Background/Purpose: Giant-cell arteritis (GCA) is a large-vessel vasculitis affecting patients >50 years, whose origin remains widely unelucidated. Recent studies demonstrated that myeloid disease-related somatic mutations were frequent in healthy aged patients, defining the concept of clonal hematopoiesis. Those mutations, especially JAK2^V617F, which occur even more frequently in patients with atherosclerosis, are suspected of inducing monocyte/macrophage inflammatory responses through IL-1β and IL-6 secretion. Because GCA pathogenesis involves myeloid cells and inflammatory cytokines, and JAK/STAT was shown to be a major inflammatory pathway, we aimed to analyze characteristics of GCA patients with associated myeloproliferative neoplasms (MPNs).

Methods: We conducted a nationwide multicenter retrospective study, including 17 patients with MPN-associated GCA (cases) and 50 GCA patients without MPN (controls), matched for age and sex. All patients satisfied the American College of Rheumatology criteria. Clinical characteristics, laboratory parameters and outcomes were analyzed and compared between groups.

Results: The most frequent MPNs associated with GCA were essential thrombocytosis (n=11), primary myelofibrosis (n=2), polycythemia vera (n=2) and chronic myelomonocytic leukemia (n=1). One case had an isolated JAK2^V617F mutation without myeloproliferation.JAK2^V617F mutation was found in 88% of cases with a median [IQR] various allele frequency of 14.5% [4.6–47.2]. Seven cases were diagnosed with MPN before GCA (median 18 [4–44] months), 1 simultaneously, and 9 after (median 12 [5–54] months). MPN–GCA cases, compared to controls, respectively, had less frequent constitutional symptoms (35% vs. 76%; p=0.003), less frequent cephalic symptoms (70% vs. 96%; p=0.003) and scalp hyperesthesia (23% vs. 56%; p=0.003), but more frequent monocular blindness (18% vs. 2%; p=0.04). GPA–MPN case’s platelet counts were significantly higher (491 [346–654] vs. 376 [299–475] ×10⁹/L; p=0.03); however, their temporal artery biopsy-positivity rates were comparable (p=0.91).

First-line therapy mostly relied on oral prednisone and aspirin for cases and controls, and did not differ between groups. No patient received JAK inhibitors during follow-up. Relapse-free survival was comparable for the 2 groups. Immunosuppressants were used as glucocorticoids-sparing agents for 12% in each group, with methotrexate being the most frequently prescribed. Mortality was higher for GCA–MPN cases (29 vs. 2%; p=0.003) with shorter overall survival (log-rank test, p=0.008), compared to GCA controls.

Conclusion: Essential thrombocytosis is the most frequent MPN associated with GCA. A high platelet count at GCA diagnosis should lead to a search for JAK2V617F mutation. Compared to controls, GCA patients with MPN seem to have a poorer prognosis with a low overall survival, probably due to the MPN or associated comorbidities.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/giant-cell-arteritis-associated-with-myeloproliferative-neoplasms-a-retrospective-case-control-study/