The use of positron emission tomography and immune biomarkers to improve the diagnosis and prognostication of giant cell arteritis

Giant cell arteritis (GCA) is a medium to large vessel vasculitis that affects the elderly. It is a difficult condition to diagnose and manage due to its non-specific clinical presentation, potential for catastrophic vascular complications and the fact that patients are often frail with multiple comorbidities. The aim of this PhD was to explore the potential role of positron emission tomography/computer tomography (PET/CT) and serological biomarkers to diagnose GCA and identify patients who may have a more complicated clinical course. It also aimed to validate or refute a recently proposed hypothesis that GCA is a varicella zoster virus (VZV) reactivation syndrome. Following a detailed literature review (Chapter 2), a GCA specific PET/CT protocol was designed to allowed visualisation of the superficial cranial arteries. These vessels are typically inflamed in GCA but had not been investigated using PET/CT by other groups. The feasibility of the protocol was demonstrated in published work presented in Chapter 3. A cohort study was designed to address the key aims of the PhD. After human research ethics approval, 64 patients newly suspected of having GCA were enrolled between 2017 and 2018. All underwent a GCA specific PET/CT protocol, survey, examination, temporal artery biopsy and serological assessment at baseline. Patients underwent repeat clinical assessment for 12 months and patients with positive biopsies had a serial PET/CT scan at 6 months. The study had a number of important outcomes. Most significantly, it demonstrated that a GCA specific PET/CT protocol incorporating the head neck and chest has high diagnostic accuracy (Chapter 4). In contrast, the burden of PET/CT detected vascular activity did not appear to add a great deal of prognostic information and persistent tracer uptake at 6 months did not predict future clinical relapse (Chapter 5). The VZV component of the study was able to disprove the hypothesis that GCA is a VZV reactivation syndrome. It did not find evidence of active VZV using a multimodal clinical, serological and biopsy immunohistochemistry assessment (Chapter 6). The work argues against treating patients with antivirals in combination with corticosteroid treatment for GCA as had been proposed by some authors. The serological biomarker component of the PhD did not identify new markers with utility in diagnosing or assessing the vasculitis burden in GCA (Chapter 7). Given mixed reports in the literature, the overwhelmingly negative findings highlighted the importance of standardized testing and adequate validation of serological markers before considering their use in clinical practice. In summary, this PhD has led to significant advances in the assessment of patients with GCA. It has established PET/CT as a valid first line diagnostic test for patients suspected of having GCA. Furthermore, it provided important insights into the interpretation of baseline and 6-month PET/CT scans, novel serological biomarkers and debunked the link between VZV and GCA