Idiopathic Systemic Capillary Leak Syndrome (Clarkson's Disease): The Mayo Clinic Experience

Abstract

Objective: To determine clinical features, natural history, and outcome of a well-defined cohort of 25 consecutive patients with idiopathic systemic capillary leak syndrome (SCLS) evaluated at a tertiary care center. Results: Of the 34 patients whose records were reviewed, 25 fulfilled all diagnostic criteria for SCLS. The median age at diagnosis of SCLS was 44 years. Median follow-up of surviving patients was 4.9 years, and median time to diagnosis from symptom onset was 1.1 years (interquartile range, 0.5-4.1 years). Flulike illness or myalgia was reported by 14 patients (56%) at onset of an acute attack of SCLS, and rhabdomyolysis developed in 9 patients (36%). Patients with a greater decrease in albumin level had a higher likelihood of developing rhabdomyolysis (p=.03). Monoclonal gammopathy, predominantly of the IgG-κ type, was found in 19 patients (76%). The progression rate to multiple myeloma was 0.7% per person-year of follow-up. The overall response rate to the different therapies was 76%, and 24% of patients sustained durable (>2 years) complete remission. The estimated 5-year overall survival rate was 76% (95% confidence interval, 59%-97%).cOnclusiOn: Systemic capillary leak syndrome, a rare disease that occurs in those of middle age, is usually diagnosed after a considerable delay from onset of symptoms. The degree of albumin decrement during an attack correlates with development of rhabdomyolysis. A reduction in the frequency and/or the severity of attacks was seen in nearly three-fourths of patients who were offered empirical therapies. The rate of progression to multiple myeloma appears to be comparable to that of monoclonal gammopathy of undetermined significance. Clin proc. 2010;85(10):905-912 Mayo

Chemotherapy‐induced skin toxicity and capillary leak syndrome

“…1 The pathophysiology of CLS is related to dysfunctional capillary endothelium with extravasation of proteins and plasma into the interstitial space and subsequent anasarca and edema, hypotension, hypovolemia, and circulatory collapse. 2 Factors associated with the development of CLS include sepsis, acute renal failure, adverse drug reactions, autoimmune and hematologic diseases, and post hematopoietic stem cell transplant (HSCT), but it may also be idiopathic. [3][4][5] Oncologic medications have also been identified as provoking factors of CLS.…”

Recurrent undifferentiated shock: Idiopathic Systemic Capillary Leak Syndrome

“…There are less than 150 reported cases worldwide [1,3]. ISCLS is of unknown etiology, but thought to be the result of transient endothelial dysfunction due to endothelial contraction, apoptosis, and injury [1] contributed by vascular endothelial growth factor (VEGF), complement, leukotrienes, and cytokines [4]. As in the patient in our case report, ISCLS is often misdiagnosed as polycythemia, polycythemia vera, or sepsis.…”

“…2). Criteria to define patients with ISCLS were described by the Mayo Clinic Experience (see Table 2) [4]. ISCLS commonly presents with shock and is managed predomi- [7] Hypoalbuminaemia (mean serum albumin of 17 gm/L) [7] • Patient is at risk of ischaemic organ failure [1] Recovery Phase (1-3 days) • Extravasated fluid is recruited back into the intravascular space • Patient is at risk of pulmonary oedema [1] nantly in the critical care setting.…”

Coupled Plasma Filtration Adsorption for Treatment of Capillary Leak Syndrome Superimposed to Acute Generalized Exanthematous Pustolosis: A Case Report

“…This condition may end in noncardiogenic pulmonary edema, compartment syndrome of the extremities with rhabdomyolysis, and the need for fasciotomy. Moreover, hypovolemic shock may lead to AKI and multiorgan dysfunction [18,19]. CLS is a diagnosis of exclusion, and main differential diagnosis has to be made with sepsis and cardiogenic shock.…”

“…Moreover, in CPFA circuit, plasma passes through the resin cartridge at a low flow rate ensuring the removal of cytokines that are not efficiently eliminated when blood passes through a hemofilter at higher flow rates [1]. A single case report has described the use of plasmapheresis in Systemyc CLS suggesting efficacy of cytokines removal in this condition [19]. We do not currently know which of the many cytokines removed was specifically responsible for the severe condition of our patient nor we know what cytokines were mostly removed by CPFA.…”