Diverticulitis: New Concepts and New Therapies

Abstract

In 2004, this Journal published a supplement “Colitis: Problems in Pathological and Clinical Diagnosis-Indeterminate, Microscopic and Diverticulitis.” One article was published on the overlap syndrome between inflammatory bowel disease and segmental colitis.1 A second article was published in the supplement on the pathologic observations of segmental diverticular disease.2 A third article was published that theorized and proposed a mechanism of chronic colon inflammation progressing to acute diverticulitis.3 In that theory, it was proposed that chronic inflammation occurs in the areas of mass diverticula as evidenced by an uncontrolled study that obtained biopsy specimens from asymptomatic subjects with mass diverticula in the sigmoid.4 Since it is accepted that diverticula form as part of a fiber deficiency disease3 and since it is known that the microflora is different in subjects eating high fiber versus low fiber,3 it was proposed that the chronic inflammation occurs as a result of alteration in the normal microflora.3 It would then follow that altering the flora or that administering anti-inflammatory agents may help prevent diverticulitis (Fig. 1).FIGURE 1: Theoretical framework of diverticulitis and proposed therapy.It is noteworthy that two articles have appeared in the recent literature that supply evidence to the hypothesis proposed above. Antonio Tursi, in a review article published this year in Expert Opinion, clearly summarizes the recent literature on the effectiveness of mesalamine in treating chronic diverticular disease.5 The pathologic observations that segmental colitis does occur in subjects with significant diverticular disease in the left colon is the premise in which mesalamine is used as an anti-inflammatory agent just as it is used in ulcerative colitis and Crohn's disease. The first study using this agent was done in 1999.6 The investigators added mesalamine to antibiotic treatment after an acute attack. They concluded there was a very significant prolongation of the symptom-free period following an attack of acute diverticulitis when mesalamine was added to antibiotic therapy.6 Another study used the same principle of adding mesalamine to antibiotic therapy and obtained similar results.7 These observations were confirmed in another published study on 90 subjects where the antibiotic was administered for 10 days followed by mesalamine for 8 weeks.8 A similar study for 12 months indicated that the effect is prolonged.9 Although these observations occurred in only three settings and by three groups, the data are impressive from an accumulative aspect even though some of the experiments were not blinded and handicapped by being relatively uncontrolled. The fact that mesalamine appears to work to decrease the length of the attack and reoccurrence in the hands of some investigators adds evidence to the theory that diverticular disease is a chronic inflammatory disease of the bowel and that diverticulitis of a recurrent nature may be fairly well controlled by altering the inflammatory response. In the first report of the use of probiotics in the treatment of symptomatic uncomplicated diverticular disease, Frič and Zavoral administered Escherichia coli Nissle strain to 15 patients after two successive attacks of diverticulitis.10 They administered antibiotics after the first attack plus an intestinal absorbent, and then administered the probiotic after a second attack. The average period of administration of the probiotic was 5.2 weeks. The authors reported that the antibiotics resulted in a remission averaging 2.43 months, whereas the probiotic-treated group had an average remission time of 14.1 months. According to their evaluation, this is highly significant. Although this study lacks controls and can be strongly criticized because of a lack of randomization with a small number of patients used, it is the first reported study in which probiotics were used in an attempt to prevent recurrent diverticulitis. Certainly, much more evaluation is needed in this area. Nevertheless, the finding that anti-inflammatory drugs and probiotics may be helpful in recurrent diverticulitis lends support to the hypothesis that chronic inflammation is related to recurrent acute diverticulitis. Certainly, well-controlled studies are needed with both anti-inflammatory agents and probiotics to determine whether these agents are truly effective.