Ulcerative colitis prednisolone. Ulcerative Colitis and Prednisolone: Balancing Benefits and Risks in Treatment

31.03.197216.08.2021 by alexxlab

How do steroids like prednisolone help manage ulcerative colitis flares. What are the potential side effects of long-term steroid use for UC. Why should patients consider alternative maintenance medications for ulcerative colitis. When might short-term steroid treatment be appropriate for UC symptoms.

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Understanding Ulcerative Colitis and the Role of Steroids

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the colon and rectum. Since the 1950s, corticosteroids, commonly known as steroids, have been a crucial tool in managing acute flare-ups of UC. These powerful anti-inflammatory medications can provide rapid relief from symptoms, but their use comes with both benefits and risks that patients and healthcare providers must carefully consider.

What are corticosteroids?

Corticosteroids are synthetic drugs designed to mimic the effects of cortisol, a hormone naturally produced by the adrenal glands. In the context of UC treatment, steroids like prednisolone work by suppressing the immune system and reducing inflammation in the colon. This can lead to a quick improvement in symptoms such as abdominal pain, diarrhea, and rectal bleeding.

The Effectiveness of Steroids in Managing UC Flares

Steroids have proven highly effective in treating acute flare-ups of ulcerative colitis. When patients experience severe symptoms, intravenous high-dose prednisone may be administered for immediate relief. For mild to moderate flares, gentler steroids like budesonide (Entocort) can be prescribed to reduce inflammation with fewer side effects.

How quickly do steroids work for UC?

One of the primary advantages of steroids is their rapid action. Many patients experience significant symptom relief within days of starting treatment. This quick response can be crucial for those suffering from severe UC flares, providing a much-needed respite from debilitating symptoms.

Short-Term Benefits vs. Long-Term Risks of Steroid Use

While steroids can offer rapid symptom relief, they are not considered a long-term solution for UC management. Dr. Laura Raffals, a gastroenterologist at the Mayo Clinic, emphasizes that “Steroids provide patients with vast relief quickly, but they’re not a long-term solution and they have a lot of side effects.”

What are the common short-term side effects of steroids?

Weight gain
Moon face (facial swelling)
Acne
Irritability
Insomnia

These short-term effects, while unpleasant, are generally manageable and reversible once steroid treatment is discontinued. However, the long-term use of steroids, even at low doses, can lead to more serious health concerns.

Long-Term Complications of Steroid Use in UC Treatment

Consistent use of steroids, particularly at higher doses, can result in significant health risks. The Mayo Clinic notes several potential complications associated with prolonged steroid use:

Osteoporosis (weakening of bones)
Increased risk of infections
High blood pressure
Diabetes
Cataracts
Muscle weakness
Thinning skin

Can steroid use affect COVID-19 severity in UC patients?

A study published in the journal Gastroenterology in August 2020 found that corticosteroid use is associated with severe COVID-19 symptoms in IBD patients. This underscores the importance of carefully weighing the benefits and risks of steroid treatment, especially during the ongoing pandemic.

Steroids as a Bridge to Long-Term UC Management

Given the potential risks associated with long-term steroid use, healthcare providers typically aim to use these medications as a short-term solution. Dr. David Hudesman, medical director of the inflammatory bowel disease center at NYU Langone Health, explains that “Steroids can reduce inflammation, but they don’t heal the inside. They’re like a Band-Aid.”

How are steroids used in conjunction with maintenance medications?

When prescribing steroids for UC flares, doctors often simultaneously introduce a long-term maintenance medication, such as mesalamine (Lialda). As the maintenance medication begins to take effect, the steroid dosage is gradually tapered off. This approach allows for immediate symptom relief while working towards a more sustainable long-term treatment plan.

Alternative Treatment Options for Ulcerative Colitis

For patients who experience frequent flares or find themselves needing multiple courses of steroids within a year, alternative treatment options should be considered. Dr. Hudesman advises against repeatedly returning to prednisone in such cases.

What are some alternatives to steroids for UC management?

Immunosuppressants: These medications work by calming the body’s immune response, reducing inflammation in the colon.
Biologics: These advanced drugs target specific molecules in the body responsible for inflammation, offering a more targeted approach to treatment.

Both immunosuppressants and biologics generally have fewer side effects compared to long-term steroid use and can be more effective in maintaining remission.

The Importance of Adherence to UC Treatment Plans

A study published in the journal PLoS One in March 2019 revealed that nearly half of inflammatory bowel disease patients stop taking their medication for various reasons. However, discontinuing maintenance medication can significantly increase the risk of relapse.

Why is it crucial to stick to prescribed UC treatments?

Dr. Hudesman emphasizes that how a patient feels does not always correlate with the actual state of their disease. Even if symptoms seem to be under control, discontinuing medication can lead to silent progression of inflammation, potentially resulting in complications or the need for surgery.

Personalized Approach to UC Management

Every patient’s experience with ulcerative colitis is unique, and treatment plans should be tailored accordingly. While steroids may be necessary for managing severe flares initially, the goal is to transition to a maintenance medication that can control the condition long-term with fewer side effects.

How do doctors determine the best treatment plan for UC patients?

Healthcare providers consider various factors when developing a treatment strategy, including:

Severity and frequency of flares
Response to previous treatments
Presence of complications
Patient preferences and lifestyle factors

Regular check-ups and open communication between patients and their healthcare providers are essential for optimizing UC management and minimizing the need for steroid use.

Monitoring and Adjusting UC Treatment Over Time

As ulcerative colitis is a chronic condition, ongoing monitoring and adjustment of treatment plans are crucial. This may involve periodic colonoscopies to assess the state of the colon, blood tests to check for inflammation markers, and regular discussions about symptom management and quality of life.

How often should UC patients have their treatment plans reviewed?

The frequency of treatment plan reviews can vary depending on the individual’s disease activity and overall health. Generally, patients should have at least annual check-ups with their gastroenterologist, with more frequent visits during active flares or when adjusting medications.

Regular monitoring allows healthcare providers to:

Assess the effectiveness of current treatments
Identify any disease progression early
Adjust medications as needed to maintain remission
Address any side effects or concerns promptly

The Future of Ulcerative Colitis Treatment

Research into new treatments for ulcerative colitis is ongoing, with the goal of developing more targeted therapies that can provide long-term remission with fewer side effects. While steroids continue to play an important role in managing acute flares, the focus is shifting towards more sustainable, long-term treatment options.

What emerging treatments show promise for UC management?

Several areas of research are showing potential for improving UC treatment:

New biologic therapies targeting different inflammatory pathways
Small molecule drugs that can be taken orally
Gut microbiome modulation through probiotics or fecal microbiota transplantation
Stem cell therapies for severe cases

As these new treatments become available, they may offer additional options for patients who don’t respond well to current therapies or who experience significant side effects from steroids and other existing medications.

Lifestyle Factors in UC Management

While medication plays a crucial role in managing ulcerative colitis, lifestyle factors can also significantly impact disease activity and overall well-being. Patients can take an active role in their UC management by focusing on various aspects of their daily life.

How can diet affect UC symptoms?

While there’s no one-size-fits-all diet for UC, many patients find that certain foods can trigger or exacerbate symptoms. Keeping a food diary can help identify potential triggers. Some general dietary recommendations include:

Eating smaller, more frequent meals
Staying hydrated
Limiting high-fiber foods during flares
Avoiding known irritants such as caffeine, alcohol, and spicy foods

Can stress management techniques help control UC flares?

Stress doesn’t cause UC, but it can exacerbate symptoms and trigger flares in some patients. Incorporating stress-reduction techniques into daily life may help manage symptoms and reduce the need for steroid interventions. Effective stress management strategies can include:

Regular exercise
Meditation or mindfulness practices
Adequate sleep
Cognitive-behavioral therapy
Support groups or counseling

Patient Education and Self-Advocacy in UC Care

Empowering patients with knowledge about their condition and treatment options is crucial for optimal UC management. Informed patients are better equipped to make decisions about their care and communicate effectively with their healthcare team.

How can patients become more involved in their UC treatment decisions?

To take an active role in their care, UC patients can:

Stay informed about the latest UC research and treatment options
Keep detailed records of symptoms, medications, and side effects
Prepare questions for healthcare providers before appointments
Discuss concerns about medications, including steroids, openly with their doctor
Explore support groups or patient advocacy organizations for additional resources and peer support

By fostering a collaborative relationship with their healthcare team, patients can ensure that their treatment plan aligns with their goals and preferences, potentially reducing the need for frequent steroid use and improving overall quality of life.

The Pros and Cons of Taking Steroids for Ulcerative Colitis

Since the 1950s, corticosteroids (steroids) have been helping those with ulcerative colitis (UC) put the disease in remission. These powerful anti-inflammatories are highly effective at treating acute flare-ups, but they also come with problems.

They’re best for short-term use, and while they can relieve symptoms, they don’t slow disease progression, notes the Crohn’s and Colitis Foundation. They also increase your risk for infections, osteoporosis, and high blood pressure. And, according to a study published in August 2020 in the journal Gastroenterology, corticosteroid use is associated with severe COVID-19 symptoms in IBD patients.

“Steroids provide patients with vast relief quickly, but they’re not a long-term solution and they have a lot of side effects,” says Laura Raffals, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minnesota. In the short term, steroids frequently cause:

Weight gain
Moon face
Acne
Irritability
Insomnia

Consistent use — even at low doses — can affect bone strength, increasing the risk of osteoporosis. And typically, the higher the dose, the higher the risk. There are many side effects from continued use of steroids, notes the Mayo Clinic, including:

“Steroids can reduce inflammation, but they don’t heal the inside,” says David Hudesman, MD, medical director of the inflammatory bowel disease center at NYU Langone Health in New York City. “They’re like a Band-Aid.”

Short-Term Steroids Can Help Relieve Symptom Flares

If your UC flare is severe and you’re in significant pain, with bloody stools and diarrhea, your doctor may prescribe an intravenous high dose of prednisone for immediate relief. “We try to minimize it to the shortest period possible and allow it to serve as a bridge to a better long-term treatment strategy,” says Dr. Raffals.

If your UC flare is mild to moderate, your doctor may prescribe a gentler steroid, such as Entocort (budesonide) to reduce inflammation. It isn’t as strong as prednisone and has fewer side effects. It’s designed to attack mild to moderate intestinal inflammation and keep inflammation at bay for three months or so. The drug is FDA-approved for use for eight weeks, although it can be prescribed for longer in certain cases, according to Massachusetts General Hospital in Boston.

At the same time, you’ll likely also be prescribed a long-term maintenance medication that’s not a steroid, such as Lialda (mesalamine), which can take time to kick in. Since steroids are not designed for long-term use, you’ll need to wind down their use as the maintenance medication begins to work. Your doctor will likely taper off your steroid dosage until you’re off it completely.

Other Medication Options for Ulcerative Colitis

But what if symptoms recur just months after you’ve stopped steroids?

“The response shouldn’t be to go back on prednisone,” Dr. Hudesman says. “You shouldn’t be on multiple courses of steroids, even two courses, within a year.”

Instead, talk to your doctor about using an immunosuppressant or biologic agent, both of which have fewer side effects. The immunosuppressant drugs will reduce inflammation by calming your body’s immune system. Biologics, on the other hand, will attach to and then interrupt a molecule in the body responsible for inflammation.

“Whatever is a reasonable time for maintenance medication, we try to give it,” Hudesman says. “If you’re not getting there, then we consider moving medications or make sure something else isn’t complicating your disease.”

RELATED: Medications for Ulcerative Colitis

Stick to Your Colitis Treatment Plan to Avoid Overusing Steroids

Some people may worry about side effects that can be caused by their maintenance medication — and they ditch their treatment while they’re in remission. According to a study published in March 2019 in the journal PLoS One, nearly half of inflammatory bowel disease patients stop taking their medication for a variety of reasons. But doing so increases the risk of relapse.

Although steroids can have dangerous side effects, you should take them as directed if you need them. The same goes for your maintenance medication.

“The most important thing to know with UC is that how you feel doesn’t correlate with what’s happening on the inside,” Hudesman says. “Even if you feel great most of the time without medication, if I did a colonoscopy, it might show severe disease. A lot of patients tolerate little flares until they can’t. Then all of a sudden, you’re talking about surgery or a very complicated disease.”

RELATED: Thinking of Stopping Your Ulcerative Colitis Medication? Think Again

The bottom line? Every patient is different. But if you’re experiencing severe UC flares, you may need a steroid initially until your maintenance medication can control your condition. The various side effects associated with prolonged steroid use give many doctors pause.

“Steroids are fast and cheap and well-known, but we prefer to get a flare under control without them if we can,” Raffals says.

You may also need to experiment with maintenance medication until you find one that works, or switch to immunosuppressant or biologic therapy.

“Ideally, the goal is to find a maintenance medication that you feel well with and that heals you from the inside,” Hudesman says.

Medical Treatment of Ulcerative Colitis

Clin Colon Rectal Surg. 2004 Feb; 17(1): 7–19.

Ulcerative Colitis

Editor in Chief David E. Beck M.D.

Guest Editor Bruce G. Wolff M.D.

Uma Mahadevan

¹Division of Gastroenterology, University of California, San Francisco, San Francisco, California

Address for correspondence and reprint requests: Uma Mahadevan M.D. UCSF/Mount Zion IBD Center, 2330 Post Street #610, San Francisco, CA 94115, ude.fscu.asti@hamamuThis article has been cited by other articles in PMC.

Abstract

Ulcerative colitis is a chronic inflammatory disease of the colon with an increasing incidence worldwide. The medical management of this disease continues to expand as drugs to induce and maintain remission are sought to avoid the need for colectomy. This article will review the standard of care for the treatment of mild, moderate, and severe ulcerative colitis. The efficacy, optimal usage, and adverse events profile of agents such as 5-aminosalicylates, corticosteroids, azathioprine, and cyclosporine will be discussed and an algorithm for their use will be developed. Alternative and experimental therapies such as monoclonal antibodies, probiotics, and heparin will also be addressed.

Keywords: Ulcerative colitis, medical therapy, cyclosporine

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that affects up to 12 per 100,000 people in Western countries.¹ The incidence may be increasing in developing nations but is more frequent in Caucasians and people of Jewish descent. Although there is an increase in families, the genetic trend is not as strong as in Crohn’s disease.² The peak age of incidence is in persons between 15 and 30 years old.¹ Protective factors against the development of UC include cigarette smoking³ and appendectomy. ⁴

The distribution of disease at diagnosis varies widely. Estimates from a Norwegian study report proctitis in 32% of patients, left-sided colitis in 33%, and more extensive colitis in 35%.⁵ Thirty-nine percent of patients with proctosigmoiditis can expect extension of their disease⁶ and 90% of all UC cases can expect a relapsing course.⁷ Approximately 4 to 9% will require colectomy in the year of diagnosis,⁵^,⁶ with a subsequent risk of colectomy at 1% per year.⁷ The majority of UC patients will require medical therapy chronically throughout their lifetime; therefore, an understanding of the appropriate use of these agents is important for the physician caring for these patients.

Prior to initiating therapy, a patient must be evaluated for extent and severity of disease. Extent of disease is best assessed by colonoscopy with biopsy of grossly affected as well as unaffected areas. If disease is distal to the splenic flexure, topical therapy such as suppositories and enemas may be the first choice. For more extensive disease, oral agents or a combination of oral and topical agents are indicated. The severity of disease can be assessed by the Truelove and Witts score⁸ (Table ). This article will focus on medications for induction and maintenance of remission in mild to moderate UC as well as colectomy-sparing therapy for severe colitis.

Table 1

Truelove and Witts’ Criteria for Evaluating the Severity of Ulcerative Colitis⁸

Variable	Mild Disease	Severe Disease	Fulminant Disease
Moderate disease includes features of both mild and severe disease.
Stools (number/day)	< 4	> 6	> 10
Blood in stool	Intermittent	Frequent	Continuous
Temperature (°C)	Normal	> 37. 5°	> 37.5°
Pulse (beats/minute)	Normal	> 90	> 90
Hemoglobin	Normal	< 75% of normal value	Transfusion required
Erythrocyte sedimentation rate (mm/hr)	≤30	>30	>30
Colonic Features on x-ray		Air, edematous wall, thumbprinting	Dilatation
Clinical signs		Abdominal tenderness	Abdominal distention and tenderness

AMINOSALICYLATES

Sulfasalazine and 5-aminosalicylate (5-ASA) drugs are the first line in drug therapy for the treatment of mild to moderate UC. Table summarizes the available agents. Type and dose of therapy are determined by location and severity of disease. For distal disease, topical therapy is the most effective method of delivery. By metanalysis, rectally administered 5-ASA is superior to placebo and rectal corticosteroids for induction and maintenance of remission in distal UC.⁹ If the patient has proctitis, 5-ASA suppositories at a dose of 500 mg twice daily will induce and maintain remission.¹⁰^,¹¹ For disease up to the splenic flexure, 5-ASA enemas are effective for induction and maintenance of remission in doses of 2 to 4 g per enema.¹²^,¹³

Table 2

Generic Name	Proprietary Names	5-ASA Delivery Mechanism	Sites of Delivery	Daily Dose, Range
Mesalamine	Rowasa Salofalk	Enema suspension	Left colon and rectum	1-4 g
Mesalamine	Canasa	Suppository	Rectum	0. 5-1.5 g
Mesalamine	Asacol	Eudragit-S coated tablets (release at pH > 7	Terminal ileum, colon	1.6-4.8 g
Mesalamine	Salofalk, Mesasal, Claversal	Mesalamine in sodium/glycerine buffer coated with Eudragit-L (release at pH > 6)	Distal jejunum, proximal ileum	1.5-4 g
Mesalamine	Pentasa	Ethylcellulose coated microgranules (time and pH dependant release)	Entire small bowel, colon	2-4 g
Sulfasalazine	Azulfidine	5-ASA azo-bound to sulfapyridine	Colon	1-4 g
Olsalazine	Dipentum	5-ASA dimer linked by azo-bond	Colon	1-3 g
Balsalazide	Colazaal	5-ASA azo-bound to inert carrier	Colon	2-6. 75 g

For more extensive disease, multiple oral 5-ASA preparations are available. Sulfasalazine was the first 5-ASA agent found to be effective in UC.¹⁴ Placebo-controlled trials have shown that sulfasalazine is effective in inducing¹⁵^,¹⁶ and maintaining¹⁷^,¹⁸ remission in mild to moderate UC. However, its use is limited by high rates of intolerance among patients. Side effects can include headache, abdominal pain, nausea, vomiting, skin rash, fever, hepatitis, hematologic abnormalities, folate deficiency, pancreatitis, systemic lupus erythematosus, and male infertility.¹⁹ Sulfasalazine should always be given with folate 1 mg daily and is contraindicated in men attempting conception.²⁰

Sulfasalazine is a combination of 5-ASA azo-bound to the antibiotic sulfapyridine. It is the 5-ASA component that is the therapeutically active compound and the sulfapyridine moiety that is the cause of many of the side effects. ²¹^,²²^,²³ This finding led to the development of alternative 5-ASA delivery systems for the treatment of UC and the discovery that it is the overall dose of mesalamine given, rather than the delivery system, that determines efficacy. Oral mesalamine agents with delayed- (Asacol) or timed-release (Pentasa) formulations at doses of 1.6 to 4.8 g/day are effective in inducing remission in mildly to moderately active UC.²⁴^,²⁵^,²⁶ Doses of 0.8 to 4.8 g/day are effective in maintaining remission. Combination therapy, with oral mesalamine 2.4 g/day and rectal mesalamine 4 g/day, is more effective than either therapy alone.²⁷ However, this may simply be a reflection of the overall dose of mesalamine received by the patient.

Olsalazine and balsalazide are 5-ASA agents that have diazo bonds, which are released by colonic bacteria. Olsalazine is effective for induction²⁸^,²⁹ and maintenance³⁰^,³¹ of remission in UC, but its use is limited by worsened diarrhea. ³² Balsalazide is composed of a 5-ASA linked to an inert carrier molecule. Although one study did show significant efficacy of balsalazide over an equivalent dose of mesalamine,³³ other studies have shown an efficacy equal to sulfasalazine³⁴ and mesalamine³⁵^,³⁶ for induction of remission in mild to moderate UC.

Though 5-ASA agents are considered safe, some toxicity can be seen. Aside from the complications attributed to sulfasalazine above, the most frequently reported side effects of 5-ASA agents include dizziness, fever, headache, abdominal pain, nausea, and rash.²⁵^,²⁶ Rare but serious adverse events include pulmonary toxicity, pericarditis, hepatitis, pancreatitis, aplastic anemia, leukopenia, and thrombocytopenia.³⁷^,³⁸^,³⁹^,⁴⁰ Though interstitial nephritis has been reported,⁴¹ the frequency of renal insufficiency was low in large safety and pharmacovigilance databases for Asacol and Pentasa. ⁴²^,⁴³ Finally, a minority of patients will experience worsening diarrhea and abdominal pain due to a hypersensitivity reaction to 5-aminosalicylate.^43a

In summary, 5-ASA agents are safe and effective for the induction and maintenance of remission in mild to moderate UC. Its use in severe colitis is not well studied. Data support the concept that the optimum use of aminosalicylates in active UC demands the highest tolerated dose, whether administered orally, rectally, or in combination. In quiescent disease, lower doses may be more tolerable to the patient and are less costly, although again, there is the general theme of dose response.

CORTICOSTEROIDS

The discovery that corticosteroids were effective in UC had a significant positive impact on a disease with a previous high mortality. Mortality rates dropped from a high of 61%⁴⁴ to 4 to 7%.⁴⁵ However, today the side effects of corticosteroids make it a less desirable though sometimes unavoidable agent in the therapy of UC.

In a population-based study in Olmstead County, Minnesota, 34% of UC patients required corticosteroids at some point in their disease course.⁴⁶ Therapy with corticosteroids resulted in complete remission in 54%, partial remission in 30%, and no response in 16%. At 1 year from initiation of corticosteroid therapy, prolonged response without steroids or surgery was seen in 49%, corticosteroid dependence in 22%, and surgery in 29%.

Resistance to corticosteroids is seen in 16 to 20% of patients.⁴⁶^,⁴⁷ Several potential mechanisms for resistance to corticosteroid therapy in patients with inflammatory bowel disease (IBD) have been described, including an increase in the expression of glucocorticoid receptor β⁴⁸ and increased expression of the multidrug resistance-1 gene (MDR-1). The latter results in an increased expression of the membrane-based drug efflux pump P-glycoprotein 170 that pumps corticosteroids out of cells, thus lowering the intracellular concentration. ⁴⁹

Corticosteroids can be administered as oral (cortisone, prednisone, prednisolone, budesonide), intravenous (prednisolone, methylprednisolone, corticotropin), or rectal (beclomethasone, tixicortol, budesonide, prednisolone metasulfobenzoate) formulations. Truelove and Witts reported the efficacy of cortisone 100 mg per day in UC in 1955.⁸ Baron and colleagues then reported that 40 mg of prednisone was more effective than 20 mg and equally effective as 60 mg, but with fewer side effects.⁵⁰ Finally, single daily dosing of prednisone 40 mg daily was equally effective as 10 mg four times a day.⁵¹ It is from these early studies that the current maxim of prednisone 40 mg per day for moderate to severe UC originated. No maintenance benefit of corticosteroids in UC has been found.⁵²

Rectal corticosteroids are effective in left-sided UC. They provide quick relief for patients with tenesmus and bleeding. Rectal hydrocortisone 100 mg⁵³ and prednisolone 10 mg⁵⁴ have been proven effective by controlled trials for induction of remission, but not for maintenance. ⁵⁵ Budesonide enemas, which have minimal systemic absorption, are also effective for induction but not for maintenance of remission in left-sided UC.⁵⁶ However, by metanalysis, topical corticosteroids were not as effective as topical mesalamine therapies for ulcerative proctitis and left-sided UC.⁵⁷ Also, rectal corticosteroids are well absorbed and can result in suppression of the adrenal axis.⁵⁸

Prednisone and prednisolone are well absorbed after oral administration and bioavailability is high, averaging over 70%. However, the absorption may be decreased in patients with severe UC in whom oral administration of prednisolone resulted in a lower peak plasma concentration and a slower rate of decrease in the plasma concentration compared with healthy volunteers.⁵⁹ Patients with severe UC who receive 60 mg/day of intravenous prednisolone have a 73% response rate in 5 days.⁶⁰ Some patients are slower responders and will require 7 to 10 days to respond. No controlled trials have addressed the effectiveness of single, multiple, or continuous infusion of corticosteroids in severe UC.⁶¹ Intramuscular corticotropin (adrenal corticotropin hormone, ACTH) at 80 U/day showed a similar benefit to cortisone 200 mg/day in patients with active UC.⁵⁵ In severe UC, corticotropin 80 to 120 U/day was similar to hydrocortisone 300 to 400 mg/day.⁶²^,⁶³^,⁶⁴ However, some deaths were reported in IV ACTH due to adrenocortical necrosis.⁶⁴

Corticosteroid toxicity is frequent and often results in resistance on the part of patients to reinitiate therapy if they have used it before. Short-term toxicities observed include moon face (47%), acne (30%), infection (27%), ecchymoses (17%), hypertension (15%), hirsutism (7%), petechial bleeding (6%), and striae (6%). Prolonged corticosteroid therapy can result in multiple serious side effects including hypertension, new onset diabetes mellitus, infection, osteonecrosis, steroid associated osteoporosis, myopathy, psychosis, cataracts, and glaucoma. ⁶⁵^,⁶⁶^,⁶⁷ Table lists potential side effects of corticosteroid therapy.

Table 3

Adverse Effects Associated with Systemic Corticosteroid Therapy

Adapted from Yang and Lichtenstein¹⁶³ with permission.
Cutaneous	Atrophy, striae, vascular effects, purpura, alopecia, pigmentation, acne, easy bruising
Cardiovascular	Hypertension, edema, atherosclerosis
Gastrointestinal	Nausea, vomiting, intestinal perforation, pancreatitis, esophagitis
Gynecological/obstetrical	Amenorrhea, gestational diabetes, adrenal suppression of infant
Neuropsychiatric	Psychosis, peripheral neuropathy, pseudotumor cerebri, depression/mood disorders, impaired cognitive function, seizures, insomnia, irritability
Metabolic	Hyperglycemia, hyperlipidemia, obesity, hypocalcemia, hypokalemia, buffalo hump
Musculoskeletal	Osteoporosis/osteopenia, aseptic necrosis, growth retardation, muscle atrophy, myopathy
Hematological	Leukocytosis, lymphopenia, eosinophenia, infection, immunosuppression, impaired fibroplasia, decreased mitotic rate
Ophthalmalogical	Cataracts, glaucoma, infection, exophthalmoses, hemorrhage
Endocrine	Hypothalamic-pituitary-adrenal axis suppression, hirsutism, moon facies
Pediatric	Growth retardation

For moderate to severe UC, the preferred initial prednisone dose is 40 mg/day administered as a single dose. The optimal tapering strategy has not been determined, but experienced clinicians will typically treat the patient with prednisone 40 mg/day for 2 to 4 weeks, then taper by 5 mg/week to a daily dose of 20 mg/day, then slow the taper to 2.5 mg/week until prednisone is discontinued. For severe UC, requiring hospitalization, hydrocortisone 300 to 400 mg/day or methylprednisolone 40 to 60 mg/day is used. Five to seven days are required prior to determining whether the patient has failed steroids.

ANTIBIOTICS

The lack of efficacy of antibiotics in the treatment of UC and Crohn’s disease is somewhat surprising given the presumed role of bacteria in the etiology of IBD. One placebo-controlled trial of ciprofloxacin in moderately active UC showed benefit⁶⁸ while another was negative.⁶⁹ The addition of intravenous ciprofloxacin to steroids in severe UC was also not of benefit.⁷⁰ Oral tobramycin had short-term efficacy⁷¹ in UC but could not maintain remission. ⁷² In acute severe UC, the combination of tobramycin and metronidazole,⁷³ oral vancomycin alone,⁷⁴ or intravenous metronidazole alone⁷⁵ were not of added benefit to corticosteroids. Finally, in a small placebo-controlled trial, rifaximin, a nonabsorbed, broad-spectrum antibiotic, was not statistically better than placebo in overall clinical outcome in patients with steroid-refractory severe UC, but did have a significant reduction in stool frequency, rectal bleeding, and sigmoidoscopic score compared with placebo.⁷⁶ Larger trials are underway.

Antibiotics should not be used without evidence of infection in patients with mild to moderate UC. Although evidence does not support their use in severe UC, in clinical practice the hospitalized patient may receive antibiotics as prophylaxis against bacterial translocation in the severely inflamed colon.

PROBIOTICS

Probiotics are live nonpathogenic organisms that confer health benefits by improving the microbial balance. While the formulation VSL3 has shown clear benefit for prevention of pouchitis after ileal-pouch surgery⁷⁷ and maintenance of remission in chronic pouchitis,⁷⁸ their benefit and that of other probiotics formulations in UC are still to be proven. Two small controlled studies have shown that E. coli Nissle is effective for maintenance of remission in UC.⁷⁹^,⁸⁰ An open label trial of VSL3 in mildly to moderately active UC demonstrated a remission rate of 63%. However, patients were on other agents such as mesalamine and steroids.⁸¹ Larger controlled trials are needed to prove efficacy in both induction and maintenance of remission in UC.

NICOTINE

Nonsmokers and former smokers have higher rates of UC than current smokers.³ Also, smokers with UC who stop smoking experience increased severity of disease.⁸² The mechanism of this effect is thought to be due to nicotine, but is not completely elucidated. ⁸³^,⁸⁴ Placebo-controlled trials of transdermal nicotine patches demonstrated efficacy in achieving clinical remission or improvement at doses of 25 mg/24 hours⁸⁵ and 22 mg/24 hours.⁸⁶ However, it was not effective for maintenance,⁸⁷ although an uncontrolled study suggested that patients who are treated with transdermal nicotine maintain their response longer than those treated with corticosteroids.⁸⁸ Nicotine enemas also demonstrated benefit in uncontrolled trials.⁸⁹^,⁹⁰ The major drawback of nicotine use is the high percentage of side effects, especially in patients who have never smoked before. These side effects include skin irritation, lightheadedness, nausea, vomiting, diaphoresis, central nervous system disturbances, and insomnia.⁸⁴

IMMUNOSUPPRESSANTS

While 5-ASA agents are the first line for induction and maintenance of remission in mild to moderate UC and steroids are used for induction of remission in moderate to severe UC, immune modifier drugs are used to induce remission in steroid-dependent or steroid-refractory disease, maintain remission in those patients for whom 5-ASA agents are inadequate, and as salvage therapy in severe disease refractory to steroid therapy.

Azathioprine/6-Mercaptopurine

6-mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are purine antimetabolite drugs demonstrated to be effective for the induction and maintenance of remission in UC and have proven steroid-sparing effects. The efficacy of 6-MP was recognized as early as 1962 in a case report by Bean.⁹¹ Though some controlled studies of AZA versus placebo and AZA versus sulfasalazine in the treatment of acute attacks of colitis found no significant benefit,⁸⁹^,⁹² others found that AZA use resulted in improved disease activity, a decreased need for steroids,⁹³ and prolonged rates of remission.⁹⁴ Multiple uncontrolled studies confirmed the benefits of AZA/6-MP.⁹⁵^,⁹⁶^,⁹⁷^,⁹⁸^,⁹⁹

Effective doses of AZA are 2.0 to 3.0 mg/kg/day and of 6-MP are 1.0 to 1.5 mg/kg/day and may take up to 17 weeks to take complete effect. ¹⁰⁰ Though some physicians begin at low doses and titrate upwards, our practice is to begin at full dose with careful monitoring of the compete blood count. There is no role for intravenous loading of AZA in severe UC.¹⁰¹ Thiopurine S-methyltransferase (TPMT) phenotype or genotype can aid in determining safety and optimal dosage of AZA/6-MP. Low to intermediate levels of TPMT are associated with leukopenia in rheumatoid arthritis¹⁰² and with Crohn’s disease.¹⁰³ Based on these observations, it is recommended that patients with normal TPMT activity receive standard doses of AZA or 6-MP. Patients with intermediate activity should receive 50% of the standard dose and those who have no TPMT activity should not be treated with the drug.¹⁰⁴ The use of metabolite levels (6-TGN [thioguanine nucleotides] and 6-MMP [6-methylmercaptopurine]) to gauge optimal dosing of AZA/6-MP is controversial. Though two studies supported its use,¹⁰⁵^,¹⁰⁶ three others failed to demonstrate a consistent relationship between clinical efficacy and erythrocyte 6-TGN concentrations. ¹⁰⁷^,¹⁰⁸^,¹⁰⁹

Allergic reactions occur in 5% of patients taking AZA or 6-MP and include pancreatitis, fever, rash, malaise, nausea, diarrhea, and some cases of hepatitis.¹¹⁰ Nonallergic reactions include bone marrow suppression leading to leukopenia, anemia or thrombocytopenia, opportunistic infection, and hepatitis. Lymphoma does not appear to be increased above what is expected in IBD,¹¹⁰^,¹¹¹^,¹¹² though there may be an increase in Epstein-Barr virus-associated lymphomas in patients treated with AZA/6-MP.¹¹³

Methotrexate

Methotrexate (MTX) has demonstrated benefit for the induction and maintenance of remission in Crohn’s disease¹¹⁴^,¹¹⁵; however, its benefit in UC is not well established. Uncontrolled data have shown response in small series of patients with UC.¹¹⁶^,¹¹⁷^,¹¹⁸ The only controlled trial in UC was by Oren and associates,¹¹⁹ which compared oral MTX 12. 5 mg/week with placebo in 67 patients with chronic active UC. No difference was found between the MTX and placebo group in remission and relapse rates. A recent study reported on patients with steroid-dependent or steroid-resistant active UC.¹²⁰ Ten patients were intolerant or resistant to AZA and were switched to MTX 12.5 mg IM/ week. Six of 10 (60%) achieved clinical remission, 40% achieved clinical response, and 20% subsequently relapsed. Available data suggest that AZA/6-MP should be the first choice for maintenance and steroid sparing in UC, but MTX can be tried in those who are intolerant or resistant to AZA/6-MP. Our usual starting dose is 25 mg SQ/week, though once remission is achieved, 15 mg SQ/week can be used for maintenance.

MTX should always be given with folic acid 1 mg per day. Use in patients who are diabetic, obese, use excessive alcohol, or have known liver abnormalities is contraindicated. MTX is teratogenic and should not be used in men or women attempting conception. Increased serum transaminases and hypersensitivity reactions such as rash and pneumonitis can sometimes be seen.

Cyclosporine

Cyclosporine (CSA) is a calcineurin inhibitor that is used as salvage therapy for induction of remission in severe, steroid-refractory UC that would otherwise require colectomy. There are four randomized trials that have demonstrated the efficacy of CSA in severe UC. The first, by Lichtiger et al, found that 9/11 (82%) steroid-refractory UC patients had clinical response with 4 mg/kg/day of CSA in combination with intravenous steroids, versus none of placebo-treated patients on intravenous steroids alone.¹²¹ Two other controlled studies suggested that CSA alone at a dose of 4 mg/kg/day without steroids is effective in inducing remission in severe UC.¹²²^,¹²³ Finally, a study by Van Assche and colleagues found that 2 mg/kg/day of CSA is equivalent to 4 mg/kg/day in achieving response in severe UC.¹²⁴

Patients who respond to 4 mg/kg/day of IV CSA are continued on the drug for 7 to 10 days. The target whole blood CSA level is 300 to 350 ng/ml for the 4 mg/kg/day dose or 150 to 250 ng/ml for the 2 mg/kg/day dose. They are then converted to oral CSA at a dose of 8 mg/kg/day or twice the IV dose in hospital.¹²⁵ The desired CSA level on oral dose is 150 to 300 ng/ml. Unfortunately, 45% of patients on oral CSA alone will require colectomy at 6 months.¹²⁶ This can be decreased to 20% by the addition of 6-MP/AZA at discharge from the hospital.¹²⁶ Patients are also continued on prednisone, which is tapered during outpatient follow-up. This regimen of triple immunosuppressive therapy with CSA, 6-MP/AZA, and prednisone can lead to significant infectious complications. For this reason, trimethoprim/sulfamethoxazole is added for prophylaxis. One uncontrolled study suggested that patients responding to IV CSA can be started on oral AZA without oral CSA, and prednisone can be tapered accordingly¹²⁷; however, the colectomy rate was 41%.

An oral, microemulsion form of CSA (Neoral) has been developed which has increased oral bioavailability and improved absorption from the small bowel. ¹²⁸ The pharmokinetic parameters of CSA microemulsion in patients with IBD appear to be similar to those of healthy volunteers.¹²⁹ Three small series have described efficacy of oral microemulsion CSA in severe UC,¹³⁰^,¹³¹^,¹³² though larger controlled trials are needed.

In a report from Mount Sinai Hospital on 111 IBD patients treated with CSA, the most frequent adverse events were paresthesias (51%), hypertension (43%), hypertrichosis (27%), renal insufficiency (23%), infections (20%), gingival hyperplasia (4%), seizures (3%), death (2%), and anaphylaxis (1%).¹³³ In a similar report from the University of Chicago on 74 patients with IBD treated with CSA, 54% experienced adverse events including severe events such as Pneumocystis carinii pneumonia in two patients, abdominal abscess, grand mal seizure, mycotic aneurysm, and renal insufficiency.¹²⁶ Table lists drug interactions of CSA and tacrolimus.

Table 4

Potential Drug Interactions of Cyclosporine and Tacrolimus

Adapted from Kornbluth, et al¹²⁵ with permission.
Inhibition of cytochrome P450	Calcium channel blockers
Increased CSA levels	Bromocriptine
	Metoclopramide
	Imidazoles
	Macrolide antibiotics
	Methylprednisolone
	Protease inhibitors
	Grapefruit juice
Induction of cytochrome P450	Rifampin
Decrease cyclosporine levels	Phenobarbital
	Phenytoin
	Carbamazepine
	Reverse transcriptase inhibitors
	St. John’s wort

CSA in severe UC is definitely effective, but its side-effect profile and tangible long-term failure rate must be discussed in depth with the patient debating colectomy versus salvage medical therapy. Also, patients who are not tolerant of AZA/6-MP are not good candidates for CSA therapy, as CSA alone has a high colectomy rate over time. Side effects may be decreased by using lower doses of IV CSA at 2 mg/kg/day, using antibiotic prophylaxis, or avoiding triple therapy with oral CSA, AZA and prednisone.

Tacrolimus

Tacrolimus is a calcineurin inhibitor like CSA. Controlled trials in severe UC have not been conducted to date, but multiple case series suggest efficacy. The first study was by Bousvaros et al¹³⁴ and described a 69% clinical response rate in 13 patients with steroid-refractory UC. However, at 1 year, only 38% of patients avoided colectomy. Three case series note salvage therapy with tacrolimus in steroid-resistant or steroid-dependent UC¹³⁵^,¹³⁶ as well as in a patient with toxic megacolon. ¹³⁷ One trial compared intravenous to oral tacrolimus in 38 patients with refractory UC.¹³⁸ Oral and IV dosing was equivalent. Eighteen of 38 patients (47%) improved within 14 days. Thirty-five of 38 patients (92%) avoided colectomy at 28 days, but at 2 years, the colectomy rate was 50%.

The dose of oral tacrolimus is 0.1 to 0.2 mg/kg/day given in divided doses twice daily. The serum trough levels are 4 to 6 ng/ml. Patients should be monitored closely for evidence of infections and trimethoprim/sulfamethoxazole prophylaxis should be used. Side effects include transient renal insufficiency, tremor, paresthesias, hyperkalemia, and hypertension.¹³⁵ These often resolve with lowering of the dose.

Infliximab

Infliximab is a chimeric monoclonal antibody to tumor necrosis factor-α (TNF), a key inflammatory cytokine. While infliximab has made a dramatic impact on the treatment of Crohn’s disease,¹³⁹ its role in UC is not clear. Sands and associates reported 11 patients in a controlled trial of infliximab in severe, steroid-refractory UC. ¹⁴⁰ Four of eight patients (50%) who received infliximab had a clinical response, although one subsequently required colectomy. Two small case series report response in severe UC,¹⁴¹^,¹⁴² but a larger randomized controlled trial was negative.¹⁴³ In this latter trial, patients with severe, steroid-refractory UC were randomized to infliximab 5 mg/kg or placebo at weeks 0 and 2. After 6 weeks, remission was achieved in 8/22 infliximab patients and 6/20 placebo (not significant). A controlled trial of infliximab in nonsteroid-refractory patients¹⁴⁴ randomized patients to either infliximab 5 mg/kg at 0, 2, and 6 weeks or intravenous prednisolone at 1.5 mg/kg daily for 2 weeks followed by a taper. Five of 6 patients receiving infliximab and 6/7 patients receiving steroids had a response. The two agents appear to be equivalent in this small study.

Clinical experience and a placebo-controlled trial¹⁴³ suggest that infliximab is not effective in steroid-refractory UC. This is further supported by a retrospective analysis of 27 patients with active UC who received infliximab.¹⁴⁵ While 44% of all UC patients achieved remission and 22% had a partial response, steroid-refractory patients were less likely to respond when compared with steroid-responsive patients (33% vs 83%; p = 0.026). Infliximab should not be used in severe, steroid-refractory UC. Evidence for its use in steroid-responsive disease is anecdotal at best and controlled studies are needed.

EXPERIMENTAL AGENTS

Heparin

Thrombotic events associated with UC and histologic evidence of microvascular thrombosis on colon biopsy suggested that anticoagulation may be an effective therapy for UC.¹⁴⁶ Uncontrolled studies did find unfractionated heparin to be of benefit,¹⁴⁷^,¹⁴⁸ but small controlled studies comparing unfractionated heparin to corticosteroids had mixed results.¹⁴⁹^,¹⁵⁰ Larger, placebo-controlled trials of low-molecular-weight heparin in studies of 100 patients and 138 patients, respectively, found no significant benefit over placebo. ¹⁵¹^,¹⁵² Heparin is not effective for the treatment of UC but does appear to be safe with no increased risk of gastrointestinal bleeding, should the need for anticoagulation for other reasons arise in these patients.

BIOLOGICS: CYTOKINES AND ANTIBODIES

Investigational agents with preliminary reports of efficacy include vepolimomab (monoclonal antibody [mAb] to vascular adhesion protein-1)¹⁵³; interleukin-2 (IL-2) antagonists such as basiliximab, which may increase response to steroids in steroid-resistant UC¹⁵⁴; anti-CD3 antibodies, such as visilizumab, which has shown preliminary efficacy in steroid-resistant UC¹⁵⁵; antibody to α4β7, such as MLN-02, which mediates recruitment of lymphocytes to the gut and demonstrated safety and efficacy in a controlled trial in patients with active UC¹⁵⁶; and interferon-β, which showed some clinical response in patients with steroid-refractory UC in a phase II, placebo-controlled trial. ¹⁵⁷ Multiple other agents exist, but for all new agents, while preliminary results are exciting, randomized controlled trials are needed before widespread use is initiated.

LEUKOCYTAPHERESIS

One novel technique for the treatment of severe UC is leuckocytapheresis. Based on the theory that inflammation and damage to the colonic mucosa are caused by products of activated granulocytes, monocytes, and macrophages, an extracorporeal leukocytapheresis column (LCAP) was developed to remove these cells from the peripheral circulation, with reported efficacy in UC.¹⁵⁸ A randomized controlled trial in 76 active UC patients reported that addition of LCAP to corticosteroids improved clinical response with a reduction in steroid dosage.¹⁵⁹ These results were corroborated by a recent randomized trial from the same group showing that LCAP was more effective than sham perfusion (80% vs 33%; p < 0.05) in eliciting clinical response in patients with active UC. ¹⁶⁰

ALGORITHM FOR THE TREATMENT OF ULCERATIVE COLITIS

Figure outlines the algorithm for the treatment of a flare of UC. When a patient presents with a flare, the diagnosis should be confirmed and the severity of the disease established. Colonoscopy with biopsy to confirm the diagnosis of UC and establish the extent of the disease should be performed in all new and established cases. A small bowel follow-through should be performed once at some point in the disease course to rule out the diagnosis of Crohn’s disease. Stool studies should be sent in all acute flares to rule out superinfection with Clostridium difficile, bacteria, or ova and parasites. In a patient with severe UC, an unprepped flexible sigmoidoscopy rather than full colonoscopy should be performed with biopsies of the rectum for histology and viral culture. This will confirm the severity of the disease and will also rule out cytomegalovirus (CMV). One study reported that 36% of patients with steroid-refractory colitis had CMV on rectal specimens. ¹⁶¹ The majority of these patients responded to antiviral therapy with foscarnet or ganciclovir. The severity of the disease can be determined by the Truelove and Witts score (Table ).

An algorithm for the medial management of mild, moderate, and severe ulcerative colitis. Progression along arrows is indicated if prior therapies fail.

For mild to moderate disease the first-line therapy is 5-ASA agents. If this is ineffective, steroids can be used to induce remission. If the patient cannot be tapered off the steroids or relapses after steroid withdrawal, immunosuppression with AZA/6-MP should be initiated for steroid-sparing and maintenance effects. In the patient with severe disease not responding to oral steroids, intravenous steroids are indicated in an inpatient setting. If there is no response after 5 to 7 days, CSA should be offered if the patient is an appropriate candidate. Patients who are intolerant of AZA/6-MP are not good candidates as colectomy rates are high in patients on CSA alone. Theoretically, MTX can be used instead, though its use in UC has less supportive evidence. Patient reluctance to use CSA or failure to respond to CSA would then lead to colectomy.

Aggressive medical therapy with immunosuppressants does not increase the risk of postoperative complications after colectomy and ileal pouch-anal anastomosis.¹⁶² Factors that predicted an increase in short-term complications were high-dose steroids and severe disease. Variations on this algorithm with experimental or anecdotal agents can be tried as long as the patient is fully informed and the physician is comfortable with these drugs. However, larger controlled trials are needed before widespread use can be adopted.

REFERENCES

1. Andres P G, Friedman L S. Epidemiology and the natural course of inflammatory bowel disease. Gastroenterol Clin North Am. 1999;28:255–281. [PubMed] [Google Scholar]2. Halfvarson J, Bodin L, Tysk C, Lindberg E, Jarnerot G. Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology. 2003;124:1767–1773. [PubMed] [Google Scholar]4. Andersson R E, Olaison G, Tysk C, Ekbom A. Appendectomy and protection against ulcerative colitis. N Engl J Med. 2001;344:808–814. [PubMed] [Google Scholar]5. Moum B, Vatn M H, Ekbom A, et al. Incidence of inflammatory bowel disease in southeastern Norway: evaluation of methods after 1 year of registration. Southeastern Norway IBD Study Group of Gastroenterologists. Digestion. 1995;56:377–381. [PubMed] [Google Scholar]6. Langholz E, Munkholm P, Davidsen M, Binder V. Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology. 1994;107:3–11. [PubMed] [Google Scholar]7. Langholz E, Munkholm P, Davidsen M, Nielsen O H, Binder V. Changes in extent of ulcerative colitis: a study on the course and prognostic factors. Scand J Gastroenterol. 1996;31:260–266. [PubMed] [Google Scholar]9. Marshall J K, Irvine E J. Rectal aminosalicylate therapy for distal ulcerative colitis: a meta-analysis. Aliment Pharmacol Ther. 1995;9:293–300. [PubMed] [Google Scholar]10. D’Arienzo A, Panarese A, D’Armiento F P, et al. 5-aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. Am J Gastroenterol. 1990;85:1079–1082. [PubMed] [Google Scholar]11. Campieri M, De Franchis R, Bianchi Porro G, Ranzi T, Brunetti G, Barbara L. Mesalazine (5-aminosalicylic acid) suppositories in the treatment of ulcerative proctitis or distal proctosigmoiditis. A randomized controlled trial. Scand J Gastroenterol. 1990;25:663–668. [PubMed] [Google Scholar]12. Sutherland L R, Martin F, Greer S, et al. 5-aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology. 1987;92:1894–1898. [PubMed] [Google Scholar]13. d’Albasio G, Trallori G, Ghetti A, et al. Intermittent therapy with high-dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis. Dis Colon Rectum. 1990;33:394–397. [PubMed] [Google Scholar]14. Svartz N. Salazopyrine, a new sulfanilamide preparation. Acta Med Scand. 1942;110:557. [Google Scholar]15. Dick A P, Grayson M, Carpenter R G, Petrie A. Controlled trial of sulphasalazine in the treatment of ulcerative colitis. Gut. 1964;50:437–442. [PMC free article] [PubMed] [Google Scholar]16. Baron J H, Connell A, Lennard-Jones J E, Jones F A. Sulphasalzine and salicylazosulphadimidine in ulcerative colitis. Lancet. 1962;1:1094–1096. [PubMed] [Google Scholar]17. Misiewicz J J, Lennard-Jones J E, Connell A M, Baron J H, Avery Jones F. Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis. Lancet. 1965;1:185–188. [Google Scholar]18. Dissanayake A S, Truelove S C. A controlled therapeutic trial of long-term maintenance treatment of ulcerative colitis with sulphazalazine (Salazopyrin) Gut. 1973;14:923–926. [PMC free article] [PubMed] [Google Scholar]19. Taffet S L, Das K M. Sulfasalazine. Adverse effects and desensitization. Dig Dis Sci. 1983;28:833–842. [PubMed] [Google Scholar]20. O’Morain C, Smethurst P, Dore C J, Levi A J. Reversible male infertility due to sulphasalazine: studies in man and rat. Gut. 1984;25:1078–1084. [PMC free article] [PubMed] [Google Scholar]21. Das K M, Eastwood M A, McManus J P, Sircus W. The metabolism of salicylazosulphapyridine in ulcerative colitis. I. The relationship between metabolites and the response to treatment in inpatients. Gut. 1973;14:631–641. [PMC free article] [PubMed] [Google Scholar]22. Klotz U, Maier K, Fischer C, Heinkel K. Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn’s disease. N Engl J Med. 1980;303:1499–1502. [PubMed] [Google Scholar]23. Khan A K, Piris J, Truelove S C. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet. 1977;2:892–895. [PubMed] [Google Scholar]24. Hanauer S, Schwartz J, Robinson M, et al. Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial Pentasa Study Group. Am J Gastroenterol. 1993;88:1188–1197. [PubMed] [Google Scholar]25. Sninsky C A, Cort D H, Shanahan F, et al. Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. A multicenter study. Ann Intern Med. 1991;115:350–355. [PubMed] [Google Scholar]26. Schroeder K W, Tremaine W J, Ilstrup D M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–1629. [PubMed] [Google Scholar]27. Safdi M, DeMicco M, Sninsky C, et al. A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis. Am J Gastroenterol. 1997;92:1867–1871. [PubMed] [Google Scholar]28. Rao S S, Dundas S A, Holdsworth C D, Cann P A, Palmer K R, Corbett C L. Olsalazine or sulphasalazine in first attacks of ulcerative colitis? A double-blind study. Gut. 1989;30:675–679. [PMC free article] [PubMed] [Google Scholar]29. Willoughby C P, Cowan R E, Gould S R, Machell R J, Stewart J B. Double-blind comparison of olsalazine and sulphasalazine in active ulcerative colitis. Scand J Gastroenterol Suppl. 1988;148:40–44. [PubMed] [Google Scholar]30. Courtney M G, Nunes D P, Bergin C F, et al. Randomised comparison of olsalazine and mesalazine in prevention of relapses in ulcerative colitis. Lancet. 1992;339:1279–1281. [PubMed] [Google Scholar]31. Sandberg-Gertzen H, Jarnerot G, Kraaz W. Azodisal sodium in the treatment of ulcerative colitis. A study of tolerance and relapse-prevention properties. Gastroenterology. 1986;90:1024–1030. [PubMed] [Google Scholar]32. Meyers S, Sachar D B, Present D H, Janowitz H D. Olsalazine sodium in the treatment of ulcerative colitis among patients intolerant of sulfasalazine. A prospective, randomized, placebo-controlled, double-blind, dose-ranging clinical trial. Gastroenterology. 1987;93:1255–1262. [PubMed] [Google Scholar]33. Green J R, Lobo A J, Holdsworth C D, et al. Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis. The Abacus Investigator Group. Gastroenterology. 1998;114:15–22. [PubMed] [Google Scholar]34. Green J R, Mansfield J C, Gibson J A, Kerr G D, Thornton P C. A double-blind comparison of balsalazide, 6.75 g daily, and sulfasalazine, 3 g daily, in patients with newly diagnosed or relapsed active ulcerative colitis. Aliment Pharmacol Ther. 2002;16:61–68. [PubMed] [Google Scholar]35. Levine D S, Riff D S, Pruitt R, et al. A randomized, double blind, dose-response comparison of balsalazide (6.75 g), balsalazide (2.25 g), and mesalamine (2.4 g) in the treatment of active, mild-to-moderate ulcerative colitis. Am J Gastroenterol. 2002;97:1398–1407. [PubMed] [Google Scholar]36. Pruitt R, Hanson J, Safdi M, et al. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-to-moderate ulcerative colitis. Am J Gastroenterol. 2002;97:3078–3086. [PubMed] [Google Scholar]37. Bitton A, Peppercorn M A, Hanrahan J P, Upton M P. Mesalamine-induced lung toxicity. Am J Gastroenterol. 1996;91:1039–1040. [PubMed] [Google Scholar]38. Iaquinto G, Sorrentini I, Petillo F E, Berardesca G. Pleuropericarditis in a patient with ulcerative colitis in longstanding 5-aminosalicylic acid therapy. Ital J Gastroenterol. 1994;26:145–147. [PubMed] [Google Scholar]39. Deltenre P, Berson A, Marcellin P, Degott C, Biour M, Pessayre D. Mesalazine (5-aminosalicylic acid) induced chronic hepatitis. Gut. 1999;44:886–888. [PMC free article] [PubMed] [Google Scholar]40. Fernandez J, Sala M, Panes J, Feu F, Navarro S, Teres J. Acute pancreatitis after long-term 5-aminosalicylic acid therapy. Am J Gastroenterol. 1997;92:2302–2303. [PubMed] [Google Scholar]41. Brouillard M, Gheerbrant J D, Gheysens Y, et al. Chronic interstitial nephritis and mesalazine: 3 new cases? [in French] Gastroenterol Clin Biol. 1998;22:724–726. [PubMed] [Google Scholar]42. Hanauer S B, Verst-Brasch C, Regalli G. Renal safety of long-term mesalamine therapy in inflammatory bowel disease (IBD) Gastroenterology. 1997;112:A991. [Google Scholar]43. Marteau P, Nelet F, Le Lu M, Devaux C. Adverse events in patients treated with 5-aminosalicyclic acid: 1993-1994 pharmacovigilance report for Pentasa in France. Aliment Pharmacol Ther. 1996;10:949–956. [PubMed] [Google Scholar]43a. Sturgeon J B, Bhatia P, Hermens D, Miner P B., Jr Exacerbation of chronic ulcerative colitis with mesalamine. Gastroenterology. 1995;108:1889–1893. [PubMed] [Google Scholar]45. Ekbom A, Helmick C G, Zack M, Holmberg L, Adami H O. Survival and causes of death in patients with inflammatory bowel disease: a population-based study. Gastroenterology. 1992;103:954–960. [PubMed] [Google Scholar]46. Faubion W A, Jr, Loftus E V, Jr, Harmsen W S, Zinsmeister A R, Sandborn W J. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121:255–260. [PubMed] [Google Scholar]47. Munkholm P, Langholz E, Davidsen M, Binder V. Frequency of glucocorticoid resistance and dependency in Crohn’s disease. Gut. 1994;35:360–362. [PMC free article] [PubMed] [Google Scholar]48. Honda M, Orii F, Ayabe T, et al. Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis. Gastroenterology. 2000;118:859–866. [PubMed] [Google Scholar]49. Farrell R J, Murphy A, Long A, et al. High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy. Gastroenterology. 2000;118:279–288. [PubMed] [Google Scholar]50. Baron J H, Connell A M, Kanaghinis T G, Lennard-Jones J E, Jones A F. Out-patient treatment of ulcerative colitis. Comparison between three doses of oral prednisone. BMJ. 1962;5302:441–443. [PMC free article] [PubMed] [Google Scholar]51. Powell-Tuck J, Bown R L, Lennard-Jones J E. A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. Scand J Gastroenterol. 1978;13:833–837. [PubMed] [Google Scholar]52. Lennard-Jones J E, Misiewicz J J, Connell A M, Baron J H, Avery Jones F. Prednisone as maintenance treatment for ulcerative colitis in remission. Lancet. 1965;191:188–189. [PubMed] [Google Scholar]53. Watkinson G. Treatment of ulcerative colitis with topical hydrocortisone hemisuccinate sodium A controlled trial employing restricted sequential analysis. BMJ. 1958:1077–1082. [PMC free article] [PubMed] [Google Scholar]54. Lennard-Jones J E, Baron J H, Connell A M, et al. A double blind controlled trial of prednisolone-21-phosphate suppositories in the treatment of idiopathic proctitis. Gut. 1962;3:207–210. [PMC free article] [PubMed] [Google Scholar]55. Truelove S. Treatment of ulcerative colitis with local hydrocortisone hemisuccinate sodium. A report on a controlled therapeutic trial. BMJ. 1958:1072–1077. [PMC free article] [PubMed] [Google Scholar]56. Lindgren S, Lofberg R, Bergholm L, et al. Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis. Scand J Gastroenterol. 2002;37:705–710. [PubMed] [Google Scholar]57. Cohen R D, Woseth D M, Thisted R A, Hanauer S B. A meta-analysis and overview of the literature on treatment options for left-sided ulcerative colitis and ulcerative proctitis. Am J Gastroenterol. 2000;95:1263–1276. [PubMed] [Google Scholar]58. Farmer R G, Schumacher O P. Treatment of ulcerative colitis with hydrocortisone enemas. Comparison of absorption and clinical response with hydrocortisone alcohol and hydrocortisone acetate. Am J Gastroenterol. 1970;54:229–236. [PubMed] [Google Scholar]60. Truelove S C, Jewell D P. Intensive intravenous regimen for severe attacks of ulcerative colitis. Lancet. 1974;1:1067–1070. [PubMed] [Google Scholar]61. Rizzello F, Gionchetti P, Venturi A, Campieri M. Medical treatment of severe ulcerative colitis. Aliment Pharmacol Ther. 2003;17(suppl 2):7–10. [PubMed] [Google Scholar]62. Meyers S, Sachar D B, Goldberg J D, Janowitz H D. Corticotropin versus hydrocortisone in the intravenous treatment of ulcerative colitis. A prospective, randomized, double-blind clinical trial. Gastroenterology. 1983;85:351–357. [PubMed] [Google Scholar]63. Powell-Tuck J, Buckell N A, Lennard-Jones J E. A controlled comparison of corticotropin and hydrocortisone in the treatment of severe proctocolitis. Scand J Gastroenterol. 1977;12:971–975. [PubMed] [Google Scholar]64. Kaplan H P, Portnoy B, Binder H J, Amatruda T, Spiro H. A controlled evaluation of intravenous adrenocorticotropic hormone and hydrocortisone in the treatment of acute colitis. Gastroenterology. 1975;69:91–95. [PubMed] [Google Scholar]65. Talar-Williams C, Sneller M C. Complications of corticosteroid therapy. Eur Arch Otorhinolaryngol. 1994;251:131–136. [PubMed] [Google Scholar]66. Singleton J W, Law D H, Kelley M L, Jr, Mekhjian H S, Sturdevant R A. National Cooperative Crohn’s Disease Study: adverse reactions to study drugs. Gastroenterology. 1979;77:870–882. [PubMed] [Google Scholar]67. Kusunoki M, Moeslein G, Shoji Y, et al. Steroid complications in patients with ulcerative colitis. Dis Colon Rectum. 1992;35:1003–1009. [PubMed] [Google Scholar]68. Turunen U M, Farkkila M A, Hakala K, et al. Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study. Gastroenterology. 1998;115:1072–1078. [PubMed] [Google Scholar]69. Mantzaris G J, Archavlis E, Christoforidis P, et al. A prospective randomized controlled trial of oral ciprofloxacin in acute ulcerative colitis. Am J Gastroenterol. 1997;92:454–456. [PubMed] [Google Scholar]70. Mantzaris G J, Petraki K, Archavlis E, et al. A prospective randomized controlled trial of intravenous ciprofloxacin as an adjunct to corticosteroids in acute, severe ulcerative colitis. Scand J Gastroenterol. 2001;36:971–974. [PubMed] [Google Scholar]71. Burke D A, Axon A T, Clayden S A, Dixon M F, Johnston D, Lacey R W. The efficacy of tobramycin in the treatment of ulcerative colitis. Aliment Pharmacol Ther. 1990;4:123–129. [PubMed] [Google Scholar]72. Lobo A J, Burke D A, Sobala G M, Axon A T. Oral tobramycin in ulcerative colitis: effect on maintenance of remission. Aliment Pharmacol Ther. 1993;7:155–158. [PubMed] [Google Scholar]73. Mantzaris G J, Hatzis A, Kontogiannis P, Triadaphyllou G. Intravenous tobramycin and metronidazole as an adjunct to corticosteroids in acute, severe ulcerative colitis. Am J Gastroenterol. 1994;89:43–46. [PubMed] [Google Scholar]74. Dickinson R J, O’Connor H J, Pinder I, Hamilton I, Johnston D, Axon A T. Double blind controlled trial of oral vancomycin as adjunctive treatment in acute exacerbations of idiopathic colitis. Gut. 1985;26:1380–1384. [PMC free article] [PubMed] [Google Scholar]75. Chapman R W, Selby W S, Jewell D P. Controlled trial of intravenous metronidazole as an adjunct to corticosteroids in severe ulcerative colitis. Gut. 1986;27:1210–1212. [PMC free article] [PubMed] [Google Scholar]76. Gionchetti P, Rizzello F, Ferrieri A, et al. Rifaximin in patients with moderate or severe ulcerative colitis refractory to steroid-treatment: a double-blind, placebo-controlled trial. Dig Dis Sci. 1999;44:1220–1221. [PubMed] [Google Scholar]77. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003;124:1202–1209. [PubMed] [Google Scholar]78. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology. 2000;119:305–309. [PubMed] [Google Scholar]79. Rembacken B J, Snelling A M, Hawkey P M, Chalmers D M, Axon A T. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet. 1999;354:635–639. [PubMed] [Google Scholar]80. Kruis W, Schutz E, Fric P, Fixa B, Judmaier G, Stolte M. Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther. 1997;11:853–858. [PubMed] [Google Scholar]81. Fedorak R, Gionchetti P, Campieri M, Madsen K, Isaacs K. VSL3 probiotic mixture induces remission in patients with active ulcerative colitis. Gastroenterology. 2003;124:A-377. [PubMed] [Google Scholar]82. Beaugerie L, Massot N, Carbonnel F, Cattan S, Gendre J P, Cosnes J. Impact of cessation of smoking on the course of ulcerative colitis. Am J Gastroenterol. 2001;96:2113–2116. [PubMed] [Google Scholar]83. Green J T, Richardson C, Marshall R W, et al. Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis. Aliment Pharmacol Ther. 2000;14:1429–1434. [PubMed] [Google Scholar]84. Sandborn W J. Nicotine therapy for ulcerative colitis: a review of rationale, mechanisms, pharmacology, and clinical results. Am J Gastroenterol. 1999;94:1161–1171. [PubMed] [Google Scholar]85. Pullan R D, Rhodes J, Ganesh S, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994;330:811–815. [PubMed] [Google Scholar]86. Sandborn W J, Tremaine W J, Offord K P, et al. Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1997;126:364–371. [PubMed] [Google Scholar]87. Thomas G A, Rhodes J, Mani V, et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med. 1995;332:988–992. [PubMed] [Google Scholar]88. Guslandi M. Long-term effects of a single course of nicotine treatment in acute ulcerative colitis: remission maintenance in a 12-month follow-up study. Int J Colorectal Dis. 1999;14:261–262. [PubMed] [Google Scholar]89. Green J T, Thomas G A, Rhodes J, et al. Nicotine enemas for active ulcerative colitis—a pilot study. Aliment Pharmacol Ther. 1997;11:859–863. [PubMed] [Google Scholar]90. Sandborn W J, Tremaine W J, Leighton J A, et al. Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study. Aliment Pharmacol Ther. 1997;11:663–671. [PubMed] [Google Scholar]91. Bean R. The treatment of chronic ulcerative colitis with 6-mercaptopurine. Med J Aust. 1962;49:592–593. [PubMed] [Google Scholar]93. Kirk A P, Lennard-Jones J E. Controlled trial of azathioprine in chronic ulcerative colitis. Br Med J (Clin Res Ed) 1982;284:1291–1292. [PMC free article] [PubMed] [Google Scholar]94. Hawthorne A B, Logan R F, Hawkey C J, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ. 1992;305:20–22. [PMC free article] [PubMed] [Google Scholar]95. Ardizzone S, Molteni P, Imbesi V, Bollani S, Bianchi Porro G, Molteni F. Azathioprine in steroid-resistant and steroid-dependent ulcerative colitis. J Clin Gastroenterol. 1997;25:330–333. [PubMed] [Google Scholar]96. Lobo A J, Foster P N, Burke D A, Johnston D, Axon A T. The role of azathioprine in the management of ulcerative colitis. Dis Colon Rectum. 1990;33:374–377. [PubMed] [Google Scholar]97. Steinhart A H, Baker J P, Brzezinski A, Prokipchuk E J. Azathioprine therapy in chronic ulcerative colitis. J Clin Gastroenterol. 1990;12:271–275. [PubMed] [Google Scholar]98. Korelitz B I, Adler D J, Mendelsohn R A, Sacknoff A L. Long-term experience with 6-mercaptopurine in the treatment of Crohn’s disease. Am J Gastroenterol. 1993;88:1198–1205. [PubMed] [Google Scholar]99. George J, Present D H, Pou R, Bodian C, Rubin P H. The long-term outcome of ulcerative colitis treated with 6-mercaptopurine. Am J Gastroenterol. 1996;91:1711–1714. [PubMed] [Google Scholar]100. Pearson D C, May G R, Fick G H, Sutherland L R. Azathioprine and 6-mercaptopurine in Crohn’s disease. A meta-analysis. Ann Intern Med. 1995;123:132–142. [PubMed] [Google Scholar]101. Mahadevan U, Tremaine W J, Johnson T, et al. Intravenous azathioprine in severe ulcerative colitis: a pilot study. Am J Gastroenterol. 2000;95:3463–3468. [PubMed] [Google Scholar]102. Black A J, McLeod H L, Capell H A, et al. Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Ann Intern Med. 1998;129:716–718. [PubMed] [Google Scholar]103. Colombel J F, Ferrari N, Debuysere H, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn’s disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000;118:1025–1030. [PubMed] [Google Scholar]104. Snow J L, Gibson L E. A pharmacogenetic basis for the safe and effective use of azathioprine and other thiopurine drugs in dermatologic patients. J Am Acad Dermatol. 1995;32:114–116. [PubMed] [Google Scholar]105. Dubinsky M C, Lamothe S, Yang H Y, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology. 2000;118:705–713. [PubMed] [Google Scholar]106. Cuffari C, Theoret Y, Latour S, Seidman G. 6-mercaptopurine metabolism in Crohn’s disease: correlation with efficacy and toxicity. Gut. 1996;39:401–406. [PMC free article] [PubMed] [Google Scholar]107. Lowry P W, Franklin C L, Weaver A L, et al. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut. 2001;49:665–670. [PMC free article] [PubMed] [Google Scholar]108. Belaiche J, Desager J P, Horsmans Y, Louis E. Therapeutic drug monitoring of azathioprine and 6-mercaptopurine metabolites in Crohn’s disease. Scand J Gastroenterol. 2001;36:71–76. [PubMed] [Google Scholar]109. Sandborn W J, Tremaine W J, Wolf D C, et al. Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn’s disease North American Azathioprine Study Group. Gastroenterology. 1999;117:527–535. [PubMed] [Google Scholar]110. Present D H, Meltzer S J, Krumholz M P, Wolke A, Korelitz B I. 6-mercaptopurine in the management of inflammatory bowel disease: short- and long-term toxicity. Ann Intern Med. 1989;111:641–649. [PubMed] [Google Scholar]111. Connell W R, Kamm M A, Dickson M, Balkwill A M, Ritchie J K, Lennard-Jones J E. Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet. 1994;343:1249–1252. [PubMed] [Google Scholar]112. Fraser A G, Orchard T R, Robinson E M, Jewell D P. Long-term risk of malignancy after treatment of inflammatory bowel disease with azathioprine. Aliment Pharmacol Ther. 2002;16:1225–1232. [PubMed] [Google Scholar]113. Dayharsh G A, Loftus E V, Jr, Sandborn W J, et al. Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Gastroenterology. 2002;122:72–77. [PubMed] [Google Scholar]114. Feagan B G, Fedorak R N, Irvine E J, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn’s disease. North American Crohn’s Study Group Investigators. N Engl J Med. 2000;342:1627–1632. [PubMed] [Google Scholar]115. Feagan B G, Rochon J, Fedorak R N, et al. Methotrexate for the treatment of Crohn’s disease. North American Crohn’s Study Group Investigators. N Engl J Med. 1995;332:292–297. [PubMed] [Google Scholar]116. Egan L J, Tremaine W J, Mays D C, Lipsky J J, Sandborn W J. Clinical outcome and pharmacokinetics after addition of low-dose cyclosporine to methotrexate: a case study of five patients with treatment-resistant inflammatory bowel disease. Inflamm Bowel Dis. 2000;6:286–289. [PubMed] [Google Scholar]117. Baron T H, Truss C D, Elson C O. Low-dose oral methotrexate in refractory inflammatory bowel disease. Dig Dis Sci. 1993;38:1851–1856. [PubMed] [Google Scholar]118. Kozarek R A, Patterson D J, Gelfand M D, Botoman V A, Ball T J, Wilske K R. Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med. 1989;110:353–356. [PubMed] [Google Scholar]119. Oren R, Arber N, Odes S, et al. Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial. Gastroenterology. 1996;110:1416–1421. [PubMed] [Google Scholar]120. Paoluzi O A, Pica R, Marcheggiano A, et al. Azathioprine or methotrexate in the treatment of patients with steroid-dependent or steroid-resistant ulcerative colitis: results of an open-label study on efficacy and tolerability in inducing and maintaining remission. Aliment Pharmacol Ther. 2002;16:1751–1759. [PubMed] [Google Scholar]121. Lichtiger S, Present D H, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994;330:1841–1845. [PubMed] [Google Scholar]122. Svanoni F, Bonassi U, Bagnolo F, et al. Effectiveness of cyclosporoine A (CsA) in the treatment of active refractory ulcerative colitis. Gastroenterology. 1998;114:A1096. [Google Scholar]123. D’Haens G, Lemmens L, Geboes K, et al. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology. 2001;120:1323–1329. [PubMed] [Google Scholar]124. Van Assche G, D’Haens G, Noman M, et al. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology. 2003;125:1025–1031. [PubMed] [Google Scholar]125. Kornbluth A, Present D H, Lichtiger S, Hanauer S. Cyclosporin for severe ulcerative colitis: a user’s guide. Am J Gastroenterol. 1997;92:1424–1428. [PubMed] [Google Scholar]126. Cohen R D, Stein R, Hanauer S B. Intravenous cyclosporin in ulcerative colitis: a five-year experience. Am J Gastroenterol. 1999;94:1587–1592. [PubMed] [Google Scholar]127. Domenech E, Garcia-Planella E, Bernal I, et al. Azathioprine without oral ciclosporin in the long-term maintenance of remission induced by intravenous ciclosporin in severe, steroid-refractory ulcerative colitis. Aliment Pharmacol Ther. 2002;16:2061–2065. [PubMed] [Google Scholar]128. Sandborn W J. Cyclosporine in ulcerative colitis: state of the art. Acta Gastroenterol Belg. 2001;64:201–204. [PubMed] [Google Scholar]129. Latteri M, Angeloni T G, Silveri N G, Manna R, Gasbarrini G, Navarra P. Pharmacokinetics of cyclosporin microemulsion in patients with inflammatory bowel disease. Clin Pharmacokinet. 2001;40:473–483. [PubMed] [Google Scholar]130. Actis G C, Aimo G, Priolo G, Moscato D, Rizzetto M, Pagni R. Efficacy and efficiency of oral microemulsion cyclosporin versus intravenous and soft gelatin capsule cyclosporin in the treatment of severe steroid-refractory ulcerative colitis: an open-label retrospective trial. Inflamm Bowel Dis. 1998;4:276–279. [PubMed] [Google Scholar]131. Navazo L, Salata H, Morales S, et al. Oral microemulsion cyclosporine in the treatment of steroid-refractory attacks of ulcerative and indeterminate colitis. Scand J Gastroenterol. 2001;36:610–614. [PubMed] [Google Scholar]132. Sood A, Midha V, Sood N. Oral cyclosporine in patients with active severe ulcerative colitis not responding to steroids. Indian J Gastroenterol. 2002;21:155–156. [PubMed] [Google Scholar]133. Sternthal M GJ, Kornbluth A. Toxicity associated with the use of cyclosporin in patients with inflammatory bowel disease. Gastroenterology. 1996;110:A1019. [Google Scholar]134. Bousvaros A, Kirschner B S, Werlin S L, et al. Oral tacrolimus treatment of severe colitis in children. J Pediatr. 2000;137:794–799. [PubMed] [Google Scholar]135. Baumgart D C, Wiedenmann B, Dignass A U. Rescue therapy with tacrolimus is effective in patients with severe and refractory inflammatory bowel disease. Aliment Pharmacol Ther. 2003;17:1273–1281. [PubMed] [Google Scholar]136. Matsuhashi N, Nakajima A, Watanabe K, et al. Tacrolimus in corticosteroid-resistant ulcerative colitis. J Gastroenterol. 2000;35:635–640. [PubMed] [Google Scholar]137. Pascu M, Muller A R, Wiedenmann B, Dignass A U. Rescue therapy with tacrolimus in a patient with toxic megacolon. Int J Colorectal Dis. 2003;18:271–275. [PubMed] [Google Scholar]138. Fellermann K, Tanko Z, Herrlinger K R, et al. Response of refractory colitis to intravenous or oral tacrolimus (FK506) Inflamm Bowel Dis. 2002;8:317–324. [PubMed] [Google Scholar]139. Hanauer S LG, Colombel J F, et al. Maintenance infliximab (Remicade) is safe, effective and steroid-sparing in Crohn’s disease: preliminary results of the Accent I trial. Gastroenterology. 2001;120:A-21. [Google Scholar]140. Sands B E, Tremaine W J, Sandborn W J, et al. Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Inflamm Bowel Dis. 2001;7:83–88. [PubMed] [Google Scholar]141. Chey W Y, Hussain A, Ryan C, Potter G D, Shah A. Infliximab for refractory ulcerative colitis. Am J Gastroenterol. 2001;96:2373–2381. [PubMed] [Google Scholar]142. Kaser A, Mairinger T, Vogel W, Tilg H. Infliximab in severe steroid-refractory ulcerative colitis: a pilot study. Wien Klin Wochenschr. 2001;113:930–933. [PubMed] [Google Scholar]143. Probert C, Hearing S D, Shreiber S, Kuhbacher T, Ghosh S, Forbes A. Infliximab in steroid-resistant ulcerative colitis: a randomized controlled trial. Gastroenterology. 2002;122:A-99. [Google Scholar]144. Ochsenkuhn T, Sackmann M, Goeke B. Infliximab for acute severe uclerative colitis: a randomized pilot study in nonsteroid refractory patients. Gastroenterology. 2003;124:A62. [Google Scholar]145. Su C, Salzberg B A, Lewis J D, et al. Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol. 2002;97:2577–2584. [PubMed] [Google Scholar]146. Dhillon A P, Anthony A, Sim R, et al. Mucosal capillary thrombi in rectal biopsies. Histopathology. 1992;21:127–133. [PubMed] [Google Scholar]147. Gaffney P R, Doyle C T, Gaffney A, Hogan J, Hayes D P, Annis P. Paradoxical response to heparin in 10 patients with ulcerative colitis. Am J Gastroenterol. 1995;90:220–223. [PubMed] [Google Scholar]148. Evans R C, Wong V S, Morris A I, Rhodes J M. Treatment of corticosteroid-resistant ulcerative colitis with heparin—a report of 16 cases. Aliment Pharmacol Ther. 1997;11:1037–1040. [PubMed] [Google Scholar]149. Panes J, Esteve M, Cabre E, et al. Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis. Gastroenterology. 2000;119:903–908. [PubMed] [Google Scholar]150. Ang Y S, Mahmud N, White B, et al. Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease. Aliment Pharmacol Ther. 2000;14:1015–1022. [PubMed] [Google Scholar]151. Bloom S, Kiilerich S, Lassen M R, O’Morain C, Forbes A, Orm S. Randomized trial of tinzaparin, a low molecular weight heparin (LMWH), versus placebo in the treatment of mild to moderately active ulcerative colitis. Gastroenterology. 2003;124:A67. [Google Scholar]152. Korzenik J, Miner P, Stanton D, et al. Multicenter, randomized, double-blind, placebo-controlled trial of Deligoparin (ultra low molecular weight heparin) for active ulcerative colitis. Gastroenterology. 2003;124:A67. [Google Scholar]153. Tuvlin J A, Kane S V. Novel therapies in the treatment of ulcerative colitis. Expert Opin Investig Drugs. 2003;12:483–490. [PubMed] [Google Scholar]154. Creed T, Hearing S, Probert C, Norman M, Dayan C. Basiliximab (IL-2 receptor antagonist) as a steroid sensitizing. Gastroenterology. 2003;124:A7. [Google Scholar]155. Plevy S, Salzberg B A, Regueiro M, et al. A humanized anti-CD3 monoclonal antibody, visilizumab, for treatment of severe steroid-refractory ulcerative colitis: preliminary results of a phase I study. Gastroenterology. 2003;124:A7. [Google Scholar]156. Feagan B, Greenberg G, Wild G, et al. A randomized controlled trial of a humanized α4β7 antibody in ulcerative colitis. Gastroenterology. 2003;124:Abstract [Google Scholar]157. Musch E, Raedler A, Andus T, et al. A phase II placebo-controlled, randomized, multicenter study to evaluate efficacy and safety of interferon beta-1a in patients with ulcerative colitis. Gastroenterology. 2002;122:A431. [Google Scholar]158. Sawada K, Ohnishi K, Fukui S, et al. Leukocytapheresis therapy, performed with leukocyte removal filter, for inflammatory bowel disease. J Gastroenterol. 1995;30:322–329. [PubMed] [Google Scholar]159. Sawada K, Muto T, Shimoyama T, et al. Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis column. Curr Pharm Des. 2003;9:307–321. [PubMed] [Google Scholar]160. Sawada K, Kusugam K, Suzuki Y. Multicenter randomized double blind controlled trial for ulcerative colitis therapy with leukocytapheresis. Gastroenterology. 2003;124:A67. [Google Scholar]161. Cottone M, Pietrosi G, Martorana G, et al. Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn’s colitis. Am J Gastroenterol. 2001;96:773–775. [PubMed] [Google Scholar]162. Mahadevan U, Loftus E V, Jr, Tremaine W J, et al. Azathioprine or 6-mercaptopurine before colectomy for ulcerative colitis is not associated with increased postoperative complications. Inflamm Bowel Dis. 2002;8:311–316. [PubMed] [Google Scholar]163. Yang Y X, Lichtenstein G R. Corticosteroids in Crohn’s disease. Am J Gastroenterol. 2002;97:803–823. [PubMed] [Google Scholar]

Medical Treatment of Ulcerative Colitis

Clin Colon Rectal Surg. 2004 Feb; 17(1): 7–19.

Ulcerative Colitis

Editor in Chief David E. Beck M.D.

Guest Editor Bruce G. Wolff M.D.

Uma Mahadevan

¹Division of Gastroenterology, University of California, San Francisco, San Francisco, California

Address for correspondence and reprint requests: Uma Mahadevan M.D. UCSF/Mount Zion IBD Center, 2330 Post Street #610, San Francisco, CA 94115, ude. fscu.asti@hamamuThis article has been cited by other articles in PMC.

Abstract

Keywords: Ulcerative colitis, medical therapy, cyclosporine

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that affects up to 12 per 100,000 people in Western countries. ¹ The incidence may be increasing in developing nations but is more frequent in Caucasians and people of Jewish descent. Although there is an increase in families, the genetic trend is not as strong as in Crohn’s disease.² The peak age of incidence is in persons between 15 and 30 years old.¹ Protective factors against the development of UC include cigarette smoking³ and appendectomy.⁴

Table 1

Truelove and Witts’ Criteria for Evaluating the Severity of Ulcerative Colitis⁸

Variable	Mild Disease	Severe Disease	Fulminant Disease
Moderate disease includes features of both mild and severe disease.
Stools (number/day)	< 4	> 6	> 10
Blood in stool	Intermittent	Frequent	Continuous
Temperature (°C)	Normal	> 37.5°	> 37.5°
Pulse (beats/minute)	Normal	> 90	> 90
Hemoglobin	Normal	< 75% of normal value	Transfusion required
Erythrocyte sedimentation rate (mm/hr)	≤30	>30	>30
Colonic Features on x-ray		Air, edematous wall, thumbprinting	Dilatation
Clinical signs		Abdominal tenderness	Abdominal distention and tenderness

AMINOSALICYLATES

Table 2

Generic Name	Proprietary Names	5-ASA Delivery Mechanism	Sites of Delivery	Daily Dose, Range
Mesalamine	Rowasa Salofalk	Enema suspension	Left colon and rectum	1-4 g
Mesalamine	Canasa	Suppository	Rectum	0. 5-1.5 g
Mesalamine	Asacol	Eudragit-S coated tablets (release at pH > 7	Terminal ileum, colon	1.6-4.8 g
Mesalamine	Salofalk, Mesasal, Claversal	Mesalamine in sodium/glycerine buffer coated with Eudragit-L (release at pH > 6)	Distal jejunum, proximal ileum	1.5-4 g
Mesalamine	Pentasa	Ethylcellulose coated microgranules (time and pH dependant release)	Entire small bowel, colon	2-4 g
Sulfasalazine	Azulfidine	5-ASA azo-bound to sulfapyridine	Colon	1-4 g
Olsalazine	Dipentum	5-ASA dimer linked by azo-bond	Colon	1-3 g
Balsalazide	Colazaal	5-ASA azo-bound to inert carrier	Colon	2-6. 75 g

CORTICOSTEROIDS

Table 3

Adverse Effects Associated with Systemic Corticosteroid Therapy

Adapted from Yang and Lichtenstein¹⁶³ with permission.
Cutaneous	Atrophy, striae, vascular effects, purpura, alopecia, pigmentation, acne, easy bruising
Cardiovascular	Hypertension, edema, atherosclerosis
Gastrointestinal	Nausea, vomiting, intestinal perforation, pancreatitis, esophagitis
Gynecological/obstetrical	Amenorrhea, gestational diabetes, adrenal suppression of infant
Neuropsychiatric	Psychosis, peripheral neuropathy, pseudotumor cerebri, depression/mood disorders, impaired cognitive function, seizures, insomnia, irritability
Metabolic	Hyperglycemia, hyperlipidemia, obesity, hypocalcemia, hypokalemia, buffalo hump
Musculoskeletal	Osteoporosis/osteopenia, aseptic necrosis, growth retardation, muscle atrophy, myopathy
Hematological	Leukocytosis, lymphopenia, eosinophenia, infection, immunosuppression, impaired fibroplasia, decreased mitotic rate
Ophthalmalogical	Cataracts, glaucoma, infection, exophthalmoses, hemorrhage
Endocrine	Hypothalamic-pituitary-adrenal axis suppression, hirsutism, moon facies
Pediatric	Growth retardation

ANTIBIOTICS

PROBIOTICS

NICOTINE

IMMUNOSUPPRESSANTS

Azathioprine/6-Mercaptopurine

Effective doses of AZA are 2.0 to 3.0 mg/kg/day and of 6-MP are 1.0 to 1.5 mg/kg/day and may take up to 17 weeks to take complete effect.¹⁰⁰ Though some physicians begin at low doses and titrate upwards, our practice is to begin at full dose with careful monitoring of the compete blood count. There is no role for intravenous loading of AZA in severe UC.¹⁰¹ Thiopurine S-methyltransferase (TPMT) phenotype or genotype can aid in determining safety and optimal dosage of AZA/6-MP. Low to intermediate levels of TPMT are associated with leukopenia in rheumatoid arthritis¹⁰² and with Crohn’s disease.¹⁰³ Based on these observations, it is recommended that patients with normal TPMT activity receive standard doses of AZA or 6-MP. Patients with intermediate activity should receive 50% of the standard dose and those who have no TPMT activity should not be treated with the drug.¹⁰⁴ The use of metabolite levels (6-TGN [thioguanine nucleotides] and 6-MMP [6-methylmercaptopurine]) to gauge optimal dosing of AZA/6-MP is controversial. Though two studies supported its use,¹⁰⁵^,¹⁰⁶ three others failed to demonstrate a consistent relationship between clinical efficacy and erythrocyte 6-TGN concentrations.¹⁰⁷^,¹⁰⁸^,¹⁰⁹

Methotrexate

Methotrexate (MTX) has demonstrated benefit for the induction and maintenance of remission in Crohn’s disease¹¹⁴^,¹¹⁵; however, its benefit in UC is not well established. Uncontrolled data have shown response in small series of patients with UC.¹¹⁶^,¹¹⁷^,¹¹⁸ The only controlled trial in UC was by Oren and associates,¹¹⁹ which compared oral MTX 12.5 mg/week with placebo in 67 patients with chronic active UC. No difference was found between the MTX and placebo group in remission and relapse rates. A recent study reported on patients with steroid-dependent or steroid-resistant active UC.¹²⁰ Ten patients were intolerant or resistant to AZA and were switched to MTX 12.5 mg IM/ week. Six of 10 (60%) achieved clinical remission, 40% achieved clinical response, and 20% subsequently relapsed. Available data suggest that AZA/6-MP should be the first choice for maintenance and steroid sparing in UC, but MTX can be tried in those who are intolerant or resistant to AZA/6-MP. Our usual starting dose is 25 mg SQ/week, though once remission is achieved, 15 mg SQ/week can be used for maintenance.

Cyclosporine

An oral, microemulsion form of CSA (Neoral) has been developed which has increased oral bioavailability and improved absorption from the small bowel.¹²⁸ The pharmokinetic parameters of CSA microemulsion in patients with IBD appear to be similar to those of healthy volunteers.¹²⁹ Three small series have described efficacy of oral microemulsion CSA in severe UC,¹³⁰^,¹³¹^,¹³² though larger controlled trials are needed.

Table 4

Potential Drug Interactions of Cyclosporine and Tacrolimus

Adapted from Kornbluth, et al¹²⁵ with permission.
Inhibition of cytochrome P450	Calcium channel blockers
Increased CSA levels	Bromocriptine
	Metoclopramide
	Imidazoles
	Macrolide antibiotics
	Methylprednisolone
	Protease inhibitors
	Grapefruit juice
Induction of cytochrome P450	Rifampin
Decrease cyclosporine levels	Phenobarbital
	Phenytoin
	Carbamazepine
	Reverse transcriptase inhibitors
	St. John’s wort

Tacrolimus

Tacrolimus is a calcineurin inhibitor like CSA. Controlled trials in severe UC have not been conducted to date, but multiple case series suggest efficacy. The first study was by Bousvaros et al¹³⁴ and described a 69% clinical response rate in 13 patients with steroid-refractory UC. However, at 1 year, only 38% of patients avoided colectomy. Three case series note salvage therapy with tacrolimus in steroid-resistant or steroid-dependent UC¹³⁵^,¹³⁶ as well as in a patient with toxic megacolon.¹³⁷ One trial compared intravenous to oral tacrolimus in 38 patients with refractory UC.¹³⁸ Oral and IV dosing was equivalent. Eighteen of 38 patients (47%) improved within 14 days. Thirty-five of 38 patients (92%) avoided colectomy at 28 days, but at 2 years, the colectomy rate was 50%.

Infliximab

Infliximab is a chimeric monoclonal antibody to tumor necrosis factor-α (TNF), a key inflammatory cytokine. While infliximab has made a dramatic impact on the treatment of Crohn’s disease,¹³⁹ its role in UC is not clear. Sands and associates reported 11 patients in a controlled trial of infliximab in severe, steroid-refractory UC.¹⁴⁰ Four of eight patients (50%) who received infliximab had a clinical response, although one subsequently required colectomy. Two small case series report response in severe UC,¹⁴¹^,¹⁴² but a larger randomized controlled trial was negative.¹⁴³ In this latter trial, patients with severe, steroid-refractory UC were randomized to infliximab 5 mg/kg or placebo at weeks 0 and 2. After 6 weeks, remission was achieved in 8/22 infliximab patients and 6/20 placebo (not significant). A controlled trial of infliximab in nonsteroid-refractory patients¹⁴⁴ randomized patients to either infliximab 5 mg/kg at 0, 2, and 6 weeks or intravenous prednisolone at 1.5 mg/kg daily for 2 weeks followed by a taper. Five of 6 patients receiving infliximab and 6/7 patients receiving steroids had a response. The two agents appear to be equivalent in this small study.

EXPERIMENTAL AGENTS

Heparin

Thrombotic events associated with UC and histologic evidence of microvascular thrombosis on colon biopsy suggested that anticoagulation may be an effective therapy for UC.¹⁴⁶ Uncontrolled studies did find unfractionated heparin to be of benefit,¹⁴⁷^,¹⁴⁸ but small controlled studies comparing unfractionated heparin to corticosteroids had mixed results.¹⁴⁹^,¹⁵⁰ Larger, placebo-controlled trials of low-molecular-weight heparin in studies of 100 patients and 138 patients, respectively, found no significant benefit over placebo.¹⁵¹^,¹⁵² Heparin is not effective for the treatment of UC but does appear to be safe with no increased risk of gastrointestinal bleeding, should the need for anticoagulation for other reasons arise in these patients.

BIOLOGICS: CYTOKINES AND ANTIBODIES

Investigational agents with preliminary reports of efficacy include vepolimomab (monoclonal antibody [mAb] to vascular adhesion protein-1)¹⁵³; interleukin-2 (IL-2) antagonists such as basiliximab, which may increase response to steroids in steroid-resistant UC¹⁵⁴; anti-CD3 antibodies, such as visilizumab, which has shown preliminary efficacy in steroid-resistant UC¹⁵⁵; antibody to α4β7, such as MLN-02, which mediates recruitment of lymphocytes to the gut and demonstrated safety and efficacy in a controlled trial in patients with active UC¹⁵⁶; and interferon-β, which showed some clinical response in patients with steroid-refractory UC in a phase II, placebo-controlled trial.¹⁵⁷ Multiple other agents exist, but for all new agents, while preliminary results are exciting, randomized controlled trials are needed before widespread use is initiated.

LEUKOCYTAPHERESIS

ALGORITHM FOR THE TREATMENT OF ULCERATIVE COLITIS

Figure outlines the algorithm for the treatment of a flare of UC. When a patient presents with a flare, the diagnosis should be confirmed and the severity of the disease established. Colonoscopy with biopsy to confirm the diagnosis of UC and establish the extent of the disease should be performed in all new and established cases. A small bowel follow-through should be performed once at some point in the disease course to rule out the diagnosis of Crohn’s disease. Stool studies should be sent in all acute flares to rule out superinfection with Clostridium difficile, bacteria, or ova and parasites. In a patient with severe UC, an unprepped flexible sigmoidoscopy rather than full colonoscopy should be performed with biopsies of the rectum for histology and viral culture. This will confirm the severity of the disease and will also rule out cytomegalovirus (CMV). One study reported that 36% of patients with steroid-refractory colitis had CMV on rectal specimens.¹⁶¹ The majority of these patients responded to antiviral therapy with foscarnet or ganciclovir. The severity of the disease can be determined by the Truelove and Witts score (Table ).

An algorithm for the medial management of mild, moderate, and severe ulcerative colitis. Progression along arrows is indicated if prior therapies fail.

REFERENCES

Steroids | Crohn’s & Colitis UK

There are many different types of steroids (also known as corticosteroids) which can be taken in different ways. The type of steroids you’ll be given will depend on how severe your Crohn’s Disease, Ulcerative Colitis or Microscopic Colitis is, and where it is in your gut.

Oral steroids are taken by mouth and swallowed. They include:

prednisolone (brand names Deltacortril®, Deltastab® and Dilacort®)
prednisone
hydrocortisone (Plenadren®)
methylprednisolone (Medrone®)
beclometasone dipropionate (Clipper®)
budesonide (Entocort® and Budenofalk®)
budesonide-MMX (Multi-Matrix system) (Cortiment®)

Intravenous steroids are given directly into a vein (in hospital). They include:

hydrocortisone
methylprednisolone

Topical steroids are given directly at the site of inflammation. Rectal steroids (suppositories, foam or liquid enemas) are a type of topical steroid. Steroids that come as a mouthwash (for treating mouth ulcers) are another type of topical steroid. Topical steroids include:

hydrocortisone (Colifoam®)
prednisolone (Predfoam®)
budesonide (Budenofalk®)

When you’re in a flare-up and feel unwell, steroids can help to quickly reduce the inflammation in your gut to help you feel better (known as remission). But they have a high risk of side effects and can’t control your Crohn’s or Colitis long-term.

4 in every 5 people with Crohn’s or Colitis will be treated with steroids at some point. Sometimes you might take steroids while also taking other medicines (in combination with other medicines).

If you have Crohn’s Disease
Intravenous, oral or topical steroids may be used to treat adults and children with Crohn’s when you’re first diagnosed, or if you’re having a flare-up.

If you have Ulcerative Colitis
Oral or rectal steroids may be used to treat adults and children with Ulcerative Colitis if you’re having a flare-up but you don’t need to stay in hospital. You may also be given steroids if you’re having a flare up but aminosalicylates (5-ASAs) aren’t right for you.

Acute Severe Ulcerative Colitis (ASUC)
Acute Severe Ulcerative Colitis (ASUC) is a serious condition. You’ll first be treated with intravenous steroids in hospital. Intravenous steroids work quickly, so you should start to feel better within a few days. If you’re not any better after three days, your IBD team will discuss other possible treatment options with you.

If you have Microscopic Colitis
Oral budesonide is used as a first treatment in adults with Microscopic Colitis (Collagenous Colitis and Lymphocytic Colitis).

Once your IBD is under control (with steroids) life quickly returns to normal. You realise how much the steroids can help you to get your life back.
Barry, age 41
Living with Crohn’s Colitis

Steroids are hormones (chemicals) that are produced naturally in your body. Steroids used to treat Crohn’s and Colitis are man-made versions of these hormones, but they are taken in higher doses than your body makes naturally. In these high doses, steroids reduce inflammation by decreasing the activity of the immune system.

The steroids used to treat Crohn’s and Colitis are not the same as the anabolic steroids used by athletes to improve their performance.

Steroids are effective as a short-term treatment during a flare-up to bring you into remission.

Taking steroids for long periods of time or repeatedly will not help to control your Crohn’s or Ulcerative Colitis and can cause unwanted side effects. Once in remission, your steroid treatment will gradually reduce and stop and you’ll be offered a different treatment to keep your symptoms under control. If you have Crohn’s or Ulcerative Colitis, you may be offered 5-ASAs, an immunosuppressant, or a biologic medicine. See our other drug treatment sheets for more information.

You shouldn’t have more than two courses of steroids in a year. If your GP has prescribed you a course of steroids, make sure you let your IBD team know at your next appointment.

Some research suggests that if you have Collagenous Colitis, ongoing treatment with a low dose of oral budesonide may be helpful in keeping you in remission.

Conventional oral steroids (such as prednisolone or prednisone) cause a range of side effects because they can affect the whole body. Budesonide is different because it works directly in the small bowel (small intestine) and colon (part of the large bowel). This means there is very little budesonide in the bloodstream and so the risk of side effects is lower than with other steroids. Budesonide-MMX® is a new type of capsule that releases budesonide throughout the entire colon and is usually used to treat Ulcerative Colitis.

How effective is budesonide?
Studies show that budesonide causes fewer side effects than conventional oral steroids, but it’s generally not as good at treating flare-ups.

Everyone responds differently when taking a new medicine.

If you’re taking oral steroids, you may start to feel better within a week, but it could take up to a month after starting treatment. You’ll usually feel better after a week or two if you’re taking rectal steroids. If you’re taking intravenous steroids, you may feel better after few days, but it can take up to 10 days after starting treatment.

You may experience side effects much sooner, see the section below on Side effects.
Steroids don’t work for everyone. Around 1 in 5 people don’t respond to steroid treatment – this known as being steroid refractory. Speak to your IBD team if your condition isn’t improving.

How you take steroids will depend on the severity and location of your Crohn’s or Colitis.

Oral steroids
Steroids are most commonly taken by mouth (orally). These could be tablets, capsules or granules, or they may be available as a dissolvable or liquid version.

Take your oral steroids in the morning to help reduce side effects. If you’ve been prescribed budesonide capsules or granules (or any other delayed-release or enteric coated steroids), you should swallow these whole with a glass of water around half an hour before food in the morning. Do not chew budesonide capsules or granules because this may stop them working.

Intravenous steroids
For severe flare-ups, steroids are injected into a vein (intravenously) to give the quickest response. This only takes place in hospital. You may then be switched to oral steroids.

Topical/rectal steroids
For Crohn’s or Colitis affecting the lower part of the colon and rectum, steroids can be applied directly to the affected area by enemas or suppositories (rectally). Enemas use a specially designed applicator (containing the drug as a liquid or foam) that is inserted into the anus and reaches into the colon. Suppositories are small ‘bullet-like’ capsules of drug inserted into the rectum through the anus. There are fewer side effects as these steroids directly target the inflamed area.

Taking rectal steroids may seem daunting, but there are a few things you can try to make it easier:

Take your steroids at night – you’re likely to have more time and this will help you stay relaxed.
Read the instructions that come with your steroids – they’ll explain the best way to take the steroids and often have pictures to help.
Go to the toilet just before taking your steroids.
Try lying on your left side (on a towel) while inserting the applicator into your anus. Extra lubricant on the applicator might help. Stay lying on your left side or on your tummy for 20-30 minutes after to give the steroids time to work. After this time you can go to the toilet to release the remaining liquid or foam.

Don’t worry if you don‘t quite get it right the first few times, or if you spill some. It’ll soon become another part of your routine.

Your dosage will depend on the type of steroid prescribed, your condition and your weight. Your IBD team will advise you on this.

For example:

Mild to moderate flare-up of Crohn’s or Colitis – you may start on oral prednisolone 40 mg (eight tablets a day), taken as a single dose in the morning. But there can be differences – your IBD team will give you the dose that’s right for you.

Severe flare-up of Crohn’s or Colitis – if you’re admitted to hospital, you may be given intravenous steroids such as hydrocortisone 100 mg four times daily or methylprednisolone 60 mg every 24 hours.

Microscopic Colitis – you may be given 9mg budesonide daily.

Talk to your IBD team before making any changes to your dosage or how you take it.

Steroids are usually only used for a short time to help you get into remission or while longer-term treatments, such as azathioprine, start to work.

You must complete your full course of steroids – you’ll usually be prescribed steroids for 8 weeks with the dose reducing over this time. You must NOT suddenly stop taking steroids, even if you feel better. See the section on Side effects to find out why.

It took me a few goes to reduce my steroid dose as the symptoms kept coming back and I had to return to the starting dose. But each time I was able to get telephone advice from my IBD nurse.
Lucy, age 45
Living with Crohn’s Disease

Carry a steroid card. Your pharmacist or doctor may give you a blue steroid card with details of your steroid treatment, including the dose and how long you’ll be taking steroids. Always carry this and show it to any healthcare professional treating you, even if you’re being treated for something not related to your Crohn’s or Colitis, such as by your dentist. You could also consider wearing a wear an emergency bracelet, like the ones made by MedicAlert.

Speak to your doctor if you think you have an infection. Steroids affect the way your immune system works so you may be more likely to get infections. Even a mild infection such as a cold or sore throat could develop into something more serious. Tell your doctor or hospital if you feel unwell and think you might have an infection.

Avoid close contact with people who have infections. This includes viruses and bacteria that cause chickenpox and shingles, measles, tuberculosis and pneumococcal disease. You could become seriously ill from these illnesses. Tell your doctor if you come into contact with anyone who has these infections.

You’ll need some checks before you start treatment to make sure steroids are right for you. Let your IBD team know if you have:

Infections. This includes any past infections (such as tuberculosis) or if you currently have an infection, or if you’re generally feeling unwell or feverish. Your treatment with steroids may have to be postponed until your infection has cleared. This is because steroids can mask the symptoms of infections and make them worse.
Liver problems. The levels of steroids in your blood may be increased if your liver isn’t working properly.
Mental health disorders. This includes psychosis, severe depression or bipolar disorder, or if someone in your family has had mental health problems.
Wounds. If you have wounds from recent surgery or are going to have surgery soon, as steroids may delay wound healing.
Pre-existing conditions, including heart failure, a recent heart attack, high blood pressure, diabetes, epilepsy, cataracts, glaucoma, an underactive thyroid, osteoporosis, obesity, stomach ulcers or systemic sclerosis. Steroids can make some conditions worse so your medical team may need to monitor your condition more closely.

And tell your IBD team if:

you’re pregnant, planning to get pregnant or breastfeeding.
you’re taking any other medicines.
you’ve had any vaccinations recently, or plan to have any vaccinations.
you’ve had surgery recently, or plan to have surgery.
you’ve ever had chicken pox or not. If you’ve not had chicken pox, you may be able to have the vaccine before you start steroids.

You’ll usually only be taking steroids short-term, so you may not see your IBD team during this time – however, you should contact your IBD team if you experience any side effects or if steroid treatment isn’t working for you.

Your doctor may want to monitor you if you’re at risk of developing weak bones (osteoporosis).

If you’re taking steroids longer-term, your doctor will also check for secondary adrenal suppression. For more information on this, see the section on Side effects.

Protecting your bones
Taking steroids can weaken your bones, so you may be given vitamin D and calcium supplements to help keep them strong. Your doctor will assess your risk of bone fractures and, if you’re considered to be at a high risk, you may have a bone density scan (also known as a DEXA scan). You may also be given another type of drug called a bisphosphonate to help keep your bones strong. If you’re pregnant, or wanting to become pregnant, speak to your doctor before starting bisphosphonate treatment as it may not be suitable for you. Steroids taken rectally (in enemas or suppositories) and locally acting steroids, such as budesonide, are less likely to cause bone weakness than steroids taken by mouth or intravenously.

Making changes to your lifestyle can help you maintain healthy bones. See our information on Bones.

Although steroids are produced naturally by the body, steroid medicines can cause unwanted side effects. Around 1 in every 2 people taking steroids experiences side effects. Your doctor will help manage any side effects by only prescribing the lowest effective dose of steroids for the shortest time. Some side effects may be mild and go away on their own. Others may be more serious and could require treatment or mean that steroids aren’t suitable for you.

Speak to your IBD team if you experience any side effects. The most common side effects while taking steroids include:

Cosmetic changes, including acne, rounded “moon” face, growth of unwanted body hair or stretch marks.
Changes in mental health or mood changes, such as depression or experiencing extreme highs and lows in your mood.
Salt and fluid retention, which can lead to raised blood pressure and ankle swelling.
Changes to your hormones, which can cause weight gain, diabetes or raised blood sugar levels.
Higher risk of infections, including colds and flu and more serious infections like pneumonia and sepsis.
Eye problems, such as glaucoma, cataract or other problems with vision.
Joint, bone and muscle problems, such as osteoporosis (weak bones), muscle and joint pain or muscle weakness.
Gut problems, such as stomach pain, stomach ulcers or nausea.
Problems with growth in children and young people.

Tell your doctor or IBD team immediately if you develop any of the following:

Allergic reaction, including a rash, itching, difficulty breathing or swelling of your face, lips, throat or tongue.
Changes in your mental health or mood, such as feeling depressed, high, or your moods go up and down. Also contact your doctor if you feel confused, irritable, anxious, have suicidal thoughts or difficulty sleeping.
If you think you have an infection, feeling feverish or generally unwell, or if you come into contact with someone with chicken pox, shingles or measles.

Do not suddenly stop taking steroids
If you’ve been taking steroids for more than a few days you’ll need to reduce the dose gradually before stopping completely. Your IBD team will carefully guide you on this.

It’s very important not to miss a dose or suddenly stop taking steroids. While you’re taking steroid medicines, you stop making enough of your own steroids – which are important in keeping your body functioning. A sudden withdrawal from steroid medication may cause secondary adrenal insufficiency, a sharp fall in blood pressure and affect blood sugar levels. You’ll need to undergo a gradual reduction (taper) of your steroid dose to give your body time to start making its own steroids again.

Some symptoms of secondary adrenal insufficiency are similar to those of Crohn’s and Colitis, and include:

fatigue
loss of appetite and weight loss
abdominal pain
nausea and vomiting
headache
joint pains
dizziness
fever

Sometimes reducing the dose of steroids can make your Crohn’s and Colitis symptoms come back (known as steroid dependence). If this happens, you’ll be offered other drugs, such as azathioprine, to help you come off steroids completely.

The side effects I’ve experienced include heart palpitations, being ratty and the dreaded moon face. The sleepless nights were annoying, but nothing that I couldn’t handle.
Rachel, age 25
Living with Crohn’s Disease

It’s generally agreed that steroids are safe for men and women wanting to conceive.

Taking steroids during pregnancy is a low risk to your baby, but you should still tell your doctor if you’re planning to get pregnant or find out you’re pregnant. Steroids are an effective treatment and there’s usually a greater risk to your baby if you’re unwell with Crohn’s or Colitis. Having active Crohn’s or Colitis at conception or during pregnancy increases the risk of pre-term birth and babies may have a lower birthweight or be smaller for their gestational age.

Although small amounts of steroids may cross the placenta, up to 40mg prednisolone daily is considered safe for the baby. If you’re taking a high dose of steroids, or you’re taking steroids long-term or repeatedly during pregnancy, your baby may be at an increased risk of intrauterine growth retardation – this is when a baby grows more slowly in the womb. Your doctors will check your baby’s growth as part of your routine antenatal appointments.

Women with Crohn’s or Colitis taking steroids may have an increased risk of developing gestational diabetes – your doctor will monitor you closely for gestational diabetes and will advise you on how to manage this condition.

There may also be a very small risk of cleft lip and palate in babies born to women taking steroids during the first three months of pregnancy, but this has not been found in all studies and not all experts agree on this.

There hasn’t been much research into taking budesonide during pregnancy, but a small study of eight pregnant women with Crohn’s did not find any adverse effects in the mother or the baby.

Tell the healthcare team involved in your birth that you’re taking steroids or have taken steroids during your pregnancy.

Steroids may pass to the baby in the milk – but it’s a very small amount, so it’s usually safe to breastfeed while taking steroids. However, if you’re taking a high dose of steroids (over 40mg prednisolone daily), check with your IBD team first – as you may need to leave some time between taking your steroids and breastfeeding.

Steroids are often taken alongside other medicines used to treat Crohn’s or Colitis, and your IBD team will consider all of your medicines when prescribing steroids. However, there are some medicines that can interact with steroids – so you should talk to your doctor or pharmacist if you’re taking, or plan to take any other medicines. This includes over the counter medicines (medicines that you can buy yourself without a prescription) or any herbal, complementary or alternative medicines or treatments.

Common medicines that interact with steroids include:

Anticoagulants (such as warfarin)
Antifungal drugs
Bronchodilators (such as salbutamol)
Diabetes drugs
Diuretics
Epilepsy drugs
HIV drugs
Live vaccines (see the section below Vaccinations while taking steroids)
Some antibiotics

There’s an increased risk of stomach ulcers and internal bleeding if you take nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen or aspirin, while you’re also taking steroids. If you need to take both, your doctor may give you an additional drug called a proton pump inhibitor to help reduce this risk.

Vaccinations while taking steroids

It’s not safe to have ‘live’ vaccines while taking high doses of steroids (over 40mg prednisolone daily for more than 7 days) or for a longer period of time (over 20mg prednisolone daily for more than 14 days) because steroids weaken your immune system. If this is the case, you’ll have to wait 3 months after you stop taking steroids before having a live vaccine. Speak to your IBD team to make sure your vaccinations are up to date before you start taking steroids, or if you’re planning to travel. If you’ve recently had a live vaccine, you should wait least 3 weeks before starting steroids.

In the UK, live vaccines include:

BCG (tuberculosis)
Chicken pox (varicella)
Measles, mumps and rubella (either as individual vaccines or as the triple MMR vaccine)
Yellow fever
Rotavirus (babies only)
Flu nasal spray (children only)

Everyone with Crohn’s or Colitis should have the annual flu jab (injection) – this is not a live vaccine and is safe to have while taking steroids.

If someone in your household is due to have a live vaccine, ask your IBD team if you need to take any special precautions.

Tell other health professionals you’re taking steroids

You must tell any doctor, dentist or other health professional treating you that you’re taking steroids. If you have a steroid alert card, always carry this with you.

You can drink alcohol in moderation while taking steroids, but you may be more likely to have stomach problems.The Department of Health recommends drinking no more than 14 units of alcohol per week – that’s around six pints of beer or six glasses of wine.

If you have Crohn’s Disease
Enteral nutrition (a special liquid diet that provides all necessary nutrients instead of eating food) is an effective alternative to steroids for children with Crohn’s. Enteral nutrition is preferred if there are concerns about steroids affecting a child’s growth. There’s not enough evidence to say whether enteral nutrition is as effective as steroids for adults with Crohn’s, but liquid diets may be used to support nutrition. Speak to your IBD team if you want to find out more about enteral nutrition.

If your symptoms return when you try to reduce or stop taking steroids (steroid dependency) you may be offered an immunosuppressant, such as azathioprine or mercaptopurine, to take in combination with steroids. If your disease is severe and you’re not getting better with steroids and/or immunosuppressants, you may be offered a biological treatment, such as infliximab or adalimumab.

If you have Ulcerative Colitis
You’ll likely be offered topical or oral 5-ASAs before steroids. If your symptoms return when you try to reduce or stop taking steroids (steroid dependency) you may be offered an immunosuppressant, like azathioprine or mercaptopurine, to take in combination with steroids. If your Colitis is severe and you’re not getting better with steroids and/or immunosuppressants, you may be offered a biological treatment, such as infliximab or adalimumab.

If you have Microscopic Colitis
As well as prescribing steroids, your doctor will help you identify lifestyle changes, such as stopping smoking and some medicines, identifying trigger foods in your diet and taking anti-diarrhoeal medicines (such as loperamide) to help control symptoms. If this doesn’t help, there may be other drug treatments you can try, although there’s much less research into the effectiveness of these. See our information on Microscopic Colitis for details.

Always speak to your IBD nurse if you have any concerns or side effects. They see lots of people with IBD and have lots of valuable experience.
Barry, age 41
Living with Crohn’s Colitis

Taking different medicines and managing side effects can be difficult – we understand and we’re here to help. Our Helpline can answer general questions about different treatment options and can help you find support from others with the conditions.

Your IBD team are also there to help you. You can talk to them about your steroid dosage, how they’ll be monitoring you and what alternatives may be available. You should also get in touch with your IBD team if you have any new symptoms or side effects.

It can take time to find the medicine that’s right for you, so keep pushing through. Don’t be afraid to ask questions and seek out extra support when you need it.

This information on steroids is general and doesn’t replace specific advice from your doctor or any other health professional. Talk to your doctor or IBD team for more information. You can also check the Patient Information Leaflet that comes with your medicine or go to medicines.org.uk/emc.

We offer more than 50 publications on many aspects of Crohn’s Disease, Ulcerative Colitis and other forms of Inflammatory Bowel Disease. You may be interested in our comprehensive booklets on each disease, as well as the following publications:

Health professionals can order some publications in bulk by using our online ordering system. If you would like a printed copy of a booklet or information sheet, please contact our helpline.

Our helpline is a confidential service providing information and support to anyone affected by Crohn’s or Colitis. Our team can:

help you understand more about Crohn’s or Colitis, diagnosis and treatment options
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be there to listen if you need someone to talk to
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Call us on 0300 222 5700
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Management of Inflammatory Bowel Disease

1. Bonner GF.
Current medical therapy for inflammatory bowel disease. South Med J.
1996;89:556–66….

2. Stenson WF. Inflammatory bowel disease. In: Yamada T, ed. Textbook of gastroenterology. 2d ed. Vol 2. Philadelphia: Lippincott, 1995:1748–1805.

3. Botoman VA, Kozarek RA. Inflammatory bowel disease. In: Taylor RB, ed. Difficult medical management. Philadelphia: Saunders, 1991:374–86

4. Nugent FW,
Roy MA.
Duodenal Crohn’s disease: an analysis of 89 cases. Am J Gastroenterol.
1989;84:249–54.

5. Owen D. Endoscopic biopsy. In: Bayless TM, ed. Current management of inflammatory bowel disease. Philadelphia: Decker, 1989:13–6.

6. Farmer RG,
Whelan G,
Fazio VW.
Long-term follow-up of patients with Crohn’s disease. Relationship between the clinical pattern and prognosis. Gastroenterology.
1985;88:1818–25.

7. Irvine EJ,
Feagan B,
Rochon J,
Archambault A,
Fedorak RN,
Groll A,

et al.
Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn’s Relapse Prevention Trial Study Group. Gastroenterology.
1994;106:287–96.

8. Helzer JE,
Chammas S,
Norland CC,
Stillings WA,
Alpers DH.
A study of the association between Crohn’s disease and psychiatric illness. Gastroenterology.
1984;86:324–30.

9. Kaplan MA,
Korelitz BI.
Narcotic dependence in inflammatory bowel disease. J Clin Gastroenterol.
1988;10:275–8.

10. Cottone M,
Rosselli M,
Orlando A,
Oliva L,
Puleo A,
Cappello M,

et al.
Smoking habits and recurrence in Crohn’s disease. Gastroenterology.
1994;106:643–8.

11. Thomas GA,
Rhodes J,
Mani V,
Williams GT,
Newcombe RG,
Russell MA,

et al.
Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med.
1995;332:988–92.

12. Russell RI.
Review article: dietary and nutritional management of Crohn’s disease. Aliment Pharmacol Ther.
1991;5:211–26.

13. Pena AS,
Truelove SC.
Hypolactasia and ulcerative colitis. Gastroenterology.
1973;64:400–4.

14. Schreiber S,
Howaldt S,
Schnoor M,
Nikolaus S,
Bauditz J,
Gasche C,

et al.
Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease. N Engl J Med.
1996;334:619–23.

15. Griffiths AM,
Ohlsson A,
Sherman PM,
Sutherland LR.
Meta-analysis of enteral nutrition as a primary treatment of active Crohn’s disease. Gastroenterology.
1995;108:1056–67.

16. Brzezinski A,
Rankin GB,
Seidner DL,
Lashner BA.
Use of old and new oral 5-aminosalicylic acid formulations in inflammatory bowel disease. Cleve Clin J Med.
1995;62:317–23.

17. Bonner GB, Ruderman WB. 5-Aminosalicylic acid preparations in the treatment of inflammatorybowel disease. In: Inflammopharmacology. Norwell, Mass.: Kluwer Academic, 1993:247–62.

18. Gendre JP,
Mary JY,
Florent C,
Modigliani R,
Colombel JF,
Soule JC,

et al.
Oral mesalamine (Pentasa) as maintenance treatment in Crohn’s disease: a multicenter placebo-controlled study. The Groupe d’Etudes Therapeutiques des Affections Inflammatoires Digestives (GETAID). Gastroenterology.
1993;104:435–9.

19. Mulder CJ,
Tytgat GN,
Weterman IT,
Dekker W,
Blok P,
Schrijver M,

et al.
Double-blind comparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis. Gastroenterology.
1988;95:1449–53.

20. Schroeder KW,
Tremaine WJ,
Ilstrup DM.
Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med.
1987;317:1625–9.

21. Riley SA,
Mani V,
Goodman MJ,
Herd ME,
Dutt S,
Turnberg LA.
Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology.
1988;94:1383–9.

22. Prantera C,
Pallone F,
Brunetti G,
Cottone M,
Miglioli M.
Oral 5-aminosalicylic acid (Asacol) in the maintenance treatment of Crohn’s disease. The Italian IBD Study Group. Gastroenterology.
1992;103:363–8.

23. Topical 5-aminosalicylic acid versus prednisolone in ulcerative proctosigmoiditis. A randomized, double-blind multicenter trial. Danish 5-ASA Group. Dig Dis Sci.
1987;32:598–602.

24. Spirt MJ.
Antibiotics in inflammatory bowel disease: new choices for an old disease. Am J Gastroenterol.
1994;89:974–8.

25. Hanauer SB,
Baert F.
Medical therapy of inflammatory bowel disease. Med Clin North Am.
1994;78:1413–26.

26. Bello C,
Goldstein F,
Thornton JJ.
Alternate-day prednisone treatment and treatment maintenance in Crohn’s disease. Am J Gastroenterol.
1991;86:460–6.

27. Vakil N,
Sparberg M.
Steroid-related osteonecrosis in inflammatory bowel disease. Gastroenterology.
1989;96:62–7.

28. Sachar DB.
Budesonide for inflammatory bowel disease. It is a magic bullet? [Editorial] N Engl J Med.
1994;331:873–4.

29. Hirschfeld S,
Clearfield HR.
Pharmacologic therapy for inflammatory bowel disease. Am Fam Physician.
1995;51:1971–5.

30. Sandborn WJ.
A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol.
1996;91:423–33.

31. Korelitz BI,
Adler DJ,
Mendelsohn RA,
Sacknoff AL.
Long-term experience with 6-mercaptopurine in the treatment of Crohn’s disease. Am J Gastroenterol.
1993;88:1198–205.

32. Pearson DC,
May GR,
Fick GH,
Sutherland LR.
Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med.
1995;123:132–42.

33. Haber CJ,
Meltzer SJ,
Present DH,
Koreitz BI.
Nature and course of pancreatitis caused by 6-mercaptopurine in the treatment of inflammatory bowel disease. Gastroenterology.
1986;91:982–96.

34. Connell WR,
Kamm MA,
Dickson M,
Balkwill AM,
Ritchie JK,
Lennard-Jones JE.
Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet.
1994;343:1249–52.

35. Feagan BG,
Rochon J,
Fedorak RN,
Irvine EJ,
Wild G,
Sutherland L,

et al.
Methotrexate for the treatment of Crohn’s disease. The North American Crohn’s Study Group Investigators. N Engl J Med.
1995;332:292–7.

36. Lichtinger S,
Present DH,
Kornbluth A,
Gelernt I,
Bauer J,
Galler G,

et al.
Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med.
1994;330:1841–5.

37. Kozarek R,
Bedard C,
Patterson D,
Justus P,
Sandford R,
Greene M,

et al.
Cyclosporin use in the precolectomy chronic ulcerative colitis patient: a community experience and its relationship to prospective and controlled clinical trials. Pacific Northwest Gastroenterology Society. Am J Gastroenterol.
1995;90:2093–6.

38. Collawn C,
Rubin P,
Perez N,
Bobadilla J,
Cabrera G,
Reyes E,

et al.
Phase II study of the safety and efficacy of a 5-lipoxygenase inhibitor in patients with ulcerative colitis. Am J Gastroenterol.
1992;87:342–6.

39. van Dullemen HM,
van Deventer SJ,
Hommes DW,
Bijl HA,
Jansen J,
Tytgat GN,

et al.
Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology.
1995;109:129–35.

40. van Deventer SJ,
Elson CO,
Fedorak RN.
Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn’s disease. Crohn’s Disease Study Group. Gastroenterology.
1997;113:383–9.

41. Bank S,
Snisky C,
Robinson M,
Katz JS,
Singleton J,
Miner P,

et al.
Safety and activity evaluation of rhIL-11 in subjects with active Crohn’s disease [Abstract]. Gastroenterology.
1997;112(4 Suppl):A927.

42. Sandborn WJ.
A preliminary report on the use of oral tacrolimus (FK 506) in the treatment of complicated proximal small bowel and fistulizing Crohn’s disease [Abstract]. Gastroenterology.
1997;112(4 Suppl):A1080.

43. Eisenberg S,
Friedman LS.
Inflammatory bowel disease in pregnancy. Practical Gastroenterol.
1990;14:10–2.

44. Habal FM,
Hui G,
Greenberg GR.
Oral 5-aminosalicylic acid for inflammatory bowel disease in pregnancy: safety and clinical course. Gastroenterology.
1993;105:1057–60.

45. Burtin P,
Taddio A,
Ariburnu O,
Einarson TR,
Koren G.
Safety of metronidazole in pregnancy: a meta-analysis. Am J Obstet Gynecol.
1995;172(2 Pt 1):525–9.

46. Dayan A,
Rubin P,
Chapman M,
Present D.
6-Mercap-topurine (6MP) use in inflammatory bowel disease (IBD) in patients of childbearing age: an increase in congenital anomalies—a case-controlled study [Abstract]. Gastroenterology.
1991;100(5 Pt 2):A824.

47. Alstead EM,
Ritchie JK,
Lennard-Jones JE,
Farthing MJ,
Clark ML.
Safety of azathioprine in pregnancy in inflammatory bowel disease. Gastroenterology.
1990;99:443–6.

48. Connell WR.
Safety of drug therapy for inflammatory bowel disease in pregnant and nursing women. Inflamm Bowel Dis.
1996;2:33–47.

49. Ekbom A,
Helmick C,
Zack M,
Adami HO.
Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med.
1990;323:1228–33.

50. Lashner BA.
Recommendations for colorectal cancer screening in ulcerative colitis: a review of research from a single university-based surveillance program. Am J Gastroenterol.
1992;87:168–75.

Rectal Specialists | Colitis | Rectal Surgeon

We diagnose and treat many conditions of the bowel and colon including colitis, rectal prolapse, constipation and many more. Read more about some of these conditions or contact us to ask a question or make an an appointment.

What is ulcerative colitis?
Ulcerative colitis is an inflammation of the lining of the large bowel (colon). Symptoms include rectal bleeding, diarrhea, abdominal cramps, weight loss, and fevers. In addition, patients who have had extensive ulcerative colitis for many years are at an increased risk to develop large bowel cancer. The cause of ulcerative colitis remains unknown.

How is ulcerative colitis treated?
Initial treatment of ulcerative colitis is medical, using antibiotics and anti-inflammatory medications such as Alzulfidine or Prednisone. These are usually necessary on a long-term basis. Prednisone has significant side effects, and, therefore, it is usually used for short periods. Flare-ups of the disease can often be treated by increasing the dosage of medications or adding new medications, such as 6-Mercaptopurine. Hospitalization may be necessary to put the bowel to rest.

When is surgery necessary?
Surgery is indicated for patients who have life-threatening complications of inflammatory bowel diseases, such as massive bleeding, perforation, or infection. It may also be necessary for those who have the chronic form of the disease, which fails medical therapy. It is important the patient be comfortable that all reasonable medical therapy has been attempted prior to considering surgical therapy. In addition, patients who have long-standing ulcerative colitis and show cancer signs may be candidates for removal of the colon, because of the increased risk of developing cancer. More often, these patients are followed carefully with repeated colonoscopy and biopsy, and only if precancerous signs are identified is surgery recommended.

What operations are available?
Historically, the standard operation for ulcerative colitis has been removal of the entire colon, rectum, and anus. This operation is called a proctocolectomy and may be performed in one or more stages. It cures the disease and removes all risk of developing cancer in the colon or rectum.

However, this operation requires creation of a Brooke ileostomy and chronic use of an appliance on the abdominal wall to collect waste from the bowel.

The continent ileostomy is similar to a Brooke ileostomy, but an internal reservoir is created. The bowel still comes through the abdominal wall, but an external appliance is not required. The internal reservoir is drained three to four times a day by inserting a tube into the reservoir. This option eliminates the risks of cancer and risks of recurrent persistent colitis, but the internal reservoir may begin to leak and require another surgical procedure to revise the reservoir.

Some patients may be treated by removal of the colon, with preservation of the rectum and anus. The small bowel can then be reconnected to the rectum and continence preserved. This avoids an ileostomy, but the risks of ongoing active colitis, increased stool frequency, urgency, and cancer in the retained rectum remain.

Are there other surgical alternatives?
The ileoanal procedure is the newest alternative for the management of ulcerative colitis. This procedure removes all of the colon and rectum, but preserves the anal canal. The rectum is replaced with small bowel, which is refashioned to form a small pouch. Usually, a temporary ileostomy is created, but this is closed in several months. The pouch acts as a reservoir to help decrease the stool frequency. This maintains a normal route of defecation, but most patients experience five to ten bowel movements per day. This operation all but eliminates the risk of recurrent ulcerative colitis and allows the patient to have a normal route of evacuation. Patients can develop inflammation of the pouch, which requires antibiotic treatment. In a small percentage of patients, the pouch fails to function properly and may have to be removed. If the pouch is removed, a permanent ileostomy will likely be necessary.

Which alternative is preferred?
It is important to recognize that none of these alternatives makes a patient with ulcerative colitis normal. Each alternative has perceivable advantages and disadvantages, which must be carefully understood by the patient prior to selecting the alternative which will allow the patient to pursue the highest quality of life.

Rectal Prolapse

What is rectal prolapse?
Rectal prolapse is a condition in which the rectum, the lower end of the colon, located just above the anus, turns itself inside out. In the earliest phases of this condition, the rectum does not stick out of the body, but as the condition worsens, it may protrude. Weakness of the anal sphincter muscle is often associated with rectal prolapse at this stage and may result in leakage of stool or mucus. The condition occurs in both sexes, although it is more common in women than men.

Why does it occur?
Several factors may contribute to the development of rectal prolapse. It may come from a lifelong habit of straining to have bowel movements or as a delayed result of stresses involved in childbirth. In rare cases, there may be a genetic predisposition in some families. It seems to be a part of the aging process in many patients who experience weakening of the ligaments that support the rectum inside the pelvis as well as loss of tightness of the anal sphincter muscle. In some cases, neurological problems, such as spinal cord transection or spinal cord disease, can lead to prolapse. In most cases, however, no single cause can be identified.

Is rectal prolapse the same as hemorrhoids?
Some of the symptoms may be the same. There may be bleeding and/or tissue that protrudes from the rectum. Rectal prolapse, however, involves a segment of the bowel located higher up within the body, while hemorrhoids develop near the anal opening.

How is rectal prolapse diagnosed?
Our physicians can diagnose this condition by taking a careful history and performing a complete anorectal examination. To demonstrate the prolapse, patients may be asked to “strain” as if having a bowel movement or to sit on the commode and “strain” prior to examination.

At times, however, a rectal prolapse may be hidden or internal. In this situation, an x-ray examination called a videodefecogram may be helpful. This examination, which takes x-ray pictures while the patient is having a bowel movement, can also assist the physician in determining whether surgery may be beneficial and which operation may be appropriate.

Anorectal manometry may also be used. This test measures whether or not the muscles around the rectum are functioning normally.

How is rectal prolapse treated?
Although constipation and straining may be causes of rectal prolapse, simply correcting these problems may not improve the prolapse once it has developed. There are many different ways to surgically correct rectal prolapse.

Abdominal or rectal surgery may be suggested. Your doctor can help you decide which method will most likely achieve the best result by taking into account many factors, such as age, physical condition, extent of prolapse and the results of various tests.

Treatment of Rectal Prolapse depends on several factors:

Patient’s age
Physical condition
Extent of prolapse
Test results

How successful is treatment?
Success depends on a number of factors, including the status of a patient’s anal sphincter muscle before surgery, whether the prolapse is internal or external, the overall condition of the patient and surgical method used. If the anal muscle has been weakened, either because of the rectal prolapse or for some other reason, it may in many cases significantly regain strength after the rectal prolapse has been corrected.

Chronic constipation and straining after surgical correction must be avoided. A great majority of patients are completely relieved of symptoms, or are significantly helped, by the appropriate procedure.

Constipation

What is constipation?
Constipation uncomfortable and has different meanings to different individuals.

Most commonly, it refers to infrequent bowel movements, but may also refer to a decrease in the volume or weight of stool, the need to strain to have a movement, a sense of incomplete evacuation, or the need for enemas, suppositories or laxatives to maintain regularity.

For most people, it is normal for bowel movements to occur from three times a day to three times a week. Other people may go a week or more without experiencing discomfort or harmful effects. About 80 percent of people suffer from constipation at some time during their lives, and brief periods of constipation are normal.

Normal bowel habits are affected by diet. The average American diet includes 12 to 15 grams of fiber per day, although for proper bowel function 25 to 30 grams of fiber and about 60 to 80 ounces of fluid are recommended each day. Exercise is also beneficial to proper function of the colon.

Eating whole grains, fruits and vegetables helps keep constipation away.

Eating foods high in fiber, including bran, shredded wheat, whole grain breads and certain fruits and vegetables will help provide the 25 to 30 grams of fiber per day recommended for proper bowel function.

How is constipation diagnosed?
Constipation may be diagnosed if bowel movements occur fewer than three times weekly on an ongoing basis. Widespread beliefs, such as the assumption that everyone should have a movement at least once each day, have led to overuse and abuse of laxatives.

What causes constipation?
There may be several, possibly simultaneous, causes for constipation, including inadequate fiber and fluid intake, a sedentary lifestyle, and environmental changes. Constipation may be aggravated by travel, pregnancy or change in diet. In some people, it may result from repeatedly ignoring the urge to have a bowel movement.

More serious causes of constipation include growths or areas of narrowing in the colon, so it is wise to seek the advice of a colon and rectal surgeon when constipation persists. Constipation may rarely be a symptom of scieroderma, lupus, or disorders of the nervous or endocrine systems, including thyroid disease, multiple sclerosis, Parkinson’s disease, stroke, and spinal cord injuries.

Can medication cause constipation?
Yes, many medications, including pain killers, antidepressants, tranquilizers, and other chiatric medications, blood pressure medication, diuretics, iron supplements, calcium supplements, and aluminum containing antacids can cause or worsen constipation.

Some people who are not actually constipated may become dependent on laxatives in an ill advised attempt to have daily bowel movements, and many cause themselves harm through laxative abuse.

When should I see a doctor about constipation?
Any persistent change in bowel habit – increase or decrease in frequency or size of stool or an increased difficulty in evacuating – warrants medical advice. Whenever constipation symptoms persist for more than three weeks, you should consult your physician. If blood appears in the stool, consult your colon and rectal surgeon right away.

How can the cause of constipation be determined?
Constipation may have many causes, and it is important to identify them so that treatment can be as simple and specific as possible. Your doctor will want to check for any anatomic causes, such as growths or areas of narrowing in the colon.

Digital examination of the anorectal area is usually the first step, since it is relatively simple and may provide clues to the underlying causes of the problem. Examination of the intestine with either a flexible lighted instrument or barium x-ray study may help pinpoint the problem and exclude serious conditions known to cause constipation, such as polyps, tumors, or diverticular disease. If an anatomic problem is identified, treatment can be directed toward correcting the abnormality.

Other tests may identify specific functional causes to help direct treatment. For example, “marker studies,” in which the patient swallows a capsule containing markers that show up on x-rays taken repeatedly over several days, may provide clues to disorders in muscle function within the intestine. Other physiologic tests evaluate the function of the anus and rectum. These tests may involve evaluating the reflexes of anal muscles that control bowel movements using a small plastic catheter, or x-ray testing to evaluate function of the anus and rectum during defecation.

In many cases, no specific anatomic or functional causes are identified and the cause of constipation is said to be nonspecific.

How is constipation treated?
The vast majority of patients with constipation are successfully treated by adding high fiber foods like bran, shredded wheat, whole grain breads and certain fruits and vegetables to the diet, along with increased fluids. Your physician may also recommend lifestyle changes. Fiber supplements containing undigestible vegetable fiber, such as bran, are often recommended and may provide many benefits in addition to relief of constipation. They may help to lower cholesterol levels, reduce the risk of developing colon polyps and cancer, and help prevent symptomatic hemorrhoids.

Fiber supplements may take several weeks, possibly months, to reach full effectiveness, but they are neither harmful nor habit forming, as some stimulant laxatives may become with overuse or abuse. Other types of laxatives, enemas or suppositories should be used only when recommended and monitored by your colon and rectal surgeon.

Designating a specific time each day to have a bowel movement also may be very helpful to some patients. In some cases, bio-feedback may help to retrain poorly functioning anal sphincter muscles. Only in rare circumstances are surgical procedures necessary to treat constipation. Your colon and rectal surgeon can discuss these options with you in greater detail to determine the best treatment for you.

Mesalamine and prednisone Drug Interactions

This report displays the potential drug interactions for the following 2 drugs:

Edit list (add/remove drugs)

Interactions between your drugs

No interactions were found between mesalamine and prednisone. This does not necessarily mean no interactions exist. Always consult your healthcare provider.

mesalamine

A total of
113 drugs
are known to interact with
mesalamine.

Mesalamine is in the drug class
5-aminosalicylates.
Mesalamine is used to treat the following conditions:

prednisone

A total of
506 drugs
are known to interact with
prednisone.

Prednisone is in the drug class
glucocorticoids.
Prednisone is used to treat the following conditions:

Drug and food interactions

No interactions were found. This does not necessarily mean no interactions exist. Always consult your healthcare provider.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major	Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate	Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor	Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown	No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

90,000 Treatment of ulcerative colitis (Crohn’s disease) in Moscow, make an appointment with a doctor for a fee and free of charge online, get a doctor’s consultation in clinics, hospitals, medical departments and medical diagnostic centers – Moscow Clinics

How to treat ulcerative colitis? Treatment is aimed at achieving remission, improving the quality of life, preventing exacerbations and complications. Etiotropic therapy, that is, aimed at the cause of the disease, is absent, since the causes of the pathology are not exactly known.Pathogenetic treatment is carried out, aimed at individual links in the mechanism of the development of the disease. The treatment uses a staged approach, which determines the tactics depending on the severity of the disease.

In patients with mild course, drugs – derivatives of aminosalicylic acid (sulfasalazine, mesalazine) are used as the main therapy. Sulfasalazine accumulates in the intestinal tissues, turning into aminosalicylic acid, which has anti-inflammatory action, and sulfapyridine, which has antibacterial action.A daily dose of 2 to 6 grams is divided into 4 doses. The course of treatment is 6-12 weeks. Abrupt withdrawal of the drug leads to an exacerbation: this is how the withdrawal syndrome manifests itself (rebound effect).

Corticosteroid hormonal drugs (dexamethasone, hydrocortisone, methylprednisolone, prednisolone) for ulcerative colitis are prescribed to patients with severe and severe disease. Treatment is carried out in short courses to stabilize the patient’s condition. Long-term use of glucocorticosteroids is not recommended due to the high likelihood of side effects.Cancellation of the drug is carried out gradually, so as not to cause withdrawal syndrome.

If sulfasalazine and corticosteroids are ineffective or intolerant, immunosuppressive therapy (suppressive immunity) is prescribed. Mostly used are azathioprine, cyclosporine, mercaptopurine. The treatment is carried out for a long time and continuously. The effect begins to be observed after 2–6 months.

Infliximab is an alternative immunosuppressive therapy. This drug blocks a specific protein (tumor necrosis factor alpha) involved in mucosal inflammation in ulcerative colitis.Suppression of TNF-alpha synthesis in most cases leads to a decrease in symptoms in the first two hours after the end of intravenous administration of the drug. Sometimes the positive effect of treatment occurs after a few days. The disadvantage of the drug is the high price and contraindications for use in patients with tuberculosis, hepatitis B and heart disease.

If conservative treatment is ineffective, an operation is performed.

medportal.ru

Ulcerative colitis, effective treatment in Moscow

In our hospital, patients with UC are treated by qualified gastroenterologists with extensive experience in the treatment of inflammatory bowel diseases. In the clinic, you can go through all the examination necessary to make and confirm the diagnosis, literally in 1-2 days: MRI, plain X-ray of the abdominal cavity, complex endoscopic examination (FGDS, colonoscopy, sigmoidoscopy), modern laboratory tests.In the complex treatment of NUC, high-tech methods of hemocorrection are used, which increase the success of therapy (achievement and prolongation of remission). If necessary, it is possible to carry out gentle laparoscopic operations for resection of the affected area of the intestine.

Ulcerative colitis (NUC) is a severe chronic recurrent bowel disease of an ulcerative-inflammatory nature, which can manifest itself as periods of exacerbation and prolonged remission.

Reasons for the development of ulcerative colitis

Many factors play a role in the development of ulcerative colitis, but the exact causes of the onset of the disease have not yet been established. Taken together, genetic, infectious, environmental, immunological factors cause malfunction of the intestine and the development of autoimmune inflammation in the mucous and submucosa of the intestinal wall. If the disease is not treated, it gradually progresses with the formation of inflammatory ulcers in the direction from the rectum to the overlying sections.

At the reception, the gastroenterologist of our hospital asks the patient in detail about the features of everyday life and work, the nature and duration of the development of the disease. This is necessary to clarify the initiating factors that provoke the disease and its exacerbation and the possibility of their elimination.

Symptoms of ulcerative colitis

Clinical manifestations of NUC depend on the severity of the disease. At the onset of the disease, patients can only be bothered by watery stools less than five times a day with a slight admixture of blood and mucus, false urge to defecate.

The specialists of our center recommend that you immediately consult a doctor when the first symptoms appear. This will increase the likelihood of permanent remission and make it easier to achieve it.

With the progression of the disease, unpleasant symptoms intensify: stools become more frequent, the amount of blood and mucus in it increases, fever appears over 38C, abdominal pain, anemia develops due to constant chronic blood loss, tachycardia, general health worsens, weight decreases.

In rare cases, patients are concerned about extraintestinal manifestations: inflammation of the oral mucosa, arthritis, inflammation of the eyelids, liver (cirrhosis), biliary tract (cholangitis, stones), skin and subcutaneous fatty tissue (polyarteritis, erythema nodosum, pyoderma).

Diagnosis and treatment of ulcerative colitis

The modern diagnostic equipment available in our clinic allows us to detect even the smallest manifestations of the disease at its initial stages.

Diagnostics

Diagnosis of ulcerative colitis at the Yauza Clinical Hospital is carried out within one or several days and includes a number of examinations that are selected individually, depending on the symptoms, severity and duration of the disease process.

In case of lesions of the rectum and sigmoid colon, a visual examination of the walls of the lower intestines using sigmoidoscopy gives an accurate idea of the presence and severity of the disease. If the ulcerative process affects the overlying parts of the intestine, colonoscopy, contrast-enhanced intestinal radiography, and MRI on a modern tomograph can additionally be prescribed.

Endoscopic examinations are performed on the basis of partner clinics, can be performed under anesthesia, which is provided by an experienced anesthesiologist.

Conservative therapy

Depending on the results of the examination, the gastroenterologist prescribes a treatment program using immunosuppressants (azathioprine) and anti-inflammatory drugs (sulfasalazines), corticosteroids (prednisolone), anti-material drugs, sedatives.

A diet is prescribed in order to reduce the irritating effect of food on the intestinal wall (mechanical and thermal sparing, limiting the consumption of vegetables and fruits, the use of food with an easily digestible and assimilable protein).

Surgical treatment

At later stages, with the development of complications, patients often require surgical treatment. In the Clinical Hospital on Yauza, it is possible to carry out minimally invasive surgical laparoscopic surgery to remove the affected area of the intestine without a wide incision. The operation is performed through small puncture incisions and provides faster recovery and the absence of an extensive postoperative scar.

Hemocorrection

The use of modern technologies in our hospital – extracorporeal hemocorrection allows you to quickly cope with an exacerbation, to better control the course of the disease.This is due to the removal of autoantibodies from the blood that support autoimmune inflammation in the intestinal wall. In addition, the use of cellular elements of blood as drug transporters makes it possible to reduce the dosage of drugs without reducing their effectiveness. This greatly facilitates the tolerance of drug treatment, reduces the side effects of hormone therapy.

The doctors of our medical center are doing everything possible to make life easier for patients with non-specific ulcerative intestinal lesions.Specialists work with the use of a modern scheme for the diagnosis and treatment of ulcerative colitis, which ensures efficiency and speed in achieving a positive result.

Cost of services

You can look at prices for services in the price list or check the phone number indicated on the website.

90,000 Case of continuously recurrent course of ulcerative colitis

Case of continuously recurrent course of ulcerative colitis

Elagina V.Yu

Scientific adviser: Ph.D. assistant Gerasimenko Yu.K.

State Budgetary Educational Institution of Higher Professional Education Saratov State Medical University named after IN AND. Razumovsky Ministry of Health of the Russian Federation

Department of Hospital Pediatrics and Neonatology

Ulcerative colitis (NUC) is a disease based on a chronic inflammatory process with diffuse lesions of the mucous membrane of the large intestine.

Nikita U., 17 years old, has been ill since August 2012, when an admixture of blood appeared in the formalized feces for the first time, about 1 time per week, weakness.Abdominal pain did not bother. In November 2012, after a colonoscopy with a biopsy, a diagnosis was made: Ulcerative colitis, acute course, moderate form, activity 2. Positive dynamics was observed against the background of therapy with budenofalk, salofalk per os and in suppositories. After the abolition of budenofalk in January 2012, the stool became mushy with an admixture of blood, the dose of salofalk was increased without a positive effect.

In May 2013, he was treated at the Clinic of Hospital Pediatrics-2 KB them.Mirotvortseva S.R., received a dairy-free diet 4 table, salofalk, budenofalk with a positive effect. 2 weeks after discharge, budenofalk was replaced with prednisolone 15 mg / day, which he received for a week, after which, against the background of a decrease in dose, an admixture of blood in the feces, decreased appetite, lethargy reappeared, but prednisolone was canceled. For a year and a half of the disease, the body weight loss was 16 kg. In connection with the recurrence of hemocolitis, the child was re-admitted to the KGP-2 on August 17, 2013, where he received salofalk therapy per os and in microclysters.Considering the severity of the condition, the duration of the disease, the lack of effect of the therapy, metipred 1 mg / kg / day per os was prescribed. Against the background of the therapy, there was a positive trend in the form of normalization of appetite, a persistent absence of blood impurities in the feces, but no weight gain was noted. During follow-up observation after 3 months, there were no symptoms of hemocolitis, the child was active, appetite was preserved, a slight increase in body weight – 2 kg in 3 months, however, manifestations of Itsenko-Cushing’s syndrome were expressed.

Thus, a feature of this case is the absence of abdominal pain in the clinical picture, the predominance of hemocolitis and trophological disorders, which could be stopped only with the appointment of systemic corticosteroids.