Postgrad MedJ_ 1996; 72: 714- 718 (© The Fellowship of Postgraduate Medicine, 1996 Current concepts Postgrad Med J: first published as 10.1136/pgmj.72.854.714 on 1 December 1996. Downloaded from The role of cigarettes and nicotine in the onset and treatment of ulcerative colitis Summary Epidemiological evidence suggests Jon Birtwistle that ulcerative colitis is a disease ofnonsmokers, while Crohn's dis- ease is a disease of smokers. The Cigarette smoking has long been associated with diseases of the lungsl'3 and relative risk of developing ulcera- cardiovascular system,47 and evidence suggests that stopping smoking is the tive colitis is not only greater in most important factor in reducing both mortality8'9 and morbidity from nonsmokers, in addition there ap- coronary heart disease. There is, however, evidence to suggest that smoking pears to be a rebound effect in may also confer some protection against ulcerative colitis." smokers who quit, with the hea- In this article, the evidence that nicotine is both protective against the viest (ex-)smokers increasing development ofulcerative colitis and a useful clinical treatment of its symptoms their relative risk of the disease is reviewed. Four main areas are examined. Firstly, there is a brief overview of the most. This factor poses an the pathophysiological mechanisms involved in the development of ulcerative ethical dilemma for health profes- colitis; secondly, the evidence of a link between tobacco and ulcerative colitis is sionals giving advice on stopping outlined; thirdly, the use of nicotine as a clinical treatmnent is evaluated and, smoking, which may thus have a finally, the possible actions of nicotine and smoking are discussed. serious detrimental effect on the health of some patients. Nicotine Ulcerative colitis is believed to be the pharmacolo- gical ingredient of tobacco that is Ulcerative colitis has been defined as "a recurrent inflammatory and responsible for this beneficial ef- ulcerative disease of the colon and rectum, characterised clinically by rectal fect and several clinical trials bleeding, diarrhoea, cramping and abdominal pain, anorexia, and weight using nicotine have demonstrated Ioss,,.12 Ulcerative colitis is one of the two major nonspecific inflammatory it to be an effective therapeutic bowel diseases, the other being Crohn's disease. Its onset is characterised by agent in the treatment of ulcera- lesions that develop in the base of the mucosal layer, originating in the tive colitis. Although the aetiology rectum and extending proximally into the colon, which eventually ulcerate of ulcerative colitis is unclear, due to immunological inflammatory processes, producing the above- current research using nicotine- mentioned symptoms. The aetiology of ulcerative colitis is unknown and based products has produced probably reflects a heterogeneous disorder. Shanahan suggests "an interac- some interesting clues, together tion between genetic predisposing factors, exogenous and endogenous with the possibility of some form triggers, and modulating factors".'3 One suggested exogenous trigger is that of therapeutic treatment based on of some harmful substance that penetrates the bowel wall, initiating the http://pmj.bmj.com/ nicotine administration. inflammatory response.'4 Epidemiological data suggests that the incidence of ulcerative colitis is 5 - 10 Keywords: ulcerative colitis, cigarette per 100 000 and the prevalence about 100 per 100 0,5 with the peak age at smoking, nicotine presentation being in the third decade.'6 Ulcerative colitis appears to be more common in whites than blacks and, in the white population, more common in Jews and northern Europeans.'2 Ulcerative colitis Cope and Heatley suggest three main factors that may have an important role on September 23, 2021 by guest. Protected copyright. in the development of ulcerative colitis: mucosal epithelial defences, mucosal * ulcerative colitis is a recurrent immune defences and inflammatory mediators. An examination ofthe mucosal inflammatory and ulcerative disease epithelium indicates that patients with ulcerative colitis have a thin mucus of the colon and rectum layer,'7 thereby making them more predisposed to intestinal mucosal assault. * onset is characterised by the The response of the colon in patients with ulcerative colitis is that of chronic development of lesions in the be an abnormal immune in mucosal layer from the rectum inflammation, suggesting that there may response extending proximally into the colon these patients. Shanahan suggests that non-autoimmune mucosal T-cell * symptoms include rectal bleeding, activation also plays a major role in the clinical symptoms of ulcerative colitis. diarrhoea, cramping and abdominal Persistent or unchecked mucosal T cell activation increases the production of pain, anorexia and weight loss cytokines which mediate the inflammatory process. Direct cytokine effects on * incidence: 5-10 per 100 000 the mucosal tissue include the stimulation ofthe growth ofintestinal crypt cells. * prevalence: 100 per 100 000 At present, the stimulus for T-cell activation remains a puzzle, although Shanahan proposes that an interaction between genetic factors and colonic Box 1 microbial flora may play a part.'3 Chronic inflammation is known to be perpetuated by numerous inflamma- tory mediators, particularly the eicosanoids, which include the prostaglandins. Department of Psychiatry, University Prostaglandin E2 (PGE2) levels are raised in ulcerative colitis. '7 There is, of Southampton, Faculty of Medicine, however, some evidence to support the role of PGE2 in the protection of the Royal South Hants Hospital, mucosa from colitis in rats,'8 although it is difficult to reconcile this view with Southampton S014 OYG, UK the evidence supporting an inflammatory role of PGE2 in the development of J Birtwistle ulcerative colitis. There are also several immunological changes that are Accepted 24 January 1996 characteristic of ulcerative colitis, namely an increase in plasma cells and Smoking and ulcerative colitis 715 specific increases in (Ig) IgG and IgM, with IgA levels immunoflobulins Postgrad Med J: first published as 10.1136/pgmj.72.854.714 on 1 December 1996. Downloaded from Conventional treatment remaining mostly unchanged.' Another effect on the is the local * anti-inflammatories alone, eg, major inflammatory response influx of mesalamine (5-aminosalicylic acid) neutrophils which are believed to mediate most change in ulcerative colitis. * anti-inflammatories combined with Neutrophils are known to release chemotaxic factors such as leukotriene B4 antibiotics, eg, sulphasalazine (LTB4) which attracts more neutrophils and other acute inflammatory cells, * corticosteroid anti-inflammatories, thereby escalating the inflammatory response.13 The treatment of ulcerative eg, prednisolone colitis has mainly concentrated upon treatment ofthe inflammatory response by * immunosuppressant therapy, eg, azathioprine the administration of anti-inflammatories alone (eg, mesalamine), antibiotics in * surgical management combination with anti-inflammatories (eg, sulphasalazine), the administration of corticosteroid anti-inflammatories (eg, prednisolone), or immunosuppres- sant therapy (eg, azathioprine).19'20 Surgical management is required when Box 2 acute emergency complications such as toxic megacolon occur or there is a failure to control the symptoms. In its acute stage, ulcerative colitis can be a life- threatening disease. Tobacco and ulcerative colitis Smoking and ulcerative colitis Ulcerative colitis has been described as a disease of nonsmokers,1121-27 while Crohn's disease is a disease of smokers.2729 A comprehensive meta-analysis * ulcerative colitis is a disease of nonsmokers and ex-smokers carried out by Calkins demonstrated a relationship between smoking and both * Crohn's disease is a disease of these diseases. In ulcerative colitis, nonsmoking was seen as a causal factor, smokers while the converse was true for Crohn's disease.30'3' * there is no evidence of a disease A questionnaire carried out by Harries et al indicated that only 8% of prodrome predisposing patients to patients with ulcerative colitis were smokers while 42% of those with Crohn's quit smoking disease were smokers. The non-smoking behaviour was not explained by a * there is a rebound effect in smokers who quit; 52% develop symptoms cessation of smoking due to the symptoms of the disease as 48% of within three years of quitting ulcerative colitis and 30% of Crohn's disease patients had never smoked. * heavy smokers who quit have an Forty per cent of ulcerative colitis patients were ex-smokers who had increased relative risk of 4.4 stopped, on average, 13 years previously." A similar difference in smoking * anecdotal evidence suggests that habits was found by Bures et al.32 The relative risk of developing ulcerative ex-smokers who recommence colitis is not only greater in nonsmokers, there also appears to be a rebound smoking experience a relief of 34 symptoms effect in smokers who quit.33 Motley et al found that 52% of ulcerative colitis patients developed the disease within three years of stopping smoking; they also suggest that smoking may delay the appearance of ulcerative colitis Box 3 in males. Heavy smokers who quit increase their relative risk of ulcerative colitis by 4.4. Boyko et al found no evidence to suggest a disease prodrome, that caused patients to stop smoking. Subjects who stopped smoking four years or more before the onset of ulcerative colitis had the greatest risk.36 This link