Oral Baricitinib in the Treatment of Cutaneous Lichen Planus.

Background: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon (IFN)-γ, a cytokine implicated in the pathogenesis of LP. Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre-and post-treatment samples. Results: An early and sustained clinical response was seen with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8+, CXCL13+ cytotoxic T-cell population in LP skin and demonstrate a rapid decrease in interferon signature within 2 weeks of treatment, most prominent in the basal layer of the epidermis. Conclusion: This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. Trial Registration Number : NCT05188521.

The First Sign of Recurrent Angioimmunoblastic T-Cell Lymphoma: A Cutaneous Presentation.

Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma with a nonspecific clinical presentation. Cutaneous manifestations of AITL are variable and include morbilliform eruptions, urticaria, papulonodules, and erythroderma. We present the case of a 74-year-old male with a medical history of AITL presenting with diffuse erythematous macules and papules coalescing into patches and plaques on the trunk and bilateral upper extremities. Histopathology demonstrated a mild perivascular lymphocytic infiltrate in the dermis. By immunohistochemistry, the lymphocytic infiltrate was strongly positive for programmed cell death protein 1 (PD-1) (CD279) as well as cluster of differentiation 3 (CD3), CD5, and (focally) B-cell lymphoma-6 (BCL-6). Many cells within the infiltrate were positive for Epstein-Barr virus (EBV) by in situ hybridization. Additionally, a bone marrow biopsy demonstrated an atypical lymphoid infiltrate with T-cell predominance, many EBV-positive cells, and clonal T-cell receptor (TCR) beta gene rearrangement. Based on these histopathological findings, a diagnosis of recurrent AITL with cutaneous involvement was made. This case is a rare example of skin findings presenting as a first sign of recurrent AITL.

Characteristics of Matched vs Nonmatched Dermatology Applicants.

Dermatology residency continues to be one of the most competitive specialties, with a match rate of 84.7% in 2019. We surveyed 475 dermatology applicants who applied to the Mayo Clinic in Scottsdale, Arizona, during the 2018-2019 application cycle and 629 dermatology applicants who applied to the Mayo Clinic in Scottsdale; Rochester, Minnesota; and Jacksonville, Florida, during the 2019-2020 application cycle. The initial survey obtained application and demographic information. The follow-up survey obtained match data. The initial 2019 and 2020 surveys were completed by 149 and 142 dermatology applicants, respectively, and 112 and 124 applicants completed the respective follow-up surveys. Our survey finds that factors associated with matching included a higher US Medical Licensing Examination (USMLE) Step 1 score, having a home dermatology program, and a higher number of interviews offered and attended. Some demographics had varying USMLE Step 1 scores but similar match rates.

High GILT Expression Is Associated with Improved Survival in Metastatic Melanoma Patients Treated with Immune Checkpoint Inhibition.

Gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II restricted presentation of multiple melanoma antigens. There is variable GILT protein expression in malignant melanocytes in melanoma specimens. High GILT mRNA expression in melanoma specimens is associated with improved overall survival, before the advent of immune checkpoint inhibitors (ICI). However, the association of GILT in metastatic melanoma with survival in patients treated with ICI and the cell type expressing GILT associated with survival have not been determined. Using RNA sequencing datasets, high GILT mRNA expression in metastatic melanoma specimens was associated with improved progression-free and overall survival in patients treated with ICI. A clinical dataset of metastatic melanoma specimens was generated and annotated with clinical information. Positive GILT immunohistochemical staining in antigen presenting cells and melanoma cells was observed in 100% and 65% of metastatic melanoma specimens, respectively. In the subset of patients treated with ICI in the clinical dataset, high GILT protein expression within melanoma cells was associated with improved overall survival. The association of GILT mRNA and protein expression with survival was independent of cancer stage. These studies support that high GILT mRNA expression in bulk tumor samples and high GILT protein expression in melanoma cells is associated with improved survival in ICI-treated patients. These findings support further investigation of GILT as a biomarker to predict the response to ICI.

Histopathologic features of necrobiosis lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is an uncommon granulomatous dermatosis that can occur in patients with or without associated diabetes mellitus (DM). Prior studies have attempted to determine distinctive histopathologic features of NL in patients with and without DM. METHODS: A retrospective review of 97 patients with NL was performed to determine the similar and distinctive histopathologic features in patients with DM and without DM. RESULTS: Of the 97 patients, 32% (n = 31) had DM. Epidermal acanthosis was seen more commonly in diabetics than nondiabetics (32.3% vs. 12.1%; p = 0.017). Naked (sarcoidal/tuberculoid) granulomas were more frequently observed in nondiabetics than diabetics (22.7% vs. 3.2%; p = 0.016). Eosinophils were more common in nondiabetics than diabetics (38.5% vs. 9.7%; p = 0.004), while neutrophilic infiltration was more common in diabetics than nondiabetics (45.2% vs. 17.5%; p = 0.004). CONCLUSIONS: This study corroborates well-documented histopathologic features of NL and shows distinctive histopathologic features of NL among patients with DM-I, DM-II, and without DM. These results support the hypothesis that there are different underlying drivers of NL between diabetics and nondiabetics.

Rates of Upstaging, Between Diagnosis and Surgery, and Clinical Management of Metastatic Cutaneous Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Cutaneous squamous cell carcinomas (cSCC) have upstage rates of approximately 10.3% to 11.1%. Data are currently limited on the rate of upstaging for metastatic cSCC. OBJECTIVE: The aim of this study was to determine the rates of upstaging, between diagnosis and surgery, and differences in management for metastatic and non-metastatic high-risk cSCC. MATERIALS AND METHODS: This was a retrospective, case-control, single institution, multi-center study. Univariate analysis was used. RESULTS: Sixty-eight subjects (34 metastatic & 34 non-metastatic) with 69 tumors were included. The overall rate of upstaging was 46.4%. The most common reasons for upstage were undocumented tumor size and under-diagnosis of poor differentiation. There were no differences in rates of upstaging. Preoperative imaging was performed in 43.6% of wide local excisions (WLE) versus 3.3% of Mohs micrographic surgery (MMS; p < .001). The median days from surgery to sentinel lymph node biopsy (SLNB), or nodal dissection was shorter for WLE versus MMS (0 vs 221 days, p < .001). CONCLUSION: Improved clinical documentation, including documenting tumor size, and the identification of pathologic risk factors, including poor differentiation and depth of invasion, are needed for proper staging. Preoperative imaging and discussion of SLNB may be beneficial for high-risk T2b and T3 tumors.

Cutaneous B cell pseudolymphoma treated with rituximab and methotrexate.

Cutaneous B cell pseudolymphoma (CBPL), or cutaneous lymphoid hyperplasia, is the most common pseudolymphoma. It typically responds well to local treatment and follows a benign course. Herein, we describe the unique case of a patient with CBPL that was refractory to a variety of treatments, with subsequent response to rituximab followed by methotrexate. This case explores the complex interplay of T and B lymphocytes, and the potential role of perifollicular T cells in treatment resistant CBPL. Further, it describes the additive therapeutic effect of rituximab and methotrexate to target both B cell and T cell populations in CBPL, a strategy already employed in a number of other conditions.

How to Sequence Therapies in Mycosis Fungoides.

OPINION STATEMENT: Choice of therapy in mycosis fungoides is based on both patient- and lymphoma-specific factors, such as disease characteristics, comorbidities, symptoms and effect on quality of life, potential associated toxicities of therapy, response and tolerance to prior lines of therapy, and convenience and practicality. Generally, we sequence therapies from least toxic, targeted, nonimmunosuppressive to more toxic, immunosuppressive and from single agent to multiple agents, as necessary. If more toxic, immunosuppressive agents are required to alleviate disease burden or symptoms, we generally use them just long enough to control the disease, then transition to a maintenance regimen with less toxic, less immunosuppressive agents.

A rare case of childhood mucous membrane pemphigoid involving the oral and genital mucosa.

Mucous membrane pemphigoid (MMP) is a rare chronic immunobullous disease that involves the mucous membranes and may result in significant scarring and complications if diagnosis is delayed. MMP typically occurs in elderly patients, with very few cases reported in children. Here, we present a 12-year-old female patient with childhood-onset oral and genital MMP, clinically suspected to be lichen sclerosus, but eventually diagnosed as MMP after multiple supportive biopsies and confirmatory direct immunofluorescence. Although treatment was challenging, the combined use of systemic corticosteroids, dapsone, and mycophenolate mofetil was ultimately successful in achieving disease control.