Incidence rate of alopecia areata in Israel: A 15-year analysis of population-based data and the emergence of young male adults as the most at-risk group.

Incidence rate and temporal trends in alopecia areata (AA) vary worldwide. As a common disorder with a major impact on life quality, there is a continuous need for comprehensive epidemiological characterization and global updates of the disease burden. We sought to perform an epidemiologic characterization of AA patients and to explore temporal trends across different subgroups using long-term health data. A retrospective population-based study was conducted in a large healthcare organization in Israel. Data were analyzed for all patients with AA between 2005 and 2019. A total of 30 805 patients for 29 504 798 person-years were identified during the study period, representing an overall incidence rate of 104.4 cases per 100 000 person-years. Young adults and patients of middle socioeconomic status had the highest incidence rate compared to the whole cohort. Incidence rates in females were lower than in males (incidence rate ratio 0.72, 95% confidence interval 0.71-0.74). In a temporal trends analysis, the yearly incidence rate for the whole cohort was stable throughout the study period. Males between the ages of 18 and 30 had a significant increase in incidence during the study years, where the incidence rate increased from 119.54 to 162.36 per 100 000 person-years. Despite the limitation of lack of analysis by subgroups of disease severity and other personal data, our study clearly indicates that young male adults of middle socioeconomic status emerge as the most at risk associated with AA over a decade and a half. In an effort to delineate risk factors for this gender gap, different stressors are speculated as triggers.

Psychologic Morbidity Among Psoriatic Arthritis Patients in Remission or With Low Disease Activity: A Comparison Between Biologic and Conventional Synthetic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: The aim of this study was to compare the effect of biologic agents and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on the psychologic status of patients with psoriatic arthritis (PsA) in remission or with low disease activity. METHODS: This is a case-control study of PsA patients in remission or with low disease activity treated at a single-center combined rheumatologic-dermatologic clinic between 2015 and 2017. Patients were assigned to 2 comparison groups according to their treatment (1) biologic drugs and (2) csDMARDs therapy. Psoriatic arthritis disease activity was evaluated by disease activity score-28. Anxiety, somatization, and depression were evaluated by patient health questionnaires (PHQ): generalized anxiety disorder-7, PHQ-15, and PHQ-9, respectively. Disability was assessed by the health assessment questionnaire disability index (HAQ-DI). RESULTS: Thirty PsA patients on biologic treatment (BT) and 14 PsA patients in csDMARDs were enrolled. No significant differences in disease duration and treatment duration between the 2 groups were found. Disease activity score-28 was significantly better in the BT group compared with the csDMARDs group (1.8 ± 0.4 vs 2.1 ± 0.4, respectively, p = 0.028). A nonsignificant tendency toward higher scores in psychologic questionnaires was seen among the non-BT group. Moderate to high correlations between all mental questionnaires and HAQ-DI were found in both groups (0.567 ≤ r ≤ 0.850, p < 0.05). Patients with mental disturbance (generalized anxiety disorder-7/PHQ-15/PHQ-9 ≥ 5) showed significant poorer performance in their HAQ-DI in comparison with patient without physiological comorbidities in both groups. CONCLUSIONS: Tight disease control in PsA patients, achieved with BT, may offer an improvement in psychological outcomes in addition to relieving clinical symptoms.

Hypoglycemia- simplifying the ways to predict an old problem in the general ward.

OBJECTIVE: To examine the association between hypoglycemic events and inpatient and outpatient mortality rates, and to characterize the profile of patients with diabetes who develop hypoglycemia during hospitalization in order to identify risk factors and potentially avoid it. RESEARCH DESIGN AND METHODS: This retrospective cohort study analyzed data of 3410 patients with diabetes hospitalized during 2012. The associations among biochemical measures, severity of hypoglycemia, inpatient length of stay, and mortality during hospitalization, one month and within one year after discharge were evaluated. RESULTS: Hypoglycemia was observed in 18.5% (633/3410) of patients with diabetes, 83% (529/633) with mild/moderate hypoglycemic values. Adjusted for age and sex, the 30-day mortality rate after discharge was higher in the group with mild/moderate hypoglycemia (HR = 1.749, CI 1.288-2.374, p < 0.001) and in the group with severe hypoglycemia (HR = 3.390, CI 2.332-6.100, p < 0.001). The mortality rate at the one-year follow-up was higher in the group with mild/moderate hypoglycemia (HR = 1.749, CI 1.288-2.374, p < 0.001) and in the group with severe hypoglycemia (HR = 3.390, CI 2.332-6.100, p < 0.001). In multivariate analysis, hemoglobin and albumin below normal values, and creatinine values above the upper limit were strongly associated with hypoglycemia (OR 1.35, 95%CI 1.1-1.6, p < 0.03; OR 1.6, 95%CI 1.33-1.89, p < 0.001; OR 1.3, 95%CI 1.08-1.55, p < 0.04, respectively). CONCLUSIONS: Hospitalized patients with diabetes and low hemoglobin, low albumin or high creatinine levels are at increased risk of developing significant hypoglycemia. Identifying accurate high-risk factors in order to intervene early and efficiently can prevent life-threatening complications.

Pemphigus and depression comorbidity: a case control study.

BACKGROUND: While quality of life can be significantly affected in pemphigus patients, few studies have systematically investigated the co-morbidity of psychiatric disorders in these patients. OBJECTIVE: To assess the association between pemphigus and depression comorbidity, using the computerized medical database of Israel's largest health maintenance organization. METHODS: In a case-control study, co-morbidities of adult pemphigus patients retrieved from the database of a large healthcare organization from 1998 to 2010 were compared with age- and gender-matched controls from the same database. The main outcome measure was the prevalence of co-morbid psychiatric disorders (anxiety, psychosis, schizophrenia and depression) in pemphigus patients and controls. The study included 255 pemphigus patients (157 women (62%) and 98 (38%) men) and 509 controls (313 women (62%) and 196 (38%) men) aged 20 years and older (a ratio of 3:2 in both groups). Mean age was 63.5 ± 15.7 years in the pemphigus group and 63.2 ± 15.7 years in the control group. RESULTS: Depression was the only psychiatric disorder significantly increased among pemphigus patients compared with controls. Alcohol abuse and smoking did not differ between groups. Depression was over-represented in a large population of pemphigus patients, indicating the disorder as a possible significant co-morbidity. After controlling for confounders including age, gender, and duration of corticosteroid therapy, the association with depression persisted (OR = 1.19, 95% CI: 1.12-1.27), p<0.001). CONCLUSION: The increased prevalence of depressive morbidity, especially in the presence of commonly prescribed corticosteroid treatment, emphasizes the need for psychiatric assessment and intervention in these patients.

Atopic dermatitis in Israeli adolescents - a large retrospective cohort study.

Prevalence of atopic dermatitis (AD) has been studied mainly in infants and young children. Surveys on AD in adolescents and adults are based largely on self-reported questionnaires and cohorts of different ages, precluding meaningful comparisons and conclusions. We aimed to provide data on the prevalence of AD and its relation to demographic factors in adolescents. A large database of youths eligible for military service was searched for subjects one year before service at the age of 18. Parameters included country of origin, age of immigration to Israel, education, and presence and severity of AD. AD rose 3-fold for both genders over the study period 1998-2008 (0.4-1%). The increase was higher in females (0.5-1.2%) than males (0.3-0.9%). Mild and moderate disease was higher in females than males. Severe AD was rarely noted. Russian (OR = 1.47), Asian (OR = 1.15) and Euro-American (OR = 1.26) origins had highest association with AD. Immigrants after age 7 had higher association with AD than Israeli-born subjects and immigrants before age 7 (1.88 vs. 1.33). More years of education was significantly associated with high prevalence of AD. The increased prevalence of AD during the 11-year period underscores the need for awareness of the condition in this population, in which AD affects health and quality of life.

Pemphigus and osteoporosis: a case-control study.

OBJECTIVE: To investigate the association between pemphigus and osteoporosis. DESIGN: Case-control study. SETTING: A large health care provider organization in Israel. PARTICIPANTS: Patients with pemphigus older than 20 years (hereinafter, pemphigus patients) were compared with a sample of age- and sex-matched controls. Interventions  Data retrieval from a large community-based medical database regarding health-related lifestyles, comorbidities, use of medications, bone mineral density scans, and drugs for osteoporosis. MAIN OUTCOME MEASURES: The prevalence of osteoporosis in patients and controls, use of bone mineral density scans, and drugs for osteoporosis. RESULTS: The study included 255 pemphigus patients and 509 controls older than 20 years. Osteoporosis was diagnosed among 40.4% of pemphigus patients compared with 6.5% of controls (P < .001; odds ratio [OR], 9.77; 95% confidence interval [CI], 6.34-15.10). After controlling for confounders, including age, sex, and duration of glucocorticosteroid therapy and proton pump inhibitor therapy, the associations with osteoporosis persisted (OR, 4.27; 95% CI, 2.44-7.47; P < .001). Similar results were obtained when using cumulative glucocorticosteroid dose. Only 73 pemphigus patients with osteoporosis (70.9%) had undergone a bone mineral density test within the past 10 years. While most pemphigus patients with osteoporosis purchased medications for osteoporosis, including calcium (95.1% of patients), cholecalciferol (89.3%), bisphosphonates (90.3%), or raloxiphene (8.8%), the duration of therapy was short. CONCLUSIONS: We found an association between pemphigus and osteoporosis, which persisted after controlling for glucocorticosteroid use. Monitoring and treatment of osteoporosis in pemphigus patients was suboptimal in this study.

Normal levels and function of endothelial progenitor cells in patients with psoriatic arthritis.

Endothelial progenitor cells (EPCs) are a population of bone marrow derived cells which have been attributed with the ability to migrate into areas of tissue ischemia and to posses reparative qualities. EPCs have been shown to be decreased in level and function in various inflammatory disorders. Psoriasis and psoriatic arthritis are associated with an increase in cardiovascular morbidity. The aim of the study was to investigate the number of EPCs among patients suffering from psoriasis and psoriatic arthritis. Patients suffering from active psoriasis and psoriatic arthritis were recruited as well as healthy controls. Disease activity was assessed with the DAS-28, BASDAI and PASI scores. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by FACS analysis using the CD34/133 and CD34/KDR. No significant difference was found between numbers of EPCs between healthy controls, patients with psoriasis and psoriatic arthritis. A significant correlation was found between levels of VGEF and the BASDAI score. The results of the current study do not support a significant role for EPCs in the pathogenesis of psoriasis and psoriatic arthritis.

Cutaneous photodamage in schizophrenia patients.

BACKGROUND: Schizophrenia patients frequently engage in unhealthy lifestyle behaviors. The adverse effects of sun exposure on the human skin are well studied but only sparse data in this area have been focused on schizophrenia patients. AIM: To assess the role of sun exposure and its effects on cutaneous photoaging in schizophrenia patients compared with age-matched healthy subjects. METHOD: Skin photoaging was assessed using a modification of Glogau's classification. We developed a rating for aged appearance, applied to facial skin, dorsal hand skin, and a total integrated score. The extent of photodamage was independently evaluated by two of the investigators certified in dermatology and plastic surgery. Each rater independently estimated the subjects' age. Raters were blinded to the subjects' demographic and clinical parameters as well as to each other's ratings. RESULTS: Seventy-four participants were enrolled. There were 37 patients, 24 men and 13 women, mean age: 42.7+/-9.7 years. The comparison group consisted of 20 men and 17 women, mean age: 42.4+/-9.2 years. Age, gender and BMI as well as smoking status did not differ significantly between groups. The variables found to differentiate between groups were: sun exposure, use of sunscreens, overall pigmentary changes, periorbital wrinkles and the intake of concurrent medications. CONCLUSION: Increased cutaneous photoaging in schizophrenia patients, evidenced by reduced sun safety behaviors, and objective clinical signs of skin photodamage were demonstrated in the present study. We suggest that preventive measures like sun safety education should be undertaken by mental health professionals.

Expression of vinculin in autoimmune cutaneous diseases.

BACKGROUND: Reports have appeared that sera of patients with systemic autoimmune disorders have demonstrated autoantibodies to vinculin. OBJECTIVE: To determine the presence and distribution of vinculin in the skin of patients with cutaneous autoimmune disorders. METHODS: Semiquantitative immunohistochemistry investigations for presence of vinculin were conducted on skin biopsy specimens from patients with pemphigus vulgaris (PV), bullous pemphigoid (BP), and various collagen vascular diseases, and from healthy controls. RESULTS: Results of staining for vinculin were positive in 2 of 7 PV patients, 6 of 9 BP patients, and all 6 cutaneous autoimmune patients. Staining results were negative in all controls. Strong immunostaining to vinculin was found in 3 of 6 vinculin-positive BP patients and 5 of 6 vinculin-positive cutaneous autoimmune patients. CONCLUSIONS: The expression and distribution of vinculin are accentuated in patients with various skin autoimmune diseases and appear to be stronger in diseases involving the basement membrane, where it is thought to be relatively more important than in other skin disorders.

Screening for common dermatologic disorders amongst Israeli adolescents.

BACKGROUND: Dermatologic disorders amongst adolescents tend to overlap with general adult dermatology, but specific data are scarce. This study was undertaken to assess the prevalence of common skin disorders in 17-year-old Israeli military conscripts. METHODS: Military recruits who underwent medical examination over approximately 1 year were included. Dermatology specialists evaluated and classified those with suspected skin disorders into categories of suitability for military tasks. Data were computerized for analysis of prevalences. Risk ratios for each category were determined for men and women. RESULTS: Of the 94,806 adolescents, 36,511 (38.5%) women and 58,295 (61.5%) men, the most prevalent diagnoses were hyperhidrosis, multiple nevi, atopic dermatitis, keratinization disorders (mostly psoriasis), and contact dermatitis. The most prominent gender differences were in hyperhidrosis, contact dermatitis, and collagen diseases. CONCLUSION: Major dermatologic problems in adolescents are documented, and the findings may be useful for the military, employers, and general health services.

Immunohistochemical expression of platelet growth factor and vascular endothelial growth factor in patients with melanoma with and without redness (Brenner sign).

OBJECTIVE: To assess whether an erythematous eruption in the vicinity of or distant from a melanoma lesion might be related to the vascular endothelial growth factor, the platelet-derived endothelial cell growth factor, or both. METHODS: Biopsy specimens from 13 patients with primary melanoma, 6 of whom had erythematous eruptions and 7 who did not, were studied by immunohistochemistry for the expression of vascular endothelial growth factor and platelet-derived endothelial cell growth factor. RESULTS: Vascular endothelial growth factor was positive in 3 of 6 patients (50%) with melanoma and redness (Brenner sign) and in 4 of 7 patients (57%) with melanoma without redness. Platelet-derived endothelial cell growth factor was positive in all 6 patients (100%) with melanoma and redness and in 4 of 7 patients (57%) with melanoma without redness. CONCLUSION: Platelet-derived endothelial cell growth factor may have a part in the pathogenesis of the redness observed in patients with melanoma, called Brenner sign, by affecting vasculature function.

Environmental risk factors for mycosis fungoides.

The rising incidence rates of mycosis fungoides (MF) call for an explanation. Thus, environmental and lifestyle factors were speculated to play a role in the development of lymphoproliferative diseases. It is thought that continuous activation of skin T helper lymphocytes leads to malignant transformation of a specific clone. Possible risk factors that have been implicated are occupational chemical exposure, radiation, drugs and infections. The carcinogenic process is probably multifactorial and multistep, combining the genetic predisposition of the individual and his immune status with various exogenous factors. Using advanced and accurate exposure assessment tools, recent epidemiological data indicate that occupational exposure to chemicals, primarily to aromatic halogenated hydrocarbons, is a major risk factor to develop MF in men (odds ratio 4.6), while exposure to pesticides, a subgroup of the aromatic halogenated hydrocarbons, is a risk factor in both genders (odds ratio 6.8 for men and 2.4 for women). Apparently, concomitant infection with Staphylococcus aureus or with Borrelia species and chronic exposure to UVR are minor risk factors for the development of MF. Further assessment of occupational and environmental exposures is essential for the evaluation of their contribution to the etiology of MF. This will allow the application of preventive and surveillance measures along with adjustment of existing health policies.

A survey of sex differences in 249 pemphigus patients and possible explanations.

BACKGROUND: Pemphigus, an immunoblistering disorder, is reported with equal or near equal frequencies in men and women despite prominent female predominance in prevalence ratios of the vast majority of autoimmune diseases. OBJECTIVE: To assess a possible correlation between pemphigus and intake of sex hormones in a cohort of pemphigus patients. METHODS: A prospective online survey using a specially designed questionnaire was conducted among patients with diagnosed pemphigus in the United States during a 1-year period from September 2005 through September 2006. RESULTS: A total of 249 pemphigus cases were enrolled, 158 women (63%) and 91 men (36%). The female-to-male ratio was 1.7:1. Age at onset of the disease ranged from 16 to 85 years, mean 4.5.4+/-12.9 [corrected] years for both sexes (not statistically significant): 45.3 for women and 45.7 for men. At the time of pemphigus diagnosis, 12% (20 of 158) of the women and 4% (4 of 91) of the men reported using hormone replacement therapy. At the time of disease onset, 46% (20 of 43) of the postmenopausal women took hormone replacement therapy. LIMITATIONS: Possible questionnaire self-reporting biases. CONCLUSIONS: The finding of a female predominance among pemphigus patients is attributed to the immunopathogenesis of the disease that makes women more susceptible to this and other autoimmune disorders and to the strikingly high proportion of hormone replacement therapy users found among postmenopausal women.

Asthma and psychiatric disorders in male army recruits and soldiers.

BACKGROUND: Numerous studies have shown an association between asthma and mental disorders. While elevated rates of asthma have been noted among psychiatric patients with anxiety disorders and post-traumatic stress disorder, several studies have found elevated rates of mental disorders among asthma patients. Such studies, however, have generally relied upon questionnaires and assessment by non-specialist physicians to diagnose mental disorders and asthma. OBJECTIVES: To examine a possible association between asthma and psychiatric diagnoses in Israeli military recruits and soldiers. METHODS: In this cross-sectional study we compared the prevalence of mental diagnoses in asthmatic recruits and soldiers with that in non-asthmatic recruits and soldiers. A total of 195,903 recruits and soldiers were examined by Israel Defense Forces recruiting offices and fitness boards. Diagnoses of asthma were based on a pulmonologist's diagnosis, including spirometry at rest and exercise testing as indicated; diagnoses of mental disorders were based on examination by a psychiatrist. RESULTS: The prevalence of asthma was found to be 7.8% (current) and 9.8% (lifetime). The prevalence of mental disorders was 13.4%. Current asthma was associated with an increased likelihood of any mental disorder (OR = 1.20, 95% Cl = 1.15-1.26), and specifically with mood and anxiety disorders (1.31, 1.19-1.46), introvert personality disorders (1.20, 1.12-1.28) and adjustment disorder (1.43, 1.26-1.62). Lifetime asthma was associated with an increased likelihood of the same disorders, but the association was not as powerful. CONCLUSIONS: The results validate the previously documented association between asthma and mental disorders, using a sample of unprecedented size and improved methodology. A multidisciplinary approach to asthma that incorporates mental health professionals in the treatment of poorly controlled asthma and perhaps of asthma in general is recommended.

Allergic contact dermatitis among maintenance and clerical workers in a military population.

Contact dermatitis is one of the leading causes of occupational morbidity and absenteeism and has become an intolerable cause of missed workdays and health problems in the Israeli military. The aim of this study was to determine the rate of contact dermatitis in maintenance and clerical workers, the common allergens causing it, and the background of atopy in the subjects in order to design preventive measures. Medical records of all recruits to the Israel Defense Forces from 2000 to 2003 were reviewed for contact dermatitis. The 102 cases found were further assessed for job assignment, atopic background, and allergens. Of the 102 cases, 60 had irritant contact dermatitis and 42 had allergic contact dermatitis, of which 33 (78.6%) were maintenance workers, mainly mechanics. 13 soldiers in the maintenance job category (39%) and 2 soldiers in the clerical group (22.2%) had atopic background. There were 55 positive reactions in patch tests, 25 of them to oil and cooling fluids, with 14.5% attributed to methylchloroisothiazolinone/methylisothiazolinone) (Kathon CG). Atopy was found to be a risk factor for allergic contact dermatitis in our study and should be screened for in job assignment procedures in the military. Oil and greases contain significant allergens, especially their preservatives.