IgA and IgG2 Deficiency Associated with Zonisamide Therapy: A Case Report

Abstract

Summary:Purpose: To report a previously undescribed adverse effect, IgA/IgG subclass deficiency associated with zonisamide (ZNS) therapy.Methods: Serum IgA and IgG subclass levels were determined by the turbidimetric immunoassay and enzymelinked immunosorbent assay, respectively, in a 2-year-old boy with postmeningitis sequelae who was treated by ZNS.Results: Four months after initiation of ZNS, combined deficiency of IgA and IgG2 was noted. After cessation of ZNS, serum IgA level was promptly increased. IgG2 level was gradually increased, but remained subnormal after 7 months.Conclusions: This case documents, for the first time, the action of ZNS on IgG immune system as well as IgA system.If patients with ZNS therapy showed IgA deficiency and recurrent infections, it is preferable to check serum IgG subclass concentrations as well. Key Words: ZonisamideEpilepsy-IgA deficiency-IgG subclass-Phenytoin.Secondary IgA deficiency has been reported in patients treated with various drugs such as epileptic drugs (AEDs), D-penicillamine, gold, and sulfasalazine (1,2). Combined deficiency of IgA and IgG subclasses has been observed in association with phenytoin (PHT) and sulfasalazine therapies (3,4). There have been only a few reports of IgA deficiency or low IgA levels in children treated with a new benzisoxazole AED: zonisamide (ZNS) (5,6). We report a patient who developed IgA and IgG2 subclass deficiency associated with ZNS therapy. CASE REPORTAt age 17 months, an otherwise healthy boy developed bacterial meningitis. He was treated with antibiotic agents and phenobarbital (PB). At that time, serum immunoglobulin levels were normal (Table 1). Because the boy had postmeningitis sequelae, i.e., spastic quadriplegia, epilepsy, and mental retardation, he was transferred to our division for rehabilitation. After discharge, he was treated with PB (40 mg/ day; serum concentration, 12.3 pglml) and muscle relaxants. At age 2 years 3 months, ZNS (80 mg/ day) was added to his regimen because of secondarily generalized seizures and increases in epileptic discharges on EEG. Four months after initiation of ZNS therapy, a deficiency in serum IgA (<5 mg/dl) and IgG2 (21.0 mg/dl; normal range at age 2-4 years; 58.5-292.1 mg/dl) levels was noted, with decreased serum levels of total IgG (379 mg/dl) ( Table 1). Serum IgG1, IgG3, and IgG4 concentrations were within normal ranges for children of his age (7) (normal range of IgG1, 390.2-955.2 mg/dl; normal range of IgG3,11.4-98.8 mg/dl; normal range of IgG4,1.2-76.7 mg/dl). Total IgG, IgA, and IgM concentrations were measured by turbidimetric immunoassay (8). IgG subclasses were determined by enzyme-linked immunosorbent assay (ELISA) (9). Three examinations during ZNS therapy consistently showed IgA deficiency and decreased total IgG levels. Serum concentration of ZNS was not in the toxic range (15.2 pglml). Because the patient showed no susceptibility to infections, intravenous y-globulin therapy was not initiated. Three weeks after discontinuation of ZNS therapy, serum IgA levels were nor...

Smoldering Myeloma Associated with Zonisamide Treatment.

“…One of the patients with immunoglobulin deficiency recovered after cessation of zonisamide (25). The present patient was incidentally found to have hyperproteinemia during a periodical health check and was subsequently diagnosed as having smoldering myelomain the early stage of the disease.…”

“…A few patients with IgA and/or IgG deficiency have been reported in association with zonisamide (24,25). One of the patients with immunoglobulin deficiency recovered after cessation of zonisamide (25).…”

IgA Deficiency and Other Immunodeficiencies Causing Mucosal Immunity Dysfunction

“…Both IgAD and CVID can be induced by drugs, including sulfasalazine, hydantoin, carbamazepine, and zonisamide (Farr et al, 1991;Truedsson et al, 1995;Maeoka et al, 1997). This observation also suggests that both disorders share common pathophysiological processes, such as transcription of constant region genes or class-switch recombination (Hammarström et al, 2000).…”

The Safety and Tolerability of Newer Antiepileptic Drugs in Children and Adolescents

“…[367,375,399] Reported immunodeficiencies include low IgA in one child and low IgA and IgG in another. [375,400] A study in 19 patients did not find a correlation between immunoglobulin levels and zonisamide dose or concentration. [401] Agranulocytosis and rash were both reported in one child.…”