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Systemic and Medical Causes
of Edema
Suman W Rathbun MD, MS
Director, Vascular Medicine
University of Oklahoma Health Sciences Center
Disclosure
• Grant support: Diagnostica Stago Inc.
APPROACH TO THE PATIENT WITH LEG PAIN AND SWELLING
New or worsening symptoms
Yes
Objective testing for DVT
Abnormal:
Treat DVT
Normal:
Withhold DVT Treatment
No
Chronic swelling
Drug Induced
Tumors
Vascular
Lymphatic
Possible Diagnoses
IM July 1995;16:50
Abscess
Muscle strain from
Baker’s cyst,
unaccustomed exercise
cyst rupture
muscle tear
Cellulitis
superficial phlebitis
Compartment
Swelling in paralyzed leg
syndrome,
Twisting leg injury
revascularization
Venous valvular
Lymphedema, lymphangitis
insufficiency
Major orthopedic surgery,
leg trama
Systemic, medical
Orthopedic
Miscellaneous
Dependency
Factitial limb swelling
Lipedema
Obesity
Reflex sympathetic dystrophy
Retroperitoneal fibrosis
Systemic causes of edema
• Cardiac disease
• Hepatic disease
• Malabsorption/protein-calorie malnutrition
• Obstructive sleep apnea
• Pregnancy and premenstrual edema
• Renal disease
• Thyroid disease
• Allergy, urticaria, angioedema
• Medications
Cardiac disease
• Increased capillary permeability from
systemic venous hypertension
• Increased plasma volume
• Right sided heart failure
• Pulmonary hypertension
• Physical exam: bilateral pitting edema, distension of jugular veins,
right upper quadrant abdominal tenderness due to liver congestion
• Diagnostic Testing: echocardiogram, BNP
• Treatment: diuretics, ACEI, ARB, other chamber specific therapies
Hepatic disease
• Increased capillary permeability from
systemic venous hypertension; portal
• Decreased plasma oncotic pressure from reduced protein synthesis
• Cirrhosis
• Physical exam: ascites, splenomegaly, jaundice, weight loss, nausea,
bruising
• Diagnostic testing: liver function tests, Hepatitis panel, CT, Albumin,
PT/INR
• Treatment: Water restriction, low sodium diet, TIPS procedure
Malabsorption/protein-calorie malnutrition
• Reduced protein synthesis leading to decreased plasma oncotic pressure
• Sometimes obstruction of lymphatic system: intestinal lymphangiectasia causing
protein loss
• Reflux of fluid into interstitial space
• Pancreatic insufficiency, biliary disease, intestinal overgrowth, sprue, celiac,
Crohn’s, lactase deficiency, AIDS enteropathy etc.
• Diarrhea, steatorrhea, weight loss, fatigue, anemia, bleeding, neuro
manifestations
• Physical exam: low BP, muscle wasting, pale, ecchymosis, motor weakness,
neuropathy, glossitis, dermatitis
• Diagnosis: CBC, iron, PT/INR, cholesterol, vitamin concentrations, bowel imaging,
fat malabsorption studies
• Treatment: Nutritional support, MCT or gluten free diet, supplements
Obstructive sleep apnea
• Pulmonary hypertension resulting in
increased capillary hydrostatic pressure
• Elevated right heart pressure
• Snoring, abrupt awakenings, morning headache, insomnia, daytime
sleepiness
• Physical exam: obesity, enlarged neck circumference
• Diagnosis: polysomnography and echocardiography
• Treatment: CPAP, oral appliance, elevate legs, compression
Pregnancy and premenstrual edema
• 92% of women in second phase of their menstrual cycle:
progesterone driven
• Progesterone acts as agonist for aldosterone, inducing natiuresis with
increased renin-secretion levels.
• Physical exam: Edema in legs, arms, face, abdomen, mammary areas
also
• Diagnostic testing: None
• Treatment: Compression stockings
Int J Womens Health 2015;7:297
Renal disease
• Increased plasma volume (salt retention)
• Decreased oncotic pressure from protein loss (nephrotic syndrome)
• Acute or chronic renal failure
• Physical exam: leg swelling and periorbital swelling
• Diagnostic testing: Creatinine and chemistries, urinalysis, CT, US, renal
biopsy
• Treatment: ACEI, ARB, fluid restriction, salt restriction, diuretics,
dialysis
Thyroid disease
• Hypo or hyperthyroidism
• Hypothyroidism: deposition of mucopolysacchrides in the dermis
resulting in edema.
• Hypothyroidism: myxedema with dry, thick skin, non pitting
periorbital edema, yellow discoloration of skin over knees, elbows,
palms and soles
• Graves: deposition of hyaluronic acid in the skin, localized pretibial
myxedema, often non pitting edema, anterior/lateral legs
• Treatment: topical steroids, compression, correct underlying cause
Graves myxedema
Allergy, urticaria and angioedema
• Increased capillary permeability
• Urticaria or hives: pruritic welts or blotches
• Angioedema: affects deeper layers of the skin, eyes and lips
• Causes: food, medications, pollen, emotional, heat/cold, exercise
• Physical exam: swollen pale patches welts on face, lips, tongue,
throat, ears with hives.
• Diagnostic testing: CBC with eosinophils, allergy testing
• Treatment: antihistamines, corticosteroids, autoimmune
• Increased extracellular fluid volume
• Ca-channel blockers: selective precapillary
sphincter dilatation with increased capillary
hydrostatic pressure and leakage of fluid
into the interstitium
• Occurs weeks after initiation of medication
• Resolves within days of discontinuation
• Soft, pitting edema
Evaluation of Systemic Causes of Edema
Acute edema: d-Dimer, follow with Doppler exam if d-Dimer elevated OR clinical suspicion of DVT
high
Age > 45 years: echocardiogram to rule out pulmonary hypertension, heart failure
Suspicion of heart disease: ECG, echocardiogram, chest radiograph
Suspicion of liver disease: ALT, AST, total bilirubin, alkaline phosphase, prothrombin time, serum
albumin
Suspicion of kidney disease: urinalysis with exam of sediment, serum lipids
Suspicion of malignancy: abdominal/pelvic CT scan
Suspicion of sleep apnea: sleep study, echocardiogram
Lymphedema: abdominal/pelvic CT scan
Medications known to cause edema
Adapted from Ely J et al. JABFM 2206;19:148
Approach to Leg Edema
Leg edema without apparent cause
History and physical exam
Unilateral Edema
Bilateral edema
Are there any red flags?
Systemic Evaluation
Acute onset
Age > 45
Clinical suspicion of systemic cause
Suspicion of pelvic malignancy
Symptoms of sleep apnea
Medications
Adapted from Ely J et al. JABFM 2206;19:148
Consider common causes