What is the cause of an amoxicillin (amoxicillin) rash?

From the Guidelines

Amoxicillin rash is generally a benign reaction and most patients can undergo a direct amoxicillin challenge without prior skin testing, as recommended by the latest practice parameter update 1. When considering the management of amoxicillin rash, it's essential to distinguish between a benign cutaneous reaction and a true allergic reaction. The former is often characterized by a maculopapular exanthem or urticarial eruption, whereas the latter involves more severe symptoms such as hives, facial swelling, difficulty breathing, or dizziness.

• Key factors to consider when evaluating an amoxicillin rash include:
  • The presence of systemic symptoms, such as fever or malaise
  • The severity of the rash, including whether it's pruritic or non-pruritic
  • The patient's medical history, including any previous reactions to penicillin-class antibiotics According to the 2022 practice parameter update 1, a single-dose amoxicillin challenge without prior allergy testing is recommended for pediatric patients with a history of benign cutaneous reaction, such as a maculopapular exanthem or urticarial eruption, not accompanied by any systemic symptoms. However, it's crucial to note that this approach has not been thoroughly examined in primary care settings, and penicillin skin testing may still be performed at the discretion of the clinician, particularly in patients who are concerned or anxious about direct challenge 1.
• Treatment for amoxicillin rash typically involves symptomatic relief, such as:
  • Over-the-counter antihistamines like diphenhydramine (Benadryl) 25-50mg every 4-6 hours or cetirizine (Zyrtec) 10mg daily
  • Cool compresses and calamine lotion to alleviate itching and discomfort It's essential to consult a healthcare provider if you develop a rash while taking amoxicillin, as they can determine the best course of action and provide guidance on whether to continue or discontinue the medication.

From the FDA Drug Label

1. 2 Severe Cutaneous Adverse Reactions Amoxicillin may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) If patients develop skin rash they should be monitored closely, and amoxicillin discontinued if lesions progress.
2. 5 Skin Rash in Patients with Mononucleosis A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin should not be administered to patients with mononucleosis.
3. 1 Clinical Trials Experience ... rash ... was one of the most common adverse reactions (greater than 1%) observed in clinical trials of amoxicillin for oral suspension
4. 2 Postmarketing or Other Experience ... Skin and Appendages:Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis [see Warnings and Precautions (5. 2)].

Amoxicillin Rash is a possible side effect of the medication. The drug label warns of severe cutaneous adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, and advises monitoring patients who develop a skin rash and discontinuing the medication if lesions progress. Additionally, a high percentage of patients with mononucleosis who receive amoxicillin may develop an erythematous skin rash. Common adverse reactions in clinical trials included rash. Postmarketing reports have also included rashes and other skin reactions 2.

From the Research

Amoxicillin Rash

• Amoxicillin rash is a common reaction in patients taking the antibiotic, with studies suggesting that over 90% of patients who experience a rash can tolerate amoxicillin on re-exposure 3.
• The rash can manifest in different forms, including maculopapular exanthem, urticaria, and serum sickness-like reactions, with varying degrees of severity and associated symptoms 3.
• Research has shown that the majority of patients who report a penicillin allergy, including amoxicillin, do not have a clinically significant reaction, with less than 5% of patients having an IgE-mediated or T lymphocyte-mediated penicillin hypersensitivity 4.

Diagnosis and Management

• Diagnosis of amoxicillin hypersensitivity can be confirmed through skin testing, with a negative predictive value of 89% for immediate hypersensitivity and 95% for nonimmediate hypersensitivity 5.
• Penicillin cross-reactivity is observed in some patients, with a higher incidence in those presenting with immediate hypersensitivity 5.
• Management of amoxicillin hypersensitivity may involve discontinuation of the antibiotic, and depending on the type of reaction, treatment with epinephrine, antihistamines, and/or glucocorticoids 6.

Patient Outcomes

• Studies have shown that patients with a history of amoxicillin hypersensitivity can be safely re-exposed to the antibiotic, with a low risk of severe reactions 7, 5.
• However, some patients may experience delayed-onset systemic symptoms, highlighting the need for careful monitoring and follow-up 3.
• The negative predictive value of skin tests is excellent, excluding severe allergy in the majority of patients, and allowing for the safe use of amoxicillin in patients with a low risk of hypersensitivity 5.