Pathogenesis:
The pathogenesis of most drug eruptions is not well understood. With few exceptions, eg, fixed drug eruption, the diagnosis cannot be based solely on the morphology of the eruption.
Clinical Features:
A drug rash may manifest as urticaria, a morbilliform exanthem, erythroderma, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), photosensitivity, lichen planus, or vasculitis, all of which have other potential causes. A high index of suspicion for drug causation is important so that an offending drug is discontinued and avoided in the future, particularly in the case of life-threatening reactions such as anaphylaxis, the drug (anticonvulsant) hypersensitivity syndrome, SJS, and TEN. Conversely, it is important not to err by labeling a child as allergic to a widely used medication, such as penicillin. There are no standardized laboratory investigations that are diagnostic for drug allergy, and the value of allergy testing is largely restricted to cases of IgE-mediated penicillin hypersensitivity. Therefore, a detailed history, evaluation of the morphology of the rash, consideration of a differential diagnosis, and careful clinical judgment are essential.
The timing of the reaction may be helpful. Medications begun recently, particularly within the past weeks, are more likely to be culpable than drugs taken for many months.
Urticaria usually occurs within hours to one day after beginning a medication, whereas maculopapular eruptions develop 7 to 10 days into treatment unless there has been a previous exposure.
Life-threatening hypersensitivity reactions to sulfonamides, carbamazepine, phenytoin, or phenobarbital characteristically occur one to four weeks after initiating therapy. Although serious adverse reactions are rare, the parents of children who are prescribed these medications should be advised to seek medical attention if a rash or fever develops within the first four to six weeks of treatment.
The morphology of the rash is an important observation.
The morphology of the rash is an important observation.
Morbilliform, maculopapularar drug eruptions, though often extremely pruritic, are usually benign and self-limited. Some, as in the common ampicillin rash may not recur on rechallenge. These eruptions may be difficult to distinguish from viral exanthems. All patients with a morbilliform eruption, particularly those caused by sulfonamides and anticonvulsant medications, should be closely monitored during the first few days for progression to SJS, TEN, or the drug (anticonvulsant) hypersensitivity syndrome which is characterized by an erythematous exanthem, fever, hepatosplenomegaly, lymphadenopathy, hepatitis, and multiorgan disease. These life-threatening drug reactions are accompanied by fever and signs of systemic toxicity. They are sometimes initially misdiagnosed as a viral or other infectious illness.
Urticarial drug eruptions are also potentially life threatening because of the risk of airway angioedema and anaphylaxis. Acute urticaria in childhood is often associated with a viral or upper respiratory tract illness for which an antibiotic may have been administered. In such cases, it is difficult to be certain whether the cause of the urticaria is the infection, the drug, or perhaps a drug-virus interaction. It is wise to discontinue the drug and consult an allergist before considering oral rechallenge if further use of the medication is anticipated. Cefaclor causes an urticarial eruption, often associated with arthralgia, in up to 3% of children who take this antibiotic.
Urticarial drug eruptions are also potentially life threatening because of the risk of airway angioedema and anaphylaxis. Acute urticaria in childhood is often associated with a viral or upper respiratory tract illness for which an antibiotic may have been administered. In such cases, it is difficult to be certain whether the cause of the urticaria is the infection, the drug, or perhaps a drug-virus interaction. It is wise to discontinue the drug and consult an allergist before considering oral rechallenge if further use of the medication is anticipated. Cefaclor causes an urticarial eruption, often associated with arthralgia, in up to 3% of children who take this antibiotic.
If urticarial reactions, the drug (anticonvulsant) hypersensitivity syndrome, vasculitis, SJS, or TEN occur as a result of drug administration, patients should be considered allergic to the medication, and the drug should not be readministered. If more than one drug is being used, all drugs that could potentially induce such a reaction, and particularly anticonvulsants, antibiotics, and sulfonamide derivatives, should be discontinued.
The most common drug reaction in childhood is the ampicillin rash, which occurs in up to 18% of children receiving oral ampicillin. The median time of onset is 9 days, with a range from 1 to 14 days. Lesions are fine, erythematous macules and papules that usually appear on the trunk, then spread peripherally. The mechanism of this eruption is poorly understood. In some cases it may be the result of a drug-virus interaction, such as with the Epstein-Barr virus or cytomegalovirus. It is not considered a true allergy, and if the findings are typical, readministration of the drug is not contraindicated.
The fixed drug eruption is characterized by one or a few discrete plaques of dusky erythema that develop hours to days after drug exposure. Central blistering is often present. The mucous membranes of the lips or penis are commonly affected, but lesions may occur on any part of the body. They typically resolve, leaving an ashy-gray postinflammatory hyperpigmentation. If the offending drug is readministered, lesions will recur in precisely the same anatomic locations. Common causative drugs include salicylates, barbiturates, phenolphthalein (found in laxatives), and tetracyclines. A nonpigmenting fixed drug eruption that presents with localized erythema and subsequently desquamates may be caused by pseudoephedrine, contained in over-the-counter remedies for upper respiratory tract symptoms
The most common drug reaction in childhood is the ampicillin rash, which occurs in up to 18% of children receiving oral ampicillin. The median time of onset is 9 days, with a range from 1 to 14 days. Lesions are fine, erythematous macules and papules that usually appear on the trunk, then spread peripherally. The mechanism of this eruption is poorly understood. In some cases it may be the result of a drug-virus interaction, such as with the Epstein-Barr virus or cytomegalovirus. It is not considered a true allergy, and if the findings are typical, readministration of the drug is not contraindicated.
The fixed drug eruption is characterized by one or a few discrete plaques of dusky erythema that develop hours to days after drug exposure. Central blistering is often present. The mucous membranes of the lips or penis are commonly affected, but lesions may occur on any part of the body. They typically resolve, leaving an ashy-gray postinflammatory hyperpigmentation. If the offending drug is readministered, lesions will recur in precisely the same anatomic locations. Common causative drugs include salicylates, barbiturates, phenolphthalein (found in laxatives), and tetracyclines. A nonpigmenting fixed drug eruption that presents with localized erythema and subsequently desquamates may be caused by pseudoephedrine, contained in over-the-counter remedies for upper respiratory tract symptoms
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