1. Prognosis for peripheral disease is generally good. Chronic disease will develop in only 10% of patients.

2. Prognosis for axial disease is similar to that of ankylosing spondylitis.

II. Enteropathic reactive arthritis is a form of spondyloarthritis that typically occurs 1 to 3 weeks after an acute intestinal infection with certain arthritogenic bacteria (e.g., Shigella flexneri, Campylobacter jejuni, and some Salmonella and Yersinia species). It is usually seen in a patient positive for HLA-B27. Occasionally, diarrhea can be subclinical, making the diagnosis less obvious. The large joints of the lower extremities are usually affected, and full Reiter's syndrome can occur (see Chapter.36). Antibiotics have not been shown to alter the disease course.

III. Other spondyloarthritides Less prominent intestinal symptoms may occur in other forms of spondyloarthritis. In fact, endoscopic studies of the colon and ileum have shown macroscopic inflammatory lesions in 18% to 50% of patients with spondyloarthritis. The prevalence of such lesions is even higher by histologic criteria. Acute inflammatory changes resemble those of bacterial enteritis, and chronic inflammatory lesions are similar to those seen in Crohn's disease. Chronic gut inflammation is associated with more severe and persistent arthritis or spondylitis, and the condition occasionally evolves into clinically apparent Crohn's disease.

IV. Whipple's disease. This rare multisystem disease has been recently shown to be caused by a gram-positive actinomycete ( Tropheryma whippelii).

A. Clinical presentation. Whipple's disease affects men ages 35 to 60. It is characterized by the insidious onset of fever, arthritis, malabsorption, generalized lymphadenopathy, skin hyperpigmentation, uveitis, or progressive encephalopathy. The typically symmetric, transient, and nondeforming polyarthritis occurs in 80% of the patients and may precede enteritis by several years.

B. Diagnosis. Until recently, the diagnosis depended on duodenal biopsy and the demonstration of deposits in lamina propria macrophages that stained with periodic acid-Schiff (PAS). In other tissues, electron microscopic demonstration of characteristic rod-shaped bacilli was necessary. However, a specific diagnosis can now be made from tissue and even from peripheral blood, with use of the polymerase chain reaction to verify the presence of the causative microorganism.

C. Treatment. Antibiotic therapy is effective, but relapses can occur. Parenteral antibiotic therapy with penicillin G (1.2 million U/d) and streptomycin (1 g/d) is recommended for the first 2 weeks, followed by oral trimethoprim/sulfamethoxazole (160/800 mg twice daily) for 1 to 2 years. Agents that do not cross the blood-brain barrier should probably be avoided.

V. Intestinal bypass arthritis (arthritis-dermatitis syndrome) Jejunoileostomy or jejunocolostomy, performed for morbid obesity, often results (after 2 to 30 months) in the arthritis-dermatitis syndrome. A symmetric and migratory nondeforming polyarthritis of the large joints is observed in 20% to 80% of patients and may become chronic in 25%. Other features include erythema nodosum, macular and vesiculopustular skin lesions, Raynaud's phenomenon, serositis, glomerulonephritis, retinal vasculitis, and superficial thrombophlebitis. The syndrome has been attributed to bacterial overgrowth in the blind loop with alteration of bowel permeability and formation of bacterial antigen-containing immune complexes.

A. Laboratory studies, including evaluation of peripheral blood, synovial fluid, stool, and joint radiography are not diagnostically helpful.

B. Treatment. NSAIDs are effective against arthritis, but courses of oral antibiotics (e.g., with tetracycline, clindamycin, or metronidazole) may offer additional help. Nevertheless, only surgical re-anastomosis of the bypassed intestinal segment provides a cure. By 1985, bypass surgery for obesity was largely abandoned, so the clinician is unlikely to see further cases.

VI. Celiac disease, or gluten-induced enteropathy, is a rare disease characterized by mucosal abnormalities of the small intestine and malabsorption. Association with many autoimmune disorders has been noted, and arthritis occurs in fewer than 50% of patients.

A. Clinical presentation and diagnosis. Arthritis is usually polyarticular and often involves hand and wrist joints. Half of patients have no intestinal symptoms. In that clinical scenario, the presence of malaise, weight loss, and low serum folate levels can be very helpful in diagnosis. Bone pain resulting from osteomalacia may also occur.

B. Treatment. Arthritis usually responds well to a gluten-free diet.

VII. Pancreatic disease. Chronic pancreatitis or pancreatic cancer can sometimes be associated with nodular subcutaneous fat necrosis and arthritis. A history of alcoholism is common.

A. Laboratory studies. Serum pancreatic enzymes are usually elevated. Synovial fluid may contain calcified necrotic fat particles, which can be confused with negatively birefringent crystals on polarized microscopy.

B. Treatment. Prompt diagnosis is essential, and therapy should be focused on the underlying pancreatic disease.

VIII. Syndromes associated with vasculitis such as Henoch-Schonlein purpura and systemic lupus erythematosus, can give rise to both abdominal pain (caused by involvement of mesenteric arteries) and arthritis. Diagnostic and treatment efforts are directed at the primary disease.

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