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1

&NA;. "Sulphasalazine." Reactions Weekly &NA;, no. 969 (September 2003): 14. http://dx.doi.org/10.2165/00128415-200309690-00044.

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2

Freeman, Hugh J., Urs P. Steinbrecher, WC Peter Kwan, and Stephanie Ensworth. "Sulphasalazine-Induced Pseudomembranous Colitis." Canadian Journal of Gastroenterology 5, no. 5 (1991): 167–70. http://dx.doi.org/10.1155/1991/420864.

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An 18-year-old female with ankylosing spondylitis developed fever, abdominal pain and diarrhea on two occasions after starting sulphasalazine therapy. Flexible sigmoidoscopy revealed pseudomembranous colitis; fecal cultures were positive forClostridium difficile; andC difficiletoxin assay was positive. Despite the frequent use of sulphasalazine in the management of inflammatory bowel disease, this complication has been apparently rare. Clinicians should be wary of the onset of diarrhea in patients receiving sulphasalazine, whether for inflammatory bowel disease or other conditions.
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3

Jennings, P. E., R. L. Blandford, and F. D. Rosenthal. "Acute sulphasalazine hepatotoxicity." Postgraduate Medical Journal 62, no. 726 (April 1, 1986): 305–6. http://dx.doi.org/10.1136/pgmj.62.726.305.

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4

Rijk, Marno C. M. "Sulphasalazine and Prednisone Compared with Sulphasalazine for Treating Active Crohn Disease." Annals of Internal Medicine 114, no. 6 (March 15, 1991): 445. http://dx.doi.org/10.7326/0003-4819-114-6-445.

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5

Bax, D. E., R. S. Amos, D. Situnayake, and B. Mcconkey. "SULPHASALAZINE IN RHEUMATOID ARTHRITIS." Lancet 325, no. 8443 (June 1985): 1450. http://dx.doi.org/10.1016/s0140-6736(85)91878-1.

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6

VYSE, T., and A. K. L. SO. "SULPHASALAZINE INDUCED AUTOIMMUNE SYNDROME." Rheumatology 31, no. 2 (1992): 115–16. http://dx.doi.org/10.1093/rheumatology/31.2.115.

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7

McCONKEY, B. "SULPHASALAZINE AND ANKYLOSING SPONDYLITIS." Rheumatology 29, no. 1 (1990): 1–3. http://dx.doi.org/10.1093/rheumatology/29.1.1.

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8

Pullar, T., J. A. Hunter, and H. A. Capell. "SULPHASALAZINE IN RHEUMATOID ARTHRITIS." Lancet 325, no. 8438 (May 1985): 1167. http://dx.doi.org/10.1016/s0140-6736(85)92477-8.

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9

Feltelius, N., and R. Hallgren. "Sulphasalazine in ankylosing spondylitis." Annals of the Rheumatic Diseases 45, no. 5 (May 1, 1986): 396–99. http://dx.doi.org/10.1136/ard.45.5.396.

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10

Amos, R. S., D. E. Bax, and M. S. Greaves. "Sulphasalazine therapy in RA." Annals of the Rheumatic Diseases 45, no. 5 (May 1, 1986): 439. http://dx.doi.org/10.1136/ard.45.5.439-a.

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11

Pullar, T., J. A. Hunter, and H. A. Capell. "Sulphasalazine and hepatic transaminases." Annals of the Rheumatic Diseases 46, no. 5 (May 1, 1987): 421. http://dx.doi.org/10.1136/ard.46.5.421-a.

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12

Parry, S. D., C. Barbatzas, E. T. Peel, and J. R. Barton. "Sulphasalazine and lung toxicity." European Respiratory Journal 19, no. 4 (April 2002): 756–64. http://dx.doi.org/10.1183/09031936.02.00267402.

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13

Domingo, J. J. Sebastian, A. Ventura, V. Pérez Ayala, and D. Castellanos. "Hypersensitivity pneumonitis by sulphasalazine." Allergy 44, no. 7 (October 1989): 522. http://dx.doi.org/10.1111/j.1398-9995.1989.tb04193.x.

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14

Long, R. "Sulphasalazine and keratoconjunctivitis sicca." Veterinary Record 116, no. 10 (March 9, 1985): 274. http://dx.doi.org/10.1136/vr.116.10.274-b.

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15

Burrows, C. "Keratoconjunctivitis sicca and sulphasalazine." Veterinary Record 116, no. 20 (May 18, 1985): 550. http://dx.doi.org/10.1136/vr.116.20.550-b.

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16

Bedford, P. "Sulphasalazine and keratoconjunctivitis sicca." Veterinary Record 116, no. 8 (February 23, 1985): 222. http://dx.doi.org/10.1136/vr.116.8.222-a.

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17

Kanwar, A. J., M. Singh, M. Yunus, and M. S. Belhaj. "Fixed Eruption to Sulphasalazine." Dermatology 174, no. 2 (1987): 104. http://dx.doi.org/10.1159/000248997.

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18

GOLDING, D. N. "Sulphasalazine for Palindromic Rheumatism." Rheumatology 27, no. 1 (1988): 79. http://dx.doi.org/10.1093/rheumatology/27.1.79.

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19

Peters, F. P., L. G. Engels, and A. M. Moers. "Pneumonitis induced by sulphasalazine." Postgraduate Medical Journal 73, no. 856 (February 1, 1997): 99–100. http://dx.doi.org/10.1136/pgmj.73.856.99.

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20

Quinn, A. G., W. R. Ellis, D. Burn, and N. Cartlidge. "Chorea precipitated by sulphasalazine." BMJ 302, no. 6783 (April 27, 1991): 1025. http://dx.doi.org/10.1136/bmj.302.6783.1025-a.

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21

YOUSSEF, P. P., and J. V. BERTOUCH. "Sulphasalazine induced aplastic anaemia." Australian and New Zealand Journal of Medicine 22, no. 4 (August 1992): 391–92. http://dx.doi.org/10.1111/j.1445-5994.1992.tb02161.x.

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22

Crao, S. S. "Sulphasalazine and gastrointestinal transit." Gut 32, no. 9 (September 1, 1991): 1087. http://dx.doi.org/10.1136/gut.32.9.1087-a.

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23

Michalowski, A. S. "Sulphasalazine in ulcerative colitis." Gut 33, no. 11 (November 1, 1992): 1582. http://dx.doi.org/10.1136/gut.33.11.1582-a.

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24

Dwarakanath, A. D., J. Michael, and R. N. Allan. "Sulphasalazine induced renal failure." Gut 33, no. 7 (July 1, 1992): 1006–7. http://dx.doi.org/10.1136/gut.33.7.1006.

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25

Price, T. R. "Sensorimotor neuropathy with sulphasalazine." Postgraduate Medical Journal 61, no. 712 (February 1, 1985): 147–48. http://dx.doi.org/10.1136/pgmj.61.712.147.

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26

Siva, A., F. Karaali, F. Karantay, S. Saip, and O. Kantarci. "Sulphasalazine in multiple sclerosis." Journal of Neuroimmunology 56-63 (1995): 51. http://dx.doi.org/10.1016/0165-5728(95)99030-m.

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27

Barnett, K. C., and E. C. Joseph. "Keratoconjunctivitis Sicca in the Dog Following 5-Aminosalicylic Acid Administration." Human Toxicology 6, no. 5 (September 1987): 377–83. http://dx.doi.org/10.1177/096032718700600506.

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1 Keratoconjunctivitis sicca (KCS) is an inflammatory eye condition, affecting the cornea and conjunctiva, caused by a deficiency in the aqueous fraction of tears. The condition is relatively common in the dog with a varied aetiology. A number of drugs have been implicated in the production of KCS in the dog including salicylazosulphapyridine (sulphasalazine). 2 This paper details clinically evident KCS in a 12-month oral toxicity study with 5-aminosalicylic acid (5-ASA), the therapeutically active metabolite of sulphasalazine. 3 The condition was first diagnosed at study week 22 and subsequently progressed both in incidence and severity. There was a distinct sex-difference in the response, with treated females being more affected than males. 4 There was a close correlation between the production of KCS and reduced lacrimation as assessed by the Schirmer tear test. 5 Although sulphasalazine causes KCS in dogs there have been no reports of ocular lesions of this type in man with this drug. It is highly probable that the dog is not a predictive model for man with regard to KCS induction by sulphasalazine or its metabolite 5-ASA.
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28

Sharma, Vinod K. "Safety Profile of the New 5-ASA Based Compounds." Canadian Journal of Gastroenterology 4, no. 7 (1990): 443–45. http://dx.doi.org/10.1155/1990/345274.

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5-aminosalicylic acid (5-ASA) preparations were anticipated to be and generally are better tolerated than sulphasalazine. Minor side effects such as headache, dizziness, abdominal pain and nausea do occur but are not more frequent than in placebo-treated patients. Approximately 10% of patients thought to be allergic to sulphasalazine are also allergic to 5-ASA. An idiosyncratic reaction with worsening of symptoms can occur. Diarrhea is more common with olsalazine, and it is due to the effect of olsalazine itself on the small bowel. not the 5-ASA component. There are case reports of pancreatitis, pericarditis and bronchospasm, retrosternal chest pain, mild neutropenia, nephrotic syndrome and hair loss associated with 5-ASA treatment. Patients with oligospermia due to sulphasalazine have improved when switched to 5-ASA. 5-ASA enemas can cause local irritation or other effects resulting from enema tip insertion.
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29

SEIDEMAN, P. "Sulphasalazine Treatment of Psoriatic Arthritis." Rheumatology 29, no. 6 (1990): 491–92. http://dx.doi.org/10.1093/rheumatology/29.6.491-a.

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30

Winkler, V., and P. Vertes. "Sulphasalazine treatment in rheumatoid arthritis." Annals of the Rheumatic Diseases 49, no. 3 (March 1, 1990): 202. http://dx.doi.org/10.1136/ard.49.3.202-a.

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31

Pałgan, K., and Z. Bartuzi. "Dress Syndrome Induced by Sulphasalazine." European Journal of Inflammation 12, no. 1 (January 2014): 187–90. http://dx.doi.org/10.1177/1721727x1401200118.

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32

ASTBURY, C., and A. J. TAGGART. "Acetylation, Sulphasalazine and its Effects." Rheumatology 26, no. 3 (1987): 229–30. http://dx.doi.org/10.1093/rheumatology/26.3.229-a.

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33

PEARS, J. S., and K. D. MORLEY. "Fatal Hypersensitivity Reaction to Sulphasalazine." Rheumatology 28, no. 3 (1989): 274–75. http://dx.doi.org/10.1093/rheumatology/28.3.274.

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34

Barbour, V. M., and P. F. Williams. "Nephrotic syndrome associated with sulphasalazine." BMJ 301, no. 6755 (October 6, 1990): 818. http://dx.doi.org/10.1136/bmj.301.6755.818-b.

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35

Suresh, Resmy, Sanjay Gupta, and Rosh Sathananthan. "Sulphasalazine Induced Three-Week Syndrome." JCR: Journal of Clinical Rheumatology 15, no. 6 (September 2009): 311–12. http://dx.doi.org/10.1097/rhu.0b013e3181bbbcea.

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36

Dubey, S., and A. O. Adebajo. "Lymphoproliferative disorder due to sulphasalazine." Case Reports 2009, mar08 1 (March 17, 2009): bcr0620080038. http://dx.doi.org/10.1136/bcr.06.2008.0038.

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37

MONGEY, A. B., and E. V. HESS. "Sulphasalazine-induced Systemic Lupus Erythematosus." Rheumatology 33, no. 8 (1994): 789. http://dx.doi.org/10.1093/rheumatology/33.8.789-a.

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38

Meenan, J. "Co-carcinogenic effect of sulphasalazine." British Journal of Cancer 68, no. 5 (November 1993): 1043–44. http://dx.doi.org/10.1038/bjc.1993.477.

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39

Brooks, H., H. G. Taylor, and F. E. Nichol. "The three week sulphasalazine syndrome." Clinical Rheumatology 11, no. 4 (December 1992): 566–68. http://dx.doi.org/10.1007/bf02283121.

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40

Ogle, C. W., C. H. Cho, and S. Dai. "Sulphasalazine and experimental stress ulcers." Agents and Actions 17, no. 2 (December 1985): 153–57. http://dx.doi.org/10.1007/bf01966585.

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41

Freeman, H. J. "Sulphasalazine-induced forms of colitis." Inflammopharmacology 2, no. 3 (September 1993): 301–5. http://dx.doi.org/10.1007/bf02660621.

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42

Deltenre, P., A. Berson, P. Marcellin, C. Degott, M. Biour, and D. Pessayre. "Mesalazine (5-aminosalicylic acid) induced chronic hepatitis." Gut 44, no. 6 (June 1, 1999): 886–88. http://dx.doi.org/10.1136/gut.44.6.886.

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BACKGROUNDTreatment of ulcerative colitis or Crohn’s disease with sulphasalazine causes several adverse effects, including hepatitis. Sulphasalazine is cleaved by colonic bacteria into 5-aminosalicylic acid and sulphapyridine. Received wisdom was that 5-aminosalicylic acid was topically active, whereas sulphapyridine was absorbed and caused immunoallergic side effects. Mesalazine, a slow release formulation of 5-aminosalicylic acid, was expected to be a safe alternative. However, several cases of acute hepatitis have been reported.CASE REPORTA 65 year old man had increased liver enzymes, anti-nuclear and anti-smooth muscle autoantibodies and IgG levels, and lesions of chronic hepatitis after 21 months of mesalazine treatment. Although liver dysfunction had been identified eight months earlier, simvastatin rather than mesalazine had been withdrawn, without any improvement. In contrast, liver enzyme and IgG levels became normal and autoantibodies disappeared after discontinuation of mesalazine administration.CONCLUSIONContrary to initial expectations, mesalazine can cause most of the sulphasalazine induced adverse effects, and hepatic side effects may be almost as frequent. When liver dysfunction occurs, mesalazine administration should be discontinued to avoid the development of chronic hepatitis and liver fibrosis.
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43

Gibson, P. R., and D. P. Jewell. "Sulphasalazine and Derivatives, Natural Killer Activity and Ulcerative Colitis." Clinical Science 69, no. 2 (August 1, 1985): 177–84. http://dx.doi.org/10.1042/cs0690177.

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1. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), sulphapyridine and azodisalicylic acid (ADS) in vitro on the natural killer (NK) activity of peripheral blood mononuclear cells (MNC) have been examined and compared with those of the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) and the cyclooxygenase inhibitor, indomethacin. 2. Sulphasalazine, sulphapyridine and ADS inhibited NK activity with 50% inhibitory concentrations (IC50) of 0.7, 2.5 and 4.0 mmol/l respectively. The effect was rapidly reversible. In contrast, 5-ASA minimally inhibited NK activity at 50 mmol/l only. 3. NDGA potently inhibited NK activity (IC50 27 μmol/l) but this was only partly reversible in short term incubations. Indomethacin had no effect at concentrations less than those inhibiting cyclo-oxygenase activity (1-10 μmol/l) but potently and reversibly inhibited NK activity at or above 25 μmol/l. 4. The inhibitory effects observed were unlikely to be due to direct toxicity of effector cells as 5-ASA, sulphapyridine and ADS had no effect on the viability of peripheral blood MNC, whereas NDGA and indomethacin lysed MNC only at maximal concentrations tested. Though sulphasalazine produced MNC lysis at and above 1 mmol/l, the rapid reversibility of the inhibition of NK activity at 1 mmol/l suggested that lysis of NK cells contributed little to the suppressive effect at this concentration. 5. The disparity of the therapeutic efficacy and effects on NK activity of sulphasalazine and its derivatives in vitro may suggest that NK activity is not a major pathogenic mechanism in ulcerative colitis. Any inhibitory effect on cellular immune function of indomethacin does not necessarily reflect an effect of cyclo-oxygenase inhibition.
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44

Miner, PB, and WL Biddle. "Maintaining Remission in Distal Ulcerative Colitis and Ulcerative Proctitis." Canadian Journal of Gastroenterology 4, no. 7 (1990): 476–80. http://dx.doi.org/10.1155/1990/864194.

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Maintenance of remission is an important consideration in the medical care of patients with ulcerative colitis. The relapse rate is high when medications are discontinued. Many types of medications have been investigated for potential efficacy of maintaining remission. This paper reviews the literature on maintenance therapy for both distal and universal ulcerative colitis. Sulphasalazine is the drug of choice since il is effective and relatively low m cost. 5-aminosalicylic acid (5-ASA) derivatives, both oral and rectal forms, are also effective. Other medications such as metronidazole, cromolyn sodium and prednisone have nor been shown to be effective maintenance therapy. Strategies for maintenance are outlined and include possible regimens with 5-ASA enemas. While 1 g of 5-ASA is effective, the long term relapse rate is similar co that seen with sulphasalazine. Patients capered co 1 g 5-ASA enemas have a good chance of maintaining remission if the colitis does not flare within the first few months, because most colites will flare up early on. Other possible regimens include intermittent enemas, eg, every other night or every third night. Patients in remission can be safely maintained in remission with sulphasalazine or one of its 5-ASA derivatives.
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45

Elsakka, Elsayed, Gamil Abd-Allah, Ahmed Abulsoud, Ahmed Mansour, and Sayed Raheem. "Sulphasalazine Prevents Fibrosis; Relevance of TGFβRI." International Journal of Biochemistry Research & Review 12, no. 3 (January 10, 2016): 1–10. http://dx.doi.org/10.9734/ijbcrr/2016/25627.

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46

Hoult, J. R. S. "Pharmacological and Biochemical Actions of Sulphasalazine." Drugs 32, Supplement 1 (1986): 18–26. http://dx.doi.org/10.2165/00003495-198600321-00005.

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47

Ireland, A., and D. P. Jewell. "Olsalazine in Patients Intolerant of Sulphasalazine." Scandinavian Journal of Gastroenterology 23, sup148 (January 1988): 101–3. http://dx.doi.org/10.3109/00365528809101561.

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48

Ireland, A., and D. P. Jewell. "Olsalazine in Patients Intolerant of Sulphasalazine." Scandinavian Journal of Gastroenterology 22, no. 9 (January 1987): 1038–40. http://dx.doi.org/10.3109/00365528708991953.

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49

PETTERSSON, T., M. GRIPENBERG, G. MOLANDER, and C. FRIMAN. "Severe Immunological Reaction induced by Sulphasalazine." Rheumatology 29, no. 3 (1990): 239–40. http://dx.doi.org/10.1093/rheumatology/29.3.239-a.

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50

Riley, S. A., P. J. Flegg, and B. K. Mandal. "CONTACT LENS STAINING DUE TO SULPHASALAZINE." Lancet 327, no. 8487 (April 1986): 972. http://dx.doi.org/10.1016/s0140-6736(86)91071-8.

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