SAT0528 CLINICAL PHENOTYPES OF IGG4-RELATED DISEASE REFLECT DIFFERENCES IN EPIDEMIOLOGICAL FEATURES, SEROLOGICAL FINDINGS, AND PROGNOSTIC OUTCOMES
Authors: M. Lanzillotta, E. Della Torre, C. Campochiaro, G. Mancuso, L. Dagna
Journal: Annals of the Rheumatic Diseases (2020)

Background: Four clinical phenotypes of IgG4-Related Disease (IgG4-RD) have been recently identified by Latent Class Analysis (LCA) - Pancreato/biliary (Group 1); Retroperitoneum/Aortitis (Group 2); Head-and-neck limited (Group 3); Mickulicz/Systemic (Group 4) - but the relevance of this classification for patient management remains unknown (1,2). Objectives: We aimed to assess whether clinical judgment can replicate LCA classification and to evaluate potential differences in epidemiological features, serological findings, and disease outcomes between disease phenotypes. Methods: The study included 179 patients. Four IgG4-RD experts were asked to classify a validation cohort of 40 patients according to published LCA derived phenotypes based on clinical judgment. Agreement between LCA and clinical clustering was calculated. To assess differences among disease phenotypes, the following variables were recorded on additional 139 patients: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD Responder Index (RI); history of atopy, diabetes, osteoporosis, relapses, and tumors; cumulative dose of glucocorticoids and use of rituximab. Results: Clinical judgment recapitulated LCA classification with strong agreement between IgG4-RD experts (κ= 0.841, p &lt; 0.0005). Group 1 showed the highest levels of serum IgG4 and IgE. Group 2 and 4 had the lowest and highest IgG4-RD RI, respectively (Table 1). Increased cumulative doses of glucocorticoids and higher relapse rate were observed in Group 3 (Fig 1). A higher incidence of diabetes mellitus was observed in Group 1 and 4. Table 1 Clinical and serological characteristics of patients cohort. Group 1 (59 pts - 45% ) Group 2 (29 pts - 22% ) Group 3 (25 pts - 19% ) Group 4 (18 pts - 14% ) P value Female n° (%) 12 (20%) 8 (28%) 11 (44%) 5 (28%) 0.18 Age 67 (61-73) 61 (56-70) 52 (40-62) 57 (51-62) &lt;0.0001 Serum IgG4 (mg/dL) 331 (184-575) 155 (49-258) 150 (80-255) 282 (166-460) 0.0009 IgG4-RD RI 9 (6-9) 6 (6-9) 9 (6-12) 9 (6-13) 0.004 Definite diagnosis n° (%) 20 (34%) 18 (62%) 20 (80%) 10 (55%) 0.0008 Probable diagnosis n° (%) 1 (0.59%) 0 (0%) 1 (0.19%) 1 (0.14%) 0.6 Possible diagnosis n° (%) 38 (64%) 10 (34%) 4 (16%) 7 (39) 0.0003 Emergency Department n° (%) 37 (63%) 14 (48%) 7 (28%) 10 (55%) 0.03 History of atopy n° (%) 7 (12%) 4 (14%) 7 (28%) 6 (23%) 0.09 ESR (mm/h) 20 (8-39) 40 (14-59) 38 (14-54) 12 (8-21) 0.04 CRP (mg/L) 5 (2-8) 10 (3-52) 8 (3-28) 3 (2-6) 0.03 Eosinophils (cell/mm 3 ) 200 (200-500) 200 (100-275) 300 (200-475) 200 (100-500) 0.3 IgE (U/mL) 283 (97-723) 69 (28-264) 120 (41-412) 219 (54-657) 0.02 Plasmablast (cell/mL) 1765 (627-4000) 1890 (1020- 4000) 2000 (370- 4780) 2690 (140-5130) 0.99 Diagnostic delay (months) 4 (2-9) 7 (4-12) 10 (3-18) 11 (2-38) 0.04 Starting prednisone dose (mg, range) 60 (37-70) 50 (40-75) 65 (40-90) 40 (30-70) 0.8 Diabetes at disease onset 10 (17%) 1 (3%) 2 (8%) 2 (11%) 0.09 Figure 1. Relapse free survival of the four different IgG4-RD phenotypes. Conclusion: Clinical phenotypes of IgG4-RD reflect differences in epidemiological features and prognostic outcomes. References: [1]Bledsoe JR, Della-Torre E, Rovati L, Deshpande V. IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach. APMIS. 2018;126:459-476. [2]Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH; ACR/EULAR IgG4-RD Classification Criteria Committee. Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019;78:406-412. Disclosure of Interests: Marco Lanzillotta: None declared, Emanuel Della Torre: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Gaia Mancuso: None declared, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp &amp; Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.