- Email: [email protected]
COELIAC DISEASE AND MALIGNANCY
771 TOXIC NEUROLOGICAL REACTION TO LITHIUM/THIORIDAZINE
SEROLOGICAL STUDIES (AS RECIPROCAL TITRE FOR ANTIBODIES AND IN IMMUNOGLOBULIN
mg/dl) FOR
SIR,-A 45-year-old woman with a 24-year history of manicdepressive psychosis had been maintained on lithium, with plasma levels ranging from 0’ 79 to 1 - 24 mmol/1. She was prescribed thioridazine 50 mg twice daily for treatment of an acute hypomanic episode. In association with a urinary tract infection her plasma lithium level rose briefly to 1.64 mmol/1 so the lithium was discontinued. 2 days later, she had severe choreoathetoid movements, akathisia, orofacial dyskinesia, and bruxism. Her plasma lithium at this time was 033 mmol/1. Treatment with procyclidine 10 mg three times daily was started and her symptoms subsided after 6 days. Less marked movement disorders, including minor orofacial dyskinesia and posturing persisted for 4 weeks. An EEG at the time and a subsequent computerised tomographic scan were normal. There was no prior indication of receptor hypersensitivity. The patient had previously been treated with combinations of lithium (plasma levels 0-57-0-71 mmol/1) and thioridazine (50 mg three times daily), of lithium (plasma levels 0 - 51 mmol/1) and chlorpromazine (200 mg three times daily), and of lithium (plasma levels 0’73-0,93 mmol/1) and haloperidol (10 mg three times daily) with no adverse reactions. No persistent effects have been observed. Toxic neurological reactions to combined lithium/neuroleptic treatment have been reported, 1,2 especially in association with high 3 plasma lithium levels and high doses of haloperidol. Spring3 described four cases of severe neurotoxicity (seizures, delirium, encephalopathy, and highly abnormal EEGs) associated with lithium/thioridazine. Thomas4described a case associated with lithium/haloperidol in a patient who had previously been given this drug combination without the development of neurotoxicity. The choreoathetoid movements observed in our case are not associated with typical lithium/neuroleptic neurotoxicity.I-3 The improvement noted with the introduction of procyclidine differs from the limited response observed by Loudon and Waring.2It is interesting that the patient had previously received lithium/ thioridazine and other lithium/neuroleptic combinations without observable interaction. Department of Psychiatry, St James’s University Hospital, Leeds LS9 7TF
H. M. A. S. STANDISH-BARRY M. A. SHELLY
the normal mean plus 2 SD in 12 patients and partial IgM deficiency (less than the normal mean minus 2 SD) occurred in another 12 patients. An immunoregulatory defect was probably responsible for the immunoglobulin perturbations. The finding of active EBV in these patients prompts us to recommend additional EBV-specific immune studies and the evaluation by EBV genome probes of the fresh tissue removed at surgery.4 The cellular origin of the malignancies in coeliac disease could be best determined in fresh suspension or frozen sections of the malignant tissues. Our laboratory would be pleased to assist in the evaluation of these patients for EBV. Department of Pathology and Laboratory Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105, USA
DAVID T. PURTILO
Galway Regional Hospital, Galway, Ireland
JOHN GREALLY
VASCULAR IgA AND C3 DEPOSITION IN GASTROINTESTINAL TRACT OF PATIENTS WITH HENOCH-SCHONLEIN PURPURA
SiR,-That
cutaneous
and renal lesions of Henoch-Schonlein
(HSP) are mediated by immunological mechanisms is supported by sevekal lines of evidence, including the simultaneous deposition of immunoglobulins (predominantly IgA), complement components (C3), and fibrin/fibrinogen in diseased cutaneous vessel walls and glomerular mesangium;5,6 the possible occurrence of circulating IgA immune complexes;and the reported benefit of plasmapheresis in HSP nephropathy.s While gastrointestinal manifestations of HSP are well-known clinically, their pathogenesis remains unclear. Deposits of immunoglobulins in affected gut have been reported in two cases.9,10 purpura
COELIAC DISEASE AND MALIGNANCY
SIR,-We wish to offer a hypothesis concerning the malignant lymphomas complicating coeliac disease in patients described by Dr Swinson and colleagues (Jan 15, p 111).One of us (D. T. P.) became interested in the possibility that Epstein-Barr virus (EBV) might be aetiological in the malignant lymphomas occurring predominantly in the small intestine of patients with coeliac disease. Lymphomas in 26 of 35 patients with the X-linked lymphoproliferative syndrome located in the terminal ileum.All of the tumours were of a B cell origin whereas Swinson et al described malignant histiocytosis as being responsible for 90% of the cases in coeliac disease. To ascertain the possible role of EBV in genesis of lymphoma in coeliac disease we studied sera from 53 patients from the Galway area, including 27 women and 22 men; a further 3 women and 1 man had coeliac disease complicated by malignant lymphoma. All 53 patients and 90% of our adult controls were seropositive. 9 patients showed reactivation (ie, anti-EA). The patients with the malignant lymphomas showed reactivation and defective antiEBNA, possibly reflecting T cell defects.2,3 Serum IgA was above
were
1 Cohen WJ, Cohen NH. Lithium carbonate, haloperidol and irreversible brain damage. J Am Med Assoc 1974; 230: 1283. 2 London JB, Waring H. Toxic reactions to lithium and haloperidol. Lancet 1976; ii: 1088 3 Spring GK. Neurotoxicity with combined use of lithium and thiondazone. J Clin Psychiatry 1979; 40: 135. 4 Thomas CJ. Brain damage with lithium/haloperidol. Br J Psychiatry 1979; 134: 552.
1. Purtilo DT, Sakamoto, K, Barnabei V, et al. Epstein-Barr virus-induced diseases in males with the X-linked lymphoproliferative syndrome (XLP). Am J Med 1982; 73: 49-56.
2. Henle
W, Henle G, Horwitz, CA. Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Human Pathol 1974; 5: 551. 3. Harada S, Sakamoto K, Seeley JK, et al. Immune deficiency in the X-linked lymphoproliferative syndrome. I: Epstein-Bar virus-specific defects. J Immunol 1982; 129: 2532-34. 4. Purtilo DT, Sakamoto K, Semundsen AK, et al. Documentation of Epstein-Barr virus infection in immunodeficient patients with life-threatening lymphoproliferative disease by clinical, virological and immunopathological studies. Cancer Res 1981; 41: 4226-35.
5. Baart de la Faille-Kuyper EH, Kater L, Kooiker CJ, Dorhout Mees EJ. IgA deposits in cutaneous blood-vessel walls and mesangium in Henoch-Schonlein syndrome. Lancet 1973; i: 892-93. 6. Giangiacomo J, Tsai C. Dermal and glomerular deposition of IgA in anaphylactoid purpura. Am J Dis Child 1977; 131: 981-83. 7. Levinsky RJ, Barratt TM. IgA immune complexes in Henoch-Schönlein purpura. Lancet 1979; ii: 1100-03. 8. McKenzie PE, Taylor AE, Woodroffe AJ, Seymour AE, Chan YL, Clarkson AR. Plasmapheresis in glomerulonephritis. Clin Nephrol 1979; 12: 97-108. 9. Morichau-Beauchant M, Touchard G, Maire P, Briaud M, Babin P, Alcalay D, Matuchansky C. Jejunal IgA and C3 deposition in adult Henoch-Schönlein purpura with severe intestinal manifestations. Gastroenterology 1982; 82: 1438-42. 10. Stevenson JA, Leong LA, Cohen AH, Border WA. Henoch-Schönlein purpura: Simultaneous demonstration of IgA deposits in involved skin, intestine and kidney. Arch Pathol Lab Med 1982; 106: 192-95.
SEROLOGICAL STUDIES (AS RECIPROCAL TITRE FOR ANTIBODIES AND IN IMMUNOGLOBULIN
mg/dl) FOR
SIR,-A 45-year-old woman with a 24-year history of manicdepressive psychosis had been maintained on lithium, with plasma levels ranging from 0’ 79 to 1 - 24 mmol/1. She was prescribed thioridazine 50 mg twice daily for treatment of an acute hypomanic episode. In association with a urinary tract infection her plasma lithium level rose briefly to 1.64 mmol/1 so the lithium was discontinued. 2 days later, she had severe choreoathetoid movements, akathisia, orofacial dyskinesia, and bruxism. Her plasma lithium at this time was 033 mmol/1. Treatment with procyclidine 10 mg three times daily was started and her symptoms subsided after 6 days. Less marked movement disorders, including minor orofacial dyskinesia and posturing persisted for 4 weeks. An EEG at the time and a subsequent computerised tomographic scan were normal. There was no prior indication of receptor hypersensitivity. The patient had previously been treated with combinations of lithium (plasma levels 0-57-0-71 mmol/1) and thioridazine (50 mg three times daily), of lithium (plasma levels 0 - 51 mmol/1) and chlorpromazine (200 mg three times daily), and of lithium (plasma levels 0’73-0,93 mmol/1) and haloperidol (10 mg three times daily) with no adverse reactions. No persistent effects have been observed. Toxic neurological reactions to combined lithium/neuroleptic treatment have been reported, 1,2 especially in association with high 3 plasma lithium levels and high doses of haloperidol. Spring3 described four cases of severe neurotoxicity (seizures, delirium, encephalopathy, and highly abnormal EEGs) associated with lithium/thioridazine. Thomas4described a case associated with lithium/haloperidol in a patient who had previously been given this drug combination without the development of neurotoxicity. The choreoathetoid movements observed in our case are not associated with typical lithium/neuroleptic neurotoxicity.I-3 The improvement noted with the introduction of procyclidine differs from the limited response observed by Loudon and Waring.2It is interesting that the patient had previously received lithium/ thioridazine and other lithium/neuroleptic combinations without observable interaction. Department of Psychiatry, St James’s University Hospital, Leeds LS9 7TF
H. M. A. S. STANDISH-BARRY M. A. SHELLY
the normal mean plus 2 SD in 12 patients and partial IgM deficiency (less than the normal mean minus 2 SD) occurred in another 12 patients. An immunoregulatory defect was probably responsible for the immunoglobulin perturbations. The finding of active EBV in these patients prompts us to recommend additional EBV-specific immune studies and the evaluation by EBV genome probes of the fresh tissue removed at surgery.4 The cellular origin of the malignancies in coeliac disease could be best determined in fresh suspension or frozen sections of the malignant tissues. Our laboratory would be pleased to assist in the evaluation of these patients for EBV. Department of Pathology and Laboratory Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68105, USA
DAVID T. PURTILO
Galway Regional Hospital, Galway, Ireland
JOHN GREALLY
VASCULAR IgA AND C3 DEPOSITION IN GASTROINTESTINAL TRACT OF PATIENTS WITH HENOCH-SCHONLEIN PURPURA
SiR,-That
cutaneous
and renal lesions of Henoch-Schonlein
(HSP) are mediated by immunological mechanisms is supported by sevekal lines of evidence, including the simultaneous deposition of immunoglobulins (predominantly IgA), complement components (C3), and fibrin/fibrinogen in diseased cutaneous vessel walls and glomerular mesangium;5,6 the possible occurrence of circulating IgA immune complexes;and the reported benefit of plasmapheresis in HSP nephropathy.s While gastrointestinal manifestations of HSP are well-known clinically, their pathogenesis remains unclear. Deposits of immunoglobulins in affected gut have been reported in two cases.9,10 purpura
COELIAC DISEASE AND MALIGNANCY
SIR,-We wish to offer a hypothesis concerning the malignant lymphomas complicating coeliac disease in patients described by Dr Swinson and colleagues (Jan 15, p 111).One of us (D. T. P.) became interested in the possibility that Epstein-Barr virus (EBV) might be aetiological in the malignant lymphomas occurring predominantly in the small intestine of patients with coeliac disease. Lymphomas in 26 of 35 patients with the X-linked lymphoproliferative syndrome located in the terminal ileum.All of the tumours were of a B cell origin whereas Swinson et al described malignant histiocytosis as being responsible for 90% of the cases in coeliac disease. To ascertain the possible role of EBV in genesis of lymphoma in coeliac disease we studied sera from 53 patients from the Galway area, including 27 women and 22 men; a further 3 women and 1 man had coeliac disease complicated by malignant lymphoma. All 53 patients and 90% of our adult controls were seropositive. 9 patients showed reactivation (ie, anti-EA). The patients with the malignant lymphomas showed reactivation and defective antiEBNA, possibly reflecting T cell defects.2,3 Serum IgA was above
were
1 Cohen WJ, Cohen NH. Lithium carbonate, haloperidol and irreversible brain damage. J Am Med Assoc 1974; 230: 1283. 2 London JB, Waring H. Toxic reactions to lithium and haloperidol. Lancet 1976; ii: 1088 3 Spring GK. Neurotoxicity with combined use of lithium and thiondazone. J Clin Psychiatry 1979; 40: 135. 4 Thomas CJ. Brain damage with lithium/haloperidol. Br J Psychiatry 1979; 134: 552.
1. Purtilo DT, Sakamoto, K, Barnabei V, et al. Epstein-Barr virus-induced diseases in males with the X-linked lymphoproliferative syndrome (XLP). Am J Med 1982; 73: 49-56.
2. Henle
W, Henle G, Horwitz, CA. Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Human Pathol 1974; 5: 551. 3. Harada S, Sakamoto K, Seeley JK, et al. Immune deficiency in the X-linked lymphoproliferative syndrome. I: Epstein-Bar virus-specific defects. J Immunol 1982; 129: 2532-34. 4. Purtilo DT, Sakamoto K, Semundsen AK, et al. Documentation of Epstein-Barr virus infection in immunodeficient patients with life-threatening lymphoproliferative disease by clinical, virological and immunopathological studies. Cancer Res 1981; 41: 4226-35.
5. Baart de la Faille-Kuyper EH, Kater L, Kooiker CJ, Dorhout Mees EJ. IgA deposits in cutaneous blood-vessel walls and mesangium in Henoch-Schonlein syndrome. Lancet 1973; i: 892-93. 6. Giangiacomo J, Tsai C. Dermal and glomerular deposition of IgA in anaphylactoid purpura. Am J Dis Child 1977; 131: 981-83. 7. Levinsky RJ, Barratt TM. IgA immune complexes in Henoch-Schönlein purpura. Lancet 1979; ii: 1100-03. 8. McKenzie PE, Taylor AE, Woodroffe AJ, Seymour AE, Chan YL, Clarkson AR. Plasmapheresis in glomerulonephritis. Clin Nephrol 1979; 12: 97-108. 9. Morichau-Beauchant M, Touchard G, Maire P, Briaud M, Babin P, Alcalay D, Matuchansky C. Jejunal IgA and C3 deposition in adult Henoch-Schönlein purpura with severe intestinal manifestations. Gastroenterology 1982; 82: 1438-42. 10. Stevenson JA, Leong LA, Cohen AH, Border WA. Henoch-Schönlein purpura: Simultaneous demonstration of IgA deposits in involved skin, intestine and kidney. Arch Pathol Lab Med 1982; 106: 192-95.