Dataset Information

Association of the HLA-B*53:01 Allele With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome During Treatment of HIV Infection With Raltegravir.

ABSTRACT: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, severe adverse event during treatment with raltegravir. The occurrence of DRESS syndrome during treatment with other drugs is strongly associated with particular HLA alleles.We performed HLA testing in 3 of the 5 patients previously reported to have developed raltegravir-induced DRESS syndrome and in 1 previously unreported patient. We then used virtual modeling to visualize interactions between raltegravir and the imputed HLA molecule.Five of the 6 patients who developed raltegravir-induced DRESS syndrome were African, and 1 was Hispanic. HLA typing was performed in 4 patients, all of whom carried both the HLA-B*53 allele and the HLA-C*04 allele to which it is commonly haplotypic. No other HLA alleles were shared by all of the tested patients. Given the approximate prevalence of HLA-B*53 carriage in African (20%) and Hispanic (6%) populations, the probability of all 4 patients being HLA-B*53 carriers, and 2 of 3 African patients being homozygous for HLA-B*53:01, is approximately 0.00002.These data implicate the prevalent African allele HLA-B*53:01 in the immunopathogenesis of raltegravir-induced DRESS syndrome. Although the immunopathogenic mechanisms are currently unknown, virtual modeling suggests that raltegravir may bind within the antigen binding cleft of the HLA-B*53:01 molecule, but not within the closely related HLA-B*35:01 molecule. Further studies are necessary to confirm the strength of the association between carriage of the HLA-B*53:01 allele and raltegravir-induced DRESS syndrome, and the potential utility of HLA screening before raltegravir treatment.

SUBMITTER: Thomas M

PROVIDER: S-EPMC5399947 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of the HLA-B*53:01 Allele With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome During Treatment of HIV Infection With Raltegravir.

Thomas Mark M Hopkins Chris C Duffy Eamon E Lee Daniel D Loulergue Pierre P Ripamonti Diego D Ostrov David A DA Phillips Elizabeth E

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20170501 9

<h4>Background</h4>Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, severe adverse event during treatment with raltegravir. The occurrence of DRESS syndrome during treatment with other drugs is strongly associated with particular HLA alleles.<h4>Methods</h4>We performed HLA testing in 3 of the 5 patients previously reported to have developed raltegravir-induced DRESS syndrome and in 1 previously unreported patient. We then used virtual modeling to visualize inter ...[more]

PMID: 28369189

Similar Datasets

Project description:BackgroundThe syndrome of drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, yet potentially fatal hypersensitivity reaction, most commonly associated with anticonvulsants, sulfonamides, and allopurinol. The reaction commonly manifests as a febrile skin eruption with lymphadenopathy and malaise between two and eight weeks following drug exposure. Internal organ involvement occurs in close to 90 percent of patients, and multiple organs may be involved in approximately half of those affected (most commonly the liver, kidney, and lung). Its long latency period and its variable clinical pattern of presentation have earned it the moniker of "the great mimicker," with delays in diagnosis leading to higher morbidity and mortality. Although less commonly affected in DRESS syndrome, lung involvement is associated with more severe clinical course and potentially worse outcome. Pulmonary symptoms may precede development of the other more common symptoms and signs of the syndrome, or they might develop later in the course of the disease. Lung involvement in DRESS presents with a plethora of manifestations from mild cough or dyspnea with nonspecific interstitial changes on chest imaging to acute respiratory distress syndrome (ARDS) with life-threatening hypoxic respiratory failure.MethodsWe performed a systematic review of literature from the PubMed database and selected cases of definite DRESS syndrome as defined by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) with a score of 6 or more who also had pulmonary involvement. Demographic data, pattern of lung involvement, culprit medication, latency period, laboratory findings, therapy, and outcome were described and compared with the literature.ResultsThe most common pulmonary radiographic findings in DRESS were interstitial infiltrates in 50% of cases, followed by acute respiratory distress syndrome (ARDS) 31%. Symptoms of cough and shortness of breath (SOB) were present in 72% of patients at the time of presentation. SOB was the more common presenting symptom (81%) compared to cough (19%). In 95% of cases, another visceral organ was involved (most commonly liver or kidneys). 45% of cases were initially misdiagnosed as pneumonia and were treated with empiric antimicrobials. In a multivariate regression, a latency of 30 days or less and an age of 60 or less were associated with development of ARDS. Gender and eosinophil count were not associated with severity of pulmonary manifestations. All patients recovered, and in the vast majority of cases (95%), parenteral steroids were used for treatment in addition to supportive care and symptomatic management.ConclusionAlbeit rare, DRESS is a potentially life-threatening syndrome which may present with a myriad of pulmonary signs and symptoms. Pulmonary manifestations are less common but are typically seen in more severe cases. Pulmonary manifestations may be a presenting sign of DRESS, and timely recognition is important in order to stop offending medication and decrease morbidity and mortality.

Dataset Information

Association of the HLA-B*53:01 Allele With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome During Treatment of HIV Infection With Raltegravir.

Publications

Association of the HLA-B*53:01 Allele With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome During Treatment of HIV Infection With Raltegravir.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets