The natural history of SCLS episodes indicates they resolve spontaneously within 2-to-4 days, and that they consist of two distinct phases: The<unk> <unk>  phase The initial stage is the<unk> <unk>  phase, lasting from 1 to 3 days, during which up to 70% of total plasma volume may invade cavities especially in the extremities. The most common clinical features are flu-like symptoms such as fatigue; runny nose; lightheadedness up to and including syncope (fainting); limb, abdominal or generalized pain; facial or other edema; dyspnea; and hypotension that results in circulatory shock and potentially in cardiopulmonary collapse and other organ distress or damage. Acute kidney injury or failure is a common risk due to acute tubular necrosis consequent to hypovolemia and rhabdomyolysis. The loss of fluid out of the<unk> es has similar effects on the circulation as dehydration, slowing both the flow of oxygen delivered to tissues and organs as well as the output of urine. Urgent medical attention in this phase consists of fluid resuscitation efforts, mainly the intravenous administration of saline solution plus hetastarch or albumin and colloids (to increase the remaining blood flow to vital organs like the kidneys), as well as glucocorticoids (steroids like methylprednisolone, to reduce or stop the<unk> <unk> . However effective on blood pressure, the impact of fluid therapy is always transient and leads to increased extravascular fluid accumulation, engendering multiple complications especially compartment<unk>  and thus limb-destructive rhabdomyolysis. Consequently, patients experiencing episodes of SCLS should be closely monitored in a hospital intensive-care setting, including for orthopedic complications requiring surgical decompression, and their fluid therapy should be minimized as much as possible. The recruitment phase The second stage features the reabsorption of the initially extravasated fluid and albumin from the tissues, and it usually lasts 1 to 2 days. Intravascular fluid overload leads to polyuria and can cause flash pulmonary edema and cardiac arrest, with possibly fatal consequences. Death from SCLS typically occurs during this recruitment phase because of pulmonary edema arising from excessive intravenous fluid administration during the earlier<unk>  phase. The severity of the problem depends on to the quantity of fluid supplied in the initial phase, the damage that may have been sustained by the kidneys, and the promptness with which diuretics are administered to help the patient discharge the accumulated fluids quickly. A recent study of 59 acute episodes occurring in 37 hospitalized SCLS patients concluded that high-volume fluid therapy was independently associated with poorer clinical outcomes, and that the main complications of SCLS episodes were recovery-phase pulmonary edema (24%), cardiac arrhythmia (24%), compartment<unk>  (20%), and acquired infections (19%). The prevention of episodes of SCLS has involved two approaches. The first has long been identified with the Mayo Clinic, and it recommended treatment with beta agonists such as terbutaline, phosphodiesterase-inhibitor theophylline, and leukotriene-receptor antagonists montelukast sodium. The rationale for use of these drugs was their ability to increase intracellular cyclic AMP (adenosine monophosphate) levels, which might counteract inflammatory signaling pathways that induce endothelial permeability. It was the standard of care until the early 2000s, but was sidelined afterwards because patients frequently experienced renewed episodes of SCLS, and because these drugs were poorly tolerated due to their unpleasant side effects. The second, more recent approach pioneered in France during the last decade (early 2000s) involves monthly intravenous infusions of immunoglobulins (IVIG), with an initial dose of 2 gr/kg/month of body weight, which has proven very successful as per abundant case-report evidence from around the world. IVIG has long been used for the treatment of autoimmune and MGUS-associated<unk> s, because of its potential immunomodulatory and anticytokine properties. The precise mechanism of action of IVIG in patients with SCLS is unknown, but it is likely that it neutralizes their proinflammatory cytokines that provoke endothelial dysfunction. A recent review of clinical experience with 69 mostly European SCLS patients found that preventive treatment with IVIG was the strongest factor associated with their survival, such that an IVIG therapy should be the first-line preventive agent for SCLS patients. According to a recent NIH survey of patient experience, IVIG prophylaxis is associated with a dramatic reduction in the occurrence of SCLS episodes in most patients, with minimal side effects, such that it may be considered as frontline therapy for those with a clear-cut diagnosis of SCLS and a history of recurrent episodes.
Capillary leak syndrome
Sepsis
Pulmonary-renal syndrome
Polycythemia vera
Edwards syndrome
Polycythemia
Thoracic insufficiency syndrome
Hyperviscosity syndrome