Xavier Guillot

Vitamin D and inflammation.

Calcitriol, or 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D3) is a well-known endocrine regulator of calcium homeostasis. More recently, local calcitriol production by immune cells was shown to exert autocrine or paracrine immunomodulating effects. Immune cells that produce calcitriol also express the vitamin D receptor (VDR) and the enzymes needed to metabolize vitamin D3 (1α-, 25-, and 24-hydroxylases). Studies of animal models and cell cultures showed both direct and indirect immunomodulating effects involving the T cells, B cells, and antigen-presenting cells (dendritic cells and macrophages) and affecting both innate and adaptive immune responses. The overall effect is a switch from the Th1/Th17 response to the Th2/Treg profile. The immunomodulating effects of vitamin D may explain the reported epidemiological associations between vitamin D status and a large number of autoimmune and inflammatory diseases. Such associations have been suggested by observational studies not only in rheumatoid arthritis, lupus, inflammatory bowel disease, and type 1 diabetes; but also in infections, malignancies, transplant rejection, and cardiovascular disease. In animal models for these diseases, vitamin D supplementation has been found to produce therapeutic effects. Thus, vitamin D is a key focus for public health efforts and may hold promise for the treatment of dysimmune diseases.

Psoriasis Onset with Tocilizumab Treatment for Rheumatoid Arthritis

To the Editor: Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the interleukin 6 (IL-6) receptor, approved in the treatment of rheumatoid arthritis (RA), with potential use in other inflammatory diseases1. We describe a case of psoriasis onset during TCZ treatment in a patient with RA. A white woman, born in 1955, for 20 years had erosive RA, negative for anticitrullinated protein antibodies. Her condition did not respond to several disease-modifying … Address correspondence to Prof. D. Wendling, University Hospital J. Minjoz – Rheumatology, Boulevard Fleming, Besancon 25030, France. E-mail: dwendling{at}chu-besancon.fr

Non-radiographic spondyloarthritis: A theoretical concept or a real entity?

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 1 aout 2012

Cryotherapy in inflammatory rheumatic diseases: a systematic review

The aim of this article was to review current evidence about cryotherapy in inflammatory rheumatic diseases (therapeutic and biological effects). For therapeutic effects, we performed a systematic review (PubMed, EMBASE, Cochrane Library, LILACS databases, unpublished data) and selected studies including non-operated and non-infected arthritic patients treated with local cryotherapy or whole-body cryotherapy. By pooling 6 studies including 257 rheumatoid arthritis (RA) patients, we showed a significant decrease in pain visual analogic scale (mm) and 28-joint disease activity score after chronic cryotherapy in RA patients. For molecular pathways, local cryotherapy induces an intrajoint temperature decrease, which might downregulate several mediators involved in joint inflammation and destruction (cytokines, cartilage-degrading enzymes, proangiogenic factors), but studies in RA are rare. Cryotherapy should be included in RA therapeutic strategies as an adjunct therapy, with potential corticosteroid and nonsteroidal anti-inflammatory drug dose-sparing effects. However, techniques and protocols should be more precisely defined in randomized controlled trials with stronger methodology.

The IL-23/Th 17 pathway in spondyloarthritis: the royal road?

Joint Bone Spine - In Press.Proof corrected by the author Available online since lundi 22 septembre 2014

Pain and immunity

Chronic neuropathic and inflammatory pain is a major public health problem. Nociceptors undergo sensitization, first in peripheral tissues then in the central nervous sytem, via neuroimmune interactions linking neurons, glial cells (microglia and astrocytes), and immune cells. These interactions may either exacerbate or attenuate the pain and inflammation, which normally reach a state of equilibrium. With more powerful or longer lasting stimuli, specific profiles of microglial and, subsequently, astrocytic activation in the dorsal horn play a key role in neuronal plasticity and transition to chronic pain. Recent insights into the interactions between the nervous system and the immune system suggest a large number of potential therapeutic targets that could be influenced either by targeted inhibition or by directing the neuroimmune response toward the antiinflammatory and analgesic end of its spectrum.

Utility of 18F-fluoro-dexoxyglucose positron emission tomography for the diagnosis of polymyalgia rheumatica: a controlled study

OBJECTIVES To compare (18)F-fluoro-dexoxyglucose PET/CT (FDG-PET/CT) findings in patients with polymyalgia rheumatica (PMR) and controls without rheumatologic disease. METHODS We retrospectively included 50 patients with a diagnosis of PMR as well as 53 patients with a neoplasm as a control group. All patients underwent FDG-PET/CT. Seventeen hotspots were analysed. We performed a semi-quantitative analysis of FDG uptake (4-point score from 0 to 3). The cut-offs for the number of sites with high activity and for FDG uptake score were assessed using receiver operating characteristics curves and odds ratios (ORs). RESULTS The two groups were comparable for the median patient age (69.3 years for PMR vs 68.1 for controls). Significant differences between the two groups were found for FDG uptake score (1.12 vs 0.34, P < 0.00001) and for the number of sites with significant uptake (score ⩾ 2): 6.36 sites vs 1.49 sites (P < 0.00001). The presence of three or more sites with significant uptake was correlated with the diagnosis of PMR with 74% sensitivity and 79% specificity (OR = 10.8). For the FDG uptake score, the cut-off was 0.53 (sensitivity 80%, specificity 77%, OR = 13.6). We found significant differences in all sites for FDG uptake score and the number of sites with significant uptake, particularly marked for shoulders, ischial tuberosities and interspinous bursitis (P < 0.00001 for FDG uptake score). CONCLUSION Our results suggest that the number of sites with significant FDG uptake and the uptake score could be relevant criteria for the diagnosis of PMR.

When gout involves the spine: five patients including two inaugural cases.

UNLABELLED Spinal involvement is uncommon during gout and may raise diagnostic challenges. We describe five cases seen at a single center. METHODS We retrospectively reviewed the medical charts of the five patients with spinal gout seen over a 3-year period. RESULTS There were four men and one woman with an age range of 52 to 87 years. One patient presented with acute neck pain and visualization by imaging studies of a discovertebral tophus, another had febrile arthritis of a lumbar facet joint, and a third presented with a synovial cyst in a lumbar facet joint. The remaining two patients had acute febrile discitis confirmed by magnetic resonance imaging, at the cervical spine and lumbar spine, respectively. Laboratory tests showed systemic inflammation in four patients and marked serum uric acid elevation in two patients. Only three patients reported a previous history of peripheral acute gout attacks. Specimens of the spinal lesions were obtained in three patients and consistently showed monosodium urate crystals with tissue inflammation or a tophus. The outcome was rapidly favorable, either with colchicine therapy alone in four patients or after surgical resection of a facet joint cyst (during surgery to stabilize the lumbar spine) in the remaining patient. The patient with neck pain due to a tophus experienced nerve root pain at the acute phase. No other neurological manifestations were recorded. CONCLUSION These case reports illustrate the diagnostic challenges raised by spinal involvement due to gout. The spinal lesions can be inaugural, as seen in two of our five patients.

Endothelial dysfunction in joint disease

Inflammatory joint diseases and autoimmune diseases with joint manifestations are associated with premature and accelerated atherogenesis. Patients with rheumatoid arthritis (RA) have a 5- to 10-year decrease in life expectancy compared to the general population, and those exhibiting extraarticular manifestations have the greatest excess mortality. RA is now established as an independent cardiovascular risk factor. Complex interactions linking conventional cardiovascular risk factors, systemic inflammation, and vascular function may explain the increased cardiovascular risk among RA patients. Endothelial dysfunction is now recognized as both the key step in early atherogenesis and a contributor to atheroma plaque progression at later stages. Endothelial dysfunction is defined as impaired endothelium-dependent blood-vessel dilation in response to a stimulus. The underlying mechanisms remain speculative. Over the last decade, a role for endothelial dysfunction in the cardiovascular complications of inflammatory joint disease has been hypothesized and several maintenance drugs targeting this phenomenon have been tested, with promising results.

Exacerbation of combined pulmonary fibrosis and emphysema syndrome during tocilizumab therapy for rheumatoid arthritis.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mardi 23 avril 2013