of pemphigus. METHODS: This was a retrospective chart review in a private medical dermatology practice setting of all pemphigus patients treated between 1993 and 2013. Clinical responses to TCN/NAM therapy after initial high-dose steroid induction therapy and pemphigus antibody levels were recorded over the course of disease flares and treatment cycles along with any related side effects. Anti-desmoglein 1 and 3 titers were compared in a subset of patients over time, and a statistical analysis was performed to correlate the clinical response with antibody levels. RESULTS: Fifty-one pemphigus patients (43 with pemphigus vulgaris, 7 with pemphigus foliaceous, and 1 with pemphigus erythematosus) received at least 3 months of TCN/NAM, and 16 patients with pemphigus vulgaris had 1 set of pemphigus antibody titers correlating to a baseline/flare and clinical remission. TCN/NAM was associated with disease control in 43 of 51 patients, with a duration of response ranging from 1 to 13 years (mean, 3.14 ± 2.97 years). Thirteen of 51 patients needed no additional treatment for complete disease control, while 33 of 51 needed intermittent topical clobetasol or short courses of oral steroids for long-term management. There were 5 nonresponders. Antidesmoglein titers trended lower in TCN/NAM responders, but only desmoglein 3 approached statistical significance (anti-desmoglein 1, P = .21; anti-desmoglein 3, P = .02). LIMITATIONS: This is a retrospective analysis from a single practice. A lack of serial autoantibody titers limited statistical analyses. CONCLUSION: TCN/NAM may be useful as a steroid-sparing therapy for pemphigus.

Linear scleroderma in an adolescent woman treated with methotrexate and excimer laser.

A 17-year-old Caucasian woman presented for evaluation and treatment of a tender expanding linear plaque on her left flank. Biopsy findings were consistent with morphea. Treatment initially included intralesional steroid injections and topical calcipotriene ointment, followed by methotrexate and excimer laser. The lesion decreased in size considerably with relief of symptomatic discomfort by 7 months. An excisional biopsy of a persistent eroded papule on the superior aspect of the morphea plaque revealed dermal thickening and sclerosis with superimposed perforation of a calcified nodule. Localized scleroderma, or morphea, is an autoimmune disease of the skin and underlying subcutaneous tissue primarily affecting the pediatric population. The excimer laser has been reported to effectively treat a variety of dermatologic conditions, including morphea. Its mechanism of action may be via depletion of T cells, altering apoptosis-mediating molecules and decreasing cytokine expression. Methotrexate is also useful for the acute and deep forms of morphea and has been shown to decrease levels of inter leukins-2 and -6, tenascin, and mast cells. This patient had a good clinical response with a combination of these two modalities. The epidermal perforation with transepidermal elimination of calcified necrotic collagen is a unique complication that may have been secondary to this combination treatment modality.

Incorporating Dermatologic Clinical Research Into Private Practice: A Review.

Clinical research is beneficial for the continued progression of medicine and the larger body of scientific knowledge. Clinical research can be incorporated into a range of settings, ranging from larger learning institutions to small private practices. With the need for continued advancement of the development of pharmaceutical interventions as well as other forms of clinical understanding, it is advantageous to create an environment where smaller, private practices feel comfortable and guided in establishing clinical research. It can be difficult to find the best methods to incorporate in-house clinical research. This review aims to address this gap in the literature, making the establishment of clinical trials, specifically clinical drug trials, more accessible in dermatology for private practices.

A novel treatment for ulcerative calcinosis cutis.

BACKGROUND: Calcinosis cutis is a term used to describe a group of disorders which result in calcium deposits in the skin. These disorders can be separated based on etiology. OBJECTIVE AND METHODS: Sodium thiosulfate has been used to systemically treat calciphylaxis with little to no adverse effects. We report two cases of ulcerative calcinosis cutis which were refractory to multiple topical treatments and did not improve with correction of underlying electrolyte abnormalities. RESULTS: Both cases showed an excellent response to topical 25% sodium thiosulfate compounded in zinc oxide. LIMITATIONS: We are limited by a small sample size (n=2) in this case series. CONCLUSIONS: We recommend topical sodium thiosulfate 25% as an alternative treatment for dystrophic calcinosis cutis.

Sunscreens: UV filters to protect us: Part 1: Changing regulations and choices for optimal sun protection.

Sunscreens are topical preparations containing any number of ultraviolet filters (UVFs). The first part of the review will focus on the recent Food and Drug Administration (FDA) regulations of 2019 and general use of these agents. While sunscreen products are becoming more regulated in the United States, we still lag behind other countries in our options for UVFs. Sun protection to prevent skin cancer and aging changes should be a combination of sun avoidance, protective structures, and clothing as well as use of sunscreen products. Newer and safer products are needed to help supplement and replace older agents as well as improve their cosmetic acceptability. This will be a review of ingredients, local toxicities (i.e. contact dermatitis, photocontact dermatitis), special considerations for children, and cosmesis of sunscreen preparations. Part 2 will focus on the environmental, ecological and human toxicities that have been increasingly related to UVFs.

Greening the office: Saving resources, saving money, and educating our patients.

OBJECTIVE: Dermatologists can benefit from adopting environmental sustainability in the management of their practices. We can also use opportunities to share best practices in environmental stewardship concepts with our colleagues, patients, and communities. Herein, we review easy steps for any health care professional, and dermatologists in particular, to adopt environmental sustainability and become more active in the fight against climate change. METHODS: This study included a select literature review, an identification of resources, and an overview of MyGreenDoctor.org. RESULTS: Many simple, cost effective, energy saving resources were identified. A reference list of climate change resources for health are organizations to help with lower their carbon footprints, educating their staff and patients, and advocacy for better environmental stewardship is presented. CONCLUSION: Going green is an easy process that can save money, boost morale, and help educate patients while reducing the carbon footprint of any size medical practice.

Management of a Unique Presentation of a Common Dermatologic Condition.

CONTEXT: Skin rashes are a common complaint seen in the primary care setting. There are many dermatologic conditions which a primary care provider (PCP) should be able to recognize and manage. One such condition is granuloma annulare (GA), which commonly presents as smooth, annular plaques on the trunk and/or extremities. Rashes like GA rarely present as unique variants and may be difficult for PCPs to determine from patient history and physical exam alone. Patch granuloma annulare (patch GA) is an example that may clinically mimic a cutaneous lymphoma known as mycosis fungoides (MF). PCPs should ideally be able to recognize the utility of performing a skin biopsy and/or referring the patient to a dermatologist when history and physical exam alone are insufficient. The histologic findings of skin biopsies often become essential in establishing a proper diagnosis and guiding patient management in unique dermatologic variants. EXAMPLE CASE: The patient in this clinical practice report is a Caucasian female in her late 60s who presented to a dermatology clinic with a two-year history of a worsening widespread eruption on her trunk and extremities. She had been evaluated previously by her PCP about 4 months prior and, without obtaining skin biopsies, treated her with a medium potency topical corticosteroid cream. The eruption had spread over her hips, buttocks, back, thighs, wrists, and elbows. Multiple skin biopsies of affected sites were taken by the second author and revealed findings consistent with patch GA. The patient was started on topical betamethasone dipropionate 0.05% ointment twice daily and noted marked improvement of her symptoms. CONCLUSIONS: Although GA is a benign condition of the skin that may be readily detected by PCPs, skin biopsies may be necessary to establish a proper diagnosis when this condition presents as a unique variant (e.g., patch GA). Therapy for patch GA often begins with a trial of high-potency topical steroid therapy in combination with ultraviolet light exposure, depending on disease severity and patient preference. Early evaluation with a skin biopsy by her PCP or an earlier referral to a dermatologist to have skin biopsies performed likely would have helped establish a prompter diagnosis and treatment plan for this patient.

Sunscreens: UV filters to protect us: Part 2-Increasing awareness of UV filters and their potential toxicities to us and our environment.

BACKGROUND: Sunscreens are topical preparations containing one or more compounds that filter, block, reflect, scatter, or absorb ultraviolet (UV) light. Part 2 of this review focuses on the environmental, ecological effects and human toxicities that have been attributed to UV filters. METHODS: Literature review using NIH databases (eg, PubMed and Medline), FDA and EPA databases, Google Scholar, the Federal Register, and the Code of Federal Regulations (CFR). LIMITATIONS: This was a retrospective literature review that involved many different types of studies across a variety of species. Comparison between reports is limited by variations in methodology and criteria for toxicity. CONCLUSIONS: In vivo and in vitro studies on the environmental and biological effects of UV filters show a wide array of unanticipated adverse effects on the environment and exposed organisms. Coral bleaching receives considerable attention from the lay press, but the scientific literature identifies potential toxicities of endocrine, neurologic, neoplastic and developmental pathways. These effects harm a vast array of aquatic and marine biota, while almost no data supports human toxicity at currently used quantities (with the exception of contact allergy). Much of these data are from experimental studies or field observations; more controlled environmental studies and long-term human use data are limited. Several jurisdictions have prohibited specific UV filters, but this does not adequately address the dichotomy of the benefits of photoprotection vs lack of eco-friendly, safe, and FDA-approved alternatives.

Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus.

Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus. Common terms and end points of pemphigus are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. This consensus statement from the International Pemphigus Committee represents 2 years of collaborative efforts to attain mutually acceptable common definitions for pemphigus. These should assist in development of consistent reporting of outcomes in future studies.

Hydrocortisone butyrate 0.1% lotion in the treatment of atopic dermatitis in pediatric subjects.

BACKGROUND: Hydrocortisone butyrate (HCB) is currently marketed as a cream, ointment, and solution. A new lotion formulation of hydrocortisone butyrate 0.1% (Locoid lotion) has been developed and evaluated. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of HCB 0.1% lotion compared to the vehicle in subjects aged 3 months to less than 18 years with mild to moderate atopic dermatitis (AD). METHODS: In this multicenter double-blind study, 284 subjects with mild to moderate AD were randomized 1:1 to receive HCB 0.1% lotion or the vehicle for a duration of 4 weeks. "Treatment success" was defined as those subjects with a final Physician Global Assessment (PGA) score of 0 or 1 that had at least a 2-point reduction in the PGA score from baseline to day 29. Safety was assessed by monitoring adverse events. RESULTS: Analyses of the final PGA score showed a significant treatment effect (P <.001) in favor of the HCB 0.1% lotion group. The safety profile of the HCB 0.1% lotion was also favorable. LIMITATIONS: The study did not assess the durability of the treatment effects (ie, safety and efficacy) after completion of the 4-week treatment period nor the potential need for longer term therapy given the chronic nature of AD. CONCLUSION: Results demonstrate the safety and efficacy of HCB 0.1% lotion in the treatment of mild to moderate AD in children 3 months to 18 years of age.

Human T-lymphotropic virus 1 associated with adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an uncommon neoplasm of mature T lymphocytes associated with infection by human T-lymphotropic virus 1 (HTLV-1), which is increasing in incidence in areas of the United States with large immigrant populations. Human T-lymphotrophic virus 1 infection is asymptomatic in most patients and has been associated with ATLL as well as tropical spastic paraparesis. Because there is considerable histologic overlap with other cutaneous T-cell lymphomas, high suspicion and clinical features must be present to make the diagnosis of ATLL.

Etanercept improves psoriatic arthritis patient-reported outcomes: results from EDUCATE.

Experience Diagnosing, Understanding Care, and Treatment With Etanercept (EDUCATE) is a multicenter, phase 4, 24-week, open-label study of the safety and efficacy of etanercept therapy in patients with psoriatic arthritis (PsA) in routine dermatologic practice. We present data on patient-reported outcomes (PROs) from EDUCATE, which demonstrate that subjects with PsA achieved clinically meaningful improvements in both skin- and joint-related PROs after 24 weeks of treatment.

The mechanisms of action of nicotinamide and zinc in inflammatory skin disease.

Nicotinamide (niacinamide), a physiologically active form of niacin (nicotinic acid), in combination with zinc is being assessed in clinical studies for the treatment of inflammatory skin diseases such as acne vulgaris and bullous pemphigoid. The basis for these investigations is the variety of potential mechanisms of action of nicotinamide and zinc, including an anti-inflammatory effect via inhibition of leukocyte chemotaxis, lysosomal enzyme release, lymphocytic transformation, mast cell degranulation, bacteriostatic effect against Propionibacterium acnes, inhibition of vasoactive amines, preservation of intracellular coenzyme homeostasis, and decreased sebum production. Other possible mechanisms involve suppression of vascular permeability and inflammatory cell accumulation, as well as protection against DNA damage. The goal of this paper is to review the pathophysiology of inflammatory skin diseases and discuss the role, mechanisms of action, and safety of nicotinamide and zinc as therapeutic options for these disorders.