Prospective studies of controversial aspects of polymyalgia rheumatica/giant cell arteritis

Kyle, Margaret Valerie (1987) Prospective studies of controversial aspects of polymyalgia rheumatica/giant cell arteritis. MD thesis, University of Glasgow.

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Abstract

This thesis reports on controversial aspects of polymyalgia rheumatica/giant cell arteritis (PMR/GCA). Controversies exist partly because previous studies tended to be small and retrospective, patients were seen by different doctors and inadequate diagnostic criteria were sometimes used. Studies were also biased towards the interests of particular specialties. In an attempt to overcome these limitations, I have studied prospectively 78 patients with active untreated PMR/GCA, referred to me largely by general practitioners. Patients were included only if specific diagnostic criteria were met. In an original case finding study in a general practice population, all patients over 65 were interviewed using a questionnaire previously shown to have high sensitivity and specificity for PMR/GCA. Patients with a positive questionnaire and ESR > 30 mm were seen again. Two new cases of PMR/GCA were detected and 17 existing cases confirmed, giving incidence and prevalence figures of 4/1000 and 33/1000 respectively. These figures are almost ten-fold higher than in previous studies, which were usually hospital-based. Clinical features and laboratory testing in all the patients were used to look for an association with stress, infection or autoimmune disease; a seasonal bias and prodromal illness were suggestive of an infective trigger. Histological classification of active arteritis, healed arteritis or normal age changes was made from 52 temporal arteries from patients in this study, 26 "positive" biopsies from other GCA cases and 10 controls. Sixty per cent of the biopsies from my patients were positive; arteritis was significantly more common in GCA (82%) but the presence of arteritis in 20% of PMR biopsies confirmed the overlap between them. The existence of "healed" arteritis was established, especially in PMR patients where positive biopsies were healed, not active. Patients with positive biopsies were significantly older than those with negative biopsies, and patients with healed biopsies had a longer history. Immunoperoxidase studies of 22 patients with PMR/GCA and 10 controls showed for the first time deposits of IgG, IgA, IgM and C3 in 4 active biopsies, particularly near the internal elastic lamina (IEL); IgG and IgA deposits were seen in 3 healed biopsies. No deposits were seen in negative biopsies. Electron microscopy was performed in 3 patients and 3 controls. Biopsies with active GCA showed fraying of the IEL on the intimal aspect with degeneration of the IEL. Smooth muscle cells were also abnormal but these findings in combination support the antigenic role of the IEL in the pathogenesis of PMR/GCA, rather than the importance of smooth muscle cells. Neither of these methods was more sensitive than standard light microscopy in detecting arteritis. Liver alkaline phosphatase levels were elevated equally commonly in both PMR and GCA patients, in approximately 40%. Isotope scans were carried out in 29 patients with active disease and follow-up scans were done in 15. Twenty-four per cent had abnormal isotope scans which surprisingly remained abnormal on follow-up, despite clinical recovery. An original method of assessing liver involvement by measuring the arterial:total blood flow ratio showed this was significantly lower in GCA, possibly due to hepatic arteritis. Patients with abnormal scans and flow ratios were more likely to have elevated alkaline phosphatase levels. Thus clear involvement of the liver in PMR/GCA was demonstrated and the mechanism suggested is arteritis.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine, Immunology
Date of Award: 1987
Depositing User: Enlighten Team
Unique ID: glathesis:1987-76675
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 13:55
Last Modified: 19 Nov 2019 13:55
URI: http://theses.gla.ac.uk/id/eprint/76675

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