SID：银屑病患者克罗恩病风险增4倍

北卡罗来纳州罗利(EGMN)——哈佛大学医学院的Wenqing Li博士在美国皮肤病研究学会(SID)年会上报告称，银屑病患者罹患克罗恩病的风险增加4倍，且银屑病关节炎患者风险更高。

研究者指出，这项对174,646例护士健康研究(NHS)和NHSⅡ受试者的前瞻性随访研究结果与全基因组关联研究结果一致，后者发现银屑病和炎性肠病存在共同的易感基因，特别是涉及白介素-23通路的基因。对银屑病和克罗恩病发病机制的进一步研究将最终揭示干预两种疾病发生和活动的新靶点。值得注意的是，银屑病患者溃疡性结肠炎发生风险并无显著增加，提示与克罗恩病相比，银屑病与溃疡性结肠炎重叠通路可能较少。

对NHS和NHSⅡ研究受试女性的随访时间分别为1996~2008年和1991 ~ 2005年。随访期间，克罗恩病和溃疡性结肠炎新发病例分别为188例和240例，所有炎性肠病诊断均由两名胃肠病医生盲法确认。对上述两项研究的合并分析包括47,618(人·年)银屑病患者前瞻性随访和47,618(人·年)非银屑病患者随访。校正年龄因素后，银屑病患者克罗恩病风险增加3.74倍。校正体重指数、体力活动、吸烟状况、饮酒、口服避孕药使用、绝经后激素治疗以及年龄等因素后的多变量分析显示，银屑病仍然是克罗恩病独立风险因素，相对风险增加3.5倍。对5,661(人·年)银屑病和银屑病关节炎共病患者前瞻性随访结果的多变量分析显示，受累患者克罗恩病风险增加6.8倍。

鉴于银屑病患者与非银屑病患者相比，BMI较高、年龄较大、酒精摄入量较多、体力活动较少，且银屑病患者更多的是目前吸烟者、口服避孕药使用者以及绝经后激素治疗者，因此进行多变量分析是恰当的。

确诊年龄<40岁的银屑病患者新发克罗恩病风险显著大于确诊年龄较晚的银屑病患者，活动性银屑病史≥10年患者的风险也相对较高。然而，按照受累体表面积，87%的银屑病患者属于轻度皮肤病，因此本研究在确定更为严重银屑病患者是否具有更高克罗恩病风险方面缺少足够效能。此外，为确保银屑病患者炎性肠病风险增加并源于银屑病治疗药物肿瘤坏死因子抑制剂的某些影响，研究者还对2004年该生物制剂被批准用于银屑病治疗年份的随访结果进行单独分析，结果未见改变。

该研究由美国国立卫生研究院资助，研究者报告无相关利益冲突。

RALEIGH, NORTH CAROLINA (EGMN)–Psoriasis patients are at a nearly fourfold increased risk of developing Crohn’s disease, and the risk is higher in psoriatic arthritis patients.

These findings from 174,646 prospectively followed participants in the Nurses’ Health Study and the Nurses’ Health Study II are consistent with the results of genomewide association studies which have found susceptibility genes common to both psoriasis and inflammatory bowel disease, especially genes in the interleukin-23 pathway, Dr. Wenqing Li said at the annual meeting of the Society for Investigative Dermatology.

“Further understanding of the mechanisms that mediate both psoriasis and Crohn’s disease could eventually lead to elucidation of new targets for interventions that may modulate the incidence or activity of both diseases,” added Dr. Li of Harvard Medical School, Boston.

Of note, the psoriasis patients were not at significantly increased risk for developing ulcerative colitis. This suggests that psoriasis may share fewer overlapping pathways with ulcerative colitis than it does with Crohn’s disease, he continued.

Women in the Nurses’ Health Study were prospectively followed from 1996 to 2008, whereas those in the NHS II were followed from 1991 to 2005. During follow-up, there were 188 incident cases of Crohn’s disease and 240 of ulcerative colitis in the study population. All diagnoses of inflammatory bowel disease were confirmed by two gastroenterologists blinded as to whether or not the affected patients also had psoriasis, Dr. Li noted.

The combined analysis of the two studies included 47,618 person-years of prospective follow-up of psoriasis patients and 2,401,883 person-years of follow-up of participants without psoriasis. The psoriasis patients had an age-adjusted 3.74-fold increased risk of developing Crohn’s disease.

Having psoriasis was still an independent risk factor for Crohn’s disease, with an associated 3.5-fold relative risk, in a multivariate analysis that was adjusted for body mass index, physical activity, smoking status, alcohol consumption, use of oral contraceptives, and postmenopausal hormone therapy as well as age.

Based upon 5,661 person-years of prospective follow-up of subjects with psoriasis and comorbid psoriatic arthritis, affected patients had a 6.8-fold increased of Crohn’s disease in a multivariate analysis.

Multivariate analysis was appropriate because patients with psoriasis had a higher BMI, tended to be older, consumed more alcohol, and were less physically active than were those without psoriasis. The psoriasis patients were also more likely to be current smokers, users of oral contraceptives, and current users of postmenopausal hormone therapy.

The risk of new-onset Crohn’s disease was significantly greater among psoriasis patients whose dermatologic disease was diagnosed when they were younger than 40 years than it was among those diagnosed later in life. The risk was also greater in those with at least a 10-year history of active psoriasis. However, as 87% of patients with psoriasis had mild skin disease based upon the involved body surface area, this study didn’t have sufficient power to determine if the risk of Crohn’s disease was greater in individuals with more severe psoriasis, according to Dr. Li.

To ensure that the increased risk of inflammatory bowel disease associated with having psoriasis wasn’t in some way affected by the use of tumor necrosis factor inhibitors to treat psoriasis, Dr. Li and coinvestigators conducted a separate analysis restricting follow-up through 2004, the year the biologic therapies were approved for psoriasis. This didn’t change the results.

The studies were sponsored by the U.S. National Institutes of Health. Dr. Li reported having no financial conflicts.