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Extraintestinal manifestations of inflammatory bowel disease

Extraintestinal manifestations of inflammatory bowel disease
Common extraintestinal manifestations
Musculoskeletal
Arthritis – Colitic type, ankylosing spondylitis, isolated joint involvement such as sacroiliitis.
Hypertrophic osteoarthropathy – Clubbing, periostitis, metastatic Crohn disease.
Miscellaneous – Osteoporosis, aseptic necrosis, polymyositis, osteomalacia.
Skin and mouth
Reactive lesions – Erythema nodosum, pyoderma gangrenosum, aphthous ulcers, vesiculopustular eruption, cutaneous vasculitis, neutrophilic dermatosis, metastatic Crohn disease, epidermolysis bullosa acquisita.
Specific lesions – Fissures and fistulas, oral Crohn disease, drug rashes.
Nutritional deficiency – Acrodermatitis enteropathica (zinc), purpura (vitamins C and K), glossitis (vitamin B), hair loss and brittle nail (protein).
Associated diseases – Vitiligo, psoriasis, amyloidosis, epidermolysis bullosa acquisita.
Hepatobiliary
Specific complications – Sclerosing cholangitis (large-duct or small-duct), bile duct carcinoma, cholelithiasis.
Associated inflammation – Autoimmune chronic active hepatitis, pericholangitis, portal fibrosis and cirrhosis, granuloma in Crohn disease.
Metabolic – Fatty liver, gallstones associated with ileal Crohn disease.
Ocular
Uveitis iritis, episcleritis, scleromalacia, corneal ulcers, retinal vascular disease, retrobulbar neuritis, Crohn keratopathy.
Metabolic
Growth retardation in children and adolescents, delayed sexual maturation.
Less common extraintestinal manifestations
Blood and vascular
Anemia due to iron, folate, or vitamin B12 deficiency or autoimmune hemolytic anemia, anemia of chronic disease, thrombocytopenic purpura; leukocytosis and thrombocytosis; thrombophlebitis and thromboembolism, arteritis and arterial occlusion, polyarteritis nodosa, Takayasu arteritis, cutaneous vasculitis, anticardiolipin antibody, hyposplenism.
Renal and genitourinary tract
Urinary calculi (oxalate stones in ileal disease), local extension of Crohn disease involving ureter or bladder, amyloidosis, drug-related nephrotoxicity.
Renal tubular damage with increased urinary excretion of various enzymes (eg, beta N-acetyl-D-glucosaminidase).
Neurologic
Up to 3% of patients may have non-iatrogenic neurologic involvement, including peripheral neuropathy, myelopathy, vestibular dysfunction, pseudotumor cerebri, myasthenia gravis, and cerebrovascular disorders. Incidence equal in ulcerative colitis and Crohn disease. These disorders usually appear 5 to 6 years after the onset of inflammatory bowel disease and are frequently associated with other extraintestinal manifestations.
Airway and parenchymal lung disease
Pulmonary fibrosis, vasculitis, bronchitis, necrobiotic nodules, acute laryngotracheitis, interstitial lung disease, sarcoidosis. Abnormal pulmonary function tests without clinical symptoms are common (up to 50% of cases).
Cardiac
Pericarditis, myocarditis, endocarditis, and heart block – More common in ulcerative colitis than in Crohn disease; cardiomyopathy, cardiac failure due to anti-TNF therapy.
Pericarditis may also occur from sulfasalazine/5-aminosalicylates.
Pancreas
Acute pancreatitis – More common in Crohn disease than in ulcerative colitis. Risk factors include 6-mercaptopurine and 5-aminosalicylate therapy, duodenal Crohn disease.
Autoimmune
Drug-induced lupus and autoimmune diseases secondary to anti-TNF-alpha therapy.
Positive ANA, anti-double-stranded DNA, cutaneous and systemic manifestations of lupus.
TNF: tumor necrosis factor; ANA: antinuclear antibody; DNA: deoxyribonucleic acid.
Modified from: Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: New insights into autoimmune pathogenesis. Dig Dis Sci 1999; 44:1.
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