Capillary leak syndrome

Usually adult age, average 45 years, rarely childhood, prevalence < 1: 1 000 000, fewer than 150 cases have been described since first described. Some cases have been described after vaccination against Covid 19. The European Medicines Agency (EMA) is currently (April 2021) investigating possible links between vaccination and the occurrence of Clarkson's syndrome.

Caused by generalized capillary hyperpermeability.

Pathogenetic association with a monoclonal gammopathy (see Monoclonal Gammopathies of Cutaneous Significance below) is discussed by some authors (Atkinson JP et al 1977).

In case reports, drugs have occasionally been described as the triggering agent (e.g., acitretin, interleukins, imiquimod).

Similarly, cases have been reported following upper respiratory tract infections.

Episodic course over several days: Between days 1-4 abdominal discomfort, nausea, generalized edema, hypotension, cardiopulmonary dysregulation, acute renal failure (partly due to hypovolemia). Thereafter, counter-regulation of extravasation and appearance of pulmonary edema.The clinical picture may be recurrent, the crises last days to weeks. From severity 1 with hypotension to the fatal severity 4.prodrome are weakness, fatigue, myalgias, hypotension, possibly diarrhea, abdominal pain, also rhinitis and cough, and possibly fever. Due to the drop in blood pressure, hypovolemic shock may occur.

sepsis, anaphylaxis, venous stasis, enteropathy with protein loss and nephrotic syndrome

The disease can lead to potentially life-threatening hypotension and multiple organ failure.

Compartment syndrome with rhabdomyolysis, cardiac arrhythmias, thrombosis, pancreatitis, pericarditis, seizures, cerebral edema, myocardial thickening, pericarditis, pulmonary edema, possibly acute and lethal.

Due to hypoperfusion, renal failure with acute tubular necrosis may occur.

A similar, sporadic clinical picture is described as episodic angioedema with eosinophilia.

Prognosis is serious: after 10 years 30-40% mortality.

1. Amoura Z et al (1997) Systemic capillary leak syndrome: report on 13 patients with special focus on course and treatment. Am J Med 103: 514-519
2. Atkinson JP et al (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
3. Duron L et al (2014) Idiopathic and secondary capillary leak syndromes: A systematic review of the literature. Rev Med Intern doi: 10.1016/j
4. Vos LE et al (2007) Acitretin induces capillary leak syndrome in a patient with pustular psoriasis. J Am Acad Dermatol 56: 339-342.
5. Xie Z et al (2014) Inflammatory markers of the systemic capillary leak syndrome (Clarkson disease). J Clin Cell Immunol PubMed PMID: 25405070
6. Zancanaro A et al (2015) Clinical and pathological findings of a fatal systemic capillary leak syndrome (clarkson disease): a case report. Medicine (Baltimore) 94:e591