Adult Henoch-Schönlein Purpura: Comprehensive Assessment of Demographic, Clinical, and Histopathological Features as Predictors for Systemic Involvement.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a small-vessel IgA-predominant vasculitis. A major challenge in managing adult HSP is the difficulty assessing the risk of systemic involvement. There is currently a paucity of data in this area. OBJECTIVE: The objective of this study was to determine demographic, clinical, and histopathological features associated with systemic involvement in adult HSP. METHODS: In this retrospective study, we reviewed demographical features and clinical and pathology data of 112 adult HSP patients seen at Emek Medical Center between January 2008 and December 2020. RESULTS: Of these patients, 41 (36.6%) had renal involvement, 24 (21.4%) had gastrointestinal tract involvement, and 31 (27.7%) had joint involvement. Age >30 years (p = 0.006) at diagnosis was an independent predictor of renal involvement. Platelet count (<150 K/µL) (p = 0.020) and apoptosis of keratinocytes on skin biopsy (p = 0.031) were also associated with renal involvement. History of autoimmune disease (p = 0.001), positive c-antineutrophil cytoplasmic antibody (p = 0.018), positive rheumatoid factor (p = 0.029), and elevated erythrocyte sedimentation rate (p = 0.04) were associated with joint involvement. Female sex (p = 0.003), Arab race (p = 0.036), and positive pANCA (p = 0.011) were associated with gastrointestinal tract involvement. LIMITATIONS: This study is retrospective. CONCLUSION: These findings may serve as a guide to stratify risk in adult HSP patients so that those at higher risk can be monitored more closely.

Ophthalmic Assessment in Patients With Darier Disease.

PURPOSE: To assess the prevalence of ophthalmic findings in patients with Darier disease, an autosomal dominant genetic skin disorder, in an effort to evaluate the need for eye examinations in the management of the disease. DESIGN: Prospective observational case series. METHODS: Thirty-six individuals with Darier disease were evaluated by both ocular assessment questionnaire and a comprehensive ophthalmic examination (visual acuity, refraction, external examination, and slit-lamp examination) with emphasis on the eyelids, conjunctiva, and cornea. In addition, questionnaire-based medical interview and skin examination were conducted. RESULTS: According to the medical questionnaire, 39% of patients reported eye problems, 36% dry eye, and 42% eye fatigue after prolonged reading. Ocular examination revealed Darier disease lesions on the eyelids in 55% of the patients, blepharitis in 44%, conjunctival hyperemia in 28%, and short tear film break-up time in 83%. There was no significant relationship between any of these ophthalmic findings and systemic retinoid therapy, sex, or age. CONCLUSIONS: The high prevalence of blepharitis and dry eye highlights the importance of ophthalmologic evaluation of patients with Darier disease.

The Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAM Syndrome.

An effective epidermal barrier requires structural and functional integration of adherens junctions, tight junctions, gap junctions (GJ), and desmosomes. Desmosomes govern epidermal integrity while GJs facilitate small molecule transfer across cell membranes. Some patients with severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, caused by biallelic desmoglein 1 (DSG1) mutations, exhibit skin lesions reminiscent of erythrokeratodermia variabilis, caused by mutations in connexin (Cx) genes. We, therefore, examined whether SAM syndrome-causing DSG1 mutations interfere with Cx expression and GJ function. Lesional skin biopsies from SAM syndrome patients (n = 7) revealed decreased Dsg1 and Cx43 plasma membrane localization compared with control and nonlesional skin. Cultured keratinocytes and organotypic skin equivalents depleted of Dsg1 exhibited reduced Cx43 expression, rescued upon re-introduction of wild-type Dsg1, but not Dsg1 constructs modeling SAM syndrome-causing mutations. Ectopic Dsg1 expression increased cell-cell dye transfer, which Cx43 silencing inhibited, suggesting that Dsg1 promotes GJ function through Cx43. As GJA1 gene expression was not decreased upon Dsg1 loss, we hypothesized that Cx43 reduction was due to enhanced protein degradation. Supporting this, PKC-dependent Cx43 S368 phosphorylation, which signals Cx43 turnover, increased after Dsg1 depletion, while lysosomal inhibition restored Cx43 levels. These data reveal a role for Dsg1 in regulating epidermal Cx43 turnover.