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.     

The long-term outcome of anti-TNF alpha therapy in perianal Crohn’s disease

Background

The aim of the present study was to evaluate the long-term outcomes of anti-tumour necrosis factor alpha therapy in perianal Crohn’s disease and identify factors predicting response to treatment.

Methods

Data from hospital clinical records and coding databases were retrospectively reviewed from a tertiary care hospital in Christchurch, New Zealand. The study included 75 adult patients with perianal Crohn’s disease commenced on anti-tumour necrosis factor alpha therapy from January 2000 to December 2012. Response to treatment was determined from records relating to clinical evaluation, magnetic resonance imaging follow-up and whether further surgical intervention was required.

Results

73% (55) of all patients and 38 of the 57 (67%) patients with perianal fistulas responded to anti-tumour necrosis factor alpha therapy. Patients with complex fistulas were less likely to improve as compared to patients without fistulising disease. Five of the 57 (13%) patients with perianal fistulas demonstrated complete healing on clinical evaluation; however, magnetic resonance imaging confirmed complete healing in only two. Patients that had taken antibiotics and those that had previously required abscess drainage were less likely to respond to treatment [relative risk (RR) = 0.707 and 0.615, respectively; p = 0.03, p = 0.0001]. Responders were less likely to require follow-up surgery (RR = 0.658, p = 0.014) including ileostomy or proctectomy.

Conclusions

Although anti-tumour necrosis factor alpha tends to improve symptoms of perianal Crohn’s disease, in the long term, it rarely achieves complete healing. Perianal fistulising disease, a history of perianal abscess and antibiotic treatment are predictors of poor response to therapy.

     

Imaging of perianal fistulizing Crohn’s disease

Perianal fistula is a complication of Crohn’s disease that carries a high morbidity. It is a channel that develops between the lower rectum, anal canal and perianal or perineal skin. The development of perianal fistulas typically connotes a more aggressive disease phenotype and may warrant escalation of treatment to prevent poor outcomes over time. Based on fistula anatomy, debris can form inside these tracts and cause occlusion, which subsequently leads to abscess formation, fever and malaise. The clinical presentation is often with complaints of pain, continuous rectal drainage of fecal matter as well as malodorous discharge. Considering that the presence of fistulas often indicates refractory and aggressive disease, early identification of its presence is important. Some patients may not have the classic symptoms of fistulizing disease at presentation and others may have significant scarring and/or pain from previous fistulizing episodes, which can make an accurate assessment on physical exam alone problematic. As a result, utilizing diagnostic imaging is the best means of identifying the early signs of perianal fistulas or abscess formation in these patients. Several imaging modalities exist which can be used for diagnosis and management. Endoscopic ultrasound and pelvic MRI are considered the most useful in establishing the diagnosis. However, a combination of multiple imaging modalities and/or examination under anesthesia is probably the most ideal. Incomplete characterization of the fistula tract(s) extent or the presence of abscess carries a high morbidity and far-reaching personal expense for the patient – promoting worsening of the disease.     

Long-term efficacy of infliximab maintenance therapy for perianal Crohn’s disease

AIM:To assess the long-term efficacy of seton drainage with infliximab maintenance therapy in treatment of stricture for perianal Crohn’s disease(CD). METHODS:Sixty-two patients with perianal CD who required surgical treatment with or without infliximab between September 2000 and April 2010 were identified from our clinic’s database.The activities of the perianal lesions were evaluated using the modified perianal CD activity index(mPDAI)score.The primary endpoint was a clinical response at 12-15 wk after su...     

Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn’s disease

AIM:To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn’s disease(CD).METHODS:The work was performed as a prospective study.All patients received infliximab combined withsurgery to treat perianal fistulizing CD,which was followed by an immunosuppressive agent as maintenance therapy.RESULTS:A total of 28 patients with perianal fistulizing CD were included.At week 30,89.3%(25/28)of the patients were clinically cured with an average healing time of 31.4 d.The CD activity index decreased to70.07±77.54 from 205.47±111.13(P0.01)after infliximab treatment.The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89(P0.01).C-reactive protein,erythrocyte sedimentation rate,platelets,and neutrophils all decreased significantly compared with the pretreatment levels(P0.01).Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up.After a median follow-up of 26.4 mo(range:14-41 mo),96.4%(27/28)of the patients had a clinical cure.CONCLUSION:Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD,and this treatment was associated with better longterm outcomes.     

Local injection of infliximab in severe fistulating perianal Crohn’s disease: an open uncontrolled study

Background  

Perianal fistulas are frequent complications of Crohn’s disease. Intravenous infliximab can control perianal disease and promote perianal fistula closure. Perifistular infliximab injections have been proposed for patients who are intolerant or unresponsive to intravenous therapy. The aim of this study was to assess the long-term efficacy of surgical treatment combined with local infliximab therapy.     

Approach to medical therapy in perianal Crohn’s disease

Perianal Crohn’s disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn’s disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn’s disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn’s disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn’s disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.     

Clinical updates on perianal fistulas in Crohn’s disease

Introduction: Perianal fistulizing disease is an aggressive and debilitating phenotype of Crohn’s disease (CD), representing a significant therapeutic challenge. New work has led to advancement in epidemiology and long-term outcomes of perianal disease. The range of therapeutic options continues to expand, including new biologic agents, biosimilars, and stem cell therapy.

Areas covered: We discuss updates to all aspects of management of perianal disease, with a focus on the last 3 years of published data. Areas considered include new data on epidemiology and prognostication, medical and surgical therapy, and stem cell therapy.

Expert commentary: The presence of perianal disease at CD diagnosis portends a significantly worse disease course. Patients with perianal disease require close monitoring to identify those who are at risk for worsening disease, suboptimal biologic drug levels, and signs of developing neoplasm. With the impending availability of local mesenchymal stem cell therapy, this becomes increasingly important as this therapy, although extremely promising, is thus far only effective in patients without proctitis.     

Surgery for Crohn’s disease and anti-TNF agents: the changing scenario

Surgery has been a mainstay of therapy for Crohn’s disease for a long time, essentially as a consequence of the fairly modest efficacy of traditional medications such as immunomodulators, antibiotics and 5-ASA, especially in severe cases. However, in the past decade and half, the advent of anti-TNF agents has greatly changed the medical approach to this disease and may modify its general management as well. Here, we have reviewed the current literature on incidence of surgery, timing of surgery and postoperative recurrence of Crohn’s disease before and after the advent of anti-TNF agents. In addition, we have reviewed the risk of perioperative complications in patients on anti-TNF agents before surgery. The data show that the use of these medications is changing or expecting to change shortly a number of surgical aspects of Crohn’s disease management.     

Management of perianal fistulas in Crohn’s disease:An upto-date review

Perianal disease is one of the most disabling manifestations of Crohn’s disease.A multidisciplinary approach of gastroenterologist,colorectal surgeon and radiologist is necessary for its management.A correct diagnosis,based on endoscopy,magnetic resonance imaging,endoanal ultrasound and examination under anesthesia,is crucial for perianal fistula treatment.Available medical and surgical therapies are discussedin this review,including new local treatment modalities that are under investigation.     

Ustekinumab for the treatment of Crohn’s disease

Introduction: Ustekinumab is a human monoclonal antibody directed against the shared p40 subunit of interleukins 12 and 23. Ustekinumab is currently approved for the treatment of psoriatic arthritis (PsA) and moderate to severe plaque psoriasis, and is being evaluated in Crohn’s disease (CD).

Areas covered: The first evidence supporting the efficacy of ustekinumab in the treatment of moderate to severe CD was published in 2008. Results from subsequent phase II and phase III randomized controlled trials (RCTs) have shown promising data on the clinical efficacy of induction and remission of moderate to severe CD. These data and the safety profile of ustekinumab will be reviewed.

Expert commentary: As a significant proportion of individuals with CD have ongoing symptoms and inflammation despite existing therapies, there is a clinical need for new agents like ustekinumab directed at different targets on the inflammatory pathway. Looking forward, more studies are needed to evaluate dosing escalation or de-escalation in addition to timing of therapy switches. In addition, further data is required to gauge the comparative effectiveness of ustekinumab to the biologic agents that are currently used in the treatment of CD.     

Emerging treatments for complex perianal fistula in Crohn＇s disease

Complex perianal fistulas have a negative impact on the quality of life of sufferers and should be treated. Correct diagnosis, characterization and classification of the fistulas are essential to optimize treatment. Nevertheless, in the case of patients whose fistulas are associated with Crohn＇s disease, complete closure is particularly difficult to achieve. Systemic medical treatments （antibiotics, thiopurines and other immunomodulatory agents, and, more recently, anti-tumor necrosis factor-α agents such as infliximab） have been tried with varying degrees of success. Combined medical （including infliximab） and less aggressive surgical therapy （drainage and seton placement） offer the best outcomes in complex Crohn＇s fistulas while more aggressive surgical procedures such as fistulotomy or fistulectomy may increase the risk of incontinence. This review will focus on emerging novel treatments for perianal disease in Crohn＇s patients. These include locally applied infliximab or tacrolimus, fistula plugs, instillation of fibrin glue and the use of adult expanded adipose-derived stem cell injection. More welldesigned controlled studies are required to confirm the effectiveness of these emerging treatments.     

Surgery for luminal Crohn’s disease

Many patients with Crohn’s disease(CD)require surgery.Indications for surgery include failure of medical treatment,bowel obstruction,fistula or abscess formation.The most common surgical procedure is resection.In jejunoileal CD,strictureplasty is an accepted surgical technique that relieves the obstructive symptoms,while preserving intestinal length and avoiding the development of short bowel syndrome.However,the role of strictureplasty in duodenal and colonic diseases remains controversial.In extensive colitis,after total colectomy with ileorectal anastomosis(IRA),the recurrence rates and functional outcomes are reasonable.For patients with extensive colitis and rectal involvement,total colectomy and end-ileostomy is safe and effective;however,a few patients can have subsequent IRA,and half of the patients will require proctectomy later.Proctocolectomy is associated with a high incidence of delayed perineal wound healing,but it carries a low recurrence rate.Patients undergoing proctocolectomy with ileal pouch-anal anastomosis had poor functional outcomes and high failure rates.Laparoscopic surgery has been introduced as a minimal invasive procedure.Patients who undergo laparoscopic surgery have a more rapid recovery of bowel function and a shorter hospital stay.The morbidity also is lower,and the rate of disease recurrence is similar compared with open procedures.     

New horizons in the imaging of perianal Crohn’s disease: transperineal ultrasonography

Introduction: perianal disease, most commonly manifest as fistula or abscess formation, affects up to 40% of patients with crohn’s disease. perianal crohn’s disease is disabling, associated with poor outcomes, and represents a therapeutic challenge for physicians. correct diagnosis and classification of perianal disease is the first crucial step for appropriate multidisciplinary management.

Areas covered: A literature search was performed of the PubMed database using the terms ‘transperineal ultrasonography’, ‘transperineal ultrasound’, ‘perianal disease’, ‘perianal fistula’, ‘perianal abscess’, ‘magnetic resonance’, ‘endoanal ultrasonography’, ‘endoscopic ultrasound’ in combination with ‘Crohn’s disease’. A comprehensive review of the relative advantages and disadvantages of the various methods of evaluation of perianal Crohn’s disease is provided. A particular focus is placed on transperineal ultrasonography, including historical and technical factors, advantages and limitations, and its current role in practice. An algorithm for integration of transperineal ultrasound into the management of perianal Crohn’s disease into clinical practice is proposed, along with future areas research.

Expert commentary: Transperineal ultrasound is a simple, safe, cheap and reliable imaging technique for evaluation of perianal Crohn’s disease, which should be used more frequently in clinical practice.     

Safe use of infliximab for the treatment of severe perianal Crohn’s disease after diagnosis and treatment of lymphoma

Inflammatory bowel disease is associated with an increased likelihood of developing lymphoma. However, it is still controversial if this risk may be attributed to the disease itself or rather represents an effect of immunosuppressive treatment. Although tumor necrosis factor alpha (TNFα) is a key cytokine for cancer immunosurveillance, the potential relationship between anti-TNFα agents and the pathogenesis of lymphoproliferative disorders remains unclear. Here, we describe the case of a patient with severe perianal Crohn’s disease, treated with infliximab monotherapy, whose unusual presentation with acute groin pain required surgical intervention and led to the diagnosis of diffuse large B-cell lymphoma. However, 10 months after this episode, treatment with infliximab was restarted because the patient continued with refractory and disabling perianal disease. Currently, with a follow-up of 36 months, under infliximab 10 mg/kg every 4 weeks, he maintains mild perianal Crohn’s disease and persists in sustained clinical and imaging remission of the lymphoproliferative disorder.     

Management of postoperative Crohn’s disease

Surgical treatment does not cure Crohn’s disease, and postoperative recurrence is a feature of the clinical course of the disease. Ileocolonoscopy remains the gold standard for the surveillance of recurrent Crohn’s disease and should be performed 6–12 months after an operation. Many other non-invasive techniques are also useful and complement endoscopy for the early diagnosis of postoperative recurrence. Anti-TNF agents show great efficacy for the prevention of postoperative recurrence, and long-term use can maintain remission. It remains undetermined whether early treatment after postoperative endoscopic recurrence is ultimately as efficacious as prophylactic therapy.     

Pulmonary manifestations of Crohn’s disease

Crohn’s disease(CD)is a systemic illness with a constellation of extraintestinal manifestations affecting various organs.Of these extraintestinal manifestations of CD,those involving the lung are relatively rare.However,there is a wide array of lung manifestations,ranging from subclinical alterations,airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases.The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis.Bronchoalveolar lavage findings show an increased percentage of neutrophils.Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine,mesalamine and methotrexate,and opportunistic lung infections due to immunosuppressive treatment.In most patients,the development of pulmonary disease parallels that of intestinal disease activity.Although infrequent,clinicians dealing with CD must be aware of these,sometimes life-threatening,conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment.The treatment of CD-related respiratory disorders depends on the specific pattern of involvement,and in most patients,steroids are required in the initial management.