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32 years

CROHN’S DISEASE

Crohn’s disease is an inflammatory condition that can affect any portion of the gastrointestinal tract from the mouth to the perianal area. Its transmural inflammatory nature coupled with the variability of intestinal distribution (i.e., which intestinal segment is affected) and systemic manifestations, gives rise to a spectrum of clinical presentations and long-term risks that have to be considered in deciding the optimal therapeutic approach.

 

The choice of therapy varies depending upon the anatomic location of disease, the severity of disease, and whether the treatment goal is to induce remission or maintain remission. Medical therapies that are used for Crohn disease include:

 

  • Oral 5-aminosalicylates (eg, sulfasalazine, mesalamine)
  • Glucocorticoids (eg, prednisone, budesonide)
  • Immunomodulators (eg, azathioprine, 6-mercaptopurine, methotrexate)
  • Biologic therapies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, ustekinumab)
CROHN'S DISEASE
ASSESSING DISEASE ACTIVITY, SEVERITY AND RISK


Crohn Disease Activity Index — Clinical trials of Crohn’s disease often use formal grading systems to describe disease activity. Two commonly used systems are the Crohn's Disease Activity Index (CDAI) (calculator 1) and the Harvey-Bradshaw Index (HBI) (calculator 2) [5], which is a simplified derivative of the CDAI. The HBI has been shown to correlate with the CDAI [6]. A drop in the CDAI of 100 points corresponds to a 3-point drop in the HBI. A CDAI of <150 (i.e., clinical remission) corresponds to an HBI of <4. These Crohn disease activity scoring systems rely on subjective symptoms, and while still utilized in clinical research trials, there is an emerging construct that defines disease burden in terms of objective findings and the presence or absence of bowel destruction. In addition, clinical trials are increasingly utilizing patient-reported outcomes to assess disease activity in Crohn disease.

In clinical practice, the following working definitions may be more useful :

 

  • Clinical remission (CDAI <150) – These patients are asymptomatic and without symptomatic inflammatory sequelae. This status is achieved either spontaneously or after medical or surgical intervention. Patients requiring glucocorticoids to remain asymptomatic are not considered to be in remission but are referred to as being "steroid-dependent".
  • Mild Crohn disease (CDAI 150-220) – These patients are typically ambulatory and tolerating an oral diet. They have <10 percent weight loss and no symptoms of systemic disease such as fever, tachycardia, abdominal tenderness, and no signs or symptoms of obstruction.
  • Moderate to severe Crohn disease (CDAI 220-450) – This group comprises patients who have failed treatment for mild to moderate disease or those patients with prominent symptoms such as fever, weight loss, abdominal pain and tenderness, intermittent nausea or vomiting, or anaemia.
  • Severe-fulminant disease (CDAI >450) – Patients with persistent symptoms despite glucocorticoids or biologic agents (infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, or ustekinumab) as outpatients, or individuals presenting with high fever, persistent vomiting, intestinal obstruction, peritoneal signs, cachexia, or evidence of an abscess.

 

Low- versus moderate/high-risk patients — In addition to the clinical parameters, the American Gastroenterological Association (AGA) stratifies patients into either a low or moderate/high risk category by assessing inflammatory status with the following tests:

 

  • Endoscopic evaluation for mucosal ulcerations and stricturing and disease extent
  • Laboratory parameters: C-reactive protein and/or fecal calprotectin
  • Presence or absence of upper gastrointestinal involvement

 

Patients with mild Crohn disease who are at low-risk for long term sequelae usually have no or mild symptoms as described above and lack signs of systemic inflammation (i.e., normal or mild elevation in C-reactive protein and/or fecal calprotectin levels) (see "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults").

 

Low-risk patients with mild Crohn disease have the following features:

 

  • No or mild symptoms
  • Normal or mild elevation in C-reactive protein and/or Fecal Calprotectin levels
  • Diagnosis at age >30 years
  • Limited distribution of bowel inflammation
  • Superficial or no ulceration on colonoscopy
  • Lack of perianal complications
  • No prior intestinal resections
  • Absence of penetrating or stricturing disease

 

Patients initially identified as low risk may be subsequently reclassified as higher risk if they develop complications or don’t respond to initial treatment. Other prognostic factors associated with a more complicated disease course include bowel damage as measured by cross sectional imaging, extra-intestinal manifestations of disease, number of flares, need for glucocorticoids, and resultant hospitalizations.

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