Acta Paediatr 81: 646-8. 1992
CASE REPORT
Phenytoin-induced IgG2 and IgG4 deficiencies in a patient with epilepsy A Ishizaka, M Nakanishi, E Kasahara, K Mizutani, Y Sakiyama and S Matsumoto Department of Pediatrics. Hokkaido University School of Medicine. Sapporo, Japan
Ishizaka A, Nakanishi M, Kasahara E, Mizutani K, Sakiyama Y, Matsumoto S. Phenytoin-induced IgG2 and IgG4 deficiencies in a patient with epilepsy. Acta Paediatr 1992;8:646-8. Stockholm. ISSN 0803-5253 A five-year-old girl with epilepsy and recurrent respiratory infections was investigated for serum IgG subclass concentrations. She was diagnosed as having a combined deficiency of IgG2 and IgG4 with a decreased serum concentration of IgA and IgG3 and was given replacement therapy with iv immunoglobulins. Since then, she has been free from respiratory infections. After phenytoin therapy was stopped, IgG subclass deficiency improved. This case describes the further action of phenytoin on the immune system, adding IgG subclass deficiency to the list. 0 IgG subclass deficiency, iu immunoglobulin, phenytoin A Ishizaka, Department of Pediatrics, Hokkaido University School of Medicine, NI5 W7,Sapporo, 060, Japan
Approximately 5% of epileptic patients treated with phenytoin develop an IgA deficiency, whereas serum IgM and total IgG concentration are usually normal (1, 2). However, the IgG antibody response to viral and bacterial antigens is changed in some patients receiving phenytoin, implying the existence of an imbalance in serum IgG subclass levels (3,4). This report describes a phenytoin-induced combined deficiency of IgG2 and IgG4 in a patient with epilepsy.
Case report In August 1987, a five-year-old girl was admitted to the hospital because of fever and respiratory tract infection and presented for evaluation of recurrent pneumonia. Between the ages of one and four years she had been treated with valproic acid to control febrile convulsions. At four years of age (in December 1985), phenytoin was added when she was diagnosed as having a primary generalized seizure. Serum IgG, IgA, IgM and IgG subclass concentrations were normal and no susceptibility to respiratory infections was noticed (Table 1). In April 1987, she had the first episode of pneumonia caused by Haemophilus injluenzae. In four subsequent months she had two episodes of otitis media and three episodes of pneumonia caused by organisms having capsular polysaccharide antigens. She was treated with antibiotics. Iv immunoglobulins (IVIG) were not administered. On admission in August 1987, chest X-ray showed a pneumonic infiltrate. Streptococcus pneumoniae were identified in sputum and throat cultures. Laser nephelo-
metry showed subnormal levels of IgG and IgA with normal levels of IgM. Lymphocyte subset analysis revealed normal numbers of CD3 +(68.3%), CD4+(43.0%), CD8+(25.6%) and CD20+(12.0%) cells. Five different samples obtained from July to August 1987 were used to determine IgG subclass levels by IgG subclass-specific monoclonal antibodies using ELISA (5). Neither IgG2 nor IgG4 was detectable in the sera. The serum concentration of IgG3 was lower than that of a healthy control. Two representative samples before initiation of IVIG treatment (e.g. July and August 1987) are shown in Table 1. A specific IgG2 antibody level to Pneumovax measured by ELISA was also deficient ( < 1 pg/ml in July 1987; normal range in age-matched controls (mean &-SD) 1 1.6f4.1 pg/ml) (6). Thus, she was diagnosed as having a combined deficiency of IgG2 and IgG4 with a decreased serum concentration of IgA and IgG3 and was given replacement therapy with WIG. Since then, her serum IgG2 and IgG4 levels have been detectable with the increase in IgG3 level. Specific IgG2 antibody to Pneumovax immediately after IVIG infusion was higher than that of healthy control subjects (32.0 pg/ml in August 1987). Following the institution of IVIG therapy, she has been successfully controlled and has been free from respiratory infections. In September 1987, epileptic seizures became so intractable that phenytoin treatment was stopped and clonazepam, carbamazepine and phenobarbital were given. After phenytoin therapy was stopped, the concentration of serum IgA increased gradually. In April 1988, IVIG replacement therapy was stopped because serum IgA concentration had been maintained
Phenytoin-induced IgG2 and IgG4 dejciency
ACTA PEDIATR 81 (1992)
647
Table I . Serum concentrations of immunoglobulins (g/l).
IgG subclassa Date of sample (WIG therapy)
Dec 1985b July 1987 Aug 1987 Before Aftef Sept 1987d Before Aft& Nov 1987 Before After June 1988‘ Dec 1988 May 1990 Normal range in age-matched children
IgG
IgA
IgM
11.0
1.60
2.65
6.2
0.20
3.95
IgG 1
IgG2
IgG3
IgG4
9.6
< 0.02
0.17
< O.OOO5
7.0 12.5
c 0.02 2.00
0.04 0.42
CASE REPORT
Phenytoin-induced IgG2 and IgG4 deficiencies in a patient with epilepsy A Ishizaka, M Nakanishi, E Kasahara, K Mizutani, Y Sakiyama and S Matsumoto Department of Pediatrics. Hokkaido University School of Medicine. Sapporo, Japan
Ishizaka A, Nakanishi M, Kasahara E, Mizutani K, Sakiyama Y, Matsumoto S. Phenytoin-induced IgG2 and IgG4 deficiencies in a patient with epilepsy. Acta Paediatr 1992;8:646-8. Stockholm. ISSN 0803-5253 A five-year-old girl with epilepsy and recurrent respiratory infections was investigated for serum IgG subclass concentrations. She was diagnosed as having a combined deficiency of IgG2 and IgG4 with a decreased serum concentration of IgA and IgG3 and was given replacement therapy with iv immunoglobulins. Since then, she has been free from respiratory infections. After phenytoin therapy was stopped, IgG subclass deficiency improved. This case describes the further action of phenytoin on the immune system, adding IgG subclass deficiency to the list. 0 IgG subclass deficiency, iu immunoglobulin, phenytoin A Ishizaka, Department of Pediatrics, Hokkaido University School of Medicine, NI5 W7,Sapporo, 060, Japan
Approximately 5% of epileptic patients treated with phenytoin develop an IgA deficiency, whereas serum IgM and total IgG concentration are usually normal (1, 2). However, the IgG antibody response to viral and bacterial antigens is changed in some patients receiving phenytoin, implying the existence of an imbalance in serum IgG subclass levels (3,4). This report describes a phenytoin-induced combined deficiency of IgG2 and IgG4 in a patient with epilepsy.
Case report In August 1987, a five-year-old girl was admitted to the hospital because of fever and respiratory tract infection and presented for evaluation of recurrent pneumonia. Between the ages of one and four years she had been treated with valproic acid to control febrile convulsions. At four years of age (in December 1985), phenytoin was added when she was diagnosed as having a primary generalized seizure. Serum IgG, IgA, IgM and IgG subclass concentrations were normal and no susceptibility to respiratory infections was noticed (Table 1). In April 1987, she had the first episode of pneumonia caused by Haemophilus injluenzae. In four subsequent months she had two episodes of otitis media and three episodes of pneumonia caused by organisms having capsular polysaccharide antigens. She was treated with antibiotics. Iv immunoglobulins (IVIG) were not administered. On admission in August 1987, chest X-ray showed a pneumonic infiltrate. Streptococcus pneumoniae were identified in sputum and throat cultures. Laser nephelo-
metry showed subnormal levels of IgG and IgA with normal levels of IgM. Lymphocyte subset analysis revealed normal numbers of CD3 +(68.3%), CD4+(43.0%), CD8+(25.6%) and CD20+(12.0%) cells. Five different samples obtained from July to August 1987 were used to determine IgG subclass levels by IgG subclass-specific monoclonal antibodies using ELISA (5). Neither IgG2 nor IgG4 was detectable in the sera. The serum concentration of IgG3 was lower than that of a healthy control. Two representative samples before initiation of IVIG treatment (e.g. July and August 1987) are shown in Table 1. A specific IgG2 antibody level to Pneumovax measured by ELISA was also deficient ( < 1 pg/ml in July 1987; normal range in age-matched controls (mean &-SD) 1 1.6f4.1 pg/ml) (6). Thus, she was diagnosed as having a combined deficiency of IgG2 and IgG4 with a decreased serum concentration of IgA and IgG3 and was given replacement therapy with WIG. Since then, her serum IgG2 and IgG4 levels have been detectable with the increase in IgG3 level. Specific IgG2 antibody to Pneumovax immediately after IVIG infusion was higher than that of healthy control subjects (32.0 pg/ml in August 1987). Following the institution of IVIG therapy, she has been successfully controlled and has been free from respiratory infections. In September 1987, epileptic seizures became so intractable that phenytoin treatment was stopped and clonazepam, carbamazepine and phenobarbital were given. After phenytoin therapy was stopped, the concentration of serum IgA increased gradually. In April 1988, IVIG replacement therapy was stopped because serum IgA concentration had been maintained
Phenytoin-induced IgG2 and IgG4 dejciency
ACTA PEDIATR 81 (1992)
647
Table I . Serum concentrations of immunoglobulins (g/l).
IgG subclassa Date of sample (WIG therapy)
Dec 1985b July 1987 Aug 1987 Before Aftef Sept 1987d Before Aft& Nov 1987 Before After June 1988‘ Dec 1988 May 1990 Normal range in age-matched children
IgG
IgA
IgM
11.0
1.60
2.65
6.2
0.20
3.95
IgG 1
IgG2
IgG3
IgG4
9.6
< 0.02
0.17
< O.OOO5
7.0 12.5
c 0.02 2.00
0.04 0.42
