Extraintestinal manifestations of inflammatory bowel disease
Section snippets
Pathogenesis of extraintestinal manifestations
The pathogenesis of extraintestinal manifestations of IBD is not well understood. Immunologic mechanisms likely are responsible for most of the common extraintestinal manifestations. The concept of an autoimmune-based process is supported by the primarily immunologic derangement underlying the development of IBD and the increased risk of autoimmune diseases among patients with IBD [115]. The complex immunologic interactions between the host immune system and bacteria have been described in
Musculoskeletal manifestations
Musculoskeletal diseases constitute the most common extraintestinal manifestations seen in patients with IBD. These abnormalities can be grouped broadly into rheumatologic disorders and metabolic bone diseases.
Dermatologic manifestations
Cutaneous disorders associated with IBD occur in 15% of patients [50]. Erythema nodosum and pyoderma gangrenosum are the 2 most commonly encountered dermatologic manifestations of IBD. The prevalence of erythema nodosum is reported to be 10% to 20% in patients with IBD [50], [89]. The lesions appear as tender, red nodules, usually on the extensor surfaces of the lower extremities. Erythema nodosum correlates well with bowel disease activity and often occurs in conjunction with peripheral
Ophthalmologic manifestations
Ophthalmologic manifestations of IBD are reported to occur in 1.6% to 4.6% of patients with UC and 3.5% to 6.3% of patients with CD [50], [90], [105], [128]. Some of these manifestations may represent treatment-related complications rather than IBD-associated manifestations. Involvement of the vascular coats of the eye in IBD also highlights the influence of genetic, bacterial, and immunologic factors in the development of extraintestinal manifestations of IBD [22], [23], [118], [133].
The two
Hematologic manifestations
The most common hematologic complication of IBD is anemia, but abnormalities of all hematopoietic cell lines may be present. The anemia in patients with IBD may be a result of iron, vitamin B12, or folate deficiency; chronic disease; or autoimmune hemolysis. Factors contributing to the development of the various forms of anemia include chronic gastrointestinal blood loss, inadequate dietary iron intake or absorption, vitamin B12 malabsorption secondary to terminal ileal disease or ileal
Genitourinary and renal manifestations
The 3 most common genitourinary and renal manifestations of IBD occurring as direct results of bowel disease are nephrolithiasis, obstructive uropathy, and fistulization to the urinary tract. These complications occur in 4% to 23% of patients with IBD [6].
The prevalence of nephrolithiasis is reported to be 7% to 10% in patients with IBD [31], [43]. The two most common stone types are uric acid and calcium oxalate. Many factors are involved in the pathogenesis of renal stones in patients with
Cardiovascular manifestations
Rarely, patients with IBD may develop pleuropericarditis [98], [107]. The pathogenesis of pleuropericarditis is unknown, although certain medications (sulfasalazine and mesalamine derivatives) have been implicated in some cases [1], [54]. There does not appear to be any correlation between the underlying disease activity and such extraintestinal manifestation. Treatment of pleuropericarditis with NSAIDs should be weighed against the risk of exacerbating underlying IBD.
Pulmonary manifestations
Patients with IBD may develop alterations in pulmonary function, including an increase in functional reserve capacity and a decrease in diffusion capacity [34], [48]. These pulmonary function abnormalities seem to be more common in active disease and may parallel underlying disease activity [80], [121].
Other pulmonary diseases that have been described in association with IBD include fibrosing alveolitis, pulmonary vasculitis, apical fibrosis, bronchiectasis, bronchitis, bronchiolitis, and
Neurologic manifestations
Neurologic disorders reported to occur in patients with IBD include peripheral neuropathy, myopathy, vasculopathy, focal central nervous system defects, seizures, confusional episodes, meningitis, and syncope [44]. Associations with IBD have not been defined clearly. Similarly a possible association between cerebrovascular accidents and IBD has been suggested but not confirmed in a rigorous manner [61], [64].
Metastatic Crohn's disease
Metastatic CD refers to the direct involvement by the primary inflammatory process at sites outside of the gastrointestinal tract. The diagnosis of metastatic disease is based the identical histologic appearance to CD, including noncaseating granulomatous lesions. Other histologic findings may include necrobiosis and granulomatous perivasculitis [56]. Patients also may have a positive antineutrophil cytoplasmic antibody (pericytoplasmic pattern) [56].
Metastatic CD is a rare diagnosis, with the
Hepatobiliary manifestations
Many hepatobiliary diseases are associated with IBD. One important disease is primary sclerosing cholangitis, with a prevalence ranging from 2.4% to 7.5% in patients with IBD. Conversely, 75% of patients with PSC also have IBD, most commonly UC [132]. Other hepatobiliary diseases reported to occur in association with IBD include pericholangitis, steatosis, chronic hepatitis, cryptogenic cirrhosis, cholangiocarcinoma, and gallstone formation. These hepatobiliary manifestations of IBD are
Summary
Numerous extraintestinal diseases have been associated with IBD. The role of the gastrointestinal tract in host response to the foreign antigens present in the gut makes the enteric immune system highly susceptible to any external perturbation to the system. Dysregulation of the enteric immune response results in pathology in various organs outside of the gut. The site-specific manifestations of this immune response are not understood fully. Better understanding of the pathogenesis of IBD and
References (134)
- et al.
Cardiac hypersensitivity to 5-aminosalicylic acid
Lancet
(1989) - et al.
Improvement of arthritis/arthralgia after treatment with infliximab in a German prospective open-label multicenter trial in refractory Crohn's disease
Gastroenterology
(2001) Genitourinary complications of inflammatory bowel disease
Radiol Clin North Am
(1987)- et al.
A randomized trial of intravenous pamidronate and calcium and vitamin D in the treatment of osteoporosis associated with Crohn's disease
Gastroenterology
(2001) - et al.
A shared and unique peptide in the human colon, eye, and joint detected by a monoclonal antibody
Gastroenterology
(1994) - et al.
Production of immunoglobulin G and G1 antibodies to cytoskeletal protein by lamina propria cells in ulcerative colitis
Gastroenterology
(1995) - et al.
Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans
Gastroenterology
(1993) - et al.
Erythema multiforme and Crohn's disease of the large intestine
Gastroenterology
(1972) - et al.
The histocompatibility antigen (HL-A 27) and disease
Semin Arthritis Rheum
(1975) Pyoderma gangrenosum
Lancet
(1998)
Longterm oral contraceptive use and bone mineral density in corticosteroid treated Crohn's disease
Gastroenterology
A shared and unique epitope(s) on human colon, skin, and biliary epithelium detected by a monoclonal antibody
Gastroenterology
Vitamin D deficiency and bone disease in patients with Crohn's disease
Gastroenterology
Activation of blood coagulation in Crohn's disease: Increased plasma fibrinopeptide A levels and enhanced generation of monocyte tissue factor activity
Gastroenterology
Clinical patterns in Crohn's disease: A statistical study of 615 cases
Gastroenterology
Unfractioned heparin in the therapy of patients with highly active inflammatory bowel disease
Am J Gastroenterol
Tropomyosin isoforms in intestinal mucosa: Production of autoantibodies to tropomyosin isoforms in ulcerative colitis
Gastroenterology
Deep venous thrombosis and pulmonary embolism in inflammatory bowel disease: Coincidence or cause?
Gastroenterology
The pancreas as a site of granulomatous inflammation in Crohn's disease
Gastroenterology
Treatment of pyoderma gangrenosum complicating Crohn's disease with infliximab
Gastroenterology
Cerebral vascular events associated with ulcerative colitis in children
Pediatr Neurol
Sweet's syndrome: A clinicopathologic review of twenty-nine cases
J Am Acad Dermatol
Coagulation studies in ulcerative colitis and Crohn's disease
Gastroenterology
The factor V Leiden mutation increases the risk of venous thrombosis in patients with inflammatory bowel disease
Gastroenterology
Long-term survival in systemic amyloid A amyloidosis complicating Crohn's disease
Gastroenterology
Asymptomatic sacroiliitis in inflammatory bowel disease: Assessment by computed tomography
Clin Imaging
Colchicine therapy of the renal amyloidosis of ulcerative colitis
Gastroenterology
Course of gut inflammation in spondyloarthropathies and therapeutic consequences
Baillieres Clin Rheumatol
A four-year longitudinal study of bone loss in patients with inflammatory bowel disease
Bone Miner
Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease
Gastroenterology
Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis
Gastroenterology
Autoimmune hemolytic anemia in ulcerative colitis: Report of three cases, review of the literature, and evaluation of modes of therapy
Dig Dis Sci
Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease
Aliment Pharmacol Ther
Oral metronidazole, an effective treatment for Sweet's syndrome in a patient with associated inflammatory bowel disease
J Rheumatol
Crohn's ileitis complicated by amyloidosis: Observations and therapeutic considerations
J Clin Gastroenterol
Sweet's syndrome associated with Crohn's disease
Acta Derm Venereol
Sweet's syndrome and pyoderma gangrenosum associated with ulcerative colitis
Acta Derm Venereol
Early sacroiliitis in patients with spondyloarthropathy: Evaluation with dynamic gadolinium-enhanced MR imaging
Radiology
The sacroiliac joint in the spondyloarthropathies
Curr Opin Rheumatol
Efficacy of thalidomide in the treatment of refractory ankylosing spondylitis
Arthritis Rheum
Ocular manifestations of immunological and rheumatological inflammatory disorders
Curr Opin Ophthalmol
Cytokine-dependent modulation of oral tolerance in a murine model of autoimmune uveitis
Ann N Y Acad Sci
T cell mechanisms in experimental autoimmune uveoretinitis: Susceptibility is a function of the cytokine response profile
Eye
Hormone replacement therapy prevents bone loss in patients with inflammatory bowel disease
Gut
The role of leukopenia in the 6-mercaptopurine-induced remission of refractory Crohn's disease
Am J Gastroenterol
Osteoporosis in patients with inflammatory bowel disease
Gut
Relationship of extraintestinal involvements in inflammatory bowel disease: New insights into autoimmune pathogenesis
Dig Dis Sci
Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype
N Engl J Med
The production and characterization of monoclonal antibodies to a human colonic antigen associated with ulcerative colitis: Cellular localization of the antigen by using the monoclonal antibody
J Immunol
Nephrolithiasis as a complication of ulcerative colitis and regional enteritis
Ann Intern Med
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