What are fistulas in Crohn’s disease. How are fistulas diagnosed and treated. Can fistulas be prevented in Crohn’s disease. What are the different types of fistulas associated with Crohn’s. How does follow-up care work after fistula treatment. What questions should patients ask their doctor about Crohn’s fistulas.

Understanding Fistulas in Crohn’s Disease

Fistulas are a common complication of Crohn’s disease, affecting up to half of all adults with this inflammatory bowel condition. These small tunnels form between two organs or between an organ and the skin surface, often due to inflammation causing sores on the intestinal wall. While they may sound alarming, understanding fistulas is crucial for effective management of Crohn’s disease.

Fistulas typically develop in the anal region for Crohn’s patients, but they can also form in the intestines, bladder, or through the bowel wall to the skin surface. In some cases, fistulas may even connect the anus and vagina. The formation of these abnormal passages can lead to various symptoms and complications, making early detection and treatment essential.

Types of Fistulas Associated with Crohn’s Disease

Several types of fistulas can occur in patients with Crohn’s disease, each with its own set of symptoms and potential complications:

• Anal fistula: The most common type, characterized by a painful bump or boil around the anus, often with drainage of fluid or fecal matter.
• Bowel-to-bladder fistula: Can cause frequent urinary tract infections, painful urination, and blood or cloudiness in the urine.
• Bowel-to-vagina fistula: May result in the passage of gas or fecal matter through the vagina.
• Bowel-to-skin fistula: Often occurs on the abdomen, causing skin irritation and increasing the risk of infection.
• Bowel-to-bowel fistula: Connects different parts of the intestines, potentially leading to diarrhea, malnutrition, and dehydration.

Diagnosis and Imaging Techniques for Crohn’s Fistulas

Accurate diagnosis of fistulas is crucial for appropriate treatment. Healthcare providers typically use a combination of physical examination and advanced imaging techniques to identify and characterize fistulas in Crohn’s disease patients.

How are fistulas diagnosed?

Fistulas are usually diagnosed through a thorough physical examination, which may reveal visible openings or drainage around the anal area. However, to fully assess the extent and complexity of fistulas, doctors often rely on various imaging tests:

• CT scans: Provide detailed cross-sectional images of the abdomen and pelvis
• Ultrasounds: Offer real-time imaging of soft tissues and can help guide procedures
• MRIs: Provide high-resolution images of soft tissues and are particularly useful for evaluating complex fistulas

These imaging techniques help doctors determine the exact location, size, and path of fistulas, which is essential for planning appropriate treatment strategies.

Treatment Options for Crohn’s Disease Fistulas

The treatment of fistulas in Crohn’s disease depends on their complexity and location. While some fistulas may respond to medical management, others may require surgical intervention.

Medical Management

For simple anal fistulas, doctors may recommend a combination of antibiotics and existing Crohn’s disease treatments, such as anti-tumor necrosis factor (anti-TNF) agents like infliximab. This approach aims to reduce inflammation and promote healing of the fistula.

Surgical Interventions

Complex anal fistulas or those involving other organs often require surgical treatment. Some common surgical options include:

1. Seton placement: A thin surgical cord is inserted into the fistula to promote drainage and healing.
2. Medical plug: A cone-shaped plug made from animal tissue is used to block the internal opening of the fistula.
3. Fistulotomy: The fistula is cut open and flattened to promote healing.
4. Ligation of the intersphincteric tract (LIFT): A procedure for complex anal fistulas that involves sealing the fistula at both ends.
5. Medical glue: A non-surgical option where glue is injected into the fistula to seal it.

In some cases, patients may require a temporary ileostomy during the healing process after fistula surgery. This involves creating a surgical opening in the abdominal wall to allow waste to exit the body while the intestine heals.

Emerging Treatments: Stem Cell Therapy for Crohn’s Fistulas

Researchers are exploring innovative treatments for Crohn’s disease fistulas, with stem cell therapy showing promising results. This experimental approach involves injecting stem cells directly into the fistula to repair damaged cells and reduce inflammation.

Is stem cell therapy effective for treating Crohn’s fistulas?

A 2021 review published in the journal Stem Cell Research & Therapy examined 29 studies on stem cell therapy for Crohn’s fistulas. The findings indicated that patients who received stem cell injections had higher rates of healing compared to those given a placebo. However, more research is needed to fully determine the effectiveness and long-term outcomes of this treatment approach.

Post-Treatment Care and Follow-Up for Fistulas

Proper post-treatment care is essential for successful healing of fistulas and preventing recurrence. After surgical intervention, patients may be advised to follow specific care instructions:

• Sitz baths: Soaking the affected area in warm water to promote healing and reduce discomfort
• Stool softeners or laxatives: Maintaining soft stools to minimize irritation of the surgical site
• Pain management: Use of prescribed pain medications or local anesthetics like lidocaine to manage post-operative discomfort

Regular follow-up appointments with healthcare providers are crucial to monitor healing progress and address any potential complications. During these visits, doctors may perform physical examinations and imaging tests to ensure proper healing of the fistula.

Preventing Fistulas in Crohn’s Disease

While it may not be possible to completely prevent fistulas in Crohn’s disease, certain measures can help reduce the risk of their formation:

How can patients reduce the risk of developing fistulas?

To minimize the chances of fistula development, patients with Crohn’s disease should:

• Adhere to prescribed treatment plans to manage inflammation
• Maintain good hygiene, especially in the perianal area
• Avoid straining during bowel movements
• Report any new symptoms or changes in their condition to their healthcare provider promptly
• Attend regular check-ups to monitor disease activity and detect potential complications early

By working closely with their healthcare team and following these preventive measures, patients can potentially reduce their risk of developing fistulas or catch them early if they do occur.

Important Questions to Ask Your Doctor About Crohn’s Fistulas

When dealing with fistulas related to Crohn’s disease, it’s essential to maintain open communication with your healthcare provider. Here are some key questions patients should consider asking their doctor:

1. What type of fistula do I have, and how severe is it?
2. What are my treatment options, and which do you recommend for my specific case?
3. What are the potential risks and side effects of the recommended treatment?
4. How long can I expect the healing process to take?
5. Will I need to make any lifestyle changes during or after treatment?
6. What signs should I watch for that might indicate complications or recurrence?
7. How often will I need follow-up appointments, and what will they involve?
8. Are there any new or experimental treatments that might be suitable for my condition?
9. How can I best manage my overall Crohn’s disease to reduce the risk of future fistulas?
10. What support resources are available for patients dealing with Crohn’s disease and fistulas?

By asking these questions, patients can gain a better understanding of their condition and actively participate in their treatment decisions. This collaborative approach can lead to improved outcomes and better quality of life for those living with Crohn’s disease and its complications.

Living with Crohn’s Disease and Fistulas: Coping Strategies and Support

Dealing with fistulas as a complication of Crohn’s disease can be challenging both physically and emotionally. Developing effective coping strategies and seeking support can significantly improve a patient’s quality of life and ability to manage their condition.

What are some effective ways to cope with Crohn’s disease and fistulas?

Patients can employ several strategies to better cope with their condition:

• Education: Learn as much as possible about Crohn’s disease and fistulas to feel more in control of the condition.
• Stress management: Practice relaxation techniques such as meditation, deep breathing, or yoga to reduce stress, which can exacerbate symptoms.
• Dietary adjustments: Work with a nutritionist to develop a diet plan that minimizes digestive discomfort and supports overall health.
• Regular exercise: Engage in appropriate physical activities to improve overall well-being and reduce stress.
• Join support groups: Connect with others who have similar experiences to share advice and emotional support.
• Seek mental health support: Consider talking to a therapist or counselor to address any emotional challenges related to living with a chronic condition.

By implementing these coping strategies, patients can improve their ability to manage the physical and emotional aspects of living with Crohn’s disease and fistulas.

Where can patients find support and resources?

Several organizations and resources are available to provide support and information for individuals dealing with Crohn’s disease and fistulas:

• Crohn’s & Colitis Foundation: Offers educational materials, support groups, and research updates.
• Online forums and communities: Platforms like HealthUnlocked and Reddit have active communities for IBD patients.
• Local support groups: Many hospitals and community centers host in-person support groups for individuals with Crohn’s disease.
• Patient advocacy organizations: Groups like the Intestinal Disease Education and Awareness Society (IDEAS) provide resources and advocate for patients.
• Social media: Following reputable organizations and healthcare providers on platforms like Twitter and Facebook can provide up-to-date information and community support.

Utilizing these resources can help patients feel more supported and informed as they navigate life with Crohn’s disease and its complications.

Advances in Fistula Research and Future Treatment Prospects

The field of Crohn’s disease and fistula treatment is continuously evolving, with researchers exploring new approaches to improve patient outcomes. Understanding these advancements can provide hope and insight into future treatment possibilities.

What are some promising areas of research for fistula treatment?

Several areas of research show potential for improving fistula treatment in Crohn’s disease:

• Biologics: Development of new and more targeted biological therapies to reduce inflammation and promote healing.
• Tissue engineering: Advancements in creating bioengineered tissues to repair fistula tracts.
• Nanotechnology: Exploration of nanoparticle-based drug delivery systems for more effective local treatment of fistulas.
• Microbiome manipulation: Investigating the role of gut bacteria in fistula formation and potential probiotic treatments.
• Gene therapy: Studying genetic factors involved in fistula development to develop targeted therapies.
• Combination therapies: Researching the most effective combinations of surgical and medical treatments for complex fistulas.

These research areas hold promise for developing more effective and less invasive treatments for Crohn’s disease fistulas in the future.

How might future treatments improve outcomes for patients with Crohn’s fistulas?

Future advancements in fistula treatment could potentially lead to several improvements:

• Higher success rates in fistula closure and healing
• Reduced recurrence rates of fistulas
• Minimally invasive treatment options with faster recovery times
• Personalized treatment approaches based on individual patient characteristics
• Improved quality of life for patients with chronic or recurrent fistulas
• Better long-term management of Crohn’s disease to prevent fistula formation

As research progresses, patients with Crohn’s disease and fistulas can look forward to potentially more effective and tailored treatment options in the coming years.

Fistulas and Crohn’s Disease: What to Know

Written by Hallie Levine

• What Are Fistulas?
• What Are the Types of Fistulas?
• How Are Fistulas Treated?
• What Is the Follow-Up Care After a Fistula?
• Can Fistulas Be Prevented?
• What Questions Should I Ask My Doctor About My Fistula?
• More

Fistulas are small tunnels that form between two organs or an organ and the surface of your body. They’re due to inflammation from your Crohn’s disease, which causes sores to form on your intestinal wall. In Crohn’s disease, they often form in your butt. They can also form in your intestines, bladder, or straight through the bowel wall to your skin surface. You may even develop a fistula between your butt and vagina.

They sound scary but are very common with Crohn’s disease. In fact, it’s estimated that up to half of all adults with this condition will eventually have a fistula.

There are several types of fistulas you may get if you have Crohn’s disease. They include:

• Anal fistula. This is the most common type of fistula among patients with Crohn’s disease. Symptoms include a painful bump or boil around your butt. You may see an open skin abscess that drains fluid or poop.
• Bowel-to-bladder fistula. You may have frequent urinary tract infections. It may hurt to pee, and your urine may look cloudy or have blood in it.
• Bowel-to-vagina fistula. You may notice that you pass gas or poop through your vagina.
• Bowel-to-skin fistula. These often occur on your stomach. The contents of your gut leak out, which hurts your skin and causes it to become very red and sore. You are also more at risk of a skin infection.
• Bowel-to-bowel fistula. This is when different parts of your gut link together, like your small and large intestines. It can cause diarrhea and even malnutrition and dehydration due to loss of nutrients.

Fistulas are usually diagnosed through a physical exam, as well as imaging tests such as CT scans, ultrasounds, and MRIs.

If you have a simple anal fistula, your doctor may recommend that you treat it with antibiotics, plus any treatment you already take for your Crohn’s disease, such as an anti-tumor necrosis factor agent like infliximab. But if you have a more complex anal fistula, or another type of fistula, like a bladder or vaginal one, you may need surgery, especially as these types of fistulas tend to pass through muscle layers or organs. Options include:

A seton. This is a thin surgical cord that’s put into the fistula to help drain infection and allow it to heal. It’s left in for several weeks and removed once the fistula starts to heal. Studies show that this treatment is most effective when it’s done at the same time as anti-TNF therapy. It can feel funny – like rubber bands hanging out of your butt – but after a few days, you won’t notice that the cord is there.

A medical plug. This is a cone-shaped plug made from animal tissue that blocks the internal opening of the fistula.

Fistulotomy. The fistula is cut open (the way you would a cardboard tube) and flattened out. It can take anywhere from a week to several months to heal.

Ligation of the intersphincteric tract (LIFT). This is for more complex anal fistulas. A cut is made in the skin above the fistula, and the sphincter muscles are moved apart. The fistula is then sealed at both ends so poop doesn’t get into it.

Medical glue. This is a nonsurgical option, where your doctor injects a glue into your fistula while you’re under general anesthetic. This helps seal the fistula, so that it heals. It’s thought to be less effective than a fistulotomy, but it’s less invasive.

You may need an ileostomy while your body heals from fistula surgery. This is a procedure where your small intestine is brought up through the abdominal wall so that your poop can leave your body through a surgically created hole known as a stoma. Your poop will be collected in an ostomy bag. This is temporary, but you may need more surgery to make sure your intestine has fully closed where the fistula was.

Researchers are also studying an experimental treatment for fistulas using stem cells. These are injected directly into the fistula. The thought is they are able to repair damaged cells and ramp down some of the inflammation associated with Crohn’s disease. A 2021 review published in the journal Stem Cell Research & Therapy looked at 29 studies and concluded that patients given stem cell injections had higher rates of healing than those given a placebo. But more research is necessary to determine how helpful it really is.

Most fistulas respond well to surgery. Your doctor may recommend that you soak the area in a warm bath, or sitz bath, and that you take stool softeners or laxatives for a week. This helps keep your poop soft, so it doesn’t irritate the area.

Your doctor may also prescribe pain pills for you to take for a few days after surgery. Local anesthetics like lidocaine can also temporarily relieve discomfort.

You’ll be followed closely to make sure that the fistula doesn’t return and that new ones don’t develop.

The best way to help prevent a fistula is to be on a therapy that helps keep your Crohn’s disease under control. A 2020 study published in JAMA Network Open, for example, found that children and young adults with Crohn’s disease who used nonsteroid therapies such as azathioprine or methotrexate (both immune system suppressors) or the anti-TNF drug infliximab were nearly 60% less likely to have fistulas than those who didn’t. If they did go on to develop one, they were 55% less likely to need ostomy surgery. This is especially important because kids with Crohn’s disease are almost twice as likely to get fistulas as adults, possibly because the condition in this age group tends to be more aggressive.

If you have a fistula and your doctor recommends surgery, it’s important to talk to them about the following:

• Surgery options
• Pre-surgery prep
• Potential complications
• Restrictions after surgery
• Recovery time
• How the surgery will affect your diet and bowel movements
• Whether you will need an ileostomy, and if you do, how to care for your ostomy pouch
• Home supplies
• Follow-up care

While fistulas are a common complication of Crohn’s disease, the good news is there are effective treatments out there to both remove them and prevent them from returning.

Top Picks

Fistula Removal | Crohn’s & Colitis Foundation

Fistulas require immediate medical attention to prevent serious infections or other problems from developing. Treatment options include medications, surgery, or both.

Fistulas form when inflammation causes sores, or ulcers, to form on the inside wall of the intestine or nearby organs. Those ulcers can extend through the entire thickness of the bowel wall, creating a tunnel to drain the pus from the infected area.  An abcess, or a collection of pus, can also cause a fistula to form.

The most common types of fistulas in Crohn’s disease patients form between two parts of the intestine, between the intestine and another organ, such as the bladder or vagina, or through to the skin surface. Women with Crohn’s disease can also develop a fistula between the rectum and vagina, which may be difficult to treat. Surgical treatment depends on individual circumstances.

Fistulas sound scary, but they are treatable. About 35 to 50 percent of adults with Crohn’s disease will develop a fistula at some point.

Fistula Symptoms

Patients can have different symptoms depending on which parts of the body are connected by the fistula.

Fistula between the small and large intestine

Fistula between the intestine and the bladder

• Urinary tract infection

• Burning with urination

• Cloudy urine or blood in the urine

Fistula between the intestine and the vagina

Fistula from the intestine to the skin

What You Should Know About Fistula Removal

While some fistulas can be treated with antibiotics and other medication, fistula removal surgery may be necessary if the infection doesn’t respond to medication or if the fistula is severe enough to require emergency surgery.

There are several surgical options to treat fistulas, including:

• A medical plug to close the fistula and allow it to heal

• A thin surgical cord, called a seton, placed into the fistula to help drain any infection and allow it to heal

• Opening up the fistula with an incision along its length to allow it to heal

• Medical glue to close the fistula

Ileostomy

Your stool will sometimes need to be diverted from the intestine while its healing from fistula surgery. This is done with an ileostomy, a procedure that brings the small intestine up through the abdominal wall so that waste can leave your body through a surgically created hole called a stoma.

• Feces are collected outside your body in an ostomy pouching system.

• An ileostomy is often used as a temporary solution to allow healing.

• You may require additional surgery to ensure the intestine is closed at the fistula location.

Anal Fistula Removal

An anal fistula is a tunnel that forms between the inside of the anus and the skin surrounding the anus. This is often repaired with a surgical procedure called a fistulotomy.

• The primary goal is to repair the fistula without damaging the anal sphincter muscles, which are necessary for fecal continence, the ability to hold fecal material in your rectum.

• Recurrence rates for anal fistulas are fairly low after surgery.

• Complications are rare and there is typically little impact on fecal continence.

Ask Your Doctor

• What are my options for fistula removal?

• What preparations will I need to make before my fistula removal surgery?

• What are the potential complications from surgery?

• What kind of restrictions will I have after my surgery?

• How long will it take me to recover from fistula removal surgery?

• How will the surgery affect my diet and bowel movements?

• If I require an ileostomy, how do I care for my ostomy pouch and keep it clean?

• What supplies will I need at home?

• Will I need additional surgeries?

Related Resources

Brochure

Surgery for Crohn’s Disease and Ulcerative Colitis.

..

A brochure with information and resources about the different types of GI surgery.

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Combined biological therapy for fistulous Crohn’s disease. Clinical Demonstration

Crohn’s disease (CD) is a chronic inflammatory progressive disease of the gastrointestinal tract, predominantly affecting the terminal ileum. Depending on the course, 3 phenotypes (forms) of CD are distinguished: inflammatory, stenosing, and penetrating [1]. In most cases, the initial stage of CD is characterized by granulomatous inflammation of the intestinal mucosa, but over time, many patients develop strictures or fistulas/fistulas as a result of uncontrolled progression of the inflammatory process in the intestine [2].

Within 20 years, 88% of patients develop strictures (18%) and fistulas/fistulas (70%) [2]. The clinical course of CD and the rate of its progression vary considerably among patients. In 43% of patients, the disease begins with a severe attack, followed by the appearance of relatively rare symptoms over the next 10 years [3]. However, in 51% of patients, CD is chronic (19%) or recurrent (32%) [3]. Observing the original group of 373 patients with CD, R. Munkholm et al. [4] showed that in 45% with an active form of the disease in the first years after the onset, it persists as an active chronic condition during the subsequent time (the period of long-term follow-up was 8 years). Of these patients, 50% had an intermittent course of the disease, and only after 8 years, 5% of patients had CD remission.

The ultimate goal of CD treatment is to heal the intestinal mucosa, increase the duration of remission of the disease, reduce the frequency and severity of complications that require hospitalization and surgery, and, as a result, improve the quality of life of patients. These goals can be achieved with adequate and timely anti-inflammatory therapy [5-7].

Treatment of patients with CD should be based on predictive factors for disease progression. According to the ECCO (The European Crohn’s and Colitis Organization) Consensus, the clinical course of CD can be predicted based on clinical symptoms at the time of diagnosis, patient age, history, extraintestinal manifestations, and the presence of stenosis and fistulas. These indicators must be taken into account when choosing the initial therapeutic tactics [8]. Several studies have confirmed that young age (under 40) and the presence of perianal fistulas (PS) can be predictors of poor outcomes and/or disability in patients [9-eleven]. PS is the most common and frequent type of fistula in CD [12]. They are difficult to treat, worsen the patient’s quality of life and increase the risk of total bowel resection [12, 13].

PS are divided into simple and complex. Simple PS include non-rectovaginal superficial, low intra- and transsphincteric fistulas with a single external opening, without clinical signs of abscess formation and acute inflammation in the absence of anal stricture. At the same time, complex include any form (in relation to the anal sphincter) of high fistulas with multiple external openings, with signs of abscess formation, rectovaginal fistulas, and fistulas with anal canal stricture. In addition, if a pronounced specific Crohn’s proctitis is determined during endoscopic verification of the diagnosis, then this fistula is classified as complex [14].

According to the recommendations of the GNCC, it is also advisable to distinguish 2 types of rectal fistulas, due to the peculiarities of CD etiopathogenesis.

1. High (rarely low) fistulas caused by a granulomatous process, in which an internal opening occurs against the background of an active non-specific destructive process from ulcers-cracks.

2. Low (banal) fistulas emanating from the Morgagni crypts, the development of which is associated with infection of the anal glands through the crypts or damaged skin of the anal canal against the background of CD.

Currently, the fistulous form of CD is an indication for the appointment of biological therapy with genetically engineered biological drugs (GEBD) at the time of diagnosis (top-down therapy).

A clinical study evaluating the effectiveness of infliximab in the treatment of patients with fistulous CD (ACCENT II) demonstrated the effectiveness of this drug in this form of the disease. Enrolled in this randomized, double-blind, controlled trial, 306 adult patients with CD who had one or more draining abdominal fistulas or PS and had a disease duration of at least 3 months were randomized to receive infliximab at weeks 0, 2, and 6. Response to infliximab (closure of 50% of draining fistulas) 195 (65%) of 282 patients. After 14 weeks, these patients were randomly assigned to receive maintenance doses of placebo ( n =99) or maintenance therapy with infliximab ( n =96). Patients who did not respond to infliximab at baseline ( n =87) were also divided into groups to receive maintenance doses of infliximab ( n =43) or placebo ( n =44) up to week 54 after the start of research [15]. By week 54, the number of patients who had a decrease in the number of fistulas among those receiving infliximab was significantly higher than in the placebo group: 46% and 23%, respectively ( p = 0. 001). Similar efficacy was observed in patients with complete remission (no draining fistulas) – 36% and 23%, respectively ( p = 0.009) [15]. The ACCENT II study also showed that infliximab therapy significantly reduces the frequency of hospitalizations and surgical interventions in patients with fistulous CD. Despite the significant effect of biological (anticytokine) therapy of the fistulous form of CD, which is characterized by a recurrent and aggressive course, the treatment of patients in this category remains a difficult task, and there is a high risk of CD recurrence. This circumstance necessitates the search for new approaches and methods of conservative therapy of the fistulous form of CD [16].

Mesenchymal stem cells (MSCs), which have immunomodulatory properties and great regenerative potential, are also used to treat fistulous forms of CD and PS [17].

Italian scientists conducted a study on the safety and efficacy of local administration of autologous bone marrow (BM) MSCs in the treatment of fistulous CD. The study included 12 patients with CD, 10 patients (2 refused) received an average of 4 injections of MSCs, which amounted to 80 million cells. The control was carried out by endoscopic methods and during magnetic resonance imaging at certain intervals for 12 months after the introduction of MSCs. In 7 cases, after the introduction of MSCs, complete closure of fistulas was registered, and in 3 cases, incomplete closure. At the same time, there was a significant decrease in the index of clinical activity of CD (IABA) simultaneously with a decrease in the index of perianal activity of CD (PABA) ( p <0.01 compared to baseline for both indices). Side effects from the introduction of MSCs were not noted in any case. Based on the obtained results, it was concluded that the local administration of autologous MSCs is a safe and, possibly, effective method of treating fistulous CD [18]. Encouraging results were obtained in a phase I and II clinical trial to assess the safety and efficacy of local administration of MSCs derived from adipose tissue in patients with fistulous CD. Patients with fistulous CD ( n =4) locally administered MSCs to demonstrate the safety of this treatment method [19]. Although the study was not designed to determine the effectiveness of this treatment, in 75% of cases, fistulas treated with MSC culture healed after 8 weeks from the moment of administration, while no side effects were observed from topical MSC administration. The obtained positive result became a prerequisite for further research, in which, in addition to safety, it was necessary to evaluate the effectiveness of local administration of MSCs. Total 49patients with PS caused by purulent-inflammatory processes in the rectum ( n = 35) and fistulas caused by granulomatous inflammation of BC ( n = 14) were randomized as follows: group 1 patients ( n =25) fibrin glue was injected into the affected area, the 2nd group ( n =24) – fibrin glue and 20 million MSCs. If the fistulas did not heal after 8 weeks, fibrin glue was re-introduced as monotherapy in the 1st group of patients and fibrin glue and 40 million MSCs in the 2nd group. Fistula healing was observed in 17 (71%) of 24 patients of the 2nd group who received fibrin glue and MSCs, compared with 4 (16%) of 25 patients of the 1st group who received fibrin glue without MSCs. The effectiveness of local administration of MSCs in groups of patients, both with fistulas caused by paraproctitis, and with the fistula form of CD, was comparable [20].

In another study, 10 patients with refractory CD who had PS had autologous BM MSCs injected locally into the fistula area at 4-week intervals [18]. Each patient received an average of 4 injections of 20 million MSCs. In all patients, a simultaneous decrease in IABP and IABP was observed, accompanied by healing of the rectal mucosa.

In 7 out of 10 patients, complete epithelialization of fistulas was registered, without the development of side effects.

A number of studies demonstrate that there are differences in efficacy between systemic and topical administration of MSCs for the treatment of fistulous CD. In the experimental model of colitis, E. Gonzalez-Rey et al. [21] showed that MSCs derived from adipose tissue, when administered intraperitoneally, migrate according to the “homing” principle, namely to the area of ​​inflammation of the colon. M. Duijvestein et al. [22] observed a similar “homing” effect using human BM MSCs when administered systemically. However, only a small number of labeled MSCs were found in the inflamed intestine upon systemic administration of cell culture. It is believed that intravenous administration of MSCs has a systemic immunomodulatory effect, ultimately contributing to the restoration of damaged tissues. With local administration of MSCs, a greater number of cells reach damaged tissues compared to systemic administration, which probably provides more intensive tissue regeneration due to the presence of a high concentration of soluble growth factors in the area of ​​damage.

We present our own clinical experience demonstrating the effectiveness of local administration of MSCs in a patient with fistulous CD.

Patient P. , born in 1974, considers herself ill since October 2007, when abdominal pains without clear localization appeared, loose stools mixed with mucus and blood, pus from the anus, pain in the elbow and knee joints. Hospitalized in the Main Military Clinical Hospital. N.N. Burdenko. Irrigoscopy in the descending colon revealed a circular narrowing of the lumen up to 1.5 cm over 2.5 cm. According to colonoscopy: the mucous membrane of the terminal ileum was edematous, pink. Bauhin’s damper is gaping. Colon mucosa with numerous longitudinal, slit-like ulcers and transverse fissures, tuberous, looks like a “cobblestone pavement”. In the sigmoid colon – a narrowing area with circular edema. In the lower ampullar section of the rectum on the anterior right wall, an opening of the fistulous passage is determined at a distance of 4 cm from the anus, the CO around the fistula is moderately infiltrated, with pressure, a purulent discharge is released.

Ano- and rectosigmoscopy: a fistulous tract is visible to the right of the anal canal, moderate pain is determined when pressed, a purulent discharge is released. The probe inserted into the external fistulous opening freely passes into the intestinal lumen through the internal opening. The rectoscope was inserted at 16 cm, catarrhal sphincteritis, moderate hyperemia of CO throughout. The vascular pattern is smeared, there is no contact bleeding. At the level of 3 cm from the anus, a rectovaginal fistula is determined, confirmed using a test with a 1% solution of methylene blue.

Thus, according to the classification proposed by the American Gastroenterology Association [23], the patient had a simple PS with a single external opening and a complex rectovaginal fistula.

The diagnosis was established: CD of the colon, complicated by chronic rectovaginal fistula and external PS, chronic continuous course, high activity. Extraintestinal manifestations – polyarthritis.

Antibacterial therapy was prescribed: metronidazole 1 g/day and ciprofloxacin 1 g/day, as well as budenofalk 18 mg/day. Positive dynamics was noted: pain in the abdomen and joints decreased, the stool was semi-formed, up to 4 times a day with a small amount of mucus, a moderate discharge of mucus was also noted from the fistula. The patient stopped taking Budenofalk on her own and 2 months later a relapse occurred: abdominal pains reappeared, diarrhea up to 15 times a day with an admixture of mucus and blood. In March 2008, the patient was re-hospitalized in the GVKG named after. N.N. Burdenko. Conducted complex therapy with the use of prednisolone, antibacterial drugs – metronidazole and ciprofloxacin, correction of protein-energy disorders. Achieved remission of the disease. Discharged with a recommendation to take azathioprine 2.5 mg per 1 kg of body weight. In October 2008 – re-hospitalization in the GVKG named after. N.N. Burdenko in connection with the relapse of the disease. Taking into account the continuous nature of the course, extraintestinal manifestations (polyarthritis), the presence of a rectovaginal fistula, PS, and sigmoid stenosis, an induction course with infliximab at a dose of 5 mg/kg was performed. In November 2008, she was hospitalized at the Central Research Institute of Gastroenterology for further treatment with infliximab. IABC at the time of admission was 343 points. The level of C-reactive protein is 46.6 µm/l. Mucous and purulent discharge from the fistulous tract was noted, she felt discomfort in the fistula zone, moderate induration in the area of ​​the external opening of the fistulous tract, and a significant limitation of sexual activity. IAPBC 12 points. During therapy with infliximab at a dose of 5 mg/kg in combination with azathioprine 2.5 mg/kg, a remission of the disease was achieved – IABP was 126 points, IABP decreased to 5 points.

In August 2009, during the next infliximab injection, a follow-up colonoscopy was performed. The mucous membrane of the ileum is edematous, pink. Colon mucosa with numerous pseudopolyps. In the lower ampullar section, along the anterior right wall, there is a fistula opening with a diameter of 1 mm at a distance of 4 cm from the anus, CO around the passage is moderately hyperemic and infiltrated, serous discharge is released when pressed.

Ano- and rectosigmoscopy: a fistulous tract is visible to the right of the anal canal, serous discharge is released when pressed. The rectoscope was inserted at 18 cm, moderate CO hyperemia throughout. There is no contact bleeding. The vascular pattern is blurred. At the level of 3 cm from the anus – rectovaginal fistula.

In October 2009, after ARVI, diarrhea appeared up to 7-10 times a day, cramping pains in the lower abdomen in the evening and at night, bloating, fever up to 37.5-37.8 ° C in the evenings, pain in the knee joints , purulent discharge from the fistulous tract. Self-administered prednisolone 20 mg/day while continuing to take azathioprine 100 mg/day.

In connection with the exacerbation of the disease on the background of biological therapy, the dose of infliximab was increased to 10 mg/kg. In combination with anticytokine therapy, systemic administration of 200 million allogeneic BM MSCs was performed twice. The patient’s condition improved – semi-formed stool, no more than 3-4 times a day, without pathological impurities; body weight increased by 7 kg, abdominal pain subsided, body temperature returned to normal, mucus secretion from the fistula decreased.

During 2010-2011 maintenance therapy with infliximab at a dose of 10 mg/kg in combination with azathioprine 2.5 mg/kg continued, providing remission: IABP was in the range from 98 to 120 points, the level of C-reactive protein was 2.0-8.6 μm/l . The amount of discharge from the fistula decreased by more than 50%, which, according to the literature, could be regarded as a “response to therapy” [24], although the fistula did not heal completely.

In March 2012, when examining the anal region on the right around the anal canal, painful swelling was noted and a fistulous tract was visible, maceration of the skin around the fistulous tract, weeping and excoriation, mucous discharge was released when pressed. SO of the rectum and distal sigmoid colon was hyperemic, there was no contact bleeding. IPABK 8 points.

On 20.03 a diagnostic and treatment colonoscopy was performed. The mucous membrane of the ileum is pink, moderately edematous. The intestinal mucosa with multiple pseudopolyps in all departments, no ulcers and erosions. At a distance of 3-4 cm from the anus (see figure, but on the color insert) in the lower ampullar section along the anterior right wall, the opening of the fistulous tract is determined. a – the internal opening of the fistula in the lower ampulla of the rectum before the introduction of MSCs. Along the perimeter of the fistulous tract, 40 million MSCs were introduced – 4 injection points, 1 ml of isotonic sodium chloride solution containing 10 million MSCs. After 4 and 8 weeks, the patient was re-introduced 40 million MSCs into the fistula area. After 12 weeks, a control ano- and rectosigmoscopy was performed. When examining the anal region, the closure of the external opening of the fistula was noted. The skin in the area of ​​the former fistulous tract is minimally changed – turgor is reduced. During endoanal ultrasound and rectoscopy, the fistulous tract was not determined (see figure, b on color insert) .Figure 1. Colonofibroscopy data in patient P., 38 years old. b – healed fistula of the rectum 12 weeks after the introduction of MSCs. Thus, complete healing of the fistula was recorded. IPABK 3 points.

Currently, the patient receives maintenance therapy with infliximab 10 mg/kg of body weight, azathioprine 100 mg/day, every 6 months – 150 million MSCs intravenously, which allows maintaining the remission of the disease: IABC at the level of 98-121 points, IPABK – 3-4 points.

It should be noted that despite treatment, the patient has a rectovaginal fistula.

The above clinical observation demonstrates the complexity of the treatment of perianal CD, which should be carried out jointly by a gastroenterologist and an endoscopist. Despite the full amount of drug therapy for perianal CD, carried out in accordance with the recommended algorithm [25], fistula healing was achieved only after several local injections of MSCs. Nevertheless, to prove the effectiveness of MSCs in the complex therapy of fistulous CD, randomized controlled trials involving a sufficient number of patients are needed.

Complications of Crohn’s disease – Health Clinic 365 Ekaterinburg

Crohn’s disease, symptoms

Causes of Crohn’s disease

Crohn’s disease. Questions for a Doctor

Diagnosis of Crohn’s Disease

Treatment of Crohn’s Disease

Crohn’s disease can lead to one or more of the following complications :

Intestinal obstruction. Crohn’s disease affects the entire thickness of the intestinal wall. Over time, some sections of the intestinal wall may thicken, and the intestinal lumen may narrow. This can impede the passage of food, and even lead to obstruction. In some cases, surgery is required to remove the affected parts of the intestine.

Ulcers. Chronic inflammation can lead to ulcers anywhere in the digestive tract, including the mouth, genital area (perineum), and anus (anus).

Fistulas. Sometimes ulcers can spread in depth to the entire thickness of the intestinal wall, forming a pathological hole in the intestinal wall and creating a fistula. A fistula is an abnormal communication between different parts of your intestines, between your intestines and skin, or between your intestines and another organ, such as your bladder or vagina. When internal fistulas (between internal organs) occur, food may not reach the areas of the intestine that are needed for absorption. An external fistula (between the intestines and the skin) can cause continuous drainage of intestinal contents through a hole in the skin, and in some cases, the fistula can become infected with microorganisms and lead to an abscess, a problem that can be life-threatening if left untreated.

Anal fissure. These are cracks in the anus or skin around. An anal fissure is often accompanied by a secondary infection, which usually causes pain during stool passage.

Nutrient malabsorption. Nutrient malabsorption often leads to anemia. This is due to the fact that the affected intestine, in Crohn’s disease, is not able to absorb enough nutrients. In addition, frequent loose stools, abdominal pain and intestinal cramps lead to loss of appetite, thereby reducing the amount of nutrients consumed.

Other health problems. In addition to inflammation and ulcers in the gastrointestinal tract, Crohn’s disease can lead to problems in other organs, such as arthritis (inflammation of the joints), damage to the eyes or skin, nail changes, kidney and gallstones, and sometimes and inflammation of the bile ducts. People with long-term Crohn’s disease often have osteoporosis, which causes bones to become more fragile.

Inflammatory bowel disease and colon cancer.

Crohn’s disease increases the risk of colon cancer. Despite this increased risk, more than 90 percent of people with inflammatory bowel disease will never develop cancer.
Your risk of getting cancer is significantly higher if you have had inflammatory bowel disease for at least eight years and if the disease has spread throughout your colon. The longer the course of the disease and the larger the affected area, the higher the risk of colon cancer. The risk of other types of cancer is also increased, including anal cancer.