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while EM typically first appears on the hands and feet before progressing
centrally.
The treatment for drug-induced urticaria is withdrawal of the causative
medication and treatment with both H1- and H2-blocking oral antihistamines for
up to 4 to 8 weeks. For cases that persist despite maximum dosing of nonsedating
H1- and H2-blocking antihistamines, oral steroids may be beneficial.

MORBILLIFORM
Morbilliform, or measles-like, describes an eruption characterized by both
erythematous macules and papules ( Fig. 68.3 ). The term “maculopapular” is
often used to describe this eruption, but morbilliform is a more precise
description. This is the most common type of drug rash. The eruption typically
starts on the trunk before spreading to involve the extremities and face, though
the mucous membranes are spared. The eruption can become diffuse and
confluent. Pruritus may be present.
A morbilliform drug eruption typically appears 7 to 14 days after medication
initiation, but in a previously sensitized patient it may appear within hours to days
of reexposure. Antibiotics, in particular penicillins ( Fig. 68.4 ), cephalosporins,
sulfonamides, and antiepileptics are common triggers.
A morbilliform drug eruption can be difficult to clinically distinguish from a
viral exanthem. One unique example is that of the morbilliform eruption that may
result from antibiotic administration, most commonly amoxicillin, during an
Epstein–Barr virus (EBV) infection. Although early studies reported an incidence
of 90% or more, a more recent study suggests that the true incidence is closer to
30%. This eruption, however, is not actually a drug hypersensitivity reaction
(DHR), but rather is a viral exanthem.
Treatment involves a balance between the severity of the eruption and the
importance of the causative medication. The rash is generally self-limited and
will resolve within 7 to 14 days of stopping the medication. However, if the rash
is mild and the medication is essential, then the medication can be continued with
close monitoring. Morbilliform drug eruptions do not progress into more severe

drug reactions, however, severe drug reactions may mimic a morbilliform drug
eruption early on. Therefore, an uncomplicated morbilliform drug eruption must
be distinguished from DHR, which has systemic involvement. If the eruption
appears within the first 2 weeks of starting a medication, then it is more likely to
be a morbilliform drug eruption. If the eruption is delayed by several weeks, then
DHR is more likely. The presence of additional clinical features, such as facial
edema and lymphadenopathy, and laboratory findings can also aid in


distinguishing the two entities. If needed, topical steroids can help provide
symptomatic relief of pruritus.

DRUG HYPERSENSITIVITY REACTION (DHR)/DRUG
REACTION WITH EOSINOPHILIA AND SYSTEMIC
SYMPTOMS (DRESS)
The cutaneous eruption of DHR, also known as drug reaction with eosinophilia
and systemic symptoms (DRESS), is a morbilliform eruption that starts on the
face and spreads cephalocaudally. Additional clinical findings and systemic
involvement distinguish DHR from a skin-limited morbilliform drug eruption.
Facial edema is present in approximately 76%, fever in 90%, and
lymphadenopathy in 54% of patients with DHR. In half of patients, there can be
mild mucosal involvement, more commonly the oral mucosa. Systemic
involvement commonly manifests with eosinophilia (95%) or atypical
lymphocytosis (67%) on complete blood count. Liver involvement is seen in 75%
of patients, and often presents as elevation of liver transaminases. In cases where
patients have a prolonged clinical course or when they appear systemically ill,
echocardiogram, renal function tests, and coagulation profiles should be checked
for cardiac, renal, and hepatic involvement. Thyroid involvement is usually
delayed in onset, so thyroid functions should be followed for 2 to 3 months after
the DHR.

FIGURE 68.1 Widespread transient erythematous edematous papules and plaques. (Reprinted
with permission from Fleisher GR, Ludwig S, Baskin MN. Atlas of Pediatric Emergency
Medicine . Philadelphia, PA: Lippincott Williams & Wilkins; 2004.)


FIGURE 68.2 Urticaria often appears as annular or polycyclic plaques with central clearing or
purpura. (Reprinted with permission from Burkhart C, Morrell D, Goldsmith LA, et al.
VisualDx: Essential Pediatric Dermatology . Philadelphia, PA: Lippincott Williams & Wilkins;
2009.)

FIGURE 68.3 A morbilliform eruption presents with erythematous macules and papules on the
trunk before spreading to the rest of the body. (Courtesy of George A. Datto, III, MD.)