Pediatric emergency medicine trisk 328

DHR is a delayed-type hypersensitivity reaction that occurs 2 to 6 weeks, with
an average of 22 days, after starting a medication. Antiepileptics (carbamazepine,
phenytoin, phenobarbital, lamotrigine) are the most common cause of DHR.
Other medications that commonly cause DHR are trimethoprimsulfamethoxazole, minocycline, dapsone, sulfasalazine, and abacavir. There
appears to be a genetic susceptibility for developing DHR to certain medications.
For example, HLA-A*31:01 is associated with an increased risk of DHR
following exposure to carbamazepine in children. Other associations with DHR
include human herpesvirus-6 (HHV6), in which reactivation has been detected in
cases of DHR. Though the exact role of HHV6 in the pathogenesis of DHR is still
unclear, some evidence suggests that HHV6 reactivation creates immune
dysregulation that causes DHR, while others suggest that DHR-induced immune
dysregulation allows for HHV6 reactivation.
The main differential diagnosis for DHR includes a cutaneous-limited
morbilliform drug eruption, Kawasaki disease, and viral exanthem. The presence
of fever, facial edema, lymphadenopathy, and laboratory abnormalities
distinguishes DHR from a cutaneous-limited morbilliform eruption. The absence
of conjunctivitis and mucous membrane involvement suggests DHR rather than
Kawasaki disease. The initiation of a potential high-risk medication weeks before
rash onset increases the likelihood that an eruption is DHR rather than a viral
exanthem.


FIGURE 68.4 This morbilliform eruption presented several days after starting ampicillin
therapy. (Reprinted with permission from Elder DE, Elenitsas R, Rubin AI, et al. Atlas and
Synopsis of Lever’s Histopathology of the Skin . 3rd ed. Philadelphia, PA: Lippincott Williams
& Wilkins; 2012.)

The most important treatment for DHR is stopping the culprit medication. Oral
steroids can typically quickly stop progression of the disease by treating systemic
inflammation. Steroids should be tapered over several weeks to prevent a rebound
of the reaction.

PUSTULAR
Acute generalized exanthematous pustulosis (AGEP) is a less commonly seen
drug eruption in children. It presents with widespread erythema overlaid with
numerous pinpoint, superficial, sterile pustules ( Fig. 68.5 ). The pustules are
fragile and easily ruptured, leaving superficial areas of desquamation over the
background of erythema. The eruption frequently starts on the face or within skin
folds before rapidly spreading to the rest of the body. Fever is usually present,
while mucous membrane involvement is not seen.
AGEP presents within a few days of starting the triggering medication, usually
an antibiotic. In one study, pristinamycin, aminopenicillins, and quinolones were
the most common causes of AGEP, but cephalosporins, macrolides, clindamycin,
tetracycline, and terbinafine are other causes.
The differential diagnosis for AGEP includes DHR and pustular psoriasis.
Careful inspection for pustules or for areas of desquamation, indicating ruptured


pustules, in addition to laboratory evaluation, will help distinguish AGEP from
DHR. Eliciting either a personal or family history of psoriasis or a history of a
high-risk medication can help favor a diagnosis of either pustular psoriasis or
AGEP, respectively.
AGEP generally resolves with desquamation within 4 to 10 days after stopping
the drug. Topical steroids and oral antihistamines can provide symptomatic relief
if needed.

FIGURE 68.5 Erythema caloricum: back. (Courtesy of Benjamin Barankin, MD, Edmonton,
Alberta, Canada. In: Stedman’s Medical Dictionary for the Health Professions and Nursing . 7th
ed. Wolters Kluwer: Philadelphia, PA; 2012.)

VESICULOBULLOUS

Fixed Drug
Fixed drug eruption generally appears as a sharply demarcated erythematous to
dusky, edematous oval, or circular plaque ( Fig. 68.6 ). The plaques may become
bullous. Lesions can appear anywhere, but the lips, face, hands, feet, and genitals
are commonly affected. They often leave hyperpigmentation that may take


months to resolve. Although usually solitary, multiple or very large lesions may
form in fixed drug eruption following repeated exposure to the triggering
medication. The lesions can be pruritic, burning, or asymptomatic.
Initially, lesions appear within 2 weeks of starting a medication, but with
repeated exposure, onset can occur in minutes to hours. Sulfonamides,
particularly trimethoprim-sulfamethoxazole, are the most common causes of
fixed drug eruption in children ( Fig. 68.7 ), though NSAIDs and tetracycline are
also frequent causes. Some foods and food additives have also been reported to
cause fixed drug reactions.
Fixed drug eruption can often be confused for arthropod bites, urticaria, or EM.
The history of recurrence in the exact same location with prominent
postinflammatory hyperpigmentation is more suggestive of a fixed drug eruption
rather than arthropod bites. Similarly, fixed drug eruption is typically not as
pruritic as arthropod bites. As noted above, urticaria is transient, so individual
lesions resolve within 24 hours, with any residual pigmentation or purpura
resolving within days rather than the months that fixed drug eruption
hyperpigmentation may last. As compared to EM, the lesions of fixed drug
eruption are larger and fewer and occur in a different distribution.
Stopping and avoiding the causative medication allows for resolution of the
fixed drug eruption and prevents recurrence. A fixed drug eruption does not
progress to more severe drug eruptions, like DHR or Stevens–Johnson syndrome
(SJS). If needed, a topical steroid can treat pruritus.