GILZ: a new link between the hypothalamic pituitary adrenal axis and rheumatoid arthritis?

The hypothalamic-pituitary-adrenal (HPA) axis is an important regulator of the stress response. In healthy individuals, the HPA axis maintains an equilibrium, ensuring that endogenous glucocorticoid (GC) levels remain within the normal range. However, hypofunction of the HPA axis may have a role in the development of inflammatory diseases, such as rheumatoid arthritis (RA). Glucocorticoid-induced leucine zipper (GILZ) is an anti-inflammatory protein, the expression of which is upregulated by GC. Although GILZ mediates the anti-inflammatory effects of GC, it may not be associated with the adverse effects that are frequently caused by exogenous GC administration. This has raised interest in GILZ potentiation as a therapeutic approach in diseases such as RA, which may mimic the anti-inflammatory effects of GC without causing harmful side effects. This review will outline the involvement of the HPA axis in RA, as a prelude to highlighting emerging evidence regarding the role of GILZ in inflammation control and RA.

Autoimmune rheumatic disease in Australian Aboriginal and Torres Strait Islander Peoples: What do we know?

Autoimmune rheumatic disease (AIRD) is a collective term, which comprises a group of multisystem inflammatory autoimmune diseases, including connective tissue disease, chronic inflammatory arthritis, sarcoidosis and systemic vasculitis. Some AIRD are prevalent in the general population, and all can cause significant morbidity and reduced quality of life, with some increasing the risk of premature mortality, such as systemic lupus erythematosus (SLE), a connective tissue disease that is more prevalent and severe in Australian Aboriginal and Torres Strait Islander Peoples with high mortality rates. To ensure that management of AIRD can be optimised for all Australians, it is important that we understand the prevalence and potential phenotypic variations of AIRD across the Australian population. However, to date there have been few described cases of AIRD other than SLE in Aboriginal and Torres Strait Islander Peoples. In this review, we summarise what is known about AIRD other than SLE in Aboriginal and Torres Strait Islander Peoples, particularly with regards to prevalence, phenotype and disease outcomes, and highlight the current gaps in knowledge.

Towards a novel clinical outcome assessment for systemic lupus erythematosus: first outcomes of an international taskforce.

Systemic lupus erythematosus (SLE) is a disease of high unmet therapeutic need. The challenge of accurately measuring clinically meaningful responses to treatment has hindered progress towards positive outcomes in SLE trials, impeding the approval of potential new therapies. Current primary end points used in SLE trials are based on legacy disease activity measures that were neither specifically designed for the clinical trial context, nor developed according to contemporary recommendations for clinical outcome assessments (COAs), such as that substantial patient input should be incorporated into their design. The Treatment Response Measure for SLE (TRM-SLE) Taskforce is a global collaboration of SLE clinician-academics, patients and patient representatives, industry partners and regulatory experts, established to realize the goal of developing a new COA for SLE clinical trials. The aim of this project is a novel COA designed specifically to measure treatment effects that are clinically meaningful to patients and clinicians, and intended for implementation in a trial end point that supports regulatory approval of novel therapeutic agents in SLE. This Consensus Statement reports the first outcomes of the TRM-SLE project, including a structured process for TRM-SLE development.

Fibromyalgia remains a significant burden in rheumatoid arthritis patients in Australia.

AIM: High rates of fibromyalgia (FM) are reported in rheumatoid arthritis (RA) patients. Advances in RA management have occurred, but information regarding current significance of FM in RA is limited. This investigation estimated the prevalence and health effects of concomitant FM in Australian RA patients. METHODS: Participants were recruited from Australian rheumatology clinics. Subjects were assessed using the 1990 and 2011 American College of Rheumatology (ACR) FM criteria and the polysymptomatic distress score (PDS) was calculated. A medical history and a clinical examination were recorded. RA Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS-28 ESR), and the Short Form-36 survey (SF-36) were completed. RESULTS: Of 117 RA patients, 33.3% (n = 39) met 1990 ACR FM criteria and 41.9% (n = 49) met 2011 ACR FM criteria. RA patients with comorbid FM had worse outcomes across all domains of health as defined by the SF-36 (P < 0.05). There was correlation between both physical and mental health outcomes and the PDS (P < 0.001). RA patients with FM on average took 1.18 extra ongoing prescribed medications (P < 0.05), despite comparable RA disease activity (DAS-28: 3.09 vs. 3.27, P = NS). Comorbid central sensitivity conditions were more common in patients with FM (P < 0.001). CONCLUSION: FM continues to demonstrate a high prevalence in a population of RA patients. RA patients with FM have more symptoms of other chronic sensitivity syndromes in addition to FM. They have a lower quality of life outcome and higher medication use. This has important clinical implications in terms of diagnosis, response to therapy, prescribing choices and clinical outcomes.

GILZ: Glitzing up our understanding of the glucocorticoid receptor in psychopathology.

Dysfunction of the hypothalamic-pituitary-adrenal axis, particularly the glucocorticoid receptor, is a commonly implicated link between stress and psychopathology. GR abnormalities are frequently reported in depression, and these anomalies must be resolved before depressive symptoms remit. This biological finding is rendered clinically relevant by the knowledge that only select antidepressants alter GR function. The relationship between GR dysfunction and other diseases associated with psychiatric stress, such as post-traumatic stress disorder (PTSD) and fibromyalgia, is also documented. However, as laboratory constraints limit the utility of GR testing, other measures of GR activity, such as levels of GR-induced genes, may have greater clinical value. In this review, glucocorticoid-induced leucine zipper (GILZ), a product of GR-initiated gene transcription, will be discussed in the context of GR dysfunction in psychopathology.