Monitoring and long-term management of giant cell arteritis and polymyalgia rheumatica

Abstract

Giant cell arteritis (GCA) is the most common type of primary vasculitis in Western countries 1,2. Polymyalgia rheumatica (PMR) is the second most common inflammatory rheumatic disease of the elderly after rheumatoid arthritis (RA) 3. The two diseases are interrelated: 40-60% of patients with GCA have symptoms of PMR 3 , and histological features consistent with GCA have been found in 16-21% of temporal artery biopsy samples from patients with PMR 3. Most of these patients with PMR, however, presented with additional features of GCA, whereas the prevalence of positive histology in unselected patients with PMR is unknown. Both GCA and PMR are heterogeneous diseases. Although systemic manifestations (such as fever, malaise and weight loss) are common in both diseases, they are not present in all patients 4-6. Up to 1 in 5 patients with GCA with ocular involvement can present without systemic manifestations of the disease 7. GCA is the most common form of large-vessel vasculitis (LVV) and has a broad spectrum of disease manifestations, which are frequently overlapping. In the majority of cases, cranial and extracranial large arteries are involved to varying degrees, leading to different clinical phenotypes 8,9. Isolated cranial or extracranial GCA, which are at either end of this continuum, are relatively uncommon 10. Predominant cranial GCA is characterized by headache, jaw claudication and visual manifestations (representing the prototypical clinical picture of temporal arteritis). By contrast, predominant large-vessel GCA is characterized by more pronounced systemic manifestations, PMR, vascular bruits, limb claudication and imaging signs of inflammation in the aorta and its major branches 10. In some of these patients, vascular stenoses or aneurysms in association with other GCA features are the presenting clinical manifestations 9,11. PMR is characterized by pain and stiffness in the shoulder and pelvic girdles, which can have an abrupt or a subtle onset 3. Up to 20% of patients with PMR can present with a normal erythrocyte sedimentation rate (ESR) 12 , although the presence of both normal ESR and C-reactive protein (CRP) levels is rare 13-15. Glucocorticoids are the cornerstone of treatment for GCA and PMR. They are effective, but glucocorticoidrelated adverse effects occur in up to 85% of patients with GCA and 65% of patients with PMR, respectively 16-22. The IL-6 receptor inhibitor tocilizumab has become available as a glucocorticoid-sparing strategy in patients with GCA 23,24 , an approach that is also being evaluated for PMR 25,26. Management of both GCA and PMR is hampered by the lack of universally accepted definitions of remission and other disease states (such as low disease activity or vessel damage without active disease). Many questions about monitoring and long-term management are still unanswered (Box 1).

Diagnostic value of [18F]FDG-PET/CT for treatment monitoring in large vessel vasculitis: a systematic review and meta-analysis

“…Concerns regarding the applicability of the findings were related to the reference standard in studies applying instruments (i.e. NIH criteria, BVAS or ITAS2010) that have not been thoroughly validated for treatment monitoring of patients with LVV [12,39].…”

“…The characteristic halo sign in the temporal arteries appears to gradually disappear upon treatment, whereas this abnormality may persist in the axillary arteries during clinical remission [11]. Magnetic resonance angiography (MRA) and computed tomography angiography (CTA) are extensively used in the diagnostic work-up of GCA, but little is known about their use to monitor treatment response [12]. These imaging modalities are also used for monitoring disease activity in TAK and aortitis, although evidence is even more scarce [13].…”

Ultrasound for diagnosis and follow-up of chronic axillary vasculitis in patients with long-standing giant cell arteritis

“…Inflammation might certainly persist despite GC therapy in a proportion of patients; however, the initial reduction and subsequent stabilization of IMT favours a hypothesis that acute inflammation is followed by myo-intimal proliferation and remodelling of the arterial wall that persists for years or is even life-long. 19,20 Repeated biopsies, as have been performed in temporal arteries (and where ongoing inflammation in one and remodelling in another subset have been found), 21 would be desirable to answer this question, but are unfortunately of course not possible.…”

Giant Cell Arteritis and Cardiac Comorbidity

“…While the goal of treatment is to achieve and maintain clinical remission, there is limited data and guidelines on what to do for patients after they achieve remission, including when and whether steroids or biologics should be discontinued. In terms of follow-up, inflammatory biomarkers and symptoms have been historically used to evaluate disease flare ups and efficacy of treatment [13]. Meanwhile, imaging has shown evidence of a chronic inflammatory and vasculitic process in areas affected by GCA, despite patients experiencing clinical remission of symptoms and return of inflammatory biomarkers back to baseline after the use of either tocilizumab or glucocorticoids [13,14].…”

“…In terms of follow-up, inflammatory biomarkers and symptoms have been historically used to evaluate disease flare ups and efficacy of treatment [13]. Meanwhile, imaging has shown evidence of a chronic inflammatory and vasculitic process in areas affected by GCA, despite patients experiencing clinical remission of symptoms and return of inflammatory biomarkers back to baseline after the use of either tocilizumab or glucocorticoids [13,14]. The long-term complications associated with the continued inflammation and vasculitis observed in imaging remain unclear.…”