Idiopathic systemic capillary leak syndrome (ISCLS) presents with recurrent potentially life-threatening episodes of hypovolemic shock associated with severe hemoconcentration and hypoproteinemia. Timely recognition is of paramount importance because ISCLS, despite resembling other kinds of hypovolemic shock, requires a peculiar approach, to prevent life-threatening iatrogenic damage. Due to the rarity of this condition with only scattered cases described worldwide, evidence-based recommendations are still lacking. Here, we summarize our 40 years’ experience in treating shock in ISCLS patients to derive a therapeutic algorithm. Records from 12 ISCLS patients (mean follow-up is 6 years, with a mean age at symptoms’ onset of 51.5 years) were informative for treatment modalities and outcome of 66 episodes of shock. Episodes are divided in three phases and treatment recommendations are the following: prodromal symptoms-signs (growing malaise, oligo-anuria, orthostatic dizziness) last 6–12 h and patients should maintain rigorous bed rest. The acute shock phase lasts 24–36 h. Patients should be admitted to ICU, placed on restrictive infusion of fluids favoring cautious boluses of high-molecular-weight plasma expanders when SAP < 70 mmHg; monitored for cerebral/cardiac perfusion, myocardial edema and signs of compartment syndrome. The post-acute (recovery) phase may last from 48 h to 1 week. Monitor for cardiac overload to prevent cardiac failure; in case of persistent renal failure, hemodialysis may be necessary; consider albumin infusion. Complications listed by frequency in our patients were acute renal failure, compartment syndrome and neuropathy, rhabdomyolysis, myocardial edema, pericardial–pleural–abdominal effusion, cerebral involvement, acute pulmonary edema and deep vein thrombosis.
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Clarkson B, Thompson D, Horwith M, Luckey EH (1960) Cyclical edema and shock due to increased capillary permeability. Am J Med 29:193–216
Druey KM, Parikh SM (2017) Idiopathic systemic capillary leak syndrome (Clarkson disease). J Allergy Clin Immunol 140:663–670
Atkinson JP, Waldmann TA, Stein SF, Gelfand JA, Macdonald WJ, Heck LW, Cohen EL, Kaplan AP, Frank MM (1977) Systemic capillary leak syndrome and monoclonal IgG gammopathy; studies in a sixth patient and a review of the literature. Medicine (Baltimore) 56:225–239
Eo TS, Chun KJ, Hong SJ, Kim JY, Lee IR, Lee KH, Eisenhut M, Kronbichler A, Shin JI (2018) Clinical presentation, management, and prognostic factors of idiopathic systemic capillary leak syndrome: a systematic review. J Allergy Clin Immunol Pract 6:609–618
Xie Z, Ghosh CC, Patel R, Iwaki S, Gaskins D, Nelson C, Jones N, Greipp PR, Parikh SM, Druey KM (2012) Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome). Blood 119:4321–4332
Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60
Gousseff M, Arnaud L, Lambert M, Hot A, Hamidou M, Duhaut P, Papo T, Soubrier M, Ruivard M, Malizia G, Tieulie N, Riviere S, Ninet J, Hatron PY, Amoura Z, Capillary Leak Syndrome R (2011) The systemic capillary leak syndrome: a case series of 28 patients from a European registry. Ann Intern Med 154:464–471
Druey KM, Greipp PR (2010) Narrative review: the systemic capillary leak syndrome. Ann Intern Med 153:90–98
Kapoor P, Greipp PT, Schaefer EW, Mandrekar SJ, Kamal AH, Gonzalez-Paz NC, Kumar S, Greipp PR (2010) Idiopathic systemic capillary leak syndrome (Clarkson's disease): the Mayo clinic experience. Mayo Clin Proc 85:905–912
Marasini B, Bergamaschini L, Boccassini G, Agostini A (1979) Systemic capillary leak syndrome. Evaluation of single protein fractions in serum and in interstitial fluid. Bibl Anat 18:41–43
Zancanaro A, Serafini F, Fantin G, Murer B, Cicardi M, Bonanni L, Dalla Vestra M, Scanferlato M, Mazzanti G, Presotto F (2015) Clinical and pathological findings of a fatal systemic capillary leak syndrome (Clarkson disease): a case report. Medicine (Baltimore) 94:e591
Pineton de Chambrun M, Luyt CE, Beloncle F, Gousseff M, Mauhin W, Argaud L, Ledochowski S, Moreau AS, Sonneville R, Verdiere B, Merceron S, Zappella N, Landais M, Contou D, Demoule A, Paulus S, Souweine B, Lecomte B, Vieillard-Baron A, Terzi N, Azoulay E, Friolet R, Puidupin M, Devaquet J, Mazou JM, Fedun Y, Mira JP, Raphalen JH, Combes A, Amoura Z, EureClark Study Group (2017) The clinical picture of severe systemic capillary-leak syndrome episodes requiring ICU admission. Crit Care Med 45:1216–1223
Sanghavi R, Aneman A, Parr M, Dunlop L, Champion D (2006) Systemic capillary leak syndrome associated with compartment syndrome and rhabdomyolysis. Anaesth Intensive Care 34:388–391
Ertel A, Pratt D, Kellman P, Leung S, Bandettini P, Long LM, Young M, Nelson C, Arai AE, Druey KM (2015) Increased myocardial extracellular volume in active idiopathic systemic capillary leak syndrome. J Cardiovasc Magn Reson 17:76
Pineton de Chambrun M, Mathian A, Luyt CE, Combes A, Amoura Z, EureClark Study Group (2018) Myocardial dysfunction is frequent in systemic capillary-leak syndrome (Clarkson disease) severe episodes. J Allergy Clin Immunol 141:1539–1540
Wu MA, Zanichelli A, Mansi M, Cicardi M (2016) Current treatment options for hereditary angioedema due to C1 inhibitor deficiency. Expert Opin Pharmacother 17:27–40
Zipponi M, Eugster R, Birrenbach T (2011) High-dose intravenous immunoglobulins: a promising therapeutic approach for idiopathic systemic capillary leak syndrome. BMJ Case Rep. https://doi.org/10.1136/bcr.12.2010.3599
Xie Z, Chan EC, Long LM, Nelson C, Druey KM (2015) High-dose intravenous immunoglobulin therapy for systemic capillary leak syndrome (Clarkson disease). Am J Med 128:91–95
Teutonico A, Chimienti D, Antonelli M, Bruno A, Libutti P, Lisi P, Basile C (2012) The systemic capillary leak syndrome: a scarcely known nephrological entity. J Nephrol 25:262–265
Vigneau C, Haymann JP, Khoury N, Sraer JD, Rondeau E (2002) An unusual evolution of the systemic capillary leak syndrome. Nephrol Dial Transplant 17:492–494
We thank Dr. Andrea Zanichelli and Dr. Antonio Castelli, whose support was precious to deal with challenging clinical pictures. We express our gratitude to Dr. Chiara Suffritti for assistance with analyses of blood samples and to Dr. Guido Di Stefano for his helpful contribution for data collection. We wish to acknowledge the help received from Dr. Andrea Zancanaro, who provided data about a patient followed in his Center.
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Wu, M.A., Colombo, R., Podda, G.M. et al. Handling shock in idiopathic systemic capillary leak syndrome (Clarkson’s disease): less is more. Intern Emerg Med 14, 723–730 (2019). https://doi.org/10.1007/s11739-019-02113-4
- Idiopathic systemic capillary leak syndrome
- Clarkson’s disease