Erez Batat

Seasonality of Asthma: A Retrospective Population Study

OBJECTIVES: Seasonal variations in asthma are widely recognized, with the highest incidence during September. This retrospective population study aimed to investigate whether this holds true in a large group of asthmatic children in primary care and to assess the impact of age, gender, urban/rural living, and population sector. METHODS: The key study outcomes were the diagnosis of asthma exacerbations and asthma medication prescriptions, recorded by family physicians during 2005 to 2009. These were analyzed by “week of diagnosis” in Clalit Health Services’ electronic medical record database. Regression models were built to assess relative strength of secular trends, seasonality, and age-group in explaining the incidence of asthma exacerbations. RESULTS: A total of 919 873 children aged 2 to 15 years were identified. Of these, 82 234 (8.9%) were asthmatic, 61.6% boys and 38.4% girls; 49.1% aged 2 to 5 years, 24.1% 6 to 9 years, and 26.8% 10 to 15 years. We observed a 2.01-fold increase in pediatric asthma exacerbations and 2.28-fold increase in prescriptions of asthma bronchodilator medications during September (weeks 37–39 vs weeks 34–36) compared with August. The association between the opening of school and the incidence of asthma-related visits to the primary care physician was greatest in children aged 2 to 5 years (odds ratio, 2.15) and 6 to 11 years (1.90-fold). Adolescents (age 12–15 years) had a lesser peak (1.81-fold). In late fall there was a second rise, lasting with fluctuations throughout winter, with a trough in summer. CONCLUSIONS: Returning to school after summer is strongly associated with an increased risk for asthma exacerbations and unscheduled visits to the primary care physician.

Psoriatic arthritis treatment and the risk of herpes zoster

Objectives To study the association between traditional disease-modifying antirheumatic drugs (c-DMARD) or anti-TNF-α agents and herpes zoster (HZ) in patients with psoriatic arthritis (PsA). Methods A retrospective cohort study was conducted in patients with PsA between 2002 and 2013. Patients were grouped as follows: no DMARDs (Group A); c-DMARDs (Group B); anti-TNF-α agents (Group C); anti-TNF-α agents in combination with c-DMARDs (Group D). Crude incidence rates (IR) were calculated as number of HZ episodes per 1000 patient-years. A Cox regression model was used to adjust for HZ risk factors (age, gender, steroid use, Charlson Comorbidity Index score, and previous treatment) in order to estimate their contribution to the risk of the first HZ event. Results The study included 3128 patients, mean age 50.26±14.54 years; 46.2% male. During a period of 20 096 person-years 182 HZ events were observed. The crude IR (95% CI) of HZ in the study population was 9.06 per 1000 patient-years, and in Groups A-D 7.36 (5.41 to 9.79), 9.21 (7.5 to 11.21), 8.64 (4.84 to 14.26), 17.86 (10.91 to 27.58), respectively. In a multivariate analysis, age (HR 1.01, 95% CI 1.00 to 1.02), treatment with steroids (HR 1.08, 95% CI 1.04 to 1.13), and a combination of anti-TNF-α agents and c-DMARDs (HR 2.37, 95% CI 1.32 to 4.22) were significantly associated with HZ events. Conclusions In our database, the risk of HZ was significantly increased with age, treatment with steroids, and combination of anti-TNF-α agents and c-DMARDs, but not with c-DMARDs or anti-TNF-α therapy alone. Time to HZ event was shorter in patients treated with anti -TNF-α agents.

Pemphigus and hematologic malignancies: A population-based study of 11,859 patients

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.

COPD and lung cancer in patients with pemphigus- a population based study

BACKGROUND Recent evidence indicates that autoimmunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). COPD was observed at higher frequency in patients with several autoimmune diseases. The association between pemphigus and COPD has not been evaluated in the past. OBJECTIVES To study the association between pemphigus and COPD using a large-scale real-life computerized database. METHODS A cross-sectional study was conducted comparing pemphigus patients with age-, sex- and ethnicity-matched control subjects regarding the prevalence of COPD and lung cancer. Chi-square and t-tests were used for bivariate analysis, and logistic regression model was used for multivariate analysis. The study was performed utilizing the computerized database of Clalit Health Services ensuring 4.4 million subjects. RESULTS A total of 1985 pemphigus patients and 9874 controls were included in the study. The prevalence of COPD was greater in patients with pemphigus as compared to the control group (13.4% vs. 10.1%, respectively; P < 0.001). In a multivariate analysis adjusting for smoking and other confounding factors, pemphigus was significantly associated with COPD (OR, 1.312-1. 5) but not with lung cancer. Study findings were robust to sensitivity analysis that included patients under pemphigus-specific treatments. CONCLUSIONS A significant association was found between COPD and pemphigus. Physicians treating patients with pemphigus might be aware of this possible association. This observation may further support the hypothesis that COPD has an autoimmune component.

Endocrine Comorbidities in Patients with Psoriatic Arthritis: A Population-based Case-controlled Study

Objective. To investigate endocrine comorbidities in patients with psoriatic arthritis (PsA). Methods. A retrospective, cross-sectional study was performed with the database of Clalit Health Services, the largest healthcare provider in Israel, between 2002 and 2014. Patients with PsA were identified and matched by age and sex to healthy controls. The following morbidities were analyzed: hypo/hyperthyroidism, hypo/hyperparathyroidism, hyperprolactinemia, Cushing disease, Addison disease, diabetes insipidus, diabetes mellitus (DM), pituitary adenoma, acromegaly, and osteoporosis. Descriptive statistics were applied. The associations between PsA and endocrine comorbidities were analyzed by univariable and multivariable analysis. Results. The study included 3161 patients with PsA, 53.4% women, mean age 58.4 ± 15.4 years, and 31,610 controls. Comparative analyses yielded higher proportion of hypothyroidism (12.7% vs 8.6%, p < 0.0001), Cushing disease (0.3% vs 0.1%, p < 0.0001), osteoporosis (13.2% vs 9.1%, p < 0.0001), and DM (27.9% vs 20.7%, p < 0.0001) in the PsA group compared with the control group. In the multivariable regression analysis, the following diseases were more frequent in the PsA group: hypothyroidism (OR 1.61, 95% CI 1.47–1.81), DM (OR 1.35, 95% CI 1.18–1.42), Cushing disease (OR 3.96, 95% CI 1.67–9.43), and osteoporosis (OR 1.56, 95% CI 1.37–1.78). Conclusion. PsA is associated with a high frequency of hypothyroidism, osteoporosis, DM, and Cushing disease. Awareness of these comorbidities may help physicians provide the optimal medical care to patients with PsA.

SAT0378 Cardiac and Cardiovascular Morbidities in Patients with Psoriatic Arthritis: A Population-Based Cohort Study

Background Psoriatic arthritis (PsA) is associated with higher prevalence and risk for cardiovascular morbidities [1,2]. Objectives The aim of the study is to substantiate these findings in our population and to examine additional aspects of cardiovascular morbidities, including congestive heart failure and cardiomyopathy. Methods A retrospective, longitudinal, cohort case control study was performed on records of patients with PsA between 2000 and 2013 from the database of Israels largest health care provider, Clalit Health Services. For each patient with PsA, 5 control patients without history of psoriasis or rheumatoid arthritis were chosen, matched for age and gender. The following morbidities were analyzed: ischemic heart disease (IHD), valvular heart disease excluding mitral valve prolapse, congestive heart failure (CHF), cardiomyopathy, idiopathic hypertrophic subaortic stenosis (IHSS), cerebrovascular accident (CVA), carotid artery disease, peripheral vascular disease (PVD), and aortic aneurism. T-test was used to compare continuous variables and Chi square test was used for categorical variables. Age, gender, socioeconomic status and ethnicity were entered into a multivariate regression model. Results The study included 3161 patients with PsA, 1474 males (46.6%) and 1687 (53.4%) females with a mean age of 58.29±15.44 years, and 15,805 controls. Comparative analysis demonstrated higher prevalence of the following in the case cohort: IHD (18.95% vs. 14.49%) p<0.0001, valvular heart disease (6.99% vs. 5.10%) p<0.0001, CHF (5.98% vs. 4.61%) p<0.001, cardiomyopathy (1.28% vs. 0.80%) p<0.010, carotid artery disease (2.53% vs. 1.99%) p=0.053. and peripheral vascular disease (4.87% vs. 3.68%) p=0.001. Prevalence of IHSS, CVA and aortic aneurism were not significantly higher in the patients compared with the control group. The following were significantly more prevalent in patients than controls in multivariate regression analysis model: IHD (P<0.0001), CHF (P<0.0001), cardiomyopathy (p=0.011), and PVD (p=0.001) valvular heart disease (P<0.0001); and there was a trend to higher prevalence of carotid artery disease in PsA patients (p=0.066). Conclusions A high prevalence of cardiovascular co-morbidities was found in this cohort of PsA patients. The spectrum of cardiac involvement was not limited to IHD, carotid artery disease and PVD, and included also increased risk of CHF, cardiomiopathies and valvular heart disease. A high index of suspicion, and close monitoring and treatment of cardiovascular risk factors are recommended. References Husni ME, Mease PJ. Managing comorbid disease in patients with psoriatic arthritis. Curr Rheumatol Rep 2010;12:281–287. Horreau C, Pouplard C, Brenaut E, Barnetche T, Misery L, Cribier B, et a l. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol 2013;27(Suppl. 3):12–29. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3830

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

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.

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

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 Hashimotos thyroiditis, Graves 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 Hashimotos thyroiditis (12.9 vs. 11.9%; P = 0.228), Gravess 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 Hashimotos 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, Hashimotos 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.