Hypersensitivity reactions to antiepileptic drugs in children

Abstract

Background Antiepileptic drugs (AEDs) can cause hypersensitivity reactions in children. These reactions are mainly cutaneous, self‐limiting, and benign, but life‐threatening severe cutaneous adverse reactions can occur. Infections can lead to skin eruptions and mimic drug hypersensitivity reactions, if a drug is taken at the same time. The aims of our study were to confirm or rule out the diagnosis of hypersensitivity reactions to AEDs in children and to detect an infection which mimics these reactions. Methods A prospective survey was conducted in a group of 100 children with histories of hypersensitivity reactions to AEDs by performing patch tests, delayed‐reading intradermal test, and, in case of negative results, challenge test. In all children, a study was performed to detect infections by viruses or Mycoplasma pneumoniae. Results Maculopapular exanthema and delayed‐appearing urticaria were the most reported hypersensitivity reactions to AEDs. Sixty‐six (66%) of 100 children had confirmed hypersensitivity reactions to AEDs. Fifty‐nine children had positive patch test. No children had positive challenge tests. The most common AEDs causing hypersensitivity reactions were carbamazepine (45.4%) and lamotrigine (43.6%). Thirty‐two children had positive tests for viruses or M pneumoniae, and nine of them had also a positive allergy work‐up. Conclusion Considering that there are no specific tests to distinguish between a viral infection and hypersensitivity reactions to AEDs in the acute phase, a diagnostic work‐up should be performed in all children with suspected hypersensitivity reactions to AEDs, as well as infectious agent study, to remove a false label of hypersensitivity.

Delayed hypersensitivity to antiepileptic drugs in children

“…23 In addition to the chemical structure of the drug (aromatic rings), risk factors which are important for the development of HRs to AEDs include age and gender, history of previous AED reactions, viral infections, concomitant medications, and genetic factors. 1,2,24 Age-related differences in drug metabolism (the reduction in glucuronide conjugation in infants, faster rate of CYP-mediated reactions in infants and children) may result in an increase in hypersensitivity to AEDs in young children. 5,[25][26][27][28] Children younger than 5 years of age have up to 5 times higher risks for development of SCARs and rashes induced by AEDs.…”

“…It remains controversial as to whether the herpes viral infection or reactivation of the latent viral genome is a triggering cofactor, or a result of HR to the drug itself. 1,2 A few pediatric studies showed the significant associations between certain HLA alleles and AED-induced HRs such as in Thai children 37 HLA-A*01:01 and HLA-B*13:01 and PHB hypersensitivity, in 37,40 Specifically, several genomewide association study investigations from Han Chinese (Taiwan), 41 European, 40,41 Canadian (mixed ethnicity), 39 Spanish Romani, 42 and Korean 43 confirmed a strong HLA-A* 31:01 association with CBZ-induced DRESS and/or MPE, but not for SJS/TEN.…”

“…Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, a condition which affects approximately 10 million children globally. [1][2][3] [1][2][3] Hypersensitivity reactions (HRs) to AEDs are mainly cutaneous and occur in 3% to 16% of children receiving anticonvulsants. 4 The most common cutaneous reactions are generalized maculopapular exanthema (MPE) and delayed urticaria.…”

“…6 AEDs, in particular aromatic compounds (such as PHT, CBZ, OXC, PHB, and LTG), 7 are among the most frequent causes of life-threatening severe cutaneous adverse reactions (SCARs), which consist of Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and, very rarely, acute generalized exanthematous pustulosis (AGEP). [1][2][3]5,[8][9][10][11] Large pediatric series revealed that AEDs were the most frequently incriminated drug group associated with DRESS and SJS/TEN. [12][13][14][15][16][17] Although most cases were related to aromatic AEDs, including LTG, rare reports of SJS/TEN related to new generation AEDs such as LEV have been published.…”

Advances and novel developments in drug hypersensitivity diagnosis

“…Considering that there are no specific tests to distinguish between a viral infection and DHRs in the acute phase, a diagnostic work‐up should be performed to remove a false label of hypersensitivity 4 . DHRs diagnosis is complex, time consuming, needs to be done by trained staff, and it is not standardized for many drugs.…”