Amyloidosis in hidradenitis suppurativa: a cross-sectional study and review of the literature.

BACKGROUND: Coexistence of hidradenitis suppurativa (HS) and amyloidosis has been anecdotally described, but the association between these conditions is yet to be firmly established. AIM: To study the association between HS and amyloidosis using a large-scale computerized database, and to perform a literature review to characterize all reported patients with coexistent HS and amyloidosis. METHODS: A cross-sectional study was conducted comparing the prevalence of amyloidosis among patients with HS and age-, sex- and ethnicity-matched healthy controls (HCs). Additionally, a review of literature was performed to summarize all reported cases with a dual diagnosis of both conditions. RESULTS: In total, 4417 patients with HS and 22 085 controls were included in the study. The prevalence of amyloidosis was increased in patients with HS compared with the HC group [n = 7 (0.2%) vs. n = 2 (0.0%), respectively; OR = 17.5; 95% CI 3.6-84.4; P < 0.001]. In a multivariate analysis, HS was still associated with amyloidosis (OR = 11.2; 95% CI 1.3-94.5; P = 0.03). The literature review identified nine patients who developed amyloidosis during the course of HS, with 44.4% eventually having renal failure. ‬Favourable outcomes were reported in patients managed by tumour necrosis factor (TNF)-α inhibitors. CONCLUSION: This study establishes the association between HS and amyloidosis. Screening for amyloidosis may be considered in patients with HS with a relevant clinical picture, mainly proteinuria. TNF-α inhibitors may be preferred in patients with a dual diagnosis of these conditions.

Drug survival in patients with psoriasis is associated with the availability of biologic medications.

BACKGROUND: Drug survival rates in patients with psoriasis had been described extensively. Different survival rates of TNF-α inhibitors (TNFIs), ustekinumab and secukinumab were reported. OBJECTIVES: To investigate drug survival rates of TNFIs, ustekinumab and secukinumab, with particular emphasis on the difference between ustekinumab and secukinumab. METHODS: Survival analysis was performed in patients with moderate-to-severe psoriasis who received adalimumab, infliximab, etanercept, ustekinumab and secukinumab treatment in 2002-2018, using the Clalit Health Services database. Stratified analysis was performed according to biologic treatment lines. Multivariate analysis was performed adjusting for demographic variables, calendar year, metabolic syndrome, psoriatic arthritis, biologic treatment line, biologic naivety, co-administration of oral treatments and previous oral systemic treatment exposure. RESULTS: Among 1459 patients treated with 3070 biologic medication courses, ustekinumab had a significantly higher crude survival as compared with TNFIs and secukinumab. The mean drug survival of ustekinumab, adalimumab, etanercept, infliximab and secukinumab was 43.5 (CI: 39.7-47.2), 38.2 (CI: 34.8-41), 33.9 (CI: 30.8-37.1), 28.2 (CI: 22.5-33.8) and 17.1 (CI: 15.6-18.6) months, respectively, with significant statistical differences for all comparisons (P < 0.001). The differences between ustekinumab and secukinumab were not significant following adjustment to factors that included treatment line (hazard rate 1.16, CI: 0.93-1.43). CONCLUSION: Different drug survival rates between ustekinumab and secukinumab are determined by the treatment line and calendar year, reflecting the availability of biologic medications, and not only by the biologic attributes of each medication.

Incidence and prevalence of psoriasis in Israel between 2011 and 2017.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease associated with a heavy burden of morbidity, disability and cost. The occurrence of the disease in Israel has not been previously investigated. OBJECTIVES: To provide standardized estimates of trends in psoriasis incidence, prevalence and mortality among patients in Israel between 2011 and 2017. METHODS: Using electronic health records from Clalit Health Services, the largest nationwide public health provider in Israel, we conducted a population-based study investigating trends in the annual incidence and prevalence of psoriasis between the years 2011 and 2017. We report age- and sex-adjusted rates, using the standard European population as a reference. RESULTS: We identified 71 094 incident psoriasis cases. The mean (SD) age of onset was 42.4 (21.0) years with a bimodal distribution, peaking in the early '30s and early '60s. Late-onset psoriasis, occurring after 40 years of age, accounted for 51.1% of incident cases. The annual psoriasis incidence rate was constant throughout the study period (280/100 000 person-years). Psoriasis prevalence rose from 2.5% in 2011 to 3.8% in 2017. CONCLUSIONS: Psoriasis prevalence is increasing in Israel, although its incidence is stable. Clinicians and policymakers should plan to address the growing demands in the clinical, economic and societal burden of psoriasis.

The association between the socioeconomic status and anxiety-depression comorbidity in patients with psoriasis: a nationwide population-based study.

BACKGROUND: Numerous studies have indicated that comorbid anxiety and depression are associated with a more severe course of illness. Yet generally, the study of the effect of psoriasis on patients' mental health has considered anxiety and depression to be separate states. OBJECTIVE: To measure the association between psoriasis and anxiety, depression and anxiety-depression co-occurrence among patients according to their socioeconomic statuses (SES). METHODS: A nationwide population-based study of psoriasis patients and age and gender frequency-matched controls (n = 255 862) was designed. Diagnostic data were obtained from Clalit Health Services, the largest managed care organization in Israel. This database was established using continuous real-time input from healthcare providers, pharmacies, medical care facilities and administrative computerized operating systems. RESULTS: After controlling for demographic and clinical variables, psoriasis was associated with anxiety (OR 1.11, 95% CI 1.01-1.23, P < 0.05), depression (OR 1.17, 95% CI 1.08-1.26, P < 0.001), and anxiety and depression co-occurrence (OR 1.32, 95% CI 1.21-1.45, P < 0.001) among patients with low SES, yet was associated only with anxiety (OR 1.15 95% CI 1.04-1.27, P < 0.001) but not depression or comorbid anxiety-depression among patients with high SES. Survival analyses indicated that between the ages of 40 and 60, the cumulative probability of psoriasis patients with low SES to suffer from anxiety, depression and their co-occurrence inclined more sharply with age as compared to psoriasis patients with high SES. CONCLUSIONS: As psoriasis patients with low SES are prone to suffer from more severe courses of anxiety and depression, the choice of treatment of psoriasis should address the SES as well as the underlying psychiatric disease.

Atopic dermatitis and the metabolic syndrome: a cross-sectional study of 116 816 patients.

BACKGROUND: Data regarding the association between atopic dermatitis (AD) and the metabolic syndrome are controversial. OBJECTIVE: To evaluate the prevalence of the metabolic syndrome and its components in a large group of patients with AD compared to a matched reference group. METHODS: A cross-sectional study of AD patients diagnosed by a dermatologist between 1998 and 2016, and a matched comparison group was performed. We analysed the association between AD and metabolic syndrome, its components and possible complications for the entire study population, adults (age > 18) and adults with moderate-to-severe AD. RESULTS: The study included 116 816 patients with AD and 116 812 comparison enrollees. AD in the entire group of patients and in the adult patients was associated with a higher prevalence of dyslipidaemia and a lower prevalence of diabetes and metabolic syndrome. Moderate and severe AD were associated, respectively, with higher prevalence rates of the metabolic syndrome (17.0% vs. 9.4%), its components (obesity: 22.2% vs. 18.6%; diabetes: 15.9% vs. 9.2%; hypertension 27.9% vs. 15.3%; dyslipidaemia 47.1% vs. 28.5%, all P values < 0.001) and cardiovascular morbidity (all P values < 0.001). Multivariate analysis demonstrated a significant overrepresentation of the metabolic syndrome in moderate-to-severe AD (P = 0.04). CONCLUSIONS: Severely affected patients with AD may have one or more undiagnosed components of metabolic syndrome.

Association between schizophrenia and an autoimmune bullous skin disease-pemphigus: a population-based large-scale study.

AIMS: Immunological hypotheses have become increasingly prominent suggesting that autoimmunity may be involved in the pathogenesis of schizophrenia. Schizophrenia was found to be associated with a wide range of autoimmune diseases. However, the association between pemphigus and schizophrenia has not been established yet. We aimed to estimate the association between pemphigus and schizophrenia using a large-scale real-life computerised database. METHODS: This study was conducted as a cross-sectional study utilising the database of Clalit Health Services. The proportion of schizophrenia was compared between patients diagnosed with pemphigus and age-, gender- and ethnicity-matched control subjects. Univariate analysis was performed using χ2 and Student's t-test and a multivariate analysis was performed using a logistic regression model. RESULTS: A total of 1985 pemphigus patients and 9874 controls were included in the study. The prevalence of schizophrenia was greater in patients with pemphigus as compared to the control group (2.0% v. 1.3%, respectively; p = 0.019). In a multivariate analysis, pemphigus was significantly associated with schizophrenia (OR, 1.5; 95% CI, 1.1-2.2). The association was more prominent among females, patients older than 60 years, and Jews. CONCLUSIONS: Pemphigus is significantly associated with schizophrenia. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid schizophrenia and be treated appropriately.

Chronic urticaria and osteoporosis: a longitudinal, community-based cohort study of 11 944 patients.

BACKGROUND: Chronic urticaria (CU) carries many risk factors for osteoporosis, but data on the relationships between CU and osteoporosis are lacking. OBJECTIVES: To evaluate the association between CU and osteoporosis in a large community-based study. METHODS: A nationwide observational longitudinal cohort study was conducted. CU was defined as four pairs of urticaria diagnoses; each pair was recorded within a period of 6 weeks and was registered by physicians in a primary-care setting. Patients with CU and their age- and sex- matched controls were followed for the incidence of osteoporosis and other laboratory data between 2002 and 2017. Data regarding systemic steroid exposure and other relevant risk factors for osteoporosis were obtained. Analyses of risk for osteoporosis were performed in Cox regression models adjusted for age, sex, exposure to systemic corticosteroids, obesity, smoking and hyper- and hypothyroid disease. RESULTS: The study included 11 944 patients with CU and 59 829 controls. During the study's observation period, 1035 (8·7%) patients with CU were diagnosed with osteoporosis, compared with 4046 (6·8%) controls. The adjusted multivariate analysis demonstrated that CU was significantly associated with a higher risk for osteoporosis (hazard ratio 1·23, 95% confidence interval 1·10-1·37, P < 0·001). CONCLUSIONS: CU may impose a risk for osteoporosis. Appropriate targeted screening should be considered.

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

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 6 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, hyperlipidaemia, 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), hyperlipidaemia (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.

The association between systemic lupus erythematosus and bipolar disorder - a big data analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that has a wide variety of physical manifestations, including neuropsychiatric features. Bipolar disorder (BD) is a chronic, episodic illness, that may present as depression or as mania. The objective of this study was to investigate the association between SLE and BD using big data analysis methods. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of BD 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, adjusting for confounders. The study was performed utilizing the chronic disease registry of Clalit Health Services medical database. RESULTS: The study included 5018 SLE patients and 25,090 matched controls. BD was found in a higher prevalence among SLE patients compared to controls (0.62% vs. 0.26%, respectively, P<0.001). BD patients had a greater prevalence of smokers compared to non-BD patients (62.5% vs 23.5%, respectively, P<0.001). In a multivariate analysis, smoking and SLE were both found to be significantly associated with BD. CONCLUSIONS: SLE was found to be independently associated with BD. These findings may imply that an autoimmune process affecting the central nervous system among SLE patients facilitates the expression of concomitant BD.

Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study.

AIMS: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease involving multiple organs, including the central nervous system. Evidence of immune dysfunction exists also in schizophrenia, a psychiatric illness involving chronic or recurrent psychosis. The aim of our study was to investigate if there is an epidemiological association between SLE and schizophrenia. METHOD: A cross-sectional study was conducted comparing patients with SLE with age and gender-matched controls regarding the proportion of patients with comorbid schizophrenia. χ 2- and t-tests were used for univariate analysis, and interaction of schizophrenia with SLE across strata of covariates was checked. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services in Israel. RESULTS: The study included 5018 patients with SLE and 25 090 controls. SLE patients had a female predominance, and a higher proportion of smoking compared with age and sex-matched controls. In multivariate analysis, SLE was found to be independently associated with schizophrenia while controlling for age, gender, socioeconomic status (SES) and smoking (OR 1.33, p = 0.042). CONCLUSIONS: We found a positive association between SLE and schizophrenia across patients of different age, gender and SES. This association can contribute to understanding the pathophysiology of the two disorders and may also have clinical implications for earlier as well as better diagnosis and treatment.

Aortic aneurysm association with SLE - a case-control study.

OBJECTIVES: Aortic aneurysm is a life threatening cardiovascular complication in patients with systemic lupus erythematosus (SLE).The purpose of this study was to investigate the association between SLE and occurrence of aortic aneurysms. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the proportion of aortic aneurysm in a case-control 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 5018 patients with SLE and 25,090 age- and sex-matched controls. The proportion of aortic aneurysm in patients with SLE was increased compared with the proportion in controls (0.6% and 0.1%, respectively, p < 0.001). In a multivariate analysis SLE was associated with the coexistence of aortic aneurysms (odds ratio 2.06, 95% confidence interval 1.21-3.51). CONCLUSIONS: Patients with SLE have a higher proportion of aortic aneurysms as compared with matched controls. Therefore, physicians treating patients with SLE should be aware of this life threatening association.

Risk of Herpes zoster in patients with psoriasis treated with biologic drugs.

BACKGROUND: Little is known about the risk of herpes zoster (HZ), among patients with psoriasis treated with biologic drugs. OBJECTIVE: To determine the incidence of HZ in patients with psoriasis and the association between HZ and use of biologic drugs in these patients. METHODS: The study was performed utilizing the medical database of Clalit Health Services in Israel. The incidence of HZ events was calculated among patients with psoriasis treated with phototherapy, traditional systemic medications and biologic drugs. Incidence rates of HZ events were calculated for each medication, as well as hazard ratios adjusted for age, sex and healthcare utilization burden. RESULTS: Among 22,330 psoriasis patients (215,656 person-years), 1321 HZ cases were diagnosed. The crude incidence rates per 1000 person-years were 6.0 for UVB phototherapy (95% confidence interval (CI), 0-12.8), 10.1 for PUVΑ (1.3-19.0), 5.4 for acitretin (2.2-8.7), 17.0 for methotrexate (10.6-23.4), 13.9 for etanercept (0.3-27.4), 19.3 for infliximab (0-45.8) and 4.6 for controls (CI, 4.3-5.0). No cases of HZ were seen among patients treated with alefacept, efalizumab or adalimumab. In a multivariate analysis, age, female sex, healthcare utilization pattern and corticosteroid treatment were associated with the time to HZ infection. The association of HZ with infliximab approached statistical significance (Hazard ratio: 1.77, 95% CI: 0.92-3.43), but none of the other biologic drugs were significantly associated with the risk of HZ. CONCLUSION: Among patients with psoriasis, treatment with some biologic drugs was associated with a higher incidence of HZ compared with controls, though the difference was not statistically significant.

Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response.

OBJECTIVE: To assess the effect of rituximab on the efficacy and safety of influenza virus vaccine in patients with rheumatoid arthritis (RA). METHODS: The study group comprised patients with RA treated with conventional disease-modifying drugs with or without rituximab. Split-virion inactivated vaccine containing 15 microg haemagglutinin/dose of B/Shanghai/361/02 (SHAN), A/New Caledonian/20/99 (NC) (H1N1) and A/California/7/04 (CAL) (H3N2) was used. Disease activity was assessed by the number of tender and swollen joints, duration of morning stiffness and evaluation of pain on the day of vaccination and 4 weeks later. CD19-positive cell levels were assessed in rituximab-treated patients. Haemagglutination inhibition (HI) antibodies were tested and response was defined as a greater than fourfold rise 4 weeks after vaccination or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated in all subjects. RESULTS: The participants were divided into three groups: RA (n = 29, aged 64 (12) years), rituximab-treated RA (n = 14, aged 53 (15) years) and healthy controls (n = 21, aged 58 (15) years). All baseline protective levels of HI antibodies and GMT were similar. Four weeks after vaccination, there was a significant increase in GMT for NC and CAL antigens in all subjects, but not for the SHAN antigen in the rituximab group. In rituximab-treated patients, the percentage of responders was low for all three antigens tested, achieving statistical significance for the CAL antigen. Measures of disease activity remained unchanged. CONCLUSION: Influenza virus vaccine generated a humoral response in all study patients with RA and controls. Although the response was significantly lower among rituximab-treated patients, treatment with rituximab does not preclude administration of vaccination against influenza.

Significant dominance of fibrinogen over immunoglobulins, C-reactive protein, cholesterol and triglycerides in maintaining increased red blood cell adhesiveness/aggregation in the peripheral venous blood: a model in hypercholesterolaemic patients.

BACKGROUND: It is not clear what is the relative importance of fibrinogen, immunoglobulins, highly sensitive C-reactive protein (hs-CRP), cholesterol and triglyceride concentrations on the appearance of aggregated red blood cells in the peripheral blood. DESIGN: Six hypercholesterolaemic patients undergoing regular LDL apheresis that were examined repeatedly before and following the procedure. RESULTS: We determined the degree of erythrocyte adhesiveness/aggregation in relation to the concentration of the above-mentioned macromolecules in 80 samples. In a linear logistic regression the respective R2 values for fibrinogen, total cholesterol, triglycerides, hs-CRP, IgG, IgM and IgA were 0.45 (P<0.0001), 0.2 (P<0.0001), 0.02 (P=0.02), 0.001 (P=NS) and 0.002 (P=NS), respectively. We further analyzed the potential of ApoA, ApoB and Lpa to participate in red cell adhesiveness/aggregation and found them to be not significant. CONCLUSIONS: In a milieu of adhesive macromolecules, lipids and inflammation-sensitive proteins including fibrinogen, total cholesterol, triglycerides, hs-CRP and immunoglobins G, M and A, fibrinogen has a dominant role in maintaining the red blood cell adhesiveness/aggregation in the peripheral venous blood. These findings are relevant for the research directed at finding new apheretic modalities to reduce the degree of red blood cell adhesiveness/aggregation in the peripheral blood.