What is the cause of a morbilliform (maculopapular) rash?

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Last updated: February 26, 2025View editorial policy

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From the Guidelines

A morbilliform rash is most commonly caused by viral infections or drug reactions, particularly to antibiotics like amoxicillin. The rash is characterized by small, confluent macules and papules that typically start on the face and spread downward to the trunk and extremities. According to a 2022 practice parameter update on drug allergy 1, aminopenicillins are associated with the development of delayed-onset morbilliform rash in less than 7% of patients, which is not related to specific IgE antibodies and may require the presence of a concurrent viral infection or another underlying illness. Some studies have investigated rechallenging testing in patients with a history of benign cutaneous reactions to amoxicillin, and the rate of reactions observed ranged from about 5% to 10% and were generally no more severe than the historical reactions 1. Other causes of morbilliform rash include non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as delavirdine, efavirenz, nevirapine, and etravirine, which can cause skin rash in 10-17% of patients 1. Management of morbilliform rash depends on identifying and addressing the underlying cause, and may include supportive treatment with antipyretics and antihistamines, discontinuation of the offending medication, and immediate medical attention for severe cases with systemic symptoms. It is essential to distinguish morbilliform rashes from more serious conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis, which present with mucosal involvement, blistering, or skin sloughing and require urgent medical care. Key points to consider in the management of morbilliform rash include:

  • Identifying the underlying cause of the rash
  • Discontinuing the offending medication if drug-induced
  • Providing supportive treatment with antipyretics and antihistamines
  • Monitoring for signs of severe disease or complications
  • Distinguishing morbilliform rash from more serious conditions like Stevens-Johnson syndrome or toxic epidermal necrolysis.

From the Research

Causes of Morbilliform (Maculopapular) Rash

  • Morbilliform eruptions can be caused by various factors, including low-risk drug exanthems, viral eruptions, and high-risk diseases such as Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, acute generalized exanthematous pustulosis, and graft-versus-host disease 2
  • Certain medications, such as antihistamines, can induce cutaneous drug eruptions, leading to morbilliform rashes 3
  • Infectious causes, such as viral diseases like measles, can also lead to morbilliform rashes 4
  • Delayed cellular hypersensitivity and adhesion molecules play a role in the development of morbilliform rashes induced by certain antibiotics, such as amoxicillin 5
  • The frequency of low-risk morbilliform drug eruptions varies among different classes of antibiotics, making it essential to consider the prevalence of antibiotic-associated drug eruptions when assessing causality 6

Drug-Induced Morbilliform Rashes

  • Antihistamines, such as hydroxyzine and cetirizine, can cause cutaneous drug eruptions, leading to morbilliform rashes 3
  • Amoxicillin-induced morbilliform rashes are thought to be caused by a delayed cell-mediated immune reaction 5
  • Other antibiotics can also lead to morbilliform rashes, with varying frequencies depending on the specific medication 6

Infectious Causes

  • Viral diseases, such as measles, can cause morbilliform rashes, especially in adults who have not been vaccinated or have weakened immune systems 4
  • Other infectious causes, such as bacterial or fungal infections, can also lead to morbilliform rashes, although these are less common 2

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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