Claudia Morselli

High-Dose Probiotics for the Treatment of Active Pouchitis

PurposePouchitis is the major long-term complication after ileal-pouch anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment in this condition. Recently, we have shown the efficacy of a highly concentrated probiotic preparation (VSL#3, 900 billions/sachet lyophilized viable bacteria) in preventing relapses of chronic pouchitis and in preventing pouchitis onset. This study was designed to evaluate the efficacy of high-dose VSL#3 in the treatment of mildly active pouchitis.MethodsTwenty-three consecutive patients with mild pouchitis, defined as a score of between 7 and 12 in the Pouchitis Disease Activity Index, which includes clinical, endoscopic, and histological criteria, were treated with VSL#3, 2 sachets b.i.d. (3600 billion bacteria/day) for four weeks. Symptomatic, endoscopic, and histologic evaluations were undertaken before and after treatment according to Pouchitis Disease Activity Index. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of ≤2, endoscopic score of ≤1, and total Pouchitis Disease Activity Index score of ≤4. Patients in remission after treatment were treated with VSL#3, 1 sachet b.i.d. (1800 billion bacteria), as maintenance treatment for six months. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire.ResultsSixteen of 23 patients (69 percent) were in remission after treatment. The median total Pouchitis Disease Activity Index scores before and after therapy were 10 (range, 9–12) and 4 (range, 2–11), respectively (P < 0.01). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 110 (range, 90–140) to 200 (range, 95–220; P < 0.001). All 16 patients who went into remission maintained remission during maintenance treatment. Only one patient experienced a transient bloating at the beginning of treatment.ConclusionsHigh doses of the probiotic VSL#3 are effective in the treatment of mild pouchitis. Further controlled studies are warranted.

Oral budesonide in the treatment of chronic refractory pouchitis

Background  Pouchitis is the major long‐term complication after ileal‐pouch nal anastomosis for ulcerative colitis. Ten to 15% of patients develop a chronic pouchitis, either treatment responsive or treatment refractory.

Probiotic therapy in the prevention of pouchitis onset : Decreased interleukin-1β, interleukin-8, and interferon-γ gene expression

Background: Probiotic therapy has been shown to prevent the onset of pouchitis and to improve the quality of life in ulcerative colitis patients who required ileal pouch anal anastomosis. Pouchitis has been associated with elevated levels of proinflammatory cytokines and chemokines. Methods: In this retrospective analysis of archived endoscopic samples from responding patients enrolled in the above‐mentioned trial, we were interested in studying mucosal gene expression of the pleiotropic proinflammatory cytokines (interleukin‐1&bgr;, interleukin‐6), TH1 cytokines (interferon‐&ggr;, tumor necrosis factor‐&agr;, interleukin‐12), regulatory cytokines (interleukin‐10, transforming growth factor‐&bgr;), and the chemokine interleukin‐8. In addition to assessment of cytokine gene expression, the presence of polymorphonuclear cells in the mucosal tissue was evaluated. Results: Data show that patients who were treated with probiotics had significant lower mucosal mRNA expression levels of interleukin‐1&bgr;, interleukin‐8, and interferon‐&ggr; compared with placebo‐treated patients. Conclusions: In addition, a lower number of polymorphonuclear cells was present in the tissue of patients within the probiotic group compared with the number of polymorphonuclear cells in the tissue of patients receiving placebo and patients having an episode of pouchitis. Conclusions: These data suggest that probiotic treatment regulates the mucosal immune response by reducing mucosal levels of neutrophil‐chemoattractant IL‐8 and tissue influx of polymorphonuclear cells, and may further act by inhibition of T‐cell activation, by reinforcement of barrier function and by a tight control of the potent pro‐inflammatory cytokine IL‐1&bgr;.

Probiotics - Role in inflammatory bowel disease

The aetiology of inflammatory bowel disease is still unclean. Whilst a specific pathogen agent associated with these diseases has not been found, the rationale for probiotic therapy in inflammatory bowel disease is based on convincing evidence involving intestinal bacteria in their pathogenesis. Encouraging results have been obtained with probiotic therapy in several animal models of experimental colitis. The administration of highly concentrated probiotic preparations represents a valid approach both for the prevention of pouchitis onset and relapses. The encouraging results obtained in ulcerative colitis and Crohns disease need to be further assessed in large double-blind trials.

Cutaneous manifestations in inflammatory bowel diseases: eight cases of psoriasis induced by anti-tumor-necrosis-factor antibody therapy.

Background: Ulcerous rectocolitis and Crohn’s disease are the best known forms of inflammatory bowel disease (IBD). Skin manifestations are not uncommon in IBD and may be divided into specific cutaneous signs, aspecific cutaneous signs, and cutaneous signs caused by drugs used for IBD therapy. The specific signs (fistulas, rhagades and ulcers) are the result of the diffusion of the intestinal inflammatory process into the skin. Aspecific cutaneous signs (stomatic aphthosis, erythema nodosum, pyoderma gangrenosum, Sweet’s syndrome, vasculitis, bullous diseases) are quite frequently found in those suffering from IBD, but also in apparently healthy subjects, and may sometimes be the first sign of the intestinal disease. Cutaneous manifestations due to drugs vary in clinical aspect and are the direct consequence of the therapies adopted, which in IBD patients can be quite numerous: steroids, immunosuppressants, 5-aminosalicylic acid, biological agents, antibiotics. Objective and Methods:Due to the frequent finding of cutaneous manifestations in patients affected by IBD, a collaboration was set up between the Dermatological Clinic of the University of Bologna and the Center for the Study of IBD of the same university hospital. The aim was to diagnose the cutaneous signs appearing during IBD and to establish their etiopathogenesis in order to assess whether they were the result of epiphenomena of the IBD or side effects of the therapies adopted. Results: The cutaneous manifestations we observed can be divided into three distinct groups: signs that were specific to the basic disease, aspecific signs and finally signs attributable to the drugs used for therapy. Particular attention was given to the aspecific signs and those consequential to therapy. The aspecific cutaneous signs seen in our clinic generally reflect those reported in the literature. The cutaneous manifestations due to drugs were further divided into three groups: rosacea, acneiform dermatitis and psoriasis-like dermatitis. The most notable aspect of our series is the high number of patients presenting psoriasiform-type dermatitides with a generally widespread diffusion. Conclusion: We would like to draw attention to the fact that all patients with psoriasis had been undergoing treatment with drugs inhibiting tumor necrosis factor α (TNF-α) as part of IBD therapy. In all cases, the cutaneous reaction started after the third or fourth infusion of the biological drug. Anti-TNF-α agents have also been successfully used to treat psoriasis in the last few years. The reason for this apparently paradoxical effect of the therapy is still unclear.

Controlled study using wireless capsule endoscopy for the evaluation of the small intestine in chronic refractory pouchitis.

Pouchitis is a common long‐term complication after ileal pouch anal anastomosis for ulcerative colitis. Chronic refractory pouchitis is a treatment‐resistant condition that affects 5–15% of patients.

Standard Treatment of Ulcerative Colitis

Ulcerative colitis (UC) is an idiopathic, chronic inflammation of the colon which may present with a range of mild to severe symptoms. The disease may be localized to the rectum or can be more extensive and involve the left side of the colon or the whole colon. Treatment in UC is directed towards inducing and maintaining remission of symptoms and mucosal inflammation. The key parameters to be assessed for the most appropriate treatment are the severity and extent of the inflammation. Meta-analyses of published trials have shown that topical treatment with 5-aminosalicylic acid (5-ASA) is the treatment of choice in active distal mild-to-moderate UC. Oral aminosalicylates are effective in both distal and extensive mild-to-moderate disease, but in distal disease, the rates of remission are lower than those obtained with topical 5-ASA. New steroids, such as budesonide and beclomethasone dipropionate (BDP), administered as enemas, constitute an alternative to 5-ASA therapy. In some studies, these have been shown to be as effective as conventional steroids but with significantly lower inhibition of plasma cortisol levels. Patients with unresponsive disease or those with more severe presentation will require oral corticosteroids and sometimes intravenous therapy. Approximately 10% of patients with unresponsive UC have severe attacks requiring hospitalization. Patients with severe disease should be managed jointly by a medical and surgical team, and intensive intravenous treatment should be started with high-dose steroids. Early recognition of failure of therapy will allow the introduction of immunosuppressive therapy with intravenous cyclosporine. Patients who respond are shifted to oral cyclosporine associated with azathioprine/6-mercaptopurine, whereas those who fail will require proctocolectomy. Oral aminosalicylates are the first-line therapy in maintenance of remission. Topical 5-ASA may play a role in distal disease. Patients who are steroid dependent can be started on azathioprine or 6-mercaptopurine although it may take up to 3 months for the treatment to become effective. They may have reversible immediate side effects, such as pancreatitis or bone marrow suppression, which disappear upon discontinuation of therapy. Close monitoring of these hematologic and biochemical parameters will improve safety. The use of biologic therapy with infliximab in more severe disease has not been established.

Antimicrobials in the Management of Inflammatory Bowel Disease

Many experimental and clinical observations suggest a potential role for intestinal microflora in the pathogenesis of inflammatory bowel disease (IBD). Manipulation of the luminal content using antibiotics may therefore represent a potentially effective therapeutic option. However, the available studies do not support the use of antimicrobials in ulcerative colitis and larger studies are required. These drugs are however effective in treating septic complications of Crohn’s disease (CD). The use of antibacterial agents as primary therapy for CD is more controversial, although this approach is frequently and successfully adopted in clinical practice. Despite the fact that properly controlled trials have been not carried out, antimicrobials are the mainstay of the treatment of pouchitis. Rifaximin is a poorly absorbed, broad-spectrum antibiotic that, thanks to its efficacy and long-term safety, could represent the preferred tool of manipulating enteric flora in patients with IBD. Preliminary data suggest that rifaximin may be beneficial in the treatment of active ulcerative colitis (and pouchitis), mild to moderate CD as well as prevention of post-operative recurrence of CD.

The management of refractory Crohn's disease

Refractoriness to conventional therapy is a common and intriguing problem in Crohns disease patients. At the present time there is no agreement on its definition and several mechanisms are involved in its determination. Immunosuppressors, such as azathioprine (AZA), 6‐mercaptopurine (6MP) and methotrexate (MTX) are effective drugs for controlling the inflammatory process and avoid chronic glucocorticosteroid treatment and its related related side‐effects. Recently, the introduction of tumour necrosis factor antibodies (infliximab) has dramatically changed the natural history of Crohns disease and its therapeutic approach. Several studies have determined the efficacy, mechanisms and safety of infliximab. However, this molecular approach has also left several questions unanswered about the mechanisms of refractoriness, possible concomitant treatments and long‐term safety and efficacy.

Management of Inflammatory Bowel Disease: Does Rifaximin Offer Any Promise?

An increasing number of both clinical and laboratory-derived observations support the importance of luminal components in driving the inflammatory response in ulcerative colitis and Crohn’s disease. Although its role is unclear, antibiotic therapy is commonly used in clinical practice for the treatment of moderately to severely active ulcerative colitis. Metronidazole and/or ciprofloxacin are currently employed in active Crohn’s disease, particularly in patients with colonic involvement and with perianal disease. Rifaximin, a rifamycin-derived antibiotic, is characterized by a wide range of antibacterial activity and a very low systemic absorption. Some preliminary data show its efficacy in severe active ulcerative colitis, pouchitis and prevention of postoperative recurrence in Crohn’s disease.