Nihal Martis1, Matthieu Jamme2, Corinne Bagnis-Isnard3, Claire Pouteil-Noble4, Claire Presne5, Cécile Vigneau6, Steven Grangé7, Stéphane Burtey8, Jean-Philippe Coindre9, Alain Wynckel10, Mohamed A Hamidou11, Tarik Kanouni12, Elie Azoulay13, Miguel Hié14, Dominique Chauveau15, Agnès Veyradier16, Eric Rondeau17, Paul Coppo18. 1. Internal Medicine Department, University Hospital of Nice; Côte d'Azur University, Nice, France; French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France. Electronic address: martis.n@chu-nice.fr. 2. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology Department, C.H. Intercommunal Poissy/Saint-Germain-en-Laye, Poissy, France. 3. Nephrology Department, Pitié-Salpêtrière Hospital, Paris, France. 4. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology Department, Édouard Herriot Hospital, Lyon, France. 5. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology Department, Hôpital Sud, Amiens, France. 6. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; University of Rennes, University Hospital of Rennes - Inserm, EHESP, Institut de recherche en santé, Environnement et Travail - UMR_S 1085, F-35000 Rennes, France. 7. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Intensive Care Unit, C.H.U Rouen, Rouen, France. 8. Nephrology Department, C.H.U. de la Conception, Marseille, France. 9. Nephrology Department, Le Mans Hospital, Le Mans, France. 10. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology Department, Hôpital Maison Blanche, Reims Cedex, France. 11. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Internal Medicine Department, Hôtel Dieu Hospital, Nantes, France. 12. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Therapeutic Apheresis Department, C.H.U de Montpellier, Montpellier, France. 13. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Medical Intensive Care Unit, Saint-Louis Hospital, Paris, France. 14. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Internal Medicine Department, Pitié-Salpêtrière Hospital, Paris, France. 15. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology and Kidney transplant Unit, Rangueil Hospital, Toulouse, France. 16. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Haemostasis Department, Lariboisière Hospital, Paris, France. 17. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Nephrology and Kidney transplant Unit, Tenon Hospital, Paris, France. 18. French Reference Centre for Thrombotic Microangiopathies, Saint-Antoine Hospital, Paris, France; Haematology Department, Saint-Antoine Hospital, Paris, France; Sorbonne University, Paris, France. Electronic address: paul.coppo@aphp.fr.
Abstract
CONTEXT: The management of systemic auto-immune diseases (SAID) -associated thrombotic microangiopathies (TMA) [SAID-TMA] remains debated. OBJECTIVES: To provide a demographic, clinical and therapeutic picture of SAID-TMA. METHODS: A cross-sectional analysis was conducted on adult patients presenting with SAID and TMA from the French National TMA Registry over a 20-year period. Clinical features were extracted and compared to those from a historical cohort of atypical haemolytic and uremic syndrome (aHUS) patients. RESULTS: Forty-one patients with SAID-TMA were compared to 78 patients with aHUS from a historical cohort. Connective tissue diseases (CTD) were systemic lupus erythematosus (n=18), primary Sjögren's syndrome (n=7), systemic sclerosis (n=11), mixed CTD (n=2) and 2 cases of vasculitides, including 7 overlapping forms and 8 cases of primary antiphospholipid syndromes (APLS). Patients with SAID-TMA generally had pre-existing chronic kidney failure (OR= 3.17, 95%CI: 1.204 to 7.923; p= 0.016) compared to aHUS patients, though creatinine levels were significantly lower (216 [IQR, 108-334] µmol/L vs. 368 [IQR, 170-722] µmol/L; p= 0.002). Patients were less likely to recover if renal replacement therapy was needed at onset (OR= 0.07; 0.02 to 0.34; p <0.0005). Two patients died. Thirty patients responded to immunosuppressive treatment and complete remission was achieved in 25 cases. By contrast, therapeutic plasma exchange (TPE) did not have an early effect on TMA features at Day-7 nor Day-15 (p >0.05). CONCLUSION: The management of SAID-TMA implies an early initiation of immunosuppressive drugs for flares of the associated SAID, whereas TPE seem ineffective. KEY MESSAGES.
CONTEXT: The management of systemic auto-immune diseases (SAID) -associated thrombotic microangiopathies (TMA) [SAID-TMA] remains debated. OBJECTIVES: To provide a demographic, clinical and therapeutic picture of SAID-TMA. METHODS: A cross-sectional analysis was conducted on adult patients presenting with SAID and TMA from the French National TMA Registry over a 20-year period. Clinical features were extracted and compared to those from a historical cohort of atypical haemolytic and uremic syndrome (aHUS) patients. RESULTS: Forty-one patients with SAID-TMA were compared to 78 patients with aHUS from a historical cohort. Connective tissue diseases (CTD) were systemic lupus erythematosus (n=18), primary Sjögren's syndrome (n=7), systemic sclerosis (n=11), mixed CTD (n=2) and 2 cases of vasculitides, including 7 overlapping forms and 8 cases of primary antiphospholipid syndromes (APLS). Patients with SAID-TMA generally had pre-existing chronic kidney failure (OR= 3.17, 95%CI: 1.204 to 7.923; p= 0.016) compared to aHUS patients, though creatinine levels were significantly lower (216 [IQR, 108-334] µmol/L vs. 368 [IQR, 170-722] µmol/L; p= 0.002). Patients were less likely to recover if renal replacement therapy was needed at onset (OR= 0.07; 0.02 to 0.34; p <0.0005). Two patients died. Thirty patients responded to immunosuppressive treatment and complete remission was achieved in 25 cases. By contrast, therapeutic plasma exchange (TPE) did not have an early effect on TMA features at Day-7 nor Day-15 (p >0.05). CONCLUSION: The management of SAID-TMA implies an early initiation of immunosuppressive drugs for flares of the associated SAID, whereas TPE seem ineffective. KEY MESSAGES.