嗜酸粒细胞性食管炎诊断延迟可增加食管狭窄风险

《胃肠病学》杂志12月刊发表的一项研究表明，嗜酸粒细胞性食管炎(EoE)患者从症状出现到确诊间隔时间越长，发展为食管狭窄的几率越大(doi:10.1053/j.gastro.2013.08.015)。

瑞士洛桑沃州地区大学医学中心(CHUV)消化科Alain M. Schoepfer医生及其同事对瑞士全国数据库中523例EoE患者资料的回顾性研究显示，患者早期很可能单纯表现为炎性内镜EoE特征，但随着疾病进展，除炎性特征外还呈现纤维化内镜特征。

此外，对多种与潜在疾病、环境及患者相关的风险因素分析表明，诊断延迟时间是食管狭窄形成唯一且最显著的风险因素。

研究者指出，目前对未经治疗的EoE自然史缺少充分研究，尤其是有关狭窄形成的资料更为缺乏。此外，长期存在EoE诊断延迟现象，从症状出现到诊断的中位时间为5年。

为此，研究者利用他们收治的323例患者和瑞士其他胃肠病医生收治的200例患者的详细病例，分析了EoE未经治疗的时间(诊断前)与食管狭窄发病率的相关性。资料包括多次近端和远端食管活检结果以及可能影响狭窄形成的98个临床因素信息。

结果显示，中位诊断延迟时间为6年(范围为0~20年以上)，75例(37.5%)患者确诊时患有食管狭窄。79.5%的患者呈现水肿、沟纹及白色渗出物等活动性炎性特征，而63.0%的患者呈现狭窄、环状和皱纹纸样食管等纤维化活动性特征。

包括狭窄在内的纤维化特征的发生率随诊断延迟时间增加而增加，延迟时间0~2年患者发生率为46.5%，而延迟时间≥20年患者上升至87.5%。

相反，炎性特征发生率随诊断延迟时间的增加而下降。

食管狭窄发生率也与诊断延迟相关，延迟时间0~2年患者发生率为17.2%，而延迟时间≥20年患者上升至70.8%。

食管狭窄发生率与确诊年龄无关，20岁之前和20岁之后确诊患者的狭窄发生率相当。此外，由研究者按照严格标准化程序诊治的323例患者食管狭窄发病率与其他胃肠病医生按照其各自诊治习惯收治的200例患者也未见差异。

对近100个狭窄形成潜在风险因素的分析显示，与诊断时食管狭窄呈显著相关的因素仅为诊断延迟时间。

研究者指出，上述结果表明，EoE患者病程是从以炎症为主的疾病向以食管狭窄等纤维化特征为主的疾病进展的连续过程，医生应尽可能减少对EoE诊断的延迟。

该研究由瑞士估价科学基金会资助，研究者报告无相关利益冲突。

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By: MARY ANN MOON, Internal Medicine News Digital Network

The longer the interval between symptom onset and the diagnosis of eosinophilic esophagitis, the greater the chance that the patient will have developed esophageal strictures, according to a report in the December issue of Gastroenterology (doi:10.1053/j.gastro.2013.08.015).

In a retrospective study of 523 cases of eosinophilic esophagitis (EoE) recorded in a national Swiss database, patients "were likely to present with purely inflammatory endoscopic EoE features early in the disease course and then progress to develop fibrotic endoscopic features, in addition to inflammatory features," said Dr. Alain M. Schoepfer of the division of gastroenerology and hepatology, Centre HospitalierUniversitaireVaudois, Lausanne, Switzerland, and his associates.

Moreover, an additional analysis of numerous potential disease-, environmental-, and patient-related risk factors demonstrated that the length of diagnostic delay is the single strongest risk factor for stricture formation, the investigators noted.

The natural history of untreated EoE has not been investigated extensively, and data regarding stricture formation are particularly lacking. In addition, eosinophilic esophagitis has long been associated with a substantial delay in diagnosis, with a median of 5 years elapsing between symptom onset and correct identification of the disorder.

Dr. Schoepfer and his colleagues examined the relationship between the duration of untreated disease (before EoE was diagnosed) and the prevalence of esophageal stricture using a database with detailed medical records of 323 patients they personally diagnosed and treated plus 200 others who were diagnosed and treated by other gastroenterologists throughout Switzerland. The database included the results from numerous biopsies of the proximal and distal esophagus for every patient, as well as information on 98 clinical factors that might influence stricture formation.

The median diagnostic delay was 6 years (range, 0 to more than 20 years).

Strictures were present at diagnosis in 75 patients (37.5%).

Features of active inflammation, such as edema, furrows, and whitish exudates, were present in 79.5% of patients while features of fibrotic activity, such as strictures, rings, and crepe-paper esophagus, were seen in 63.0%.

The prevalence of fibrotic features including strictures increased with increasing duration of diagnostic delay. This prevalence was 46.5% among patients who were diagnosed as having EoE within 0-2 years of symptom onset, rising to 87.5% among those diagnosed 20 years or more after symptom onset.

In contrast, the prevalence of inflammatory features alone decreased with increasing duration of diagnostic delay.

The prevalence of esophageal strictures likewise correlated with diagnostic delay. It was 17.2% among patients diagnosed within 0-2 years of symptom onset, compared with 70.8% among those diagnosed 20 years or more after symptom onset, the investigators said.

The prevalence of strictures did not differ by patient age at diagnosis. It was comparable between patients who were diagnosed before they reached 20 years of age and those diagnosed after age 20. The prevalence of strictures also did not differ between the 323 patients diagnosed and treated by Dr. Schoepfer and his associates, who were managed according to a strict standardized protocol, and the 200 other patients who were managed by numerous other gastroenterologists according to their own individual practice preferences.

In an analysis of nearly 100 potential risk factors for stricture formation, only the length of diagnostic delay was found to be significantly associated with the presence of strictures at diagnosis.

These findings demonstrate that a patient’s disease course "is a continuum – a march from a disease predominantly inflammatory in nature to a disease with endoscopic fibrotic features, including strictures, in addition to existing inflammation," the researchers said.

Clinicians should make every effort to reduce the delay in diagnosis of EoE, they added.

This study was supported by the Swiss National Science Foundation. No relevant financial conflicts of interest were reported.