Immune Thrombocytopenic Purpura and Subsequent Development of Systemic Lupus Erythematosus

Background Immune Thrombocytopenic Purpura (ITP) is an immune-mediated disorder, characterized by isolated thrombocytopenia (<100,000/mm 3 ). It is part of Systemic Lupus Erythematosus (SLE) classification criteria, and may be one of the first manifestations of the disease, often occurring years before its diagnosis. Objectives To assess the incidence of SLE in a cohort of patients with ITP, and to identify predictors for its development. Methods Retrospective cohort study. We included patients with ITP treated in a University Hospital between 2000 and 2018, with at least one year of follow-up. Patients with SLE or other secondary causes of ITP were excluded. Demographic, clinical, laboratory and treatment data were recorded. Patients meeting SLE classification criteria (ACR 1997/ SLICC 2012) during the follow-up were identified, and incidence density of SLE was calculated. Patients with ITP were grouped according to the development or non-development of SLE, and comparisons were made. Univariate analysis was performed to identify factors associated with the future development of SLE. Results 186 patients were included, 64.5% women, with a median age of 27.2 years (IQR 6.3-63.9). After a follow-up of 1801.4 person/years (py), 10 patients (5.4%) developed SLE, with a median time of 22.9 months (IQR 9.8-60.9) between ITP diagnosis and development of SLE. The incidence density of SLE was 5.6/1000 py (95% CI 2.9-9.9/1000 py). Patients who developed SLE had significantly higher proportion of chronic ITP (80% vs 40.3%; p 0.01), lower proportion of complete response (10% vs 54.6%; p 0.006), and more relapses (60% vs 30.6%; p 0.05). The median duration of ITP in SLE patients was significantly longer (67.5 vs 4 months, p<0.001). The presence of ANA (p<0.001), nuclear homogeneous pattern (p<0.001), ANA titres >1/640 (p 0.02), hypocomplementemia (p<0.001), LAC (p<0.001), hypergammaglobulinemia (p<0.001), leukopenia (p 0.006) and hemolytic anemia (p 0.005) were significantly associated with the future development of SLE. Conclusion In this cohort of ITP patients, the more refractory course of ITP, as well as the presence of high titre - nuclear homogeneous ANA, hypocomplementemia, LAC, hypergammaglobulinemia and other cytopenias were associated with the subsequent development of SLE. Table 1. Baseline characteristics at ITP diagnosis and comparison between groups. ITP developing SLE (n= 10) ITP non-developing SLE (n= 176) p Age, years, median (IQR) 19.0 (12.4-31.6) 28.3 (5.8-64.5) 0.36 Female gender, n, (%, 95% CI) 9 (90.0, 50.1-98.8) 111 (63.1, 55.6-69.9) 0.08 Follow-up time, years, median (IQR) 6.9 (4.9-10.1) 10.2 (4.6-14.8) 0.49 Rheumatologist evaluation at ITP diagnosis, n (%, 95% CI) 8 (80.0, 43.6-95.4) 23 (13.1, 8.8-18.9) <0.001 ANA positivity, n (%, 95% CI) 10 (100) 35 (30.7, 22.8-39.9) <0.001 Hypocomplementemia, n (%, 95% CI) 6 (60.0, 27.9-85.3) 7 (10.1, 4.8-20.1) <0.001 Lupus anticoagulant, n (%, 95% CI) 4 (40.0, 14.7-71.9) 6 (6.1, 2.7-13.1) <0.001 Polyclonal hypergammaglobulinemia, n (%, 95% CI) 5 (55.6, 23.4-83.6) 14 (11.6, 6.9-18.7) <0.001 Splenomegaly, n (%, 95% CI) 3 (33.3, 10.2-68.8) 17 (12.8, 8.0-19-7) 0.09 Megakaryocytic hyperplasia in bone marrow, n (%, 95% CI) 4 (80.0, 24.9-97.9) 47 (64.4, 52.5-74.7) 0.48 Hemolytic anemia, n (%, 95% CI) 1 (10.0, 1.2-49.9) 1 (0.6, 0.1-3.9) 0.005 Leukopenia, n (%, 95% CI) 3 (30.0, 9.3-64.3) 11 (6.3, 3.5-10.9) 0.006 Rituximab therapy, n (%, 95% CI) 5 (50.0, 21.2-78.8) 40 (22.7, 17.1-29.6) 0.05 Hydroxychloroquine therapy, n (%, 95% CI) 7 (70.0, 35.7-90.7) 4 (2.3, 0.8-5.9) <0.001 Splenectomy, n (%, 95% CI) 2 (20.0, 4.6-56.4) 15 (8.5, 5.2-13.7) 0.22 Duration of ITP treatment, months, median (IQR) 67.5 (40-113) 4 (1-14.5) <0.001 Newly diagnosed ITP (<3 months), n (%, 95% CI) 1 (10.0, 1.2-49.9) 82 (46.6, 39.3-54.1) 0.02 Persistent ITP (3-12 months), n (%, 95% CI) 1 (10.0, 1.2-49.9) 23 (13.1, 8.8-18.9) 0.78 Chronic ITP (>12 months), n (%, 95% CI) 8 (80.0, 43.6-95.4) 71 (40.3, 33.3-47.8) 0.01 Figure 1. ANA characteristics at ITP diagnosis. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Gelsomina Alle: None declared, Marina Scolnik Speakers bureau: GSK, Janssen, Pfizer, Roche, Lilly, Grant/research support from: Janssen, GSK, Valeria Scaglioni: None declared, JOHN FREDY JARAMILLO GALLEGO: None declared, Mayra Alejandra Tobar Jaramillo: None declared, Rodolfo Nicolas Alvarado: None declared, Enrique Soriano Speakers bureau: Amgen, Abbvie, BMS, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, UCB, Consultant of: Abbvie, Janssen, Pfizer, Amgen, Sandoz, Novartis, Grant/research support from: Novartis, Pfizer, Amgen, Elea, Javier Rosa Speakers bureau: Eli Lilly, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Amgen, Novartis, Pfizer.