Human Leukocyte Antigens and Sulfamethoxazole/Cotrimoxazole-Induced Severe Cutaneous Adverse Reactions: A Systematic Review and Meta-Analysis.

Importance: Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 ratio, are antibacterial sulfonamides commonly used for treating various diseases. A substantial prevalence of severe cutaneous adverse reactions (SCARs) following the administration of these drugs has been reported. However, the association between human leukocyte antigen (HLA) genotypes and SMX/CTX-induced SCARs has remained unclear. Objective: To investigate the association between HLA genotypes and SMX/CTX-induced SCARs. Data sources: A comprehensive search was conducted in CENTRAL (Cochrane Library), MEDLINE, and Embase from inception to January 17, 2023. Study Selection: Case-control studies that recruited patients who had experienced SCARs following SMX or CTX were included, and HLA alleles were analyzed. Data Extraction and Synthesis: Two independent authors extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. The Newcastle-Ottawa Scale for case-control studies was used to assess study quality. Odds ratios (ORs) were calculated using a random-effects model for meta-analysis. Main Outcomes and Measures: The prespecified outcome was the OR comparing SMX/CTX-induced SCARs with healthy or SMX/CTX-tolerant controls based on different HLA alleles. Results: Six studies involving 322 patients with SCAR were included, including 236 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis, 86 with drug reaction with eosinophilia and systemic symptoms, 8448 healthy controls, and 229 tolerant controls. Significant associations were found in HLA-A*11:01 (OR, 2.10; 95% CI, 1.11-4.00), HLA-B*13:01 (OR, 5.96; 95% CI, 1.58-22.56), HLA-B*15:02 (OR, 2.23; 95% CI, 1.20-4.14), HLA-B*38:02 (OR, 3.47; 95% CI, 1.42-8.48), and HLA-C*08:01 (OR, 2.63; 95% CI, 1.07-6.44) compared with tolerant controls. In the Stevens-Johnson syndrome/toxic epidermal necrolysis subgroup, significant associations were found in HLA-B*15:02 (OR, 3.01; 95% CI, 1.56-5.80) and HLA-B*38:02 (OR, 5.13; 95% CI, 1.96-13.47). In the drug reaction with eosinophilia and systemic symptoms subgroup, significant associations were found in HLA-A*68:01 (OR, 12.86; 95% CI, 1.09-151.34), HLA-B*13:01 (OR, 23.09; 95% CI, 3.31-161.00), HLA-B*39:01 (OR, 4.56; 95% CI, 1.31-15.82). Conclusions and Relevance: The results of this systematic review and meta-analysis suggest that multiple HLA alleles (HLA-A*11:01, HLA-B*13:01, HLA-B*15:02, HLA-B*38:02, and HLA-C*0801) are associated with SMX/CTX-induced SCARs.

Cutaneous adverse reactions associated with COVID-19 vaccines: Current evidence and potential immune mechanisms.

As the number of vaccinated individuals has increased, there have been increasing reports of cutaneous hypersensitivity reactions. The main COVID-19 vaccines administered include messenger ribonucleic acid vaccines, non-replicating viral vector vaccines, inactivated whole-virus vaccines, and protein-based vaccines. These vaccines contain active components such as polyethylene glycol, polysorbate 80, aluminum, tromethamine, and disodium edetate dihydrate. Recent advances in understanding the coordination of inflammatory responses by specific subsets of lymphocytes have led to a new classification based on immune response patterns. We categorize these responses into four patterns: T helper (Th)1-, Th2-, Th17/22-, and Treg-polarized cutaneous inflammation after stimulation of COVID-19 vaccines. Although the association between COVID-19 vaccination and these cutaneous adverse reactions remains controversial, the occurrence of rare dermatoses and their short intervals suggest a possible relationship. Despite the potential adverse reactions, the administration of COVID-19 vaccines is crucial in the ongoing battle against severe acute respiratory syndrome coronavirus 2.

Small-Molecule Inhibitors and Biologics for Palmoplantar Psoriasis and Palmoplantar Pustulosis: A Systematic Review and Network Meta-Analysis.

BACKGROUND: The comparative efficacy of biologics and small-molecule inhibitors in treating palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) remains uncertain. OBJECTIVE: The aim was to perform a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics and small-molecule inhibitors for the treatment of PP and PPP. METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for eligible studies from inception to May 13, 2023. This NMA was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension Statement for Network Meta-Analyses guidelines. Frequentist random-effects models NMA was performed with the surface under the cumulative ranking curve calculated for ranking. Our primary outcome was the proportion of patients achieving a clear/minimal Palmoplantar Psoriasis/Pustulosis Physician Global Assessment score (PPPGA 0/1 or PPPPGA 0/1) response at 12-16 weeks. Secondary outcomes consisted of the percentage of overall improvement in palmoplantar score and of improvement ≥ 75%, at 12-16 weeks. RESULTS: The study comprised a total of 29 randomized controlled trials (RCTs), involving 4798 psoriasis patients with palmoplantar diseases. For PP, 16 RCTs with nine different treatments, including adalimumab, apremilast, bimekizumab, etanercept, guselkumab, infliximab, ixekizumab, secukinumab, and ustekinumab were included for the analysis. In the NMA of PP, secukinumab 300 mg ranked highest (odds ratio [OR] 33.50, 95% confidence interval [CI] 4.37-256.86) in achieving PPPGA 0/1, followed by guselkumab 100 mg (OR 18.68, 95% CI 10.07-34.65). In the case of PPP, seven RCTs with six treatments, including apremilast, etanercept, guselkumab, imsidolimab, spesolimab, and ustekinumab, were included for the analysis. In the NMA of PPP, although no treatment demonstrated a significant difference compared to placebo in achieving PPPPGA 0/1, guselkumab 100 mg showed the greatest statistically significant improvement in the palmoplantar score (weighted mean difference 31.73, 95% CI 19.89-43.57) as a secondary outcome. CONCLUSION: Among all available biologics and small-molecule inhibitors, secukinumab 300 mg and guselkumab 100 mg had the most favorable efficacy in treating PP and PPP, respectively.

Management of Atopic Dermatitis During the COVID-19 Pandemic: Key Questions and Review of the Current Evidence.

Since the outbreak of COVID-19, management of atopic dermatitis (AD) has been widely discussed. Key issues include the risk of COVID-19 infection and related outcomes in AD patients, the efficacy and safety of COVID-19 vaccination in AD populations, and management of AD in the COVID-19 pandemic. Recent studies have shown that patients with AD have a slightly increased risk of COVID-19 infection but are not associated with a worse outcome than the non-AD population. COVID-19 vaccination is generally effective and safe in patients with AD. However, temporary discontinuation of certain systemic immunomodulatory agents after vaccination is suggested. During the pandemic, continuation of all immunomodulating agents is suggested, but these agents should be paused when patients with AD are infected with COVID-19 until recovery. Further studies are warranted to investigate the long-term interaction between AD and COVID-19 to aid clinical decisions during the pandemic.

Cross-cultural adaptation and validation of the Traditional Chinese version of the Core Outcome Measures Index in patients with low back pain.

PURPOSE: This study aimed to carry out a cross-cultural adaptation of the Core Outcome Measures Index (COMI) for use in Traditional Chinese-speaking patients with low back pain (LBP) and to investigate its psychometric properties. METHODS: A total of 224 patients with LBP > 6 weeks who visited our spine center from May 2018 to May 2019 were included in the study. Patients completed a booklet of questionnaires including the following: (1) pain Numeric Rating Scale, (2) Oswestry Disability Index, (3) Roland-Morris Disability Questionnaire, (4) EuroQol-five dimension (EQ-5D), and (5) COMI. Patients were sent a second booklet (also containing a transition question to indicate any change in condition) to be completed again within one month after the first. Fifty-two patients did not receive any intervening treatment (group 1), while the other 172 patients received medical treatment (group 2) between the two questionnaires. RESULTS: The intraclass correlation coefficient (ICC) for the COMI summary score was 0.94 (95% CI 0.89-0.97); the standard error of measurement (SEM) was 0.41 and the minimum detectable change (MDC) score was 1.14. The COMI summary scores showed a low floor effect (1.8%) and ceiling effect (0.4%). All COMI item scores demonstrated the hypothesized correlations with their corresponding full-length questionnaires except for the pain item (correlation stronger than hypothesized). Standardized response means (SRM) for the COMI items in the treated group were between 0.58 and 1.30. Regarding the ability of the COMI change score to differentiate between good and poor outcomes, the area under the receiver operating characteristic (AUROC) curve was 0.77 [standard error (SE) 0.07, 95% confidence interval (CI) 0.68-0.84] and the minimal clinically important change (MCIC) score was ≥ 1.85 points. CONCLUSION: The Traditional Chinese COMI represents a practical and reliable tool for the assessment of Traditional Chinese-speaking patients with back problems.

Dupilumab in the treatment of genodermatosis: A systematic review.

Dupilumab interferes with the signaling pathways of IL-4 and IL-13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome, epidermolysis bullosa pruriginosa, and hyper-IgE syndrome, are Th2 skewed diseases with activation of type 2 inflammation. We performed this systematic review to investigate the therapeutic role of dupilumab in the treatment of genodermatosis. A systematic search was conducted of the PubMed, Embase, Web of Science, and Cochrane databases from inception to December 13, 2021. The review included studies with relevant terms including "dupilumab," "genodermatosis", "Netherton syndrome", "ichthyosis", "epidermolysis bullosa" and "hyper-IgE syndrome". The initial search yielded 2,888 results, of which 28 studies and 37 patients with genodermatosis were enrolled. The assessed genodermatoses included Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with genetic disorders. Most of the reported cases showed significant clinical improvement after the initiation of dupilumab treatment without major adverse events. Decreased immunoglobulin E levels and cytokine normalization have also been documented. In conclusion, Dupilumab may have a potential therapeutic role in certain genodermatoses skewed towards T helper 2 (Th2) immunity, including Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with some genetic disorders.

Association between bullous pemphigoid and atopic dermatitis: a population-based case-control study in Taiwan.

Although bullous pemphigoid (BP) and atopic dermatitis (AD) share pathogenic mechanisms, their relationship remains controversial. Therefore, we conducted a population-based case-control study to investigate the association between BP and AD in Taiwan. Based on the Taiwan National Health Insurance Research Database, 9344 patients with BP and 18,688 age- and sex-matched controls were enrolled between 2000 and 2013. Furthermore, the study included 7,196 BP patients and 14,392 controls, matched for age, sex, and propensity score of comorbidities, with a case to controls ratio of 1:2. Logistic regression analysis was performed to examine the association between AD and BP. In the age- and sex-matched cohorts, AD (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.50-1.95) was independently associated with BP. In the age, sex, and comorbidities-matched cohorts, AD (OR 1.76, 95% CI 1.55-2.00) remained a significant risk factor for BP. Other significant risk factors included psoriasis, hypertension, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, neuropsychiatric diseases, and autoimmune connective tissue disease. Limitations of this study include the lack of information on disease severity and phenotypes of BP and misclassification of diseases as potential sources of bias. In conclusion, AD increased the risk of developing BP by 76%, and this association was independent of many BP comorbidities. Further studies are warranted to investigate the clinical and pathophysiological relevance of factors contributing to BP and AD.

JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review.

Atopic dermatitis (AD) is a chronic, inflammatory, pruritic form of dermatosis with heterogeneous manifestations that can substantially affect patients' quality of life. AD has a complex pathogenesis, making treatment challenging for dermatologists. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a central role in modulating multiple immune axes involved in the immunopathogenesis of AD. In particular, Th2 cytokines, including interleukin (IL)-4, IL-5, IL-13, IL-31, and thymic stromal lymphopoietin, which contribute to the symptoms of chronic inflammation and pruritus in AD, are mediated by JAK-STAT signal transduction. Furthermore, JAK-STAT is involved in the regulation of the epidermal barrier and the modulation of peripheral nerves related to the transduction of pruritus. Targeting the JAK-STAT pathway may attenuate these signals and show clinical efficacy through the suppression of various immune pathways associated with AD. Topical and oral JAK inhibitors with variable selectivity have emerged as promising therapeutic options for AD. Notably, topical ruxolitinib, oral upadacitinib, and oral abrocitinib were approved by the U.S. Food and Drug Administration for treating patients with AD. Accordingly, the present study reviewed the role of JAK-STAT pathways in the pathogenesis of AD and explored updated applications of JAK inhibitors in treating AD.

Zusammenhang zwischen bullösem Pemphigoid und psychiatrischen Erkrankungen: Eine systematische Übersicht und Metaanalyse.

HINTERGRUND UND ZIELE: Trotz des wohlbekannten Zusammenhangs zwischen bullösem Pemphigoid (BP) und neurologischen Erkrankungen ist der Zusammenhang zwischen BP und psychiatrischen Erkrankungen nach wie vor ungeklärt. In dieser Studie war es unser Ziel, den Zusammenhang zwischen BP und verschiedenen psychischen Störungen zu untersuchen. PATIENTEN UND METHODEN: Die Datenbanken PubMed, Embase und Cochrane Library wurden bis zum 30. Mai 2021 hinsichtlich der Identifizierung geeigneter Kohorten- und Fall-Kontroll-Studien durchsucht. Anschließend wurden Metaanalysen der rohen Schätzwerte sowie der bereinigten Schätzwerte der Odds-Ratio (OR) für Fall-Kontroll-Studien und der Hazard-Ratio (HR) für Kohortenstudien durchgeführt. ERGEBNISSE: Es wurden 16 Studien mit 637 285 Patienten in die qualitative Synthese eingeschlossen. In der Metaanalyse der bereinigten Schätzwerte für Fall-Kontroll-Studien zeigten Patienten mit BP eine signifikant höhere Prävalenz psychischer Störungen (OR 1,77, 95 %-Konfidenzintervall (KI) 1,07-2,92) und Schizophrenie (OR 2,63, 95 %-KI 2,03-3,39). Hinsichtlich der Analyse der bereinigten Schätzwerte für Kohortenstudien stellte BP kein signifikant höheres Risiko für Depression (HR 1,09, 95 %-KI 0,94-1,26) und Schizophrenie (HR 1,35, 95 %-KI 0,76-2,39) dar. SCHLUSSFOLGERUNGEN: Bei psychiatrischen Erkrankungen, insbesondere Schizophrenie, besteht ein signifikant höheres Risiko, dass sie einem BP vorausgehen.

Association between bullous pemphigoid and psychiatric disorders: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Despite the well-established association between bullous pemphigoid (BP) and neurological diseases, the association between BP and psychiatric disorders remains unclear. In this study, we aimed to investigate the association between BP and various psychiatric disorders. PATIENTS AND METHODS: PubMed, Embase, and Cochrane Library databases were searched for the identification of eligible cohort and case-control studies until May 30, 2021. Meta-analyses of crude estimates and adjusted estimates of odds ratio (OR) for case-control studies and hazard ratio (HR) cohort studies were then conducted. RESULTS: Sixteen studies involving 637,285 patients were included for the qualitative synthesis. In the meta-analysis of adjusted estimates for case-control studies, patients with BP exhibited a significantly higher prevalence of psychiatric disorders (OR 1.77, 95 % confidence interval (CI) 1.07-2.92) and schizophrenia (OR 2.63, 95 % CI 2.03-3.39). Regarding the analysis of adjusted estimates of cohort studies, BP presented no significantly higher risk of depression (HR 1.09, 95 % CI 0.94-1.26) and schizophrenia (HR 1.35, 95 % CI 0.76-2.39). CONCLUSIONS: Psychiatric disorders, especially schizophrenia, have a significantly higher risk of preceding BP.

New Onset and Exacerbations of Psoriasis Following COVID-19 Vaccines: A Systematic Review.

BACKGROUND: Vaccination has been promoted to control viral transmission in response to the coronavirus disease 2019 (COVID-19) pandemic. Cases of new-onset or exacerbation of psoriasis, an immune-mediated inflammatory disease, were reported following COVID-19 vaccination. However, a comprehensive review examining the association between COVID-19 vaccination and the occurrence or exacerbation of psoriasis has yet to be performed. OBJECTIVE: The aim of this systematic review is to investigate the demographics, clinical variables, and outcomes associated with psoriasis following COVID-19 vaccination. METHODS: A systematic literature search was conducted using the PubMed, Embase, Web of Science, and Cochrane databases from database inception to April 25, 2022. The review included studies with relevant terms, including 'psoriasis,' 'psoriasis vulgaris,' 'guttate psoriasis,' 'pustular psoriasis,' 'palmoplantar pustulosis,' 'psoriatic erythroderma,' 'psoriatic arthritis,' 'COVID-19,' and 'vaccine.' We included all studies reporting at least one patient who developed new-onset psoriasis or experienced a psoriasis flare following at least one dose of any COVID-19 vaccine. A flare was defined as the worsening of disease conditions after vaccination according to the study by Gregoire et al. The appraisal tool described by Murad et al. was used to assess the quality of case reports and series, whereas the National Institute of Health quality assessment tool was used to assess observational studies. RESULTS: The initial search yielded 367 results, including 7 studies reporting new-onset psoriasis, 32 studies reporting psoriasis flares, and 4 studies reporting both. The most commonly observed psoriasis subtype was plaque-type psoriasis. mRNA vaccines, including those produced by Moderna and BioNTech/Pfizer, were frequently associated with subsequent psoriasis episodes. First, second, and third vaccine doses were associated with psoriasis incidents, with the second dose most frequently associated with psoriasis flares. Delayed onset was observed, ranging from 2 to 21 days in the new-onset group and from 1 to 90 days in the flare group. Most patients experienced favorable outcomes, with improvement or resolution occurring within 3 days to 4 months. CONCLUSIONS: Both new-onset psoriasis and psoriasis flares were reported as cutaneous adverse events following COVID-19 vaccination. Psoriatic patients may require regular follow-up before and after COVID-19 vaccination. TRIAL REGISTRATION: Review registration number PROSPERO database: CRD42022304157.

Ocular Abnormalities in Patients with Vitiligo: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitiligo is a skin depigmentation disorder that results from the autoimmune destruction of cutaneous melanocytes. Several ocular abnormalities, including uveitis, dry eye, glaucoma, and retinal diseases, have been reported in patients with vitiligo. The aim of our study was to investigate the association of ocular abnormalities with vitiligo. METHODS: This meta-analysis was registered in PROSPERO (CRD42021224167) and adhered to MOOSE checklist and PRISMA guidance for all processes. PubMed, Embase, Web of Science, and Cochrane databases were searched for studies examining the association between ocular abnormalities and vitiligo from inception to December 10, 2020. Studies recruiting patients with Sjogren's syndrome or Vogt-Koyanagi-Harada syndrome were excluded. The primary outcomes were the Schirmer test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) of vitiligo patients compared to the controls. The risk of bias of the selected studies was assessed using the Newcastle-Ottawa Scale (NOS) of case-control studies. RESULTS: This meta-analysis of 16 case-control studies showed that patients with vitiligo had significantly lower Schirmer test values (mean difference [MD], -1.65; 95% CI, -2.81 to -0.49), shorter TBUTs (MD, -4.66; 95% CI, -7.05 to -2.26), higher ocular surface disease indices (MD, 18.02; 95% CI, 5.7-30.35), and thinner subfoveal choroidal thicknesses (MD, -53.10; 95% CI, -69.84 to -36.36). No significant differences were found in the prevalence of glaucoma and the level of intraocular pressure. CONCLUSIONS: Our study supports an association between dry eye and thinner subfoveal choroidal thickness in patients with vitiligo. Dermatologists should be aware of these possible comorbidities and refer vitiligo patients with ocular symptoms to ophthalmologists for further management.