Morbilliform drug reaction

Author: Dr Delwyn Dyall-Smith FACD, Dermatologist, Australia, 2009. Updated by A/Prof Amanda Oakley, January 2016.

What is morbilliform drug reaction?

Morbilliform drug eruption is the most common form of drug eruption. Many drugs can trigger this allergic reaction, but antibiotics are the most common group. The eruption may resemble exanthems caused by viral and bacterial infections.

Morbilliform drug eruption is also called maculopapular drug eruption, exanthematous drug eruption and maculopapular exanthem.

Who gets morbilliform drug eruption?

About 2% of prescriptions of new drugs cause a drug eruption. About 95% of these are morbilliform drug eruptions.

They mainly affect people prescribed beta-lactam antibiotics (penicillins, cephalosporins), sulfonamides, allopurinol, anti-epileptic drugs and nonsteroidal anti-inflammatory drugs (NSAID). Numerous other drugs have been reported to cause morbilliform drug eruptions, including herbal and natural therapies.

Predisposing factors include:

What causes morbilliform drug eruption?

Morbilliform drug eruption is a form of allergic reaction. It is mediated by cytotoxic T-cells and classified as a Type IV immune reaction. The target of attack may be drug, a metabolite of the drug, or a protein bonded to the drug. Inflammation follows the release of cytokines and other effector immune cells.

What are the clinical features of morbilliform drug eruption?

On the first occasion, a morbilliform rash usually appears 1–2 weeks after starting the drug, but it may occur up to 1 week after stopping it. On re-exposure to the causative (or related) drug, skin lesions appear within 1–3 days. It is very rare for a drug that has been taken for months or years to cause a morbilliform drug eruption.

Morbilliform drug eruption usually first appears on the trunk and then spreads to the limbs and neck. The distribution is bilateral and symmetrical.

The primary lesion is a pink-to-red flat macule or papule.

The rash may be associated with a mild fever and itch. As it improves, the redness dies away and the surface skin peels off.

What are the complications of morbilliform drug eruption?

In the early phase, it may not be possible to clinically distinguish an uncomplicated morbilliform eruption from other more serious cutaneous adverse reactions (SCAR). These are:

Patients with the following symptoms/signs should be hospitalised for specialist assessment and supportive care.

How is morbilliform drug eruption diagnosed?

A strong clinical suspicion of morbilliform drug eruption depends on:

To identify the possible causative drug, a drug calendar, including all prescribed and over-the counter products, may be helpful. The starting date of each new drug is documented together with the onset of the rash. The calendar must extend back at least 2 weeks and up to one month. Drugs can then be classified as unlikely or likely causes based on:

There are no routine tests to make the diagnosis or to identify the culprit drug. Differential diagnosis includes measles, rubella, scarlet fever, non-specific toxic erythema associated with infection, Kawasaki disease, connective tissue disease and acute graft-versus-host disease.

Tests are not usually necessary if the cause has been identified and stopped, the rash is mild and the patient is well. They may include:

Eosinophilia is supportive but not diagnostic. Further investigations will depend on clinical features, progress of the patient, and the results of the initial tests.

What is the treatment for morbilliform drug eruption?

The most important thing is to identify the causative drug and if possible, stop it. If the reaction is mild, and the drug is essential and not replaceable, obtain a specialist opinion whether it is safe to continue the drug before doing so.

How can morbilliform drug eruption be prevented?

It is not possible to completely prevent morbilliform eruptions. Prescribers must be vigilant. Their incidence may be reduced by:

What is the outlook for morbilliform drug eruption?

If the causative drug is ceased, the rash begins to improve within 48 hours and clears within 1–2 weeks.

If the drug is continued, the rash may:

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