GCA and PMR

Clinical and immunogenetic characterization of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) through the establishment of the UK GCA Consortium.

Aim:

The aims of this study are the clinical and epidemiological characterisation of giant cell arteritis (GCA ) and polymyalgia rheumatic (PMR), alongside the identification and validation of diagnostic, prognostic and monitoring biomarkers in either the blood (including genetic and soluble biomarkers) or the tissue (temporal artery). The UK GCA Consortium has been established to facilitate this work in GCA

Method:

Multicentre observational study.

Background:

Giant cell arteritis (GCA) is the commonest primary systemic vasculitis. It affects the over-50s and diagnosis can be difficult against a background of age-related symptoms. Diagnosis may be confirmed with a temporal artery biopsy. GCA is a medical emergency: if not treated with steroids immediately, the thickening of the inflamed blood vessel wall can cause irreversible visual loss or stroke. These irreversible ischaemic complications occur in 21%, despite steroid treatment. 30-78% relapse and 50% remain steroid dependent for at least 2-3 years. Steroid treatment can cause fractures (35%), severe infections (21%), diabetes, hypertension or psychosis (Proven et al., 2003), and has been implicated in 21-37% of all GCA deaths. Recent evidence also suggests that aneurysm or dilatation of the aorta, particularly the thoracic aorta, may occur as a late complication in up to 20% of patients with GCA; it is currently believed that this arises due to damage to the aortic wall from the inflammatory attack.

 Thus GCA remains a major healthcare challenge. In the elderly, GCA is even more common than rheumatoid arthritis (incidence in the over-70s is 53/100,000/year) and yet it receives relatively little research attention.

Thus, major sequelae of GCA include:

· Ischaemic manifestations (usually at onset of disease)

· Complications of steroid treatment

· Aneurysm

PMR, characterised by inflammatory limb-girdle pain with early morning stiffness and a systemic inflammatory response, demonstrated by elevation in inflammatory markers. Approximately 10% of patients with PMR will go on to develop late GCA and approximately half of all patients presenting with GCA also have symptoms of PMR. Most individuals with GCA also have a systemic inflammatory response. Although several different sets of classification criteria exist, there is still no universally-agreed set of core outcome measures for clinical characterisation of PMR which will be necessary for genetic association studies.

Like GCA, patients with PMR may experience complications related to long-term steroid treatment.

Although GCA and PMR appear closely related, it remains unclear whether GCA and PMR are the same disease, or separate diseases which may share common pathogenetic features.

Funding:

Originally funded by a Research into Ageing (now part of Age UK) Clinical Training Fellowship to Dr Sarah Mackie.

 Additional funding for individual substudies has been provided by the Wellcome Trust/ Academy of Medical Sciences (Clinical Lecturer Starter grant), Mason Medical Research Trust, Leeds Teaching Hospitals Charitable Foundation and Biomedical Health Research Centre and NIHR (Biomedical Research Unit).

Contact:

Professor Ann Morgan, a.w.morgan@leeds.ac.uk

Professor of Molecular Rheumatology

 OR

 Dr Sarah Mackie

S.L.Mackie@leeds.ac.uk, NIHR Clinician Scientist