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The article discusses updates on giant cell arteritis (GCA) treatment and management. Topics explored include the approval of tocilizumab (TCZ) by the British National Institute for Health and Care Excellence (NICE) and National Health Service (NHS) England for treating patients with GCA, the clinical guidelines for GCA diagnosis, and the challenges associated with disease activity assessment during therapeutic administration of TCZ.

The author discusses development of research regarding therapies for treatment of large vessel vasculitis (LVV). Topics discussed include illustration of stages involved in disease progression, observation of high-dose glucocorticoids (GC) as mainstay in LVV treatment, utilization of Methotrexate as adjunctive therapy leads to reduction in GC exposure, involvement of Leflunomide as steroid-sparing for treatment of giant cell arteritis (GCA) and elucidation of Abatacept as anti-T cell therapy.

Importance: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are related inflammatory disorders occurring in persons aged 50 years and older. Diagnostic and therapeutic approaches are heterogeneous in clinical practice.Objective: To summarize current evidence regarding optimal methods for diagnosing and treating PMR and GCA.Evidence Review: MEDLINE, EMBASE, and Cochrane databases were searched from their inception dates to March 30, 2016. Screening by 2 authors resulted in 6626 abstracts, of which 50 articles met the inclusion criteria. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool or American College of Cardiology Foundation/American Heart Association methodology.Findings: Twenty randomized clinical trials for therapy (n = 1016 participants) and 30 imaging studies for diagnosis and/or assessing response to therapy (n = 2080 participants) were included. The diagnosis of PMR is based on clinical features such as new-onset bilateral shoulder pain, including subdeltoid bursitis, muscle or joint stiffness, and functional impairment. Headache and visual disturbances including loss of vision are characteristic of GCA. Constitutional symptoms and elevated inflammatory markers (>90%) are common in both diseases. Ultrasound imaging enables detection of bilateral subdeltoid bursitis in 69% of PMR patients. In GCA, temporal artery biopsy remains the standard for definitive diagnosis. Ultrasound and magnetic resonance imaging (MRI) of large vessels revealing inflammation-induced wall thickening support the diagnosis of GCA (specificity 78%-100% for ultrasound and 73%-97% for MRI). Glucocorticoids remain the primary treatment, but the optimal initial dose and tapering treatment regimens are unknown. According to consensus-based recommendations, initial therapy for PMR is prednisone, 12.5 to 25 mg/day or equivalent, and 40 to 60 mg/day for GCA, followed by individualized tapering regimens in both diseases. Adjunctive methotrexate may reduce cumulative glucocorticoid dosage by 20% to 44% and relapses by 36% to 54% in both PMR and GCA. Use of tocilizumab as additional treatment with prednisone showed a 2- to 4-fold increase in remission rates of GCA in a randomized clinical trial (N = 30).Conclusions and Relevance: Diagnosis of PMR/GCA is made by clinical features and elevated inflammatory markers. In PMR, ultrasound imaging may improve diagnostic accuracy. In GCA, temporal artery biopsy may not be required in patients with typical disease features accompanied by characteristic ultrasound or MRI findings. Consensus-based recommendations suggest glucocorticoids as the most effective therapy for PMR/GCA. Methotrexate may be added to glucocorticoids in patients at risk for relapse and in those with glucocorticoid-related adverse effects or need for prolonged glucocorticoid therapy. [ABSTRACT FROM AUTHOR]

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease in persons over the age of 50 years. There are many diseases which mimic PMR, for which reason a careful diagnostic approach is required. While it is thought to be exquisitely responsive to glucocorticosteroid therapy, many patients respond incompletely and/or develop serious side effects over the protracted disease course. Improved methods for classification and disease assessment together with standardized treatment approaches and outcome assessments can serve to improve the care of patients with this disease. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is a large-vessel vasculitis predominantly affecting older people, with a peak incidence between 70 and 79 years of age. If untreated, ischaemic complications can be catastrophic for the patient, including blindness. We review the current treatment paradigms for this condition, the mainstay of which is immediate high-dose glucocorticoid therapy with a gradual dose tapering. Adverse events of glucocorticoid therapy are often observed after 12-24 months and corticosteroid-sparing adjuvant therapies are used in severe disease, multiple flares or patients at high risk of prolonged therapy. The current understanding of the pathogenesis of GCA is explored. This has informed the identification of new potential targets and approaches to treatment. Blockade of interleukin (IL)-6 (tocilizumab) and IL-1 (gevokizumab) are being evaluated in phase III clinical trials. It is hoped that improved risk stratification of organ damage and relapses will be developed using imaging and biomarkers, allowing for individualised treatment for patients; however, there remains further work to be done before this becomes a reality. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are linked conditions that occur in the elderly. GCA is a vasculitis of large- and medium-sized vessels causing critical ischemia. It is a medical emergency owing to the high incidence of neuro-ophthalmic complications. PMR is an inflammatory disease characterized by abrupt-onset pain and stiffness of the shoulder and pelvic girdle muscles. Both conditions are associated with a systemic inflammatory response and constitutional symptoms. The pathogeneses are unclear. The initiating step may be the recognition of an infectious agent by activated dendritic cells. The key cell type involved is CD4+ T cells and the key cytokines are IFN-g (implicated in granuloma formation) and IL-6 (key to the systemic response). The pathogenesis of PMR may be similar to that of GCA, however, PMR exhibits less clinical vascular involvement. The mainstay of therapy is corticosteroids, and diseasemodifying therapy is indicated in relapsing disease. This article reviews recent guidelines on early recognition, investigations and management of these diseases, as well as advances in imaging. INSETS: The International polymyalgia rheumatica classification criteria.;Key issues. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) or temporal arteritis (TA) with polymyalgia rheumatica (PMR) is among the most common reasons for long-term steroid prescription. GCA is a critically ischaemic disease, the most common form of vasculitis and should be treated as a medical emergency. Visual loss occurs in up to a fifth of patients, which may be preventable by prompt recognition and treatment. The British Society for Rheumatology (BSR) and the British Health Professionals in Rheumatology (BHPR) have recently published guidelines on the management of PMR. The purpose of this concise guidance is to draw attention to the full guidelines to encourage the prompt diagnosis and urgent management of GCA, with emphasis on the prevention of visual loss. They provide a framework for disease assessment, immediate treatment and referral to specialist care for management and monitoring of disease activity, complications and relapse. [ABSTRACT FROM AUTHOR]

The article focuses on the guidelines of British Society for Rheumatology (BSR) and British Health Professional in Rheumatology (BHPR) for managing polymyalgia rheumatic (PMR). It says that the guidelines is aiming for a safe and specific diagnostic process for PMR with the use of continued assessment. Moreover, the conditions which decreases the probability of PMR including inflammatory rheumatic diseases, drug-induced myalgia, and chronic pain syndromes are also presented.

Rheumatology has been witnessing dramatic developments. Improvement in our understanding of the pathogenesis of diseases and advancements in therapeutics has forced us to re-look at our approach to the disease. The emphasis is on early recognition, proper assessment and regular follow-up. Musculoskeletal ultrasonography (MSUS) has emerged as a promising tool in fulfilling most of these requirements. It has proved to be of significant utility in a variety of rheumatic diseases and has been in regular use in several European countries. In this review we have discussed in detail its use in various rheumatic diseases, the upcoming developments in the field of MSUS and various issues related to its incorporation into routine care of rheumatic patients. In our opinion MSUS is the future of rheumatology and we shouldn't be left behind just because of our reluctance to understand and appreciate this fascinating technology. [ABSTRACT FROM AUTHOR]

Autoimmunizing mechanisms are very hard to study in humans, so we have focused on vital clues in thymomas and hyperplastic thymuses in myasthenia gravis (MG). According to our multi-step hypothesis: thymic epithelial cells (TEC) present epitopes from the isolated acetylcholine receptor (AChR) subunits they express, and autoimmunize helper T cells; subsequently, these evoke “early antibodies” that then attack rare thymic myoid cells expressing intact AChR; in the resulting germinal centers, autoantibodies diversify to recognize native AChR. We have studied: 1) thymomas, to identify autoimmunizing cell types, focusing on IFN-α, against which many patients have high titer autoantibodies, as in another highly informative autoimmune syndrome. Although IFN-α is much easier to label than the sparse and delicate AChR subunits, we have not yet located obviously autoimmunizing micro-environments; 2) hyperplastic MG thymuses, where we find (a) upregulation of complement receptors and regulators on hyperplastic TEC and deposition of activated C3b complement component on them, (b) absence of complement regulators from almost all myoid cells, indicating vulnerability to attack, and (c) deposition of C3b, and even of the terminal membrane attack complex, especially on the myoid cells close to the infiltrating germinal centers. The changes are very similar in over 50% of the so-called seronegative patients with generalized MG (SNMG) but without detectable autoantibodies against AChR or MuSK, consistently with other evidence that they belong to the spectrum of AChR-seropositive MG. Together, moreover, our findings implicate both myoid cells and TEC in autoimmunization, and thus strongly support our hypothesis. [ABSTRACT FROM AUTHOR]

New data suggest that the first 2 years of treatment for giant-cell arteritis carry substantial risks, including myocardial infarction and death. Will these findings have implications for clinical practice? [ABSTRACT FROM AUTHOR]

The article presents the double-blind randomized placebo-controlled pilot study which explored the value of leflunomide (LEF) as additional treatment to corticosteroid in inducing remission in patients with new-onset polymyalgia rheumatica (PMR). It also assesses the steroid-sparing ability, side-effects profile and complications of the treatment. It claims that LEF was proven to be effective in treating such diseases as Takayasu arteritis and granulomatosis with polyangiitis.

The article presents the randomized, double-blind, placebo-controlled study which examined the effectiveness and safety of the drug gevokizumab as treatment of giant cell arteritis (GCA) as of May 2014.

The article presents the study which examined the results and cost effectiveness analysis of the fast track pathway in giant cell arteritis (GCA) that was introduced in 2012. The pathway is intended to lessen multiple referral routes, delayed review and treatment, as well as improve outcomes. In the study, the incremental cost effectiveness ratio (ICER) was used to compare the cost of fast-track pathway against the standard referral route.