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.
Similar content being viewed by others
References
Svartz N: Salazopyrin, a new sulfonilamide preparation. Acta Med Scand 110:557–598, 1942
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
Dixon JS: Biochemical and clinical changes in rheumatoid arthritis: Their relation to the action of antirheumatoid drugs. Semin Arthritis Rheum 12:191–207, 1982
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
Goldman P, Peppercorn MA: Salicylazosulfapyridine in clinical practice. Gastroenterology 65:166–169, 1973
Goldman P, Peppercorn MA: Sulfasalazine. N Engl Med 293:20–23, 1975
Baron JH, Connell AM, Lennard-Jones JE, Jones FA: Sulphasalazine and salicylazosulphadimidine in ulcerative colitis. Lancet 1:1094–1096, 1962
Dick AP, Grayson MJ, Carpenter RG, Petrie A: Controlled trial of sulphasalazine in the treatment of ulcerative colitis. Gut 5:437–442, 1964
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
Dissanayake AS, Truelove SC: A controlled therapeutic trial of long term maintenance therapy for ulcerative colitis with sulphasalazine (Salazopyrin). Gut 14:923–926, 1973
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
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
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
Peppercorn MA, Goldman P: Distribution studies of salicylazosulfapyridine and its metabolites. Gastroenterology 64:240–245, 1973
Peppercorn MA, Goldman P: The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther 181:555–562, 1972
Azad Khan AK, Piris J, Truelove SC: An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 2:892–895, 1977
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
Collins JR: Adverse reactions to salicylazosulfapyridine (azulfidine) in the treatment of ulcerative colitis. South Med J 61:354–358, 1968
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
Taffet SL, Das KM: Desensitization of patients with inflammatory bowel disease to sulfasalazine. Am J Med 73:520–524, 1982
Das KM, Eastwood MA: Acetylation polymorphism of sulphapyridine in patients with ulcerative colitis and Crohn's disease. Clin Pharmacol Ther 18:514–520, 1975
Das KM, Dubin R: Clinical pharmacokinetics of sulphasalazine. Clin Pharmacokinet 1:406–425, 1976
Azad Khan AK, Howes DT, Piris J, Truelove SC: Optimum dose of sulphasalazine for maintenance treatment of ulcerative colitis. Gut 21:232–240, 1980
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
Jamshidi K, Arlander T, Garcia, MC, Windschith HW, Swaim WR: Azulfidine agranulocytosis with bone marrowmegakaryocytosis, histiocytosis, plasmacytosis. Minn Med 55:545–548, 1972
Spriggs AI, Smith RS, Griffith H, Truelove, SC: Heinzbody anemia due to salicylazosulphapyridine. Lancet 1:1039–1042, 1958
Pounder RE, Craven ER, Henthorn JS, Bannatyne JM: Red cells abnormalities associated with sulphasalazine maintenance therapy for ulcerative colitis. Gut 16:181–185, 1975
Gabor EP: Hemolytic anemia as adverse reaction to salicylazosulfapyridine. N Engl J Med 289:1372, 1973
Wheelan KR, Cooper B, Stone MJ: Multiple hematologic abnormalities associated with sulfasalazine. Ann Intern Med 97:726–727, 1982
Bateson M: Megaloblastic anaemia associated with sulphasalazine treatment. Br Med J 2(6080):190, 1977
Kane S, Boots MA: Megaloblastic anaemia associated with sulphasalazine treatment. Br Med J 2(6097):1287–1288, 1977
Schneider RE, Beeley L: Megaloblastic anemia associated with sulphasalazine treatment. Br Med J 2(6077):1638–1639, 1977
Davies G, Palek J: Selective erythroid and megakaryocytic aplasia after sulfasalazine administration. Arch Intern Med 140:1122, 1980
Nja A: Et tilfelle av agranulocytose etter behandling med salazopyrin. Nord Med 28:2334, 1945
Levy CW: Agranulocytose ved salazpyrinbruk. T Norsk Laegeforen 69:255, 1949
Koskinen P: Pancytopenia during salazopyrin treatment. A case report. Ann Chir Gynaecol Fenn (Suppl) 43:180–183, 1954
Evans RS, Ford WP: Studies of the bone marrow in immunological granulocytopenia following administration of salicylazosulfapyridine. Arch Intern Med 101:244–251, 1958
Roth DA, Lindert ME: A fatal case of azulfidine-induced agranulocytosis. Gastroenterology 37:787–789, 1959
Ritz NO, Fisher MJ: Agranulocytosis due to administration of salicylazosulfapyridine (azulfidine). JAMA 172:237–240, 1960
Vinggard HE: Tre titfaelde of medikamental agranulocytose. Ogestr Laeg 124:144–146, 1962
Thirkettle JL, Gough KR, Read AE: Agranulocytosis associated with sulphasalazine (salazopyrin) therapy. Lancet 1:1395–1397, 1963
Panitz F: Agranulocytosis due to administration of salicylazosulfapyridine (azulfidine). Med Bull US Army Eur 20:270–271, 1963
Darling VE: Drug agranulocytosis: A case study. Nurs Times 61:1220, 1964
Cochrane P, Atkins P, Ehsanullah S: Agranulocytosis associated with sulphasalazine therapy. Postgrad Med J 49:669–672, 1973
Maddocks JL, Slater DN: Toxic epidermal necrolysis, agranulocytosis and erythroid hyopplasia associated with sulphasalazine. J R Soc Med 73:587–588, 1980
Bottiger LE, Engstedt L, Lagercrantz R: The occurrence of Heinz-bodies during azulfidine treatment of ulcerative colitis. Gastroenterology 100:33–41, 1963
Kaplinksy N, Frankel O: Salicylazosulphapyridine-induced Heinz-body anemia. Acta Haematol 59:310–314, 1978
Goodacre RL, Ali MAM, Vanderlinden B, Hamilton JD, Castelli M, Seaton T: Hemolytic anemia in patients receiving sulfasalazine. Digestion 17:503–508, 1978
Van Hees PA, Van Elferen LW, Van Rossum JM, Van Tongeren JH: Hemolysis during salicylazosulfapyridine therapy. Am J Gastroenterol 70:501–505, 1979
Tydd TF, Dyer NH: Sulphasalazine lung. Med J Aust 1:570–573, 1976
Jones ER, Malone DNS: Sulphasalazine induced lung disease. Thorax 27:713–717, 1972
Eastwood M: Sulphasalazine-induced lung disease. Lancet 2(7881):659–660, 1974
Davies D, MacFarlane A: Fibrosing alveolitis and treatment with sulphasalazine. Gut 15:185–188, 1974
Thomas P, Seaton A, Edwards J: Respiratory disease due to sulphasalazine. Clin Allergy 4:41–47, 1974
Constantinidis K: Eosinophilic pneumonia: An unusual side effect of therapy with salicylazosulfapyridine. Chest 70:315–316, 1976
Berliner S, Neeman A, Shoenfeld Y, Eldar M, Rousso I, Kadish V, Pinkhas J: Salazopyrin-induced eosinophilic pneumonia. Respiration 39:119–120, 1980
Williams T, Eidus L, Thomas P: Fibrosing alveolitis, bronchiolitis obliterans, and sulfasalazine therapy. Chest 81:766–768, 1982
Editorial: Sulphasalazine-induced lung disease. Lancet 2(879):504–505, 1974.
Eade OE, Whorwell PJ, Smith CL, Alexander JR: Pulmonary function in patients with inflammatory bowel disease. Am J Gastroenterol 73:154–156, 1980
Dujovne CA, Chan CH, Zimmerman HJ: Sulfonamide hepatic injury. N Engl J Med 277:785–788, 1967
Fries J, Siraganian R: Sulfonamide hepatitis: Report of a case due to sulfamethaxazole and sulfisaxazole. N Engl J Med 274:95–97, 1966
Tonder M, Nordoy A, Elgio K: Sulfonamide-induced chronic liver disease. Scand J Gastroenterol 9:93–96, 1974
Seaman WE, Ishak KG, Plotz PH: Aspirin induced hepatotoxicity in patients with systemic lupus erythematosus. Ann Intern Med 80:1–8, 1974
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
Randall RE: Renal failure following antibiotics. Ann Intern Med 66:1052–1053, 1967 (abstract)
Carvatti CM, Hooker TH: Acute massive hepatic necrosis with fatal liver failure. Am J Dig Dis 16:803–808, 1971
Mihas AA, Goldenberg DJ, Slaughter RL: Sulfasalazine toxic reactions-hepatitis, fever, and skin rash with hypocomplementemia and immune complexes. JAMA 239:2590–2591, 1978
Sotolongo RP, Neefe LI, Rudzki M, Ishak G: Hypersensitivity reactions to sulfasalazine with severe hepatotoxicity. Gastroenterology 75:95–99, 1978
Chester AC, Diamond LH, Shreiner GE: Hypersensitivity to salicylazosulfapyridine-renal and hepatic toxic reactions. Arch Intern Med 138:1138–1139, 1978
Gulley RM, Mirza A, Kelley C: Hepatotoxicity of salicylazosulfapyridine: A case report and review of the literature. Am J Gastroenterol 72:561–564, 1979
Kanner RS, Tedesco FJ, Kalser MA: Azulfidine-(sulfasalazine) induced hepatic injury. Am J Dig Dis 23:956–958, 1978
Rafoth R: Systemic granulomatous reaction to salicylazosulfapyridine in a patient with Crohn's disease. Am J Dig Dis 19:465–469, 1974
Callen JP, Soderstrom RM: Granulomatous hepatitis associated with salicylazosulfapyridine therapy. South Med J 71:1159–1160, 1978
Namias A: Reversible sulphasalazine-induced granulomatous hepatitis. J Clin Gastroenterol 3(2):193–198, 1981
Werlin SL, Losek JD: Sulfasalazine hepatotoxicity. Am J Dis Child 135:1070–1071, 1981
Smith MD, Gibson GE, Rowland R: Combined hepatotoxicity and neurotoxicity following sulphasalazine administration. Aust NZ J Med 12:76–80, 1982
Jacobs E, Pavlet P, Rahier J: Hypersensitivity reaction to sulfasalazine-another case. Gastroenterology 75:1193, 1978
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
Griffiths MB, Kane MA: Sulphasalazine-induced lupus syndrome in ulcerative colitis. Br Med J 2(6096):1188–1189, 1977
Jaup BH: Salosulfapyridin-induziertes lupus-erythematodes-syndrom bei colitis ulcerosa. Dtsch Med Wochenschr 103:1211–1213, 1978
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
Crisp AJ, Hoffbrand BI: Sulphasalazine-induced systemic lupus erythematosus in a patient with Sjogren's syndrome. J R Soc Med 73:60–61, 1980
Reid J, Holt S, Housley E, Sneddon DJC: Raynaud's phenomenon induced by sulphasalazine. Postgrad Med J 56:106–107, 1980
Cameron AJ, Baron JH, Priestly BL: Erythema multiforme, drugs, and ulcerative colitis. Br Med J 2:1174–1178, 1966
Strom J: Toxic epidermal necrolysis (Lyell's syndrome)—a report on four cases with three deaths. Scand J Infect Dis 1:209–216, 1969
Hensen EJ, Claas FH, Vermeer BJ: Drug-dependent binding of circulating antibodies in drug-induced toxic epidermal necrolysis. Lancet 2(8238):151–152, 1981
Yelo J, Shiel GD, Uldall PR: Unusual cause of yellow skin. Br Med J 4:452, 1968
Block M, Genant H, Kirsner J: Pancreatitis as an adverse reaction to salicylazosulfapyridine. N Engl J Med 282:380–382, 1970
Werlin S, Grand R: Bloody diarrhea—a new complication of sulfasalazine. J Pediatr 92(3):450–451, 1978
Schwartz AG, Targan S, Saxon A, Weinstein WM: Sulfasalazine-induced exacerbation of ulcerative colitis. N Engl J Med 306:409, 1982
Adler RD: Sulfasalazine-induced exacerbation of ulcerative colitis. N Engl J Med 307:315, 1982
Pokorney BH, Nichols TW: Pseudomembranous colitis. Am J Gastroenterology 76:374–376, 1981
Franklin J, Rosenberg I: Impaired folic acid absorption in inflammatory bowel disease: Effects of salicylazosulfapyridine (azulfidine). Gastroenterology 64:517–525, 1973
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
Halsted CH, Gandhi G, Tamura T: Sulfasalazine inhibits the absorbtion of folates in ulcerative colitis. N Engl J Med 305:1513–1514, 1981
Toth A: Reversible toxic effect of salicylazosulfapyridine on semen quality. Fertil Steril 31:538–540, 1979
Toth A: Male infertility due to sulphasalazine. Lancet 2(8148):904, 1979
Birnie GG, McLeod TIF, Watkinson G: Incidence of sulphasalazine-induced male infertility. Gut 22:452–455, 1981
Freeman JG, Reece VAC, Venables CW: Sulphasalazine and spermatogenesis. Digestion 23:68–71, 1982
Levi AJ, Fisher AM, Hughes L, Hendry WF: Male infertility due to sulphasalazine. Lancet 2(8137):276–278, 1979
Toovey S, Hudson E, Hendry WF, Levi AJ: Sulphasalazine and male infertility; reversibility and possible mechanism. Gut 22:445–451, 1981
Grieve J: Male infertility due to sulphasalazine. Lancet 2(8140):464, 1979
Traub AI, Thompson W, Carville J: Male infertility due to sulphasalazine. Lancet 2(8143):639–640, 1979
Collen M: Azulfidine-induced oligospermia. Am J Gastroenterol 74:441–442, 1980
Dhar J, Selhub J, Rosenberg IH: Azulfidine inhibition of folic acid absorption: Confirmation of a specific saturable transport mechanism. Gastroenterology 70:878A, 1976
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
O'Morain CA, Smethurst P, Hudson E, Levi AJ: Further studies on sulfasalazine induced male infertility. Gastroenterology 82:1140, 1982
Heiny BM: Sinustachykardie neve nebenwiskung bei der therapie mit salazosulfapyridin. Dsch Med Wochenschr 102:371, 1977
Neeman A, Berliner S, Shoenfeld Y, Kadish V, Pinkhas J: Salazopyrine-induced tachycardia. Biomedicine 33:1–2, 1980 (letter)
Svartz N, Kallner S: Cyanosis in treatment with sulfonamide compounds. Acta Med Scand 104:309–312, 1940
Attar A, Anuras S: Sulfasalazine and hair loss. Gastroenterology 80:1102, 1981 (abstract)
Wallace IW: Neurotoxicity associated with a reaction to sulphasalazine. Practitioner 204:850–851, 1970
Goldstein PD, Alpers DH, Keating JP: Sulfapyridine metabolites in children with inflammatory bowel disease receiving sulfasalazine. J Pediatr 95:638–640, 1979
Holdsworth CD: Sulphasalazine desensitization. Br Med J 282:110, 1981
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)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Taffet, S.L., Das, K.M. Sulfasalazine. Digest Dis Sci 28, 833–842 (1983). https://doi.org/10.1007/BF01296907
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01296907