Treatment of Granuloma Annulare With Pentoxifylline and Oral Vitamin E: A Case Series.

Granuloma annulare (GA) is a difficult-to-treat granulomatous skin disorder characterized by multiple annular, raised, and erythematous lesions. While numerous therapies have been proposed, there is currently no clear gold standard of treatment. We present a series of five patients with biopsy-proven generalized GA who were treated with pentoxifylline and oral vitamin E. Each patient in this series had at least a one-year history of GA refractory to other treatments. After three months of treatment, four of the five patients demonstrated objective improvement in their lesions through before and after clinical photographs. No patients suffered any adverse events on this treatment regimen. As our series has demonstrated modest benefits in concurrence with previously published studies, we recommend combination therapy with pentoxifylline and vitamin E as a strong contender for first- or second-line treatment for generalized GA. Pentoxifylline and vitamin E are advantageous for their tolerability, cost-effectiveness, minimal drug interactions, and convenience.

Prostaglandin E2 and IL-23 interconnects STAT3 and RoRγ pathways to initiate Th17 CD4+ T-cell development during rheumatoid arthritis.

BACKGROUND: The chronic inflammation associated with rheumatoid arthritis (RA) leads to focal and systemic bone erosion of the joints resulting in a crippling disability. Recent reports indicate an increase in the incidence of RA in the coming years, placing a significant burden on healthcare resources. The incidence of RA is observed to be increasing with age and a significant proportion of those new cases will be aggressively erosive. FINDINGS: The altered physiology, due to immune disturbances, contributes towards RA pathogenesis. The imbalance of inflammatory cytokines and non-cytokine immune modulators such as prostaglandin E2 (PGE2) and IL-23-induced pathogenic IL-17, plays a crucial role in persistent inflammation and bone degradation during RA. However, the molecular mechanism of IL-23, a key cytokine, and PGE2 in the development and perpetuation of IL-17 producing effector Th17 cells is poorly understood. CONCLUSION: This review focuses on research findings that provide insight into the contribution of PGE2 and IL-23 during the development of pathogenic Th17 cells. We also highlight the key transcriptional factors required for Th17 development and therapeutic strategies to disrupt the interaction between IL-23 and IL-17 to prevent the end-organ damage in RA.

Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death by Phagocytes Is Prevented with Decoy FcγReceptors.

Autoimmune vasculitis is an endothelial inflammatory disease that results from the deposition of immune-complexes (ICs) in blood vessels. The interaction between Fcgamma receptors (FcγRs) expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is essential to prevent the IC-mediated blood vessel damage. Thus we tested if uncoupling the interaction of FcγRs and ICs prevents endothelium damage. Herein, we demonstrate that dimeric FcγR-Igs prevented nitric oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) in an in vitro vasculitis model. Dimeric FcγR-Igs significantly inhibited the IC-induced upregulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release by murine monocytic cell line. However, FcγR-Igs did not affect the exogenously added NO-induced upregulation of pro-apoptotic genes such as Bax (15 fold), Bak (35 fold), cytochrome-C (11 fold) and caspase-3 (30 fold) in HUVECs. In conclusion, these data suggest that IC-induced NO could be one of the major inflammatory mediator promoting blood vessel inflammation and endothelial cell death during IC-mediated vasculitis which can be effectively blocked by dimeric decoy FcγRs.

Determining empirical thresholds for "definitely large" amounts of food for defining binge-eating episodes.

Binge episodes involve "definitely large" amounts of food, yet limited data exist regarding the upper limits of food consumption in non-binge eating episodes. Study 1 examined the concurrent validity of a self-report measure developed to measure "usual" food consumption. Results support good concurrent validity for most items across response versions. Study 2 identified the upper limits of normal food consumption (i.e., 85(th) percentile of participants' largest reported usual servings). Thresholds differed across types of foods, and men reported higher thresholds than women for several foods. Type of food and gender should be considered when assessing for "definitely large" amounts of food.

Defining Features of Unhealthy Exercise Associated with Disordered Eating and Eating Disorder Diagnoses.

OBJECTIVES: The current study sought to compare different features of unhealthy exercise on associations with disordered eating and their ability to identify individuals with eating disorders. A secondary aim of the study was to compare prevalence and overlap of different aspects of unhealthy exercise and potential differences in their gender distribution. DESIGN: Cross-sectional epidemiological study. METHODS: A community-based sample of men (n=592) and women (n=1468) completed surveys of health and eating patterns, including questions regarding exercise habits and eating disorder symptoms. RESULTS: Compulsive and compensatory features of exercise were the best predictors of disordered eating and eating disorder diagnoses compared to exercise that was excessive in quantity. Further, compulsive and compensatory aspects of unhealthy exercise represented overlapping, yet distinct qualities in both men and women. CONCLUSIONS: Including the compulsive quality among the defining features of unhealthy exercise may improve identification of eating disorders, particularly in men. Results suggest that the compensatory aspect of unhealthy exercise is not adequately captured by the compulsive aspect of unhealthy exercise. Thus, interventions that target unhealthy exercise behaviors among high-risk individuals, such as athletes, may benefit from addressing both the compulsive and compensatory aspects of unhealthy exercise. Future prospective longitudinal studies will aid in determining the direction of the association between these features of unhealthy exercise and the onset of eating pathology.

A preliminary examination of a nonpurging compensatory eating disorder.

OBJECTIVE: To evaluate correlates of a compensatory eating disorder (CED) characterized by recurrent nonpurging compensatory behaviors in the absence of objectively large binge episodes among normal weight individuals who endorse undue influence of weight/shape on self-evaluation as possible indicators of clinical significance and distinctiveness. METHOD: Women with CED (n = 20), women with bulimia nervosa (BN) (n = 20), and controls (n = 20) completed an interview and questionnaires assessing eating disorder and general psychopathology and weight history. RESULTS: Compared with controls, women with CED reported significantly greater body image disturbance and disordered eating, higher anxiety proneness, increased perfectionism, and greater weight suppression. Compared with BN, CED was associated with significantly less body image disturbance, disordered eating, weight suppression, and lower likelihood of being overweight in childhood. However, CED and BN did not differ on anxiety proneness or perfectionism. DISCUSSION: CED merits further examination to determine whether it is a clinically significant and distinct eating disorder.

Comparing operational definitions of DSM-5 anorexia nervosa for research contexts.

OBJECTIVE: DSM-5 anorexia nervosa (AN) criteria include several changes that increase reliance on clinical judgment. However, research contexts require operational definitions that can be applied reliably and that demonstrate validity. The present study evaluated different operational definitions for DSM-5 AN. METHOD: DSM-5 AN criteria were applied to diagnostic interview data from 364 women varying two features: threshold for determining low weight for Criterion A (body mass index [BMI] <17.0 kg/m(2) vs. <18.5 kg/m(2)) and explicit endorsement of weight phobia (Criterion B explicit vs. inferred). Resulting groups of individuals with DSM-5 AN were compared on estimated frequency. In addition, AN groups were compared to non-eating disorder controls and individuals with an other specified feeding or eating disorder (OSFED) on external validators. RESULTS: All operational DSM-5 definitions produced higher lifetime frequency estimates than reported for DSM-IV AN, with a particularly large increase associated with the broadest definition. All definitions produced significant differences in comparison to controls on external validators that were associated with medium to large effect sizes. Only definitions that required a lower weight threshold or explicit endorsement of weight phobia demonstrated significant differences compared to OSFED on external validators, and these were of small effect size. The specific combination of BMI <18.5 kg/m(2) with inferred weight phobia exhibited few meaningful distinctions from the OSFED group. DISCUSSION: To balance inclusivity, syndromal reliability, and validity, an operational definition for DSM-5 AN in research contexts should define low weight as BMI <18.5 kg/m(2) and require measurable rather than inferred weight phobia.

Psychological factors predict eating disorder onset and maintenance at 10-year follow-up.

The present study sought to identify psychological factors that predict onset and maintenance of eating disorders. Secondary analyses were conducted using data from an epidemiological study of health and eating behaviours in men and women (N = 1320; 72% female) to examine the prospective and independent influence of the Eating Disorder Inventory Perfectionism, Interpersonal Distrust, and Maturity Fears subscales in predicting the onset and maintenance of eating disorders at 10-year follow-up. Multivariate models indicated higher Perfectionism (p = .025), lower Interpersonal Distrust (p < .001), and higher Maturity Fears (p = .037) predicted increased risk for eating disorder onset at 10-year follow-up, but only Perfectionism (p = .004) predicted eating disorder maintenance. Differential prediction of eating disorder onset versus maintenance highlights potentially different psychological foci for prevention versus treatment efforts.

Influence of peer context on the relationship between body dissatisfaction and eating pathology in women and men.

OBJECTIVE: This study examined the influence of peer context on the relationship between body dissatisfaction and eating pathology in women and men. METHOD: Secondary analyses were conducted using survey data from a large community sample of women and men (N = 2,060). RESULTS: The frequency of friend comments on weight and diet moderated the relationship between body dissatisfaction and eating pathology such that more frequent comments strengthened the relationship between body dissatisfaction and eating pathology in women. This effect was not significant in analyses of men. Instead, friend comments were directly related to eating pathology in men. DISCUSSION: Both women and men may benefit from peer-led interventions, with the greatest potential benefits for women with high body dissatisfaction, consistent with results from selective peer-led prevention programs in sororities.

Parental disorders, childhood abuse, and binge eating in a large community sample.

OBJECTIVE: Genetic and nonshared environmental factors are implicated in the etiology of binge eating behaviors (BEB), with genetic risk expressed as parental psychopathology. Traumatic experiences including child abuse predict onset of BEB. It is not clear if each separately contribute to BEB, or whether parental pathology leads to abuse which in turn influences BEB. METHOD: Data were obtained from the National Comorbidity Survey-Replication (N = 2960). Through structural equation modeling, we estimated unique and combined effects of mother's and father's internalizing (INT) and externalizing (EXT) disorders, and child abuse on BEB. RESULTS: Parental INT and EXT psychopathology contributed to child abuse and BEB. Abuse predicted BEB and partially mediated associations between parental psychopathology and BEB. DISCUSSION: Results emphasize the value of models that incorporate nature and nurture to understand risk for psychopathology in offspring, with childhood abuse being one mediator of how parental psychopathology may reflect genetic risk and influence environmental risk.