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On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.86 no.3 Rio de Janeiro May/June 2011
Systemic capillary leak syndrome*
Aline Lopes BressanI; Alexandre GrippII; Elisa Fontenelle de OliveiraIII; Roberto Souto da SilvaIV
IPostgraduate studies in Dermatology from the State University of Rio de Janeiro. Medical assistant at the Dermatology ward from the Pedro Ernesto University Hospital -Rio de Janeiro (RJ), Brazil
IIMasters in Dermatology - Assistant professor of Dermatology responsible for the Dermatology ward from the Pedro Ernesto University Hospital- Rio de Janeiro (RJ), Brazil
IIIFull member of the Brazilian Society of Dermatology (SBD) - Substitute professor of Dermatology at the Pedro Ernesto University Hospital; Dermatologist at Jesus Municipal Hospital ; Head of the Pediatric Dermatology Clinic from the Professor Azulay Dermatology Institute - Santa Casa de Misericórdia Hospital - Rio de Janeiro (RJ), Brazil
IVSpecialist in Dermatology from the Brazilian Society of Dermatology - Doctor at the general clinic of Dermatology from the Pedro Ernesto University Hospital - Rio de Janeiro (RJ), Brazil
The systemic capillary leak syndrome is rare and caused by increased capillary permeability. Several etiologies are involved. In our Department of Dermatology the main one is unstable psoriasis. Several treatments are used and many are still under study. Our objective was to present this potentially fatal medical condition that occurs in our specialty.
Keywords: Capillary permeability; Fatal outcome; Psoriasis
The systemic capillary leak syndrome is rare and it is caused by increased capillary permeability which causes accumulation of fluids and proteins into the interstitial or extravascular space with subsequent hypovolemic shock.1 It is a serious condition and can be potentially fatal if not treated at the right time and with appropriate therapy. It is most prevalent between the fourth and fifth decades of life and both sexes are affected.2 However, there are some reports in children.
Three forms of this syndrome are recognized:3
Idiopathic: attacks last for days, reccur at regular intervals and have as triggering factors menstruation, sinus and allergy to pollen.4 It is the most prevalent form.
Associated with skin diseases: erythroderma and pustular psoriais;5
Drug-induced: retinoids, granulocytes stimulating factor.3
The mechanism which leads to increase in capillary permeability is not yet established but several hypotheses have been suggested. They are:
Endothelial damage is caused by cytokines, such as interleukins 2 and 6, interferon gamma and tumor necrosis factor alpha.6
Leukotriene B4 plays a central role in capillary permeability and, in vitro, its increase was detected.6
Components of serum from patients with the syndrome cause increase of reactive oxygen species which leads to apoptosis of endothelial cells
Plasma concentration of vascular endothelial growth factor (V(EGF) is higher in patients with extensive skin disease and can act in the microvasculature to induce increased permeability. As an example, generalized pustular psoriasis is accompanied by pathological proteinuria and elevated plasma levels of VEGF, which is produced by psoriatic plaque. Increased renal vascular permeability is measured in laboratory as proteinuria.7 There are reports of systemic capillary leak syndrome after the use of acitretin and its cause seems to be increased VEGF both by psoriatic plaque as well as by stimulating the transcription of its gene by etinoic acid.
Findings are characterized by 3 phases:
Prodromal: flu-like symptoms, abdominal pain, nausea, dizziness 2 (idiopathic form).
Acute: loss of water, electrolytes and proteins for the extravascular space, with edema, compartmental syndrome, weight gain, rash, itching, sweating, renal failure and hypovolemic shock. (Figures 1 e 2).8
Late (plasma expansion): fluid returns to the intravascular space and it is responsible for causing acute pulmonary edema, respiratory distress syndrome in adults, pericardial effusion, cardiac tamponade and cardiogenic shock. Severe hypoxia associated with pulmonary congestion and normal cardiac function occurs. It is in this phase where the major complications that endanger patients'lives occur.9
Hypoalbuminaemia, neutrophilia, hemoconcentration with or without associated paraproteinemia are detected in laboratory tests.
Atkinson et al noted that up to 70% of the intravascular volume can spill during an episode.2 Therefore profound hypoalbuminaemia and hemoconcentration are present and limit the effectiveness of plasma expanders.
The systemic capillary leak syndrome has been reported as a complication of erythroderma which commonly arises from unstable psoriasis and is the main cause of leak syndrome in our service. Other causes of erythroderma are: drug eruptions and malignancies. Psoritiac erythroderma increases in 25 30% the daily loss of proteins, which may generate edema, muscular weekness and hypoalbuminaemia. There is compensatory hypermetabolism and increased basal metabolic rate. Accelerated blood flow may cause hypothermia which is intensified by heat evaporation through the dilated permeable cappilaries. This temperature change is kept due to the inability to respond with vasoconstriction and/or vasodilation. It can be fatal, especially in the elderly and in people who suffer from heart diseases.
Skin manifestations are diverse: purpuric lesions, subcutaneous infiltration, livedo, rash in sunexposed areas, erythematous papules and they occur during the attacks in the idiopathic form. 10
Cappilary leak occurs in infections (sepsis, dengue shock syndrome), hereditary angioedema caused by deficiency of C1 esterase, systemic mastocytosis, chemotherapy, malignancy and hemophagocytic syndrome and these should be discarged against new cases of shock with laboratory evidence of plasma extravasation. To characterize an idiopathic form it should also be discarded Carbon monoxide poisoning, maternal status of postpartum and pustular psoriasis.2
All cases require monitoring of serum protein and calcium and adequate hidroelectrolyte, haemodynamic and temperature balance. Premisses should have a nice and humidified temperature so as to avoid hypothermia and improve skin hydration. Appropriate nutrition and control of urea, creatinine and infections are important. Sedating antihistamines can be prescribed to relieve itching and reduce anxiety. Analysis of VEGF, still being studied, might be a useful predictor for clinical outcome and its handling.7
Different therapeutics such as immunoglobulin IV, theophylline, terbutaline, steroids (our option when the cause is unknown or when psoriasis is associated with acute respiratory distress syndrome or acute pulmonary edema), indomethacin, spironolactone, cyclosporine (our choice when the etiology is unstable psoriasis ), plasmapheresis, prostacyclin, gingko biloba and pentastarch have been tried. Other options under study are: inhibition of apoptosis by anticaspases or antioxidants and inhibitory action on the vascular factor of endothelial growth or on pathways it mediates.
1. Amoura Z, Papo T, Ninet J, Hatron PY, Guillaumie J, Piette AM, et al. Systemic capillary leak syndrome: report on 13 patients with special focus on course and treatment. Am J Med. 1997;103:514-9. [ Links ]
2. Dhir V, Arya V, Malav IC, Suryanarayanan BS, Gupta R, Dey AB. Idiopathic systemic capillary leak syndrome: case report and systematic review of cases reported in the last 16 years. The Japanese Society of Internal Medicine. 2006;899-904. [ Links ]
3. Vos EL, Vermeer MH, Pavel S. Acitretin induces capillary leak syndrome in a patient with pustular psoriasis. J Am Acad Dermatol. 2007;56:339-42. [ Links ]
4. Barnadas et al. Systemic capillary leak syndrome. J Am Acad Dermatol. 1995;32:364-366. [ Links ]
5. Gripp AC, Jaime TJ, Stolarczuk DA, Dantas MM, Miranda CVR. Síndrome de extravasamento capilar como complicação da psoríase eritrodérmica e seu difícil manejo. Pôster apresentado no 630 Congresso Brasileiro de Dermatologia - Fortaleza, Ceará. 2008. [ Links ]
6. Vigneau C, Haymann JP, Khoury N, Sraer JD, Rondeau E. An unusual evolution of the systemic capillary leak syndrome. Nephrol Dial Transplant. 2002;17:492-4. [ Links ]
7. Creamer D, Allen M, Jaggar R, Stevens R, Bicknell R, Barker J. Mediation of systemic vascular hipermeability in severe psoriasis by circulating vascular endothelial growth factor. Arch Dermatol. 2002;138: 791-6. [ Links ]
8. Bonadies N, Baud P, Peter HJ, Buergi U, Mueller BU. A case report of Clarkson's disease: If you don't Know it, you'll miss it. Eur J Intern Med. 2006;17:363-5. [ Links ]
9. Tahirkheli NK, Greipp PR. Systemic capillary leak syndrome. Long-term follow up. J Am Coll Cardiol. 1996;27: (Suppl 1):S28. [ Links ]
10. Fardet L, Kerob D, Rybojad M, Vignon-Pennamen MD, Schlemmer B, Guermazi A, et al. Idiopathic systemic capillary leak syndrome: cutaneous involvement can be misleading. Dermatology. 2004;209:291-5. [ Links ]
Mailing address: Received on 04.05.2010. * Work carried out at the Dermatology service from the Pedro Ernesto University Hospital - Rio de Janeiro (RJ), Brazil.
Aline Lopes Bressan
Rua Cachambi, 34/402
Tel: (21) 2201-3590
Approved by the Advisory Board and accepted for publication on 06.05.2010.
Conflict of interest: None
Financial funding: None
Received on 04.05.2010.
* Work carried out at the Dermatology service from the Pedro Ernesto University Hospital - Rio de Janeiro (RJ), Brazil.