Coma Blister After Trazodone Misuse: A Case Report.

ABSTRACT: Coma blisters are epidermal and subepidermal bullous lesions that can arise throughout the body after a prolonged impairment of consciousness. Coma blister-like lesions have been well-documented in adults after barbiturate-induced intoxication. More recently, other drugs and substances have been associated with the development of these bullae, which has broadened the scope of medications that put patients at risk of developing coma blister-like lesions. We present a unique case of a noncomatose patient who developed coma blister-like lesions after trazodone misuse. This case illustrates the need to further investigate the mechanism behind drug-induced coma bullae-like lesions so that clinicians can better identify and discontinue drugs that precipitate such lesions.

Epidemiology of Chronic Dermatologic Conditions in Skin of Color.

Across the board, common dermatologic conditions disproportionately affect patients of color. While the causes of these disparities have been tied to the environment, societal structure, access to care, health literacy, and biological factors, there is limited understanding of the extent and impact of dermatologic healthcare inequity. This study provides a resource on the epidemiology of common dermatologic diseases across racial lines and points out current lapses in scientific understanding of the disparate impact of certain conditions. This study will review epidemiological data on atopic dermatitis (AD), adult acne, pseudofolliculitis, dermatophytosis, psoriasis, vitiligo, melasma, hyperpigmentation, keloids, hidradenitis suppurativa (HS), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. J Drugs Dermatol. 2023;22(11):e21-e23    doi:10.36849/JDD.7131e.

Cutaneous malakoplakia arising on the ankle of a patient with pyoderma gangrenosum.

Malakoplakia is a rare chronic inflammatory condition that most commonly involves the urogenital tract. Cutaneous malakoplakia is extremely rare and many patients diagnosed with skin involvement are immunosuppressed. While the clinical presentation of cutaneous malakoplakia is variable, the histopathologic features are quite distinct and include sheets of closely packed dermal histiocytes with foamy-appearing cytoplasm and Michaelis-Gutmann bodies that are positive with certain immunohistochemical stains. While the exact pathogenesis of malakoplakia is unknown, it has been associated with certain bacterial infections. Treatment generally involves a combination of surgery and antimicrobial agents and/or modulation of immunosuppressant therapy if appropriate. Herein, the authors report a unique case of cutaneous malakoplakia arising in a patient on chronic immunosuppressive therapy for the management of pyoderma gangrenosum.

Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial.

Importance: Cutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians. Objective: To study the efficacy and safety of apremilast as an add-on therapy in patients with recalcitrant cutaneous dermatomyositis. Design, Setting, and Participants: This phase 2a, open-label, single-arm nonrandomized controlled trial was conducted at a single center from June 2018 to June 2021. Participants were 8 patients with recalcitrant cutaneous dermatomyositis, defined by a cutaneous disease activity severity index (CDASI) score greater than 5 despite treatment with steroids, steroid-sparing agents, or both. Data were analyzed from June 2018 to June 2021. Interventions: Apremilast 30 mg orally twice daily was added to ongoing treatment regimens. Main Outcomes and Measures: The primary outcome was the overall response rate (ORR) at 3 months. Key secondary outcomes were the safety and toxicity of apremilast and the durability of response at 6 months. The CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly until month 7. Skin biopsies were performed at baseline and 3 months after apremilast (defined as 3 months into active apremilast therapy) and tested for gene expression profiling and immunohistochemical stains. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Results: Among 8 patients with recalcitrant cutaneous dermatomyositis (all women; mean [SD] age, 54 [15.9] years), a response was found at 3 months after apremilast among 7 patients (ORR, 87.5%). The mean (SD) decrease in CDASI was 12.9 (6.3) points at 3 months (P < .001). Apremilast was well tolerated, with no grade 3 or higher adverse events. Sequencing of RNA was performed on skin biopsies taken from 7 patients at baseline and at 3 months after therapy. Appropriate negative (ie, no primary antibody) and positive (ie, tonsil and spleen) controls were stained in parallel with each set of slides studied. Of 39 076 expressed genes, there were 195 whose expression changed 2-fold or more at P < .01 (123 downregulated and 72 upregulated genes). Gene set enrichment analysis identified 13 pathways in which apremilast was associated with downregulated expression, notably signal transducers and activators of transcription 1 (STAT1), STAT3, interleukin 4 (IL-4), IL-6, IL-12, IL-23, interferon γ (IFNγ), and tumor necrosis factor α (TNFα) pathways. In immunohistochemical staining, there was a mean (SD) decrease in phosphorylation levels STAT1 (22.3% [28.3%] positive cells) and STAT3 (13.4% [11.6%] positive cells) at the protein level, a downstream signaling pathway for the downregulated cytokines. Conclusions and Relevance: These findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways. Trial Registration: ClinicalTrials.gov Identifier: NCT03529955.

Cutaneous manifestations of lupus erythematosus: a practical clinicopathological review for pathologists.

Accurate diagnosis of connective tissue diseases is often challenging, and relies upon careful correlation between clinical and histopathological features, direct immunofluorescence studies and laboratory work-up. Lupus erythematosus (LE) is a prototype of connective tissue disease with a variety of cutaneous and systemic manifestations. Microscopically, cutaneous LE is classically characterised by an interface dermatitis although other histopathological patterns also exist, depending upon the clinical presentation, location and chronicity of the skin lesions. In this article, we review the clinical, serological, histopathological and direct immunofluorescence findings in LE-specific and LE non-specific skin lesions, with an emphasis upon lesser-known variants, newly described features and helpful ancillary studies. This review will guide general pathologists and dermatopathologists in accurately diagnosing and subclassifying cutaneous LE.

A Case of Recalcitrant Linear Morphea Responding to Subcutaneous Abatacept.

INTRODUCTION: Linear morphea is an inflammatory condition that is often treated with systemic glucocorticoids and methotrexate, with mycophenolate mofetil being used as an alternative agent. However, there are few published reports on beneficial effect of abatacept for refractory disease. We present a case of a woman in her 30s who presented with linear morphea on her scalp, with a notable response following the addition of subcutaneous abatacept. METHODS: Computational analysis was performed comparing the immune cell scores of skin biopsies from 5 morphea skin biopsies from 3 unique patients and 15 healthy control skin biopsies. P < 0.05 was considered statistically significant. RESULTS: Immune cell scores demonstrated a statistically significant enrichment of activated CD4 memory T cells, M1 macrophages, monocytes, and memory B cells comparing skin biopsies of morphea vs healthy controls (p < 0.05 for all). DISCUSSION: Abatacept may be considered for recalcitrant cases of morphea. Our computational analysis supports a well-designed study to assess abatacept as first line therapy.

Connective Tissue Diseases in the Skin: Emerging Concepts and Updates on Molecular and Immune Drivers of Disease.

Cutaneous manifestations are common across the spectrum of autoimmune diseases. Connective tissue diseases manifesting in the skin are often difficult to classify and require integration of clinical, histopathologic, and serologic findings. This review focuses on the current understanding of the molecular and immune drivers involved in the pathogenesis of cutaneous lupus erythematosus, dermatomyositis, scleroderma/systemic sclerosis, and mixed connective tissue disease. Recent research advances have led to the emergence of new ancillary tools and useful diagnostic clues of which dermatopathologists should be aware to improve diagnostic accuracy for these diseases.

Immunophenotypic switch in cutaneous T-cell lymphoma: A series of three cases and review of the literature.

Primary cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of neoplasms with variable clinical behavior. Immunophenotypic switch (IS) is a phenomenon that occurs during lymphoma progression and is defined by an alteration in the immunophenotypic expression of a tumor with retention of its genotypic signature. This has been well-recognized in hematopoietic neoplasms; however, it has been rarely reported in CTCL and its clinical implications are not well understood. We present the clinical, histopathologic, immunophenotypic, and genetic findings of three cases of CTCL that demonstrated IS post treatment with variable outcomes. We add our cases to the small number previously reported to increase awareness of this phenomenon and its diagnostic challenge.

Acute graft-vs-host disease following liver transplantation.

Acute graft-vs-host disease (GVHD) is a T cell-mediated reaction in which donor T lymphocytes attack host tissue in the setting of immunosuppression. The most common cause of acute GVHD is allogeneic stem cell transplantation, with solid-organ transplantation being a much less common cause. Early diagnosis and treatment are imperative to decrease morbidity and mortality. Dermatologists play a fundamental role in the diagnosis of this condition because skin involvement is among the earliest signs of acute GVHD. We present a case of acute GVHD following liver transplantation, focusing on diagnostic criteria and a comparison to acute GVHD following hematopoietic stem cell transplantation.

Hair and Nail Changes During Long-term Therapy With Ibrutinib for Chronic Lymphocytic Leukemia.

IMPORTANCE: Ibrutinib, a Bruton tyrosine kinase inhibitor, is a new targeted agent approved by the US Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and Waldenström macroglobulinemia. Ibrutinib is overall well tolerated but long-term treatment is required until disease progression or intolerable toxic effects occur. Little is known regarding its cutaneous adverse effects. OBJECTIVE: To describe the hair and nail manifestations associated with the long-term use of ibrutinib for the treatment of CLL. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 66 patients with CLL enrolled in a single-arm phase 2 clinical trial of ibrutinib for CLL between March 2014 and October 2015 at the National Institutes of Health. MAIN OUTCOMES AND MEASURES: The primary outcome, nail and hair changes associated with ibrutinib therapy, was assessed by an 11-question survey. In addition, the severity of nail changes was determined from a 0 to 3 rating scale for both onychoschizia and onychorrhexis. RESULTS: Among 66 patients (43 men and 23 women with ages ranging from 55 to 85 years), 44 (67%) reported brittle fingernails at a median of 6.5 (95% CI, 6-12) months after starting ibrutinib therapy. Fifteen patients (23%) developed brittle toenails after a median of 9 (95% CI, 6-15) months of ibrutinib therapy. Textural hair changes were reported in 17 patients (26%), at a median of 9 (95% CI, 6-12) months of ibrutinib treatment. CONCLUSIONS AND RELEVANCE: Hair and nail abnormalities are commonly associated with ibrutinib and appear several months after initiating therapy. Ibrutinib inhibits Bruton tyrosine kinase by covalently binding to cysteine 481. Whether ibrutinib affects the hair and nails by binding and altering cysteine-rich proteins of hair and nails or by means of another mechanism remains unknown. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01500733.