Management of perianal Crohn’s disease

Opinion statement Perianal manifestations of Crohn’s disease usually coexist with active inflammation of other primary sites of the disease. Although treatment of active proximal disease may sometimes alleviate perianal symptoms, it is reasonable to separately treat symptomatic perianal disease. The diversity of perianal manifestations in Crohn’s disease mandates a tailored, individualized approach in every case. Medical therapy is the best treatment option for hemorrhoids and anal fissures. The medical management of patients with perianal Crohn’s disease includes the use of systemic antibiotics, immunosuppressive agents, and infliximab. Infliximab is now recognized as a very efficacious agent for treating fistulizing Crohn’s disease, including perianal fistulae. It may also reduce the need for surgical intervention in specific cases. Abscesses and fistulae are treated by control of sepsis, resolution of inflammation and optimal preservation of continence, and quality of life. Abscesses require surgical drainage that may need to be prolonged to achieve complete healing. Fistulae may be treated medically, especially in cases of concurrent proctitis. Refractory fistulae may require surgical treatment including an occasional need for fecal diversion or proctectomy. The role of new treatment options such as natalizumab and CDP571 is evolving and requires further investigation.     

Perianal fistulae following infliximab treatment: clinical and endosonographic outcome

BACKGROUND: Management of perianal and rectovaginal fistulae complicating Crohn's disease (CD) is unsatisfactory. Infliximab is effective in the treatment of fistulating CD. However, reopening of fistulae is frequent, suggesting the persistence of deep fistula tracts despite superficial healing. In this study, the clinical and endosonographic behavior of perianal fistulae were evaluated following infliximab infusions, as well as the role of anal endosonography (AE) in predicting their outcome. METHODS: Thirty CD patients presenting with perianal and/or rectovaginal fistulae received an infusion of infliximab at a dose of 5 mg/kg at weeks 0 (entry into the study), 2, and 6. Laboratory and clinical assessments were repeated at same intervals and at week 10. AE was performed at entry and at week 10. Thereafter, the perianal region was re-examined every 6 months, and patients were investigated regarding draining of the fistula in the previous months. RESULTS: Fifteen patients (53.6%) showed closure of the fistulae at week 10, but only 5 patients had the fistula tracts disappeared at AE. Clinical and AE closure of rectovaginal fistulae was less prevalent than that of perianal fistulae [14.3% versus 63.6% at week 6 (p = 0.035); 28.6% versus 59.1% at week 10 (p = 0.21); 14.3% versus 22.7% at AE (p = 1.00)]. The behavior of fistulae was not affected by their number and AE classification, presence of rectal disease, or setons. Twenty patients with perianal fistulae were followed for a median of 15.5 months. Patients with closed perianal fistulae at week 10 and disappearance of fistulae tract at AE showed a lower relapse rate than those with endosonographic persistence of fistula tract. CONCLUSIONS: Infliximab can heal perianal and rectovaginal fistulae in approximately 60% and 30% of patients, respectively. Despite closure, most fistula tracts are still detectable at AE. Persistence of the internal tract is a condition at higher risk of fistula recurrence.     

Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn’s disease with anal endosonographic monitoring: a single-centre experience

During infliximab treatment of perianal Crohn's disease (CD), the healing of the skin opening precedes fistula tract healing and this contributes to abscess formation and fistula recurrence. The aims of this study were to evaluate the efficacy of combined treatment with infliximab and setons for complex perianal fistulas in CD and to define the optimal time for seton removal by anal endosonography (AE). Nine consecutive patients with CD were studied. Perianal sepsis was eradicated when necessary and setons were placed before infliximab therapy. Setons were removed after AE evidence of fistulous tracts healing. Patients received a mean of 10+/-2.3 infliximab infusions. At week 6 all patients showed a reduction in mean CD activity index (p<0.005) and perianal disease activity index (p<0.0001). Complete fistula response was achieved in eight of nine patients. In six patients after a mean of 9.2 infusions, infliximab treatment was discontinued. Clinical and AE response persisted at 19.4+/-8.8 months (range 3-28 months) in five of these patients. One patient had fistula recurrence 20 weeks after infliximab discontinuation and responded rapidly to retreatment. At the time of this report, two patients were still on infliximab and in remission after a mean follow-up of 25+/-5 months. Combined therapy with infliximab and setons with AE monitoring of the response showed high efficacy in the management of patients with CD with complex perianal fistulas.     

Multidisciplinary and evidence-based management of fistulizing perianal Crohn's disease

Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence-based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial toimprove outcomes.     

Diagnostic and treatment recommendations on perianal Crohn's disease.

Treatment of perianal fistulas in Crohn's disease should be defined on an individual basis. A combined medical and surgical approach is the optimal treatment. Adequate management of perianal fistula disease is based on the presence or absence of active proctitis, anatomic location, and fistula type. Furthermore, the presence of perianal abscesses must be ruled out. This evaluation includes digital rectal examination, endoscopy, and examination under anesthesia combined with pelvic magnetic resonance imaging or anorectal endoscopy ultrasonography findings.     

Perianal Crohn's Disease

Perianal Crohn’s disease usually is associated with involvement of another primary site of Crohn’s disease. However, there is conflicting evidence on the relationship between proximal disease activity and perianal symptoms. Therefore, although it is reasonable to treat active proximal disease, symptomatic perianal disease may have to be treated on its own right. Hemorrhoids and anal fissures are best treated medically. Fistulae and abscesses are treated with control of sepsis and resolution of inflammation while preserving continence and quality of life. Abscesses require surgical drainage, which needs to be prolonged for healing to be complete. Fistulae may be treated with medications first, especially if the rectum is diseased. Refractory fistulae respond better to surgical treatment and sometimes require fecal diversion. The medical management of patients with perianal Crohn’s disease consists of rectal mesalamine, systemic antibiotics, immunosuppressive agents, and infliximab. The role of infliximab is evolving and it may reduce the need for surgical intervention in some cases. Perianal hygiene and skin protection help to reduce local discomfort.     

Treatment of perianal fistula and abscess: Crohn’s and non-Crohn’s

Opinion statement The management of perianal abscesses and fistulas is relatively straightforward in most cases and based on a sound knowledge of the anatomy of the anorectum and adherence to established medical and surgical principles. Asymptomatic fistulas should not be treated, whereas abscesses require surgical drainage under general anesthesia. Fistula treatment includes drainage of any associated sepsis and eradication of the fistula track to prevent recurrence while preserving sphincter integrity. A small percentage of anal abscesses and fistulas are complex and very challenging to manage, particularly in conditions such as rectovaginal fistulas and abscesses and/or fistulas complicating Crohn’s disease. Treatment strategies in these situations rely on an accurate clinical assessment of the degree of rectal inflammation and perianal pathology. Treatment should combine aggressive medical therapy (antibiotics, immunomodulators, and anti-tumor necrosis factor antibody treatment) and minimal surgical interventions. Patients with proctitis have a significantly lower healing rate and a significantly higher complication rate with aggressive surgical interventions.     

Impact of medical therapies on inflammatory bowel disease complication rate

Crohn's disease and ulcerative colitis are progressive diseases associated with a high risk of complications over time including strictures, fistulae, perianal complications, surgery, and colorectal cancer. Changing the natural history and avoiding evolution to a disabling disease should be the main goal of treatment. In recent studies, mucosal healing has been associated with longer-term remission and fewer complications. Conventional therapies with immunosuppressive drugs are able to induce mucosal healing in a minority of cases but their impact on disease progression appears modest. Higher rates of mucosal healing can be achieved with anti-tumor necrosis factor therapies that reduce the risk of relapse, surgery and hospitalization, and are associated with perianal fistulae closure. These drugs might be able to change the natural history of the disease mainly when introduced early in the course of the disease. Treatment strategy in inflammatory bowel diseases should thus be tailored according to the risk that each patient could develop disabling disease.     

Type of fistula determines response to infliximab in patients with fistulous Crohn's disease

OBJECTIVES: Infliximab has been shown to be efficacious for treating perianal fistulae in patients with Crohn's disease. There is limited information regarding response to infliximab in patients with other types of fistulae. METHODS: Sixty consecutive patients with fistulous Crohn's disease and at least three months of follow-up after three infliximab infusions were evaluated. Patients with enteroenteric fistulae were excluded. Complete response was defined as complete closure of the fistulae or complete cessation of fistula drainage. RESULTS: Thirty-five patients had external fistulae, 16 had internal fistulae, and 9 had mixed (both external and internal) fistulae. Complete response rates were significantly higher in patients with external fistulae (69%) compared to those with internal fistulae (13%); p= 0.001, or those with mixed fistulae (11%); p= 0.01. In the external fistula group, patients with perianal fistulae had a higher rate of complete response (78%) compared to those with abdominal wall fistulae (38%); p= 0.04. The rate of complete response to infliximab was significantly lower among 14 patients with rectovaginal fistulae (14%) compared to those with perianal fistulae (78%); p= 0.0007. In the mixed fistula group only 11% of the patients achieved complete response. This is significantly lower than the rate observed for patients with perianal fistulae (78%); p= 0.004. The Cox proportional hazards model showed that the hazard of relapse for smokers who achieved complete response was nearly twice that of nonsmokers; however, this difference did not reach statistical significance. CONCLUSION: There is an association between type of fistulae and complete response to infliximab in patients with fistulous Crohn's disease. External fistulae in general and perianal fistulae in particular have a higher rate of closure in response to infliximab compared to other types of fistulae.     

结核性肛周脓肿延误诊断临床分析(附5例报告)

2015年12月至2017年12月,航空总医院普外科收治的320例肛周脓肿患者中5例患者术后30d内切口未愈合,最终诊断为结核性肛周脓肿;其中3例并发肺结核,给予2R-H-E-Z/4R-H-E抗结核药物化疗方案治疗后,切口均愈合,平均愈合时间(25.5±3.6)d,无复发。分析延误诊断原因主要为:结核性肛周脓肿临床较少见,临床表现缺乏特异性,医务人员对此病的认识不足,未对患者病史进行详细分析,未进行脓液抗酸杆菌检查及肛周病变组织病理学检查。对于肛周脓肿的患者,应仔细询问患者病史,常规进行脓液分泌物抗酸杆菌检查、组织病理学检查。确诊为结核性肛周脓肿后应给予规范抗结核药物化疗方案治疗6个月至1年。     

Update on anal fistulae: surgical perspectives for the gastroenterologist

Anal fistulae are common and debilitating; they are characterized by severe pain and discharge. They arise following infection near the anal canal, or as a primary event from an abscess in the abdomen, fistulating into the vagina or perianal skin. The term 'cryptoglandular' is given to abscesses arising from the anal glands.For many years, the treatment of choice was to lay open the fistula; however, this risks causing incontinence with potentially devastating consequences. Alternative surgical treatments include setons, fibrin glue, collagen plugs and flaps to cover the internal fistula opening. These have achieved varying degrees of success, as will be discussed. The present review also discusses anal fistulae in light of much recently published literature. Currently, anal fistulae remain challenging and require specialist expertise; however, new treatment options are on the horizon.     

Does Infliximab Infusion Impact Results of Operative Treatment for Crohn’s Perianal Fistulas?

PURPOSE: Infliximab is an effective treatment for active intestinal Crohn's disease; however, the efficacy of infliximab in perianal Crohn's disease is controversial. This study was designed to compare patients with Crohn's disease who underwent perianal fistula surgery with or without infliximab infusion. METHODS: A retrospective chart review of 226 consecutive patients with Crohn's disease who underwent operative treatment with or without infliximab (3-6 infusions of 5 mg/kg) from March 1991 through December 2005 was completed. Patients were classified as completely healed, minimally symptomatic (seton placement with minimal drainage and/or infliximab dependence), and failure (persistent or recurrent symptomatic fistula, diverting procedure, or proctectomy). RESULTS: A total of 226 patients underwent operative treatment alone (n = 147) or in combination with infliximab infusion (n = 79). Age, gender, and preoperative history of intestinal and perianal Crohn's disease were similar between groups. Mean follow-up was 30 (range, 6-216) months. Operative treatment consisted of seton drainage (n = 112), conventional fistulotomy (n = 92), fibrin glue injection (n = 14), advancement flap (n = 5), collagen plug insertion (n = 2), and transperineal repair (n = 1). Eighty-eight patients (60 percent) healed completely with operative treatment alone, and 47 patients (59 percent) healed after operative treatment in combination with infliximab (P = not significant). CONCLUSIONS: Operative treatment of perianal fistulas in patients with Crohn's disease resulted in complete healing in approximately 60 percent of patients. Preoperative infliximab infusion did not affect overall healing rates.     

Metronidazole Therapy for Crohn's Disease and Associated Fistulae

Because of reports suggesting the efficacy of metronidazole therapy in the healing of perianal fistulae in Crohn's disease, the effect of metronidazole on symptoms of Crohn's disease and associated perianal fistulae were evaluated in eight consecutive patients. The criterion for entry into the study was the presence of resistant fistulae in patients with Crohn's disease. The duration if intestinal Crohn's ranged from 1/2-30 years and fistulae from 1–14 years. All patients had ileocolitis or pancolitis. Two had enteroenteric fistulae in addition to perianal fistulae. All had had previous surgery, half for fistulae and half for intestinal complications, usually obstruction. All had been on Prednisone. All hut one had received multiple other drugs including Azathioprine, Azulfidine, antibiotics, and rectal steroids. Patients were placed on metronidazole 1000 to 1500 mg/day orally in divided doses. The umber of draining fistulae was reduced 20-fold and the number of detectable fistulous openings by 50%. All patients had relief of fistula-associated pain; general Crohn's disease symptoms improved as well. Complete resolution of all symptoms occurred in half the patients. All patients experienced side effects, six had numbness of toes and five had metallic taste. Resolution of side effects occurred on discontinuation of metronidazole after 1–3 wk off the drug in all except one patient. All patients noted continued improvement in Crohn's symptoms during 6 months of follow-up after cessation of their therapy. Other side effects that have been reported with metronidazole therapy were not seen in our patients.     

Características clínicas y tratamiento de la enfermedad de Crohn perianal fistulizante en Colombia: resultados de un registro multicéntrico

IntroductionPerianal fistulizing Crohn's disease (CD) is a phenotype with a poor prognosis. There are no studies in our country. Our objective is to determine the clinical, sociodemographic and treatment characteristics of perianal fistulizing CD in a Colombian multicenter registry.Materials and methodsA retrospective, multicenter observational study was carried out, with prospective data collection, in the main reference centers for inflammatory Bowel disease (IBD) in the country. Continuous variables were expressed as medians and interquartile ranges. The categorical outcome variables were compared by the Chi-square test.ResultsSixty-five patients with perianal fistulizing CD were documented, with a median age of appearance of perianal fistula of 31.0 years (range: 24-42), predominantly in men (61.5%; H:M ratio: 1.4:1). Complex perianal fistulas were more frequent than simple ones (75.35 vs. 24.6%). Regarding medical treatment, 66.2% of the patients received antibiotics, 64.6% steroids, 78.5% biological therapy, 47.7% non-cutting setons, and 46.2% required surgical management, other than seton placement. Only 29.2% achieved complete remission of the fistula, and 9.2% of the patients ended up in a definitive colostomy. CD patients with complex fistulas received more biological therapy, compared to CD patients with simple fistulas (84.8 vs. 56.3%; P: 0.038).ConclusionsPerianal fistulizing CD has a poor prognosis in our setting, only 3 out of 10 patients achieve complete remission despite treatment. A multidisciplinary management is essential for the comprehensive management of this difficult pathology.     

Surgical Management of Inflammatory Bowel Disease

Opinion statement Surgery continues to be a central component in the treatment of patients with inflammatory bowel disease (IBD). The most important aspect of caring for patients with IBD is a close and ongoing interaction between the surgeon and gastroenterologist both before and after surgery. Surgery in patients with chronic ulcerative colitis (CUC) is curative. In the appropriate patient, we recommend proctocolectomy with ileal pouch anal anastomosis (IPAA). In contrast, patients with Crohn’s disease cannot be cured with surgery. Instead, surgery is used in conjunction with maximal medical therapy to treat symptoms of the disease and improve the patient’s quality of life. Surgical interventions should be limited in scope. Small bowel disease should be treated with either limited resection or strictureplasty, if possible, to conserve bowel length. For limited involvement of the colon, segmental resection yields good results. Minimal surgical intervention, drainage of abscesses, placing draining setons, and aggressive medical therapy is recommended as treatment of perianal Crohn’s disease.     

Current status and influence of operation on perianal Crohn's disease

Two hundred and two patients with Crohn's disease have been examined during the year 1984 to assess the frequency of perianal disease. One hundred and ten have had evidence of perianal complications (54%). In 30% of patients with perianal disease, the anal manifestations preceded any evidence of intestinal disease. Perianal disease was associated with pain in only 39%. Operations for perianal disease rarely achieved healing and were frequently associated with complications. Attempts to lay open a fistula-in-ano caused healing in only one of 12 cases and 6 developed incontinence. A high proportion of patients with Crohn's ulcers and strictures required proctectomy (87%). Proctectomy was performed in 27 patients with perianal disease of whom only 8 (30%) had primary healing of the proctectomy wound compared with complete healing in all 9 patients having a proctectomy without perianal disease (p less than 0.01). These results imply that patients with perianal Crohn's disease should be treated conservatively and that proctectomy, particularly in patients with rectal strictures, is associated with very high incidence of persistent perineal sinus.     

Combination therapy with oral tacrolimus (FK506) and azathioprine or 6-mercaptopurine for treatment-refractory Crohn's disease perianal fistulae

Our aim was to report the clinical experience with combination treatment using tacrolimus and either azathioprine (AZA) or 6-mercaptopurine (6MP) in patients with Crohn's disease (CD) perianal fistulae. The medical records of all patients with Crohn's disease perianal fistulae seen at the Mayo Clinic from 1996-1998 who were treated with tacrolimus were reviewed. Clinical response was classified as: complete response, partial response, and nonresponse. Eleven patients were treated with oral tacrolimus for a mean duration of 22 weeks. The initial oral dose of tacrolimus ranged from 0.15 to 0.31 mg/kg/day. Azathioprine or 6MP was continued in combination with tacrolimus in seven patients and initiated simultaneously with tacrolimus in four patients. All patients improved clinically, seven had a complete response, and four had a partial response. The mean time to initial improvement was 2.4 weeks, and the mean time to complete response was 12.2 weeks. The most frequent adverse events were nausea, paresthesias, nephrotoxicity, and tremor. Patients with nephrotoxicity had a significantly higher mean initial tacrolimus dose (0.31 mg/kg/day) compared with patients who did not have nephrotoxicity (0.25 mg/kg/day) (p = 0.035); however, there was not a statistically significant association between the starting dose or mean blood level and clinical response. Combination therapy with oral tacrolimus and AZA or 6MP may be effective treatment for CD perianal fistulae. Higher initial tacrolimus doses increase the risk of nephrotoxicity without improving clinical response.     

Abdominal Surgery for Crohn's Disease

The majority of patients with Crohn's disease will eventually need surgery because of failed medical treatment or complications. There are relatively few randomized controlled trials on which rational surgical treatment has been based; most studies are retrospective. Limited resection margins, irrespective of microscopic disease, do not affect operative recurrence rates. Recent evidence suggests that side-to-side wide stapled anastomosis may be associated with reduced re-operation rates. Unfavourable conditions for anastomotic healing include malnutrition and sepsis; it remains uncertain whether exteriorisation or primary anastomosis with a proximal defunctioning loop ileostomy is the most appropriate treatment under these circumstances. Preliminary imaging is required to detect associated abscesses which should be drained prior to resection. Staged surgery with enteral or parenteral nutrition (TPN) may then allow a delayed safe primary anastomosis. Enteric fistulae require resection of affected bowel. High output fistulae need flud and electrolyte replacement with total parenteral nutrition (TPN). The role of anti-TNF α antibodies (infliximab) in the management of abdominal fistulae is discussed. Strictureplasty is a safe technique in a fit patient and is important for bowel conservation. Segmental resection of colonic disease is controversial but also conserves bowel; subtotal colectomy is less likely to lead to re-operation for recurrence, but the functional outcome is less favourable. Ileoanal pouch construction for selected patients with known Crohn's disease is highly controversial and cannot be recommended at the present time. Carcinoma is uncommon but may occur in a bypassed segment of bowel, including a defunctioned rectal stump. Surveillance remains controversial. The decision to operate on patients with Crohn's disease must be in a multi-diciplinary setting. Surgery is often complex, particularly with fistulating or recurrent disease, and decision making in some aspects of operative management can be difficult.     

Perianal Crohn’s disease： Is there something new？

Perianal lesions are common in patients with Crohn's disease, and display aggressive behavior in some cases. An accurate diagnosis is necessary for the optimal management of perianal lesions. Treatment of perianal Crohn's disease includes medical and/or surgical options. Recent discoveries in the pathogenesis of this disease have led to advances in medical and surgical therapy with good results. Perianal lesions in Crohn's disease remain a challenging aspect for both gastroenterologists and surgeons and lead to a greatly impaired quality of life for all patients affected by this disease. A multidisciplinary approach is mandatory to obtain the best results.     

Current treatment of rectovaginal fistula in Crohn's disease

Rectovaginal fistula (RVF) continues to be the most difficult perianal manifestation of Crohn's disease to treat. This devastating and disabling complication has a significant impact on patients' quality of life and presents unique management challenges. Current therapeutic approaches include many medical therapeutics and surgical treatments with a wide range of success rates reported. However, current evidence is lacking to support any recommendation. The choice of repair depends on various patient and disease factors and basic surgical tenets. In this article, we review the current options to consider in the treatment of Crohn's-related RVF, and try to evaluate their effects on fistulae closure and quality of life.