Crohn's Disease

Inflamed
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Capsular Endoscopy in Crohn's Disease

As many individuals with Crohn's Disease (CD) demonstrate small-bowel (SB) involvement, all newly diagnosed patients should undergo evaluation of the SB; traditionally, this has been performed via a radiographic studies such as barium follow-throughs. However, in recent times, wireless capsule endoscopy (WCE) has emerged as an important diagnostic tool in this regard; this may soon become the gold standard. An important disadvantage of WCE is that the device may end up being impacted in strictures (which are not uncommon in CD); thus, it is best avoided in patients in whom these are suspected or known to be present.


Conservative management of small bowel obstruction

Conservative management of intestinal obstruction includes decompressing and resting the bowel, and correction of any physiologic derangements caused by the obstruction . Intravenous fluid (IV) resuscitation should be performed with isotonic fluid; aggressive replacement of electrolytes should only be done after adequate renal function is confirmed. A bladder catheter to closely monitor urine output is the minimum requirement for gauging the adequacy of resuscitation; other invasive measures, such as arterial cannulation or central venous pressure monitoring can be used depending on the clinical picture. Antibiotics are used to prevent intestinal overgrowth of bacteria and translocation across the bowel wall; these should have coverage against gram-negative organisms and anaerobes, with the exact agent used determined by local susceptibility and availability. Note that the presence of fever and leukocytosis should prompt inclusion of antibiotics in the initial treatment regimen.


Endoscopic Features of Crohn's Disease

The endoscopic appearance of Crohn's Disease (CD) is highly variable and changes based on disease activity and duration. Classically, CD is characterized by "skip lesions", i.e. areas of disease separated by normal mucosa; the inflammation often does not extend circumferentially. The rectum is usually spared, and the most severe lesions are usually seen in the cecum and right colon. In early/mild CD: - The colonic mucosa may appear endoscopically normal. - Small, punched-out aphthous ulcers may be seen. In moderate CD: - Aphthous ulcers coalesce into larger ulcers, which may take on the appearance of a star (stellate ulcers). In severe CD: - A cobblestone appearance (submucosal edema and injury) may be seen - Patients with severe disease may have large, linear and deep serpiginous ulcers


Histological Features of Crohn's Disease

The microscopic findings of CD can be highly variable; the following are the most characteristic: - Areas of chronic inflammation - Skip lesions - Transmural inflammation with multiple lymphoid aggregates - Non-caseating granulomas - Submucosal fibrosis Note that it is unusual to see all of the above histopathologic features in a single slide.


Legionellosis in Crohn's Disease

Infliximab is known to raise the risk of infection with intracellular pathogens, such as Mycobacterium tuberculosis, Listeria monocytogenes, Histoplasma capsulatum and Legionella pneumophila. Note that legionella pneumophila is readily diagnosable via a urinary antigen test; early recognition of the disease, and rapid empirical treatment with a fluoroquinolone or macrolide antibiotic significantly reduces mortality and morbidity.


Patients unresponsive to steroids

In the "step-up" approach to the therapy of Crohn's Disease, inability to achieve remission on corticosteroid therapy alone is an indication for progression into the next "step" - addition of an immunomodulatory drug (such as azathioprine). Adding azathioprine or mercaptopurine to a conventional glucocorticosteroid or budesonide should be considered when: - there are two or more inflammatory exacerbations in a 12-month period, or - the glucocorticosteroid dose cannot be tapered. In such circumstances, it is not acceptable to continue the steroid therapy alone.


Patients unresponsive to steroids

Budesonide and mesalasine are a first-line treatment in patients who are unable to tolerate conventional steroid treatment, who decline systemic corticosteroids, or in whom systemic corticosteroid treatment is contraindicated for another medical reason. The combination is not an acceptable second line treatment in patients who are unresponsive to conventional corticosteroids; in such individuals, a second line agent such as azathioprine or mercaptopurine should be considered.


Radiographic features of small bowel obstruction

Plain radiographs of the abdomen are 50% to 60% sensitive for detection of small bowel obstruction; features suggestive of this diagnosis include: - Dilated loops of small bowel, which are predominantly central - Three instances of dilatation over 3 cm - Visible valvulae conniventes - Fluid levels (in an erect radiograph - note that this is not the standard study) Obstruction may also present with the following features: - a gasless abdomen - the string-of-beads sign - small pockets of gas within a fluid-filled small bowel Note that Computerized Tomography (CT) is a more sensitive technique for detection of small bowel obstruction. In addition, this will demonstrate the underlying pathology in ~80% of cases.


Risks and Benefits of Biologics

A relatively new form of treatment, biologics have improved the quality of life of a significant number of patients with Crohn's Disease (CD). However, these agents are known to give rise to a variety of adverse effects, some of which are quite serious; these include: - Infections - Immunogenicity and loss of response - Injection and cytokine release reactions - Autoimmunity - Malignancies - Liver function abnormalities - Heart failure - Demyelination - Skin eruptions It should be appreciated that in CD, the risk-benefit profile of biologic therapy is greatly in favour of the drugs; however, as of the time of writing, most authorities recommend their use only in patients for whom other modalities of medical therapy have failed to show benefit. Note that monotherapy is usually prefered; combined drug regimens (including combination with steroids) are best avoided.


Smoking and Crohn's Disease

The relationship between smoking and inflammatory bowel disease (IBD) is a frequent source of confusion to both doctors and patients. This is because smoking exerts beneficial effects in individuals with ulcerative colitis (UC), but is deleterious in patients with Crohn's Disease (CD). Therefore, all patients diagnosed with CD should be strongly advised to stop smoking.


The step-up approach to treatment of Crohn's Disease

At the time of writing, most authorities recommend a sequential ('step-up') approach in the management of Crohn's Disease (CD); this is based on the principle of using the least toxic drugs first. In the step-up approach, first-line agents include corticosteroids, 5-aminosalicylic acid (5-ASA) and antibiotics; the next step involves addition of an immunomodulator. Surgery and biologic therapy is a last resort. Note that corticosteroids and immunomodulators do not appear to alter the long-term course of the disease; therefore, the possibility of starting off treatment with more potent agents (such as biologics) has been a subject of much discussion lately. While this has been termed the 'top-down' approach, it is yet to enter general practice.


Thiopurine Methyltransferase (TPMT) Levels

Azathioprine, 6-mercaptopurine (6-MP), and thioguanine are collectively known as thiopurines; they play an important role in the management of many different conditions, such as inflammatory bowel disease, acute lymphocytic leukaemia, and myasthenia gravis. Azathioprine, the parent drug, is metabolized into its active form via a pathway involving multiple enzymes, one of which is Thiopurine Methyltransferase (TPMT); the activity of this enzmye varies by individual due to genetic polymorphism. Thus, measurement of TPMT activity is encouraged prior to treatment with thiopurine drugs; patients with low activity (~10% prevalence) or especially absent activity (~0.3% prevalence) are at a higher risk of drug-induced bone marrow toxicity.


Toxic megacolon - when is surgery indicated?

Toxic Megacolon (TM) is a rare, but potentially lethal complication of Crohn's Disease (CD). Many authorities recommend initial medical management with intravenous corticosteroids and broad-spectrum antibiotics, with surgery indicated if distension persists or improvement is not observed on maximal medical therapy after 24 to 72 hours. However, other authorities recommend early surgery, as there is evidence that early intervention in patients without evidence of perforation has been shown to result in significantly lower mortality.


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