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Systemic amyloidosis complicating inflammatory bowel disease
August 1997
CORRESPONDENCE 731
Systemic Amyloidosis Complicating Inflammatory Bowel Disease Dear Sir: Lovat et al.1 discuss the long-term survival and regression of amyloidosis in their patients with Crohn’s disease complicated by systemic amyloidosis. This was accomplished by renal transplantation and its associated immunomodulating therapy. These results are encouraging. There is usually a very poor prognosis among this type of patient. I would like to remind the readers of the successes noted by other investigators in the therapy of inflammatory bowel disease complicated by amyloidosis, especially with the use of colchicine, which was not mentioned by Lovat et al. Overall, surgical therapy for these patients has been dismal. However, excision of the diseased bowel alone or combined surgical and medical therapy may delay or even halt the progression of renal amyloidosis.2 – 6 Resolution of the nephrotic syndrome, due to renal amyloidosis, also occurred when surgical resection of all diseased bowel was followed by colchicine therapy for a period of 5 years.7 There is experience with medical therapy alone. Three years of continuous therapy with azathioprine and sulfasalazine resulted in a clinical remission of the Crohn’s disease. Proteinuria decreased from ú5 g/day to normal 7 years later.8 Our group at The Mount Sinai Hospital, New York, described 2 patients with ulcerative colitis complicated by amyloidosis and nephrotic syndrome who were treated with colchicine.9 One patient experienced a 50% reduction in her daily protein excretion within 2 months from 13.70 to 6.50 g. This trend continued, reaching a level of 0.37 g 9 years later. Her renal function remained normal during this period. The second patient also responded quickly. Within several months, there was a marked decrease in the proteinuria. This continued during the 8 months of therapy. Proteinuria decreased to 0.53 g/day from a pretreatment level of 9 g. There was a marginal increase in creatinine clearance from 29 to 49 mL/min. During the period of colchicine therapy, both patients were treated medically for their ulcerative colitis. Because complete intestinal remissions were not obtained, it seems unlikely that the reduced proteinuria could be ascribed to any significant reduction in the underlying colitis of these patients. Whether the reduction of the proteinuria could be a result of spontaneous improvement of the amyloidosis is difficult to establish. However, such an occurrence is unusual.10 – 12 The mechanism of action of colchicine in the therapy of amyloidosis is unclear. I advise the initiation of colchicine therapy, for even asymptomatic systemic amyloidosis, in patients with inflammatory bowel disease. This may prevent, or at least delay, the transplantation required for the patients cited by Lovat et al.1 Others have suggested that their excellent results obtained with colchicine in preventing or reversing
/ 5e1f$$0014
07-08-97 09:37:27
gasa
the amyloidosis in familial Mediterranean fever and Crohn’s disease were attributed to the early stage when therapy was started.5,13 The evidence also supports the use of colchicine alone or as adjunctive therapy, despite more advanced amyloid-induced nephrotic syndrome.7,8,14 SAMUEL MEYERS, M.D.
Clinical Professor of Medicine Division of Gastroenterology, Department of Medicine Mount Sinai School of Medicine, City University of New York New York, New York 1. Lovat L, Madhoo S, Pepys MB, Hawkins PN. Long-term survival in systemic amyloidosis A complicating Crohn’s disease. Gastroenterology 1997;112:1362–1365. 2. Shorvon PJ. Amyloidosis and inflammatory bowel disease. Am J Dig Dis 1977;22:209–213. 3. Mandelbaum I, Bryk D. Idiopathic chronic uncerative colitis and amyloidosis. J Mt Sinai Hosp 1955;22:24–33. 4. Rashid H, Blake D, Gokal D, Gooptu D, Kerr DNS. The association of renal amyloidosis and regional enteritis: report of two cases and review of literature. Clin Nephrol 1980;14:154–157. 5. Fitchen JH. Amyloidosis and granulomatous ileocolitis: regression after surgical removal of the involved bowel. N Engl J Med 1975;292:352–353. 6. Mandelstam P, Simmons DE, Mitchell B. Regression of amyloid in Crohn’s disease after bowel resection. A 19-year follow-up. J Clin Gastroenterol 1989;11:324–326. 7. Ravid M, Schapira J, Kedar I, Feigl D. Regression of amyloidosis secondary to granulomatous ileitis following surgical resection and colchicine administration. Acta Hepatogastroenterol 1979; 26:513–515. 8. Verbanck J, Lameire N, Praet M, Ringoir S, Elewaut A, Barbier F. Renal amyloidosis as a complication of Crohn’s disease. Acta Clin Belg 1979;34:6–13. 9. Meyers S, Janowitz HD, Gumaste VV, Abramson RG, Berman LJ, Venkataseshan VS, Dickman SH. Colchicine therapy of the renal amyloidosis of ulcerative colitis. Gastroenterology 1988;94: 1503–1507. 10. Wallenstein J, Serebro HA, Calle S, Gann M. Chronic regional enteritis complicated by a nephrotic syndrome. JAMA 1966;198: 555–558. 11. Lowenstein J, Gallo G. Regression of the nephrotic syndrome in renal amyloidosis. N Engl J Med 1970;282:128–132. 12. Dikman SH, Churg J, Kahn T. Morphologic and clinical correlates in renal amyloidosis. Hum Pathol 1981;12:160–169. 13. Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J. Colchicine in the prevention and treatment of amyloidosis of familial Mediterranean fever. N Engl J Med 1986;314:1001–1005. 14. Ravid M, Robson M, Kedar I. Prolonged colchicine treatment in four patients with amyloidosis. Ann Intern Med 1977;87:568–577.
WBS-Gastro
CORRESPONDENCE 731
Systemic Amyloidosis Complicating Inflammatory Bowel Disease Dear Sir: Lovat et al.1 discuss the long-term survival and regression of amyloidosis in their patients with Crohn’s disease complicated by systemic amyloidosis. This was accomplished by renal transplantation and its associated immunomodulating therapy. These results are encouraging. There is usually a very poor prognosis among this type of patient. I would like to remind the readers of the successes noted by other investigators in the therapy of inflammatory bowel disease complicated by amyloidosis, especially with the use of colchicine, which was not mentioned by Lovat et al. Overall, surgical therapy for these patients has been dismal. However, excision of the diseased bowel alone or combined surgical and medical therapy may delay or even halt the progression of renal amyloidosis.2 – 6 Resolution of the nephrotic syndrome, due to renal amyloidosis, also occurred when surgical resection of all diseased bowel was followed by colchicine therapy for a period of 5 years.7 There is experience with medical therapy alone. Three years of continuous therapy with azathioprine and sulfasalazine resulted in a clinical remission of the Crohn’s disease. Proteinuria decreased from ú5 g/day to normal 7 years later.8 Our group at The Mount Sinai Hospital, New York, described 2 patients with ulcerative colitis complicated by amyloidosis and nephrotic syndrome who were treated with colchicine.9 One patient experienced a 50% reduction in her daily protein excretion within 2 months from 13.70 to 6.50 g. This trend continued, reaching a level of 0.37 g 9 years later. Her renal function remained normal during this period. The second patient also responded quickly. Within several months, there was a marked decrease in the proteinuria. This continued during the 8 months of therapy. Proteinuria decreased to 0.53 g/day from a pretreatment level of 9 g. There was a marginal increase in creatinine clearance from 29 to 49 mL/min. During the period of colchicine therapy, both patients were treated medically for their ulcerative colitis. Because complete intestinal remissions were not obtained, it seems unlikely that the reduced proteinuria could be ascribed to any significant reduction in the underlying colitis of these patients. Whether the reduction of the proteinuria could be a result of spontaneous improvement of the amyloidosis is difficult to establish. However, such an occurrence is unusual.10 – 12 The mechanism of action of colchicine in the therapy of amyloidosis is unclear. I advise the initiation of colchicine therapy, for even asymptomatic systemic amyloidosis, in patients with inflammatory bowel disease. This may prevent, or at least delay, the transplantation required for the patients cited by Lovat et al.1 Others have suggested that their excellent results obtained with colchicine in preventing or reversing
/ 5e1f$$0014
07-08-97 09:37:27
gasa
the amyloidosis in familial Mediterranean fever and Crohn’s disease were attributed to the early stage when therapy was started.5,13 The evidence also supports the use of colchicine alone or as adjunctive therapy, despite more advanced amyloid-induced nephrotic syndrome.7,8,14 SAMUEL MEYERS, M.D.
Clinical Professor of Medicine Division of Gastroenterology, Department of Medicine Mount Sinai School of Medicine, City University of New York New York, New York 1. Lovat L, Madhoo S, Pepys MB, Hawkins PN. Long-term survival in systemic amyloidosis A complicating Crohn’s disease. Gastroenterology 1997;112:1362–1365. 2. Shorvon PJ. Amyloidosis and inflammatory bowel disease. Am J Dig Dis 1977;22:209–213. 3. Mandelbaum I, Bryk D. Idiopathic chronic uncerative colitis and amyloidosis. J Mt Sinai Hosp 1955;22:24–33. 4. Rashid H, Blake D, Gokal D, Gooptu D, Kerr DNS. The association of renal amyloidosis and regional enteritis: report of two cases and review of literature. Clin Nephrol 1980;14:154–157. 5. Fitchen JH. Amyloidosis and granulomatous ileocolitis: regression after surgical removal of the involved bowel. N Engl J Med 1975;292:352–353. 6. Mandelstam P, Simmons DE, Mitchell B. Regression of amyloid in Crohn’s disease after bowel resection. A 19-year follow-up. J Clin Gastroenterol 1989;11:324–326. 7. Ravid M, Schapira J, Kedar I, Feigl D. Regression of amyloidosis secondary to granulomatous ileitis following surgical resection and colchicine administration. Acta Hepatogastroenterol 1979; 26:513–515. 8. Verbanck J, Lameire N, Praet M, Ringoir S, Elewaut A, Barbier F. Renal amyloidosis as a complication of Crohn’s disease. Acta Clin Belg 1979;34:6–13. 9. Meyers S, Janowitz HD, Gumaste VV, Abramson RG, Berman LJ, Venkataseshan VS, Dickman SH. Colchicine therapy of the renal amyloidosis of ulcerative colitis. Gastroenterology 1988;94: 1503–1507. 10. Wallenstein J, Serebro HA, Calle S, Gann M. Chronic regional enteritis complicated by a nephrotic syndrome. JAMA 1966;198: 555–558. 11. Lowenstein J, Gallo G. Regression of the nephrotic syndrome in renal amyloidosis. N Engl J Med 1970;282:128–132. 12. Dikman SH, Churg J, Kahn T. Morphologic and clinical correlates in renal amyloidosis. Hum Pathol 1981;12:160–169. 13. Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J. Colchicine in the prevention and treatment of amyloidosis of familial Mediterranean fever. N Engl J Med 1986;314:1001–1005. 14. Ravid M, Robson M, Kedar I. Prolonged colchicine treatment in four patients with amyloidosis. Ann Intern Med 1977;87:568–577.
WBS-Gastro