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Lymphedema
Jon S. Parham, DO, MPH
image BASICS
DESCRIPTION
  • Accumulation of lymphatic fluid in the interstitial tissue causing swelling
  • Lymphedema can develop when lymphatic vessels are missing or impaired (primary) or when lymph vessels are damaged or lymph nodes are removed (secondary).
  • Most common in the lower limb (80%) but also can occur in the arms, face, trunk, and external genitalia
EPIDEMIOLOGY
Incidence
  • Predominant sex: female > male
  • Predominant age: any age
  • 13% of patients with breast cancer treated with surgery; 42% of those treated with surgery and radiation therapy; 25% after GYN cancer surgery
  • Milroy disease presents at birth; estimated to be between 1/6,000 and 1/300 live births
  • Meige disease develops during puberty.
Prevalence
  • 120 million people worldwide are affected with lymphatic filariasis in 73 countries but no primary infections in United States.
  • 10 million people are affected by nonfilarial secondary lymphedema in the United States.
ETIOLOGY AND PATHOPHYSIOLOGY
Secondary lymphedema:
  • Postoperative: gradual failure of distal lymphatics, which have to “pump” lymph at a greater pressure through damaged proximal ducts
  • Risk is higher with postoperative radiation because radiation reduces regrowth of ducts due to fibrous scarring.
  • Trauma; recurrent infection; malignancy, including metastatic disease, and marked obesity
  • Developing countries: Most common cause is filariasis (Wucheria bancrofti).
Genetics
  • Milroy disease: autosomal dominant; diagnosed either at birth or the 1st year of life
  • Lymphedema praecox has onset between the ages of 1 and 35 years.
  • Lymphedema tarda occurs in those >35 years of age.
RISK FACTORS
  • Filariasis: most common cause worldwide
  • Mastectomy
  • Prior trauma, infection of affected limb
  • History of prior surgical (particularly if lymph nodes were removed) or radiation therapy for malignancy (radiation can damage lymph nodes and cause skin dermatitis)
  • Long history of venous insufficiency
  • Obesity, DVT
GENERAL PREVENTION
Healthy body weight maintenance; treatment of congestive heart failure (CHF) and venous insufficiency
COMMONLY ASSOCIATED CONDITIONS
Venous disease
image DIAGNOSIS
PHYSICAL EXAM
  • Initial: pitting edema, can spread proximally
  • Later: nonpitting; after first year, does not spread proximally/distally but spreads radially
  • Hyperkeratosis (thicker skin)
  • Papillomatosis (rough skin)
  • Increase in skin turgor
  • Positive Stemmer sign (inability to pinch the skin of the dorsum of the second toe between the thumb and forefinger): must exclude heart failure
DIFFERENTIAL DIAGNOSIS
  • CHF, renal failure, lipidemia
  • Hypoalbuminemia, protein-losing nephropathy
  • DVT, chronic venous disease
  • Postoperative complications following ipsilateral surgery
  • Cellulitis, Baker cyst, idiopathic edema
DIAGNOSTIC TESTS & INTERPRETATION
  • Lack of response to elevation or diuretic therapy may indicate a lymphatic insufficiency (2)[B].
  • Diuretics increase excretion of salt and water, thereby decreasing plasma volume, venous capillary pressure, and filtration. Diuretics improve filtration edema but do not improve lymph drainage over the long term.
  • Some relevant protein biomarkers for lymphedema have been identified and show promise for earlyand latent-stage diagnosis (3)[B].
Initial Tests (lab, imaging)
  • Comprehensive chemistry panel: evaluates for hepatic or renal impairment
  • Urinalysis: protein-losing nephropathy
  • Ultrasound: evaluates for acute/chronic DVT; gives information about soft tissue changes but does not tell about truncal anatomy of the lymphatics (1)[B]
  • Duplex ultrasound: Lymphedema causes gradual impedance of venous return that aggravates the edema; 82% of patients with unexplained limb edema were diagnosed using a combination of duplex ultrasound and lymphoscintigram (4)[A].
Follow-Up Tests & Special Considerations
  • Lymphangiogram: direct cannulation of lymphatics through the skin; risk for infection, local inflammation; not used commonly (4)[C]
  • Fluorescence microlymphography may be highly sensitive (91.4%) and specific (85.7%), atraumatic and is without radiation in diagnosis of leg lymphedema (5)[B]
  • Lymphoscintigram: radiolabeled protein technetium-99m-labeled colloid
    • Measures lymphatic function, lymph movement, lymph drainage, and response to treatment
    • Sensitivity, 73-97%; specificity, 100%
    • Best to use 1 hour and delayed images together (4)[A]
  • Indocyanine green lymphography: reported
    • Superior to lymphoscintigraphy in early diagnosis of arm (6)[B]
    • Accurately screens post surgically for subclinical lymphedema (7)[B]
  • CT scan: calf skin thickening, thickening of the SC compartment, increased fat density, thickened perimuscular aponeurosis; typical honeycomb appearance (4)[B]
  • MRI: circumferential edema, increased volume of SC tissue, honeycomb pattern above the fascia between the muscle and subcutis; cannot differentiate primary from secondary lymphedema (4)[B]
image TREATMENT
GENERAL MEASURES
  • Seek optimal weight, early treatment of cellulitis, avoid trauma to affected area (direct injury, venipunctures, inept nail care, extreme heat/cold).
  • Achieve mechanical reduction and maintenance of limb size: compression garments via professionals.
  • Elevate affected limb/area, but avoid stasis.
  • Avoid BP cuffs in affected limbs.
  • Prevent skin infection with daily cleansing, inspection, and skin care (with emollients).
  • Treatment of varicose veins may benefit some.
MEDICATION
  • Diuretics of limited benefit and may lead to volume depletion
  • Benzopyrenes (flavonoids and coumarin) (not available for prescription use in the United States)
    • Micronized purified flavonoid fraction (Daflon 500 mg) is effective in decreasing venous stasis and idiopathic cyclic edema, chronic venous insufficiency, and postmastectomy lymphedema. It also reduces capillary permeability and the inflammatory component (8)[C].
  • Coumarin reduces edema fluid by increasing the number of macrophages and enhancing proteolysis, resulting in the removal of protein, increasing softness in the limbs, and decreasing elevated skin temperature with subsequent symptom improvement and decreased secondary infection. Some reports of hepatotoxicity (8)[C].
ISSUES FOR REFERRAL
  • Refer to physical therapist with lymphedema training for manual decongestive therapy.
    • In patients with recurrent or metastatic disease, discuss with oncologist prior to initiation of complete decongestive therapy in order not to promote the spread of cancer.
  • Provide education for patient/family for self-administration of therapy in future.
  • Education for family about bandaging
  • Fitting for compression garments
P.627

ADDITIONAL THERAPIES
  • Exercise: Lymph flow occurs as a result of inspiratory reduction in the intrathoracic pressure associated with inspiration. Best results are achieved with combination of flexibility, strength, and aerobic training (4)[B]. Compression with custom-made elastic stocking (minimum pressure is 40 mm Hg).
    • Protection against external incidental trauma
    • Decreases the intrinsic trauma on the skin due to chronically increased interstitial pressures, which cause stretch of the skin and SC tissues
    • No data on preference of custom-made versus prefabricated
    • Replace every 3 to 6 months or when starting to lose elasticity (1)[B].
  • Multilayer bandaging: inner layer of tubular stockinette followed by foam and padding to protect the joint flexures and to even out the contours of the limb so that pressure is distributed evenly; outer layer of at least two short-stretch extensible bandages; more effective than hosiery alone (1)[B]
  • Pneumatic pumps: development of high pressure up to 150 mm Hg; can reduce limb girth by 37-68.6%; wear a compression stocking when not using pump; high risk of genital edema; no metastasis in limb due to risk of spread (1)[B]
  • Thai “Schnogh”, a novel, intense tourniquet technique, has initially shown at least 50% limb volume reduction (9)[C]
SURGERY/OTHER PROCEDURES
  • Bypass procedures: creation of lymphatic-venous anastomosis or lymph node transplantation (most effective) via microsurgery showed a reduction in use of conservative compression therapy (10)[B]: reserved for refractory cases only. In a pilot study, low-level laser therapy was shown not to be inferior to manual lymphatic drainage or the combination of the two in arm volume reduction in breast cancer-related lymphedema and required ≤1/2 the treatment time (11)[C].
  • Thoracic sympathetic ganglion block for breast cancer-related lymphedema, a new treatment showed better life quality and arm size reduction >50% (11)[B]
  • Debulking procedures (Charles procedure): radical excision of SC tissue with primary or staged skin grafting (8)[C]
    • Men had less improvement than women.
    • Main risk is infection and necrosis of the skin graft.
    • Liposuction is cosmetically preferred to debulking.
COMPLEMENTARY & ALTERNATIVE MEDICINE
Heat therapy: Hot water immersion, microwave, and electromagnetic irradiation may be helpful (1)[C].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Systemic signs of infection
  • May admit to specialized rehabilitation unit for combination treatment in patients with heart failure or severe pulmonary disease
  • IV antibiotics for infection
Nursing
  • Leg elevation
  • Encourage patient mobilization/exercise.
  • Patient education for bandaging/wound care
Discharge Criteria
  • Resolution of signs/symptoms of infection (e.g., elevated WBC count, fever, abnormal vital signs)
  • Clinical improvement in wound appearance
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Lymphedema will return in several days if patient stops wearing compression garments during the day and bandaging at night.
Patient Monitoring
  • Daily visit to therapist for acute treatment
  • Monthly visits for maintenance care
DIET
Low sodium; weight loss-oriented if needed
PATIENT EDUCATION
  • Use compression garments, especially when exercising.
  • Avoid affected limb(s) being dependant for long period of time: Patient should perform daily skin examination.
  • http://www.nlm.nih.gov/medlineplus/lymphedema.html
PROGNOSIS
No cure, but treatment can produce good results with daily care
REFERENCES
1. Warren AG, Brorson H, Borud LJ, et al. Lymphedema: a comprehensive review. Ann Plast Surg. 2007;59(4):464-472.
2. Mortimer PS. Implications of the lymphatic system in CVI-associated edema. Angiology. 2000;51(1):3-7.
3. Lin S, Kim J, Lee MJ, et al. Prospective transcriptomic pathway analysis of human lymphatic vascular insufficiency: identification and validation of a circulating biomarker panel. PLoS One. 2012;7(12):e52021.
4. Brennan MJ, Miller LT. Overview of treatment options and review of the current role and use of compression garments, intermittent pumps, and exercise in the management of lymphedema. Cancer. 1998;83(12 Suppl):2821-2827.
5. Keo HH, Husmann M, Groechenig E, et al. Diagnostic accuracy of fluorescence microlymphography for detecting limb lymphedema. Eur J Vasc Endovasc Surg. 2015;49(4):474-479.
6. Mihara M, Hara H, Araki J, et al. Indocyanine green (ICG) lymphography is superior to lymphoscintigraphy for diagnostic imaging of early lymphedema of the upper limbs. PloS One. 2012;7(6):e38182.
7. Akita S, Mitsukawa N, Rikihisa N, et al. Early diagnosis and risk factors for lymphedema following lymph node dissection for gynecologic cancer. Plast Reconstr Surg. 2013;131(2):283-290.
8. Tiwari A, Cheng KS, Button M, et al. Differential diagnosis, investigation, and current treatment of lower limb lymphedema. Arch Surg. 2003;138(2):152-161.
9. Chanwimalueang N, Ekataksin W, Piyaman P, et al. Twisting Tourniquet(©) Technique: introducing Schnogh, a novel device and its effectiveness in treating primary and secondary lymphedema of extremities. Cancer Med. 2015;4(10):1514-1524.
10. Basta MN, Gao LL, Wu LC. Operative treatment of peripheral lymphedema: a systematic metaanalysis of the efficacy and safety of lymphovenous microsurgery and tissue transplantation. Plast Reconstr Surg. 2014;133(4):905-913.
11. Ridner SH, Poage-Hooper E, Kanar C, et al. A pilot randomized trial evaluating low-level laser therapy as an alternative treatment to manual lymphatic drainage for breast cancer-related lymphedema. Oncol Nurs Forum. 2013;40(4):383-393.
Codes
&NA;
ICD10
  • I89.0 Lymphedema, not elsewhere classified
  • Q82.0 Hereditary lymphedema
  • I97.89 Oth postproc comp and disorders of the circ sys, NEC
Clinical Pearls
&NA;
  • Use short-stretch bandages for wrapping (not ACE wraps).
  • Avoid heat/whirlpool: typically worsens condition.
  • Much higher risk for cutaneous-sourced infections than patients with only venous insufficiency
  • Lymphoscintigram is a standard diagnostic, but consider Indocyanine green lymphography or fluorescence microlymphography.