Results
Two hundred and nineteen children (48.9% boys; median [IQR] age, 8.4 years [4.8-12.4 years]) with cystic fibrosis were included in the study. The median age at diagnosis of CF was 3 (2-6) months; the duration of follow up was 5.8 (3.3-10.1) years (Table 1). Seventy-six (24.7%) patients carried at least one del F508 mutation whereas nearly half of the children were demonstrated to have other mutations. Some of the children were colonized chronically with Pseudomonas aeruginosa (n=36, 16.5%) and Staphylococcus aureus (n=56, 25.6%). Nearly all patients (99%) were using medications chronically (Table 2), 214 (97.7%) of them received at least one course of antibiotics within last year. One fourth of the patients had been administered at least one course of parenteral antibiotic treatment in hospital in the last 1 year.
Twenty-two patients were referred to the pediatric allergy department with 24 suspected drug related hypersensitivity reactions (Figure 1). The route of administration of these drugs were mainly oral (n=13) than parenteral (n=9). Most of the suspected DHRs were non-immediate (n=16, 66.6%) type and the offending drugs were amoxicillin clavulanic acid (n=7), macrolides (n=4), trimethoprim sulfamethoxazole (TMP/SMX) (n=2), piperacillin tazobactam (n=1), pancrelipase (n=1) and ursodeoxycholic acid (n=1). Eight (33.3%) of the DHRs were classified as immediate [ceftriaxone (n=2), ceftazidime (n=2), meropenem (n=1), ambisome (n=2), vancomycin (n=1)]. The presenting clinical presentations were maculopapular eruption (41.6%) and urticaria (37.5%), accompanied by angioedema (8.3%), flushing (12.5%) and vomiting (8.3%). None of the patients experienced anaphylaxis or severe cutaneous adverse reactions.
We performed 9 skin tests (with beta-lactam protocol in 6 patients) and 24 DPTs to determine the actual drug allergy (Figure 1). None of the skin tests revealed a positive result, however 2 DPTs with TMP/SMX were positive. Twelve-year-old boy (CF mutation Q720X/Q720X) developed generalized maculopapular eruption on second day of TMP/SMX treatment, after 3 to 4 hours of ultimate dose which resolved within two days of cessation of drug at ages of seven and eleven. The patient presented with maculopapular eruption again after six hours of DPT with TMP/SMX. Nine-year-old girl (CF mutation E92K) experienced generalized urticaria and angioedema of face, 4 hours after last dose of TMP/SMX, on day 3 of treatment. The HSR resolved with administration of antihistamine and systemic corticosteroid within 6 hours. The skin testing with TMP/SMX (0.8 mg/ ml) (18) demonstrated to be negative, nevertheless the DPT confirmed generalized urticaria had occurred two hours after administration of TMP/SMX, suggesting that the TMP/SMX was the culprit drug.
In summary, actual drug allergy was demonstrated in 2 of 219 patients (0.9%) with nonbeta-lactam antibiotics after diagnostic work up for DHRs. Due to low prevalence of actual drug allergy in our cohort, we were not able to define any risk factor for occurrence of DHRs in children with cystic fibrosis.