PURPOSE OF THE STUDY:
To evaluate outcomes of the diagnostic workup in pediatric patients with a history of mild nonimmediate reactions (NIR) (>6 h) to amoxicillin (AMX) or amoxicillin-clavulanic acid (AMX/CL) and who underwent a Drug Provocation Test (DPT) with the culprit drug.
STUDY POPULATION:
The study included 354 children with a history of mild NIR to AMX or AMX/CL who underwent DPT with the culprit drug at a single pediatric hospital. Patients with chronic urticaria, uncontrolled asthma, and severe cutaneous adverse reactions were excluded.
METHODS:
The study was a 5-year retrospective review examining children with a history of mild NIR to AMX or AMX/CL and underwent DPT to the culprit drug. NIR was defined as a reaction to the culprit drug occurring >1 h to 48 h. Diagnostic workup included delayed intradermal testing (IDT) to the culprit drug before DPT. Patients underwent a graded DPT (1/10 - 2/10 - 7/10 of the full dose [25 mg/kg] every 30 min) and observed for 2 h after last dose. Negative DPTs received a single full dose on the 2nd day and resumed twice daily dosing for 5 days. Lymphocyte transformation testing (LTT) was performed in DPT positive patients.
RESULTS:
Of the 354 patients, 34 (9.6%) had prior history of NIR to AMX and 320 (90.4%) to AMX/CLV. Before the index reaction, 60% previously tolerated the culprit drug. The mean age of index reaction was 4.8 years, whereas the mean latency period between index reaction and DPT was 2.5 years. All patients experienced a skin eruption with the index reaction: delayed urticaria (48.6%), maculopapular exanthem (17.2%), macular exanthema (9.3%), papular exanthema (6.5%), angioedema (4%), undefined rash (4%), and scarlatiniform or morbilliform rash (1.1%). Only 4 children had gastrointestinal symptoms, and no one had respiratory symptoms with the index reaction. Delayed IDT was negative in all but one child who had a positive late reading; however, DPT was continued in this patient. Of the 354 patients, only 23 (6.5%) had a positive DPT (2 AMX; 21 AMX/CL). Eleven out of 23 reacted within 2 h to 8 h of the last DPT dose on either day 1 or day 2. Eleven out of 23 reacted at home 24 h to 48 h after the last dose on day 5. Only one out of 23 reacted within 30 min of the 1/10 DPT dose. All 23 positive DPT reactions were mild and self-resolving or only required antihistamines. Results reinforced the poor utility of delayed IDT in NIR to AMX or AMX/CL. LTT was performed only on 16 of the 23 DPT positive patients and only 6 of 16 (37.5%) were positive.
CONCLUSIONS:
Given the overlap between immediate and NIR, it is appropriate to perform a graded DPT protocol in children experiencing reactions within 2 h to 6 h, whereas only conducting a single dose DPT for those reacting >6 hours. Collecting a thorough and accurate drug reaction history is crucial in determining the next steps for the DPT. Additionally, IDT and LTT did not predict reactivity. Even though the NPV for a prolonged DPT is almost comparable to the one for a single-day DPT, prolonged DPT is associated with a higher parental confidence about patient’s future intake of the culprit drug, when needed.
REVIEWER COMMENTS:
DPT remains the gold standard for confirmatory diagnosis of drug reactions. This retrospective study demonstrated that for mild NIR (>6 hours after last drug intake) to AMX or AMX/CL, a DPT with a single, 1-time therapeutic dose is safe to administer. Overall, it is important to personalize DPTs (graded versus single dose) to each patient’s case after risk-benefit evaluation based on a detailed reaction history.
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