Erythema Multiforme and Epidermal Necrolysis Following COVID-19 Vaccines: A Systematic Review.

The outbreak of COVID-19 pandemic has raised urgent vaccine development to prevent viral transmission. Cutaneous adverse events such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been observed following COVID-19 vaccination. In this systematic review, we aimed to investigate the clinical features and outcomes of EM/SJS/TEN following COVID-19 vaccination. A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane databases up to July 3, 2022. We included studies reporting patients who developed EM, SJS, or TEN following COVID-19 vaccination. A total of 47 studies involving 90 patients with EM and 16 patients with SJS/TEN were reviewed and outlined. EM predominantly occurred after the messenger ribonucleic acid vaccines (70.4%), mostly after the first (47.5%) and second doses (42.4%), with delayed onsets ranging from 1 day to 30 days. SJS/TEN were observed following either the first (55.6%)- or second-dose (33.3%) vaccination, with onset times ranging from 6 hours to 14 weeks. Three EM cases and 1 SJS case showed recurrence upon reexposure to the same vaccines. No mortality was reported. Most patients exhibited improvement or resolution after treatment, with resolution times ranging from 6 days to 8 weeks. In conclusion, EM and epidermal necrolysis, including SJS and TEN, have emerged as potential cutaneous adverse events following COVID-19 vaccine administration. Further research is warranted to elucidate the pathogenesis and casual relationship between COVID-19 vaccines and EM/SJS/TEN.

An Infant With Progressive Yellowish Papules and Nodules.

A 6-month-old girl presented with yellowish papules and nodules on the face and trunk that appeared 2 months prior, initially on the scalp, then gradually spread. What is your diagnosis?

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.

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.