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.

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.

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.

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.

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.

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.

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.

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.

Increased use of mental health services related to isotretinoin treatment: a 5-year analysis.

BACKGROUND: The association between exposure to Isotretinoin, the development of depression and suicide attempts is controversial. OBJECTIVE: To retrospectively assess pattern of utilization of mental health services in the Israeli Defense Forces (IDF) during a 5-year period for all subjects exposed to Isotretinoin in comparison to a control group consisting of army conscripts suffering from psoriasis. All subjects were young adults (18 to 21 years old) in compulsory military service. METHOD: Exposure to Isotretinoin mandates reporting and marking as a coded medical profile in the IDFs' computerized medical record of each conscript and soldier. Medical data, tracked by military medical profiles, were summarized from medical records of all subjects treated by Isotretinion during the years 1999-2003 and for the control group for the same period. Use of mental health services was the a-priori defined primary outcome measure. RESULTS: During the study period 1419 subjects were exposed to Isotretinoin and 1102 suffered from psoriasis. Utilization of mental health services was highest for the index group wherein 17.2% (245/1419) of subjects were evaluated or treated compared to 12.5% in the control group (psoriasis). The inter-group differences were statistically significant; Chi-square=15.9 (df=2), p=0.0003. CONCLUSIONS: We suggest that psychiatric evaluation be regularly undertaken prior to initiation of Isotretinion treatment in young adults at risk, as well as providing follow-up visits during and at completion of treatment.

Multiple common naevi in Israeli adolescents.

The most prominent known phenotypic risk factor for the development of melanoma is a large number of common melanocytic naevi. The aims of this study were to determine the prevalence of multiple common naevi in a group of 17-year-olds and to identify possible associated risk factors. The study subjects were approximately 40,000 female and 60,000 male 17-year-old Jewish Israelis presenting to army recruitment centres for compulsory military service during a 1-year period from January 2003 to December 2003. Data were gathered on whole-body naevi count, years of education, place of residence and place of birth of the recruit, his/her parents and paternal grandparents. The count of whole-body naevi was carried out by military physicians. The multiple naevi phenotype was defined by the presence of more than 50 naevi. The prevalence of the phenotype was highest amongst recruits of American origin and lowest amongst those of Asian and African origin (P < 0.0001). The prevalence differed in different population centres, the highest being in the coastal cities of Haifa and Tel Aviv. This pattern corresponded to the geographical distribution of melanoma in Israel. Amongst male conscripts, the phenotype was more common in the better educated group (> or =12 years) than in the poorer educated conscripts (< or = 11 years) (P = 0.051). When adjusted for the factors studied, a significant correlation was found between a high multiple common naevi count and American and European origin and residence in coastal cities, reflecting the complex interplay between endogenous and exogenous factors of melanoma.

Acute generalized exanthematous pustulosis: a retrospective analysis showing a clear predilection for women.

The clinical reaction pattern acute generalized exanthematous pustulosis is increasingly recognized today as drug intake details are more meticulously recorded and diagnostic guidelines are formulated. Nevertheless, the diagnosis and etiology remain unclear. This examination of the clinical and histologic features of acute generalized exanthematous pustulosis, undertaken in a retrospective study of 13 patients in an urban medical center, was aimed at determining the underlying mechanism of the etiology of the disease. Findings include a female predominance and the overwhelming prevalence of acetaminophen as the culprit agent, adding two more components to what is known about acute generalized exanthematous pustulosis. The possible mechanisms of the disease are discussed, enlightened by its appearance in two women in the study who were pregnant when the reaction first erupted.

Chlorpyrifos exacerbating pemphigus vulgaris: a preliminary report and suggested in vitro immunologic evaluation model.

BACKGROUND: There is accumulating evidence on the role of pesticides in the etiology of pemphigus vulgaris (PV). OBJECTIVE: To determine whether chlorpyrifos, an organophosphate pesticide, is involved in the immunopathology of PV. METHODS: Normal human skin biopsy specimens incubated with progressively diluted chlorpyrifos solutions were used as indirect immunofluorescence substrates for sera from two PV patients previously exposed to the agent and from healthy controls. Involvement of T-cell lymphocytes was assessed by release of interferon-g in the presence of chlorpyrifos. RESULTS: In one PV patient, immunofluorescence was strongly positive for the specimen incubated with the pesticide and weakly positive for the specimen incubated with medium alone. Immunofluorescence was negative in the patient under immunosuppression with prednisolone and in all controls. Both patients tested positive on interferon-g assay; controls tested negative. CONCLUSIONS: Findings suggest an immunopathogenic role of chlorpyrifos in PV. Interferon-g cytokine assay with the pesticide combined with immunofluorescence tests may provide an in vitro diagnostic tool in suspected pesticide-induced/exacerbated pemphigus.

Affective psychosis following Accutane (isotretinoin) treatment.

Isotretinoin (Accutane) ranks in the top 10 of the US Food and Drug Administration's database of drugs associated with reports of depression and suicide attempts. However, this association is still controversial because up to 5.6% of patients with moderate acne may have pre-existing suicidal ideations, improvement of acne often reduces associated depression, and isotretinoin users are reportedly no more likely than those taking antibiotics for acne to have depression or commit suicide. We describe a series of cases of manic psychosis that developed in a 1-year period (2003) in association with isotretinoin treatment and resulted in suicidality and progression to long-standing psychosis. Cases were drawn from 500 soldiers who had been evaluated in a military specialists dermatology clinic for severe acne. Data were summarized from medical records of five severe acne patients treated by isotretinion during their compulsory military service. Data from their draft board examinations and service records, as well as repeated clinical assessments by certified psychiatrists at the Israel Defense Forces (IDF) Mental Health Department clinic, were evaluated. Five young adults developed manic psychosis within a mean of 7.6 months of exposure to isotretinoin. In three cases, this was accompanied by a suicide attempt, and in three cases, psychosis lasted for longer than 6 months. Either a personal history of obsessive-compulsive disorder, neurological insult or family history of a major psychiatric illness were present in all cases. The present case-series is suggestive of an increase in the likelihood of an association between exposure to isotretinion and manic psychosis. Associated risk factors were both family and personal history of psychiatric morbidity. Further studies are needed to establish our findings.

Teledermatology: quality assessment by user satisfaction and clinical efficiency.

BACKGROUND: The Israel Defense Forces implemented a pilot teledermatology service in primary clinics. OBJECTIVES: To assess user satisfaction and clinical short-term effectiveness of a computerized store and forward teledermatology service in urban and rural units. METHODS: A multi-center prospective uncontrolled cohort pilot trial was conducted for a period of 6 months. Primary care physicians referred patients to a board-certified dermatologist using text email accompanied by digital photographs. Diagnosis, therapy and management were sent back to the referring PCP. Patients were asked to evaluate the level of the CSAFTD service, effect of the service on accessibility to dermatologists, respect for privacy, availability of drugs, health improvement and overall satisfaction. PCPs assessed the quality of the teledermatology consultations they received, the contribution to their knowledge, and their overall satisfaction. RESULTS: Tele-diagnosis alone was possible for 95% (n=413) of 435 CSAFTD referrals; 22% (n=95) of referrals also required face-to-face consultation, Satisfaction with CSAFTD was high among patients in both rural and urban clinics, with significantly higher scores in rural units. Rural patients rated the level of service, accessibility and overall satisfaction higher than did urban patients. PCPs were satisfied with the quality of the service and its contribution to their knowledge. Rural physicians rated level of service and overall satisfaction higher than did urban physicians. Tele-referrals were completed more efficiently than referral for face-to-face appointments. CONCLUSIONS: CSAFTD provided efficient, high quality medical service to rural and urban military clinics in the IDF.

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.

Stress in a case of SAPHO syndrome.

In this article, we describe a case of seemingly stress-induced SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome in a man who exhibited the central features of palmoplantar psoriasis and anterior chest involvement. We also review the etiology, pathogenesis, and treatment of SAPHO syndrome and emphasize the important differences between this syndrome and psoriatic arthritis.

Pemphigus in Israel--an epidemiologic analysis of cases in search of risk factors.

BACKGROUND: Despite the high incidence of pemphigus in the Jewish population, data on the epidemiology and etiology of the disease in Israel are sparse. OBJECTIVE: This study was conducted to identify clinical and epidemiologic features of pemphigus patients in Israel, while searching for risk factors that induce or exacerbate the disease. METHODS: Demographic and clinical information was recorded from the charts of 55 pemphigus patients treated over a 5 year period. A sample of 22 patients was compared to 22 age and gender-matched controls by means of a questionnaire querying details on lifestyle, including occupation, diet, sun exposure, and smoking. RESULTS: The findings show that the typical Israeli pemphigus patient is middle-aged, married, and of East European or Middle Eastern origin. The most common diagnosed clinical variant was pemphigus vulgaris, followed by pemphigus erythematosus. Some 70% of patients were treated with two or more immunosuppressive drugs and 62% entered long-lasting remission. Twenty-three percent of patients were exposed through their work to chemical substances, mainly pesticides, at the beginning of the disease and 18% of patients were continually exposed to ultraviolet radiation 5 years prior to onset of the disease. CONCLUSIONS: There is a possible correlation between occupational exposure to pesticides and UV radiation, and pemphigus induction.

Cutaneous lymphomas and association to sex hormones.

Male gender is interpreted as a risk factor for developing mycosis fungoides and perhaps other cutaneous and extracutaneous lymphomas. In this review the authors examine epidemiologic, clinical, pathologic, and molecular data in an effort to understand whether and to what extent gender or sex hormones are involved in the pathogenesis of lymphoproliferative disorders.

PEMPHIGUS: an acronym for a disease with multiple etiologies.

The acronym PEMPHIGUS is suggested to encompass the numerous factors involved in the pathogenesis and course of the disease. In the following review the authors present studies documenting these factors. The acronym can serve as a handy tool to direct the physician's investigation of a case of pemphigus, aiding in its diagnosis and in the prevention of future flare-ups.