Department of Dermatology, Rambam Health Care Campus, Haifa, Israel.
School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
JAMA Dermatol. 2018 Mar 1;154(3):281-285. doi: 10.1001/jamadermatol.2017.5799.
The association between pemphigus and neurologic diseases was not evaluated systematically in the past. In a recent uncontrolled cross-sectional study, Parkinson disease was found to be significantly associated with pemphigus; in the same study, epilepsy had a nonsignificant association with pemphigus. Several case reports have suggested that pemphigus coexists with multiple sclerosis and dementia.
To estimate the association between pemphigus and 4 neurologic conditions (dementia, epilepsy, Parkinson disease, and multiple sclerosis), using one of the largest cohorts of patients with pemphigus.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective population-based cross-sectional study was performed between January 1, 2004, and December 31, 2014, using the database of Clalit Health Services, the largest public health care organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. A total of 1985 patients with a new diagnosis of pemphigus and 9874 controls were included in the study.
The proportion of dementia, epilepsy, Parkinson disease, and multiple sclerosis was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control participants. Logistic regression was used to calculate odds ratios (ORs) for dementia, epilepsy, Parkinson disease, and multiple sclerosis. The association was examined after a sensitivity analysis that included only patients treated with long-term, pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab) and after adjustment for several confounding factors.
When comparing the 1985 cases (1188 women and 797 men; mean [SD] age, 72.1 [18.5] years) with the 9874 controls (5912 women and 3962 men; mean [SD] age, 72.1 [18.5] years), dementia was seen in 622 cases (31.3%) vs 1856 controls (18.8%), with an OR of 1.97 (95% CI, 1.77-2.20). Epilepsy was present in 74 cases (3.7%) vs 210 controls (2.1%), with an OR of 1.78 (95% CI, 1.36-2.33). Parkinson disease was seen in 175 cases (8.8%) vs 437 controls (4.4%), with an OR of 2.09 (95% CI, 1.74-2.51). Multiple sclerosis was present in 2 cases (0.1%) vs 6 controls (0.01%), with an OR of 1.65 (95% CI, 0.34-8.22). Study findings were robust to sensitivity analysis that included patients receiving pemphigus-specific treatments. Estimates were not altered significantly after controlling for comorbidities and overuse of health care.
An association was observed between pemphigus and specific neurologic diseases, including dementia, Parkinson disease, and epilepsy. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid neurologic disorders and receive appropriate treatment.
过去并未系统评估天疱疮与神经疾病之间的关联。在最近一项未对照的横断面研究中，发现帕金森病与天疱疮显著相关；在同一研究中，癫痫与天疱疮无显著关联。一些病例报告表明，天疱疮与多发性硬化症和痴呆并存。
使用天疱疮患者中最大的队列之一，估计天疱疮与 4 种神经疾病（痴呆、癫痫、帕金森病和多发性硬化症）之间的关联。
设计、环境和参与者：这是一项回顾性基于人群的横断面研究，于 2004 年 1 月 1 日至 2014 年 12 月 31 日期间在以色列最大的公共医疗保健组织 Clalit 健康服务的数据库中进行，在普通社区诊所、初级保健和转诊中心以及门诊和住院护理中进行。共纳入了 1985 例新诊断为天疱疮的患者和 9874 名对照者。
比较诊断为天疱疮的患者与年龄、性别和种族匹配的对照参与者之间痴呆、癫痫、帕金森病和多发性硬化症的比例。使用 logistic 回归计算痴呆、癫痫、帕金森病和多发性硬化症的优势比（OR）。在包括仅接受长期、天疱疮特异性药物（皮质类固醇、免疫抑制剂或利妥昔单抗）治疗的患者的敏感性分析后，并在调整了几个混杂因素后，对关联进行了检验。
在比较 1985 例病例（1188 名女性和 797 名男性；平均[SD]年龄，72.1[18.5]岁）和 9874 名对照者（5912 名女性和 3962 名男性；平均[SD]年龄，72.1[18.5]岁）时，622 例（31.3%）患有痴呆症，1856 例（18.8%）对照者患有痴呆症，OR 为 1.97（95%CI，1.77-2.20）。74 例（3.7%）患有癫痫症，210 例（2.1%）对照者患有癫痫症，OR 为 1.78（95%CI，1.36-2.33）。175 例（8.8%）患有帕金森病，437 例（4.4%）对照者患有帕金森病，OR 为 2.09（95%CI，1.74-2.51）。2 例（0.1%）患有多发性硬化症，6 例（0.01%）对照者患有多发性硬化症，OR 为 1.65（95%CI，0.34-8.22）。研究结果在包括接受天疱疮特异性治疗的患者的敏感性分析中是稳健的。在控制合并症和过度使用医疗保健后，估计值没有显著改变。
观察到天疱疮与特定的神经疾病之间存在关联，包括痴呆、帕金森病和癫痫。治疗天疱疮患者的医生应意识到这种可能的关联。患有天疱疮的患者应仔细评估是否存在合并的神经疾病，并给予适当的治疗。
