Can amoxicillin (amoxicillin) cause a rash in patients with a viral infection?

From the Guidelines

Yes, amoxicillin can cause a rash in patients with viral infections, particularly in those with Epstein-Barr virus (infectious mononucleosis), with a reported incidence of 30%-100%. This phenomenon, known as "amoxicillin rash," occurs due to an interaction between the virus and the antibiotic, and not as a result of a true allergic reaction 1. The rash typically appears as a nonpruritic morbilliform rash. According to the 2022 practice parameter update on drug allergy, aminopenicillins, such as amoxicillin, are associated with the development of delayed-onset maculopapular exanthem (MDE) in less than 7% of patients, which is often related to concurrent viral infections or other underlying illnesses 1.

Key points to consider:

• The rash is not a true allergic reaction, but rather an interaction between the virus and the antibiotic
• Patients who develop a rash while taking amoxicillin during a viral illness should not automatically be labeled as allergic to penicillins
• The mechanism involves the virus altering how the immune system responds to the drug
• If a patient develops a rash while taking amoxicillin during what might be a viral infection, they should consult their healthcare provider for evaluation
• In many cases, these patients can safely take amoxicillin in the future once the viral infection has resolved, though this should be determined by a healthcare professional, and a single-dose amoxicillin challenge without prior allergy testing may be recommended for pediatric patients with a history of benign cutaneous reaction 1.

From the FDA Drug Label

A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. If patients develop skin rash they should be monitored closely, and amoxicillin discontinued if lesions progress. Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis, and linear IgA bullous dermatosis have been reported.

Amoxicillin can cause a rash in patients with a viral infection, as evidenced by the high percentage of patients with mononucleosis who develop an erythematous skin rash after receiving amoxicillin 2. It is essential to monitor patients closely for skin rash and discontinue amoxicillin if lesions progress. Various types of rashes have been reported, including erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis, and linear IgA bullous dermatosis 2.

From the Research

Amoxicillin and Viral Infection-Related Rash

• Amoxicillin can cause a rash in patients with a viral infection, as evidenced by several studies 3, 4, 5, 6, 7.
• The incidence of rash after amoxicillin treatment in children with infectious mononucleosis was found to be 29.5% in a retrospective study 6.
• A study published in the Journal of Family Practice found that skin reactions to ampicillin, a similar antibiotic, are more frequent in patients with a viral illness, infectious mononucleosis, and lymphocytic leukemia 3.
• The mechanism of antibiotic-induced rash in patients with infectious mononucleosis is thought to be a transient virus-mediated immune alteration that sets the stage for loss of antigenic tolerance and the development of a reversible, delayed-type hypersensitivity reaction to the antibiotic 5.
• Differential diagnosis is often challenging in cases of skin eruptions over the course of antibiotic therapy and concomitant viral infection, and confirming or ruling out drug hypersensitivity is not always a clear-cut question 7.

Characteristics of the Rash

• The rash is often maculopapular, and may be accompanied by mild-to-moderate systemic symptoms 7.
• The absence of eosinophilia may be an initial marker to help identify DRESS-like rashes, which can be caused by viral infections during amoxicillin intake 7.
• A quick clinical improvement and the confirmation of a viral infection able to explain the symptoms can help to finally rule out DRESS syndrome 7.

Clinical Implications

• A rapid, correct diagnosis of DRESS-like rashes during viral infections allows more appropriate management and avoids unnecessary, life-long exclusion of useful and effective antibiotics because of a falsely "amoxicillin-allergy" labelling 7.
• Clinicians should be aware of the similarities and differences between DRESS syndrome and DRESS-like rashes during viral infections and amoxicillin intake in children, in order to make an early detection and provide appropriate management 7.