Definitions of and Instruments for Disease Activity, Remission, and Relapse in Polymyalgia Rheumatica: A Systematic Literature Review.

OBJECTIVE: To perform a systematic literature review on definitions and instruments used to measure remission, relapse, and disease activity in polymyalgia rheumatica (PMR), to inform an OMERACT project to endorse instruments for these outcomes. METHODS: A search of Pubmed/MEDLINE, EMBASE, CINAHL, Cochrane, and Epistemonikos was performed May 2021 and updated August 2023. Qualitative and quantitative studies published in English were included if they recruited people with isolated PMR regardless of treatment. Study selection and data extraction was performed independently by two investigators and disagreement was resolved through discussion. Data extracted encompassed definitions of disease activity, remission and relapse, and details regarding the instruments used to measure these outcomes. RESULTS: From the 5,718 records, we included 26 articles on disease activity, 36 on remission, and 53 on relapse; 64 studies were observational and 15interventional, and none used qualitative methods. Some heterogeneity was found regarding definitions and instruments encompassing the domains pain, stiffness, fatigue, laboratory markers (mainly acute phase reactants), and patient and physician global assessment of disease activity. However, instruments for clinical signs were often poorly described. Whilst measurement properties of the polymyalgia rheumatica activity score (PMR-AS) have been assessed, data to support its use for measurement of remission and relapse is limited. CONCLUSION: Remission, relapse, and disease activity have been defined heterogeneously in clinical studies. Instruments to measure these disease states still need to be validated. Qualitative research is needed to better understand the concepts of remission and relapse in PMR. REVIEW REGISTRATION: PROSPERO identification: CRD42021255925.

Abnormalities at three musculoskeletal sites on whole-body positron emission tomography/computed tomography can diagnose polymyalgia rheumatica with high sensitivity and specificity.

PURPOSE: To evaluate the sensitivity and specificity of PET/CT findings in PMR and generate a diagnostic algorithm utilizing a minimum number of musculoskeletal sites. METHODS: Steroid-naïve patients with newly diagnosed PMR (2012 EULAR/ACR classification criteria) were prospectively recruited to undergo whole-body 18F-FDG PET/CT. Each PMR case was age- and sex-matched to four PET/CT controls. Control scan indication, diagnosis and medical history were extracted from the clinical record. Qualitative and semi-quantitative scoring (maximum standardized uptake value [SUVmax]) of abnormal 18F-FDG uptake at 21 musculoskeletal sites was undertaken for cases and controls. Results informed the development of a novel PET/CT diagnostic algorithm using a classification and regression trees (CART) method. RESULTS: Thirty-three cases met the inclusion criteria and were matched to 132 controls. Mean age was 68.6 ± 7.4 years for cases compared with 68.2 ± 7.3 for controls, and 54.5% were male. Median CRP was 49 mg/L (32-65) and ESR 41.5 mm/h (24.6-64.4) in the PMR group. The predominant control indication for PET/CT was malignancy (63.6%). Individual musculoskeletal sites proved insufficient for diagnostic purposes. A novel algorithm comprising 18F-FDG uptake ≥ 2 adjacent to the ischial tuberosities in combination with either abnormalities at the peri-articular shoulder or interspinous bursa achieved a sensitivity of 90.9% and specificity of 92.4% for diagnosing PMR. CONCLUSIONS: The presence of abnormal 18F-FDG uptake adjacent to the ischial tuberosities together with findings at the peri-articular shoulder or interspinous bursa on whole-body PET/CT is highly sensitive and specific for a diagnosis of PMR. TRIAL REGISTRATION: Clinical Trial Registration: Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au , ACTRN1261400696695.

Fusion of positron emission tomography/computed tomography with magnetic resonance imaging reveals hamstring peritendonitis in polymyalgia rheumatica.

Objectives: To characterize 18F-fluorodeoxyglucose (18F-FDG) uptake on whole-body PET/CT in PMR, and identify its precise anatomic correlate using MRI. Methods: Patients with newly diagnosed PMR according to the 2012 EULAR/ACR classification criteria were prospectively recruited. Participants with GCA were excluded. A whole-body 18F-FDG PET/CT scan was performed in all untreated patients. Qualitative and semiquantitative [standardized uptake value maximum (SUVmax)] scoring of abnormal 18F-FDG uptake was undertaken. MRI of the pelvis, knee and wrist and hand was performed in three representative patients with anatomical correlation of FDG-avid sites carried out using Medview fusion software. Results: Twenty-two patients with PMR were recruited. Their mean age was 68.3 years (s.d. 6.3) and 13/22 were male. On whole-body PET/CT, 18F-FDG uptake adjacent to the ischial tuberosities was observed in 21 participants (95.4%) and recorded the highest mean SUVmax value [3.6 (s.d. 1.7)]. A high frequency of posteromedial knee (61.9%) and wrist and/or hand involvement (66.7%) was also appreciated. MRI of the pelvis revealed high T2 signal surrounding the proximal hamstring tendon origins of both semimembranosus and the conjoint tendon of the semitendinosus and biceps femoris. At the knee, peritendonitis at the distal insertion of the semimembranosus was observed. PET/MRI fusion at the pelvis and knee confirmed semimembranosus peritendonitis as the anatomical correlate of 18F-FDG uptake adjacent to the ischial tuberosities and of posteromedial knee structures. Conclusion: Hamstring peritendonitis is a common and distinctive manifestation of PMR on whole-body PET/CT. Trial registration: Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au, ACTRN1261400696695.

Immune Checkpoint Inhibitor-induced Polymyalgia Rheumatica.

Polymyalgia rheumatica (PMR) immune-related adverse events (ICI-PMRs) represent a novel, distinct entity, despite many clinical, laboratory, and imaging similarities to classical PMR. Important questions remain in differentiating ICI-PMR from classical PMR, as well as other immune-related adverse events and PMR mimics. Despite this, ICI-PMR currently takes treatment cues from classical PMR, albeit with considerations relevant to cancer immunotherapy. Comparisons between ICI-PMR and classical PMR may provide further bidirectional insights, especially given that important questions remain unanswered about both diseases. The cause of classical PMR remains poorly understood, and ICI-PMR may represent a model of induced PMR, with important therapeutic implications.

Characterising polymyalgia rheumatica on whole-body 18F-FDG PET/CT: an atlas.

The impact of modern imaging in uncovering the underlying pathology of PMR cannot be understated. Long dismissed as an inflammatory syndrome with links to the large vessel vasculitis giant cell arteritis (GCA), a pathognomonic pattern of musculotendinous inflammation is now attributed to PMR and may be used to confirm its diagnosis. Among the available modalities, 18F-fluorodeoxyglucose (18F-FDG) PET/CT is increasingly recognized for its high sensitivity and specificity, as well as added ability to detect concomitant large vessel GCA and exclude other relevant differentials like infection and malignancy. This atlas provides a contemporary depiction of PMR's pathology and outlines how this knowledge translates into a pattern of findings on whole body 18F-FDG PET/CT that can reliably confirm its diagnosis.