What is the cause of a rash after taking cephalexin (Cefalexin, a cephalosporin antibiotic)?

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From the Guidelines

If you develop a rash after taking cephalexin, you should stop the medication and contact your healthcare provider immediately, as this could be a sign of an allergic reaction. This reaction could range from mild, such as a simple rash, to severe, like anaphylaxis. Cephalexin is an antibiotic in the cephalosporin family, and allergic reactions occur in about 1-3% of patients taking it 1. The cause of the rash is likely an allergic reaction to the medication, which can be due to the body's immune system reacting to the drug as a foreign substance. If you've had previous allergic reactions to penicillin, you have a higher risk (about 2-4.8%) of reacting to cephalexin due to cross-reactivity between these antibiotic classes, although this cross-reactivity is considered low 1. Some key points to consider include:

  • The risk of cross-reactivity between penicillin and cephalosporins is lower than previously thought, with estimates ranging from 2.0% to 4.8% 1.
  • Cephalexin skin testing may be useful for patients with anaphylactic or convincing histories of IgE-mediated reactions, but its sensitivity is reliant on testing soon after the reaction 1.
  • For patients with a history of allergy to one cephalosporin who require treatment with another cephalosporin, they can receive the indicated cephalosporin by a direct drug challenge if the R1 side chains are dissimilar and the reaction was nonanaphylactic 1. Your doctor may recommend antihistamines like diphenhydramine (Benadryl) 25-50mg every 6 hours for mild symptoms, but severe reactions require immediate medical attention 1. They will likely switch you to an alternative antibiotic from a different class, such as azithromycin, doxycycline, or fluoroquinolones, depending on what infection is being treated. Make sure to document this reaction and inform all healthcare providers about this allergy in the future to prevent re-exposure. It's also important to note that patients with a suspected non-severe, delayed-type allergy to a cephalosporin can receive penicillins with dissimilar side chains, and cephalosporins with a dissimilar side chain can be used in patients with a suspected non-severe, delayed-type allergy to a cephalosporin, irrespective of time since the index reaction 1.

From the FDA Drug Label

Hypersensitivity AlIergic reactions in the form of rash, urticaria, angioedema, and, rarely, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis have been observed. The cause of a rash after taking cephalexin is likely due to a hypersensitivity or allergic reaction to the drug 2.

  • Possible allergic reactions include:
    • Rash
    • Urticaria
    • Angioedema
    • Erythema multiforme
    • Stevens-Johnson syndrome
    • Toxic epidermal necrolysis

From the Research

Causes of Rash after Taking Cephalexin

  • A rash after taking cephalexin can be caused by a generalized eruptive pustular drug rash, as seen in a case study where a 38-year-old woman developed a generalized pustular eruption 18 hours after taking oral cephalexin 3.
  • Another possible cause is an allergic reaction to cephalexin, which can occur in patients with a history of penicillin allergy, although the cross-allergy risk is lower than previously thought 4.
  • Cephalexin can also cause a rash in patients with infectious mononucleosis, similar to the ampicillin rash that occurs in these patients 5.
  • Hypersensitivity reactions to cephalosporins, including cephalexin, can cause a range of symptoms including rash, and can be due to various immunopathologic mechanisms 6.

Factors Contributing to Rash

  • The mechanism by which cephalexin causes a rash is not fully understood, but may be related to the immune system's response to the antibiotic 5.
  • The presence of certain side chains on the cephalosporin molecule may also play a role in the development of a rash 6.
  • Patients who are allergic to penicillin may be more likely to develop a rash after taking cephalexin, although this risk is lower than previously thought 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cephalosporin Allergy: Current Understanding and Future Challenges.

The journal of allergy and clinical immunology. In practice, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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