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Results for “Drug Hypersensitivity Syndrome”

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At least 19 recordsLinked to original sources
PubMed2026

Trimethoprim/sulfamethoxazole-triggered drug-induced hypersensitivity syndrome in an HLA B*13:01-positive kidney transplant recipient: a case report with implications for HLA-severe cutaneous adverse reaction associations in transplant care.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe cutaneous adverse reaction (SCAR) with a reported mortality rate of approximately 2-10%. DIHS/DRESS typically develops 2-8 weeks after exposure to an offending drug. An important focus of contemporary SCAR research is the growing evidence that specific human leukocyte antigen (HLA) alleles confer a markedly increased risk of drug-specific hypersensitivity reactions. We report a case of a kidney transplant recipient who developed DIHS/DRESS after prolonged trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis and carried the HLA-B13:01 allele. HLA-B13:01 is a strong genetic risk factor for TMP/SMX-induced DIHS/DRESS, particularly in Southeast Asian populations. Herein, we highlight the potential clinical relevance of pre-transplant HLA typing in predicting SCAR risk in transplant recipients. TMP/SMX-associated DIHS/DRESS may be under-recognized in transplant settings, where awareness of HLA-associated risk remains limited despite robust evidence from non-transplant populations. Transplant clinicians should be aware that DIHS/DRESS can occur outside the typical latency period, especially during immunosuppressant tapering, highlighting the need to integrate pharmacogenomic risk assessments into transplant care.

Humans↗
PubMed2025

Demographics, Overlap, and Latency of Severe Cutaneous Adverse Reactions in an FDA Database.

IMPORTANCE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS-TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruption (GBFDE), are rare but life-threatening drug hypersensitivity syndromes. Due to their low incidence and diagnostic complexity, large-scale characterization of SCAR is challenging. OBJECTIVE: To characterize the demographics, causative agents, trends, latency, and phenotypic overlap of SCAR using a large-scale, sanitized pharmacovigilance dataset from FAERS (FDA Adverse Event Reporting System). DESIGN: Cross-sectional study of spontaneous adverse event reports. Cases were drawn from the U.S. Food and Drug Administration Adverse Event Reporting System (FDA FAERS) from January 2004 to December 2023 and subjected to sanitization and deduplication. Disproportionality analysis was used to characterize causative agents. Machine learning (random forest classifiers) was used to analyze predictors of drug latency and mortality. SETTING: Global pharmacovigilance reports submitted to FAERS. PARTICIPANTS: A total of 56,683 deduplicated SCAR reports were identified, representing 0.33% of reports during the study period. EXPOSURES: Suspected causative drugs, including both small molecules and biologics. MAIN OUTCOMES AND MEASURES: Main outcomes included the frequency and distribution of SCAR syndromes, reporting trends over time, latency from drug start to reaction onset, drug-specific disproportionality (PRR, ROR, IC), and co-reporting between SCAR types and related conditions. RESULTS: A total of 56,683 unique SCAR reports were identified, including SJS-TEN (28,871), DRESS (22,444), AGEP (6,183), and GBFDE (150). We identified 237 drugs with significant disproportionality for SCAR overall. Co-reporting between SCARs was significantly enriched (p < 1e-200), suggesting overlapping phenotypes. Latency varied by drug and syndrome (median: GBFDE 3 days, AGEP 4 days, SJS-TEN 12 days, DRESS 20 days). CONCLUSIONS AND RELEVANCE: SCAR syndromes display distinct but overlapping phenotypes, with variable latency and diverse causative agents. These findings, based on the largest SCAR dataset to date, highlight the need for improved classification frameworks and molecular validation. Large-scale pharmacovigilance, integrated with genomic and histopathologic data, will be critical to improving diagnosis, mechanistic understanding, and clinical management of SCAR.

Acute Generalized Exanthematous Pustulosis↗
PubMed2025

HLA-B Alleles With Shared Peptide Binding Specificities Define Global Risk of Co-trimoxazole-Induced Severe Cutaneous Adverse Drug Reactions.

BACKGROUND: Co-trimoxazole is a leading global cause of severe cutaneous adverse drug reactions (SCAR) including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Co-trimoxazole-induced SCAR are associated with HLA class I alleles including HLA-B&#x2217;13:01 and HLA-B&#x2217;38:02 in Southeast Asian (SEA) populations. However, the global generalizability of these associations is unknown but critical for population-appropriate risk stratification and diagnosis. OBJECTIVE: To determine HLA risk factors associated with co-trimoxazole-induced SJS/TEN and DRESS in populations from the United States and South Africa. METHODS: We performed high-resolution HLA typing on dermatologist-adjudicated co-trimoxazole-induced patients with SCAR in the United States (n = 63) and South Africa (n = 26) compared with population controls. Peptide binding and docking analyses were performed using MHCcluster2.0 and CB-Dock2. RESULTS: In a multiple logistic regression model, HLA-B&#x2217;44:03 (corrected P [Pc] < .001; odds ratio [OR] = 4.08), HLA-B&#x2217;38:01 (Pc < .001; OR = 5.66), and HLA-C&#x2217;04:01 (Pc = .003; OR = 2.50) were independently associated with co-trimoxazole-induced SJS/TEN in the United States. HLA-B&#x2217;44:03 was also associated with co-trimoxazole-induced DRESS in South Africa (Pc = .019; OR = 10.69). Distinct HLA-B variants with shared peptide binding specificities (SPBS) and HLA-C&#x2217;04:01 identified 94% and 78% of co-trimoxazole-induced SJS/TEN and DRESS in the United States, respectively. The SEA risk allele HLA-B&#x2217;13:01, with SPBS to HLA-B&#x2217;44:03, was identified in just one of 63 US patients with SCAR. CONCLUSIONS: HLA alleles with SPBS to SEA-related risk alleles, including HLA-B&#x2217;44:03 (SPBS with HLA-B&#x2217;13:01) and HLA-B&#x2217;38:01 (SPBS with HLA-B&#x2217;38:02) but also HLA-C&#x2217;04:01, predisposed to co-trimoxazole-induced SCAR in the United States and South Africa. These findings provide biological plausibility and strategies for global risk prediction and diagnosis of co-trimoxazole-induced SCAR.

Humans↗
PubMed1975

[The bullous variant of erythema annulare centrifugum Darier in Candida albicans infections].

A 15-year old male patient with Down-Syndrome suffering from a unusual vesicular type of erythema annular centrifugum Darier and a concurrent intestinal infection with candida albicans is described. Histology, immunhistological assay, and clinical observation allowed to differentiate Erythema annulare centrifugum from erythema exsudativum multiforme as well as dermatitis herpetiformis. On the basis of immunological findings and the clinical course, a hypersensitivity to candida albicans like a so-called "id-reaction" is assumed to be the main etiological factor in this case.

Adolescent↗
PubMed1979

The allopurinol hypersensitivity syndrome.

Hypersensitivity reactions to allopurinol, a drug commonly used in the treatment of hyperuricemia, are being reported with increasing frequency. Of thirty-eight patients reviewed herein (including seven from our hospital and thirty-one from a review of the literature), ten deaths (26%) were related to complications of allopurinol hypersensitivity. Preexisting renal disease was present in 97% of patients, and, in the majority of these, the dosage of allopurinol was not reduced despite instructions contained in the package insert for this drug. At least 78% of patients were taking a thiazide diuretic prior to starting allopurinol therapy. Over 60% of patients had received allopurinol for asymptomatic hyperuricemia. Hallmarks of this hypersensitivity syndrome include a prolonged illness initially manifested by fever, a prominent cutaneous reaction, eosinophilia, hepatic abnormalities, and acute renal failure. Other involvement such as gastrointestinal bleeding is common. The mechanism of the hypersensitivity reaction is not clear, but it may represent an immune complex disease prolonged by the persistence of a currently undefined antigen. Treatment with systemic corticosteroids, often for several months, is usually necessary for the gradual resolution of this potentially fatal syndrome.

Adult↗
PubMed1979

Some gerontologic considerations in the practice of dermatology.

Gerontology and geriatrics are areas of increasing importance in medicine today. Although changes in the appearance and behavior of human skin have long been noted to accompany aging, physicians have only recently begun to consider the impact of such an age-associated change on the manifestations of dermatologic disease and on the dermatologic management of elderly patients. Gerontologic studies in such fields as immunology, epidermal cell kinetics, DNA damage and repair, and therapeutics are potentially of great relevance to the practicing dermatologist and deserve increased emphasis within our specialty.

Age Factors↗