Severe cutaneous adverse drug reactions: diagnostic approach and genetic study in a Brazilian case series

Perelló, Maria Inês; Castro, Andrea; Arraes, A C Nogueira; Sc, Costa; Pedrazzi, Denise Lacerda; Dias, Gabriela Andrade Coelho; Hanhoerster, Leonardo M.; Porto, L.; Kuschnir, Fábio Chigres; Costa, Eduardo

doi:10.23822/eurannaci.1764-1489.193

Cited by 8 publications

(3 citation statements)

References 51 publications

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“…In 2018, the allopurinol drug label was updated to include pharmacogenetic guidance, however, despite the evidence supporting the association, replication across different races/ancestries, and guidance from medical societies, testing is recommended rather than required. Since this update, studies have also confirmed the HLA‐B*58:01‐ allopurinol association in Vietnamese, 72 Brazilian, 73 and Malaysian patients 74 . Notably, the 2020 ACR gout treatment guideline update added an additional recommendation for HLA‐B*58:01 screening in African Americans 75 …”

Section: Human Leukocyte Antigen: the Untapped Hotspot For Pharmacogenomic Actionability?mentioning

confidence: 89%

Translational Pharmacogenomics: Discovery, Evidence Synthesis and Delivery of Race‐Conscious Medicine

Davis

Limdi

2021

Clin Pharma and Therapeutics

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Response to medications, the principal treatment modality for acute and chronic diseases, is highly variable, with 40–70% of patients exhibiting lack of efficacy or adverse drug reactions. With ~ 15–30% of this variability explained by genetic variants, pharmacogenomics has become a valuable tool in our armamentarium for optimizing treatments and is poised to play an increasing role in clinical care. This review presents the progress made toward elucidating genetic underpinnings of drug response including discovery of race/ancestry‐specific pharmacogenetic variants and discusses the current evidence and evidence framework for actionability. The review is framed in the context of changing demographics and evolving views related to race and ancestry. Finally, it highlights the vital role played by cohort studies in elucidating genetic differences in drug response across race and ancestry and the informal collaborations that have enabled the field to bridge the “bench to bedside” translational gap.

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Section: Human Leukocyte Antigen: the Untapped Hotspot For Pharmacogenomic Actionability?mentioning

confidence: 89%

Translational Pharmacogenomics: Discovery, Evidence Synthesis and Delivery of Race‐Conscious Medicine

Davis

Limdi

2021

Clin Pharma and Therapeutics

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“…Severe cutaneous adverse reactions to pharmaceuticals include various conditions, including DIHS and SJS/TEN [ 2 ]. There are seven and five diagnostic criteria for DIHS and SJS/TEN, respectively (Table 2 ) [ 1 , 4 ]; however, both DIHS and SJS/TEN result in severe systemic symptoms; moreover, there may be overlapping cases [ 5 ], which impedes diagnosis in some cases. Furthermore, the difficulty in the diagnosis of DIHS could be attributed to rash, fever, and liver lesions usually disappearing after discontinuation of the suspected drug [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Atypical drug-induced hypersensitivity syndrome with multiple organ failure rescued by combined acute blood purification therapy: a case report

et al. 2023

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Background Drug-induced hypersensitivity syndrome (DIHS), including Stevens-Johnson syndrome (SJS), is a severe rash that often develops 2–6 weeks after the intake of the causative drug; however, its diagnosis is sometimes difficult. This article describes a case in which a patient with DIHS-induced multiple organ failure was successfully treated with blood purification therapy. Case presentation A male patient in his 60s was admitted to our hospital with autoimmune encephalitis. The patient was treated with steroid pulse therapy, acyclovir, levetiracetam, and phenytoin. From the 25th day, he presented with fever (≥ 38 °C) as well as miliary-sized erythema on the extremities and trunk, followed by erosions. DIHS and SJS were suspected; accordingly, levetiracetam, phenytoin, and acyclovir were discontinued. On the 30th day, his condition further deteriorated, and he was admitted to the intensive care unit for ventilatory management. The next day, he developed multi-organ failure and was started on hemodiafiltration (HDF) for acute kidney injury. Although he presented with hepatic dysfunction and the appearance of atypical lymphocytes, he did not meet the diagnostic criteria for DIHS or SJS/toxic epidermal necrolysis. Therefore, he was diagnosed with multi-organ failure caused by severe drug eruption and underwent a 3-day treatment with plasma exchange (PE) in addition to HDF. Accordingly, the patient was diagnosed with atypical DIHS. After being started on blood purification therapy, the skin rash began to disappear; moreover, the organ damage improved, with a gradual increase in urine output. Eventually, the patient was weaned off the ventilator and transferred to the hospital on the 101st day. Conclusions HDF + PE could effectively treat multi-organ failure caused by atypical DIHS, which is difficult to diagnose.

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“…149 In the studies found in this review, allopurinol has been patch tested in 62 patients with zero positive results. 50,52,58,83,245 There is no definite explanation for these (false-) negative results, but there may be several possible causes: (a) the final responsible agent is a drug metabolite that is not formed in the skin during patch testing; (b) there is no immune mechanism involved; (c) concomitant factors that are responsible in inducing transient drug intolerance, such as viral infection, are not present at the time of testing; and (d) wrong choice of vehicle (limited skin penetration), drug concentration, or exposure time. 52 When administered orally, allopurinol is rapidly converted into its oxidative metabolite 8-oxypurinol, 52 which may be the culprit in drug hypersensitivity to allopurinol, as these reactions appear to be primarily mediated by an oxypurinol-specific T cell response.…”

Section: Groups Of Patientsmentioning

confidence: 99%

Patch testing in drug reaction with eosinophilia and systemic symptoms (DRESS): A literature review

Groot

2022

Contact Dermatitis

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The literature on positive patch test results in drug reaction with eosinophilia and systemic symptoms (DRESS) is reviewed. One hundred and five drugs were identified that have together caused 536 positive patch tests in 437 DRESS patients. By far, the most reactions (n = 145) were caused by carbamazepine, followed by amoxicillin, isoniazid, phenytoin, ethambutol, fluindione, phenobarbital, rifampicin, and ceftriaxone; 43 drugs each caused a single case only. The drug classes causing the highest number of reactions were anticonvulsants (39%), beta‐lactam antibiotics (20%), antituberculosis agents (11%), non‐beta‐lactam antibiotics (6%), and iodinated contrast media (5%). The sensitivity of patch testing (percentage of positive reactions) is high for anticonvulsants (notably carbamazepine), beta‐lactam antibiotics (notably amoxicillin), and, possibly, iodinated contrast media. Allopurinol and sulfasalazine frequently cause DRESS but never give positive patch tests. Patch testing in DRESS appears to be safe, although mild recurrence of DRESS symptoms, mostly skin reactions, may not be rare. Multiple drug hypersensitivity was found to occur in 16% of all patients, but it is argued that the true frequency is higher. Clinical aspects of DRESS, including diagnosing the disease and identifying culprit drugs (patch tests, intradermal tests, in vitro tests, challenge tests) are also provided, emphasizing the role of patch testing.

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Severe cutaneous adverse drug reactions: diagnostic approach and genetic study in a Brazilian case series

Cited by 8 publications

References 51 publications

Translational Pharmacogenomics: Discovery, Evidence Synthesis and Delivery of Race‐Conscious Medicine

Translational Pharmacogenomics: Discovery, Evidence Synthesis and Delivery of Race‐Conscious Medicine

Atypical drug-induced hypersensitivity syndrome with multiple organ failure rescued by combined acute blood purification therapy: a case report

Patch testing in drug reaction with eosinophilia and systemic symptoms (DRESS): A literature review

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