Although researchers are still probing the etiology of Crohn’s disease, possible causes include allergies and other immune disorders, lymphatic obstruction, and infection (although no infecting organism has been isolated). Genetic factors may also play a role: Crohn’s disease sometimes occurs in monozygotic twins, and up to 5% of patients with the disease have one or more affected relatives. However, no simple pattern of inheritance has been identified.

Inflammation spreads slowly and progressively, beginning with lymphadenia and obstructive lymphedema in the submucosa, where Peyer’s patches develop in the intestinal mucosa. Lymphatic obstruction causes edema, with mucosal ulceration and development of fissures, abscesses and, occasionally, granulomas. The mucosa may acquire a characteristic “cobblestone” look.

As the disease progresses, fibrosis occurs, thickening the bowel wall and narrowing the lumen. Serositis (serosal inflammation) also develops, causing inflamed bowel loops to adhere to other diseased or normal loops. This may result in bowel shortening. Because inflammation usually occurs segmentally, the bowel may become a patchwork of healthy and diseased segments. Eventually, the diseased parts of the bowel become thicker, more narrow, and shorter.

Anal fistula, resulting from severe diarrhea and enzymatic corrosion of the perineal area, is the most common complication. A perineal abscess may also develop during the active inflammatory state. Fistulas may develop to the bladder or vagina or even to the skin in an old scar area. Other complications include intestinal obstruction, nutritional deficiencies (caused by malabsorption and maldigestion) and, rarely, peritonitis.

Generally, the patient reports signs and symptoms of gradual onset, marked by periods of remission and exacerbation. Because signs and symptoms may be intermittent, he may have postponed seeking medical attention for some time.

The patient typically complains of fatigue, fever, abdominal pain, diarrhea (usually without obvious bleeding) and, occasionally, weight loss. Questioning may reveal that his diarrhea worsens after emotional upset or after ingestion of poorly tolerated foods, such as milk, fatty foods, and spices.

The patient with regional enteritis, often a young adult, may report similar signs and symptoms as well as anorexia, nausea, and vomiting. Typically, this patient describes his abdominal pain as steady, colicky, or cramping. It usually occurs in the right lower abdominal quadrant. On inspection, the patient’s stool may appear soft or semiliquid, without gross blood (a distinguishing clinical feature from the bloody diarrhea seen in ulcerative colitis). Palpation may reveal tenderness in the right lower abdominal quadrant; it may also disclose an abdominal mass, indicating adherent loops of bowel.

Like patients with ulcerative colitis, patients with Crohn’s disease and Crohn’s colitis may develop extraintestinal symptoms. Gallstones caused by malabsorption of bile salts and nephrolethiases with urate or calcium oxatate stones can develop. Oral aphthous lesions are common.