Infectious Disease
Corey Diamond, PharmD
Cutaneous adverse reactions are a common occurrence when it comes to antibiotic use, impacting a significant portion of patients. These reactions can range from mild rashes to severe life-threatening conditions such as Stevens-Johnson syndrome. As antibiotics are among the most frequently prescribed medications worldwide, understanding the prevalence, risk factors, and management of these adverse effects is crucial for clinicians.
A research paper published February 2024 in the Journal of Allergy and Clinical Immunology gives further insight into the problem. The researchers found that oral sulfonamides and cephalosporins were associated with the highest risk of serious cutaneous adverse reactions compared with other antibiotics.
Abstract overview
Lee and colleagues conducted a population-based nested case-control study centered in Ontario, Canada, that included over 100,000 patients. The researchers used collected adverse event outcome data from adults 66 years or older who received at least one antibiotic prescription between April 2002 and March 2022.
Patients were included in the analysis if they received hospitalization for a serious cutaneous adverse reaction within 60 days of the antibiotic prescription. A regression analysis was then performed, using macrolides as the control group, to determine the strength association between the cutaneous adverse reactions and the prescribed antibiotic.
The researchers found that, compared to macrolides, oral sulfonamides and cephalosporins had the strongest association with serious cutaneous adverse reactions. The results were statistically significant, with sulfonamides and cephalosporins having an adjusted odds increase of 190% and 160%, respectively, of giving patients a serious cutaneous adverse reaction event. Additionally, fluoroquinolones, nitrofurantoin, and penicillin had a significant adjusted odds increase of 120%, 30%, and 40%, respectively, for cutaneous adverse reactions, although the association was weaker, according to the authors.
Other evidence
Despite the commonality of antibiotic-related cutaneous adverse reactions, there are few studies in the literature that narrow down the precise incidence rates and mechanisms by which they occur. A 2023 report, which was based on data from FDA’s Adverse Event Reporting System and published in Expert Opinion on Drug Safety, found similar results to these recent research findings. The report cited severe cutaneous adverse reactions being most associated with sulfonamides, glycopeptides, penicillin, carbapenems, and cephalosporins.
Likewise, a systematic review and meta-analysis published in JAMA Dermatology from April 2023 found that sulfonamides were associated with 32% of antibiotic-related Stevens-Johnson syndrome and toxic epidermal necrolysis cases, followed by penicillin (22%) and cephalosporins (11%).
Recognizing two uncommon but serious reactions
Stevens-Johnson syndrome and toxic epidermal necrolysis usually begin with flu-like symptoms, including fever, malaise, and loss of appetite, occurring 1 to 3 days after starting the problem medication. Painful skin and mucosal lesions then develop, with erythematous macules progressing into blisters and areas of skin peeling.
The degree of skin involvement distinguishes the two: Stevens-Johnson syndrome affects less than 10% of the body surface area, toxic epidermal necrolysis involves over 30%, and the overlap syndrome affects 10% to 30% of body surface area.
Mucosal involvement is a key feature, with the mouth, eyes, and genitals commonly affected. This can result in severe complications such as conjunctivitis, oral ulcers, and genital erosions, as well as systemic symptoms such as difficulty swallowing and breathing.
Other serious reactions
Other severe cutaneous adverse reactions include drug reaction with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis.
Drug reactions with eosinophilia and systemic symptoms is marked by a widespread rash, fever, swollen lymph nodes, as well as the internal organs such as the liver, kidneys, and lungs. It typically appears 2 to 6 weeks after drug exposure and has a high risk of mortality due to multi-organ failure.
Acute generalized exanthematous pustulosis is characterized by the rapid onset of numerous sterile pustules on a red, inflamed base, often accompanied by fever and an increase in neutrophils. It usually develops within days of drug exposure and resolves quickly after the individual stops the medication.
All severe cutaneous adverse reactions require swift recognition and treatment, including immediate discontinuation of the causative drug and supportive care. Systemic corticosteroids may be necessary in some cases, particularly for managing drug reactions with eosinophilia and systemic symptoms. ■