Anne Claire Desbois1,2, Lucie Biard1,2, Damien Sène1,2, Isabelle Brocheriou1,2, Philippe Rouvier1,2, Bertrand Lioger1,2, Lucile Musset1,2, Sophie Candon1,2, Thierry Zenone1,2, Matthieu Resche-Rigon1,2, Jean-Charles Piette1,2, Neila Benameur1,2, Patrice Cacoub1,2, David Saadoun3,4. 1. From the Départements Hospitalo-Universitaires (DHU) Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Department of Pathology, Laboratory of Immunology, and Pharmacy Department; Département de Biostatistiques, Hôpital Saint-Louis; AP-HP, Groupe Hospitalier Lariboisière, Department of Internal Medicine, Paris; Hôpital Bretonneau, Centre Hospitalier de Tours, Department of Internal Medicine, Tours; Hôpital Necker, Laboratory of Immunology, Paris; Centre Hospitalier de Valence, Department of Internal Medicine, Valence, France. 2. A.C. Desbois, MD, PhD, DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology; L. Biard, MD, PhD, Département de Biostatistiques, Hôpital Saint-Louis; D. Sène, MD, PhD, AP-HP, Groupe Hospitalier Lariboisière, Department of Internal Medicine; I. Brocheriou, MD, PhD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Pathology; P. Rouvier, MD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Pathology; B. Lioger, MD, PhD, Hôpital Bretonneau, Centre Hospitalier de Tours, Department of Internal Medicine; L. Musset, MD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratory of Immunology; S. Candon, MD, PhD, Hôpital Necker, Laboratory of Immunology; T. Zenone, MD, Centre Hospitalier de Valence, Department of Internal Medicine; M. Resche-Rigon, MD, PhD, Département de Biostatistiques, Hôpital Saint-Louis; J.C. Piette, MD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology; N. Benameur, MD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Pharmacy; P. Cacoub, MD, PhD, DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology; D. Saadoun, MD, PhD, DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology. Dr. Cacoub and Dr. Saadoun are co-senior authors. 3. From the Départements Hospitalo-Universitaires (DHU) Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Department of Pathology, Laboratory of Immunology, and Pharmacy Department; Département de Biostatistiques, Hôpital Saint-Louis; AP-HP, Groupe Hospitalier Lariboisière, Department of Internal Medicine, Paris; Hôpital Bretonneau, Centre Hospitalier de Tours, Department of Internal Medicine, Tours; Hôpital Necker, Laboratory of Immunology, Paris; Centre Hospitalier de Valence, Department of Internal Medicine, Valence, France. david.saadoun@aphp.fr. 4. A.C. Desbois, MD, PhD, DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology; L. Biard, MD, PhD, Département de Biostatistiques, Hôpital Saint-Louis; D. Sène, MD, PhD, AP-HP, Groupe Hospitalier Lariboisière, Department of Internal Medicine; I. Brocheriou, MD, PhD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Pathology; P. Rouvier, MD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Pathology; B. Lioger, MD, PhD, Hôpital Bretonneau, Centre Hospitalier de Tours, Department of Internal Medicine; L. Musset, MD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Laboratory of Immunology; S. Candon, MD, PhD, Hôpital Necker, Laboratory of Immunology; T. Zenone, MD, Centre Hospitalier de Valence, Department of Internal Medicine; M. Resche-Rigon, MD, PhD, Département de Biostatistiques, Hôpital Saint-Louis; J.C. Piette, MD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology; N. Benameur, MD, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Pharmacy; P. Cacoub, MD, PhD, DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology; D. Saadoun, MD, PhD, DHU Inflammation, Immunopathologie, Biothérapie, Université Pierre et Marie Curie, and AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology. Dr. Cacoub and Dr. Saadoun are co-senior authors. david.saadoun@aphp.fr.
Abstract
OBJECTIVE: To report the incidence, predictors, and outcome of rituximab (RTX)-associated autoimmune disease flare. METHODS: We conducted a retrospective study in a tertiary referral center from 2005 to 2015. Disease flare was defined as the onset of a new organ involvement or worsening of autoimmune disease within 4 weeks following RTX. RESULTS: Among the 185 patients, we identified 7 disease flares (3.4%). All were due to type II mixed cryoglobulinemia vasculitis. Vasculitis flare occurred after a median time of 8 days (range 2-16) following RTX infusion and included acute kidney insufficiency (n = 7), purpura with cutaneous (n = 7), gastrointestinal (GI) tract involvement (n = 4), and myocarditis (n = 1). Patients with RTX-associated cryoglobulinemia vasculitis flare had these conditions more frequently: renal involvement (p = 0.0008), B cell lymphoproliferation (p = 0.015), higher level of cryoglobulin (2.1 vs 0.4 g/l, p = 0.0004), and lower level of C4 (0.02 vs 0.05, p = 0.023) compared to patients without flare after RTX (n = 43). Four patients (57%) died after a median time of 3.3 months. The 1-year survival rate was poorer in patients with vasculitis flare after RTX compared to their negative counterpart [43% (95% CI 18-100) vs 97% (95% CI 92-100), p < 0.001]. Immunofluorescence analysis of kidney biopsy in patients with worsening RTX-associated vasculitis highlighted the presence of RTX-, IgM-, and IgG1-positive staining of endomembranous deposits and thrombi within kidney lesions. CONCLUSION: RTX-associated cryoglobulinemia vasculitis flare is associated with high mortality rate. We provided evidence that kidney lesions are due to immune complex deposition and to glomerular obstruction by cryoglobulinemia and RTX.
OBJECTIVE: To report the incidence, predictors, and outcome of rituximab (RTX)-associated autoimmune disease flare. METHODS: We conducted a retrospective study in a tertiary referral center from 2005 to 2015. Disease flare was defined as the onset of a new organ involvement or worsening of autoimmune disease within 4 weeks following RTX. RESULTS: Among the 185 patients, we identified 7 disease flares (3.4%). All were due to type II mixed cryoglobulinemia vasculitis. Vasculitis flare occurred after a median time of 8 days (range 2-16) following RTX infusion and included acute kidney insufficiency (n = 7), purpura with cutaneous (n = 7), gastrointestinal (GI) tract involvement (n = 4), and myocarditis (n = 1). Patients with RTX-associated cryoglobulinemia vasculitis flare had these conditions more frequently: renal involvement (p = 0.0008), B cell lymphoproliferation (p = 0.015), higher level of cryoglobulin (2.1 vs 0.4 g/l, p = 0.0004), and lower level of C4 (0.02 vs 0.05, p = 0.023) compared to patients without flare after RTX (n = 43). Four patients (57%) died after a median time of 3.3 months. The 1-year survival rate was poorer in patients with vasculitis flare after RTX compared to their negative counterpart [43% (95% CI 18-100) vs 97% (95% CI 92-100), p < 0.001]. Immunofluorescence analysis of kidney biopsy in patients with worsening RTX-associated vasculitis highlighted the presence of RTX-, IgM-, and IgG1-positive staining of endomembranous deposits and thrombi within kidney lesions. CONCLUSION: RTX-associated cryoglobulinemia vasculitis flare is associated with high mortality rate. We provided evidence that kidney lesions are due to immune complex deposition and to glomerular obstruction by cryoglobulinemia and RTX.
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Keywords:
AUTOIMMUNITY; CRYOGLOBULINEMIA; RITUXIMAB; SIDE EFFECT; TREATMENT OUTCOME; VASCULITIS
Authors: Luca Quartuccio; Alessandra Bortoluzzi; Carlo Alberto Scirè; Antonio Marangoni; Giulia Del Frate; Elena Treppo; Laura Castelnovo; Francesco Saccardo; Roberta Zani; Marco Candela; Paolo Fraticelli; Cesare Mazzaro; Piero Renoldi; Patrizia Scaini; Davide Antonio Filippini; Marcella Visentini; Salvatore Scarpato; Dilia Giuggioli; Maria Teresa Mascia; Marco Sebastiani; Anna Linda Zignego; Gianfranco Lauletta; Massimo Fiorilli; Milvia Casato; Clodoveo Ferri; Maurizio Pietrogrande; Pietro Enrico Pioltelli; Salvatore De Vita; Giuseppe Monti; Massimo Galli Journal: Clin Rheumatol Date: 2022-09-28 Impact factor: 3.650
Authors: Janina Paula T Sy-Go; Charat Thongprayoon; Loren P Herrera Hernandez; Ziad Zoghby; Nelson Leung; Sandhya Manohar Journal: Kidney Int Rep Date: 2021-09-04