Idiopathic edema: Pathogenesis, clinical features, and treatment

Abstract

Previously published findings are reviewed and new data are presented relating to the clinical features, pathophysiology, and treatment of the idiopathic edemas, a group of disorders diagnosed by exclusion of the known causes of edema. The disorders occur almost exclusively in women, show diurnal (postural), not “cyclic” fluctuations in severity, often cause discomfort and occasionally pain, and may be aggravated by prolonged orthostasis, hot environments, menses, and some drugs. Among the pathophysiologic factors known to be important in edema formation, in general: (1) Hypoproteinemia is more commonly the result than the cause of idiopathic edema; (2) elevated capillary hydrostatic pressure is seldom the primary cause, except perhaps in rare cases of occult congestive heart failure; (3) changes in tissue pressure may limit the progression of, but do not initiate, the edema; (4) changes in capillary wall permeability and (5) changes in capillary diffusion area, perhaps because of excessive dilatation of precapillary sphincters appear to be of importance; (6) abnormalities of lymphatic flow are not demonstrable; and (7) the upright posture is an important contributor to the excessive transudation in over 80% of the patients studied (“orthostatic edema”) but not in the remaining minority of patients (“nonorthostatic edema”). By balance studies with constant diets and by an abbreviated “posture test”, it has been shown that (A) the majority of patients with “orthostatic edema” have excessive orthostatic sodium (Na) retention that results from an excessive orthostatic fall in glomerular filtration rate, frequently associated with excessive renal tubular reabsorption of the subnormal filtered Na load because of orthostatic hyperaldosteronism, and (B) about 30%–40% of patients with orthostatic edema have “orthostatic water retention”, demonstrable by an inability to excrete more than 55% of a 20 ml/kg water load during 4 hr in the upright posture. In most of these patients but not in most other types of edema, orthostatic excretion of the water load is restored to normal by ethanol (a known inhibitor of vasopressin release). Improvement in orthostatic renal excretion by external compression of the legs and persistence of excessive orthostatic changes in leg volume despite restricted Na intake support microscopic evidence that a capillary “leak” may be the primary cause of most orthostatic edemas. Reduced dopamine excretion has been reported and linked to the causation of some types of idiopathic edema. Obesity is often associated with edema that differs from other idiopathic edemas in that it usually disappears with caloric restriction and weight loss. In occasional patients, undue sensitivity to heat may play a role as important as that of posture. Treatment of idiopathic edema includes avoidance of excessive salt intake, reduction of the duration of standing and sitting, and administration of conventional diuretics, preferably at 7 or 8 p.m., followed by recumbency for several hours before sleep. Hyperaldosteronism has responded to subtotal adrenalectomy (which is not recommended) and constitutes a strong indication for the use of spironolactone, which facilitates recumbent excretion of Na retained in the upright posture. Sympathomimetic amines (ephedrine, phenylephrine, and preferably dextroamphetamine) are the only agents that will usually significantly reduce the excessive weight gain from morning to evening (the hallmark of orthostatic edema), perhaps by preventing excessive capillary pooling and transudation. They have been used safely, effectively, and without loss of their efficacy, for up to 20 yr in several patients. Elastic stockings and garments are occasionally useful and regular exercise, especially swimming, may be beneficial.