Showing posts with label Crohn#039;s. Show all posts
Showing posts with label Crohn#039;s. Show all posts

Crohn's disease - 2011 review

Crohn's disease is a chronic inflammatory condition affecting the GI tract at any point from the mouth to the rectum.

Symptoms and signs may consist of:

- diarrhea
- abdominal pain
- fever
- weight loss
- abdominal masses
- anemia

Extraintestinal manifestations of Crohn's disease include:

- osteoporosis
- inflammatory arthropathies
- scleritis
- nephrolithiasis
- cholelithiasis
- erythema nodosum

Laboratory findings

Acute phase reactants, such as CRP and ESR, are often increased with inflammation and may correlate with disease activity.

Levels of vitamin B12, folate, albumin, prealbumin, and vitamin D can help assess nutritional status.

Procedures often used to diagnose Crohn's disease:

- colonoscopy with ileoscopy
- capsule endoscopy
- computed tomography (CT) enterography
- small bowel follow-through

Diagnostic tools for extraintestinal manifestations or complications (e.g., abscess, perforation):

- ultrasonography
- computed axial tomography (CT)
- scintigraphy
- MRI

Medical management

Mesalamine products are used for mild to moderate colonic disease. Antibiotics (e.g., metronidazole, fluoroquinolones) are often used for treatment.

Patients with moderate to severe Crohn's disease are treated with:

- corticosteroids
- azathioprine
- 6-mercaptopurine
- anti-tumor necrosis factor agents (e.g., infliximab, adalimumab)

References

Diagnosis and management of Crohn's disease. Wilkins T, Jarvis K, Patel J. Am Fam Physician. 2011 Dec 15;84(12):1365-75.

Image source: Colon (anatomy), Wikipedia, public domain.

Vedolizumab (anti-integrin) is effective for treatment of ulcerative colitis and Crohn's disease

The integrin superfamily consists of 30 proteins that promote cell-cell or cell-matrix interactions. The name integrins derives from the idea that they coordinate (i.e., "integrate") signals.

All integrins are cell surface proteins composed of 2 polypeptide chains, α and β. Integrins are classified into several subfamilies based on the β chains.



Lymphocyte Trafficking. This video describes how lymphocytes travel through the blood stream and into a lymph node. This video is from: Janeway's Immunobiology, 7th Edition, Murphy, Travers, & Walport. Source: Garland Science.

7 Integrin, a cell adhesion molecule, is present in the form of α4β7 integrin or αEβ7 integrin. α4β7 Integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, mucosal addressin cell adhesion molecule-1, which is preferentially expressed in gut-associated lymphoid tissues.

Vedolizumab is a monoclonal antibody being developed by a subsidiary of Takeda Pharmaceuticals for the treatment of ulcerative colitis and Crohn's disease. It binds to integrin α4β7 (LPAM-1, lymphocyte Peyer's patch adhesion molecule 1). Blocking the α4β7 integrin results in gut-selective anti-inflammatory activity by blockade of lymphocyte trafficking.

Sunanda Kane, M.D., a gastroenterologist at Mayo Clinic specializing in the care and evaluation of patients with IBD, discusses two articles recently published in NEJM that found patients with ulcerative colitis or Crohn's disease benefited from treatment with vedolizumab compared with placebo. She discusses how vedolizumab is different than other drugs currently used to treat IBD.



Recruitment of Leukocytes to Sites of Infection can be remembered by the mnemonic: "SIP of wine":

S
electins
Integrins
Penetration of of the basement membrane (BM) by PMN

Selectins are first in the chain of events. They upregulate TNF and IL-1. Integrins cause release of VCAM and VLA.

Adhesion molecules, 3 groups are remembered by the mnemonic SIS:

S
electins
Integrins
Superfamily Ig

References:

http://www.ncbi.nlm.nih.gov/pubmed/21047673
http://www.nejm.org/doi/full/10.1056/NEJMe1307415
http://www.nejm.org/doi/full/10.1056/NEJMoa1215739
http://www.nejm.org/doi/full/10.1056/NEJMoa1215734