Study authors from University of Arizona College of Medicine-Tucson pointed out that Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) are SCARs. Classic causal agents of SCARs are antibiotics, anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol, and are well characterized, they advised.
In a report in the Journal of Cutaneous Medicine & Surgery, the study team sought to provide an updated and stratified list of medications with significant reporting odds ratios (RORs) of SCARs.
To do that, the researchers employed a case/noncase analysis using the FDA’s Adverse Event Reporting System.
“As expected, the prototypical medication classes made up the majority of reported cases of SJS, TEN, AGEP, and DRESS (77%, 64%, 75%, and 72%, respectively),” the researchers wrote. “In addition, several infrequently or previously undescribed classes/medications implicated in SCARs were identified to have significant ROR signals, including acetylcysteine, anticoagulants, diuretics, immunotherapies, proton pump inhibitors, antivirals, and antifungals.”
The findings of strong reporting odds include:
• Among these reported for SJS were acetylcysteine (ROR: 64.38) and fluconazole (ROR: 17.13)
• For TEN, the researchers identified furosemide (ROR: 26.32), spironolactone (ROR: 14.45), fluconazole (ROR: 30.21), amphotericin B (39.06), and acetylcysteine (ROR: 93.12)
• For AGEP, they identified acyclovir (ROR: 61.72), valacyclovir (ROR: 30.76), and enoxaparin (ROR: 27.37)
• For DRESS, the study identified vemurafenib (ROR: 17.35), acyclovir (ROR: 30.63), abacavir (ROR: 26.62), raltegravir (ROR: 23.27), and valacyclovir (ROR: 21.77).
“Our analysis provides an updated tool for physicians to reference when identifying suspected SCARs and a basis for future studies to investigate atypical medication causality,” the researchers wrote.
Interestingly, Thai researchers reported late last year in Experimental Dermatology about a possible risk factor in hypersensitivity reactions.
“Vitamin D deficiency has been reported to be associated with allergic diseases and dermatological disorders,” the researchers wrote. “We investigated the role of vitamin D in drug-induced non-immediate hypersensitivity reactions by measuring serum vitamin D levels in 60 patients diagnosed with non-immediate drug hypersensitivity reactions and in 60 patients who tolerated the same medication without any allergic reactions.”
The results indicated that serum vitamin D levels were significantly lower in patients with severe reactions (13.56 ± 6.23 ng/mL) compared with patients with mild reactions (17.50 ± 7.49 ng/mL) and the drug-tolerant control group (17.42 ± 7.28 ng/mL), with P values of 0.031 and 0.015, respectively.
“The proportion of severe vitamin D deficiency (< 10 ng/mL) was much higher in SCAR patients compared to drug-tolerant subjects (36.7% vs. 11.7%, P value = 0.005),” according to the study. “After adjusting for age, gender, region of residence, and concurrent illnesses, patients with severe vitamin D deficiency had significantly increased in-hospital mortality (odds ratio 16.04; 95% CI, 1.25-206.12, P value = 0.03).”
The authors concluded that the risk of developing SCARs and in-hospital mortality was increased in patients with severe vitamin D deficiency. They call for further investigations to better understand the role of vitamin D in the development of SCARs.
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