Immunoglobulin G4-Related Disease-Associated Dermatitis with Pruritus: A Positive Response to Dupilumab.

Immunoglobulin G4-related disease (IgG4-RD) is a rare fibro-inflammatory condition characterized by IgG4-expressing plasma cell infiltration of the skin and other organs, leading to profound itchiness. Oral corticosteroids are the first-line therapy for IgG4-RD but relapses and potential side effects are common. In this case, we discuss a patient with a hyperpigmented, scaling dermatitis on his arms, back, and chest with lichen amyloidosis (LA) that incompletely responded to corticosteroids. He had reduced quality of life secondary to chronic pruritus. Dupilumab, an IL-4 and IL-13 inhibitor, was initiated. He experienced a transient worsening, followed by complete resolution of his itch with remission of his rash. While the pathogenesis of IgG4-RD is not entirely understood, a T-helper 2 (Th2) immune response has been implicated, with interleukins (IL) 4, 5, 10, and 13 playing a role in IgG4 class switch, resulting in eosinophilia and elevated IgE. The strong response of dupilumab in this case may provide evidence in favor of the involvement of IL-4 and IL-13 in the pathogenesis of cutaneous IgG4-RD. Future clinical studies involving larger patient populations may be warranted.

Oral Janus kinase inhibitors in the treatment of atopic dermatitis: A systematic review and meta-analysis.

Background: Janus kinase (JAK) inhibitors are being evaluated as promising upcoming treatments for atopic dermatitis (AD). Objectives: To systematically assess the efficacy of oral JAK inhibitors in patients with AD and provide comparisons among JAK inhibitors. Methods: A systematic literature review of JAK inhibitors in the treatment of AD was conducted and reported based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses using PubMed, ClinicalTrials.gov, CENTRAL, MEDLINE/Ovid, Embase and sponsor websites from inception to 30 September 2021. References of relevant articles were reviewed by two authors. Only RCTs of JAK inhibitors for treating AD with more than one study were included. Data was extracted and the meta-analysis was performed using the metan procedure in STATA version 12.1. Risk of bias was assessed with the Cochrane Risk of Bias Tool. The four outcomes analysed included Eczema Area Severity Index (EASI)-75 response (≥75% improvement of EASI score from baseline), percent change in EASI score, percent of subjects achieving Investigator Global Assessment (IGA) of clear or almost clear (IGA 0/1), and ≥ 4-point improvement in pruritus numerical rating scale (NRS). Results: Fourteen randomized controlled trials (7051 subjects) assessing three different oral JAK inhibitors (abrocitinib, baricitinib and upadacitinib) in patients with moderate-to-severe AD were included in the meta-analysis. Abrocitinib (100 and 200 mg), baricitinib (1, 2 and 4 mg) and upadacitinib (15 and 30 mg) were all found to be more efficacious compared to placebo in all four outcomes analysed. Upadacitinib 30 mg was more effective than all other dosages of JAK inhibitors in achieving EASI-75, decrease in percent change of EASI, IGA 0/1 response rate, and ≥ 4-point improvement in pruritus NRS. Conclusions: JAK inhibitors were found to be an effective treatment for AD. Upadacitinib, at 30 mg, was found to be the most efficacious oral JAK inhibitor for AD. More clinical trial studies with comparisons among JAK inhibitors are needed to confirm these results as well as explore long-term efficacy and safety of these molecules.

A comparative study of histopathologic features in alopecia areata and pattern hair loss.

BACKGROUND: When peribulbar infiltrates are absent, other histopathologic findings are necessary to distinguish alopecia areata (AA) from pattern hair loss (PHL). The purpose of this study is to determine which histopathologic features are most useful for differentiation. METHODS: A retrospective slide review was conducted of AA and PHL scalp biopsy specimens from 2014 to 2019 at a tertiary referral center. RESULTS: Ninety-six cases were retrieved, of which 38 were AA. Peribulbar infiltrates were identified in 24 AA (63.2%) cases. A catagen/telogen shift was observed more frequently in AA than PHL (25 cases, 65.5% vs. 10 cases, 17.2%; p ≤ 0.0001). Lymphocytes (4 cases, 10.5% vs. 1 case, 1.7%; p = 0.058) and melanin (25 cases, 65.8% vs. 5 cases, 8.6%; p ≤ 0.0001) in fibrous tracts were more common in AA. Apoptotic bodies within vellus hairs were more frequently identified in AA (32 cases, 84.2% vs. 37 cases, 63.8%; p = 0.030). Small dystrophic follicles were also more common in AA (16 cases, 42.1% vs. 1 case, 1.7%; p < 0.0001). CONCLUSIONS: Common features of AA other than peribulbar infiltrates include a catagen/telogen shift, melanin in fibrous tracts, and small dystrophic follicles. Practitioners should consider these features when distinguishing AA from PHL in specimens without peribulbar infiltrates. The retrospective design limits our ability to exclude multifactorial alopecia, such as telogen effluvium.

A Retrospective Review of Tofacitinib in the Treatment of Refractory Dermatomyositis.

Dermatomyositis (DM) is an autoimmune myopathy with characteristic dermatologic features.1 Tofacitinib is an immunomodulator with proven efficacy against numerous immune-mediated disorders, including rheumatoid arthritis (RA) and psoriasis.2 Several reports have demonstrated oral tofacitinib’s ability to treat the cutaneous and extracutaneous manifestations of refractory dermatomyositis (DM).1,4,5 However, evidence for sustained improvement remains limited.2,3 The goal of this study is to investigate the long-term response of recalcitrant DM to oral and topical tofacitinib at varied dosing regimens.

Eosinophils and melanoma: Implications for immunotherapy.

New therapies such as immune checkpoint blockers (ICB) have offered extended survival to patients affected by advanced melanoma. However, ICBs have demonstrated debilitating side effects on the joints, liver, lungs, skin, and gut. Several biomarkers have been identified for their role in predicting which patients better tolerate ICBs. Still, these biomarkers are limited by immunologic and genetic heterogeneity and the complexity of translation into clinical practice. Recent observational studies have suggested eosinophil counts, and serum levels of eosinophil cationic protein are significantly associated with prolonged survival in advanced-stage melanoma. It is likely that eosinophils thereby modulate treatment response through mechanisms yet to be explored. Here, we review the functionality of eosinophils, their oncogenic role in melanoma and discuss how these mechanisms may influence patient response to ICBs and their implications in clinical practice.

Neonatal lupus erythematosus presenting as orolabial ulcerations: Two cases and a review of the literature.

We report two unrelated infants who presented with orolabial ulcerations as a presenting manifestation of neonatal lupus erythematosus (NLE). Subsequent positive anti-SSA/SSB titers confirmed the diagnosis. In both infants, the ulcerations were painless and spontaneously resolved. NLE should be included in the differential diagnosis of orolabial ulcerations in the newborn, especially since mothers of affected infants may be asymptomatic.