Jérôme Hadjadj1, Aurélien Guffroy2, Christophe Delavaud3, Guillaume Taieb4, Isabelle Meyts5,6, Anne Fresard7, Nathalie Streichenberger8, Anne-Sophie L'Honneur9, Flore Rozenberg9, Maud D'Aveni10, Claire Aguilar11,12, Jérémie Rosain13, Capucine Picard13,14,15, Nizar Mahlaoui12,15, Marc Lecuit11, Olivier Hermine1,12,14, Olivier Lortholary11,12, Felipe Suarez16,17,18. 1. Department of Haematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, France et Université Paris Descartes, 149 rue de Sèvres, 75015, Paris, France. 2. Department of Clinical Immunology and Internal Medicine, National Reference Center for Autoimmune diseases, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 3. Department of Adult Radiology, Necker Hospital, Paris, France. 4. Department of Neurology, CHU Montpellier, Hôpital Guy de Chauliac, Montpellier, France. 5. Department of Microbiology and Immunology, Childhood Immunology, KU Leuven, Leuven, Belgium. 6. Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium. 7. Department of Infectious Diseases, CHU Saint-Etienne, Saint-Etienne, France. 8. Department of Pathology - Université Claude Bernard Lyon1 - Institut NeuroMyogène CNRS UMR 5310 - INSERM U1217, Hospices Civils de Lyon, Lyon, France. 9. Department of Virology, Université Paris Descartes et Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France. 10. Department of Hematology, University Hospital, Nancy, France. 11. Sorbonne Paris Cité, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, APHP-Hôpital Necker-Enfants Malades, IHU Imagine, Université Paris Descartes, Paris, France. 12. Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris Descartes University, Paris, France. 13. Study Center for Primary Immunodeficiencies, Necker-Enfants Malades Hospital, Assistance Publique Hôpitaux de Paris (APHP), Necker Medical School, Paris, France. 14. INSERM U1163 & CNRS ERL 8254, Institut Imagine, Sorbonne Paris Cité, Paris, France. 15. Pediatric Immuno-Haematology and Rheumatology Unit, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. 16. Department of Haematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, France et Université Paris Descartes, 149 rue de Sèvres, 75015, Paris, France. felipe.suarez@aphp.fr. 17. Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Hôpital Universitaire Necker-Enfants Malades, Paris Descartes University, Paris, France. felipe.suarez@aphp.fr. 18. INSERM U1163 & CNRS ERL 8254, Institut Imagine, Sorbonne Paris Cité, Paris, France. felipe.suarez@aphp.fr.
Abstract
PURPOSE: Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the polyomavirus JC (JCV) in immunocompromised patients. We report a series of patients with primary immune deficiencies (PIDs) who developed PML. METHODS: Retrospective observational study including PID patients with PML. Clinical, immunological, imaging features, and outcome are provided for each patient. RESULTS: Eleven unrelated patients with PIDs developed PML. PIDs were characterized by a wide range of syndromic or genetically defined defects, mostly with combined B and T cell impairment. Genetic diagnosis was made in 7 patients. Before the development of PML, 10 patients had recurrent infections, 7 had autoimmune and/or inflammatory manifestations, and 3 had a history of malignancies. Immunologic investigations showed CD4+ lymphopenia (median 265, range 50-344) in all cases. Six patients received immunosuppressive therapy in the year before PML onset, including prolonged steroid therapy in 3 cases, rituximab in 5 cases, anti-TNF-α therapy, and azathioprine in 1 case each. Despite various treatments, all but 1 patient died after a median of 8 months following PML diagnosis. CONCLUSION: PML is a rare but fatal complication of PIDs. Many cases are secondary to immunosuppressive therapy warranting careful evaluation before initiation subsequent immunosuppression during PIDs.
PURPOSE: Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the polyomavirus JC (JCV) in immunocompromised patients. We report a series of patients with primary immune deficiencies (PIDs) who developed PML. METHODS: Retrospective observational study including PID patients with PML. Clinical, immunological, imaging features, and outcome are provided for each patient. RESULTS: Eleven unrelated patients with PIDs developed PML. PIDs were characterized by a wide range of syndromic or genetically defined defects, mostly with combined B and T cell impairment. Genetic diagnosis was made in 7 patients. Before the development of PML, 10 patients had recurrent infections, 7 had autoimmune and/or inflammatory manifestations, and 3 had a history of malignancies. Immunologic investigations showed CD4+ lymphopenia (median 265, range 50-344) in all cases. Six patients received immunosuppressive therapy in the year before PML onset, including prolonged steroid therapy in 3 cases, rituximab in 5 cases, anti-TNF-α therapy, and azathioprine in 1 case each. Despite various treatments, all but 1 patient died after a median of 8 months following PML diagnosis. CONCLUSION: PML is a rare but fatal complication of PIDs. Many cases are secondary to immunosuppressive therapy warranting careful evaluation before initiation subsequent immunosuppression during PIDs.
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