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|Year : 1981 | Volume
| Issue : 2 | Page : 116-9
Primary acquired hypogammaglobulinemia (a case report).
Agarwal MB, Sanzgiri PS, Mehta BC
|How to cite this article:|
Agarwal M B, Sanzgiri P S, Mehta B C. Primary acquired hypogammaglobulinemia (a case report). J Postgrad Med 1981;27:116
Acquired hypogammaglobulinemia is a relatively common disorder as against congenital immune deficiency which is rare. Many of these patients have a disease like thymoma, lymphoproliferative disorders, multiple myelomal or protein loosing enteropathy to account for the deficiency of humoral immunity. Primary acquired immunoglobulin deficiency is suspected when a patient who was asymptomatic in the first decade of life, suffers from recurrent suppurative infections and has hypogammaglobulinemia in the absence of the disorders, mentioned above and a normal or abnormal T cell function., We are reporting case who had primary acquired hypogamlobulinemia (PAH).
The humoral and cell mediated immunity was screened by using the following parameters:
(1) Humoral immunity: Paper electrophoresis was used for protein fractionation. Immunoglobulins were quantitated by single radial immunodiffusion technique of Mancini et al as adopted by Baxi et al using monospecific anti IgG, anti IgA and anti IgM. The levels of isoagglutinins were measured by the conventional double dilution technique as described by Bhatia. The antibodies to O and H antigen of S. typhi (Basal, fifteen days and one month after 2 intracutaneous doses of 0.1 ml of TAB vaccine at an interval of 10 days) were determined by the standard widal agglutination test. Serum tetanus antitoxin level (basal and 2 weeks after immunisation) was estimated by using passive hemagglutination technique as described by Levine et al. B-lymphocytes in the -peripheral blood were measured as cells with complement receptors by using the technique of Ehlenberger and Nussenweig as adopted by Gangal et al.
(2) Cell mediated immunity: The Dinitrochlorobenzene (DNCB-Eastman organic chemicals, NY) skin sensitization test was carried out and read as described by Catalona et al. Peripheral blood `T' lymphocytes were measured utilizing the surface receptor for sheep red blood cells by the E. rosette technique as described by Hoffman and Kunkel. In vitro blastic transformation index using phytohemagglutinin was estimated as per Valentine.
Besides these, histopathology of lymphnode biopsy after an antigenic stimulation was also studied.
S. Y., a 33 year old male patient was first seen by us in December 1979. He was a full term normal delivery from a non-consanguinous marriage. He had no illness till 1970 except for a bout of measles in 1962. In 1970, at the age of 23 years, he developed chickenpox from which he recovered uneventfully. Ever since then, he has had recurrent infections mainly in the form of purulent ear discharge, sinusitis, bronchitis, pneumonia and urinary tract infections. He also suffered from chronic mastoiditis needing radical mastoidectomy in 1975, a brain abscess needing evacuation and post-operative osteomyelitis of the skull bone in June 1976, recurrence of the brain abscess needing surgery in August 1976 and right sided empyema needing drainage in 1978. Besides these, he has had 3 episodes of viral hepatitis (confirmed by biochemical tests)) in 1974, 1975 and 1976, recurrent giardiasis and amoebiasis during 1976-79. Many of these infective episodes were treated with combination antibiotics with complete recovery. Patient had an episode of Steven-Johnson syndrome in April 1979 following septran and antipyretic therapy given for an episode of pulmonary infection. He had bilateral dry eczema over ankles and the legs i 1964-65 (at the age of 16-17 years) . He has 3 brothers and 1 sister and none of them or parents had any significant history. His general and systemic examinations were unremarkable. Investigations showed Haemoglobin to be 15.6 g/dl, PVC 48%, Retic 0.9%, WBC (T) 17500/cmm,, with differential count as N-74%, E--6%, L-18% and M-2%; platelets were 240,000/cmm, ESR was 2 mm at the end of one hour- R.BC morphology was normal, blood group was O' Rh +ve, Blood sugar was 82 mg%. BUN 10 mg%, S. Creatinine-0.8 mg%, Uric acid 3 mg% and Bilirubin 0.6 mg%. X-ray chest was normal; Serum proteins were 5.9 gm% with albumin of 3.5 gm% and globulin of 2.4 gm%. Estimation of immunoglobulins showed non-detectable IgM and IgA and a marked deficiency of IgG i.e. 290 mg%, (Normal: 690-1780 mg%). Isoantibodies in serum were absent and there was no response to TAB and tetanus toxoid vaccination. Indirect hemagglutination test for amoebiasis was negative. The counts of 'B' and `T' lymphocytes in the peripharal blood was 38% (Normal: 10-20%) and 60% (Normal 70-80%) respectively.
The lymphoblastic transformation test using phytohemagglutinin revealed an index of 36% (Normal: 30-70%) and the dinitrochlorobenzene contact sensitization test showed a grade 1V response (Normal). Histopathology of a lymphnode excised 15 days after an antigenic stimulus (injection of tetanus toxoid) revealed absence of germinal follicle and sinusoidal plasma cells together with a normal paracortical region (suggestive of ;deficiency of `B' cell dependent area together with a normal 'T' cell dependent area).
Patient is on prophylactic antibiotic therapy over last 3 months and he receives LM, immunoglobulins in doses of 30 c.c. at 4-6 weekly intervals
Acquired hypogammaglobulinemia is a much more common disorder than Bruton's disease. The diagnosis is usually based on the absence of infections in the first decade of life followed by occurrence of reccurrent pyogenic infections together with hypogammaglobulinemia. Many of these patients show progressive deterioration in their immune system including the T cell immunity., 
The pathogenesis of this disorder is unknown. An increase in suppressor 'T' cells has been postulated as a cause. Patients show either a failure of heavy chain glycosylation of IgG or a deficiency p of 5 nucleotidase. Majority of the cases show no clearcut genetic transmission, although occassional case with an autosomal recessive inheritance is on record.,  The presence of normal or increased number of circulating peripheral blood B lymphocytes (like in the present case) suggests that the disorder is a result of diminished synthesis or release of Ig rather than production of a fewer immunoglobulin-synthesizing cells., 
Recurrent chronic sino-bronchopulmonary infections caused by pyogenic organisms like Pneumococci and H. influenzae form the commenest mnifestations., ,  Malabsorption, autoimmune disorders like rheumatoid arthritis and pernicious anemia and malignant disorders including lymphoreticular hyperplasia,  is form important complications.
Giardiasis with or without malabsorption is common. Present patient developed Recurrent parasitic infestations of the gut despite therapy. A curious feature in this patient was the occurrence of a number of viral infections e.g. measles, chickenpox and 3 episodes of viral hepatitis despite a normal `T' cell function. Equally curious was the episode of Steven-Johnson Syndrome.
The laboratory investigations in these cases show a humoral deficiency while the cell mediated immunity may or may not be abnormal., Patients with normal cell mediated immunity should be followed up sequentially to detect additional deficiencies which may develop.
Treatment in these cases is not simple, although their IgG level is usually higher than that found in Bruton's disease. Regular replacement of large amount of I.M. gammaglobulin is extremely painful and costly. Development of intravenous preparations of gammaglobulin is a revolutionary change and it will certainly make the management simple.
We are thankful to Dr. C. K. Deshpande, Dean, Seth G.S. Medical College and K.E.M. Hospital for permission to publish this paper. We are also thankful to Dr. H. M. Bhatia and Dr. A. J. Baxi from Blood Group Reference Centre, Bombay, Dr. F. D. Dastur, Chief of the Tetanus Unit, K.E.M. Hospital, Dr. V. V. Joshi, Professor of Pathology, K.E.M. Hospital, Dr. S. H. Advani, Asstt. Professor of Medicine and Hematology, Tata Memorial Hospital and Dr. (Mrs.) S. G. Gangal, Chief, Division of Immunology, Cancer Research Centre and Tata Memorial Centre for their valuable help in investigation of this patient.
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