Permanent intrinsic B cell immunodeficiency caused by phenytoin hypersensitivity.
We report a patient who, 3 weeks after initiation of therapy, experienced a hypersensitivity reaction to phenytoin manifested as rash, lymphadenopathy, elevated serum transaminase levels, and subsequent panhypogammaglobulinemia with IgG, 180 mg/dl (control range 639 to 1349); IgA, 15 mg/dl (control range 70 to 312); and IgM, 0 mg/dl (control range 56 to 352). Repeated in vitro lymphocyte analysis documented normal T cell-mediated immunity including T cell surface markers (E rosettes), lymphocyte proliferation after mitogen stimulation, and T cell phenotypes (T4 or helper and T8 or suppressor cells). However, the patient had a paucity of circulating B-lymphocytes as assessed by the number of lymphocytes with surface membrane immunoglobulin (patient value of 0 compared to the control range 16 to 435 cells per microliter of blood) and by the number of lymphocytes bearing the B1 antigen (patient value of 13 compared to the control range 48 to 358 cells per microliter of blood). Hemolytic plaque assay revealed decreased immunoglobulin production (number of immunoglobulin-secreting cells per million circulating mononuclear cells) as compared to control subjects (patient unstimulated mean of 100 as compared to a control mean of 1753) and minimal enhancement on stimulation with pokeweed mitogen (patient stimulated mean of 250 as compared to control mean of 8946). Coculture experiments with the reverse hemolytic plaque assay revealed no evidence of suppression. No reversal of this patient's immunodeficiency has occurred 3 years after phenytoin withdrawal.
Guerra
I C
IC
Fawcett
W A
WA
Redmon
A H
AH
Lawrence
E C
EC
Rosenblatt
H M
HM
Shearer
W T
WT
D000328:Adult; D000361:Agammaglobulinemia / Q000209:etiology; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology*; D004342:Drug Hypersensitivity / Q000150:complications* / Q000209:etiology; D004834:Epilepsy, Post-Traumatic / Q000188:drug therapy; D006462:Hemolytic Plaque Technique; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007136:Immunoglobulins / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000139:chemically induced*; D008214:Lymphocytes / Q000145:classification; D008297:Male; D010672:Phenytoin / Q000009:adverse effects* / Q000627:therapeutic use; D012397:Rosette Formation
D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D010672:Phenytoin