Granulomatous Uveitis and Conjunctivitis Due to Common Variable Immune Deficiency: A Case Report

Purpose: To describe a case of granulomatous anterior uveitis and histologically confirmed chronic granulomatous conjunctivitis in the presence of common variable immune deficiency (CVID).

Methods: Interventional case report.

Results: A 72-year-old female with a history of CVID treated with regular intravenous immunoglobulin (IVIG) infusions developed chronic conjunctivitis and granulomatous anterior uveitis. She responded to topical steroids, but there was recurrence upon cessation of steroid therapy. Conjunctival biopsy demonstrated micro-granulomas in the stroma and epithelium. Treatment with IVIG was maintained throughout.

Conclusion: Although rare, a diagnosis of CVID should be considered in patients with recurrent conjunctivitis and uveitis of unknown etiology, especially if there is a clinical history suggestive of defective immunity. They tend to respond well to continued steroid therapy, and IVIG therapy should not be stopped.     

Insulin and IGF1 enhance IL‐17‐induced chemokine expression through a GSK3B‐dependent mechanism: a new target for melatonin's anti‐inflammatory action

Obesity is a chronic inflammation with increased serum levels of insulin, insulin‐like growth factor 1 (IGF1), and interleukin‐17 (IL‐17). The objective of this study was to test a hypothesis that insulin and IGF1 enhance IL‐17‐induced expression of inflammatory chemokines/cytokines through a glycogen synthase kinase 3β (GSK3B)‐dependent mechanism, which can be inhibited by melatonin. We found that insulin/IGF1 and lithium chloride enhanced IL‐17‐induced expression of C‐X‐C motif ligand 1 (Cxcl1) and C‐C motif ligand 20 (Ccl20) in the Gsk3b^+/+, but not in Gsk3b^?/? mouse embryonic fibroblast (MEF) cells. IL‐17 induced higher levels of Cxcl1 and Ccl20 in the Gsk3b^?/? MEF cells, compared with the Gsk3b^+/+ MEF cells. Insulin and IGF1 activated Akt to phosphorylate GSK3B at serine 9, thus inhibiting GSK3B activity. Melatonin inhibited Akt activation, thus decreasing P‐GSK3B at serine 9 (i.e., increasing GSK3B activity) and subsequently inhibiting expression of Cxcl1 and Ccl20 that was induced either by IL‐17 alone or by a combination of insulin and IL‐17. Melatonin's inhibitory effects were only observed in the Gsk3b^+/+, but in not Gsk3b^?/? MEF cells. Melatonin also inhibited expression of Cxcl1, Ccl20, and Il‐6 that was induced by a combination of insulin and IL‐17 in the mouse prostatic tissues. Further, nighttime human blood, which contained high physiologic levels of melatonin, decreased expression of Cxcl1, Ccl20, and Il‐6 in the PC3 human prostate cancer xenograft tumors. Our data support our hypothesis and suggest that melatonin may be used to dampen IL‐17‐mediated inflammation that is enhanced by the increased levels of insulin and IGF1 in obesity.     

Laser division of congenital complete tracheal rings

Congenital complete tracheal rings are a rare and life threatening problem in young children and they are often challenging to manage. Whilst historically associated with high mortality rates increasing experience with this tracheal pathology has led to much improved survival rates and slide tracheoplasty has become the treatment of choice. We present 3 cases in which an open procedure was not deemed possible and they underwent laser division (CO2, KTP) of their complete rings. Two patients subsequently required stent insertion. All patients are alive and well at a mean follow up of 3 years and 5 months. Whilst laser division of complete tracheal rings has only been described in a small number of cases it may provide an alternative approach in patients who are not able to undergo an open procedure or in an emergency situation.     

Review: Can we identify how programmes aimed at promoting self‐management in musculoskeletal pain work and who benefits? A systematic review of sub‐group analysis within RCTs

Background: There are now several systematic reviews of RCTs testing self‐management for those with chronic musculoskeletal pain. Evidence for the effectiveness of self‐management interventions in chronic musculoskeletal pain is equivocal and it is not clear for which sub‐groups of patients SM is optimally effective. Aims: To systematically review randomized controlled trials of self‐management for chronic musculoskeletal pain that reported predictors, i.e., ‘baseline factors that predict outcome independent of any treatment effect’; moderators, i.e., ‘baseline factors which predict benefit from a particular treatment’; or mediators i.e., ‘factors measured during treatment that impact on outcome’ of outcome. Method: We searched relevant electronic databases. We assessed the evidence according to the methodological strengths of the studies. We did meta‐regression analyses for age and gender, as potential moderators. Results: Although the methodological quality of primary trials was good, there were few relevant studies; most were compromised by lack of power for moderator and mediator analyses. We found strong evidence that self‐efficacy and depression at baseline predict outcome and strong evidence that pain catastrophizing and physical activity can mediate outcome from self‐management. There was insufficient data on moderators of treatment. Conclusions: The current evidence suggests four factors that relate to outcome as predictors/mediators, but there is no evidence for effect moderators. Future studies of mediation and moderation should be designed with ‘a priori’ hypotheses and adequate statistical power.