Oxcarbazepine-Induced Immunoglobulin Deficiency

Abstract

We are reporting the first case of oxcarbazepine-induced immunoglobulin deficiency. Although this is known to be a rare adverse reaction to various pharmacologics (1,4,5), including the anticonvulsant carbamazepine (3, 6, 10, 11), it has not been previously described with oxcarbazepine.A 49-year-old white female was referred for further investigation of low serum immunoglobulins found as part of an evaluation for chronic bacterial vaginitis and suspected immune deficiency. Her infectious history was significant for one episode of pneumonia, several episodes of sinusitis, and chronic bladder infections.As a part of her immunologic evaluation, causes of secondary hypogammaglobulinemia were considered. She had no evidence of gastrointestinal protein loss and no evidence of malignancy and was not taking any immunosuppressive medications. She had been given oxcarbazepine (1,800-mg total daily dose), a derivative of the anticonvulsant carbamazepine, for chronic pain.At referral, immunoglobulin levels were low (immunoglobulin G [IgG], 576 mg/dl; IgA, Ͻ11 mg/dl; IgM, Ͻ4 mg/dl) and she had a B-cell deficiency (1%, 18 B cells/mm 3 [normal, 5 to 15%, 75 to 375 B cells/mm 3 ]). She maintained positive (immune) IgG responses to measles, rubella, mumps, tetanus, and diphtheria. Antibody responses 1 month after pneumococcal vaccination were poor (protective antibody, 1.3 g/ml, to only 2 out of 12 serotypes tested).Suspecting a potential adverse reaction to oxcarbazepine, this medication was discontinued; immunoglobulin levels and B-cell numbers remained low for at least 2 months. Her IgG and IgM levels returned to normal after 8 months (IgG, 977 mg/dl; IgA, Ͻ7 mg/dl; IgM, 62 mg/dl), with normalized B-cell numbers (5%; 85 B cells/mm 3 ), and remained normal at 12 months (IgG, 1,065 mg/dl; IgA, Ͻ15 mg/dl; IgM, 64 mg/dl; 113 B cells/mm 3 [7%]), with protective antibody responses to 5 out of 12 pneumococcal serotypes ( Fig. 1 and 2). She continued to have IgA deficiency. Her chronic pain returned with the discontinuation of oxcarbazepine.

Immunologic Evaluation in the Patients with Infantile Spasm

“…Eeg-Olofsson et al found low serum IgA in patients with focal, mainly temporal lobe epilepsy and lower levels of IgA (23.9%) were detected in another study consisting of the patients with IS and Lennox-Gastaut syndrome. [17][18][19] Because most of our IS cases were in the structural/metabolic, the etiological condition; hospitalization and nutritional deficiency due to hypoxic-ischemic encephalopathy, prematurity, and metabolic disorders could have resulted in immune disturbances ( Table 1). The previous antiepileptic treatment of our 5 IS cases consisted of phenobarbital (3), carbamazepine (1) and valproic acid (1).…”

Differences in epileptic symptoms depending on the type of autoimmune-mediated limbic encephalitis

“…For example, valproic acid inhibits histone deacetylation and potentially exerts immunomodulatory and anti-tumor effects [108][109][110]. Oxcarbazepine, a derivative of carbamazepine that also inhibits histone deacetylation [111], affects the immune system, especially the production of immunoglobulin, to improve the efficacy of anti-epilepsy therapy [112]. Clobazam is a derivative of benzodiazepine that is used to treat refractory epilepsy (particularly complex partial seizures with secondary generalized seizures) as a monotherapy or in combination with other drugs.…”

Common Variable Immunodeficiency

“…57,58 Other common medications associated with hypogammaglobulinemia include rituximab, azathioprine, sulfasalazine, and several anticonvulsants (carbamazepine, levetiracetam, oxcarbazepine, and phenytoin). 59–63…”

“…57,58 Other common medications associated with hypogammaglobulinemia include rituximab, azathioprine, sulfasalazine, and several anticonvulsants (carbamazepine, levetiracetam, oxcarbazepine, and phenytoin). [59][60][61][62][63] The physical examination of a patient with a suspected CVID requires an in-depth focus on the involved organ systems. The chest examination often may reveal wheezing, rhonchi, or crackles in patients with CVID-associated lung disease.…”