Bidirectional associations between psoriasis and migraine: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: To evaluate the association between psoriasis and migraine. PATIENTS AND METHODS: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for relevant observational studies from their respective inception to May 1, 2022. A random-effects model meta-analysis was performed to calculate the risk estimates quantifying the associations between psoriasis and migraine. We also performed a sensitivity analysis by including only studies with adjusted risk estimates and a subgroup analysis according to the severity of psoriasis. RESULTS: We included 9 studies with 6,742,075 participants. The meta-analysis illustrated increased odds for prevalent migraine among patients with psoriasis (pooled OR: 1.69, 95% CI: 1.26-2.28) and increased odds for prevalent psoriasis among those with migraine (OR: 1.88, 95% CI: 1.32-3.67). A subgroup analysis of cohort studies demonstrated an increasingly higher risk of incident migraine in patients with mild psoriasis and severe psoriasis (IRR being 1.37 (95% CI 1.30-1.44) and 1.55 (95% CI 1.29-1.86), respectively). CONCLUSIONS: This meta-analysis revealed significant bidirectional associations between migraine and psoriasis. Greater severity of psoriasis appears to be associated with a higher risk of developing migraine. Clinicians should evaluate symptoms of migraine in patients with psoriasis and provide proper treatments.

Systematic review and critical appraisal of psoriasis clinical practice guidelines: a Global Guidelines in Dermatology Mapping Project (GUIDEMAP).

BACKGROUND: Clinical practice guidelines (CPGs) developed with rigorous methods can help optimize clinical care for patients with psoriasis. OBJECTIVES: To conduct an updated systematic review and comprehensive critical appraisal of global psoriasis CPGs. METHODS: A search of MEDLINE and Embase for psoriasis CPGs published between 1 January 2015 and 31 March 2021 was performed. Other guideline repositories were also searched for relevant CPGs. Descriptive analysis was conducted to summarize included guidelines. Three critical appraisal tools were used to assess the quality of included CPGs: the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, Lenzer et al.'s red flags, and the US Institute of Medicine's (IOM) criteria of trustworthiness. RESULTS: We included 33 psoriasis CPGs, with 25 openly accessible. Most CPGs were from high sociodemographic index countries in North America and Europe. Five CPGs received 'excellent quality' appraisals across all six AGREE II domains. Stakeholder involvement, rigour of development and applicability were the three domains with the lowest appraisal scores for AGREE II. Twenty-two CPGs raised at least one red flag indicative of potential bias. By the IOM's standards, external review of the guideline draft prior to publication and clear updating procedures were most often not addressed by guidelines, and only three CPGs were assessed as having higher overall trustworthiness. CONCLUSIONS: Most psoriasis guidelines were unable to consistently demonstrate high quality across multiple appraisal tools. The EuroGuiDerm guideline on the systemic treatment of psoriasis vulgaris was the only CPG to receive 'excellent quality' across all six AGREE II domains, to raise no Lenzer's red flags, and to have higher trustworthiness by IOM criteria.

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.

Biologics for pediatric moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis.

BACKGROUND AND OBJECTIVES: To compare the efficacy and safety of biologic treatments for moderate-to-severe pediatric psoriasis approved by the US Food and Drug Administration and European Medicines Agency. PATIENTS AND METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials (RCTs) were searched for the identification of eligible RCTs until May 7, 2021. Fixed-effect frequentist network meta-analysis (NMA) was performed with the surface under the cumulative ranking curve (SUCRA) calculated for ranking. Our primary outcomes included ≥ 90 % improvement of Psoriasis Area and Severity Index score (PASI 90) at 12-16 weeks and discontinuation owing to adverse events (DAE) through the first 12-16 weeks. RESULTS: Five RCTs involving 798 pediatric psoriasis patients were included. Compared to placebo, all biologic regimens exhibited a significantly higher PASI 90 response but did not differ in the risk for DAE. Based on the SUCRA, secukinumab-low dose (SEC-L) ranked first in the achieved PASI 90 response (84.7 %), followed by ixekizumab (70.8 %). CONCLUSIONS: Among all biologic treatments, SEC-L showed the best PASI 90 response without increasing the risk for DAE. More long-term studies are warranted.

Small molecule inhibitors and biologics in treating nail psoriasis: A systematic review and network meta-analysis.

BACKGROUND: Various systemic immunomodulating therapies have been investigated to treat nail psoriasis, but the efficacy remains unclear. OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. METHODS: Eligible studies in online databases were identified until March 10, 2020. To assess the efficacy of small molecule inhibitors and biologics, network meta-analyses with surface under the cumulative ranking curve of improvement in nail score at 10 to 16 and at 24 to 26 weeks, as well as 100% improvement of Nail Psoriasis Severity Index (NAPSI), were performed. RESULTS: Thirty-nine studies with a total of 13 treatment arms involving 15,673 patients with nail psoriasis were included. An network meta-analysis showed that tofacitinib (weighted mean difference, 56.67; 95% confidence interval [CI], 35.87-77.48) and ixekizumab (weighted mean difference, 59.40; 95% CI, 45.87-72.93) presented the most improvement of nail score at 10 to 16 weeks and 24 to 26 weeks, respectively. For 100% improvement of the Nail Psoriasis Severity Index, ixekizumab showed the best efficacy among all treatments (odds ratio, 2.98; 95% CI, 1.74-5.10). LIMITATIONS: Insufficiency of eligible data and no long-term follow-up data. CONCLUSION: Tofacitinib and ixekizumab presented the best efficacy for treating nail psoriasis in 10 to 16 weeks and 24 to 26 weeks, respectively.

Treating toxic epidermal necrolysis with systemic immunomodulating therapies: A systematic review and network meta-analysis.

BACKGROUND: Various systemic immunomodulating therapies have been used to treat toxic epidermal necrolysis (TEN), but their efficacy remains unclear. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) evaluating the effects of systemic immunomodulating therapies on mortality for Stevens-Johnson syndrome (SJS)/TEN overlap and TEN. METHODS: A literature search was performed in online databases (from inception to October 31, 2019). Outcomes were mortality rates and Score of Toxic Epidermal Necrolysis (SCORTEN)-based standardized mortality ratio (SMR). A frequentist random-effects model was adopted. RESULTS: Sixty-seven studies involving 2079 patients were included. An NMA of 10 treatments showed that none was superior to supportive care in reducing mortality rates and that thalidomide was associated with a significantly higher mortality rate (odds ratio, 11.67; 95% confidence interval [CI], 1.42-95.96). For SMR, an NMA of 11 treatment arms showed that corticosteroids and intravenous immunoglobulin combination therapy was the only treatment with significant survival benefits (SMR, 0.53; 95% CI, 0.31-0.93). LIMITATIONS: Heterogeneity and a paucity of eligible randomized controlled trials. CONCLUSIONS: Combination therapy with corticosteroids and IVIg may reduce mortality risks in patients with SJS/TEN overlap and TEN. Cyclosporine and etanercept are promising therapies, but more studies are required to provide clearer evidence.

Topical calcineurin inhibitors and risk of lymphoma: a systematic review and meta-analysis.

The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus have been used widely as corticosteroid-sparing agents in treating various cutaneous diseases. However, the association between TCIs and risk of malignancy remains controversial. By systematic review and meta-analysis, we aimed to investigate the association between TCIs and lymphoma. Eligible studies in online databases were identified from the date of inception to August 30, 2020. To assess the outcome of TCI-related risk of lymphoma, analysis of cohort studies comparing the incidence of lymphoma with and without treatment with TCIs was performed. Furthermore, the subgroup analyses of Hodgkin lymphoma and non-Hodgkin lymphoma were also conducted. The pooled results revealed that using topical tacrolimus (RR 1.68, 95 % CI 1.39-2.04) or pimecrolimus (RR 1.40, 95 % CI 1.13-1.74) significantly increased the risk of lymphoma. TCI users also showed higher incidence of lymphoma in the range of 0.02-0.09 %, compared to that of 0.02-0.06 % in the control group. Additionally, subgroup analyses showed both tacrolimus (RR 1.89; 95 % CI 1.53-2.32) and pimecrolimus (RR 1.38; 95 % CI 1.09-1.74) had significantly higher risk of non-Hodgkin lymphoma, but no increased risk of Hodgkin lymphoma. In conclusion, TCI-exposed patients have a significantly increased risk of lymphoma, especially non-Hodgkin lymphoma.

Effects of Anti-Calcitonin Gene-Related Peptide for Migraines: A Systematic Review with Meta-Analysis of Randomized Clinical Trials.

We aimed to evaluate the response rate of migraines by using anti-calcitonin gene-related peptide (anti-CGRP) for patients with migraines. We searched three main medical databases up to 29 March 2019. No restriction on language and publication time were applied. Eligible trials included randomized clinical trials investigating a 50%, 75%, and 100% response rate of migraine patients after anti-CGRP intervention. The collected data were dichotomous, and risk ratios (RRs) with a 95% confidence interval (CI) were used to present the quantitative synthesis results. The systematic review identified 16 eligible randomized clinical trials (RCTs) with 9439 patients. Eight of the 16 trials with 2516 patients reported a 50% response rate, and the pooled results showed a significant benefit from anti-CGRP. However, the effects seem to gradually reduce from the first month (RR 1.99, 95% CI 1.59 to 2.49) to the third month (RR 1.48, 95% CI 1.26 to 1.75) of treatment. The magnitude of effect was influenced by the type of anti-CGRP, according to the test for differences between subgroups (I-square = 53%). The funnel plots and Egger's tests did not show serious small study effects in the results. In conclusion, the current evidences confirmed that anti-CGRP treatment can reduce migraine pain in the short term (within three months), but the long-term effect should be investigated in the future. Moreover, its effects may be influenced by the type and dose of anti-CGRP. Therefore, future studies should make direct comparisons among anti-CGRP medications.

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.

New Onset and Exacerbation of Autoimmune Bullous Dermatosis Following COVID-19 Vaccination: A Systematic Review.

BACKGROUND: Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination. OBJECTIVE: We aimed to provide an overview of clinical characteristics, treatments, and outcomes of AIBDs following COVID-19 vaccination. METHODS: We conducted a systematic review and searched the Embase, Cochrane Library, and Medline databases from their inception to 27 March 2024. We included all studies reporting ≥ 1 patient who developed new-onset AIBD or experienced flare of AIBD following at least one dose of any COVID-19 vaccine. RESULTS: We included 98 studies with 229 patients in the new-onset group and 216 in the flare group. Among the new-onset cases, bullous pemphigoid (BP) was the most frequently reported subtype. Notably, mRNA vaccines were commonly associated with the development of AIBD. Regarding the flare group, pemphigus was the most frequently reported subtype, with the mRNA vaccines being the predominant vaccine type. The onset of AIBD ranged from 1 to 123 days post-vaccination, with most patients displaying favorable outcomes and showing improvement or resolution from 1 week to 8 months after treatment initiation. CONCLUSIONS: Both new-onset AIBD and exacerbation of pre-existing AIBD may occur following COVID-19 vaccination. Healthcare practitioners should be alert, and post-vaccination monitoring may be essential.

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.

Systematic Review and Critical Appraisal of Urticaria Clinical Practice Guidelines: A Global Guidelines in Dermatology Mapping Project (GUIDEMAP).

BACKGROUND: Management of urticaria can be optimized with clinical practice guidelines (CPGs). However, the quality of recent urticaria CPGs remains unclear. OBJECTIVE: To identify and appraise urticaria CPGs worldwide published in the last 5 years. METHODS: A search for relevant urticaria CPGs was conducted between January 1, 2017, and May 31, 2022, using the following databases: MEDLINE, Embase, National Institute for Health and Care Excellence (NICE) Evidence Search, Guidelines International Network, ECRI Guidelines Trust, Australian Clinical Practice Guidelines, Trip Medical Database, and DynaMed. The included CPGs were critically appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, Lenzer et al's red flags, and the Institute of Medicine (IOM) criteria of trustworthiness. RESULTS: We included 21 urticaria CPGs. Most guidelines reviewed treatment recommendations of chronic spontaneous urticaria. The majority of guidelines were from European and Asian countries with high and high-middle sociodemographic index, written in English, and openly accessible. Seventeen guidelines (81%) had at least 1 AGREE II domain rated poor quality. Applicability, rigor of development, and stakeholder involvement were the 3 AGREE II domains that scored the lowest across guidelines. Appraisal with Lenzer et al's red flags showed that 18 guidelines (86%) raised at least 1 red flag indicating potential bias. The top 3 domains raising red flags were: no inclusion of nonphysician experts/patient representative/community stakeholders, no or limited involvement of a methodologist in the evaluation of evidence, and lack of external review. Based on IOM's criteria of trustworthiness, 20 guidelines (95%) had 1 or more criteria that did not meet best practice standards. The 3 domains with the highest number of best practice standards not met were updating procedures, rating strength of recommendations, and external review. Guidelines scored highest for the AGREE II domains of defining scope and purpose and clarity of presentation, and had the most fully met IOM's best practice standard for articulation of recommendations. However, only 1 urticaria CPG by NICE was identified as rigorously developed across all 3 appraisal tools. CONCLUSIONS: The quality of urticaria CPGs in the last 5 years varied widely. Only the NICE urticaria guideline consistently demonstrated excellent quality, high trustworthiness, and low risk of bias. Use of a rigorous framework to rate certainty of evidence and grade strength of recommendation, involvement of methodologists, stakeholder engagement with external review, and clear guidance for updating can help improve the quality of future CPGs.

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.