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Association Between Pemphigus and Neurologic Diseases

Educational Objective
To learn about the increased incidence of serious neurologic problems in a cohort of patients with pemphigus and to speculate on common pathologic pathways.
1 Credit CME
Key Points

Question  Is there an association between pemphigus and neurologic diseases?

Findings  This population-based cross-sectional study of 1985 patients with pemphigus revealed a statistically significant comorbidity between pemphigus and epilepsy, dementia, and Parkinson disease. This association retained its statistical significance after multivariable and sensitivity analyses.

Meaning  Clinicians should be aware of this association; further research is warranted to elucidate the mechanism of this link.


Importance  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.

Objective  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.

Main Outcomes and Measures  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.

Results  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.

Conclusions and Relevance  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.

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Article Information

Accepted for Publication: October 20, 2017.

Corresponding Author: Khalaf Kridin, MD, Department of Dermatology, Rambam Health Care Campus, PO Box 9602, Haifa 31096, Israel (dr_kridin@hotmail.com).

Published Online: February 16, 2018. doi:10.1001/jamadermatol.2017.5799

Author Contributions: Drs Kridin and Cohen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Kridin, Zelber-Sagi, Cohen.

Acquisition, analysis, or interpretation of data: Kridin, Comaneshter, Cohen.

Drafting of the manuscript: Kridin.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Kridin, Comaneshter, Cohen.

Administrative, technical, or material support: Cohen.

Study supervision: Kridin, Zelber-Sagi, Cohen.

Conflict of Interest Disclosures: None reported.

Meeting Presentation: This paper was presented at the Annual Meeting of the American Academy of Dermatology; February 16, 2018; San Diego, California.

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