Skin and eye manifestations of inflammatory bowel disease
- Mark A Peppercorn, MD
Mark A Peppercorn, MD
- Professor of Medicine
- Harvard Medical School
- Adam S Cheifetz, MD
Adam S Cheifetz, MD
- Associate Professor of Medicine
- Harvard Medical School
- Section Editors
- Paul Rutgeerts, MD, PhD, FRCP
Paul Rutgeerts, MD, PhD, FRCP
- Section Editor — Inflammatory Bowel Disease
- Emeritus Professor of Medicine
- University Hospital, Leuven, Belgium
- Jonathan Trobe, MD
Jonathan Trobe, MD
- Section Editor — Ophthalmology
- Professor of Ophthalmology and Visual Sciences
- Professor of Neurology
- University of Michigan Kellogg Eye Center
A variety of conditions arise outside of the gastrointestinal tract that are associated with inflammatory bowel disease (IBD); these are termed extraintestinal manifestations of IBD (table 1). Some of these entities are associated more with Crohn disease than ulcerative colitis, including oral lesions, clubbing, gallstones, pancreatitis, and renal and urologic conditions such as calcium oxalate stones and amyloidosis. Other extraintestinal findings, including skin and eye disorders, are seen with equal frequency in both Crohn disease and ulcerative colitis and may dominate the clinical presentation. Some of the extraintestinal manifestations mirror the course of the luminal disease, while others are unrelated to gastrointestinal activity.
The exact prevalence of extraintestinal findings in patients with IBD has not been extensively studied, although they appear to be common. A study using administrative health data at a tertiary center in Canada estimated that a total of 6 percent of patients with IBD had one of six major extraintestinal diseases that were studied . However, a study from the Mayo Clinic found that 40 percent of IBD patient had one or more extraintestinal manifestations .
The pathogenesis of extraintestinal manifestations is incompletely understood.
A variety of skin disorders may be seen in association with inflammatory bowel disease (IBD).
Erythema nodosum — Erythema nodosum is the cutaneous disorder most frequently seen with ulcerative colitis and Crohn disease, occurring in 4 percent of patients . It typically appears as raised, tender, red or violet subcutaneous nodules that are 1 to 5 cm in diameter (picture 1). The nodules are most commonly located on the extensor surfaces of the extremities, particularly over the anterior tibial area. Biopsy of these lesions shows focal panniculitis, although the diagnosis is most often clinical and biopsy is rarely required. (See "Erythema nodosum".)
- Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol 2001; 96:1116.
- Ricart E, Panaccione R, Loftus EV Jr, et al. Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study. Inflamm Bowel Dis 2004; 10:207.
- Farhi D, Cosnes J, Zizi N, et al. Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients. Medicine (Baltimore) 2008; 87:281.
- Powell FC, Schroeter AL, Su WP, Perry HO. Pyoderma gangrenosum: a review of 86 patients. Q J Med 1985; 55:173.
- Keltz M, Lebwohl M, Bishop S. Peristomal pyoderma gangrenosum. J Am Acad Dermatol 1992; 27:360.
- Thornton JR, Teague RH, Low-Beer TS, Read AE. Pyoderma gangrenosum and ulcerative colitis. Gut 1980; 21:247.
- Agarwal A, Andrews JM. Systematic review: IBD-associated pyoderma gangrenosum in the biologic era, the response to therapy. Aliment Pharmacol Ther 2013; 38:563.
- von den Driesch P, Gomez RS, Kiesewetter F, Hornstein OP. Sweet's syndrome: clinical spectrum and associated conditions. Cutis 1989; 44:193.
- Chiu G, Rajapakse CN. Cutaneous polyarteritis nodosa and ulcerative colitis. J Rheumatol 1991; 18:769.
- Najarian DJ, Gottlieb AB. Connections between psoriasis and Crohn's disease. J Am Acad Dermatol 2003; 48:805.
- Lee FI, Bellary SV, Francis C. Increased occurrence of psoriasis in patients with Crohn's disease and their relatives. Am J Gastroenterol 1990; 85:962.
- Scarpa R, Manguso F, D'Arienzo A, et al. Microscopic inflammatory changes in colon of patients with both active psoriasis and psoriatic arthritis without bowel symptoms. J Rheumatol 2000; 27:1241.
- Fidder H, Schnitzler F, Ferrante M, et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut 2009; 58:501.
- Cullen G, Kroshinsky D, Cheifetz AS, Korzenik JR. Psoriasis associated with anti-tumour necrosis factor therapy in inflammatory bowel disease: a new series and a review of 120 cases from the literature. Aliment Pharmacol Ther 2011; 34:1318.
- Cheesbrough MJ. Epidermolysis bullosa acquisita and Crohn's disease. Br J Dermatol 1978; 99:53.
- Burgdorf W. Cutaneous manifestations of Crohn's disease. J Am Acad Dermatol 1981; 5:689.
- Tweedie JH, McCann BG. Metastatic Crohn's disease of thigh and forearm. Gut 1984; 25:213.
- Abide JM. Metastatic Crohn disease: clearance with metronidazole. J Am Acad Dermatol 2011; 64:448.
- Abbas AM, Almukhtar RM, Loftus EV Jr, et al. Risk of melanoma and non-melanoma skin cancer in ulcerative colitis patients treated with thiopurines: a nationwide retrospective cohort. Am J Gastroenterol 2014; 109:1781.
- Ariyaratnam J, Subramanian V. Association between thiopurine use and nonmelanoma skin cancers in patients with inflammatory bowel disease: a meta-analysis. Am J Gastroenterol 2014; 109:163.
- Kappelman MD, Farkas DK, Long MD, et al. Risk of cancer in patients with inflammatory bowel diseases: a nationwide population-based cohort study with 30 years of follow-up evaluation. Clin Gastroenterol Hepatol 2014; 12:265.
- Singh S, Nagpal SJ, Murad MH, et al. Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2014; 12:210.
- Long MD, Martin CF, Pipkin CA, et al. Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease. Gastroenterology 2012; 143:390.
- Petrelli EA, McKinley M, Troncale FJ. Ocular manifestations of inflammatory bowel disease. Ann Ophthalmol 1982; 14:356.
- Lyons JL, Rosenbaum JT. Uveitis associated with inflammatory bowel disease compared with uveitis associated with spondyloarthropathy. Arch Ophthalmol 1997; 115:61.
- Suhler EB, Smith JR, Wertheim MS, et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol 2005; 123:903.
- Ruby AJ, Jampol LM. Crohn's disease and retinal vascular disease. Am J Ophthalmol 1990; 110:349.
- Knox DL, Snip RC, Stark WJ. The keratopathy of Crohn's disease. Am J Ophthalmol 1980; 90:862.
- Schulman MF, Sugar A. Peripheral corneal infiltrates in inflammatory bowel disease. Ann Ophthalmol 1981; 13:109.
- Kaneko E, Nawano M, Honda N, et al. Ulcerative colitis complicated by idiopathic central serous chorioretinopathy with bullous retinal detachment. Dig Dis Sci 1985; 30:896.