A review of topical probiotic therapy for atopic dermatitis.

Atopic dermatitis (AD) is a common, chronic skin disorder that is associated with dysbiosis of the skin microbiome along with an impaired skin barrier and abnormal immune signalling. Particularly, AD has been associated with increased abundance of Staphylococcus aureus and decreased overall bacterial diversity. Topical probiotic formulations are garnering further interest in the treatment of AD and may be derived from commensal bacteria found on healthy epithelium or from exogenous bacteria. Strains chosen for clinical trials have often demonstrated antimicrobial actions to S. aureus in vitro. Multiple randomized clinical trials with topical probiotics have resulted in significant improvements in clinical severity, decreased abundance of S. aureus in treated lesional skin and increased bacterial diversity. Side-effects from available studies have been minimal apart from one patient who developed a furuncle in the treatment area. Topical probiotics have been shown to be safe and potentially efficacious in AD; however, further research including larger, longer-term clinical trials need to be performed before topical probiotics should be recommended to patients.

Real-world utilization of Delphi consensus diagnostic criteria for suspected pyoderma gangrenosum.

We found that the systematic use of Delphi consensus diagnostic criteria resulted in substantial changes in management patterns in cases of suspected pyoderma gangrenosum (PG), including a reduction in systemic corticosteroid use, and significantly improved clinical outcomes. This improvement may have resulted from a combination of reduced misdiagnosis, optimized management and reduced iatrogenic harm. Increased utilization of validated diagnostic criteria for PG could optimize provider heuristics, increase diagnostic accuracy, and optimize management and clinical outcomes.

Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: A systematic review.

BACKGROUND: Alopecia areata (AA) is an immune-mediated disease resulting in nonscarring hair loss. Systematic reviews on the psychosocial and psychiatric comorbidities, health-related quality of life, and interventions targeting psychosocial well-being are limited. OBJECTIVE: To conduct a systematic review of the psychosocial comorbidities, health-related quality of life, and treatment options targeting psychosocial well-being in adult and pediatric AA patients. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines within the PubMed database. Specific search terms included, but were not limited to, alopecia areata, psychosocial, psychiatry, and quality of life. Studies were then evaluated for their design and categorized into corresponding levels of evidence according to the guidelines adapted from the Oxford Center for Evidence Based Medicine. FINDINGS: Seventy-three reports met inclusion criteria, involving approximately 414,319 unique participants. AA patients were found to have psychiatric comorbidities, particularly anxiety and depression. Health-related quality of life is reduced in AA patients, but data on pediatric AA quality of life are limited. Psychotherapy is often recommended as adjuvant treatment. CONCLUSION: AA has substantial psychosocial impact on patients and results in reduced health-related quality of life. Addressing this should be an active part of treatment.

Updated therapies for the management of Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a large volume of our clinical practice and its management can be challenging. Traditional DMARDs have been used over last six decades and observational studies have substantiated an effective use of many of these drugs. However, in last two decades use of anti-TNF agents has brought a new dimension in treatment of PsA and in many other autoimmune diseases. Regulatory role of the Th17 cells and its cytokines in the pathogenesis of PsA has successfully paved the foundations of anti-IL antibody based therapies in PsA. Newer therapies targeting the IL-23/IL-17 cytokines and its signaling proteins are now in development and bringing new promises for management of PsA. Herein, we provide an overview of the landscape of drug therapies, including IL-17, IL-12/23, IL-23 inhibitors, and janus kinase (JAK) inhibitors, as well as those in development, such as RORγt inhibitors, anti-NGF agents, mTOR inhibitors and T cell ion-channel blockers.

The cutaneous and intestinal microbiome in psoriatic disease.

Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases of multifactorial etiology. In addition to genetic and environmental factors, evidence supports involvement of a dysregulated human microbiome in the pathogenesis of psoriatic disease. In particular, alterations in the composition of the microbiome, termed dysbiosis, can result in downstream proinflammatory effects in the gut, skin, and joints. Both the cutaneous and intestinal microbial populations are implicated in the pathogenesis of psoriatic disease, although exact mechanisms are unclear. Herein, we review the relationship between the human microbiome and psoriatic disease. Further insight into the functions of the microbiome may allow for greater understanding of inflammatory disease processes and identification of additional therapeutic targets.

Successful Management of Anti-TNF-Induced Psoriasis Despite Continuation of Therapy in a Pyoderma Gangrenosum Patient

Pyoderma gangrenosum is an inflammatory, neutrophil-mediated disorder that is difficult to treat. Tumor necrosis factor and other inflammatory mediators are among the most promising therapeutic targets. We present a case of a 60-year-old woman with recalcitrant pyoderma gangrenosum treated with adalimumab, who paradoxically developed psoriasis. Secukinumab, an interleukin-17 inhibitor, was added to her regimen, resulting in successful treatment of her psoriasis. Secukinumab was later replaced by methotrexate, resulting in remission of both pyoderma gangrenosum and maintenance of a psoriasis-free state. We conclude that paradoxically induced psoriatic lesions can resolve with adjunct therapy despite continuation of anti-tumor necrosis factor agents. J Drugs Dermatol. 2020;19(2)199-201. doi:10.36849/JDD.2020.4662

Eosinophilic fasciitis presenting as a unilateral, solitary plaque.

Eosinophilic fasciitis is a rare connective tissue disorder characterized by inflammation of the fascia that leads to painful, indurated skin. Because of its variable clinical presentation and overlap with conditions, such as morphea, the diagnosis of eosinophilic fasciitis can be challenging and relies on clinical presentation, histopathologic and laboratory analysis, and response to therapy. Herein, we present an unusual, solitary, isolated plaque with pathologic features and response to therapy most consistent with eosinophilic fasciitis.

End stage scurvy in the developed world: A diagnostic conundrum but not to be mistaken for pyoderma gangrenosum.

Scurvy is a clinical syndrome, resulting from ascorbic acid deficiency. Prevalence of the condition is now extremely low in the Western population and its diagnosis can be challenging without a high index of suspicion. When cases do present, they are often misdiagnosed initially. Therefore, a thorough history, physical exam, and laboratory evaluation are key to showing this now rare but extremely well-known disease. We report a case of scurvy manifesting as persistent non-healing lower-extremity ulcerations, initially mistaken for pyoderma gangrenosum. The patient responded to appropriate replacement therapy, but ulcers were slow to heal. As was the case in our patient, symptom reversal may require additional nutritional replacement. We encourage physicians to consider nutritional deficiencies in their differential diagnoses and highlight the incidence of malnutrition in the proper clinical setting to avoid diagnostic delay.

Mohs micrographic surgery for cutaneous malignancies: A focus review of its indications in pediatric age groups.

Mohs micrographic surgery (MMS) is a highly specialized technique that has been successful in the treatment of a variety of skin tumors. The technique can be performed as an outpatient procedure and encompasses surgical excision and intraoperative assessment of tumor margins in one setting by the same physician. The process ensures precise margin control with maximal preservation of healthy tissues. Mohs micrographic surgery has been practiced worldwide, including in the United States, Europe (United Kingdom, Germany, Spain, Netherlands, Switzerland), and Australia. Although it is commonly performed in adults with greater success, it has been discussed less frequently in children. In this article, we describe several cutaneous tumors in children and the role of Mohs micrographic surgery in their management. A PubMed search was conducted to review the most common cutaneous tumors in children treated using Mohs micrographic surgery. In this review, we discuss indications for Mohs micrographic surgery and pertinent studies examining success rates in children. Mohs micrographic surgery has been used to treat several tumors in children and offers the advantage of high cure rates and tissue conservation. This report emphasizes the benefits of Mohs micrographic surgery in children and highlights several cutaneous tumors for which it has been used to treat successfully.

Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.

ERAP1, ERAP2, and LNPEP are aminopeptidases implicated in autoimmune pathophysiology. In this study, we show that ERAP2 is upregulated and ERAP1 is downregulated in patients with psoriasis who are homozygous for autoimmune-linked variants of ERAP. We also demonstrate that aminopeptidase expression is not uniform in the skin. Specifically, the intracellular antigen-processing aminopeptidases ERAP1 and ERAP2 are strongly expressed in basal and early spinous layer keratinocytes, whereas granular layer keratinocytes expressed predominantly LNPEP, an aminopeptidase specialized in the processing of extracellular antigens for presentation to T cells. In psoriasis, basal keratinocytes also expressed the T-cell- and monocyte-attracting chemokine, CCL2, and the T-cell-supporting cytokine, IL-15. In contrast, TGF-ß1 was the major cytokine expressed by healthy control basal keratinocytes. SFRP2-high dermal fibroblasts were also noted to have an ERAP2-high expression phenotype and elevated HLA-C. In psoriasis, the SFRP2-high fibroblast subpopulation also expressed elevated CXCL14. From these results, we postulate that (i) an increased ERAP2/ERAP1 ratio results in altered antigen processing, a potential mechanism by which ERAP risk alleles predispose individuals to autoimmunity; (ii) ERAP2-high expressing cells display a unique major histocompatibility complex-bound peptidome generated from intracellular antigens; and (iii) the granular layer peptidome is skewed toward extracellular antigens.

Development of a Skin-Directed Scoring System for Stevens-Johnson Syndrome and Epidermal Necrolysis: A Delphi Consensus Exercise.

Importance: Scoring systems for Stevens-Johnson syndrome and epidermal necrolysis (EN) only estimate patient prognosis and are weighted toward comorbidities and systemic features; morphologic terminology for EN lesions is inconsistent. Objectives: To establish consensus among expert dermatologists on EN terminology, morphologic progression, and most-affected sites, and to build a framework for developing a skin-directed scoring system for EN. Evidence Review: A Delphi consensus using the RAND/UCLA appropriateness criteria was initiated with a core group from the Society of Dermatology Hospitalists to establish agreement on the optimal design for an EN cutaneous scoring instrument, terminology, morphologic traits, and sites of involvement. Findings: In round 1, the 54 participating dermatology hospitalists reached consensus on all 49 statements (30 appropriate, 3 inappropriate, 16 uncertain). In round 2, they agreed on another 15 statements (8 appropriate, 7 uncertain). There was consistent agreement on the need for a skin-specific instrument; on the most-often affected skin sites (head and neck, chest, upper back, ocular mucosa, oral mucosa); and that blanching erythema, dusky erythema, targetoid erythema, vesicles/bullae, desquamation, and erosions comprise the morphologic traits of EN and can be consistently differentiated. Conclusions and Relevance: This consensus exercise confirmed the need for an EN skin-directed scoring system, nomenclature, and differentiation of specific morphologic traits, and identified the sites most affected. It also established a baseline consensus for a standardized EN instrument with consistent terminology.