1. Systemic and Medical Causes of Edema
Suman W Rathbun MD, MS
Director, Vascular Medicine
University of Oklahoma Health Sciences Center

2. Disclosure
Grant support: Diagnostica Stago Inc.

3. APPROACH TO THE PATIENT WITH LEG PAIN AND SWELLING
New or worsening symptoms
Yes No
Objective testing for DVT
Chronic swelling
Drug Induced
Abnormal:
Treat DVT
Normal:
Withhold DVT Treatment
Tumors
Vascular
Lymphatic
Possible Diagnoses
Systemic, medical
Orthopedic
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
Miscellaneous
Dependency
Factitial limb swelling
Lipedema
Obesity
Reflex sympathetic dystrophy
Retroperitoneal fibrosis
IM July 1995;16:50

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

11. 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

12. 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

13. Graves myxedema

14. 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

16. 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

17. 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

18. Approach to Leg Edema Systemic Evaluation
Leg edema without apparent cause
History and physical exam
Bilateral edema
Unilateral Edema
Are there any red flags?
Acute onset
Age > 45
Clinical suspicion of systemic cause
Suspicion of pelvic malignancy
Symptoms of sleep apnea
Medications
Systemic Evaluation
Consider common causes
Adapted from Ely J et al. JABFM 2206;19:148