NICE guideline Ulcerative Colitis May 2019

NICE guideline Crohn’s May 2019

Definition

IBS is a group of idiopathic, chronic, relapsing and remitting, inflammatory intestinal disorders.

Types

1. Ulcerative Colitis (UC)

2. Crohn’s Disease (CD)

3. Microscopic Colitis

4. Indeterminate Colitis and Inflammatory Bowel Disease Unclassified (IBDU)

IBD multidisciplinary team
NICE Quality statement.
Informed whenever a patient known to them is admitted.
Composed of gastroenterologist, colorectal surgeon, clinical nurse specialist CNS, dietician, pharmacist, pathologist, and radiologist

Incidence

IBD affects 0.5% of UK population.; more common in Caucasian than Afro-Caribbean or Asian descent ; prevalence of IBD is rising

Ulcerative Colitis is the most common type of inflammatory bowel disease, affects around 146,000 people in the UK
Prevalence of approximately 240 per 100,000
UC can develop at any age, but main peak occurs aged 15-25y and 55-65y

Crohn’s Disease affects around 115,000 people in the UK
Prevalence of 145 per 100,000 population
Onset of CD has two age peaks: aged 15-30y and 50-70y

Aetiology

The cause is unknown (possibly: genetic predisposition + environmental tigger + altered immune reaction)
Smoking and genetic pre-disposition are two important risk factors in the aetiology of Crohn’s disease.
Other risk factors for IBD: combined oral contraceptive, appendectomy (CD), gastroenteritis (CD).

Symptoms and Signs

Diarrhoea (blood-stained/ not blood-stained), nocturnal diarrhoea
Rectal bleeding
Urgency of defecation
Abdominal pain
Constipation (e.g ‘acute’ inflammatory stricture)
Strictures and recto-vaginal or recto-vesical fistulae (CD)
Perianal abscess, skin takes, fissures and strictures (CD)
Mouth ulcers (CD)

Systemic symptoms:
Anorexia
Fever
Lethargy (anaemia)
Weight loss

Extra-intestinal features
Erythema nodosum (UC and CD)
Psoriasis
Pyoderma gangrenosum (UC and CD)
Peripheral or axial arthropathies
Arthritis: sacroiliitis, ankylosing spondylitis
Anterior uveitis, iritis, episcleritis
Skin granulomas
Primary sclerosing cholangitis, often UC (jaundice, pruritus and fatigue)
Secondary osteoporosis

Pathophysiology

UC
Inflammation affects inner bowel mucosa
Usually limited to rectum and distal colon (proctosigmoiditis) or rectum (proctitis), or left-sided colitis (colonic disease distal to splenic flexure) or pan-colitis
Endoscopy: one continuous area of inflammation
Rectal bleeding is common

Crohn’s
Transmural inflammation
Patches of inflammation, ulceration and fissuring of the mucosa
Endoscopy include ‘cobblestoning’, ulceration and ‘skip lesions’.
Granulomas
Mouth ulcers, strictures, rectal fistula and malabsorption can occur

Microscopic Colitis
Bowel appears normal on colonoscopy but histological changes are present
Persistent watery diarrhoea without blood is the most common symptom

IBDU
Less common
No clear diagnosis from endoscopy or histology

Complications

Anaemia

Acute exacerbation (‘flare’)—> Sepsis
Flares should be confirmed using serum ESR/CRP and/or faecal calprotectin; consider sending stool for microbiology to exclude infection (e.g. C Difficile)

Social and psychological well-being

Secondary osteoporosis
The risk is compounded by repeated or long term courses of steroids and malabsorption of calcium and vitamin D.
NICE states that fragility fracture risk should be assessed if >7.5mg daily prednisolone (or equivalent) for >3 months

Colorectal and small bowel cancers
Risk increases with duration of IBD: 2% after 10 years, 8% after 20 years and 18% after 30 years of the disease.
This compares with a lifetime risk of developing bowel cancer of 7% in males and 6% in females.
Colonoscopic surveillance every 1 to 5 years depending on duration and severity of IBD.

Acute bowel obstruction
Intestinal strictures
Bowel abscesses, in the wall of the intestine or adjacent structures
Fistulae between the intestine and adjacent structures, such as perianal skin, bladder, and vagina (particularly if ilecolonic CD)
Toxic megacolon

Anaemia + Malnutrition —> Failure to thrive and delayed puberty
Children and young people with CD and UC should regularly have their height measured.

Toxic megacolon
Life-threatening complication of IBD (especially UC) or infectious colitis
Acute non-obstructive colonic distension >6cm (megacolon) accompanied by systemic toxicity (fever, abdominal pain, or shock).

Investigations

Blood
FBC
CRP, ESR (not always raised!)
B12 and folate, ferritin
U&Es, bone profile, LFTs
TFTs
IgG TTA (coeliac disease)

Stool
Stool culture (to rule out infective cause)
Faecal calprotectin

Calprotectin
A protein biomarker released into the bowel when inflammation is presen
Helps to distinguish between inflammatory bowel disease and other diseases like irritable bowel syndrome

High sensitivity (88%) and negative predictive value (987%)
Faecal calprotectin below 50 mcg/g (100 mcg/ml) rules out IBD
Values greater than 50 mcg/g warrant specialist gastroenterology assessment within 4 weeks
False positive elevation can occur in gastroenteritis and NSAID use

Classification as mild/moderate/severe UC and Crohn’s

UC severity

According to the Truelove and Witts' Severity Index

• bowel movements/day

• blood in stools

• pyrexia

• heart rate

• anaemia

• ESR

CD severity
According to the Crohn’s activity Index (CDAI) and the Harvey-Bradshaw Index

The Harvey-Bradshaw index represents a simpler version of CDAI, and incorporates:

• general well-being (0 = very well, 1 = slightly below average, 2 = poor, 3 = very poor, 4 = terrible)

• abdominal pain (0 = none, 1 = mild, 2 = moderate, 3 = severe)

• number of liquid stools per day

• abdominal mass (0 = none, 1 = dubious, 2 = definite, 3 = tender)

• complications, with one point for each: arthralgia, uveitis, erythema nodosum, pyoderma gangrenosum, aphthous ulcers, anal fissures, fistulae or abscesses, fever

A score of less than 5 is generally considered to represent clinical remission

General principles of treatment

1. Treatment is directed at the induction and maintenance of remission and the relief of symptoms.

2. Active treatment of acute IBD flare should be distinguished from preventing relapse.

3. The duration of corticosteroid course (usually 4 to 8 weeks) depends on the corticosteroid chosen.
   Suggested regimen: start at prednisolone 40mg OD, reduce by 5mg every week, resulting in an 8-week course of treatment
   Calcium and Vitamin D should be co-prescribed with courses of oral corticosteroids.
   Steroid alternative is needed if ≥2 flare-ups in 12m OR steroid dose not reducible below 15mg OR relapse within 6w of stopping steroids

4. The aims of drug treatment are to reduce symptoms and maintain or improve quality of life, while minimising toxicity related to drugs over both the short and long term.

5. The extent and location of disease should be considered when selecting treatment: local treatment (suppositories or enemas) for inflammation restricted to distal bowel/rectum vs systemic treatment for more extensive bowel inflammation.

6. Do not give NSAIDs as it may reactivate CD disease and induce GI complications

7. Loperamide hydrochloride or codeine phosphate can be occasionally used to manage diarrhoea associated with IBD on the advice of a specialist.
   However their use is contraindicated in acute ulcerative colitis (increase the risk of toxic megacolon) or active Crohn’s colitis

8. Macrogol osmotic laxative may be useful for proximal faecal loading in proctitis.

9. In fistulating Crohn's disease, surgery and medical treatment aim to close and maintain closure of the fistula.

Drug treatment UC

First-line:
Aminosalicylates (sulfasalazine, mesalazine) oral and/or topical ASA (e.g. rectal suppository, enema or foam for proctitis, proctosigmoiditis, left-sided colitis)
Second-line: Add on corticosteroids (oral vs topical; ONLY 4-8w duration) if oral +/-topical aminosalicylates are not effective
Topical ASA PLUS high-dose oral ASA are recommended first-line treatments for a flare-up of extensive UC

Second-line:
Immunosuppressive drugs: e.g. azathioprine, mercaptopurine

Third-line:
Biological drugs:
Monoclonal antibodies which TNF-alpha adalimumab, golimumab, infliximab, vedolizumab
Janus kinase inhibitor tofacitinib

Maintenance therapy for UC:

1. ASA as oral or rectal or both modalities. Single daily dose oral ASA may be more effective than multiple daily dosing, but may result in more side-effects.

2. Oral azathioprine or mercaptopurine (or methotrexate +folic acid) may be used if there has been two or more inflammatory exacerbations in a 12-month period that required treatment with systemic corticosteroids, or if remission is not maintained by ASA, or following a single acute severe episode.

3. Treatment with biological drugs and janus kinase inhibitors may be continued into the maintenance phase, if effective and tolerated in acute disease.

Treatment of acute severe ulcerative colitis

1. Admit

2. Intravenous corticosteroids (such as hydrocortisone or methylprednisolone) +/- intravenous ciclosporin +/- surgery
   Infliximab can be used as an alternative to ciclosporin

3. Send stool more microbiology cultures

4. Screen for cytomegalovirus activation

Drug treatment CD

First-line:
Corticosteroids: oral prednisolone/iv hydrocortisone induce remission at 1st presentation OR single relapse in 12m ;
Oral budesonide for ileal, ileocaecal or right-sided colitis (anatomical site of drug absorption, budesonide MR 9mg once daily for 2 months, does not require gradual tapering)

Second-line: if two or more flare-ups in 12m,
Azathioprine or mercaptopurine PLUS corticosteroids/budesonide to induce remission and to maintain remission as monotherapy azathioprine or mercaptopurine.
Methotrexate is alternative to azathioprine or mercaptopurine.

Thiopurine methyltransferase (TPMT) activity is assessed before prescribing azathioprine. Azathiprine should not be prescribed if TPMT activity is low: in such cases use alternative of methotrexate and add this to the corticosteroid.

Third-line:
Monoclonal antibodies that acts as TNF-alpha inhibitors [inflixamab or adalimumab (or ustekinumab, and vedolizumab] can be combined with an immunosuppressant (to treat severely active CD) or used as monotherapy (to maintain remission).

Maintaining remission following Crohn’s surgery: post-operative Azathioprine PLUS 3 months metronidazole
NICE recommends use of Azathioprine in combination with up to 3 months metronidazole post-operatively in those who have had complete macroscopic resection surgery for ileocolonic Crohn’s disease to maintain remission, and to consider azathioprine alone for people who cannot tolerate metronidazole.

Non-drug management

1. Assess the impact of symptoms on daily living

2. Advise about support groups e.g. Crohn's and Colitis UK

3. Encourage the patient to stop smoking as this may reduce the risk of of Crohn’s disease

4. Ensure the patient has secondary care follow up and attend colo-rectal cancer surveillance (if the symptoms started more than 10 years ago)

5. If shared care drug arrangements are in place, prescribe and monitor IBD drugs

6. For extra-intestinal manifestations, refer to rheumatology, dermatology or ophthalmology

7. Consider assessing for risk of osteoporosis (especially if there is a history of low BMI, ow trauma fracture, continued use or repeated use glucocorticosteroids)

8. Vaccinate (influenza and pneumonia) BEFORE starting immunosuppressive or biologic therapy. Patients on immunosuppressive drugs should not be given live vaccines

9. Specialist enteral nutrition may be an alternative to conventional corticosteroids if there is concern about growth or side effects.
   Polymeric diets can be used treat CD.

10. Assess changing skin lesions and provide advice on sun protection, particularly for patients taking azathioprine.

Surgery

50% of CD patients will undergo surgery within 10y of diagnosis; lifetime risk of surgery in CD patients is >70%
Lifetime risk of surgery in UC patients is 20-30%

There is an increased likelihood of surgery for patients with any of the following:

• Stool frequency greater than 8 per day

• Pyrexia

• Tachycardia

• Colonic dilation on x-ray

• Low albumin

• Low Hb

• high platelet count

• CRP >45 mg/litre

Surgery may be considered as an alternative to medical treatment early in the disease for people whose disease is limited to the distal colon.

It should also be considered early in the course of the disease for children and young people whose disease is limited to the distal colon or distal lieum and who have growth impairment despite optimal medical treatment and/or refractory disease.

Management of fistulating Crohn's disease such as perianal fistulae

1. Local drainage and surgery

2. Treat infection: metronidazole +/- ciprofloxacin given for 1 month, but no longer than 3 months because of concerns about peripheral neuropathy (other antibacterials should be given for managing bacterial overgrowth in the small bowel).

3. Suppress inflammation: azathioprine or mercaptopurine (or infliximab), and used thereafter as maintenance for at least one year

For the management of non-perianal fistulating Crohn's disease (including entero-gynaecological and enterovesical fistulae) surgery is the only recommended approach.

Management of strictures
Between 50-80% of people with Crohn’s disease eventually need surgery for strictures causing symptoms of obstruction, fistulas, perforation or failure of medical therapy
Strictures can be managed by balloon dilatation or surgery

Taking into account the patient’s wishes, the number and extent of previous resections, and the potential consequences of small bowel syndrome

Prescribing of IBD drugs should always be part of a shared care protocol: follow local guidelines
look out for gradual decreases in the white blood cell count, albumin or increases in liver enzymes.

Monitoring patients on aminosalicylates

Monitor full blood count, liver function and renal function before starting an oral aminosalicylate, at 3 months of treatment, and then annually during treatment.
Moreover, the BNF specifically emphasizes the need to prescribe ASAs by brand as ASA drug delivery characteristics vary between formulations.

Monitoring patients on azathioprine, mercaptopurine and methotrexate

Azathioprine requires weekly FBC for the first 8 weeks and then 3 monthly
Mercaptopurine requires regular monitoring of LFTs
Usage of azathioprine and mercaptopurine increases the lifetime risk of developing skin cancer
Live vaccines are contraindicated whilst taking these drugs

Monitoring patients on infliximab

Infliximab (a chimeric monoclonal antibody blocking TNF-α) and adalimumab (TNF inhibitor) are alternative treatment options for patients with severe active fistulising Crohn’s disease or severe relapses of UC if ciclosporin is contraindicated or clinically inappropriate.
It is given in secondary care by intravenous infusion.
Vaccinate patients against influenza and pneumococcus BEFORE starting biologic agents
Live vaccines are contraindicated whilst taking these drugs

Side effects include:
Serious infections of joints and soft-tissue
Reactivation of TB and hepatitis B, lethal hepatosplenic T-cell lymphoma and demyelinating CNS disorders
Pancytopenia, leukopenia and neutropenia
Liver damage

Fertility issues for patients with IBD

Contraception

Issues to consider:

1. Malabsorption

2. History of prolonged mobility

3. Extra-intestinal problems e.g. primary sclerosing cholangitis

4. Osteoporosis

5. Venous thromboembolism

6. Potential teratogenicity of IBD treatments (eg methotrexate)

Oral contraceptives are less reliable if there is a history of malabsorption or small bowel resection.
Colectomy or ileostomy do not affect the reliability of contraception.
Patients should be warned that diarrhoea may affect absorption of oral contraceptives.

Avoid pregnancy if taking immunosuppressives (eg methotrexate)
Both male and female patients need to use effective contraception for
3 months after taking methotrexate or mercaptopurine (teratogenicity)
6 months after taking Infliximab or similar drugs (teratogenicity)

Male and female subfertility
There is no evidence that IBD affects fertility but pelvic surgery or pelvis sepsis can affect tubal function
Men with inflammatory bowel disease who have had pelvic surgery may suffer from erectile dysfunction or ejaculatory problems
Ileo-anal pouch surgery can also lead to retrograde-ejaculation and erectile dysfunction
Drugs like methotrexate and sulfasalazine can lead to reversible oligospermia
Infliximab can affect sperm quality by reducing sperm motility; no evidence of teratogenesis

IBD and bone health in children

IBD is a cause of secondary osteoporosis.
NICE recommends monitoring bone mineral density in children and young people with risk factors (low body mass index (BMI), low trauma fracture or continued or repeated glucocorticosteroid use)

Monitor the height and body weight of children and young people against expected values on centile charts (and/or Z scores) at the following intervals according to disease activity

* Every 3-6 months if they have active disease/undergoing puberty/systemic corticosteroids

* Every 12 months if none of the above criteria are met

IBD and delayed puberty

Consider referral to a secondary care paediatrician for pubertal assessment if observations suggest:

• Slow pubertal growth

• Not developed pubertal features appropriate for their age