Association Between Pemphigus and Neurologic Diseases

Abstract

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.

Comorbidities in Autoimmune Skin Diseases

“…A similar constellation of comorbidities had recently been confirmed by a systematic review for bullous pemphigoid (BP), 11 in which multiple sclerosis, dementia, Parkinson disease, cerebrovascular disorders, and epilepsy were found to be significantly associated with BP, which is more common than pemphigus. The results reported in this issue by Kridin et al 10 further support the hypothesis of an immunologic cross-reactivity between the skin and the brain, in which neurologic alterations elicit an improper immune response that may be responsible for skin autoimmunity. In a recent review of comorbidities of subepidermal autoimmune bullous diseases, Kridin 12 noted that, in the case of BP, the cross-reactivity between the neuronal and the epithelial isoforms of BP antigen-1, which are both encoded by the dystonin gene, is the most accepted explanation of the association between BP and neurological diseases.…”

Epidemiology of Pemphigus

“…Anxiety and depression have been reported to correlate with disease activity ( Tabolli et al., 2008 ) and to persist during quiescent periods ( Tabolli et al., 2014 ). A large-scale population-based cross-sectional study disclosed an association of pemphigus with several neurological conditions, namely dementia (OR = 2.0; 95% CI = 1.8–2.2), epilepsy (OR = 1.8; 95% CI = 1.4–2.3), and Parkinson disease (OR = 2.1; 95% CI = 1.7–2.5) ( Kridin et al., 2018f ). The association of pemphigus with Parkinson disease and epilepsy was demonstrated in an earlier cross-sectional study ( Hsu et al., 2016b ).…”

Ischemic stroke and acute pemphigus – two partners in crime

“…The Dsg1, from the desmosomes structure of patients with pemphigus vulgaris, was found to be expressed in the corpus callosum of the mouse brain and was localized around the plasma membrane regions of oligodendrocytes. The desmo-glein1-γ expression is not restricted to the skin, as it is also expressed in the brain, skeletal muscle, and liver, among other tissues (5). at the patients with bullous pemphigoid, BP180 is strongly expressed in the cortex and hippocampus, the neuronal isoforms of BP230 are widely expressed in the human central and peripheral nervous system.…”