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Lymphedema, Pediatric


Basics


Description


  • Lymphedema is a chronic progressive swelling in subcutaneous tissues, typically in an extremity or the genitals, due to protein-rich accumulation of interstitial fluid from disruption of the lymphatic system. It can be of primary or secondary origin.
  • Primary lymphedema has 3 forms, all of which stem from a developmental abnormality of lymphatic flow. Not all primary lymphedemas are clinically evident at birth.
    • Congenital lymphedema, due to anomalous development of lymph system
      • Present at birth
      • Lower to upper extremity ratio: 3:1
      • 2/3 of cases are bilateral.
      • May improve with age
    • Lymphedema praecox (65 " “80% of primary lymphedema)
      • Usually becomes evident at puberty but may appear between infancy and age 35 years
      • 70% unilateral lower extremity (L > R)
    • Lymphedema tarda: presents at age 35 years or older
  • Secondary lymphedema is from an acquired abnormality of lymphatic flow, an injury to the lymphatic system.
    • Common causes in children include the following:
      • Postsurgical obstruction
      • Burns
      • Insect bites
      • Infection
      • Scar tissue from radiation
      • Neoplasm
      • Trauma

Epidemiology


  • Most lymphedemas in childhood are primary (or idiopathic) lymphedema (96%).
  • Congenital lymphedema comprises 10 " “25% of primary lymphedema cases; lymphedema praecox, 65 " “80%; and lymphedema tarda, 10%.
  • Affected males " ”most likely congenital and bilateral; affected females " ”most likely unilateral lymphedema praecox
  • Secondary lymphedema is more common in adults and rare in children. In the United States, it is commonly from breast cancer; worldwide, due to filariasis.
  • Affects 1.15 of 100,000 in children <20 years

Risk Factors


Genetics
  • Milroy disease
    • Also known as hereditary lymphedema type IA
    • A rare, autosomal dominant condition that affects lymphatic function
    • Associated with mutations in the FLT4 gene that encodes vascular endothelial growth factor receptor 3
  • Meige disease
    • Hereditary lymphedema type II " ”familial lymphedema praecox
  • Fabry disease
    • A serious, X-linked inborn error of glycosphingolipid catabolism associated with progressive renal failure, cardiovascular disease, neuropathy, and angiokeratosis
  • Lymphedema-distichiasis
    • An autosomal dominant condition that presents with lymphedema and double rows of eyelashes
    • The condition is associated with mutations in the FOXC2 gene.
  • Other genetic conditions prone to lymphedema: Down, Turner, Noonan, yellow nail, Klippel-Trenaunay-Weber, and pes cavus

Pathophysiology


  • Abnormal accumulation of interstitial fluid due to the lymphatic load overwhelming the transport capacity of lymph vessels
  • Lymph flow occurs under a low pressure system; unlike generalized edema, capillary filtration remains normal in patients with lymphedema.
  • Initially, edema is pitting, whereas chronic edema is generally nonpitting as a result of fibrosis.

Diagnosis


History


  • Unilateral, heavy, often aching lower extremity edema in healthy pubertal female strongly suggests lymphedema praecox.
  • Heavy, aching pitting edema distal to site of extremity surgery or trauma suggests secondary lymphedema.
  • Sites of previous cellulitis, infection, or insect bites can be associated with secondary lymphedema.

Physical Exam


  • Heavy, aching pitting edema in unilateral limb is suggestive of lymphedema.
  • Lymphedema responds to elevation.
  • Risk factors include obesity and inflammatory arthritis.
  • Primary lymphedema sites: extremities, usually legs, rare in upper limbs; the foot is always involved in lower extremity lymphedema.
  • Chronic inflammation leads to fibrosis and nonpitting or "woody " ¯ edema with induration.
  • Hair loss and hyperkeratosis of the affected limb develop over time.
  • Intense sharp pain in affected limb is uncommon and suggests secondary lymphedema due to thrombophlebitis, cellulitis, or reflex sympathetic dystrophy.
  • Global edema suggests other disease states.
  • Red streaking of extremity, fever, chills, or nodal enlargement suggests development of cellulitis or lymphangitis.
  • History and physical exam are primary source for diagnosis.

Diagnostic Tests & Interpretation


Lab
Not usually necessary but may be useful to rule out other causes of edema ‚  
  • Urinalysis for proteinuria as seen with glomerulonephrosis
  • Serum total protein and albumin to rule out hypoproteinemia
  • Liver function tests to assess functional status
  • Pregnancy test

Imaging
Usually unnecessary to make diagnosis but may help to plan or evaluate therapy ‚  
  • Lymphangiography is no longer used because related dyes caused inflammation and worsening of lymphatic obstruction.
  • Radionuclide lymphoscintigraphy, when indicated, is the preferred method of imaging to define anatomy and to evaluate lymph flow and obstruction.
  • CT and MRI may be valuable if a malignancy is suspected or to differentiate subcutaneous from adipose swelling.
  • Doppler ultrasound may be helpful if deep vein thrombosis is suspected.

Differential Diagnosis


  • Infection
    • Cellulitis
    • Lymphangitis
    • Herpes simplex virus type 2
  • Tumors
    • Pelvic mass
    • Multiple enchondromatosis
  • Metabolic
    • Cushing disease
    • Hyperthyroidism
    • Lipedema
  • Anatomic
    • Venous stasis
    • Deep vein thrombosis
    • Hemihypertrophy
    • Arteriovenous fistula or malformation
    • Popliteal arterial aneurysm
    • Popliteal cyst (Baker cyst)
  • Miscellaneous
    • Heart failure
    • Glomerulonephrosis
    • Cirrhosis
    • Hypoproteinemia
    • Reflex sympathetic dystrophy

Treatment


General Measures


  • Therapy should be instituted as soon as possible and before fibrosis develops.
  • Goals of therapy are to minimize or decrease edema and to prevent infection, fibrosis, and skin changes.
  • Compression garments (e.g., Jobst stockings or elastic wraps) is recommended long term but compliance can be a challenge.
  • Extremity elevation, especially at night
  • Exercise, stay active for a lifetime; muscle contraction assists lymph flow and does not exacerbate swelling.
  • Weight control
  • Diligent skin care and appropriately fitting shoes to avoid infection
  • Manual massage decompression can be helpful for digital edema and for infants who may not tolerate compression garments.
  • Automated intermittent pneumatic compression machines shown to facilitate home regimen compliance
  • Psychological effects of cosmesis are prominent and should not be overlooked.
  • Patient education and support groups can be found through the National Lymphedema Network.

Diet


In children with chylous reflux syndromes, a diet low in long-chain triglycerides may be of benefit. ‚  

Special Therapy


  • Complex decongestive physiotherapy (CDP) is part of a specialized treatment with an initial reductive phase 1 and a maintenance phase 2 provided by a licensed physical therapist or occupational therapist certified in the treatment of lymphedema.
  • Treatment is time sensitive and should be instituted as soon as possible to prevent fibrosis developing.
  • Phase 1 consists of manual lymph-drainage therapy, compression therapy specialized bandaging, fitting for appropriate tailored compression garment, and detailed skin and nail care.
  • Phase 2 consists of self-management for drainage techniques, skin care, use and care of compression garments, and exercise advice

Medication


  • Diuretics: not generally used in children and adolescents; efficacy for adults is debated
  • Prophylactic antibiotic use is indicated for patients with recurrent cellulitis or lymphangitis.

Surgery/Other Procedures


  • Microsurgical treatment has been proven to show excellent outcomes in carefully selected patient populations via lymphatic-venous anastomoses or lymphatic-venous-lymphatic anastomoses.
  • Traditional surgery has 1 of 2 goals: removal of excess edematous tissue or attempts to restore lymph drainage
    • Both may decrease the rate of infections but have poor cosmetic results.
    • Recommended only for those with uncontrolled swelling with significant disability

Ongoing Care


Prognosis


  • Edema persists throughout life.
  • Lymphedema can be staged and monitored via circumferential measurements. Guidelines have been established by the American Physical Therapy Association.
  • Natural history: plateau in severity of edema after an initial few years of progression in 50%, slow constant progression in 50%

Complications


  • Cellulitis and lymphangitis are the most common complications and are treated with antibiotics; published series showed 24% of cases developed infection and half of these required hospitalization.
  • Poor long-term compliance with compression garments due to uncomfortable nature of therapy
  • Lymphangiosarcoma (rare)
  • Psychological problems
  • Physical limitations
  • Chronic inflammation and edema ultimately lead to fibrosis and induration of the involved area.

Additional Reading


  • Gary ‚  DE. Lymphedema diagnosis and management. J Am Acad Nurse Pract.  2007;19(2):72 " “78. ‚  [View Abstract]
  • Kerchner ‚  K, Fleischer ‚  A, Yosipovitch ‚  G. Lower extremity lymphedema update: pathophysiology, diagnosis, and treatment guidelines. J Am Acad Dermatol.  2008;59(2):324 " “331. ‚  [View Abstract]
  • Mayrovitz ‚  HN. The standard of care for lymphedema: current concepts and physiological considerations. Lymph Res Biol.  2009;7(2):101 " “108. ‚  [View Abstract]
  • Rockson ‚  SG. Current concepts and future directions in the diagnosis and management of lymphatic vascular disease. Vasc Med.  2010;15(3):223 " “231. ‚  [View Abstract]
  • Schook ‚  CC, Mulliken ‚  JB, Fishman ‚  SJ, et al. Differential diagnosis of lower extremity enlargement in pediatric patients referred with a diagnosis of lymphedema. Plast Reconstr Surg.  2011;127(4):1571 " “1581. ‚  [View Abstract]
  • Zuther ‚  JE. Lymphedema Management: The Comprehensive Guide for Practitioners. 2nd ed. New York, NY: Thieme; 2009.

Codes


ICD09


  • 457.1 Other lymphedema
  • 757.0 Hereditary edema of legs
  • 997.99 Complications affecting other specified body systems, not elsewhere classified

ICD10


  • I89.0 Lymphedema, not elsewhere classified
  • Q82.0 Hereditary lymphedema
  • I97.89 Oth postproc comp and disorders of the circ sys, NEC

SNOMED


  • 234097001 Lymphedema (disorder)
  • 254199006 Hereditary lymphedema (disorder)
  • 440121002 postsurgical lymphedema (disorder)

FAQ


  • Q: Is the swelling going to go away?
  • A: No, this is a chronic condition requiring long-term management.
  • Q: Could this have been prevented?
  • A: No, primary lymphedema is typically due to abnormal embryologic development.
  • Q: If the lymph channels have been abnormal since birth, why does the swelling present during adolescence?
  • A: No one really knows; hormones may play a role in lymphedema.
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