Marc Pineton de Chambrun1, Marie Gousseff2, Wladimir Mauhin3, Jean-Christophe Lega4, Marc Lambert5, Sophie Rivière6, Antoine Dossier7, Marc Ruivard8, François Lhote9, Gilles Blaison10, Laurent Alric11, Christian Agard12, David Saadoun13, Julie Graveleau14, Martin Soubrier15, Marie-Josée Lucchini-Lecomte16, Christine Christides17, Annick Bosseray18, Hervé Levesque19, Jean-François Viallard20, Nathalie Tieulie21, Pierre-Yves Lovey22, Sylvie Le Moal23, Béatrice Bibes24, Giuseppe Malizia25, Pierre Abgueguen26, François Lifermann27, Jacques Ninet28, Pierre-Yves Hatron5, Zahir Amoura29. 1. Service de médecine interne 2, CHU La Pitié-Salpêtrière, APHP, Université Paris 6, France; Service de réanimation médicale, CHU La Pitié-Salpêtrière, APHP, Université Paris 6, France. 2. Service de médecine interne, CH Bretagne Atlantique, Vannes, France. 3. Service de médecine interne 2, CHU La Pitié-Salpêtrière, APHP, Université Paris 6, France. 4. Service de médecine interne et vasculaire, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, CHU, Pierre-Bénite, France and UMR 5558, Laboratoire de Biométrie et Biologie Évolutive, CNRS, Université Claude-Bernard Lyon 1, France. 5. Service de médecine interne, Hôpital Claude Huriez, CHRU Lille, France. 6. Service de médecine interne, Hôpital Saint-Eloi, CHRU Montpellier, France. 7. Service de médecine interne, CHU Bichat, Paris, APHP, France. 8. Service de médecine interne, Hôpital d'Estaing, CHU de Clermont-Ferrand, France. 9. Service de médecine interne, Hôpital Delafontaine, Saint-Denis, France. 10. Service de médecine interne et rhumatologie, Hôpital Pasteur, Colmar, France. 11. Service de médecine interne, Pôle digestif, CHU Purpan, Toulouse, France. 12. Service de médecine interne, CHU Hôtel-Dieu, Nantes, France. 13. Service de médecine interne et immunologie clinique, CHU La Pitié-Salpêtrière, APHP, Paris, France. 14. Service de médecine polyvalente, CH Saint-Nazaire, France. 15. Service de rhumatologie, Hôpital Gabriel-Montpied, CHU Clermont-Ferrand, France. 16. Service de médecine Interne, CH Notre-Dame de la Miséricorde, Ajaccio, France. 17. Service de médecine interne, CH Avignon, France. 18. Service de médecine interne, CHU Grenoble, France. 19. Normandie univ, UNIROUEN, U1096, Service de médecine interne, Rouen, France. 20. Service de médecine interne, Hôpital Haut-Lévêque, CHU Bordeaux Sud, Pessac, France. 21. Service de rhumatologie, Hôpital Pasteur 2, CHU Nice, France. 22. Service d'hématologie, Hôpital du Valais-Institut Central, Sion, Switzerland. 23. Service de médecine interne, CH de Saint-Brieuc, France. 24. Service de médecine interne, CHP Saint-Grégoire, France. 25. Divisione di Gastroenterologia, Ospedale V. Cervello, Palermo, Italy. 26. Service des maladies infectieuses et tropicales, CHU d'Angers, France. 27. Service de médecine interne, CH Dax, France. 28. Service de médecine interne, CHU Edouard Herriot, Lyon, France. 29. Service de médecine interne 2, CHU La Pitié-Salpêtrière, APHP, Université Paris 6, France. Electronic address: zahir.amoura@aphp.fr.
Abstract
BACKGROUND: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. METHODS: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. RESULTS: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. CONCLUSIONS: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.
BACKGROUND: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. METHODS: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. RESULTS: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. CONCLUSIONS: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.
Authors: Marie-Ange Bozzini; Gregorio P Milani; Mario G Bianchetti; Emilio F Fossali; Sebastiano A G Lava Journal: Eur J Pediatr Date: 2018-06-23 Impact factor: 3.183
Authors: Jae Il Shin; Keum Hwa Lee; I Re Lee; Ji Hyun Oh; Dong Wook Kim; Jae Won Shin; Tae Seong Eo; Andreas Kronbichler; Michael Eisenhut; Hans J van der Vliet Journal: J Clin Med Date: 2018-11-06 Impact factor: 4.241