Pathophysiology of Crohn’s disease
1) Crohn’s disease is marked by transmural inflammatory disease of the GI tract (may involve other organs) GI involvement – 2) anorectum (15%) 3) colon only (20% and typically in older age presentation) 4) small intestine only (15%) 5) mainly ileum and cecum (50% and especially in young presentation 6) can occasionally involve stomach, esophagus, and mouth  Extraintestinal involvement of Crohn’s disease– 7) arthritis (20%) 8) erythema nodosum 9) uveitis 10) ankylosing spondylitis (10%)
Signs and Symptoms
1) abdominal pain (relieved by defecation) 2) diarrhea 3) fever 4) weight loss 5) growth retardation 6) intestinal obstruction 7) bowel perforation 8) palpable right lower quadrant mass 9) fecaluria and pneumonuria (feces and air from urethra, aka “bubbles in urine”)
Characteristic Test Findings
Barium enema – 1) string sign, owing to strictures 2) “cobblestoning” 3) skip areas (disease is discontinuous) 4) thickened and edematous bowel walls 5) aphthous (superficial) ulcers in mucosa 6) deep ulcers and fissures in mucosa  Laboratory – 7) leukocytosis 8) hypocalcemia 9) hypoalbuminemia 10) pellagra (niacin deficiency) 11) megaloblastic anemia (vitamin B12 deficiency) 12) antibodies against Saccharomyces cerevisiae (ASCA) in 70% of patients
Histology/Gross Pathology
1) transmural inflammation is one of halllmarks of Crohn’s disease 2) transmural nodular lymphoid aggregates and fibrosis 3) mesenteric fat wraps 4) noncaseating granulomas 5) pneumatosis cystoides intestinalis (air in bowel wall)
Associated Conditions
1) adenocarcinoma of small bowel (100 times increased risk) 2) sclerosing cholangitis 3) cholelithiasis 4) amyloidosis 5) oxalate kidney stones 6) culture of Pseudomonas and atypical mycobacteria (role is unknown) from small bowel lesions 7) most patients have smoking history (role is unknown)
Biochemistry
1) cause of disease is unknown 2) immune-mediated damage by cytoxic T cells sensitized to outside antigen in genetically susceptible patients may have a role
Inheritance/Edpidemiology
1) more common in patients of European descent, especially Jews 2) female to male, 1.6:1 3) strong family predisposition exists 4) susceptibility loci on chromosomes 16 and 12
Treatment
1) corticosteroids 2) metronidazole (for perianal disease) 3) sulfasalazine 4) cyclosporine 5) 6-mercaptopurine 6) anti-TNF-alpha substances 7) surgical resection of strictures and obstruction only when absolutely required (to grossly normal margins) 8) integrative techniques used include acupuncture, medical hypnosis, and herbals and supplements
Tips for USMLE
hallmarks are transmural involvement, skip lesions, and cobblestoning.
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