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Sulfasalazine

Adverse effects and desensitization

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Conclusion

It is clear that sulfasalazine plays a major role in the medical therapy of ulcerative colitis and Crohn's disease. In ulcerative colitis, continued sulfasalazine therapy prevents relapses. It is also apparent that this medication can cause a varied spectrum of adverse effects in 10–45% of the people who are dependent upon it. From this review, we know that the toxic manifestations of sulfasalazine can involve almost any organ system, and more recently described side effects related to the medication such as male infertility are just being recognized.

Awareness of the wide spectra of adverse effects of sulfasalazine and prompt appropriate measures might allow the patients to avoid major complications and obtain continued benefit from the drug. Although in some cases this may entail discontinuing the medication permanently, most often side effects can be remedied by temporary discontinuation of the drug and then reintroducing the drug very slowly up to a maintenance level not to exceed 2 g/day. A knowledge of the adverse effects of sulfasalazine as well as the indications for its use will allow physicians to provide better care for patients with inflammatory bowel disease.

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References

  1. Svartz N: Salazopyrin, a new sulfonilamide preparation. Acta Med Scand 110:557–598, 1942

    Google Scholar 

  2. Svartz N: The treatment of 124 cases of ulcerative colitis with salazopyrine and attempts at desensibilization in cases of hypersensitiveness to sulfa. Acta Med Scand (Suppl) 206:465–472, 1948

    Google Scholar 

  3. Dixon JS: Biochemical and clinical changes in rheumatoid arthritis: Their relation to the action of antirheumatoid drugs. Semin Arthritis Rheum 12:191–207, 1982

    Google Scholar 

  4. Bird HA, Dixon JS, Pickup ME, Rhind VM, Lowe JR, Lee MR, Wright V: A biochemical assessment of sulphasalazine in rheumatoid arthritis. J Rheumatol 9:36–45, 1982

    Google Scholar 

  5. Goldman P, Peppercorn MA: Salicylazosulfapyridine in clinical practice. Gastroenterology 65:166–169, 1973

    Google Scholar 

  6. Goldman P, Peppercorn MA: Sulfasalazine. N Engl Med 293:20–23, 1975

    Google Scholar 

  7. Baron JH, Connell AM, Lennard-Jones JE, Jones FA: Sulphasalazine and salicylazosulphadimidine in ulcerative colitis. Lancet 1:1094–1096, 1962

    Google Scholar 

  8. Dick AP, Grayson MJ, Carpenter RG, Petrie A: Controlled trial of sulphasalazine in the treatment of ulcerative colitis. Gut 5:437–442, 1964

    Google Scholar 

  9. Misiewicz JJ, Lennard-Jones JE, Connell AM, Parson JH, Avery Jones F: Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis. Lancet 1:185–188, 1965

    Google Scholar 

  10. Dissanayake AS, Truelove SC: A controlled therapeutic trial of long term maintenance therapy for ulcerative colitis with sulphasalazine (Salazopyrin). Gut 14:923–926, 1973

    Google Scholar 

  11. Anthonisen P, Barany F, Folkenburg O, Holtz S, Janum S, Kristensen M, Rios P, Walen A, Worning H: The clinical effect of salazosulphapyridine (Salazopyrin) in Crohn's disease. A controlled double-blind study. Scand J Gastroenterol 9:549–554, 1974

    Google Scholar 

  12. Das KM, Eastwood MA, McManus JPA, Sircus W: The metabolism of salicylazosulphapyridine in ulcerative colitis. I. The relationship between metabolites and response to treatment in inpatients. II. The relationship between metabolism and progress of the disease studied in outpatients. Gut 14:631–641, 1973

    Google Scholar 

  13. Das KM, Eastwood MA, McManus JPA, Sircus W: The role of the colon in the metabolism of salicylazosulphapyridine. Scand J Gastroenterol 9:137–141, 1974

    Google Scholar 

  14. Peppercorn MA, Goldman P: Distribution studies of salicylazosulfapyridine and its metabolites. Gastroenterology 64:240–245, 1973

    Google Scholar 

  15. Peppercorn MA, Goldman P: The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther 181:555–562, 1972

    Google Scholar 

  16. Azad Khan AK, Piris J, Truelove SC: An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 2:892–895, 1977

    Google Scholar 

  17. Van Hees PAM, Bakker JH, Van Tongeren JHM: Effect of sulphapyridine, 5-aminosalicylic acid, and placebo in patients with idiopathic proctitis. A study to determine the active therapeutic moiety of sulphasalazine. Gut 21:632–635, 1980

    Google Scholar 

  18. Collins JR: Adverse reactions to salicylazosulfapyridine (azulfidine) in the treatment of ulcerative colitis. South Med J 61:354–358, 1968

    Google Scholar 

  19. Das KM, Eastwood MA, McManus JPA, Sircus W: Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 289:491–495, 1973

    Google Scholar 

  20. Taffet SL, Das KM: Desensitization of patients with inflammatory bowel disease to sulfasalazine. Am J Med 73:520–524, 1982

    Google Scholar 

  21. Das KM, Eastwood MA: Acetylation polymorphism of sulphapyridine in patients with ulcerative colitis and Crohn's disease. Clin Pharmacol Ther 18:514–520, 1975

    Google Scholar 

  22. Das KM, Dubin R: Clinical pharmacokinetics of sulphasalazine. Clin Pharmacokinet 1:406–425, 1976

    Google Scholar 

  23. Azad Khan AK, Howes DT, Piris J, Truelove SC: Optimum dose of sulphasalazine for maintenance treatment of ulcerative colitis. Gut 21:232–240, 1980

    Google Scholar 

  24. Singleton JW, Law DH, Kelley ML, Mekhjian HS, Sturdevant RAL: National Cooperative Crohn's Disease Study: Adverse reactions to study drugs. Gastroenterology 77:870–882, 1979

    Google Scholar 

  25. Jamshidi K, Arlander T, Garcia, MC, Windschith HW, Swaim WR: Azulfidine agranulocytosis with bone marrowmegakaryocytosis, histiocytosis, plasmacytosis. Minn Med 55:545–548, 1972

    Google Scholar 

  26. Spriggs AI, Smith RS, Griffith H, Truelove, SC: Heinzbody anemia due to salicylazosulphapyridine. Lancet 1:1039–1042, 1958

    Google Scholar 

  27. Pounder RE, Craven ER, Henthorn JS, Bannatyne JM: Red cells abnormalities associated with sulphasalazine maintenance therapy for ulcerative colitis. Gut 16:181–185, 1975

    Google Scholar 

  28. Gabor EP: Hemolytic anemia as adverse reaction to salicylazosulfapyridine. N Engl J Med 289:1372, 1973

    Google Scholar 

  29. Wheelan KR, Cooper B, Stone MJ: Multiple hematologic abnormalities associated with sulfasalazine. Ann Intern Med 97:726–727, 1982

    Google Scholar 

  30. Bateson M: Megaloblastic anaemia associated with sulphasalazine treatment. Br Med J 2(6080):190, 1977

    Google Scholar 

  31. Kane S, Boots MA: Megaloblastic anaemia associated with sulphasalazine treatment. Br Med J 2(6097):1287–1288, 1977

    Google Scholar 

  32. Schneider RE, Beeley L: Megaloblastic anemia associated with sulphasalazine treatment. Br Med J 2(6077):1638–1639, 1977

    Google Scholar 

  33. Davies G, Palek J: Selective erythroid and megakaryocytic aplasia after sulfasalazine administration. Arch Intern Med 140:1122, 1980

    Google Scholar 

  34. Nja A: Et tilfelle av agranulocytose etter behandling med salazopyrin. Nord Med 28:2334, 1945

    Google Scholar 

  35. Levy CW: Agranulocytose ved salazpyrinbruk. T Norsk Laegeforen 69:255, 1949

    Google Scholar 

  36. Koskinen P: Pancytopenia during salazopyrin treatment. A case report. Ann Chir Gynaecol Fenn (Suppl) 43:180–183, 1954

    Google Scholar 

  37. Evans RS, Ford WP: Studies of the bone marrow in immunological granulocytopenia following administration of salicylazosulfapyridine. Arch Intern Med 101:244–251, 1958

    Google Scholar 

  38. Roth DA, Lindert ME: A fatal case of azulfidine-induced agranulocytosis. Gastroenterology 37:787–789, 1959

    Google Scholar 

  39. Ritz NO, Fisher MJ: Agranulocytosis due to administration of salicylazosulfapyridine (azulfidine). JAMA 172:237–240, 1960

    Google Scholar 

  40. Vinggard HE: Tre titfaelde of medikamental agranulocytose. Ogestr Laeg 124:144–146, 1962

    Google Scholar 

  41. Thirkettle JL, Gough KR, Read AE: Agranulocytosis associated with sulphasalazine (salazopyrin) therapy. Lancet 1:1395–1397, 1963

    Google Scholar 

  42. Panitz F: Agranulocytosis due to administration of salicylazosulfapyridine (azulfidine). Med Bull US Army Eur 20:270–271, 1963

    Google Scholar 

  43. Darling VE: Drug agranulocytosis: A case study. Nurs Times 61:1220, 1964

    Google Scholar 

  44. Cochrane P, Atkins P, Ehsanullah S: Agranulocytosis associated with sulphasalazine therapy. Postgrad Med J 49:669–672, 1973

    Google Scholar 

  45. Maddocks JL, Slater DN: Toxic epidermal necrolysis, agranulocytosis and erythroid hyopplasia associated with sulphasalazine. J R Soc Med 73:587–588, 1980

    Google Scholar 

  46. Bottiger LE, Engstedt L, Lagercrantz R: The occurrence of Heinz-bodies during azulfidine treatment of ulcerative colitis. Gastroenterology 100:33–41, 1963

    Google Scholar 

  47. Kaplinksy N, Frankel O: Salicylazosulphapyridine-induced Heinz-body anemia. Acta Haematol 59:310–314, 1978

    Google Scholar 

  48. Goodacre RL, Ali MAM, Vanderlinden B, Hamilton JD, Castelli M, Seaton T: Hemolytic anemia in patients receiving sulfasalazine. Digestion 17:503–508, 1978

    Google Scholar 

  49. Van Hees PA, Van Elferen LW, Van Rossum JM, Van Tongeren JH: Hemolysis during salicylazosulfapyridine therapy. Am J Gastroenterol 70:501–505, 1979

    Google Scholar 

  50. Tydd TF, Dyer NH: Sulphasalazine lung. Med J Aust 1:570–573, 1976

    Google Scholar 

  51. Jones ER, Malone DNS: Sulphasalazine induced lung disease. Thorax 27:713–717, 1972

    Google Scholar 

  52. Eastwood M: Sulphasalazine-induced lung disease. Lancet 2(7881):659–660, 1974

    Google Scholar 

  53. Davies D, MacFarlane A: Fibrosing alveolitis and treatment with sulphasalazine. Gut 15:185–188, 1974

    Google Scholar 

  54. Thomas P, Seaton A, Edwards J: Respiratory disease due to sulphasalazine. Clin Allergy 4:41–47, 1974

    Google Scholar 

  55. Constantinidis K: Eosinophilic pneumonia: An unusual side effect of therapy with salicylazosulfapyridine. Chest 70:315–316, 1976

    Google Scholar 

  56. Berliner S, Neeman A, Shoenfeld Y, Eldar M, Rousso I, Kadish V, Pinkhas J: Salazopyrin-induced eosinophilic pneumonia. Respiration 39:119–120, 1980

    Google Scholar 

  57. Williams T, Eidus L, Thomas P: Fibrosing alveolitis, bronchiolitis obliterans, and sulfasalazine therapy. Chest 81:766–768, 1982

    Google Scholar 

  58. Editorial: Sulphasalazine-induced lung disease. Lancet 2(879):504–505, 1974.

  59. Eade OE, Whorwell PJ, Smith CL, Alexander JR: Pulmonary function in patients with inflammatory bowel disease. Am J Gastroenterol 73:154–156, 1980

    Google Scholar 

  60. Dujovne CA, Chan CH, Zimmerman HJ: Sulfonamide hepatic injury. N Engl J Med 277:785–788, 1967

    Google Scholar 

  61. Fries J, Siraganian R: Sulfonamide hepatitis: Report of a case due to sulfamethaxazole and sulfisaxazole. N Engl J Med 274:95–97, 1966

    Google Scholar 

  62. Tonder M, Nordoy A, Elgio K: Sulfonamide-induced chronic liver disease. Scand J Gastroenterol 9:93–96, 1974

    Google Scholar 

  63. Seaman WE, Ishak KG, Plotz PH: Aspirin induced hepatotoxicity in patients with systemic lupus erythematosus. Ann Intern Med 80:1–8, 1974

    Google Scholar 

  64. Seaman WE, Plotz PH: Effect of aspirin on liver tests in patients with RA or SLE and in normal volunteers. Arthritis Rheum 19:155–160, 1976

    Google Scholar 

  65. Randall RE: Renal failure following antibiotics. Ann Intern Med 66:1052–1053, 1967 (abstract)

    Google Scholar 

  66. Carvatti CM, Hooker TH: Acute massive hepatic necrosis with fatal liver failure. Am J Dig Dis 16:803–808, 1971

    Google Scholar 

  67. Mihas AA, Goldenberg DJ, Slaughter RL: Sulfasalazine toxic reactions-hepatitis, fever, and skin rash with hypocomplementemia and immune complexes. JAMA 239:2590–2591, 1978

    Google Scholar 

  68. Sotolongo RP, Neefe LI, Rudzki M, Ishak G: Hypersensitivity reactions to sulfasalazine with severe hepatotoxicity. Gastroenterology 75:95–99, 1978

    Google Scholar 

  69. Chester AC, Diamond LH, Shreiner GE: Hypersensitivity to salicylazosulfapyridine-renal and hepatic toxic reactions. Arch Intern Med 138:1138–1139, 1978

    Google Scholar 

  70. Gulley RM, Mirza A, Kelley C: Hepatotoxicity of salicylazosulfapyridine: A case report and review of the literature. Am J Gastroenterol 72:561–564, 1979

    Google Scholar 

  71. Kanner RS, Tedesco FJ, Kalser MA: Azulfidine-(sulfasalazine) induced hepatic injury. Am J Dig Dis 23:956–958, 1978

    Google Scholar 

  72. Rafoth R: Systemic granulomatous reaction to salicylazosulfapyridine in a patient with Crohn's disease. Am J Dig Dis 19:465–469, 1974

    Google Scholar 

  73. Callen JP, Soderstrom RM: Granulomatous hepatitis associated with salicylazosulfapyridine therapy. South Med J 71:1159–1160, 1978

    Google Scholar 

  74. Namias A: Reversible sulphasalazine-induced granulomatous hepatitis. J Clin Gastroenterol 3(2):193–198, 1981

    Google Scholar 

  75. Werlin SL, Losek JD: Sulfasalazine hepatotoxicity. Am J Dis Child 135:1070–1071, 1981

    Google Scholar 

  76. Smith MD, Gibson GE, Rowland R: Combined hepatotoxicity and neurotoxicity following sulphasalazine administration. Aust NZ J Med 12:76–80, 1982

    Google Scholar 

  77. Jacobs E, Pavlet P, Rahier J: Hypersensitivity reaction to sulfasalazine-another case. Gastroenterology 75:1193, 1978

    Google Scholar 

  78. Alarcon-Segovia D, Herskovic T, Dearing W, Bartholomew LG, Shorter RG: Lupus erythematosus cell phenomenon in patients with chronic ulcerative colitis. Gut 6:39–47, 1965

    Google Scholar 

  79. Griffiths MB, Kane MA: Sulphasalazine-induced lupus syndrome in ulcerative colitis. Br Med J 2(6096):1188–1189, 1977

    Google Scholar 

  80. Jaup BH: Salosulfapyridin-induziertes lupus-erythematodes-syndrom bei colitis ulcerosa. Dtsch Med Wochenschr 103:1211–1213, 1978

    Google Scholar 

  81. Basu MK, Asquith P: Oral manifestations of inflammatory bowel disease.In Clinics in Gastroenterology-Inflammatory Bowel Disease. RE Farmer (ed). London, WB Saunders, 1980, pp 307–321

    Google Scholar 

  82. Crisp AJ, Hoffbrand BI: Sulphasalazine-induced systemic lupus erythematosus in a patient with Sjogren's syndrome. J R Soc Med 73:60–61, 1980

    Google Scholar 

  83. Reid J, Holt S, Housley E, Sneddon DJC: Raynaud's phenomenon induced by sulphasalazine. Postgrad Med J 56:106–107, 1980

    Google Scholar 

  84. Cameron AJ, Baron JH, Priestly BL: Erythema multiforme, drugs, and ulcerative colitis. Br Med J 2:1174–1178, 1966

    Google Scholar 

  85. Strom J: Toxic epidermal necrolysis (Lyell's syndrome)—a report on four cases with three deaths. Scand J Infect Dis 1:209–216, 1969

    Google Scholar 

  86. Hensen EJ, Claas FH, Vermeer BJ: Drug-dependent binding of circulating antibodies in drug-induced toxic epidermal necrolysis. Lancet 2(8238):151–152, 1981

    Google Scholar 

  87. Yelo J, Shiel GD, Uldall PR: Unusual cause of yellow skin. Br Med J 4:452, 1968

    Google Scholar 

  88. Block M, Genant H, Kirsner J: Pancreatitis as an adverse reaction to salicylazosulfapyridine. N Engl J Med 282:380–382, 1970

    Google Scholar 

  89. Werlin S, Grand R: Bloody diarrhea—a new complication of sulfasalazine. J Pediatr 92(3):450–451, 1978

    Google Scholar 

  90. Schwartz AG, Targan S, Saxon A, Weinstein WM: Sulfasalazine-induced exacerbation of ulcerative colitis. N Engl J Med 306:409, 1982

    Google Scholar 

  91. Adler RD: Sulfasalazine-induced exacerbation of ulcerative colitis. N Engl J Med 307:315, 1982

    Google Scholar 

  92. Pokorney BH, Nichols TW: Pseudomembranous colitis. Am J Gastroenterology 76:374–376, 1981

    Google Scholar 

  93. Franklin J, Rosenberg I: Impaired folic acid absorption in inflammatory bowel disease: Effects of salicylazosulfapyridine (azulfidine). Gastroenterology 64:517–525, 1973

    Google Scholar 

  94. Swinson C, Perry J, Lumb M, Levi AJ: Role of sulphasalazine in the aetiology of folate deficiency in ulcerative colitis. Gut 22:456–461, 1981

    Google Scholar 

  95. Halsted CH, Gandhi G, Tamura T: Sulfasalazine inhibits the absorbtion of folates in ulcerative colitis. N Engl J Med 305:1513–1514, 1981

    Google Scholar 

  96. Toth A: Reversible toxic effect of salicylazosulfapyridine on semen quality. Fertil Steril 31:538–540, 1979

    Google Scholar 

  97. Toth A: Male infertility due to sulphasalazine. Lancet 2(8148):904, 1979

    Google Scholar 

  98. Birnie GG, McLeod TIF, Watkinson G: Incidence of sulphasalazine-induced male infertility. Gut 22:452–455, 1981

    Google Scholar 

  99. Freeman JG, Reece VAC, Venables CW: Sulphasalazine and spermatogenesis. Digestion 23:68–71, 1982

    Google Scholar 

  100. Levi AJ, Fisher AM, Hughes L, Hendry WF: Male infertility due to sulphasalazine. Lancet 2(8137):276–278, 1979

    Google Scholar 

  101. Toovey S, Hudson E, Hendry WF, Levi AJ: Sulphasalazine and male infertility; reversibility and possible mechanism. Gut 22:445–451, 1981

    Google Scholar 

  102. Grieve J: Male infertility due to sulphasalazine. Lancet 2(8140):464, 1979

    Google Scholar 

  103. Traub AI, Thompson W, Carville J: Male infertility due to sulphasalazine. Lancet 2(8143):639–640, 1979

    Google Scholar 

  104. Collen M: Azulfidine-induced oligospermia. Am J Gastroenterol 74:441–442, 1980

    Google Scholar 

  105. Dhar J, Selhub J, Rosenberg IH: Azulfidine inhibition of folic acid absorption: Confirmation of a specific saturable transport mechanism. Gastroenterology 70:878A, 1976

    Google Scholar 

  106. Sharon P, Ligumsky M, Rachmilewitz D: Role of prostaglandins in ulcerative colitis: Enhanced production during active disease and inhibition by sulfasalazine. Gastroenterology 75:638–640, 1978

    Google Scholar 

  107. O'Morain CA, Smethurst P, Hudson E, Levi AJ: Further studies on sulfasalazine induced male infertility. Gastroenterology 82:1140, 1982

    Google Scholar 

  108. Heiny BM: Sinustachykardie neve nebenwiskung bei der therapie mit salazosulfapyridin. Dsch Med Wochenschr 102:371, 1977

    Google Scholar 

  109. Neeman A, Berliner S, Shoenfeld Y, Kadish V, Pinkhas J: Salazopyrine-induced tachycardia. Biomedicine 33:1–2, 1980 (letter)

    Google Scholar 

  110. Svartz N, Kallner S: Cyanosis in treatment with sulfonamide compounds. Acta Med Scand 104:309–312, 1940

    Google Scholar 

  111. Attar A, Anuras S: Sulfasalazine and hair loss. Gastroenterology 80:1102, 1981 (abstract)

    Google Scholar 

  112. Wallace IW: Neurotoxicity associated with a reaction to sulphasalazine. Practitioner 204:850–851, 1970

    Google Scholar 

  113. Goldstein PD, Alpers DH, Keating JP: Sulfapyridine metabolites in children with inflammatory bowel disease receiving sulfasalazine. J Pediatr 95:638–640, 1979

    Google Scholar 

  114. Holdsworth CD: Sulphasalazine desensitization. Br Med J 282:110, 1981

    Google Scholar 

  115. Korelitz BI, Present DH, Rubin PH, Fochias SE: Desensitization to sulfasalazine in allergic patients with IBD: An important therapeutic modality. Gastroenterology 82:1104, 1982 (abstract)

    Google Scholar 

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  1. Departments of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461, Bronx, New York

    Sanford L. Taffet MD &  Kiron M. Das MD, PhD

  2. New York Medical College, 10595, Valhalla, New York

    Sanford L. Taffet MD &  Kiron M. Das MD, PhD

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Taffet, S.L., Das, K.M. Sulfasalazine. Digest Dis Sci 28, 833–842 (1983). https://doi.org/10.1007/BF01296907

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