Clarkson disease in critically and non-critically ill patients: insights from the Italian IRIS-CLS registry. - National Genomics Data Center (CNCB-NGDC)

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Clarkson disease in critically and non-critically ill patients: insights from the Italian IRIS-CLS registry.

Riccardo Colombo, Jonathan Montomoli, Teresa Lanzi, Antonella Tosoni, Claudia Agabiti Rosei, Giuseppe Visani, Franco Verlicchi, Chiara Cogliati, Manuela Nebuloni, Maddalena Alessandra Wu

Author Information

Riccardo Colombo: Division of Anesthesiology and Intensive Care, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy. ORCID
Jonathan Montomoli: Division of Anesthesiology and Intensive Care, Infermi Hospital, Romagna Local Health Authority, Rimini, Italy. ORCID
Teresa Lanzi: Division of Internal Medicine, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Via G.B. Grassi 74, 20157, Milan, Italy.
Antonella Tosoni: Pathology Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy.
Claudia Agabiti Rosei: UOC 2 Medicine, ASST Spedali Civili Di Brescia, Brescia, Italy. ORCID
Giuseppe Visani: Division of Hematology and Stem Cell Transplantation, AST 1, Pesaro, Italy.
Franco Verlicchi: Transfusion Medicine Faenza-Lugo, Transfusion Service Ravenna, Romagna Health Unit, Ravenna, Italy. ORCID
Chiara Cogliati: Division of Internal Medicine, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Via G.B. Grassi 74, 20157, Milan, Italy. ORCID
Manuela Nebuloni: Pathology Unit, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy. ORCID
Maddalena Alessandra Wu: Division of Internal Medicine, ASST Fatebenefratelli Sacco, Luigi Sacco Hospital, University of Milan, Via G.B. Grassi 74, 20157, Milan, Italy. maddalena.wu@unimi.it. ORCID

PMID: 40057670 DOI: 10.1007/s11739-025-03890-x

Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a poorly understood paroxysmal permeability disorder. This study aimed to characterize the clinical features and severity markers of ISCLS in critically and non-critically ill patients. We analyzed prospectively and retrospectively collected data on ISCLS cases from the Italian IRIS-CLS Registry (January 1995-December 2023). A total of 124 acute episodes were identified in 32 patients; 61 episodes in 26 patients having complete records were included in the analysis. Monoclonal gammopathy was found in 20/23 adults but was absent in all three pediatric patients, who exhibited IgA deficiency instead. At admission, patients presented with hypotension (systolic arterial pressure 87 mmHg [80-105]), tachycardia (110 bpm [96-130]), and hemoconcentration (hematocrit 57% [48-62.7]). ICU admission was required in 70.5%, and cardiac involvement occurred in 49.2% of episodes. Fluid volume infused correlated positively with rhabdomyolysis severity, and the need for renal replacement therapy was more frequent in patients receiving��3 L. No pharmacologic treatment was effective during the crises. Mortality was 9.8% per episode, and the day-1 Sequential Organ Failure Assessment score was a predictor of death (p��=��0.0181). Immunoglobulin prophylaxis reduced attack frequency from 0.67 (0.4-1.07) to 0.4 (0.1-0.52) per year (p��=��0.033). Two adults (8.7%) developed multiple myeloma during follow-up. This study provides a comprehensive overview of ISCLS in both critically and non-critically ill patients. We highlight clinical-biochemical-instrumental red-flags and emphasize the need for increased awareness and early recognition since effective treatments for acute shock remain elusive.

Capillary leakage Clarkson disease Hemoconcentration Hypovolemic shock Idiopathic systemic capillary leak syndrome Paroxysmal permeability disorders

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