What options do we have for induction therapy for Crohn's disease?

The first goal of Crohn's disease treatment is to induce a response. The choice of induction therapy depends on a number of factors. First, disease severity will dictate the level of intensity of treatment. Moderate to severely active Crohn's disease needs to be treated more aggressively than mild disease. Second, it is important to consider the disease distribution, since some medications (e.g. 5-aminosalicylates, budesonide, antibiotics) are more effectively delivered to the small bowel or the colon. Third, prior medications need to be considered. A patient na?ve to immunomodulators and anti-TNF agents will be managed very differently from a patient who has already failed two anti-TNF drugs. A fourth critical factor is considering the individual patient. The balance of benefits and risks will depend upon the patient's expected disease course, and how much risk they are at personally for serious adverse events related to treatment. In addition, patients' preferences for treatment need to be addressed since they will choose therapies differently based on their personal experience with symptoms, thresholds for risk taking, and fears about their disease and treatment. The basic armamentarium for induction therapy for Crohn's disease includes: 5-aminosalicylates, antibiotics, budesonide, systemic corticosteroids, thiopurines, methotrexate, and anti-TNF agents. These drugs can be used alone or combined in difference treatment algorithms to optimize therapy. The art of treating the IBD patient is in understanding the options and being able to apply an individualized regimen based upon unique patient and disease factors.     

Medical therapy for Crohn's disease: top-down or step-up?

The emergency of effective biological therapy in the treatment of Crohn's disease (CD) has led to a clinical debate about 'step-up versus top-down strategy'. Step-up refers to the classic therapeutic approach, namely progressive intensification of treatment as disease severity increases. Top-down refers to the early introduction, in all CD patients, of intensive therapies, including biological agents and immunosuppressive drugs, with the aim of avoiding complications and improving quality of life, starting from the assumption that these drugs may interfere with the natural history of the disease. Very recently the Belgian IBD research group together with the Gut Club of North Holland designed 'the Step Up versus Top Down Trial'. Combination of infliximab with immunosuppressives at onset was better than the current standard approach in terms of both induction and maintenance of remission. However, several observations still limit the use of infliximab as first-line treatment in adult CD patients. In particular, the epidemiological observation that over 50% of CD patients have a mild disease over time and will never require aggressive therapies is against the indiscriminate use of top-down strategy. Lack of markers able to identify high-risk patients, discussions about long-term safety and the high costs of infliximab are further factors supporting a more careful approach to the management of CD.     

True or false? The hygiene hypothesis for Crohn's disease

The "hygiene hypothesis" for Crohn's disease postulates that multiple childhood exposures to enteric pathogens protect an individual from developing Crohn's disease later in life, while individuals raised in a more sanitary environment are more likely to develop Crohn's disease. In this issue of the American Journal of Gastroenterology, two Canadian case-control studies come to diametrically opposed conclusions regarding the hygiene hypothesis for Crohn's disease. This difference may be partially related to differences in study population (population based vs hospital based), age of onset, different genetic determinants, urban/rural residence (40% rural vs principally urban), or different exposures from the putative causative agent. As of now, the veracity of the hygiene hypothesis for Crohn's disease is not confirmed.     

Henoch-Schönlein purpura complicating adalimumab therapy for Crohn's disease

Anti-tumour necrosis factor-α (TNF) therapy has revolutionised the management of chronic inflammatory conditions. With ever increasing numbers of patients being treated with these agents, uncommon adverse reactions will inevitably occur more frequently. Cutaneous manifestations are associated with many of these chronic conditions and can complicate anti-TNF therapy in about 20% of cases. Vasculitic complications are rarely associated with anti-TNF therapy. Henoch-Schönlein purpura (HSP), a small vessel vasculitis, has been described following infliximab and etanercept therapy but never with adalimumab, a fully humanized TNF antibody. The risk of such immune-mediated reactions is theoretically less with adalimumab compared to infliximab but can still occur. Here we report the first case in the literature of HSP that can be attributed to the use of adalimumab in a 19-year-old male with recalcitrant Crohn’s disease.     

Is an ileal pouch an alternative for patients requiring surgery for Crohn's proctocolitis?

Background Most surgeons consider Crohn's colitis to be an absolute contraindication for a continent ileostomy, due to high complication and failure rates. This opinion may, however, be erroneous. The results may appear poor when compared with those after pouch surgery in patients with ulcerative colitis (UC), but the matter may well appear in a different light if the pouch patients are compared with Crohn's colitis patients who have had a proctocolectomy and a conventional ileostomy. Methods We assessed the long–term outcomes in a series of patients with Crohn's colitis who had a proctocolectomy and a continent ileostomy (59 patients) or a conventional ileostomy (57 patients). The median follow–up time was 24 years for the first group and 27 years for the second group. Results The outcomes in the two groups of patients were largely similar regarding both mortality and morbidity; the rates of recurrent disease and reoperation with loss of small bowel were also similar between groups. Conclusions The possibility of having a continent ileostomy, thereby avoiding a conventional ileostomy—even if only for a limited number of years—may be an attractive option for young, highly motivated patients.