Drug Eruption

A drug eruption is a rash that is a reaction to drug use. It is a leading cause of hospital dermatology consultations. The two most common patterns are morbilliform (maculopapular) and urticarial (hives).

Morbilliform. This is a generalized rash with intensely red ("drug red") macules and papules, often confluent in areas. It is usually pruritic. The onset is usually several days after drug initiation but can occasionally be more delayed. It frequently starts proximally and extends distally. Fever is typically absent.

Urticarial. A hive is a transient (any individual lesion lasting less than 24 hours) wheal, papule, or plaque that represents dermal edema. It has an erythematous, irregular border, often with central pallor. Lesions are often confluent. Pruritus (itching) is almost universally present.

Another variant is a fixed drug eruption, which is the formation of an erythematous lesion (sometimes plaque, bulla or erosion) at the same site with each challenge of the drug. It occurs within hours of drug exposure.

Which drugs most commonly cause drug eruptions?

The overall allergic reaction rate to drugs in one large study was 2.2%. Each patient received an average of eight drugs. Rashes were attributed to 51 drugs, with 75% of reactions being due to antibiotics, blood products, and inhaled mucolytics.

Drug	Reaction Rate per 1000 Recipients
Amoxicillin	51
Trimethoprim-sulfamethoxazole	34
Ampicillin	33
Ipodate	28
Blood	22
Semisynthetic penicillins	21
Cephalosporins	21
Erythromycin	20
Dihydralazine hydrochloride	19
Penicillin G	19
Quinidne	13
Cimetidine	13
Source: Bigby, M et al. Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982. JAMA. 1986 Dec 26;256(24):3358-63

Hives are often caused or exacerbated by aspirin and other non-steroidal anti-inflammatories.

Common causes of fixed drug eruptions include: analgesics, antimicrobial agents, especially sulfonamides, barbiturates, and pseudoephedrine. Howver, a large number of drugs have been implicated.

With what can it be confused?

Morbilliform drug eruption can be confused with other erythematous rashes such as viral exanthem, toxic erythema, and exfoliative erthyroderma. A viral exanthem will often be accompanied by other signs of viral illness. Toxic erythema is caused by a toxin and occurs in illnesses such as scarlet fever. The texture of this rash is described as "sand paper", there is often fever, an identifiable focus of infection, lymphadenopathy, and with some (e.g Kawasaki syndrome) there is mucus membrane involvement. Exfoliative erythroderma can result from a chronic generalized dermatosis (e.g. psoriasis); malignance ( e.g. Sezary syndrome); or chronic exposure to an allergy-provoking drug.

Urticaria can result from multiple causes including infection, external allergens such as latex, physical modalities such as cold and pressure, possibly emotions, and sometimes foods. Other conditions that can be mistaken for urticaria include erythema marginatum, erythema multiforme, and juvenile rheumatoid arthritis (Still's disease). Erythema marginatum is associated with rheumatic fever. The lesions are transient, erythematous and annular, but are usually not pruritic. The lesions of erythema multiforme last longer than 24 hours. The rash of juvenile rheumatoid arthritis is transient, "salmon colored", small (2-3 mm), and associated with fever spikes.

How is it diagnosed?

There is no laboratory test that can diagnose a drug eruption, although peripheral blood eosinophilia is sometimes present, especially with urticarial eruptions. Diagnosis is dependent on the appearance of the rash and a thorough history, including over-the-counter medications and herbal and alternative preparations. As mentioned above, the average hospital patient is on an average of 8 drugs (probably even more today), making the task of teasing out a drug reaction challenging. The key variables are temporal relationship to a new drug and knowledge of the prior odds of a drug reaction for a specific drug (see table above).

A graphical depiction of drug history, as show below, is often helpful. In this example, a patient came in already on the first three drugs, and received furosemide following admission for three days. On day three, ceftriaxone and azithromycin were started, followed by Tylenol on day seven. The rash began on day six. The three drugs the patient was already on are unlikely offenders. The furosemide that was discontinued three days before the rash began is less likely to be the cause than one of the antibiotics. Since cephalosporins are frequent causes of allergic drug rashes, this drug would be discontinued first. Since Tylenol was started after the rash, it is not involved.

Drugs	Hosp. Admit						Rash Starts		Consult Called
Propanolol
Famotidine
Simvistatin
Furosemide
Ceftriaxone
Azithromycin
Tylenol
	Day 0	Day 1	Day 2	Day 3	Day 4	Day 5	Day 6	Day 7	Day 8

How is it treated?

The provoking drug must be identified and discontinued. If the cause is not clear and the patient is on multiple medications, all drugs not absolutely required should be eliminated. Ideally, all possible offenders should be discontinued or substituted. Pruritus can be treated with antihistamines (e.g. hydroxyzine). Moisturizers and emollients can help with during the later stage of desquamation. There is little role for topical or systemic steroids.

What is the prognosis?

Following identification and discontinuation of the provoking drug, a morbilliform eruption clears slowly over 1 to 2 weeks; urticarial rashes usually clear in days. The rash sometimes continues to worsen immediately upon discontinuation of the drug. Complications include increased loss of body heat and fluids due to increased blood flow to the skin, if the rash is widespread. Usually this is not a problem. If the offending drug is not discontinued the rash may worsen possibly resulting in toxic epidermal necrolysis (the desquamation of large sheets of skin). Allergic interstitial nephritis can also develop. It is rare but when it occurs it is usually associated with penicillins or cephalosporins. The patient should be educated about his allergy, advised to avoid the offending drug in the future, and a notation made in the medical record and clearly on the chart.

Image links	Other useful links
DermnetNZ.com: Morbilliform drug rash	Bigby, M et al. Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982. JAMA. 1986 Dec 26;256(24):3358-63 Blume, Je et al. Drug eruptions. e-medicine. March 28, 2007

Date created 04/19/2007

Last updated 01/03/2009