Golimumab may induce exacerbation of inflammatory bowel disease when it is used for the treatment of ankylosing spondylitis: a case report with a review of literature.

Golimumab is a human IgG monoclonal antibody specific for human tumor necrosis factor alpha. Golimumab has been approved for use in rheumatological conditions; however, its use in inflammatory bowel disease is still being evaluated in clinical trials. We report a case of an exacerbation of ulcerative proctitis after starting on golimumab for ankylosing spondylitis.

Qingchang suppositry induced remission in patients with mild-to-moderate ulcerative proctitis: a multicenter, prospective, randomized, parallel-controlled clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of Qingchang suppository (, QCS), a preparation of Chinese herbal medicine, in the induction of remission in patients with mild-to-moderate ulcerative proctitis (UP). METHODS: We performed a multicenter, prospective, randomized, parallel-controlled trial to evaluate the efficacy of QCS induction therapy in 140 adult patients with mild-to-moderate UP and TCM syndrome of dampness-heat in large intestine. The patients were randomized to receive QCS (study group) or Salicylazosulfapyridine (SASP) suppository (control group) one piece each time, twice a day, per anum for 12 weeks. Mayo score and main symptoms score were evaluated at weeks 0, 2, 4, 8 and 12, rectosigmoidscopy was taken at weeks 0, 4, 8 and 12, Geboes score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and safety indexes were assessed at weeks 0 and 12. The primary efficacy endpoint is clinical remission rate, the secondary efficacy endpoints are clinical response rate, mucosa healing rate, Geboes score, the remission rates of the main symptoms, the median day to the remission of the symptom, etc. RESULTS: There were no statistical difference in the clinical remission rates, the clinical response rates, the mucosa healing rates, Geboes score, ESR and CRP between the two groups. The remission rates of tenesmus and anal burning sensation of the study group were significantly higher than those of the control group (76.5% vs 25.0%, P = 0.009; 74.51% vs 29.63%, P = 0.003). The median day to the remission of purulent bloody stool of the study group was significantly less than that of control group [11 (1, 64) vs 19 (2, 67), P = 0.007]. The patients receiving QCS had a significantly higher mucosa healing rate at week 4 than the patients receiving SASP suppository (71.42% vs 52.85%, P = 0.023). No adverse event occurred in the study group while the adverse events incidence of the control group was 5.7% (P = 0.049). CONCLUSIONS: QCS could induce the remission of UP as effectively and safely as SASP suppository, and was superior to SASP suppository in relieving the symptoms of tenesmus, anal burning sensation and purulent bloody stool and the time to reach mucosa healing.

Claudin-2 regulates colorectal inflammation via myosin light chain kinase-dependent signaling.

BACKGROUND: Claudins have been demonstrated to be associated with inflammatory bowel disease (IBD), but the specific role of claudin-2 in colorectal inflammation remains undefined. AIMS: We aimed to determine the role of claudin-2 in TNFα-induced colorectal inflammation. METHODS: We used claudin-2 (-/-) mice to assess the role of claudin-2 in colon. The mice were intraperitoneally injected with 3 µg of recombinant murine TNFα, and the NF-κB signaling and mRNA expression levels of proinflammatory cytokines and myosin light chain kinase (MLCK) were evaluated. Moreover, in claudin-2 (-/-) mice, colitis was induced by the administration of dextran sodium sulfate (DSS). The involvement of claudin-2 in colorectal inflammation was also investigated using the Caco-2 human colon adenocarcinoma cell line, and the expression of claudin-2 was downregulated using claudin-2 siRNA. RESULTS: TNFα-induced colorectal inflammation via NF-κB signaling activation was enhanced in claudin-2 (-/-) mice compared with that in claudin-2 (+/+) mice. MLCK expression level in the colon tissue of claudin-2 (-/-) mice treated with TNFα was enhanced in comparison to that of the claudin-2 (+/+) mice. DSS-induced colitis was more severe in the claudin-2 (-/-) mice than in the claudin-2 (+/-) mice. In in vitro experiments, the decreased expression of claudin-2 enhanced the expressions of IL-6, IL-1ß and MLCK. CONCLUSIONS: Our findings concerning the role of claudin-2 in epithelial inflammatory responses enrich our collective understanding of mucosal homeostasis and intestinal diseases such as IBD. Furthermore, the results of this study indicate that claudin-2 and MLCK are potential therapeutic targets for treatments against intestinal disease.

[Perianal ulcerations caused by potassium permanganate bath]. / Perianale Ulzerationen durch Kaliumpermanganatbäder.

A 73-year-old female patient presented with acute very painful perianal ulcerations. She reported using various ointments and later potassium permanganate baths because of maceration of the rima ani as a manifestation of her psoriasis vulgaris. Suddenly after starting the potassium permanganate baths, necrotic areas developed with then became ulcerated. After excluding the relevant differential diagnostic considerations, we diagnosed ulcerations caused by a caustic burn from potassium permanganate. After stooping potassium permanganate baths and employing modern moist wound therapy, we attained complete healing after 8 months of treatment.

Preclinical Model of Perianal Fistulizing Crohn's Disease.

BACKGROUND: Fistulizing anoperineal lesions (FAPLs) are common and severe complications of Crohn's disease (CD), exposing patients to the risk of anal sphincter alteration and permanent stoma. Due to the limited efficacy of current treatments, identifying new local therapies is mandatory. However, testing new treatments is currently limited because no relevant preclinical model of Crohn's-like FAPL is available. Thus, a reliable and reproducible experimental model of FAPLs is needed to assess new therapeutic strategies. METHODS: Twenty-one rats received a rectal enema of 2,4,6-trinitrobenzensulfonic acid (TNBS) to induce proctitis. Seven days later, a transsphincteric fistula tract was created with a surgical thread, instilled with TNBS twice a week until its removal at day 7 (group 1), day 14 (group 2), or day 28 (group 3). In each rat, pelvic MRI was performed just before and 7 days after thread removal. Rats were sacrificed 7 days after thread removal for pathological assessment of the fistula tract. RESULTS: The optimal preclinical model was obtained in group 3. In this group, 7 days after thread removal, all animals (9 of 9) had a persistent fistula tract visible on MRI with T2-hypersignal (normalized T2 signal intensity: 2.36 ± 0.39 arbitrary units [a.u.] [2.08-2.81]) and elevation of the apparent diffusion coefficient (1.33 ± 0.16 10-3 millimeter squared per seconds [1.18-1.49]). The pathological examination of the fistula tract revealed acute and chronic inflammation, granulations, fibrosis, epithelialization, and proctitis in the adjacent rectum. CONCLUSIONS: This reproducible preclinical model could be used to assess the effectiveness of innovative treatments in perianal fistulizing CD.

Vulval fixed drug eruption due to paracetamol.

Paracetamol is a readily available non-prescription analgesic. Fixed drug eruption (FDE) is a well-reported side effect of paracetamol, usually the classic, pigmenting type. In women, it may present as a chronic, erosive vulvitis. We describe a case of FDE due to paracetamol presenting as a chronic erosive vulvitis in an older woman taking multiple medications. Diagnosis was delayed because paracetamol is available without prescription, taken intermittently and may be omitted from the clinical history. Cessation of paracetamol led to prompt resolution of symptoms. Consideration should be given to paracetamol as a cause of FDE presenting as a chronic erosive vulvitis.

Phase I trial of orally administered pentosan polysulfate in patients with advanced cancer.

Tumor angiogenesis is critically important to tumor growth and metastasis. We have shown that pentosan polysulfate (PPS) is an effective inhibitor of heparin-binding growth factors in vitro and can effectively inhibit the establishment and growth of tumors in nude mice. Following completion of our Phase I trial of s.c. administered PPS, we performed a Phase I trial of p.o. administered PPS in patients with advanced cancer to determine the maximum tolerated dose (MTD) and toxicity profile and to search for any evidence for biological activity in vivo. Patients diagnosed with advanced, incurable malignancies who met standard Phase I criteria and who did not have a history of bleeding complications were enrolled, in cohorts of three, to receive PPS p.o. t.i.d., at planned doses of 180, 270, 400, 600, and 800 mg/m2. Patients were monitored at least every 2 weeks with physical exams and weekly with hematological, chemistry, stool hemoccult, and coagulation blood studies, and serum and urine samples for PPS and basic fibroblastic growth factor (bFGF) levels were also taken. The PPS dose was escalated in an attempt to reach the MTD. Eight additional patients were enrolled at the highest dose to further characterize the toxicity profile and biological in vivo effects of PPS. A total of 21 patients were enrolled in the three cohorts of doses 180 (n = 4), 270 (n = 3), and 400 (n = 14) mg/m2. The most severe toxicities seen were grade 3 proctitis and grade 4 diarrhea; however, 20 of the 21 patients had evidence of grade 1 or 2 gastrointestinal (GI) bleeding. These toxicities became evident at a much earlier time point as the dose was increased, but their severities were similar at all dose levels. There were no objective responses, although three patients had prolonged stabilization of previously progressing disease. Pharmacokinetic analysis suggested marked accumulation of PPS upon chronic administration. Serum and urine bFGF levels failed to show a consistent, interpretable pattern; however the data suggested an inverse relationship between PPS and bFGF levels in vivo. A MTD could not be determined using the daily t.i.d. dosing schedule due to the development of grade 3/4 GI toxicity (proctitis) at all dose levels studied. PPS, administered p.o. at doses of 400 mg/m2 t.i.d., did not cause significant systemic toxicity, but most patients developed moderate-to-severe GI toxicity within 1-2 months. The cause of the GI toxicity was unclear, but it was readily reversible upon cessation of the agent. The suggestion of an inverse relationship between PPS and bFGF supports further study of PPS as an antiangiogenic agent. The tested doses and schedule cannot be recommended for further study. Subsequent murine experiments showed PPS to be more effective as an anticancer agent when it is given intermittently. We propose a study of PPS given on a weekly schedule in further clinical trials.

Possible role of mucosal mast cells in the recovery process of colitis induced by dextran sulfate sodium in rats.

To clarify the role of mucosal mast cells in the lesion sites of colitis induced by dextran sulfate sodium (DSS) in rats, we investigated the histological changes and alterations relevant to mucosal mast cells in the spontaneous recovery process of colitis. Oral administration of 4% DSS solution for 11 days resulted in surface epithelial loss, crypt loss and goblet cell depletion in the rectal mucosa. A marked infiltration of inflammatory cells into the mucosa, which was consistent with a significant increase in myeloperoxidase (MPO) activity, was observed. In addition, mucosal mast cell number and rat mast cell protease (RMCP) I and II levels in the rectum increased at day 0 after DSS treatment, and most of the mucosal mast cells were degranulated. After replacing 4% DSS solution with water, re-epithelialization and restoration of goblet cells were observed at day 5 and day 10, respectively, but crypt damage was hardly recovered even at day 20. The elevated myeloperoxidase activity was significantly decreased from day 5 after DSS treatment. The increased number of mucosal mast cells was further elevated up to about 1.5-fold at day 10 and day 20 after DSS treatment and little degranulation was observed. In the spontaneous recovery process, the increased rat mast cell protease II level in the rectum was maintained for 20 days, while the increased rat mast cell protease I level was gradually decreased and recovered to control level. These results suggest that proliferated mucosal mast cells remained for 20 days, although most of infiltrated inflammatory cells disappeared in spontaneous recovery process of colitis. It may therefore be presumed that proliferated mucosal mast cells play a role in spontaneous recovery process of the colitis induced by DSS.

Waiting-list induced proctitis: the hydrogen peroxide enema.

Hydrogen peroxide is a widely available disinfectant that has been reported to cause colitis. We report a case of a 67-year-old man who presented with an acute proctitis caused by a self-inflicted 3% hydrogen peroxide enema. The patient's intention was to cure himself of a recently diagnosed prostate cancer, because the waiting list for oncological consultation was deemed too long. The pathogenesis of hydrogen peroxide mucosal injury and a review of the literature is discussed.

Influence of trimebutine on inflammation- and stress-induced hyperalgesia to rectal distension in rats.

The effects of trimebutine and its major metabolite, N-desmethyltrimebutine on inflammation- and stress-induced rectal hyperalgesia have been evaluated in rats fitted with electrodes implanted in the longitudinal striated muscle of the abdomen. Intermittent rectal distension was performed before and 3 days after induction of rectal inflammation by local infusion of trinitrobenzenesulphonic acid (in ethanol). Stress consisted of 2h partial restraint and rectal distension was performed before and 30min after the end of the partial restraint session. The animals were treated intraperitoneally with trimebutine or desmethyltrimebutine (5, 10 or 20mgkg(-1)) or vehicle 15min before rectal distension. Naloxone (1mgkg(-1)) or saline was injected subcutaneously before trimebutine and desmethyltrimebutine. Before treatment trimebutine at the highest dose (20mgkg(-1)) reduced the abdominal response to rectal distension for the highest volume of distension (1.6mL) whereas desmethyltrimebutine was inactive. After rectocolitis the abdominal response to rectal distension was enhanced and trimebutine at 5mgkg(-1) reduced and at 10 mgkg(-1) suppressed inflammation-induced hyperalgesia, an effect reversed by naloxone. Desmethyltrimebutine was inactive. Stress-induced hypersensitivity was attenuated or suppressed, or both, by trimebutine and desmethyltrimebutine at doses of 5, 10 or 20mgkg(-l); greater efficacy was observed for desmethyltrimebutine and the effects were not reversed by naloxone. It was concluded that trimebutine and desmethyltrimebutine are active against inflammation- and stress-induced rectal hyperalgesia but act differently. The effect of trimebutine on inflammation-induced hyperalgesia is mediated through opioid receptors.

Paclitaxel-carboplatin induced radiation recall colitis.

Some chemotherapeutic agents can "recall" the irradiated volumes by skin or pulmonary reactions in cancer patients who previously received radiation therapy. We report a recall colitis following the administration of paclitaxel-containing regimen in a patient who had been irradiated for a carcinoma of the uterine cervix. A 63-year-old woman underwent a Wertheim operation because of uterine cervix carcinoma. After 8 years of follow-up, a local recurrence was observed and she received curative external radiotherapy (45 Gy) to the pelvis. No significant adverse events were observed during the radiotherapy. Approximately one year later, she was hospitalized because of metastatic disease with multiple pulmonary nodules, and a chemotherapy regimen consisting of paclitaxel and carboplatin was administered. The day after the administration of chemotherapy the patient had diarrhea and rectal bleeding. Histological examination of the biopsy taken from rectal hyperemic lesions showed a radiation colitis. The symptoms reappeared after the administration of each course of chemotherapy and continued until the death of the patient despite the interruption of the chemotherapy. In conclusion, the probability of recall phenomena should be kept in mind in patients who received previously with pelvic radiotherapy and treated later with cytotoxic chemotherapy.

[Peri-rectal infectious cellulitis with septicemia of anal origin. Suppository on trial]. / Cellulite infectieuse péri-rectale avec septicémie à point de départ anal. Le suppositoire en accusation.

Rectal route with local or general effects, is an interesting possibility of treatment. Easy use and rapid absorption are two major advantages. But this therapeutic modality is not riskless. We report a case of septicemia with peri-rectal cellulitis which was generated by two ano-rectal ulcerations after using Trophires suppositories. The infection was favoured by local application of cortisone. Our original observation, with ano-rectal ulcerations and short use of suppository, confirms the idea of short-term treatment stopped in case of unwanted symptom.

[Non-gastroduodenal digestive toxicity of non-steroidal anti-inflammatory agents]. / Toxicité digestive non gastro-duodénale des anti-inflammatoires non stéroïdiens.

Recent data have confirmed that non-steroidal anti-inflammatory drugs can cause serious damage to the gastrointestinal tract involving localizations other than the well-known gastroduodenal complications. Perforation and hemorrhage of the small bowel have been reported as well as ulcerations, stenoses and diaphragm disease. The same type of lesions can occur in the large bowel in addition to ischemia and collagen colitis. Diverticular diseases of the colon can be complicated by use of non-steroidal anti-inflammatory drugs which may also trigger flare-ups of inflammatory diseases. Use in suppository form can complicate rectitis and rectal stenosis. Non-steroidal anti-inflammatory drugs apparently increase intestinal permeability by inhibiting the cyto-protective effect of prostaglandins. The exact frequency of such complications remains to be determined, but prolonged treatment in elderly subjects appears to increase risk. Current data have not shown greater or lesser toxicity for any specific drug. Non-steroidal anti-inflammatory drugs should be entertained as the cause of intestinal disorders in patients under long-term treatment.

Rectal involvement in neutropenic enterocolitis.

Neutropenic enterocolitis is a common gastrointestinal complication in children undergoing chemotherapy for a variety of malignancies. It usually involves ileum and caecum, and involvement of rectum has rarely been reported. The authors report neutropenic enterocolitis in a child undergoing chemotherapy for acute lymphoblastic lymphoma which presented with ileus along with a mass like lesion in the rectum.

Proctitis química por ergotamina: «no siempre es una colitis ulcerosa» / Chemical proctitis due to ergotamine: «not always an ulcerative colitis»

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