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Crohn's Disease

Essentials

  • The most common symptoms are abdominal pain, diarrhoea, fever, weight loss and blood in the stools.
  • Symptoms usually develop gradually.
  • The responsibility of the primary care physician is to recognise the possibility of Crohn's disease and refer the patient for further investigations.
  • The aim of treatment is symptom control, sustained remission without glucocorticoids, mucosal healing and the prevention of complications and relapses.
  • Patients with Crohn's disease should be encouraged to give up smoking.
  • Severe disease requires management in a hospital with expertise in Crohn's disease.

Epidemiology

  • The prevalence of Crohn's disease is high in the Nordic countries, Western Europe, North America and Australia. In Finland, the incidence is 9/100 000/year and the prevalence about 200 per 100 000 inhabitants.
  • Smoking increases the risk of onset of Crohn's disease, the activity of the disease and the likelihood of having to undergo surgery.
  • The age of onset for Crohn's disease is usually 20-30 years.
    • However, the disease may also start in childhood.

Clinical presentation

  • Clinical presentation and the development of complications are determined by
    • the behaviour of the disease
    • the location of the disease in the intestinal tract.
  • The disease is limited to the small bowel in about 30% of patients and to the large bowel in 25-30% of patients. Ileocolonic disease accounts for 40% of cases.
    • Pathological changes may occur in any part of the intestinal tract.
    • Approximately one third of the patients have perianal fistulae.
  • Extraintestinal involvement occurs in some patients (e.g. peripheral arthritis, sacroiliitis, erythema nodosum, uveitis, episcleritis, cholangitis).
  • Early age at disease onset, widespread inflammation, smoking, perianal problems and the need for glucocorticoid treatment are predictive factors for high risk of progression.
  • Symptoms
    • Abdominal pain
    • Diarrhoea
    • Low-grade fever
    • Bleeding from the rectum
    • Weight loss
    • Signs of intestinal obstruction
    • Perianal problems
    • Growth retardation in children
  • Clinical findings
    • Abdominal tenderness, resistance in palpation
    • Perianal fissures and fistulae
    • Oral aphthae
  • The disease is classified as being either inflammatory, structuring or fistulating (penetrating), but the behaviour of the disease may change over the years.
  • Complications may include
    • bowel obstructions
    • abscesses
    • fistulae
    • intestinal bleeding.

Diagnosis and investigations Anti-Saccharomyces Cerevisiae (Asca) and Perinuclear Antineutrophil Cytoplasmic Antibodies (Panca) in the Diagnosis of Crohn's Disease and Ulcerative Colitis

  • Common laboratory findings
    • Increased ESR and CRP
    • Mild anaemia
    • Leucocytosis and thrombocytosis
    • Increased faecal calprotectin (this test can be carried out in primary care before referral)
    • Decreased plasma albumin concentration
  • Ileocolonoscopy with biopsies for histology is the first line investigation.
  • Endoscopic findings in Crohn's disease include
    • segmental or patchy inflammation
    • cobblestone appearance of the mucous membranes
    • aphthous ulcers or larger, often longitudinal or fissural ulcers
    • strictures.
  • Histological findings include chronic inflammation that extends deep into the submucosa or even through the entire bowel wall as well as granulomas, which are quite rarely detected in mucosal biopsies.
  • Imaging studies, mainly magnetic resonance imaging, can be used for assessing the small bowel.
    • Moreover, small bowel capsule endoscopy can be used provided that the patient's symptoms, or the findings of imaging studies, are not suggestive of small bowel strictures.
  • Gastroscopy is performed on patients with upper abdominal symptoms or when assessing the extent of the disease.
  • In 10-15% of cases it is not possible to make a differential diagnosis between ulcerative colitis and Crohn's disease (intermediate form, "IBD unclassified", or IBDU).

Differential diagnosis

  • Ulcerative colitis Ulcerative Colitis
  • Functional diarrhoea Functional Bowel Disorders and the Irritable Bowel Syndrome (IBS) (normal inflammatory markers, normal faecal calprotectin)
  • Infectious colitis Prolonged Diarrhoea in Adults (stool cultures, serological investigations, endoscopic or histological findings as necessary)
  • Clostridium difficile colitis Clostridioides Difficile Diarrhoea (history of antimicrobial drug use, detection of Cl. difficile from stools)
  • Intestinal tuberculosis (medical history, detection of tuberculosis from mucosal samples, endoscopic and histological findings)
  • Ischaemic colitis (patients over 50 years of age, vascular risk factors present, endoscopic and histological findings)
  • Post radiotherapy colitis (may occur several years after treatment, endoscopic and histological findings)
  • Mucosal changes caused by NSAIDs (history of NSAID use, location of the changes, histology)

Arrangement of treatment

  • The responsibility of the primary care physician is to recognise the possibility of Crohn's disease and refer the patient for further investigations.
  • Diagnosis and treatment are usually the responsibility of a specialist.
  • The management of a patient with severe Crohn's disease requires a hospital that can provide gastroenterological expertise, adequate out of hours investigations and facilities for emergency surgery.
  • In a non-acute phase, the monitoring can also be carried out in primary care.
    • The primary care must be provided with adequate care instructions by the specialist team.

Pharmacotherapy Budesonide for Maintenance of Remission in Crohn's Disease, Cyclosporine for Induction of Remission in Crohn's Disease, Natalizumab for Induction of Remission in Crohn's Disease, Lymphoma Risk Among Inflammatory Bowel Disease Patients Treated with Azathioprine or 6-Mercaptopurine, Thalidomide and Thalidomide Analogues for Induction of Remission in Crohn's Disease, Aminosalicylates for Induction of Remission or Response in Crohn's Disease, Azathioprine or 6-Mercaptopurine for Inducing Remission of Crohn's Disease, Recombinant Human Interleukin 10 for Induction of Remission in Crohn's Disease, Enteral Nutrition Vs. Steroid Therapy for Induction of Remission in Crohn's Disease, Oral 5-Aminosalicylic Acid for Maintenance of Medically-Induced Remission in Crohn's Disease, Methotrexate for Induction of Remission in Refractory Crohn's Disease, Omega 3 Fatty Acids (Fish Oil) for Maintenance of Remission in Crohn's Disease, Probiotics for Maintenance of Remission in Crohn's Disease

Immunomodulating drugs commonly used in the treatment of Crohn's disease

DrugLaboratory monitoringDoseTherapeutic indications
Immunosuppressants
AzathioprineWeeks 0, 2, 4, 6 and 8 and thereafter every 3 months: CBC (complete blood count), ALT (alanine aminotransferase), ALP (alkaline phosphatase)2-2.5 mg/kg/dayMaintenance of remission, fistulae
6-mercaptopurineWeeks 0, 2, 4, 6 and 8 and thereafter every 3 months: CBC, ALT, ALP1-1.5 mg/kg/dayMaintenance of remission, fistulae
MethotrexateWeeks 0, 2, 4, 6 and 8 and thereafter every 3 months: CBC, ALT, ALP, creatinine15-25 mg per weekMaintenance of remission
Cytokine-mediated effect
InfliximabCBC, ALT, CRP before each infusion5 mg/kg by intravenous infusion every 8 weeks after an induction period (weeks 0, 2 and 6)Induction and maintenance of remission, fistulae Infliximab in Chronic Active Crohn's Disease
AdalimumabMonths 0 and 1: CBC, ALT, CRP and thereafter every 3 months: CBC, ALT, CRP40 mg by subcutaneous injection every 2 weeks after an initial dose (160-80 mg)Induction and maintenance of remission, fistulae
VedolizumabCBC, ALT, CRP before each infusion300 mg by intravenous infusion every 8 weeks after an induction period (weeks 0, 2 and 6)Induction and maintenance of remission, fistulae
UstekinumabCBC, ALT, CRP before initial infusion and thereafter every 2-3 monthsInduction by 6 mg/kg initial infusion, thereafter 90 mg subcutaneously 8 weeks after the infusion. Maintenance therapy: 90 mg subcutaneously every 12 (-8) weeks.Induction and maintenance of remission, fistulae

Surgery Interventions for Prevention of Post-Operative Recurrence of Crohn's Disease, Laparoscopic Versus Open Surgery for Small Bowel Crohn's Disease, Oral 5-Aminosalicylic Acid for Maintenance of Surgically-Induced Remission in Crohn's Disease

  • Indications for immediate surgery
    • Intestinal perforation and related peritonitis
    • Often abscesses
    • Major intestinal haemorrhage
    • Perianal abscesses (incision)
  • Indications for elective surgery
    • Symptomatic intestinal strictures
    • Intestinal fistulae
    • Continuous development of anaemia due to haemorrhage
    • Treatment of perianal fistulae (usually by placement of the so-called Seton drains)
    • Dysplastic changes, cancer
  • The aim of surgery is to conserve as much bowel as possible by removing only the worst affected bowel sections.
    • Strictures of the small bowel can also be treated by stricturoplasty.
  • Segmental resection in Crohn's disease that is limited to the large bowel is more beneficial than subtotal colectomy.
  • Crohn's disease is usually considered to be a contraindication to ileal pouch-anal anastomosis (IPAA).

Endoscopic treatment of strictures

  • The strictures to be dilated must not be complicated or longer than 4 cm.
  • The dilatation is carried out with the aid of an elongated balloon.
  • Complications following endoscopic dilatation may include bowel perforation, sepsis and haemorrhage.

Endoscopic follow-up

  • Patients with Crohn's disease affecting the large bowel should be regularly followed up by endoscopy due to the cancer risk caused by the inflammation (see Ulcerative Colitis).

References

  • Maaser C, Sturm A, Vavricka SR ym. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis 2019;13(2):144-164. [PubMed]
  • Torres J, Bonovas S, Doherty G ym. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis 2020;14(1):4-22. [PubMed]
  • Sandborn WJ, Feagan BG, Rutgeerts P ym. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med 2013;369(8):711-21. [PubMed]
  • Feagan BG, Sandborn WJ, Gasink C ym. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med 2016;375(20):1946-1960. [PubMed]

Evidence Summaries ⬆