PO:21:019 | Clinical phenotypes in IgG4-related disease: ACR/EULAR classification and practical limitations

Mattia Caliste¹, Flavia D'Auria², Linda Mastromanno¹, Francesca Carfora², Carla Giordano³, Cristiano Alessandri¹, Marcella Visentini², Fabrizio Conti¹, Roberta Priori^1|4 | ¹Dipartimento Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma; ²Dipartimento Medicina Traslazionale e di Precisione, Sapienza Università di Roma; ³Dipartimento Scienze Radiologiche, Oncologiche e Anatomo-patologiche, Sapienza Università di Roma; ⁴Saint Camillus International University of Health Science, UniCamillus, Roma, Italy

Background. IgG4-related disease (IgG4-RD) is a rare, immune-mediated fibroinflammatory condition that can affect virtually any organ. Traditional diagnostic criteria (Umehara et al.) include clinical/radiological evidence of organ involvement, elevated serum IgG4, and specific histopathology. However, serum IgG4 elevation is inconsistent, and biopsy is not always feasible. The 2019 ACR/EULAR classification criteria introduced a point-based system (threshold ≥20) to improve disease classification.

Materials and Methods. We retrospectively reviewed the clinical data of patients suspected to have IgG4-RD, which is defined by typical organ involvement, elevated serum IgG4 levels, and the exclusion of alternative diagnoses. Each patient was scored using ACR/EULAR criteria and assessed per diagnostic standards. Patients were grouped into four clinical phenotypes (head and neck, retroperitoneal/aortitis, systemic, pancreatobiliary) as described by Lanzillotta et al. Statistical analysis was performed using RStudio.

Results. A total of 46 patients were included: 17 head and neck, 16 retroperitoneal/aortitis, 7 systemic, and 6 pancreatobiliary. Mean age was 57.9 years; 58.7% were male. The systemic phenotype showed the highest number of involved sites (mean 2.1). Serum IgG4 levels did not significantly differ among groups. Biopsy rates varied: 100% in systemic, 93.8% in head and neck, 83.3% in pancreatobiliary, and 31.2% in retroperitoneal/aortitis (p < 0.001). Definitive diagnosis was most frequent in systemic (85.7%), while retroperitoneal/aortitis was more often categorized as possible diagnosis (62.5%). Two patients (4.3%) failed to meet either diagnostic or classification criteria. All systemic cases scored ≥20 points. In the head and neck group, three scored below threshold, one of whom was not biopsied. Among retroperitoneal/aortitis patients, 66% scored <20, and none had undergone biopsy. One non-biopsied pancreatobiliary case also failed to meet the score threshold.

Conclusions. The ACR/EULAR criteria improve classification of suspected IgG4-RD by incorporating clinical parameters. However, histopathology remains essential for accurate diagnosis and inclusion in clinical trials, especially in retroperitoneal/aortitis and head and neck phenotypes. Most non-biopsied retroperitoneal/aortitis cases did not meet classification thresholds. Histological evaluation supports more precise diagnosis in head and neck cases. Conclusions for other phenotypes are limited by small sample sizes, though biopsy was commonly performed.