Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

化浊解毒方对溃疡性结肠炎的治疗作用及机制

目的探讨化浊解毒方治疗溃疡性结肠炎(UC)的治疗作用及机制。方法120例UC患者按照随机数字表法分为观察组、对照组各60例。观察组予中药化浊解毒方口服,每日1剂,早晚2次温服;对照组予美沙拉嗪肠溶片口服,1.0 g/次,3次/d。2组疗程均4周。对比2组治疗前后Geboes指数、结肠镜下黏膜表现、生活质量评分、疾病活动指数及血清炎性因子IL-8、IL-35水平,凝血指标血清FIB水平,统计治疗后1年内复发情况。结果治疗后,观察组Geboes指数、疾病活动指数及血清炎性因子IL-8水平、凝血指标血清FIB水平均较本组治疗前降低,生活质量评分、血清炎性因子IL-35水平升高(P<0.05);且观察组治疗后疾病活动指数及血清炎性因子IL-8水平、凝血指标血清FIB水平均低于对照组,生活质量评分、血清炎性因子IL-35水平均高于对照组(P<0.05)。与对照组相比,治疗组糜烂、溃疡改善不明显(P>0.05),充血水肿、颗粒样变等肠镜表现改善情况均优于对照组(P<0.05)。治疗结束1年观察组复发率为10.64%,对照组为23.53%,2组差异有统计学意义(P<0.05)。结论化浊解毒方能改善UC患者临床症状,修复肠黏膜病理损伤,降低复发率;其机制可能与调节血清炎性因子IL-8、IL-35和凝血因子FIB水平有关。     

Outcome of a conservative approach in severe ulcerative colitis.

BACKGROUND: Severe ulcerative colitis is potentially life threatening even though a policy of intensive medical management and early colectomy in recent years reduced mortality to almost zero. However, colectomy, with or without ileal-anal anastomosis, has its own problems (morbidity, pouchitis, cuffitis) and no reliable prognostic index of surgical outcome has been developed. Intravenous steroids are still the mainstay of medical therapy but their maximal duration before stating a 'treatment failure' has not been defined. AIM OF THE STUDY: To evaluate the effectiveness, safety and outcome of an intensive medical approach in a series of patients with severe ulcerative colitis. PATIENTS AND METHODS: One hundred and forty-nine episodes of severe ulcerative colitis in 115 patients admitted to a Gastroenterology Unit in a 7-year period were retrospectively evaluated. Intravenous glucocorticosteroids--methylprednisolone 1 mg/kg/day--and topical steroids were administered, and supportive treatments with intensive monitoring were extended to all the patients. Second-line strategies for steroid-refractoriness were prolonged glucocorticosteroids treatment, oral ciclosporin, infliximab or surgery. RESULTS: The median number of Truelove criteria at admission was 3 (range 2-5), median CRP 34 mg/l (range 10-196). Median follow-up after discharge was 49 months. In 84 (57%) episodes an early response was noted, while 65 (43%) did not respond within 10 days to the standard steroid treatment. In the non-responders group, 28 patients went into remission with a prolonged steroid treatment (slow responders); 15 patients were treated with ciclosporin (eight responders) and 6 with infliximab (four responders). A total of 24 colectomies was performed in this group of patients (in 21 cases within 30 days from admission). Slow responders showed lower albumin levels (P = 0.02), higher cumulative dose of glucocorticosteroids in the year prior to admission (P = 0.02) and higher age (P = 0.03), in comparison with early responders. Major complications were noted in four episodes which responded to medical treatment. Disease-related mortality was zero. CONCLUSIONS: Medical treatment and use of second-line therapies were effective in the present series of patients. A group of slow responders has been identified and, if an intensive medical monitoring is guaranteed, steroids can be safely prolonged after the first 10 days of treatment. Cumulatively, about 80% of the patients responded to short-term medical treatment, only 5% of the patients underwent colectomy in the follow-up period. Major adverse events were recorded in four patients, who had recovered completely after adequate medical treatment.     

Carcinoid tumors and inflammatory bowel disease.

Three cases are described in which carcinoid tumors arose in previously established inflammatory bowel disease: two were in the ileum in cases of Crohn's disease, and one was in the rectum in a case of ulcerative colitis. Review of this association in the literature suggests that it may be more than fortuitous.     

Long‐standing ulcerative colitis complicated by right subclavian artery occlusion and upper limbs arteriolitis with digital ischemia

A 48‐year‐old male patient with long‐standing ulcerative colitis since February 2001 which was diagnosed by endoscopy, developed acute digital ischemia affecting both hands with fixed colour changes in the left index finger which was followed shortly by digital ulceration. Magnetic resonance angiography (MRA) of both upper limbs showed evidence of vasculitis affecting digital arterioles on both sided and right subclavian occlusion. The patient received pulse methylprednisolone followed by cyclophosphamide pulse therapy, the latter continuing on a monthly basis for 6 months with appreciable improvement and remission of the vasculitic process; follow‐up MRA showed reperfusion of the previously occluded subcalvian artery. To the authors’ knowledge vasculitis complicating the course of ulcerative colitis is a rare association and is only sporadically reported in the literature. This rare entity should be diagnosed early and aggressively treated; MRA is a very promising diagnostic tool that is suitable for both diagnosis and follow‐up of patients with this rare entity.     

N-3 fatty acids only delay early relapse of ulcerative colitis in remission

Relapse prevention by dietary n-3 fatty acids (5.1 g/day) was studied in a double-blind, placebo-controlled trial of 64 patients with ulcerative colitis in remission and off steroids. 5-ASA compounds were stopped three months after randomization and clinical disease activity monitored for two years. Macroscopic and histologic activity and extension was assessed by colonoscopy at entry and at exit. Both treatment groups were well matched at start. Nine patients on placebo and eight on n-3 fatty acids stopped taking their medication prematurely. Actuarial relapse-free survival was improved by n-3 fatty acids only during months 2 and 3 (2P<0.05–0.01), but cumulative relapse rate at two years was similar for those taking placebo (18/33=55%) and n-3 fatty acids (18/31=58%). There was also no consistent difference in clinical, macroscopic, and histologic disease activity between treatment groups. The n-3 fatty acids temporarily retard, but do not prevent, relapse of ulcerative colitis.     

Bacterial invasion into the colonic mucosa in ulcerative colitis

Abstract This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine-orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.     

Hepatic angiomyolipoma developing during the follow-up of ulcerative colitis: Report of a case and review of the literature

Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5×7.5×7cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma.     

Disease association of antibodies to human and mycobacterial hsp70 and hsp60 stress proteins.

Structural homology between microbial and human stress proteins has been postulated to be a basis for autoimmunization in chronic inflammatory diseases. Therefore, we estimated by ELISA titration the antibody levels to mycobacterial (M) and human (H) recombinant hsp70 and M-hsp65 heat-shock proteins in sera of patients with Crohn's disease (n = 29), ulcerative colitis (n = 20) and nontuberculous mycobacterial disease of the lungs (n = 20). Antibodies to H-hsp60, separated by two-dimensional gel electrophoresis, were tested in six sera of each group of patients. In Crohn's disease, antibody titres to the M-hsp65 antigen without detectable H-hsp60 binding were significantly elevated in 52% of the patients. In contrast titres to both M-hsp70 and H-hsp70 were demonstrable and correlated, but increased over control values only in four (14%) patients. The antibody pattern in ulcerative colitis was found to be quite different: anti-H-hsp60 binding was demonstrable in most patients, although anti-M-hsp65 titres were not elevated. Furthermore, 25% of patients had significantly elevated titres to M-hsp70, but not to H-hsp70. In non-tuberculous mycobacterial pulmonary disease, about 50% of patients had elevated titres to both hsp65 and hsp71 mycobacterial antigens but not to the corresponding human proteins; patients with Mycobacterium xenopi infection had the highest titres in this group. These results demonstrate the existence of distinct disease-associated patterns in the human antibody response to stress protein antigens. However, these data are not sufficient to imply sensitization with mycobacteria in patients with inflammatory bowel diseases, since certain epitopes of heat-shock proteins are shared by several bacterial genera.     

Are HLA-DR or TAP Genes Genetic Markers of Severity in Ulcerative Colitis?

The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n=91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n=200) were included. HLA-DRB103 was less frequent in UC patients than in healthy controls (8% vs 28%,PC<0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively (PC<0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.