Clarksons disease

Clarksons disease

• Systemic capillary leak syndrome (SCLS) is a dangerous systemic condition characterized by increased capillary permeability.
• The condition is characterized by episodes of hypotension, edema, and hypovolemia.

Synonyms

• Clarkson’s syndrome
• Capillary leak syndrome

Incidence

<1/1,000,000

How common is Clarksons disease?

• SCLS has been reported in fewer than 150 cases since it was first described in 1960.

Age of Onset

• Adulthood

What are the Symptoms of Clarksons disease?

• With a mean age of onset of 45, occurrences in children or the elderly are uncommon. The illness is typified by recurrent periods of crisis and quiescence.
• There can be a few weeks to several years between crises. They have been documented after infections, primarily in the upper respiratory tract, during the perimenstrual or postpartum phases, and, infrequently, following strenuous physical exertion.
• They can range in severity from grade 1 (hypotension responding to oral hydration) to grade 4 (fatal attacks), last days or weeks, and evolve in three stages.
• Prodromes include generalized weakness, weariness, myalgias, orthostatic hypotension, potential ENT (rhinorrhea, cough) and digestive (diarrea, stomach discomfort) signs, sporadic fever, and weight gain can all precede a crisis.
• Following is the leak phase, which is characterized by oliguria, arterial hypotension, and a fast development of facial or upper limb edema while sparing the lungs.
• Hypovolemic shock with maintained consciousness can result from hypotension.
• Polyuria and weight loss are caused by extensive edema resorption in the post-leak phase.
• Biological aspects are a typical correlation of hemoconcentration with hypoalbuminemia without albuminuria, hyperleukocytosis and a proteinemia decline in the 350-750 kDa range.
• Persistent widespread edema, mild hemoconcentration, visceral effusions, and hypotension have all been observed in chronic instances.
• In both the acute and post-leak stages, complications might arise. In the former, these can include cardiac arrhythmias, thrombosis, pancreatitis, pericarditis (see this word), seizures, cerebral edema, thickening of the myocardium, and compartment syndrome with rhabdomyolysis.
• The post-leak phase can also result in deadly pericarditis and rhabdomyolysis, but cardiovascular overload is more common.
• At this point, reports of fatal acute pulmonary edema have also been made. Acute tubular necrosis brought on by hypoperfusion and rhabdomyolysis can cause renal failure.

Very Common Symptoms

• Leukocytosis 
• Pedal edema

Common Symptoms

• Abdominal pain
• Constitutional symptom 
• Diarrhea
• Fatigue
• Hypotension
• Myalgia
• Pancreatitis
• Pulmonary edema
• Rhinorrhea
• Weight loss

Occasional Symptoms

• Abnormal renal tubule morphology
• Arrhythmia
• Cardiorespiratory arres
• Cough
• Multiple myeloma
• Myocarditis
• Oliguria
• Pericarditis
• Pleural effusion
• Renal insufficiency
• Venous thrombosis

What are the causes of this condition?

• Unknown etiological capillary hyperpermeability is the cause of Clarksons disease. Several physiopathological ideas have been explored such as an inflammation-mediated mechanism or a destruction of the capillary endothelium by the monoclonal gammopathy.

How to diagnose Clarksons disease?

• The physical and biological examination, the recurrence of crises, and the correlation between hemoconcentration and hypoalbuminemia are the main diagnostic criteria.
• The presence of paraprotein, an aberrant monoclonal immunoglobulin, is suggestive but not conclusive.

What is the differential diagnosis?

• Differential diagnosis includes sepsis, anaphylaxis, any other cause of capillary leakage and inferior vena cavainterruption.
• Chronic cases might be misdiagnosed as Gleich syndrome, venous stasis, protein-losing enteropathy and nephrotic syndrome.

How is Clarksons disease treated?

• As a result, management is symptomatic and preventive. There is no curative treatment. Administering intravenous fluids is not advised since it worsens edema, fails to raise arterial pressure, and raises the possibility of vascular overload during the post-leak phase.
• Early administration of oral electrolyte-containing fluids might lessen the severity of an attack, so patient education regarding early prodrome detection is essential.
• Intravenous immunoglobulines are a promising preventive measure; beta-adrenergic agonists (terbutaline) and PDE inhibitors (theophylline) have demonstrated positive benefits in a small number of instances but have substantial adverse effects.

What is the prognosis of Clarksons disease?

• The prognosis is still dismal because after ten years, fatality rates still exceed 30–40%, despite advancements in diagnosis and treatment that have extended patient survival.