Reported cases of hypersensitivity syndrome due to medicines exposure in the central Portugal pharmacovigilance unit: ten years case review

C. A. Fontes Ribeiro1,2, N. Craveiro1,3, C. Alves1,4, F. Batel Marques1,3. 1AIBILI, Central Portugal Regional Pharmacovigilance Unit, Portugal, 2School of Medicine, University of Coimbra, Pharmacology and Experimental Therapeutics, Portugal, 3School of Pharmacy, University of Coimbra, Pharmacology, Portugal, 4University of Beira Interior, CICS-UBI – Health Sciences Research Centre, Portugal

Introduction: The hypersensitivity syndrome (HS) after drug exposure is a rare but potentially fatal adverse drug reaction (ADR). The aim of this study was to review all the HS reported to the central Portugal regional pharmacovigilance unit (UFC).

Methods: The 1722 spontaneous reports (SR) received at the UFC between 2001 and 2010 were searched for all clinical conditions associated with HS. ADRs were classified according to their severity and previously knowledge. Patient gender and age, suspected drug, therapeutic indication, date of exposure, date of first and last ADR symptoms and case narrative were extracted from UFC data. All SmPC were analyzed.

Results: 21 cases have matched the inclusion criteria. Allopurinol accounts for 42.9% of the included cases, carbamazepine for 38.1%, phenobarbital for 4.7%, sulfassalazine for 4.7%, strontium ranelate for 4.7% and docetaxel for 4.7%. Median age of the patients were 59.5 years (17 to 75) and 73.7% were female. Median time between drug exposure and ADR was 28 days (2 to 85) and the median time since the beginning of the first symptoms and the final outcome was 28 days (15 to 60). All 21 patients experience a cutaneous disorder (exanthema–16, purpuric rash–1, descamative lesion–1, non-specific-3), 90.5% experience fever, 71.4% eosinophilia, 100% a hepatic disorder, 47.6% adenopathies, 9.5% renal failure and 4.7% respiratory failure; 15 cases match DRESS clinical criteria. Seven patients with carbamazepine therapy were submitted to patch testing, resulting in 6 positive and 1 inconclusive results. In patients with allopurinol therapy, 4 were submitted to patch testing resulting in 3 negative results and 1 slight positive (with allopurinol 10%). All patients were hospitalized due to the ADR, 1 resulting in death and 4 in a life threatening condition. HS was an identified entity in the carbamazepine, strontium ranelate and phenobarbital SmPCs, but not in those of allopurinol or sulfassalazine.

Conclusions: The identified cases suggest a strong association between HS and exposure to suspected drugs. Healthcare providers should be aware of delayed ADRs, since an early diagnosis is critical to the final outcome.