JAK-STAT pathway inhibitors in dermatology.

The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions, this review presents the main available drugs, their immunological effects, and their pharmacological characteristics, related to clinical efficacy and safety, aiming to validate the best dermatological practice.

Prevalence of immune-mediated inner ear disease in non-segmental vitiligo: A cross-sectional study.

BACKGROUND: Sensorineural hearing loss (SNHL) is associated with non-segmental vitiligo (NSV); however, the aetiology of SNHL has not been explored. The concomitance of autoimmune disease in vitiligo patients demands the investigation of immune-mediated inner ear disease (IMIED) as a cause of SNHL in NSV. The anti-Hsp70 antibody is a serological marker of IMIED, which may help in the early diagnosis of this disease. OBJECTIVE: To evaluate the prevalence of IMIED in NSV patients. METHODS: Cross-sectional study involving NSV adult patients and a control group, evaluated through audiometry and serological dosage of the anti-Hsp70 antibody. RESULTS: In total, 112 cases and 23 controls were evaluated. Bilateral SNHL was found in 28 (25.0%; 95%CI 17.9%-32.1%) patients and in 1 (4.3%) control (p = 0.019). Six cases (5.4%; 95%CI 2.7%-8.0%) presented bilateral SNHL of unexplained aetiology, and anti-Hsp70 antibody positivity, fulfilling the diagnostic criteria for IMIED. No controls met the diagnostic criteria for IMIED. Serum anti-Hsp70 antibodies were higher in cases with IMIED: median 220.9 vs. 85.1 ng/ml (p = 0.001). CONCLUSION: The prevalence of IMIED is remarkable in NSV adult patients.

Association study between vitiligo and autoimmune-related genes CYP27B1, REL, TNFAIP3, IL2 and IL21.

The aetiology of vitiligo has not been fully elucidated, and several hypotheses have been investigated; among them, the most explored assumes an autoimmune basis for the disease. Supporting this hypothesis is the frequent co-occurrence of autoimmune diseases with vitiligo. In addition, various genetic loci associated with vitiligo harbour key immune response genes. Our general hypothesis is that autoimmunity-associated genes participate in the control of vitiligo susceptibility. To investigate this hypothesis, we tested for association between vitiligo and genes CYP27B1, REL, TNFAIP3 and IL2/IL21, all previously related to autoimmune diseases associated with vitiligo. The study was performed using two independent population samples: a family-based discovery set (211 trios) and a replication set (131 cases/119 controls). Statistically significant association with vitiligo was detected between markers of the REL and IL2 gene in the family-based sample. Both association signals were concentrated among patients displaying autoimmune comorbidity and non-segmental vitiligo. Evidence for validation was detected for IL2 marker. Our findings suggest REL and IL2 as new vitiligo susceptibility genes and reinforce the hypothesis of a shared genetic mechanism controlling vitiligo and other autoimmune diseases.

Assessment of psoriasis severity in Brazilian patients with chronic plaque psoriasis attending outpatient clinics: a multicenter, population-based cross-sectional study (APPISOT).

PURPOSE: Data on chronic plaque psoriasis severity and its potential clinical and lifestyle implications in the Brazilian population are limited. The primary aim of this study was to assess the clinical severity of plaque psoriasis in Brazil. Further objectives included evaluating potential associations between disease severity and demographic, lifestyle, and clinical characteristics, health-related quality of life (HRQOL), and work productivity. MATERIALS AND METHODS: This observational (non-interventional) cross-sectional study was conducted in 26 dermatologic clinics across 11 Brazilian states. Psoriasis severity was assessed using investigator judgment and Finlay's Rule of Tens: a Psoriasis Area and Severity Index (PASI) score >10, a Body Surface Area (BSA) > 10%, or a Dermatology Life Quality Index (DLQI) score >10. RESULTS: Among 1125 patients, 205 (18.2%) had moderate-to-severe disease. On multiple regression analyses, psoriasis severity was significantly (directly) associated with the presence of physical inactivity and comorbid pain, anxiety, and depression; and significantly (inversely) associated with HRQOL and work productivity. LIMITATIONS: Cross-sectional studies cannot assess temporal trends, and observational studies cannot conclusively determine causality or exclude biases and confounding due to unmeasured variables. CONCLUSIONS: Among Brazilian patients with moderate-to-severe psoriasis, disease severity had far-reaching adverse impacts on lifestyle, comorbidities, HRQOL, and work productivity.