Showing papers by "Arnon D. Cohen published in 2018"

Underlying Systemic Diseases in Pyoderma Gangrenosum: A Systematic Review and Meta-Analysis

Abstract: There is little consensus regarding the prevalence and distribution of underlying systemic diseases among patients with pyoderma gangrenosum. The objective of this study was to synthesize existing data on the prevalence of associated systemic diseases in patients with pyoderma gangrenosum. We performed a systematic review and meta-analysis of observational studies in MEDLINE, EMBASE, and Scopus (1823–2017). The quality of evidence was assessed using a modified Newcastle–Ottawa Scale. A meta-analysis was performed using random-effects models to estimate pooled prevalence rates with 95% confidence intervals. Twenty-one eligible studies comprising 2611 patients with pyoderma gangrenosum were included in the quantitative synthesis. The overall random-effects pooled prevalence of associated systemic diseases was 56.8% (95% confidence interval 45.5–67.4). The leading underlying disease was inflammatory bowel disease (17.6%; 95% confidence interval 13.0–22.7), followed by arthritis (12.8%; 95% confidence interval 9.2–16.9), hematological malignancies (8.9%; 95% confidence interval 6.5–11.6), and solid malignancies (7.4%; 95% confidence interval 5.8–9.1). In 16.3% (95% confidence interval 7.7–27.1) of cases, the onset of pyoderma gangrenosum was attributed to the pathergy phenomenon. More than half of patients with pyoderma gangrenosum present with a relevant underlying disease. Inflammatory bowel disease and arthritis are the most frequently associated diseases. Relative to the reported literature, the pooled prevalence of arthritis and hematological malignancies is lower, while the pooled prevalence of solid malignancies is higher. Owing to the high level of heterogeneity among most of the comparisons, results should be interpreted with caution.

Chronic urticaria and the metabolic syndrome: a cross-sectional community-based study of 11 261 patients.

Abstract: Background Emerging evidence suggests that chronic urticaria (CU) is associated with chronic, low grade, inflammatory process. Objective To evaluate the association between CU and metabolic syndrome and its components in a large community-based medical database. Methods A cross-sectional study of CU patients and matched controls was performed. CU was defined as eight urticaria diagnoses (with each two diagnoses registered within a period of six weeks) from 2002 to 2012. Data regarding the prevalence of metabolic syndrome, its components, and possible complications were collected. Results The study included 11,261 patients with CU and 67,216 controls. In a univariate analysis, CU was significantly associated with higher body mass index (BMI) and a higher prevalence of obesity, diabetes, hyperlipidemia, hypertension, metabolic syndrome, chronic renal failure, and gout. Multivariate analysis demonstrated a significant association between CU and metabolic syndrome (OR = 1.12, 95% CI 1.1-1.2, p < 0.001) and its components- obesity (OR = 1.2, 95% CI 1.1-1.3, p < 0.001), diabetes (OR = 1.08, 95% CI 1.01-1.15, p = 0.001), hyperlipidemia (OR = 1.2, 95% CI 1.1-1.2, p < 0.001), and hypertension (OR = 1.1, 95% CI 1.1-1.2, p < 0.001). Conclusions CU patients may have one or more undiagnosed components of metabolic syndrome despite their young age. Thus, appropriate targeted screening is advised. This article is protected by copyright. All rights reserved.

Are obesity and rheumatoid arthritis interrelated

Abstract: OBJECTIVES In recent years, both the prevalence of obesity and the incidence of RA have been rising. Our aim was to assess the association between overweight or obesity and rheumatoid arthritis (RA). DESIGN Patients who were diagnosed with RA were compared with population-based controls, matched for age and sex (by a ratio of 1:5). Body measurements and smoking status were collected from medical records. Body mass index was classified in WHO categories of underweight, normal, overweight and obese (<18.5, 18.5-<25, 25-<30, ≥30 kg/m2 ). χ2 and t-tests and logistic regression models were used to compare the study groups and to assess the association between obesity and RA. SETTING A cross-sectional analysis performed utilizing the database of Clalit Health Services, the largest healthcare provider organisation in Israel. Data were collected from the beginning of computerised database usage (around year 2000) until 2015. PARTICIPANTS CHS covers over 4.4 million enrollees, of which all RA patients and matched controls were selected. MAIN OUTCOME MEASURES Proportion of obesity (BMI≥30.0 kg/m2 ) among RA patients and controls. RESULTS The study included 11 406 patients with RA and 54 701 controls. The proportion of obese subjects among RA patients was higher in comparison with controls, (33.4% vs 31.6%, respectively). In multivariate regression model, smoking and obesity were found to be associated with RA, whereas male gender was found as inversely related to RA. CONCLUSIONS Our findings demonstrate that obesity is significantly associated with RA. This finding underlines the role that obesity plays in inflammation and autoimmune conditions.

Is there an association between dipeptidyl peptidase-4 inhibitors and autoimmune disease? A population-based study.

Abstract: The association of dipeptidyl peptidase-4 inhibitors (DPP4is) with autoimmune diseases is controversial. While these agents were proposed as a novel therapeutic approach for several inflammatory diseases by blocking T cell proliferation and cytokine production, they were found to trigger inflammatroy bowel disease, inflammatory arthritis and bullous pemphigoid. Our objective is to examine the association between DPP4i and autoimmune diseases. This study was conducted as a cross-sectional study utilizing the database of Clalit Health Services. The prevalence of 15 autoimmune-/immune-mediated diseases was compared between patients on DPP4i treatment and age-, sex-, and ethnicity-matched controls. Univariate analysis was performed using chi-square and the Student t test and multivariate analysis was performed using a logistic regression model. The study included 283 patients treated with DPP4i agents and 5660 age-, sex-, and ethnicity-matched diabetic control subjects. The prevalence of Crohn’s disease (1.1 vs. 0.3%; odds ratios (OR), 3.56; 95% CI, 1.04–12.21, P = 0.031), psoriasis (2.5 vs. 1.2%; OR, 2.12; 95% CI, 0.99–4.66; P = 0.050), and Hashimoto’s thyroiditis (16.6 vs. 12.6%; OR, 1.38; 95% CI, 1.00–1.91; P = 0.049) was significantly higher in patients on DPP4i treatment than in controls. The prevalence of the remaining autoimmune diseases did not differ significantly between DPP4i-treated patients and their matched control subjects. In conclusion, this population-based study demonstrates an association of DPP4i intake with three autoimmune and inflammatory diseases noted to be part of a distinct autoimmune cluster that includes multiple sclerosis, psoriasis, thyroiditis, bullous pemphigoid, and inflammatory bowel disease. Experimental studies are required to define the role of DPP4i in this autoimmune cluster.

Chronic hypnotic use at 10 years-does the brand matter?

Abstract: Chronic use of sedative-hypnotics is very common, although not guideline-endorsed. The incidence among new users is not well studied, and there are currently no recommendations favoring any specific agent. We quantified the risk for chronic use in first-time hypnotic users, and the association of the initial choice of hypnotic with later usage patterns. We used the computerized database of Israel’s largest healthcare provider. All 236,597 new users of sedative-hypnotics between the years 2000–2005 were followed for 10 years. Filled prescriptions in the second, fifth, and tenth years were recorded. The association of the first hypnotic choice (benzodiazepine/Z-drug) with chronic consumption was assessed using multivariate logistic regression. Average age on first use was 63.7 (SD ± 16.4) years. 58.6% were women. Benzodiazepines were initiated in 154,929 (65.5%) of the cases. Benzodiazepine users were older and of lower socioeconomic status, compared to Z-drug users (p < 0.001). On the tenth year, 103,912 (66.8%) of new users claimed ≤ 30 DDDs of hypnotics, 3,1724 (20.4%) were long-term users (≥ 180 DDD/year), and 828 (0.5%) used excessively (≥ 720 DDD/year). Z-drugs were associated with an increased risk of long-term use on the second year [17.3% vs. 12.4%, RR = 1.40 (1.37–1.43)] as well as on the fifth [21.9% vs. 13.9%, RR = 1.58 (1.55–1.61)] and tenth year [25.1% vs. 17.7%, RR = 1.42 (1.39–1.45)], p < 0.0001. Similar results were also observed for daily and excessive use (p < 0.001). One in five new users of sedative-hypnotics will become a long-term user, but only 0.5% will become excessive users. Z-drugs were associated with an increased risk of chronic use.

Helicobacter pylori infection is positively associated with an increased BMI, irrespective of socioeconomic status and other confounders: a cohort study.

Abstract: BACKGROUND Data on the association of Helicobacter pylori infection and BMI are conflicting. The fact that both H. pylori infection and BMI are associated with low socioeconomic status (SES) makes this relationship difficult to characterize. MATERIALS AND METHODS We aimed to evaluate the association between BMI and H. pylori infection after adjusting for multiple covariates. We analyzed a cohort of 235 107 individuals aged 18 years or older, who performed a C urease breath test (C-UBT), from 2007 to 2014. Data on BMI, age, sex, SES, ethnicity, and medications were extracted from a nationwide population-based database. BMIs were classified according to the WHO recommendations: underweight ( 35 kg/m). STUDY RESULTS The positivity rate for H. pylori among underweight, normal weight, overweight, and obese class I and class II or more was 55.6, 58.5, 63.0, 64.5, and 65.5%, respectively (P<0.001, Plinear trend 0.007). The association between BMI and H. pylori infection was significant across all SES, sex, ethnicity, and age categories. After adjusting for age, sex, ethnicity, and SES, being overweight and obese class I and class II or more were associated significantly with H. pylori positivity: odds ratio 1.13 [95% confidence interval (CI): 1.11-1.15], 1.14 (95% CI: 1.11-1.17), and 1.15 (95% CI: 1.11-1.19), respectively, P value less than 0.001 for all. CONCLUSION Among individuals who were referred to a C-UBT by primary care physician, after adjusting for multiple covariates including SES, we found a positive association between H. pylori infection and an increased BMI.

Biologics combined with conventional systemic agents or phototherapy for the treatment of psoriasis: real-life data from PSONET registries.

Abstract: Background Biologics have greatly improved psoriasis management. However, primary and secondary non-response to treatment requires innovative strategies to optimize outcomes. Objective To describe the use of combined treatment of biologics with conventional systemic agents or phototherapy in daily clinical practice. Methods We collected data on frequency of use, demographics, treatment characteristics and drug survival of biologics combined with conventional systemic agents or phototherapy in five PSONET registries. Results Of 9922 biologic treatment cycles, 982 (9.9%) were identified as combination treatment. 72.9% of treatment cycles concerned concomitant use of methotrexate, 25.3% concerned concomitant UVB therapy, acitretin or cyclosporin and 1.8% concerned combined treatment with PUVA, fumaric acids or a second biologic. Substantial variation was detected in type and frequency of combination treatments prescribed across registries. Patients initiated on combined treatment had generally severe disease and were affected with psoriasis for many years. The extent to which patients had been priory treated with biologic monotherapy and the proportion of patients affected with psoriatic arthritis differed between registries. Survival rates for etanercept, adalimumab, infliximab and ustekinumab with methotrexate ranged between 43-92%, 28-83%, 65-87% and 53-77% respectively across registries after one year with no consistent superior survival for a particular biologic. Longest survival on a biologic combined with methotrexate, acitretin or cyclosporin was 103, 78 and 34 months respectively. Conclusion Methotrexate was the most commonly used concomitant treatment for patients on a biologic. Wide geographical variations in treatment selection and persistence of combination treatment exist. Data derived from ongoing studies may help to determine whether combined treatment is superior to biologic monotherapy. This article is protected by copyright. All rights reserved.

The epidemiology of psoriatic arthritis in Israel - a population-based study.

Abstract: There is limited information on the epidemiology of psoriatic arthritis (PsA) in general and in Middle Eastern populations in particular. The aims of this study were to estimate the prevalence and incidence rates of PsA and their temporal trends in the general population in Israel. In this study, a cohort of adult patients with PsA was derived from the database of Clalit Health Services (CHS), Israel’s largest health fund, with over 4.4 million members. The crude and age- and sex-standardized prevalence and incidence rates of PsA from 2006 to 2015 in the general population were calculated. The variation in PsA prevalence was assessed in relation to several demographic factors. Among the 2,931,199 individuals aged 18 years and older registered in the CHS database in 2015, 4490 patients had a diagnosis of PsA (322 incident cases), resulting in overall crude prevalence and incidence rates of 0.153% (95% CI 0.149%, 0.158%) and 10.9 (95% CI 9.8, 12.3) per 100,000 population, respectively. The reported prevalence of PsA in Israel has doubled between 2006 and 2015 (from 0.073% to 0.153%). In contrast, the global incidence rate remained stable, with a gradual increase in incidence among individuals aged 51 to 70 years. PsA is associated with Jewish ethnicity, high socioeconomic status, and higher body mass index. The prevalence and incidence of PsA in Israel are within the range of previous estimates from Southern European populations. An increase in the reported prevalence of PsA was observed over the past decade in the general population in Israel.

Coexistent Solid Malignancies in Pemphigus: A Population-Based Study

Abstract: 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; χ2andttests 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.

The link between schizophrenia and hypothyroidism: a population-based study.

Abstract: Schizophrenia is considered to be of the severe psychiatric disorders characterized by chronic debilitating course marked with frequent relapses and high clinical and financial burden. Aberrations of thyroid hormone levels have been documented in several psychiatric conditions including bipolar disease. The aim of this study is to provide insight into whether an association exists between hypothyroidism and schizophrenia. A population-based cross-sectional study was conducted using data retrieved from the largest medical records database in Israel, the Clalit Health Services (CHS). Patients were defined as having hypothyroidism or schizophrenia when there was at least one such documented diagnosis in their medical records. The proportion of schizophrenia was compared between hypothyroid and age- and sex frequency-matched healthy controls. A logistic regression model was used to estimate the association between psychiatric manifestations and hypothyroidism in a multivariate analysis adjusted for age, gender, and smoking status. The study included 40,843 patients with hypothyroidism and 40,918 age- and sex frequency-matched controls. The proportion of schizophrenia in hypothyroid patients was higher than that in controls (2.01% vs. 1.25%, respectively, p < 0.0001). Multivariate logistic regression demonstrated a robust independent association between hypothyroidism and schizophrenia (OR 1.62, p ≤ 0.001). Our study confirms a higher proportion of hypothyroidism among patients with schizophrenia. The awareness of such interrelation should drive physicians treating patients with schizophrenia to consider screening for hypothyroidism. Further studies are required to elucidate the underlying mechanism or the common denominator favoring the co-occurrence of schizophrenia and hypothyroidism.

Psoriasis and Hidradenitis Suppurativa: A Large-scale Population-based Study.

Abstract: Background The coexistence of psoriasis and hidradenitis suppurativa (HS) has been described, but the association between these conditions is yet to be firmly established. Objectives To study the association between psoriasis and HS using a large-scale real-life computerized database. Methods A cross-sectional study was conducted comparing the prevalence of HS among patients with psoriasis and among age-, sex- and ethnicity-matched control subjects. Results A total of 68,836 patients with psoriasis and 68,836 controls were included in the study. The prevalence of HS was increased in patients with psoriasis as compared to the control group (0.3% vs. 0.2%, respectively; OR, 1.8; 95% CI, 1.5-2.3; P Limitations Retrospective data collection. Conclusions A positive association was observed between HS and psoriasis. Further longitudinal observational studies are necessary to establish these findings in other study populations.

Mortality in bullous pemphigoid: A systematic review and meta-analysis of standardized mortality ratios

Abstract: There are inconsistent data on mortality rates in patients with bullous pemphigoid (BP). Trends in mortality in BP throughout the years are yet to be established. The aim of the present study was to study the mortality in BP patients relative to the general population and to estimate trends in standardized mortality over the past 30 years. We performed a systematic review and meta-analysis of observational studies in Medline, Embase and Scopus (1823-2017). Reference lists of included studies were also searched for eligible studies. Quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). A meta-analysis was performed using random-effects models to estimate pooled standardized mortality ratios (SMR) with 95% confidence intervals (CI). Meta-regression models were used to investigate the secular trends in SMR. Ten studies were included covering the period 1960-2015 (1736 patients, 746 deaths). Pooled all-cause SMR was 3.6 (95% CI, 2.6-5.0). There was no trend in all-cause SMR across the last three decades (regression coefficient 0.02 [change in logSMR/year]; 95% CI, 0.04-0.08; P = 0.545). In conclusion, there is a 3.6-fold increased mortality among patients with BP as compared with the age-matched general population. The excess mortality in BP has not changed significantly over the past 30 years.

Rheumatoid arthritis and thyroid dysfunction: A cross-sectional study and a review of the literature.

Abstract: Thyroid dysfunction appears to show increased prevalence in many autoimmune diseases; however, this comorbidity has not been properly investigated in patients with RA. This issue was addressed in this cross-sectional study. Using the database of the Clalit Health Services (CHS) in Israel, RA patients were paired with age- and sex-matched controls to compare the prevalence of hypothyroidism and hyperthyroidism. Chi-squared and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study included 11,782 patients with RA and 57,973 controls. The rate of thyroid dysfunction diseases in RA patients was increased compared with the prevalence in controls (16.0% and 11.7%, p RA is associated with thyroid dysfunction. Therefore, physicians treating patients with RA should be aware of the possibility of comorbid thyroid dysfunction and treat accordingly.

Ischemic heart disease and ankylosing spondylitis-assessing the role of inflammation.

Abstract: To assess the association of ankylosing spondylitis (AS) and ischemic heart disease (IHD) compared to traditional cardiovascular (CV) risk factors. Primary care and hospital records of patients with AS were analyzed, using the largest health maintenance organization in Israel, the “Clalit” Health Services data. These patients were compared with age- and gender-matched controls regarding the proportion of IHD in a cross-sectional study. Parameters including socioeconomic status, body mass index (BMI), smoking habits, and coexistent medical conditions hypertension, hyperlipidemia, and diabetes mellitus (DM) - as well as the use of NSAIDs and anti-TNFs were also assessed. The study included 4076 AS patients compared to 20,290 age- and gender-matched controls without AS. The proportion of IHD was higher among AS patients as compared to controls (14.1 vs. 6.36%, respectively, p < 0.01) and patients treated with anti-TNFs had a lower risk for IHD compared to non-anti-TNF users. The proportion of hypertension, hyperlipidemia, DM, and smoking was also higher among AS patients. However, in multivariate analyses following adjustment to these risk factors, AS was not found to be associated with IHD nor anti-TNF therapy to be a protective factor. Patients with AS have more traditional CV risk factors, thus are in a higher risk for IHD. AS itself was not shown to be independently associated with IHD. These findings emphasize the multifactorial process leading to increased proportion of IHD among AS patients and the need for a stringent control of traditional risk factors in these patients.

Epilepsy among Systemic Lupus Erythematosus Patients: Insights from a Large Database Analysis.

Abstract: OBJECTIVE Epilepsy is characterized by a relevant epidemiological and clinical burden. In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE). However, so far, relatively few and small size-based studies have been conducted. We aimed to investigate the link between seizure and SLE utilizing a large sample of subjects and extensive data analysis. METHODS Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of epilepsy 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 performed utilizing the medical database of Clalit Health Services. RESULTS The study included 5,018 patients with SLE and 25,090 age- and gender-frequency-matched controls. The proportion of epilepsy was found significantly higher among SLE patients (4.03 vs. 0.87%, p < 0.001). Using logistic regression, adjusting for multiple confounding factors, older age (≥70 years) resulted as negative predictor (OR 0.42 [95% CI 0.27-0.62], p <0.001), whereas the presence of SLE was a positive predictor of epilepsy (OR 4.70 [95% CI 3.94-5.82], p < 0.001). Interaction between SLE and elderly age resulted in high OR of 5.47 for epilepsy (95% CI 2.53-11.9). CONCLUSION Our study confirms the higher prevalence of epilepsy in SLE patients. Physicians should be aware of such findings and have a lower threshold for suspecting epileptic seizures in these patients. Further studies are needed to better elucidate the mechanisms by which SLE favors the insurgence of seizures.

Psoriasis in Israel: demographic, epidemiology, and healthcare services utilization

Abstract: BACKGROUND Updated data regarding the epidemiology of psoriasis and related healthcare utilization are lacking OBJECTIVE To investigate the epidemiology, comorbidities, healthcare services utilization, and drug use in a large group of patients with psoriasis from Clalit Health Services (CHS) database METHODS A controlled cross-sectional study was performed Case patients were defined when there was at least one documented diagnosis of psoriasis registered by a CHS dermatologist between the years 1998-2016 The extracted data included metabolic, cardiovascular and psychiatric comorbidities; community clinic visits; in- and outpatient services utilization profiles and drug use data, which included pharmacy claims of topical and systemic treatments, including phototherapy and climatotherapy Comparative analysis was performed by a univariate and multivariate analysis, adjusting for age, gender, obesity, and smoking RESULTS The study included 118,680 patients with psoriasis (prevalence of 269%) and 118,680 age- and gender-matched controls Patients with psoriasis had increased prevalence of metabolic, cardiovascular, and psychiatric illnesses Psoriasis was significantly associated with an increased healthcare utilization The mean (SD) number of annual dermatologist clinic visits and emergency room visits was 72 ± 124 and 29 ± 77 in psoriasis patients as compared to 29 ± 79 and 27 ± 74 in the control group (P < 0001) Topical steroids were the most applied treatment in psoriasis patients (155%), and topical vitamin D analogs were second in use (146%) Traditional systemic treatment for psoriasis was used in 38% of the patients, and biologic treatments were used in 16% of the patients CONCLUSIONS Our study quantifies healthcare services utilization and drug use in patients with psoriasis

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.

High proportions of dementia among SLE patients: A big data analysis

Abstract: Objective Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a wide range of systems including the peripheral and central nervous system. Cognitive impairment leading to dementia is one of the harmful central nervous system afflictions of SLE. The aim of this study was to investigate the association of SLE with dementia. Methods A cross-sectional study was conducted using Clalit Health Care database, the largest health maintenance organization in Israel with more than 4.4 million enrollees. Systemic lupus erythematosus patients were compared in a 1:5 ratio to age- and sex-matched controls. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. Results The study included 4886 SLE patients and 24 430 age-frequency- and sex-frequency-matched controls without SLE. The proportion of dementia was higher among SLE patients compared to controls (1.56% and 0.51%, respectively; P < .001). This finding was consistent across all age groups by univariate analysis. In a multivariate logistic regression analysis, SLE was significantly associated with dementia (odds ratio = 1.51, 95% confidence interval, 1.11-2.04). Conclusion Systemic lupus erythematosus is significantly associated with dementia. This finding should give rise to search for SLE in patients with an ambiguous cause for dementia, especially those with an early onset cognitive decline.

Bipolar Disorder Associated with Another Autoimmune Disease-Pemphigus: A Population-based Study.

Abstract: 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 i...

Cross-sectional analysis of the associations between fibromyalgia and diabetes mellitus.

Abstract: Background The fibromyalgia syndrome (FMS) is a chronic condition consisting of widespread musculoskeletal pain and tenderness together with mood and cognitive dysfunction. Diabetes mellitus (DM) is a common condition causing significant and detrimental morbidity and mortality. Data on the association between the two conditions is scarce and mainly based on small populations therefore lack solid evidence. Objectives To evaluate the association of FMS with DM. Material and methods This cross-sectional study used the Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. FMS patients were compared to age- and sex-matched controls regarding chronic comorbid conditions. χ2 and student's t-tests were used for univariate analysis. Results The study included 14,296 FMS patients and 71,324 age- and sex-matched controls. The FMS group had a significantly higher proportion of DM patients compared to non-FMS controls (19.8% and 17.4 respectively; OR 1.17 , 95% CI: 1.12-1.23, p Conclusions DM was found to be more common amongst FMS patients compared to matched controls to suggest that the pathophysiology of DM might lead a patient to develop FMS. Consequently, physicians treating DM patients should be aware of the possible risk and asses for clinical signs of FMS in order to diagnose and treat it in time to better their patients' quality of life and disease management.

Chronic urticaria and irritable bowel syndrome: a cross-sectional study of 11 271 patients.

Abstract: The human body interacts with the environment mainly through three major tissues: the lungs, skin, and gastrointestinal (GI) tract. In each one, an intensive nervous network is present, conjugated with abundant mast cells (MC). While MC-mediated disorders in airways and the skin are extensively discussed, MC-mediated disorders of the GI tract remain relatively uncommon. Since the GI tract is one of the three main environment-interacting tissues, it is reasonable that MC-mediated disorders of the GI may have the same weight and impact as asthma or chronic urticaria (CU). This article is protected by copyright. All rights reserved.

Autoimmune Thyroid Diseases and Thyroid Cancer in Pemphigus: A Big Data Analysis.

Abstract: There is a little consensus regarding the association of pemphigus with autoimmune thyroid diseases. While this association had been confirmed by some observational studies, others had refuted it. We aimed to study the association between pemphigus and Hashimoto's thyroiditis, Grave's disease, and thyroid cancer using a large-scale real-life computerized database. A cross-sectional study was performed to compare pemphigus patients with age-, sex-, and ethnicity-matched control subjects regarding the prevalence of overt thyroid diseases. Chi-square and t-tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed using the computerized database of Clalit Healthcare Services ensuring 4.5 million individuals. A total of 1,985 pemphigus patients and 9,874 controls were included in the study. The prevalence of Hashimoto's thyroiditis (12.9 vs. 11.9%; P = 0.228), Graves's disease (0.7 vs. 0.7%; P = 0.986), and thyroid cancer (0.7 vs. 0.5%; P = 0.305) were comparable among patients with pemphigus and control subjects. In sex-stratified analysis, pemphigus associated significantly with Hashimoto's thyroiditis among male patients (OR, 1.36; 95% CI, 1.04-1.79). In multivariate analysis adjusting for potential confounding factors, no independent associations between the conditions were revealed. Study findings were robust to sensitivity analysis that included only patients under pemphigus-specific treatments. In conclusion, Hashimoto's thyroiditis was found to be associated with pemphigus only among male patients, but not among all patients. Physicians treating patients with pemphigus might be aware of this possible association. This study does not provide a clue for an association of pemphigus with Grave's disease or thyroid cancer.

Alzheimer's Disease in Systemic Sclerosis Patients: A Nationwide Population-Based Cohort Study.

Abstract: BACKGROUND Neurological features are often overlooked in systemic sclerosis (SSc) patients and little is known about the link between dementia and SSc. OBJECTIVES We sought to investigate whether an association exists between Alzheimer's disease (AD) and SSc, as well as assess the impact of a dual diagnosis on mortality rates, by performing an extensive data analysis on a large subject sample. METHODS We utilized the medical database of the Clalit-Health-Services in a case-control study. Patients with SSc were compared with age- and sex-matched controls with regard to the prevalence of AD and its impact on their mortality. RESULTS Our study included 2,431 SSc patients and 12,377 age- and sex-matched controls. The mean age of the study population was 63.32±18.06 years and the female to male ratio was 4.5:1. 134 (5.5%) cases had AD as a co-morbidity in comparison with 749 (5.9%) of the controls. The mortality rate was 12.5% among controls and 26.2% among SSc cases. On the Cox multivariate survival analysis, diagnosis of SSc and AD demonstrated significant HRs (2.35 (95% CI 2.05-2.69, p < 0.0001) and 2.19 (95% CI 1.94-2.48, p < 0.0001), respectively). SSc patients with AD had a relative risk of death of 2.35 (95% CI: 1.44-3.83) in comparison with SSc patients without AD. CONCLUSION AD is a predictor of death in SSc and therefore preemptive screening may be warranted. Further studies are needed to evaluate whether improvements in the medical regimen for SSc may lead to a reduction in AD development and possibly to increased survival as well.

Pericarditis among giant cell arteritis patients: From myth to reality.

Abstract: BACKGROUND Giant cell arteritis (GCA) is an inflammatory disease of unknown etiology affecting adults age > 50 years. GCA (also known as temporal arteritis) is a vasculitis of large and medium-size vessels that involves the extracranial branches of the carotid artery. Common manifestations include constitutional symptoms, headache, jaw claudication, scalp tenderness, and vision loss. Cardiac involvement in GCA is considered to be as low as 5%, and < 30 cases of pericarditis among GCA patients have been reported in the literature. The aim of this study was to evaluate the association between GCA and pericarditis by conducting a cross-sectional study utilizing the database of the largest healthcare provider in Israel. HYPOTHESIS GCA is associated with pericarditis. METHODS The proportion of past documentation of pericarditis among patients diagnosed with GCA was compared with that of their age- and sex-matched controls. Univariate analysis was performed using the χ2 and t tests; multivariate analysis was performed using logistic regression. RESULTS The study included 4329 GCA patients and 21 611 controls. GCA patients had higher rates of cardiovascular risk factors. Pericarditis was observed in 53 GCA patients and 72 controls (1.22% vs 0.33%, respectively; P < 0.001), significantly higher among GCA patients in comparison with controls. A significant interaction was found between GCA, pericarditis, and young age (<70 years). CONCLUSIONS The study showed an independent association between GCA and pericarditis, especially among young patients. Proper screening should be applied whenever a suspicion arises as to the existence of comorbidity in patients with either disease.

Short article: Crohn's disease and pemphigus: is there an association?: a population-based study.

Abstract: Background Although the coexistence of Crohn's disease (CD) and pemphigus has been reported in several individuals, the association between the two conditions was not investigated systematically in the past. A recent association between pemphigus and ulcerative colitis has been reported. The study aims to estimate the association between pemphigus and CD using a large-scale real-life computerized database. Patients and methods A cross-sectional study was carried out comparing pemphigus patients with age-matched, sex-matched, and ethnicity-matched control participants in terms of the prevalence of CD. χ-Test and t-test were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was carried out utilizing the computerized database of Clalit Health Services ensuring 4.5 million patients. Results A total of 1985 pemphigus patients and 9874 controls were included in the study. The prevalence of CD was comparable in patients with pemphigus and controls [0.4 vs. 0.3%, respectively; odds ratio (OR): 1.2; 95% confidence interval (CI): 0.5-2.5; P=0.688]. In an age-stratified analysis, a significant association was observed between pemphigus and CD in patients younger than 40 years (2.1 vs. 0.4%, respectively; OR: 5.1; 95% CI: 1.0-25.7; P=0.027). In a multivariate analysis adjusting for potential confounding factors, no independent association between the two conditions was found (OR: 0.9; 95% CI: 0.4-2.0; P=0.828). Study findings were robust to sensitivity analysis that included patients under pemphigus-specific treatments. Conclusion Unlike ulcerative colitis, CD was not associated with pemphigus. Further research is warranted to understand the pathophysiology of these observations better.