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Data regarding the association between pemphigus and rheumatoid arthritis (RA) is inconclusive and yet to be firmly established. In the current study, we aimed to evaluate the risk of developing RA during the course of pemphigus. A large-scale population-based longitudinal cohort study was conducted to evaluate the hazard ratio (HR) of RA among 1985 patients with pemphigus relative to 9874 age-, sex-, and ethnicity-matched control subjects. A multivariate Cox regression model was utilized. The incidence of RA was 1.07 (95% CI, 0.62-1.72) and 0.36 (95% CI, 0.24-0.52) per 1000 person-years among patients with pemphigus and controls, respectively. The lifetime prevalence of RA was 2.3% (95% CI, 1.7-3.1%) among cases and 1.8% (95% CI, 1.5-2.0%) among controls. Patients with pemphigus were more than twice as likely to develop RA as compared to control subjects (adjusted HR, 2.54; 95% confidence interval [CI], 1.31-4.92). The increased risk was robust to a sensitivity analysis that included only cases managed by pemphigus-related systemic medications (adjusted HR, 2.56; 95% CI, 1.30-5.05). In conclusion, pemphigus is associated with an increased risk of RA. Physicians treating patients with pemphigus should be aware of this possible association. Further research is required to better understand the mechanism underlying this association.

Objectives: Recent evidence suggests a notable role for inflammation and immune dysregulation in the neuroprogression of bipolar disorders (BD). Several autoimmune comorbidities have been reported in association with BD. However, the epidemiological relationship between pemphigus and BD has not yet been elucidated. We aimed to estimate the association between pemphigus and BD using a large-scale, real-life computerized database., Methods: Data for this study were retrieved from the database of the Clalit Health Services, the largest, state-mandated, health service organization in Israel. This study was designed as a cross-sectional study. The proportion of patients with BD was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control subjects. A logistic regression model was performed to estimate how pemphigus and other covariates contributed as risk factors for BD., Results: A total of 1,985 pemphigus cases and 9,874 controls were included in the study. The prevalence of BD was greater in cases with pemphigus than in controls (1.0% v. 0.5%, respectively; P = 0.023). This coexistence was more prominent among patients of Jewish ethnicity. After controlling for confounders, such as age, sex, ethnicity, socioeconomic status, drug abuse, alcohol abuse, smoking, healthcare utilization, and comorbidities, pemphigus demonstrated a substantial independent association with BD (OR, 1.7; 95% CI, 1.0 to 2.9)., Conclusions: Pemphigus is significantly associated with BD. Patients with pemphigus should be assessed for comorbid BD. Experimental research is needed to better recognize the biological mechanisms underlying this observation.

Background: The association of nonparaneoplastic pemphigus with comorbid hematologic malignancies has yet to be established., Objective: To estimate the association between pemphigus and the common types of hematologic malignancies., Methods: A cross-sectional study was conducted comparing pemphigus patients with age-, sex- and ethnicity-matched control subjects regarding the prevalence of 6 comorbid hematologic malignancies. The study was performed using the computerized database of Clalit Health Services ensuring the availability of 4.5 million patients., Results: The study included 1985 pemphigus patients and 9874 control subjects. The prevalence of chronic leukemia (0.9% vs 0.4%, odds ratio [OR] 2.1, 95% confidence interval [CI] 1.2-3.6), multiple myeloma (0.8% vs 0.4%, OR 2.2, 95% CI 1.2-3.9), and non-Hodgkin lymphoma (1.8% vs 1.2%, OR 1.5, 95% CI 1.0-2.2) was greater in patients with pemphigus than in controls. The association with chronic leukemia remained significant following the adjustment for immunosuppressive therapy (adjusted OR 2.0, 95% CI 1.1-3.7). No significant associations were observed between pemphigus and acute leukemia, Hodgkin lymphoma, myelodysplastic syndrome, and polycythemia vera., Limitations: Lack of immunopathologic validation of the diagnosis of pemphigus., Conclusion: A significant association was observed between pemphigus and chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma. Further research is warranted to establish this observation in other cohorts., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucous membranes. The mean platelet volume (MPV) is an index of platelet activation reported to be influenced by inflammation. We investigated the MPV in patients with PV relative to controls. This case-control study included 160 patients with PV and 640 age- and sex-matched controls. The MPV, platelet count, and other inflammatory parameters were measured for all study participants. A significantly decreased MPV was observed in patients with PV compared with controls, 9.1 (1.5) fL versus 10.3 (1.4) fL, P < .001. A significant negative association between MPV and PV was demonstrated in multivariate analysis (odds ratio, 0.59; 95% confidence interval, 0.51-0.68, P < .0001). Patients having PV with laryngeal involvement had significantly lower MPVs than those without involvement of the larynx, 8.81 (1.5) fL versus 9.32 (1.4) fL, P = .032. Disease activity (before and after treatment) does not affect the MPV. Patients with PV showed decreased MPV values compared to healthy controls. The MPV may be a feasible diagnostic marker in patients with PV.

Importance: The association of pemphigus vulgaris and pemphigus foliaceus with comorbid malignancies is yet to be firmly established., Objective: To estimate the association between pemphigus and a wide range of nonhematologic malignancies using one of the largest cohorts of patients with pemphigus to date., Design, Setting, and Participants: For this cross-sectional study, we used the computerized database of Clalit Health Services, the largest public health care provider organization in Israel insuring 4.4 million individuals in the settings of general community clinics, primary care and referral centers, and ambulatory and hospitalized health care. The study included 1985 patients with pemphigus and 9874 control patients and was conducted from January 2004 to December 2014., Main Outcomes and Measures: The prevalence of 17 different solid malignancies was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched control patients; χ2 and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The association was examined following a sensitivity analysis that included only cases treated with long-term pemphigus-specific medications (corticosteroids, immunosuppressants, or rituximab), and following the adjustment for several confounding factors., Results: Overall, the total sample included 11 859 eligible patients, of whom 1985 were patients with pemphigus (mean [SD] age at presentation, 72.1 [18.5] years; 1188 women [59.8%]). In patients with pemphigus compared with control patients, there was a greater prevalence of esophageal cancers (0.4% vs 0.1%; odds ratio [OR], 2.9; 95% CI, 1.1-7.4) and laryngeal cancers (0.6% vs 0.3%; OR, 2.0; 95% CI, 1.0-4.1). No significant associations between pemphigus and other solid malignancies were observed. Estimates were not altered significantly after controlling for comorbidities, health care overutilization, immunosuppressive therapy, and other malignancy-specific risk factors (ie, smoking and alcohol abuse in laryngeal cancer, gastroesophageal reflux disease in esophageal cancer)., Conclusions and Relevance: Significant associations were observed between pemphigus and solid malignancies of the larynx and the esophagus. Physicians treating patients with pemphigus should be aware of these findings. Further observational studies are warranted to establish this association in other cohorts.

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.

Although pemphigus is associated with increased mortality, little is known regarding factors that influence prognosis. To identify prognostic factors for mortality at five- and 10-year periods after an initial diagnosis of pemphigus. A retrospective cohort study was performed. Data were collected for all patients with a new diagnosis of pemphigus between 1990 and 2011, who were actively followed for at least five years at our centre. The endpoint was overall survival at five and 10 years after pemphigus diagnosis. Based on the test sample, associations between clinical variables and overall survival were assessed using univariate and multivariate analyses. A total of 184 patients were included in the study (mean age: 52.2 ± 16.1). The major risk factors for lethal outcome at both five and 10 years after diagnosis were age ≥65 years at diagnosis (with a multivariate hazard ratio [HR] of 5.9 and 4.2 at five and 10 years, respectively) and neurological disease at diagnosis (with a multivariate HR of 5.4 and 5.1 at 5 and 10 years, respectively). Diabetes mellitus was an independent risk factor for mortality at five years (multivariate HR: 3.8). Two risk factors were independently associated with lethal outcome at 10 years: serum albumin levels <3.5 g/dL (multivariate HR: 3.3) and lung disease at diagnosis (multivariate HR: 3.8). Mucosal involvement in patients with pemphigus vulgaris was not associated with increased mortality. Prognosis of patients with pemphigus is influenced by older age, hypoalbuminaemia, diabetes mellitus, and neurological and respiratory comorbidities at diagnosis.

Background: The coexistence of pemphigus and ulcerative colitis (UC) has been described, but the association between the two entities was not examined in the past. The primary endpoint of this study was to investigate the association between pemphigus and UC., Materials and Methods: Patients with pemphigus were compared to age-, sex- and ethnicity-matched control subjects regarding the prevalence of UC in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was conducted utilizing the computerized database of Clalit Health Services., Results: The study enrolled 1985 pemphigus patients and 9874 controls. The prevalence rate of UC was greater in patients with pemphigus than in controls (0.9% vs. 0.4%, respectively; p = .004). In a multivariate analysis pemphigus was independently associated with UC (odds ratio 1.9, 95% confidence interval 1.1-3.3, p = .034). This association was stronger among younger patients, and persisted after performing a sensitivity-analysis including only patients who were prescribed pemphigus-specific medications., Conclusions: Pemphigus is significantly associated with UC. Thus, physicians treating patients with pemphigus should be aware of this possible association. Further research is warranted to better understand the mechanism underlying this association.

Little is known about differences in epidemiological features and prognosis between pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The objective of this study was to compare PV and PF patients regarding ethnic variations and mortality rates. Mortality of PV and PF patients was compared with age- and sex-matched control subjects in the general population. The study cohort comprised 207 patients with PV and 30 with PF diagnosed during the period 2000 to 2015. The incidence rate of PV among Jews was 3.6-fold higher than among Arabs (p<0.001), whereas no ethnic predisposition to PF was noted (p = 0.379). The risk of death for patients with PV was almost 3-fold higher than in the general population (standardized mortality ratio (SMR) 2.6). For patients with PF, the risk of mortality was not significantly increased relative to the general population (SMR 1.4). There is a racial predisposition to PV, whereas PF is sporadic. Mortality among patients with PV is higher compared with PF and the general population.

The association between pemphigus and hepatitis viruses has not been investigated sufficiently and remains unclear. Our objective was to assess the association between pemphigus and chronic hepatitis B (HBV) and hepatitis C (HCV) infections using a large-scale real-life computerized database. This study was conducted as a cross-sectional study utilizing the database of Clalit Health Services. The proportion of chronic HBV and HCV infections was compared between patients diagnosed with pemphigus and age-, sex-, and ethnicity-matched controls. Univariate analysis was performed using chi-square and Student's t test, and multivariate analysis was performed using a logistic regression model. A total of 1985 pemphigus patients and 9874 controls were enrolled in the study. The prevalence of HBV chronic infection in patients with pemphigus was significantly higher than in control subjects (1.2 vs. 0.6%, respectively, p = 0.008). The prevalence rate of HCV carrier state was comparable between pemphigus patients and control subjects (1.1 vs. 1.0, respectively, p = 0.732). A multivariate analysis revealed a significant association between pemphigus and HBV with a multivariate odds ratio (OR) of 1.9 [95% confidence interval (CI), 1.2-3.90], whereas no association between pemphigus and HCV was identified (OR 1.1, 95% CI, 0.7-1.7). In conclusion, patients with pemphigus have a greater proportion of chronic HBV but not HCV infection relative to matched controls.

Background: The epidemiology of pemphigus in different ethnic populations exposed to similar environments is unknown. Trends in the incidence of pemphigus based on an immunopathologically validated cohort have not been investigated., Objectives: We sought to estimate the incidence of pemphigus in Israel and to investigate differences between the 2 major ethnic populations., Methods: Pemphigus incidence was retrospectively estimated from January 2000 to December 2015 in 2 Israeli regions with a total population of 1.56 million inhabitants., Results: One hundred eighty patients with pemphigus (mean age, 54.70 ± 16 years) were identified. The overall estimated incidence was 7.2 per million inhabitants per year (95% confidence interval, 6.2-8.3). The incidence in the Jewish population was threefold higher than that in Arabs (9.6 vs 3.2 cases per million per year, respectively; P < .0001) and higher among women than men (9 vs 5.3 cases per million per year, respectively; P < .0001). The incidence decreased from 8.4 cases per million per year in 2000 to 2005 to 7.0 and 6.0 (95% confidence interval, 4.5-7.9) in 2006 to 2010 and 2011 to 2015, respectively (P = .068)., Limitations: This study was limited by the retrospective design and the small population., Conclusions: The incidence of pemphigus in Israel is among the highest reported worldwide and is significantly more frequent among Jews., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

All-cause and cause-specific mortality among patients with pemphigus compared with the general population is yet to be established. This study investigated overall mortality and cause-specific mortality in a large immunopathologically validated cohort of patients with pemphigus. Mortality of patients with pemphigus was compared with age- and gender-matched control subjects in the general population. All-cause and cause-specific standardized mortality ratios (SMRs) were estimated. The study cohort included 245 patients newly-diagnosed with pemphigus between January 1990 and June 2016, contributing 2,679.4 person-years of follow-up. Overall, 48 deaths were observed during a mean follow-up period of 10.9 ± 8.1 years, which was more than twice the number expected (SMR 2.4; 95% confidence interval (95% CI) 1.82-3.20). The SMRs for death due to infections (22.6; 95% CI 13.6-35.3), namely pneumonia (25.7; 95% CI 11.7-48.8) and septicaemia (8.6; 95% CI 1.7-25.0), and due to cardiovascular diseases (2.8; 95% CI 1.0-6.0) were significantly higher than expected. Overall mortality among patients with pemphigus is 2.4-times greater than for the general population, mainly due to infections. [ABSTRACT FROM AUTHOR]