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PubMed1996

Progression of ulcerative proctosigmoiditis: incidence and factors influencing progression.

OBJECTIVE: To assess the changing distribution of disease within the large bowel in patients presenting with ulcerative proctitis or proctosigmoiditis. To evaluate the influence of clinical exacerbations, smoking, parity and family history in disease extension. DESIGN: Retrospective single-centre study in a university hospital. METHODS: Case records of patients presenting over a 40-year period were examined to evaluate the clinical course and disease distribution from initial presentation to final follow-up. For each patient whose disease extended to the more proximal colon, an age- and sex-matched control patient was identified whose disease remained confined to the original site. Patients completed a questionnaire to provide information on family history, smoking and parity. The differences in clinical exacerbations, family history, smoking and parity were then compared between the two groups. RESULTS: Among 145 patients presenting with proctitis or proctosigmoiditis followed prospectively for a median period of 10.9 years, the disease extended in 53 patients. Using actuarial methods the disease progressed beyond the rectosigmoid area in 16% of patients at 5 years and 31% at 10 years. Among the patients whose disease progressed, progression was preceded in 68% of cases by a clinical exacerbation of the colitis. When patients whose disease progressed were compared with those whose disease remained confined to the original site, no differences were detected in the number of clinical exacerbations, smoking habit, family history or parity. CONCLUSIONS: The factors that are associated with the extension of colitis are probably different from those that predisposed an individual to develop inflammatory bowel disease initially.

Adult↗
PubMed1996

The topical treatment of distal ulcerative colitis.

In the absence of a definitively curative medical treatment of distal ulcerative colitis, the major objective of drug therapy is to optimize the quality of life by rapidly suppressing the symptoms of inflammation, without introducing major side effects. Conventional steroids administered topically decrease inflammation in about two-thirds of patients with active distal ulcerative colitis after 3-4 weeks of therapy. However, the risk of the systemic side-effects associated with their prolonged use discourages long-term treatment with these drugs. Enemas containing topically acting steroids are likely to replace conventional steroid enemas in the near future, especially in those patients who need long-term or high-dose therapy. The efficacy, safety and acceptance of rectal formulations of 5-aminosalicylic acid (5-ASA) in the short-term treatment of active ulcerative colitis are now well established. This 5-ASA enemas may be the best initial treatment when the disease is limited to the distal colon. Combination therapy of a topical corticosteroid with 5-ASA enema is a promising treatment for patients with active distal ulcerative colitis. Lignocaine, bismuth subsalicylate and short-chain fatty acids are new drugs under investigation with as yet unproven value. Better information concerning the natural history of the disease and a more careful definition of subgroups of patients may make it possible to personalize dosage, formulation and duration of the active medical treatment for patients with distal ulcerative colitis.

Administration, Topical↗
PubMed2004

Diagnosis and treatment of ulcerative proctitis.

Proctitis refers to inflammation of the rectum, a diagnosis made by endoscopic evaluation. Symptoms of proctitis include rectal bleeding, urgency, tenesmus, diarrhea or constipation, and occasionally rectal pain. The causes of proctitis include infection, medication, ischemia, radiation, and ulcerative proctitis. Ulcerative proctitis is an important and increasingly common subcategory of ulcerative colitis (UC) in which inflammation is limited to the rectum. Historically, oral aminosalicylates have been the mainstay of acute and maintenance therapy. A growing body of data, however, indicates that topical aminosalicylates are effective first line agents in ulcerative proctitis and distal UC. Topical aminosalicylates act more effectively and rapidly to induce and maintain remission compared with their oral counterparts or topical steroids. Rarely ulcerative proctitis is refractory to topical therapy and in these instances systemic corticosteroids, antibiotics, immunomodulators, or surgery is required. This review highlights the pathogenesis, diagnosis, and treatment of ulcerative proctitis.

Acute Disease↗
PubMed1986

Local disodium cromoglycate is ineffective in ulcerative proctosigmoiditis.

Conflicting results have emerged from studies using oral and rectal disodium cromoglycate (DSCG) in inflammatory bowel disease. In the present double-blind study, 43 patients with active ulcerative proctosigmoiditis received either placebo (n = 22) or 600 mg DSCG (n = 21) rectally as enemas for eight weeks. Assessment was made from clinical investigations, endoscopy, laboratory tests, biopsies, and diary cards. No statistically significant differences in bowel frequency, rectal bleeding, general well-being, abdominal pain, and severity and extent of the disease were found between the groups during the study. There was no significant change in the histologic parameters. No side-effect was encountered. It is concluded that DSCG did not improve symptoms or inflammatory changes in ulcerative proctosigmoiditis.

Adolescent↗
PubMed2004

Review article: problematic proctitis and distal colitis.

About two-thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure, and therefore may be effectively treated with topical treatment, allowing the delivery of the active drug directly to the site of inflammation and limiting systemic absorption and potential side-effects. Topical aminosalicylate therapy is the most effective approach, and most patients will benefit hugely, provided that the formulation reaches the upper extent of the disease. Therefore, the choice of topical preparation should be based on the proximal extent of the disease and on patient preference. Oral aminosalicylates are less effective than topical therapies; however, a combination of oral and topical aminosalicylates can be successful in refractory patients. Alternatives to aminosalicylates are the new glucocorticoids, budesonide and beclometasone dipropionate, either as enemas or oral formulations (only beclometasone dipropionate). A combination of oral or rectal new glucocorticoids with rectal aminosalicylates should be considered in patients refractory to either approach. When these measures fail, treatment with oral glucocorticoids is necessary. An intensive intravenous steroid regimen is also helpful for patients refractory to oral steroids. Alternative treatments include short-chain fatty acid enemas, nicotine enemas and patches, acetarsol suppositories, ciclosporin enemas and epidermal growth factor enemas. Several factors potentially having a negative impact on therapeutic response include concurrent enteric pathogens, coexistent irritable bowel syndrome, patient nonadherence to therapy, inadequate dosing and duration of therapy, and proximal progression of the disease. Surgical colectomy may be required in those rare patients refractory or intolerant to pharmacotherapy.

Aminosalicylic Acids↗
PubMed2005

Colonic spread and serum pharmacokinetics of budesonide foam in patients with mildly to moderately active ulcerative colitis.

BACKGROUND: Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option. AIMS: To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation. METHODS: Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of gamma-scintigraphy for 6 h. Serum samples were taken simultaneously. RESULTS: Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum C(max) and AUC(0-8 h) values of 0.8 +/- 0.5 ng/mL and 3.7 +/- 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h. CONCLUSIONS: In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis.

Administration, Rectal↗
PubMed2006

Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis.

BACKGROUND: Rectal budesonide is an effective treatment of active ulcerative proctitis or proctosigmoiditis. AIM: To compare the therapeutic efficacy, tolerability and safety, and patient's preference of budesonide foam vs. budesonide enema. METHODS: Patients with active ulcerative proctitis or proctosigmoiditis (clinical activity index > 4 and endoscopic index > or = 4) were eligible for this double-blind, double-dummy, randomized, multicentre study. They received 2 mg/25 mL budesonide foam and placebo enema (n = 265), or 2 mg/100 mL budesonide enema and placebo foam (n = 268) for 4 weeks. Primary endpoint was clinical remission (clinical activity index < or = 4) at the final/withdrawal visit (per protocol). RESULTS: A total of 541 patients were randomized--533 were evaluable for intention-to-treat analysis and 449 for per protocol analysis. Clinical remission rates (per protocol) were 60% for budesonide foam and 66% for budesonide enema (P = 0.02362 for non-inferiority of foam vs. enema within a predefined non-inferiority margin of 15%). Both formulations were safe and no drug-related serious adverse events were observed. Because of better tolerability and easier application most patients preferred foam (84%). CONCLUSION: Budesonide foam is as effective as budesonide enema in the treatment of active ulcerative proctitis or proctosigmoiditis. Both budesonide formulations are safe, and most patients prefer foam.

Administration, Rectal↗
PubMed1981

Serum and salivary immunoglobulin A and free secretory component in ulcerative colitis.

Patients with ulcerative colitis have been investigated for evidence of defects in secretory immunity. Total serum IgA concentration, serum IgA antibody titres to Candida albicans, salivary IgA and free secretory component concentrations have been measured in thirty-six patients with ulcerative colitis and thirty-six normal controls. None of the parameters was significantly different between patients with proctitis and patients with extensive colitis or between the colitis patients and normal controls.

Adolescent↗
PubMed1980

The management of radiation proctitis.

This paper deals with the clinical features, diagnosis and treatment of acute and delayed forms of radiation injury of the rectum. A series of thirty-seven patients with this condition is reported and the current literature is reviewed. Although there have been no major advances in the treatment of this problem, an improvement in results of operative procedures can be expected with a better understanding of the pathology, the use of parenteral nutrition, and the introduction of several new techniques of bowel anastomosis. Aspects of prevention are also discussed.

Female↗
PubMed1984

Altered blood lymphocyte subclasses in patients with ulcerative colitis.

Peripheral blood lymphocytes were studied by flow cytofluorimetry and monoclonal antibody techniques in 107 patients with ulcerative colitis and in 20 healthy controls of similar ages. Total T, T helper (TH), and T cytotoxic/suppressor (TC/S) lymphocytes were defined by the monoclonal antibodies OKT3, OKT4 and OKT8, respectively, while B lymphocytes were defined by surface immunoglobulin. Patients had a significantly (P less than 0.05) lower proportion of TC/S lymphocytes than the controls, and patients with quiescent disease had a reduced proportion of B lymphocytes compared to controls and those with active disease. Patients with marked mucosal dysplasia had a significantly (P less than 0.025) lower proportion of TH lymphocytes and a higher (P less than 0.01) proportion of B lymphocytes than those without dysplasia. There were no significant associations between lymphocyte levels and any other clinicopathological features assessed.

Adult↗
PubMed1982

Reactive arthritis associated with Clostridium difficile.

A case of reactive arthritis in a patient with a previously documented history of Reiter's syndrome is described. The precipitating agent appears to have been Clostridium difficile. High levels of toxin were demonstrable in the faeces and neutralising antitoxin was detected in the patient's serum but not synovial fluid. Resolution of the polyarthropathy was slow despite successful eradication of the C. difficile with a course of vancomycin.

Adult↗
PubMed2000

Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease.

OBJECTIVE: We measured the mucosal levels of interleukin 1beta (IL-1beta), IL-2, IL-6, and IL-8 in affected segments of radiation-induced proctosigmoiditis and compared these with the levels in normal controls and inflammatory bowel disease (IBD) patients. METHODS: Thirteen patients with histologically proven radiation proctosigmoiditis, 32 patients with active ulcerative colitis (UC), 35 patients with Crohn's disease, and 15 normal subjects undergoing routine colonoscopy were included in the study. All patients underwent colonoscopy and mucosal biopsies were obtained from both diseased and normal-appearing areas. Mucosal levels of IL-1beta, IL-2, IL-6, and IL-8 were determined by solid-phase enzyme-linked immunosorbent assay (ELISA) using the Quantikine method (R&D Systems, Minneapolis, MN). All the data were statistically analyzed using Student's t test. RESULTS: The mucosal levels of IL-2, IL-6, and IL-8 were significantly higher in both diseased segments (5.62 +/- 0.13, 1.60 +/- 0.31, and 21.45 +/- 4.03 pg/ml, respectively) and normal-appearing segments (3.83 +/- 0.78, 1.36 +/- 0.34, and 13.45 +/- 3.18 pg/mg) in the radiation proctitis group compared to those of normal control subjects (1.74 +/- 0.23, 0.67 +/- 0.09, and 4.99 +/- 1.39 pg/mg). These differences were statistically significant (p < 0.05). In the UC group, IL-1beta, IL-6, and IL-8 levels in diseased segments were 4.98 +/- 0.53, 2.22 +/- 0.28, and 88.85 +/- 8.05 pg/mg, respectively. In Crohn's disease patients, IL-1beta, IL-6, and IL-8 levels were 5.45 +/- 0.93, 2.88 +/- 0.58, and 61.68 +/- 10.02 pg/mg, respectively. All these levels were significantly higher (p < 0.05) compared with IL-1beta, IL-6, and IL-8 levels from normal segments of IBD patients. Compared with the radiation proctitis patients, the levels of IL-6 and IL-8 were significantly higher in the IBD group. CONCLUSIONS: The mucosal levels of IL-2, IL-6, and IL-8 were significantly higher in both diseased and normal segments of colon in patients with radiation proctitis, compared with normal controls. Only IL-1beta levels were significantly higher in diseased segments, compared with endoscopically normal-appearing segments in radiation proctitis. These results indicate that there is a similarity in the activation of mucosal cytokines between IBD and radiation proctosigmoiditis. This may partly explain the beneficial effects of similar topical and systemic agents such as steroids and mesalamine compounds when used in radiation-induced proctosigmoiditis.

Colitis, Ulcerative↗
PubMed2001

Effect of ecabet sodium enema on mildly to moderately active ulcerative proctosigmoiditis: an open-label study.

OBJECTIVES: Ecabet sodium (ES), a nonabsorbable antigastric ulcer agent, has been shown to adhere to the region of an ulcer. It topically enhances gastric mucosal defensive factors such as the endogenous prostaglandins, capsaicin-sensitive sensory nerves, nitric oxide, and mucin. All of these mucosal defensive factors play an important role in maintaining the mucosal integrity of the colon and rectum. Therefore, we investigated the effect of ES in patients with mildly to moderately active ulcerative proctosigmoiditis. METHODS: In an open-label study, seven patients with mildly to moderately active ulcerative colitis (UC) who had an inflamed mucosa in the rectum and/or sigmoid and were resistant to 4-wk topical and systemic standard treatment were treated with an ES enema b.i.d. for 14 days. The enema consisted of ES (1 g) and tepid water (20 or 50 ml). These patients were assessed by the Clinical Activity Index, colonoscopically, and histologically before and after the ES therapy. The ES therapy was started after obtaining informed consent from the patients. RESULTS: Six of the seven patients responded to therapy and achieved clinical, endoscopic, and histological remissions. One patient was withdrawn because of increased stool frequency. All six patients who completed the study showed a significant change in the mean Clinical Activity Index score from 5.3+/-1.4 (mean +/- SD) to 0.5+/-0.8 (p < 0.05), in the colonoscopic score from 3.0+/-0.9 to 0.8+/-0.4 (p < 0.05), and in the histological score from 2.7+/-0.5 to 0.5+/-0.6 (p < 0.05), and achieved remission at the end of the study. There were no side effects attributable to the ES therapy. Five of the six patients are still in clinical remission after a median follow-up period of 5 months. CONCLUSIONS: The ES enemas proved to be a safe and potentially useful adjuvant therapy currently available for treating patients with mildly to moderately active ulcerative proctosigmoiditis. A controlled study is necessary to confirm our results.

Abietanes↗
PubMed1987

Osteoporosis in patients with inflammatory bowel disease.

Bone mineral content in spinal trabecular and peripheral cortical bone was measured in 75 unselected patients with small and/or large intestinal inflammatory bowel disease. Osteoporosis, defined as a bone mineral content greater than 2 SD below the age and sex matched normal mean value was present in 23 patients (30.6%). Three amenorrhoeic females aged 34, 38, and 42 years had severe clinical osteoporosis and a further three patients had one or more vertebral crush fractures. Eighteen of the 23 patients with osteoporosis had small intestinal disease with one or more resections and the mean lifetime steroid dose in those with osteoporosis was significantly higher than in those with normal bone mineral content. Bone mineral content in spinal trabecular bone showed significant negative correlations with lifetime steroid dose and serum alkaline phosphatase and a significant positive correlation with serum albumin. Peripheral cortical bone mineral content was positively correlated with body weight, height and body mass index. We conclude that the prevalence of osteoporosis is increased in patients with inflammatory bowel disease, severe clinical osteoporosis developing in some relatively young patients. The pathogenesis of this bone loss is probably multifactorial; steroid therapy is likely to be an important contributory factor.

Adult↗
PubMed1992

Use of coculture of colonic mucosal biopsies to investigate the release of eicosanoids by inflamed and uninflamed mucosa from patients with inflammatory bowel disease.

Eicosanoid production was measured in cultured biopsies of colonic mucosa from control patients, with the irritable bowel syndrome, and from patients with proctosigmoiditis and with colonic Crohn's disease. Cultured inflamed colonic mucosa from patients with proctosigmoiditis and Crohn's disease produced more prostaglandin E2 and leukotrienes C4 than control tissues. In addition, eicosanoid production by macroscopically uninflamed or 'quiescent' mucosa from the right colon was examined in patients with proctosigmoiditis and between skip lesions in Crohn's disease patients. In the proctosigmoiditis group quiescent mucosa produced eicosanoids in similar quantities to control tissue. Coculture of quiescent plus inflamed tissue however, generated a marked increase in eicosanoid output in 12 of 20 of the patients and this was similar to the quantity obtained from two pieces of inflamed tissue. In the Crohn's disease group, quiescent mucosa produced more eicosanoids than control mucosa but production was markedly stimulated by coculture with inflamed mucosa in all patients. These findings suggest that in some patients with proctosigmoiditis and in all patients with Crohn's disease quiescent mucosa appears to be sensitised. A small but significant increase in the macrophage population may be partly responsible but it is likely that these and other cells are primed to release eicosanoids, and may be induced to do so by soluble mediators produced by actively inflamed tissue.

Adult↗