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

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.