Life-Threatening Drug Eruptions in Pediatrics

During a presentation titled “Severe Cutaneous Adverse Reactions (SCAR): Life-Threatening Drug Eruptions in the Pediatric Population,” Robert Sidbury, MD, MPH, of Seattle Children’s Hospital and the University of Washington, highlighted several life-threatening medication reactions, and he also reviewed less serious “mimics” such as urticaria multiforme, serum sickness like reaction, and erythema multiforme.

When treating severe, possibly life-threatening cutaneous reactions in children, “the stakes are high, and it is a fraught evaluation,” Sidbury said, since the same symptoms can appear with a minor or major condition.

Fever and rash can either be harmless or life-threatening, he said, with causes ranging from bug bites and drug rash to graft-versus-host disease to tick-borne illness or even Kawasaki disease.

Sidbury recommended an “ABC approach” during diagnosis:

• A: Appearance (Does the child look sick?)
• B: B cells/T cells (Consider immunosuppression.)
• C: Contacts (for example, tick contact)
• D: Drugs (Has there been exposure to any high-risk medications?)
• E: Ecchymosis or petechia
• F: fever for five days

Sidbury and colleagues map the following factors when making a diagnosis: medications (high risk versus low risk); timing of fever, rash, itching, and eosinophilia versus atypical lymphocytosis; and morphology, including involvement of mucous membranes.

“There’s no such thing as low risk,” he said. “Any drug can cause any morphology.”

Using case studies, Sidbury also reviewed several important skin reactions. Serum sickness like reaction often is caused by antibiotics and can result from vaccinations, so clinicians should be aware of recent immunizations. The reaction usually involves fever, rash, arthritis, and edema, as well as possible urticarial eruptions with bruising and facial edema. Onset is one to three weeks after medication exposure, and the reaction resolves in two to four weeks.

Giant urticaria (also known as urticaria multiforme) is another common reaction, generally occurring after an infection in patients aged 1 to 5 years. Although children are not very sick, the rash is often dramatic, which is usually the reason they are brought to emergency department. Of note, urticaria does not blister. It can be challenging to distinguish this from a serum sickness-like reaction, although it is more important to distinguish both from other conditions (e.g., erythema multiforme).

Sidbury also reviewed mycoplasma-induced rash and mucositis, which has very little skin involvement and generally has an infectious trigger that should be the target of treatment. Kawasaki disease, he said, often presents with non-exudative conjunctivitis and a polymorphic rash that is not blistering, unlike Stevens-Johnson syndrome. Drug rash with eosinophilia and systemic symptoms (DRESS) may occur three to four weeks after drug exposure, according to Sidbury. However, he stressed that 40% of children with DRESS do not have eosinophilia. Autoimmune thyroid dysfunction, which can occur four to 12 weeks after discharge, is an important consideration for allergists treating patients with DRESS.

For practitioners, Sidbury offered some tips: Always consider whether the rash started on the outside of the body and worked its way in, or vice versa. Children and caregivers should receive general counsel that if they take any new medication by mouth and unfamiliar symptoms develop, they should STOP the medication and call the prescribing doctor.