Capillary leak syndrome

Classification according to ICD-10
R60.1	Generalized edema
R57.1	Hypovolemic shock
ICD-10 online (WHO version 2019)

The capillary leak , even Clarkson syndrome called, is a very rare, serious disease with a generalized edema . It is caused by an increased permeability of the capillaries , which results in a leakage of plasma and plasma proteins into the interstitium .

In the Anglo-American literature, the capillary leak syndrome is referred to as capillary leak syndrome (CLS) or systemic capillary leak syndrome (SCLS).

pathology

The capillary leak syndrome is caused by intervals of severe hypovolemic shock (volume deficiency shock ) with generalized edema, combined with arterial hypotension with blood thickening ( hemoconcentration ) - caused by the loss of plasma water - and hypoalbuminemia (reduced concentration of the plasma protein albumin , here caused by the excess of blood the interstitium) without albuminuria . The cause of these symptoms is a greatly increased permeability of the capillary walls of the blood vessels, which leads to a massive escape of plasma into the interstitium. The extravasation - that is the fluid flowing into the tissue - contains macromolecules up to a molar mass of 200 kDa , sometimes up to 900 kDa.

Each disease interval consists of two phases:

The so-called initial phase is characterized by abdominal pain , nausea , generalized edema and arterial hypotension (low arterial blood pressure). These symptoms last for about one to four days and can lead to cardiovascular collapse. Acute renal insufficiency (acute kidney failure) or tubular damage can result from hypovolemia ( insufficient blood volume) and rhabdomyolysis (dissolution of the striated muscle fibers ).

In the second phase, the extravasated fluid begins to migrate. The extreme amount of intravascular fluid leads to polyuria (greatly increased urine output) and can lead to pulmonary edema (water lung ).

Pathogenesis

The pathomechanism that leads to capillary leak syndrome is still largely unclear. Certain cytokines such as interleukin-2 (see also: Vascular Leak Syndrome ), leukotrienes or apoptosis (programmed cell death) of endothelial cells are discussed for the increased permeability of the capillaries . In 2010 a patient with a clear familial predisposition was reported for the first time, so that there may also be genetic causes for the disease.

Monoclonal gammopathy , mostly of the IgG subtype , is present in around 82 percent of patients . Some doctors are of the opinion that monoclonal gammopathy is pathogenic even if there is no sign of amyloidosis , i.e. an accumulation of abnormally changed proteins in the interstitium.

Incidence

Capillary leak syndrome is a very rare disease. Only 57 cases were described worldwide up to 2002. The age of the sick was between 9 and 67 years, the mean value was 46 years. Men were affected just as often as women. So far (as of 2010) four cases in children have been described.

therapy

Due to the very small number of clinically known cases, there is no standard therapy for the treatment of capillary leak syndrome. Terbutaline and theophylline were sometimes used successfully as prophylactic treatment methods. The more chronic form of capillary leak syndrome is obviously well treatable with glucocorticoids such as prednisone , diuretics such as furosemide , and with theophylline.

Any monoclonal gammopathy that may be present is usually closely monitored as it can develop into multiple myeloma .

forecast

The five-year survival rate is around 25%.

Initial description

The capillary leak syndrome was first described in 1960 by the American B. Clarkson. It is therefore also known as Clarkson's syndrome .

Individual evidence

↑ M. Müller and A. Schmidt: 52-year-old patient with recurrent shock of unknown origin, haemoconcentration and hypoalbuminemia. In: Der Internist 45, 2004, pp. 587-591. doi : 10.1007 / s00108-004-1162-2
↑ ^a ^b ^c ^d ^e ^f ^g capillary leak syndrome. In: Orphanet (Rare Disease Database).
↑ S. Kawabe et al: Systemic capillary leak syndrome. In: Intern Med 41, 2002, pp. 211-215. doi : 10.2169 / internalmedicine.41.211 . PMID 11929183 . (Review)
↑ J. Hollenberg, J. Frykman, LG Lundberg, S. Forsberg: A case report of systemic capillary leak syndrome (Clarkson's disease). In: Acta Anaesthesiol Scand 54, 2010, pp. 649-652 PMID 20148770 .
↑ ^a ^b N. K. Tahirkheli and PR Greipp: Treatment of the systemic capillary leak syndrome with terbutaline and theophylline, a case series. In: Ann Intern Med 130, 1999, pp. 905-909. PMID 10375339
↑ L. Airaghi et al.: Chronic systemic capillary leak syndrome. Report of a case and review of the literature. In: J Intern Med 247, 2000, pp. 731-735. doi : 10.2169 / internalmedicine.46.6129 PMID 10886496 (Review)
↑ K. Keller et al .: Chronic systemic capillary leak syndrome: a case responding to prednisolone treatment. In: Scand J Rheumatol 38, 2009, pp. 400-401. PMID 19863213
↑ Z. Amoura et al.: Systemic capillary leak syndrome: report on 13 patients with special focus on course and treatment. In: Am J Med 103, 1997, pp. 514-519. PMID 9428835
↑ C. Vigneau et al: An unusual evolution of the systemic capillary leak syndrome. In: Nephrol Dial Transplant 17, 2002, pp. 492-494. PMID 11865098
↑ B. Clarkson et al: Cyclical edema and shock due to increased capillary permeability. In: Am J Med 29, 1960, pp. 193-216. PMID 13693909