The natural history of fistulizing Crohn's disease: A population-based study

Schwartz, Doron; Loftus, E V; Tremaine, WJ; Panaccione, Remo; Sandborn, W.J.

doi:10.1016/s1590-8658(00)80117-6

Cited by 12 publications

(21 citation statements)

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“…1 Although the introduction of anti-tumour necrosis factor (TNF) a antibodies has offered an important advance in the treatment of fistulising Crohn's disease, 2 3 the management of this complication remains a major therapeutic challenge. Fistulae may occur in Crohn's disease as complications of surgery or abscess formation but more often they develop spontaneously as a result of active luminal disease.…”

mentioning

confidence: 99%

Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn's disease

Kirkegaard

Hansen²,

Bruun³

et al. 2004

Gut

188

168

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Background: Fistulae are a troublesome complication of Crohn's disease but little is known of the final effector molecules responsible for matrix degradation. Although matrix metalloproteinases (MMPs) have been strongly implicated in tissue injury in Crohn's disease, their role in fistula formation is unknown. Aim: To determine the expression pattern of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in fistulae of patients with Crohn's disease. Patients and methods: Resected fistula specimens were obtained from patients with Crohn's disease (n = 11) and classified according to the predominant histological features-that is, acute versus chronic inflammation. Patients with fistulae due to other diseases (n = 9) and normal colon (n = 5) served as controls. MMP and TIMP protein expression was measured by single or double labelled immunohistochemistry, and mRNA expression by in situ hybridisation. MMP activity was measured by gelatin zymography. Results: Compared with normal colon, strong MMP-3 expression was consistently observed in fistulae in Crohn's disease, irrespective of the stage of inflammatory activity. MMP-3 transcripts and protein were localised in large mononuclear cells and fibroblasts. MMP-9 transcripts and protein were expressed in granulocytes and only in fistulae with acute inflammation. Staining for MMP-1 and MMP-7 was weak and negative for MMP-10, whereas MMP-2 was equally expressed in normal colon and fistulae. TIMP-1, TIMP-2, and TIMP-3 expression was low in all samples. Similar expression patterns were found in fistulae of the disease control group. Fistulae also expressed active MMP-2 and MMP-9, as measured by gelatin zymography. Conclusion: MMP-3 and MMP-9 are markedly upregulated in intestinal fistulae and may contribute to fistula formation through degradation of the extracellular matrix, irrespective of the underlying disease process.

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confidence: 99%

Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn's disease

Kirkegaard

Hansen²,

Bruun³

et al. 2004

Gut

188

168

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“…1 The risk of developing Crohn's perianal fistulas increases the more distal the disease involvement. The typical course for patients with perianal Crohn's disease includes long time periods of actively draining fistulas and frequent relapses.…”

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confidence: 99%

“…1 The risk of developing Crohn's perianal fistulas increases the more distal the disease involvement. 1,2,13 Approximately, 5% of individuals will have isolated perianal disease without any evidence of luminal inflammation. 2 The frequency of perianal fistulas in patients with Crohn's disease range from 17% to 43% in reports from referral centers.…”

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confidence: 99%

“…Only 12% of patients with isolated ileal disease develop a perianal fistula compared with 92% of patients with rectal involvement. 1 This underscores the difficulty in making the diagnosis of Crohn's disease in patients who present with only perianal pathology. [3][4][5][6][7][8][9][10][11][12] Three population-based studies have shown similar rates of perianal fistulas between 21% and 23% in patients with Crohn's disease.…”

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confidence: 99%

“…1 Nearly, one-third of the patients required a major operation such as a proctectomy, proctocolectomy or diverting ileostomy because of refractory disease. 1 Nearly, one-third of the patients required a major operation such as a proctectomy, proctocolectomy or diverting ileostomy because of refractory disease.…”

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confidence: 99%

See 2 more Smart Citations

Guidelines for the Multidisciplinary Management of Crohnʼs Perianal Fistulas

Schwartz

Ghazi

Regueiro

et al. 2015

Inflammatory Bowel Diseases

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Fistula response to methotrexate in Crohn's disease: a case series

Marion

2003

Aliment Pharmacol Ther

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Summary Background : Controlled trials have demonstrated the efficacy of methotrexate in the induction and maintenance of remission in luminal Crohn's disease; however, its effect on fistulizing disease is unknown. Aim : To describe the response to methotrexate therapy in a series of patients with fistulizing Crohn's disease. Methods : A retrospective chart review was conducted of all patients with Crohn's disease receiving methotrexate in one practice. The response of patients with fistulizing and luminal disease was assessed using clinical and laboratory criteria. Fistula response was categorized as either complete or partial closure. Results : Thirty‐seven courses of methotrexate therapy were given to 33 patients with luminal and/or fistulizing Crohn's disease. In 16 patients with fistulas, four (25%) had complete closure, five (31%) had partial closure and all had failed or were intolerant to 6‐mercaptopurine therapy. Overall, response to methotrexate was seen in 23 of 37 (62%) treatment courses in patients with luminal and/or fistulizing Crohn's disease. Two of the 33 patients (6%) had a significant adverse event. Conclusions : In this case series, 56% of patients with Crohn's fistulas on methotrexate showed a complete or partial response to therapy. Further studies are needed to confirm the role of methotrexate alone, and in combination with other therapies, for the treatment of fistulizing Crohn's disease.

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The natural history of fistulizing Crohn's disease: A population-based study

Cited by 12 publications

References 0 publications

Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn's disease

Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn's disease

Guidelines for the Multidisciplinary Management of Crohnʼs Perianal Fistulas

Fistula response to methotrexate in Crohn's disease: a case series

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