Are There Definite Disease Subsets in Polymyalgia Rheumatica? Suggestions from a Narrative Review

Background: Polymyalgia rheumatica (PMR) has a multifaceted onset and course, and making a distinction between true PMR and so-called "polymyalgic syndrome" (that is, similar manifestations caused by different conditions) is far from easy in clinical practice. The existence of subsets within true PMR may further complicate the diagnostic question. Distinguishing PMR subsets from PMR-mimicking conditions does not just carry nomenclature value and speculative significance. Indeed, the correct diagnosis influences treatment, prognosis, epidemiological assessments, and health policies. Objectives: We aimed to (1) ascertain the presence of a definite and peculiar subset/subgroup/cluster of PMR in the scientific literature; (2) describe any possible subset/cluster/subgroup of PMR identified in at least two different studies. Methods: We performed a non-systematic (PRISMA protocol not followed) literature search on Embase and Medline (OVID interface). The following search terms were used: polymyalgia rheumatica, subset, cluster, subgroup, subclinical giant cell arteritis, mimicking conditions, polymyalgia rheumatica-like conditions, immunotherapy, checkpoint inhibitor, acute-phase reactants or acute-phase proteins, vaccination, infection, and calcium pyrophosphate deposition disease or chondrocalcinosis. Each paper's reference list was scanned for additional publications meeting this study's aim. Abstracts submitted at conferences or from non-peer-reviewed sources were not included. Results: The initial search yielded 2492 papers, of which 2389 articles were excluded based on title and abstract screening. A total of 103 articles underwent a full-length review, and 84 of them were finally assessed for eligibility. A total of seven large subsets of PMR could be identified: (1) PMR with normal acute-phase reactants; (2) PMR with an infection trigger; (3) PMR with a vaccination trigger; (4) PMR with subclinical giant cell arteritis (GCA); (5) PMR and calcium pyrophosphate deposition disease (CPPD); (6) PMR following immune checkpoint inhibitor (ICI) therapy; (7) PMR with peculiar clinical clusters (based on clinical or statistic clustering methods). Conclusions: PMR with normal baseline acute-phase reactants and PMR with an infection or a vaccination trigger could be categorized as subsets of disease. PMR with subclinical GCA and most cases of PMR/CPPD should be categorized as mimickers. Finally, further studies are required to better categorize some peculiar clinical subsets emerging from cluster analyses, and ICI-induced PMR.