Systemic capillary leak syndrome

Version: 3.0
Published: 20 October 2018
Condition for which Ig use is in exceptional circumstances only

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Specific Conditions
  • Systemic capillary leak syndrome
Indication for Ig Use
  • Prevention of recurrent life-threatening episodes of hypotensive shock with hypoalbuminaemia in diagnosed Systemic capillary leak syndrome (SCLS)
Level of Evidence Insufficient data (Category 4a)
Description and Diagnostic Criteria Systemic capillary leak syndrome (SCLS) is an extremely rare condition that is characterised by recurrent life-threatening attacks of reversible capillary hyperpermeability accompanied by haemoconcentration and hypoalbuminaemia.
Justification for Evidence Category Based on clearly documented studies, intravenous immunoglobulin (IVIg) prophylaxis was associated with an 89 percent decrease in the number of systemic capillary leak syndrome (SCLS) flares (252 pre-treatment to 29 post-treatment) in 27 patients for periods of up to 13 years (median duration of follow up 32 months). 15 out of 27 patients receiving IVIg experienced no SCLS episodes for periods of up to 12 years, and 24 out of 27 subjects had at least a 50 percent reduction in the number of flares.
 
The optimal dose, schedule, and duration of IVIg therapy remain to be determined. While most patients (78 percent) received 2 g/kg/month, three patients have remained episode-free for greater than two years on 1 to 1.25 g/kg/month. Only a small number were controlled with 0.4 g/kg/month.
Diagnosis Requirements

A diagnosis must be made by an Immunologist, General Medicine Physician, Intensivist or an Emergency Medicine Physician.
Qualifying Criteria for Ig Therapy
  • Recurrent episodes of unexplained hypotension and oedema requiring hospital admission
  • AND
  • Haemoconcentration, shock and hypoproteinemia as a result of the loss of plasma into the extravascular space
  • AND
  • Other causes of shock, haemoconcentration and hypoproteinemia have been excluded
Review by a General Physician or Immunologist is required within six months to assess the evidence of clinical benefit, and annually thereafter.
Review Criteria for Assessing the Effectiveness of Ig Use
Review by a General Physician or Immunologist is required within six months to assess the evidence of clinical benefit, and annually thereafter.

Clinical effectiveness of Ig therapy may be assessed by:
 

On review of the initial authorisation period

  • Reduction in SCLS-related symptoms including oedema and hypotension post Ig treatment compared to the qualifying assessment
  • AND
  • A reduction in the number of episodes requiring hospital admission compared to pre-treatment

On review of a continuing authorisation period

  • Further improvement in or stabilisation of the number of episodes requiring hospital admission compared to the previous review period
  • AND
  • A trial of Ig weaning towards cessation of Ig therapy is planned for patients who are clinically stable to identify those in remission or a reason provided as to why a trial is not planned
Dose
  • Induction Dose (IVIg) - 1 - 2g/kg in single or divided doses.
  • Maintenance Dose (IVIg) - 0.4 - 2g/kg monthly.
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Refer to the current product information sheet for further information on dose, administration and contraindications.
 Dose Calculator
Bibliography
Abgueguen, P, Chennebault, JM & Pichard, E, 2010, ‘Immunoglobulins for the treatment of systemic capillary leak syndrome’, American Journal of Medicine, vol. 123, no. 6, pp. e3–4. https://www.ncbi.nlm.nih.gov/pubmed/20569743

Druey, KM & Greipp, PR 2010, ‘Narrative review: the systemic capillary leak syndrome’, Annals of Internal Medicine, vol. 153, no.2, pp. 90–8. https://www.ncbi.nlm.nih.gov/pubmed/20643990

Gousseff, M, Arnaud, L, Lambert, M, et al 2011, ‘The systemic capillary leak syndrome: a case series of 28 patients from a European registry’, Annals of Internal Medicine, vol. 154, no. 7, pp. 464–71. https://www.ncbi.nlm.nih.gov/pubmed/21464348

Govig, BA & Javaheri, S 2010, ‘The systemic capillary leak syndrome (letter)’, Annals of Internal Medicine, vol. 153, no.11, pp. 764. https://www.ncbi.nlm.nih.gov/pubmed/21135305

Lambert, M, Launay, D, Hachulla, E, et al 2008, ‘High-dose intravenous immunoglobulins dramatically reverse systemic capillary leak syndrome’, Critical Care Medicine, vol. 36, no.7, pp. 2184–7. https://www.ncbi.nlm.nih.gov/pubmed/18552679

Marra, AM, Gigante, A & Rosato, E 2014, ‘Intravenous immunoglobulin in systemic capillary leak syndrome: a case report and review of the literature’, Expert Review of Clinical Immunology, vol. 10, no. 3, pp. 349-52. https://www.ncbi.nlm.nih.gov/pubmed/24490827

Ontario Regional Blood Coordinating Network, 2016, ‘Ontario Intravenous Immune Globulin (IVIG) Utilization Management Guidelines, Version 3.0; [Online]. Available from: http://transfusionontario.org/en/.
 
UK Department of Health, 2011, ‘Clinical Guidelines for Immunoglobulin Use: Second Edition Update’, Available from:  
https://www.gov.uk/government/publications/clinical-guidelines-for-immunoglobulin-use-second-edition-update

Xie, Z, Chan, EC, Long, LM, et al 2015, ‘High dose intravenous immunoglobulin therapy of the Systemic Capillary Leak Syndrome (Clarkson disease)’, American Journal of Medicine, vol. 128, no. 1, pp. 91–95. https://www.ncbi.nlm.nih.gov/pubmed/25193271

Zipponi, M, Eugster, R & Birrenbach, T 2011, ‘High-dose intravenous immunoglobulins: A promising therapeutic approach for idiopathic systemic capillary leak syndrome’, BMJ Case Reports, doi: 10.1136/bcr.12.2010.3599.. https://www.ncbi.nlm.nih.gov/pubmed/22696704