A systematic assessment of medical diagnoses preceding the first diagnosis of multiple sclerosis: Supplementary materials

Objective: To explore the occurrence of diseases and symptoms in the five
years prior to diagnosis in patients with multiple sclerosis (MS) in a
case-control study. Methods: Using ambulatory claims data we
systematically assessed differences in the occurrence of diseases and
symptoms in the five years prior to first diagnosis in patients with MS
(n=10,262) as compared to patients with two other autoimmune diseases –
Crohn’s disease (n=15,502) and psoriasis (n=98,432) - and individuals
without these diseases (n=73,430). Results: Forty-three ICD-10 codes were
recorded more frequently for patients with MS before diagnosis as compared
to controls without autoimmune disease. Many of these findings were
confirmed in a comparison to the other control groups. A high proportion
of these ICD-10 codes represent symptoms suggestive of demyelinating
events or other neurological diagnoses. In a sensitivity analysis
excluding patients with such recordings prior to first diagnosis, no
association remained significant. Seven ICD-10 codes were associated with
lower odds ratios of MS, four of which represented upper respiratory tract
infections. Here, the relations with MS were even more pronounced in the
sensitivity analysis. Conclusions: Our analyses suggest that patients with
MS are frequently not diagnosed at their first demyelinating event but
often years later. Symptoms and physician encounters before MS diagnosis
seem to be related to already ongoing disease rather than a prodrome. The
observed association of upper respiratory tract infections with lower ORs
of MS diagnosis suggests a link between protection from infection and MS
that however needs to be validated and further investigated.

研究目的：本项病例对照研究旨在探索多发性硬化症（multiple sclerosis, MS）患者确诊前五年内的疾病与症状发生情况。
研究方法：本研究利用门诊就诊索赔数据，系统评估了多发性硬化症患者（n=10,262）在首次确诊前五年内的疾病与症状发生情况，并与另外两种自身免疫性疾病患者——克罗恩病（Crohn’s disease，n=15,502）、银屑病（psoriasis，n=98,432）患者，以及无上述疾病的对照个体（n=73,430）进行对比。
研究结果：相较于无自身免疫性疾病的对照人群，多发性硬化症患者在确诊前有43项ICD-10编码的记录频率显著更高，其中多数发现在与其他对照组的对比中得到了验证。上述ICD-10编码中，较高比例对应提示脱髓鞘事件或其他神经系统疾病的症状。在一项排除首次确诊前存在上述记录的患者的敏感性分析中，未发现显著的关联。另有7项ICD-10编码与多发性硬化症的比值比（odds ratios, OR）呈负相关，其中4项对应上呼吸道感染。在敏感性分析中，此类与多发性硬化症的关联更为显著。
研究结论：本研究分析结果提示，多发性硬化症患者往往并非在首次脱髓鞘事件时即得到确诊，而是通常在数年后才被确诊。多发性硬化症确诊前出现的症状与就诊经历，似乎与已处于进展中的疾病相关，而非前驱症状。本次观察到的上呼吸道感染与多发性硬化症确诊比值比降低的关联，提示感染防护与多发性硬化症之间存在潜在联系，但该结论仍需进一步验证与深入研究。