Immunosuppressants and operation in ulcerative colitis.

Ulcerative colitis (UC) has many pathophysiologic features characteristic of immune diseases. These features provide the rationale for immunomodulatory therapy offered for treatment of UC in recent years. The association between UC and other autoimmune diseases, such as autoimmune anemia, pernicious anemia, systemic lupus erythematosus, and Hashimoto’s thyroiditis, has been previously described but there is no increase in the incidence of these disorders in patients with UC. Both UC and Crohn’s disease are characterized by a production of mucosal immunoglobulin G, Tand B-cell mucosal lymphocytosis, and macrophage activation during exacerbation of the disease. Autoantibodies are known to be present in UC, the most common being antineutrophil cytoplasmic antibody (ANCA). In UC, the staining pattern is perinuclear (pANCA), as opposed to Wegner’s granulomatosis, which has a cytoplasmic staining pattern. pANCA is expressed by 60% to 80% of patients with UC and by only 20% to 30% of patients with Crohn’s disease. Of interest is the fact that the vast majority of patients with pouchitis express pANCA. Antibody-producing cells are synthesized in reaction to intestinal antigens. T helper cells and B cells regulate the immune response, activating cytokines and resulting in altered immunoglobulin production. Importantly, the absolute number of lymphocytes in UC is normal, as are both delayed hypersensitivity and the subset of circulating T cells. The ratio of CD4 (helper) to CD8 (suppressor) T cells is the variable factor, and although the ratio is normal in remission, it is altered in exacerbation with T helper predominance. The B-cell population is less affected in UC, and natural killer cells are not defective, but there is an increase in lymphocyte production of interleukin2. The peripheral lymphocytes of UC patients have cytotoxic properties; this cytotoxicity is non–complement-dependent and is completely eliminated after colectomy. In summary, the immunopathology of UC involves an initiating antigen triggering a disproportionate inflammatory cascade. This cascade consists of inflammatory cell recruitment from the colonic blood supply with resultant release of inflammatory mediators. Mucosal function is altered by these changes, with increased permeability, mucous secretion, platelet activation, and tissue damage. Immunosuppressive agents are known to affect T-cell function and modulate cytokine function. This is the basis for the addition of cyclosporine, azathioprine, and 6-mercaptopurine to the conservative armamentarium for treating UC. The impact of prolonged steroid treatment as another indication for operation was evaluated by Sher and colleagues. They compared a matched group of patients treated either medically or surgically. Each group consisted of 20 patients matched for duration and severity of disease. Medically treated patients who required at least one hospital admission were compared with patients treated by a three-stage restorative proctocolectomy. Weight loss and transfusion requirements were both notably increased in the medically treated group. Sixty-five percent of patients in this group had major steroid-related complications, but the major surgical complication rate was only 15%.