Guy Shalom

Hidradenitis suppurativa and metabolic syndrome: a comparative cross-sectional study of 3207 patients

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease.

Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500 000 Person-year Study

IMPORTANCE The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. OBJECTIVE To describe the risk for HZ in patients with psoriasis and its relation to treatment. DESIGN, SETTING, AND PARTICIPANTS A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95,941 patients with psoriasis in the analysis, with 522,616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. MAIN OUTCOMES AND MEASURES Incidence of HZ associated with systemic therapies. RESULTS In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). CONCLUSIONS AND RELEVANCE Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.

Is preeclampsia a significant risk factor for long-term hospitalizations and morbidity?

Objective: The present study was aimed to evaluate long-term morbidity of patients with hypertensive disorders of pregnancy. Study design: A retrospective cohort study was conducted, including women who gave birth between the years of 1988 to 1998, and had a follow-up until December 2009. Data were extracted by linking a computerized database of hospitalizations with computerized database containing maternal records from the same regional medical center. The exposed group comprised 2072 patients with mild or severe preeclampsia in one or more of their pregnancies and the comparison group included 20742 patients without preeclampsia. Excluded from the study were patients with chronic hypertension and pre-gestational diabetes before the index pregnancy. Data included subsequent hospitalizations in internal medicine, oncology, nephrology, neurology, cardiac intensive care unit, and hematology, as well as a diagnosis of chronic hypertension during the follow-up period. Results: Patients with preeclampsia had significantly higher rates of chronic hypertension diagnosed after the index pregnancy as compared with patients without preeclampsia (12.5% vs. 0.9%; OR = 15.8, 95% CI 12.9–19.3; p < 0.001). Likewise, patients with preeclampsia were more likely to be hospitalized at least once (13.7% vs. 11.4%; OR = 1.2, 95% CI 1.1–1.4; p = 0.002) as compared with patients without preeclampsia. Exposed women had 582 hospitalizations (0.28 hospitalization/patient), while the non-exposed patients had a total of 4687 hospitalizations (0.23 hospitalization/patient; p < 0.001). Conclusion: Preeclampsia is a significant risk factor for long-term morbidity such as chronic hypertension and hospitalizations later in life.

Biologic drug survival in Israeli psoriasis patients

Background Drug survival is defined as the time period of treatment with a certain drug until its cessation. The role of previous exposure to traditional systemic treatments in biologic survival is still unknown. Objective To investigate the drug survival rates of biologic treatments in patients with psoriasis and to identify predictor factors. Methods Survival analysis was performed on patients with severe psoriasis who received adalimumab, infliximab, etanercept, and ustekinumab for treatment of psoriasis, drawn from the Clalit Health Services database. Multivariate analysis was performed adjusting for demographic variables; metabolic syndrome and its components; psoriatic arthritis; biologic naivety; coadministration of methotrexate, acitretin, or cyclosporine; and previous standard systemic treatment exposure. Results Among 907 patients treated with 1575 biologic treatments, ustekinumab had a significantly higher survival rate than tumor necrosis factor inhibitors. Biologic naivety and concomitant methotrexate intake were positive predictors for drug survival, whereas the female sex and the duration of previous systemic treatments were negative predictors. Limitations Data regarding disease severity or duration could not be drawn from the Clalit Health Services database. Conclusion Ustekinumab had better retention rates in comparison with other investigated biologics in patients with severe psoriasis, most of whom used it as a third line therapy.

Psoriasis and obstructive sleep apnea.

Psoriasis is a chronic inflammatory skin disorder that is associated with the metabolic syndrome and its components. An association between obstructive sleep apnea (OSA) and the metabolic syndrome was previously observed.

Healthcare Services Utilization and Drug Use in Patients with Chronic Urticaria

TO THE EDITOR Chronic urticaria (CU) is defined as continuous urticaria occurring in a period of 6 weeks or more while off treatment (Zuberbier, 2012). Second-generation antihistamines with up-dosing up to fourfold constitute the firstand second-line treatments for CU, and are the mainstay of pharmacologic management for most patients (Bernstein et al., 2014). About 40–70% of patients attending tertiary care clinics will become symptom-free at appropriate doses of antihistamines treatment. Antihistamine therapy failure is considered only after the patient does not respond to augmented dosage (Zuberbier et al., 2014). Third-line therapies, is used as add-on therapy and include omalizumab, cyclosporine, and the leukotriene receptor antagonist, montelukast. Many other treatments have been used in patients with refractory CU such as sulfasalazine, colchicine, methotrexate, mycophenolate mofetil, azathioprine, and cyclophosphamide (Grattan et al., 1992; Grattan et al., 2000; Jiang et al., 2008; Di Lorenzo et al., 2008; Mitzel-Kaoukhovet al., 2010; Perez et al., 2010; Pho et al., 2011; Orden et al., 2014). Nonetheless, the level of evidence supporting use of the modalities beyond third-line treatments is rather weak and based on anecdotal reports or small case series. Notably, systemic corticosteroids may eliminate urticarial lesions in the short-term; however, their long-term use (more than 10 days) is undesirable due to cumulative severe adverse effects (Makris et al., 2013; Zuberbier et al., 2014). The aim of our study was to investigate utilization of health-care services and drug use among patients with CU using a large community-based database from Clalit Health Services (CHS). Our study was designed as a crosssectional study of CU patients and ageand gender-matched controls, based on CHS database–a large public healthcare provider organization in Israel. We used a conservative definition for CU as follows: four couples of urticaria diagnoses, recorded within a period of 6 weeks, registered by physicians in community services, out-patient clinics, or during hospitalization, from January 2002 to December 2012. The control group consisted of randomly selected ageand gender-matched patients without CU, extracted from the general population of CHS enrollees. Patients with one or more diagnoses of urticaria were excluded from the control group. Health-care services utilization during 2013 was extracted for both cases and controls. Drug use data was based on pharmacy claims during 2013. Since ~50% of CU patients experience spontaneous resolution within 6–12 months from symptoms onset, patients with high use of CU-related medications during 2013 were considered patients with persistent disease. To assess the number of patients with chronic steroid treatment, we evaluated the lag period between two consecutive systemic corticosteroid prescriptions among patients treated with more than one prescription. This subgroup of patients was subLETTER TO THE EDITOR

Chronic Urticaria and Atopic Disorders: a Cross-sectional Study of 11,271 Patients

Chronic urticaria (CU) and atopic disorders such as atopic dermatitis (AD), allergic rhinoconjunctivitis (AR), and asthma are related to aberrant immune function. The relationship between atopic disorders and CU is controversial, mostly since epidemiological data are lacking. The aim of our study was to investigate the association between CU and asthma, AD, and AR using a database of Clalit Health Services (CHS) - the largest healthcare provider organization in Israel. This article is protected by copyright. All rights reserved.

Chronic Urticaria and the Metabolic Syndrome: a Cross-sectional Community-based Study of 11,261 Patients

Emerging evidence suggests that chronic urticaria (CU) is associated with chronic, low‐grade, inflammatory process.

Demographic and health care service utilization by 4417 patients with hidradenitis suppurativa

Background Data on the health care utilization of patients with hidradenitis suppurativa (HS) in primary care settings are scarce. Objective To investigate the health care service utilization of patients with HS. Methods In a cross‐sectional study, patients with HS were compared with 2 age‐ and sex‐matched control groups—general population enrollees of Clalit Health Services and a group of patients with psoriasis. Health care services data included inpatient and outpatient community clinic visits and pharmacy claims for topical and systemic treatments. Multivariate analysis of the data for patients with HS and controls was performed. Results The study included 4417 patients with HS, 22,085 general population enrollees, and 4417 patients with psoriasis. On the basis of multivariate analyses, patients with HS had more annual dermatology clinic visits compared with the general population enrollees (odds ratio [OR], 6.49; 95% confidence interval [CI], 7.06‐5.97) and patients with psoriasis (OR, 1.32; 95% CI, 1.44‐1.21), more annual surgical clinic visits (OR, 3.78; 95% CI 3.28‐4.36 and OR, 1.65; 95% CI, 1.42‐1.91, respectively), and more hospitalizations (OR, 2.21; 95% CI, 1.89‐2.56 and OR, 1.51; 95% CI, 1.28‐1.78, respectively). Limitations Underestimation of HS frequency was possible. Conclusions The burden on health care systems due to patients with HS is greater than that due to patients with psoriasis and the general population.

Glycaemic control in patients with diabetes and concomitant psoriasis.

1 NHS National Services Scotland. Cancer statistics, skin cancer. Available at: http://www.isdscotland.org/Health-Topics/Cancer/CancerStatistics/Skin/ (last accessed 16 June 2016). 2 Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364:2507–16. 3 Hodi FS, O’Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363:711–23. 4 John L, Cowey CL. The rapid emergence of novel therapeutics in advanced malignant melanoma. Dermatol Ther 2015; 5:151–69. 5 Larkin J, Acland K, Algurafi H et al. Melanoma focus group consensus guidelines. 2013 position paper: follow-up of high risk cutaneous melanoma patients in the U.K. Available at: http:// melanomafocus.com/wp-content/uploads/2014/02/CutaneousMelanoma-Follow-Up-Position-Paper-30Jan14.pdf (last accessed 16 June 2016). 6 Marsden JR, Newton-Bishop JA, Burrows L et al. Revised U.K. guidelines for the management of cutaneous melanoma. Br J Dermatol 2010; 163:238–56. 7 National Institute for Health and Care Excellence. Melanoma: assessment and management. NICE guideline NG14. Available at: https://www.nice.org.uk/guidance/ng14 (last accessed 16 June 2016).