Predicting possible zonisamide hypersensitivity syndrome.
Zonisamide (ZNS) is an anticonvulsant (AC) that contains a sulpha moiety potentially triggering hypersensitivity syndrome reactions (HSR). The lymphocyte toxicity assay (LTA) is an in vitro drug rechallenge test, which is believed to reflect a decreased capacity of the individual to detoxify reactive metabolites. The study examined whether cross-reactivity is present between ZNS and other AC and/or sulphonamides and if this HSR may be predicted using the LTA. The second aim was to determine age-related differences in ZNS-induced HSR. LTA was previously validated in patients who received sulphamethoxazole (SMX) or AC.


METHODS
Forty adult patients who displayed clinical HSR to SMX (20) or AC (20) participated in the study. Each group was represented with an equal number of individuals above and below the age of 60. LTA-SMX, LTA-AC and LTA-ZNS from 20 patients who previously presented a clinical reaction to one of the drugs and who had a positive LTA result to the specific drug were compared with 20 individuals who received the same drugs but did not present reactions. Binary logistic regression was used to evaluate the statistical significance.


RESULTS
In vitro results correlated with the clinical diagnosis. LTA presented a significant difference (P < 0.0001) between control and hypersensitive patients. In each age group, only a single patient had a severe clinical manifestation of SMX-HSR. These individuals tested positive to both SMX and ZNS.


CONCLUSIONS
Sulphamethoxazole-HSR but not AC-HSR patients may present a cross-reactivity to ZNS-HSR. The use of LTA to predict a possible ZNS reaction is recommended for SMX-sensitive individuals who prescribed ZNS.
Neuman
Manuela G
MG
In Vitro Drug Safety and Biotechnology Laboratory, MaRS Discovery Centre, University of Toronto, Toronto, ON, Canada. manuela.neuman@utoronto.ca
Shear
Neil H
NH
Malkiewicz
Izabella M
IM
Kessas
Mona
M
Lee
Amy W
AW
Cohen
Lawrence
L
D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019937:Diagnostic Techniques and Procedures; D003875:Drug Eruptions / Q000175:diagnosis* / Q000209:etiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000175:diagnosis*; D005076:Exanthema / Q000139:chemically induced / Q000175:diagnosis; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013420:Sulfamethoxazole / Q000009:adverse effects / Q000378:metabolism; D055815:Young Adult; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide; D013420:Sulfamethoxazole