Mikito Takayasu described his eponymous “pulseless” arteritis in 1908, while Bayard Horton presented the first histologically defined cases of temporal arteritis in 1932. Although both conditions describe systemic arterial inflammation, they are considered separate diseases based on age of onset (giant cell arteritis GCA in the elderly versus Takayasu arteritis TAK in the young), geography (GCA in Caucasians versus TAK in non-Caucasians), and vascular involvement (GCA cranial versus TAK extra-cranial). However, this dichotomous view may be oversimplistic. Large vessel (LV) involvement in cranial GCA was described in 1946. Since then, numerous studies conducted across diverse geographic regions, using various diagnostic modalities and endpoints, have reported LVV in GCA in up to 83%. LV involvement is observed in relatively younger GCA cases, often associated with relapsing disease and a relatively poor response to glucocorticoids (GC) 1, 2. On the other hand, the age cutoff for TAK has moved from 50 to 60 years, posing the semantic question for patients with LV involvement in their 50s—young GCA or old TAK 3. Cranial GCA is increasingly reported among non-Caucasian populations 4, whereas LV-GCA is commonly identified on imaging in both GCA and PMR (GPSD) 1. Should we therefore transition from a dichotomous to a spectrum concept as we plan novel trials and therapies for these conditions, be deviled by conventional GC toxicity? This cautious migration in our outlook is encouraged by pathophysiological and imaging overlaps. Our proposal to consider both disorders within a unified clinical spectrum does not imply identity. However, there is sufficient similarity to warrant trials of common treatment targets employing similar protocols and a common imaging approach. Both GCA and TAK cause granulomatous inflammation of large and medium-sized vessels, although the vascular distribution differs 5, 6. GCA is genetically associated with HLA-class II alleles, whereas the major risk factor for TAK is HLA-B*52, a class I allele 1, 6, resembling other MHC-I-opathies 7. In both conditions, a common IL-12B gene polymorphism is present, and CD4+ and CD8+ T cells contribute to pathogenesis, alongside monocytes/macrophages, natural killer cells, and dendritic cells 2, 6. The similarities (notwithstanding the differences) suggest that they could be regarded as separate phenotypes within the LVV spectrum. Isolated idiopathic aortitis (IA) is an example of the spectrum since it is often classified as either GCA or TAK, depending on the patient's age and where it is diagnosed. Despite variations in disease pathology and distribution, multiple studies highlight clinical features of TAK that may also manifest in GCA 6. These include musculoskeletal complaints, arthralgia, synovitis, myalgia, visual disturbances, vision loss, and constitutional symptoms. The inclusion of TAK with GPSD within the LVV spectrum would address a unified approach in clinical trials, classification criteria, and treatment strategies. There are shared and divergent immunopathophysiological mechanisms too between GCA and TAK (Figure 1). The HLA associations differ: HLA-B*52 in TAK versus HLA-DRB1*04 in GCA. The Th1 and Th17 pathways, mediated by macrophages, play key roles in both diseases, and common cytokine pathways (IL-6, IL-12/23, and IFN-γ) contribute to disease amplification 6. Proteomic signatures of the two diseases were very similar, including cytokines, chemokines, and tissue remodeling proteins 8. The key steps for disease initiation are thought to be similar to vascular dendritic cell activation and granulomatous inflammation 6. While imaging findings vary in detail—reflecting TAK's anatomical distribution and higher incidence of stenotic disease—the diagnostic approaches bear notable similarities, with ultrasonography, PET/PET-CT, and CT/MR angiography playing central roles. In particular, POCRUS—the sequential application of clinical pretest probability, such as the Southend GCAPS, followed by targeted ultrasound using standardized assessment, such as eight-vessel ultrasound to compute Halo count, Halo score, and OGUS—may assist diagnosis, disease assessment (remission, smoldering disease, and vascular remodeling), and disease stratification 9. This suggests that a unified diagnostic strategy could be applied to both conditions. Such targeted imaging can therefore be seen as a unifying step that links the state of the vessel wall to clinical decision-making. In practice, there is considerable variation in resource availability/access, and POCRUS can provide a scalable solution to underpin LVV management. There is emerging evidence for the limited efficacy of GC within the LVV spectrum. For example, although cranial GCA may often respond to GC alone, LV-GCA and relapsing PMR require additional therapeutic agents, either synthetic disease-modifying antirheumatic drugs (DMARDs) or biologics 10. Treatment strategies, therefore, need to be tailored to disease phenotype, implying early disease stratification that would then lead to early, stratified therapy. Early stratification would also provide impetus for a proactive rather than a traditional reactive approach, in which complex therapies are escalated based on whether the patient has a remitting or relapsing disease. We call for a harmonized international data collection effort. There is an unmet need for real-world phenotype data, treatment response, imaging follow-up, and long-term outcomes. Several existing national registries (e.g., the JPVAS, Chinese, and Turkish TAK registries) require harmonization. There needs to be an international effort to outline core dataset elements: demographics, imaging findings, treatment, response definitions, and patient-reported outcome measures. This effort should align with and collaborate with the OMERACT, EULAR, ACR, and APLAR working groups. There is a lack of validated treat-to-target endpoints and response criteria for clinical trials. There is an urgent need for imaging endpoints in clinical trials, as only a few GCA, PMR, or TAK trials to date have investigated imaging for diagnosis, stratification, or response. In this era of personalized precision medicine, we need an international research effort to coordinate the search for biomarkers for diagnosis, prognosis, stratification of treatment targets, response, and damage. All authors contributed to the conception of the article, drafting and critical revision of the manuscript, and approved the final version for submission. This editorial was written by the three of us, inspired by the discussions held during the APLAR 2025 Pre-Congress Workshop, “Giant Cell Arteritis, Polymyalgia Rheumatica, and Takayasu Arteritis: A Unified Spectrum of Large Vessel Vasculitis.” We would like to express our sincere gratitude to the following colleagues who participated in the workshop as faculty members (listed in alphabetical order): Dr. Li-Ching Chew, Dr. Haner Direskeneli, Dr. K.S.M. van der Geest, Dr. Toshio Kawamoto, Dr. Nakako Mabuchi, Dr. Daiki Nakagomi, Dr. Alwin Sebastian, Dr. Takahiko Sugihara, Dr. Xinping Tian, and Dr. Hajime Yoshifuji. We would also like to thank the APLAR secretariat for assistance with organizing this meeting; AbbVie GK, FUJIFILM Medical Co. Ltd., and CANON MEDICAL SYSTEMS CORPORATION for loaning the ultrasound machines used in the hands-on seminar; Sunplanet Co. Ltd. for coordinating the hands-on seminar; and healthy volunteers for their participation. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have nothing to report. The authors have nothing to report. M.H. has received research grants and a speaker's fee from Bristol Myers Squibb, Chugai Pharmaceutical, and AbbVie Japan. B.D. has received consultancy fees and unrestricted educational grants for ultrasound workshops from Novartis, AbbVie, and Sanofi. K.O.K. reports no disclosures. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Harigai et al. (Wed,) studied this question.