I
I
Diphenylhydantoin-lnduced Hypogammaglobulinemia in a Patient Infected with Human Immunodeficiency Virus BRADLEY E. BRITIGAN, M.D., Iowa City, Iowa
A case is reported of reversible panhypogammaglobnlinemia in a hnmAn immunodeficiency virus (HIV)-infected patient. Onset and resolution were temporally correlated with initiation and termination, respectively, of diphenylhydantoin therapy for a possible seizure. A rapid alteration in peripheral T-cell subpopulations was also noted in association with diphenylhydantoin administration. This case is compared with previous reports of diphenylhydantoin-associated hypogAmmAglobulinemla in non-HIV-infected patients. In addition, the ease is discussed with regard to possible deleterious effects associated with the use of diphenylhydRntoin as therapy for HIV-associated seizures or as an antiretroviral agent in HIV disease.
From the Department of Internal Medicine, Veterans Administration Medical Center and The University of Iowa College of Medicine, Iowa City, Iowa. Requests for reprints should be addressed to Bradley E. Britigan, M.D.. Department of Internal Medicine, The University of Iowa, Iowa City, Iowa 52242. Manuscript submitted April 20, 1990, and accepted in revised form August 28, 1990.
524
April 1991 The American Journal of Medicine Volume 90
eizures have been a common sequela of neuro-
S logic diseases associated with human immunodeficiency virus (HIV) infection [1], often occurring in the absence of identifiable abnormalities of the central nervous system. It has been recommended that HIV-infected individuals receive anticonvulsant therapy after their first seizure unless a reversible precipitating factor can be identified [1]. Diphenylhydantoin has been a standard therapy for generalized seizure disorders for many years [2]. Among the side effects associated with diphenylhydantoin has been selective IgA deficiency [3-5]. However, panhypogammaglobulinemia has been reported infrequently [5,6-12]. An increased frequency of hypersensitivity reactions in HIV-infected patients treated with diphenylhydantoin has been recently reported [1]. However, specific details of these reactions were not described. The current communication reports a case of reversible hypogammaglobulinemia associated with initiation of diphenylhydantoin therapy in a previously hypergammaglobulinemic HIV-infected individual.
CASE REPORT The patient is a 27-year-old homosexual man who was found to be HIV-seropositive (enzyme-linked immunoassay and Western blot) in June 1986 when he was admitted to The University of Iowa Hospitals and Clinics (UIHC) for treatment of a drug overdose that was thought to represent a suicide attempt. He denied any history of intravenous drug use. During that admission, he was also noted to be infected with hepatitis B (hepatitis B surface antigen, E antigen, and core antibody positive). Laboratory studies of the patient's serum showed the following values: lactate dehydrogenase (LDH) 225 IU/L (normal: 100 to 225 IU/L), aspartate aminotransferase (AST) 50 IU/L (normal: 7.5 to 40.0 IU/ L), total bflirubin 0.9 mg/dL (normal: 0.26 to 1.00 mg/dL), gamma glutamyl transpeptidase (GGT) 28 IU/L (normal: 10 to 85 IU/L), and alkaline phosphatase (ALP) 95 IU/L (normal: 30 to 115 IU/L). At that time, he also had borderline hypergammaglobulinemia with total protein of 7.2 g/dL (normal: 6.0 to 8.0 g/dL), albumin of 3.7 g/dL (normal: 3.5 to 5.0 g/dL), and gammaglobulin of 1.7 g/dL (normal: 0.74 to 1.70 g/dL).
DIPHENYLHYDANTOIN-INDUCED HYPOGAMMAGLOBULINEMIA IN HIV DISEASE / BRITIGAN
TABLE I Course of the Patient's Immunoglobulin Levels, Liver Function Tests, and Lymphocyte Subsets Date
TP
AIb
6-02-86 6-12-86 1-06-88 12-25-88 6-14-89 6-21-89 7-26-89 8-23-89 9-22-89 10-25-89 1-10-90 3-28-90
7.0 7.2 7.3 5.9 5.6 5.7 6.6 6.9 6.6
4.4 3.7 3.9 3.2 4.0 4.0 3.9 4.1 3.6 3.6 3.9 4.2
7.2 7.5
-yG
IgM
IgG
IgA
IgE
AST
ALT
50
AP
GGT
TB
95
28
0.9
1,466 829 766 609
0.4 1.0 1.2 2.0 1.1 1.2 1.2 1.1 0.6 0.7
CD4
CD8
CD20
422
986
334
241
1,106
1.7
43
416
I
Diphenylhydantoin-lnduced Hypogammaglobulinemia in a Patient Infected with Human Immunodeficiency Virus BRADLEY E. BRITIGAN, M.D., Iowa City, Iowa
A case is reported of reversible panhypogammaglobnlinemia in a hnmAn immunodeficiency virus (HIV)-infected patient. Onset and resolution were temporally correlated with initiation and termination, respectively, of diphenylhydantoin therapy for a possible seizure. A rapid alteration in peripheral T-cell subpopulations was also noted in association with diphenylhydantoin administration. This case is compared with previous reports of diphenylhydantoin-associated hypogAmmAglobulinemla in non-HIV-infected patients. In addition, the ease is discussed with regard to possible deleterious effects associated with the use of diphenylhydRntoin as therapy for HIV-associated seizures or as an antiretroviral agent in HIV disease.
From the Department of Internal Medicine, Veterans Administration Medical Center and The University of Iowa College of Medicine, Iowa City, Iowa. Requests for reprints should be addressed to Bradley E. Britigan, M.D.. Department of Internal Medicine, The University of Iowa, Iowa City, Iowa 52242. Manuscript submitted April 20, 1990, and accepted in revised form August 28, 1990.
524
April 1991 The American Journal of Medicine Volume 90
eizures have been a common sequela of neuro-
S logic diseases associated with human immunodeficiency virus (HIV) infection [1], often occurring in the absence of identifiable abnormalities of the central nervous system. It has been recommended that HIV-infected individuals receive anticonvulsant therapy after their first seizure unless a reversible precipitating factor can be identified [1]. Diphenylhydantoin has been a standard therapy for generalized seizure disorders for many years [2]. Among the side effects associated with diphenylhydantoin has been selective IgA deficiency [3-5]. However, panhypogammaglobulinemia has been reported infrequently [5,6-12]. An increased frequency of hypersensitivity reactions in HIV-infected patients treated with diphenylhydantoin has been recently reported [1]. However, specific details of these reactions were not described. The current communication reports a case of reversible hypogammaglobulinemia associated with initiation of diphenylhydantoin therapy in a previously hypergammaglobulinemic HIV-infected individual.
CASE REPORT The patient is a 27-year-old homosexual man who was found to be HIV-seropositive (enzyme-linked immunoassay and Western blot) in June 1986 when he was admitted to The University of Iowa Hospitals and Clinics (UIHC) for treatment of a drug overdose that was thought to represent a suicide attempt. He denied any history of intravenous drug use. During that admission, he was also noted to be infected with hepatitis B (hepatitis B surface antigen, E antigen, and core antibody positive). Laboratory studies of the patient's serum showed the following values: lactate dehydrogenase (LDH) 225 IU/L (normal: 100 to 225 IU/L), aspartate aminotransferase (AST) 50 IU/L (normal: 7.5 to 40.0 IU/ L), total bflirubin 0.9 mg/dL (normal: 0.26 to 1.00 mg/dL), gamma glutamyl transpeptidase (GGT) 28 IU/L (normal: 10 to 85 IU/L), and alkaline phosphatase (ALP) 95 IU/L (normal: 30 to 115 IU/L). At that time, he also had borderline hypergammaglobulinemia with total protein of 7.2 g/dL (normal: 6.0 to 8.0 g/dL), albumin of 3.7 g/dL (normal: 3.5 to 5.0 g/dL), and gammaglobulin of 1.7 g/dL (normal: 0.74 to 1.70 g/dL).
DIPHENYLHYDANTOIN-INDUCED HYPOGAMMAGLOBULINEMIA IN HIV DISEASE / BRITIGAN
TABLE I Course of the Patient's Immunoglobulin Levels, Liver Function Tests, and Lymphocyte Subsets Date
TP
AIb
6-02-86 6-12-86 1-06-88 12-25-88 6-14-89 6-21-89 7-26-89 8-23-89 9-22-89 10-25-89 1-10-90 3-28-90
7.0 7.2 7.3 5.9 5.6 5.7 6.6 6.9 6.6
4.4 3.7 3.9 3.2 4.0 4.0 3.9 4.1 3.6 3.6 3.9 4.2
7.2 7.5
-yG
IgM
IgG
IgA
IgE
AST
ALT
50
AP
GGT
TB
95
28
0.9
1,466 829 766 609
0.4 1.0 1.2 2.0 1.1 1.2 1.2 1.1 0.6 0.7
CD4
CD8
CD20
422
986
334
241
1,106
1.7
43
416
