Clinical features and diagnosis of peripheral lymphedema
- Emile R Mohler III, MD
Emile R Mohler III, MD
- Section Editor — Vascular Medicine
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Babak Mehrara, MD
Babak Mehrara, MD
- Associate Professor of Surgery
- Cornell Weill Medical Center
- Section Editors
- John F Eidt, MD
John F Eidt, MD
- Section Editor — Vascular and Endovascular Surgery
- Professor of Surgery, Texas A&M Health Science Center
- Vice Chair of Vascular Surgical Services, Baylor Heart and Vascular Hospital at Dallas
- Joseph L Mills, Sr, MD
Joseph L Mills, Sr, MD
- Section Editor — Vascular and Endovascular Surgery
- Professor and Chief
- Division of Vascular Surgery and Endovascular Therapy
- Baylor College of Medicine
- Harold Burstein, MD, PhD
Harold Burstein, MD, PhD
- Section Editor — Breast Cancer
- Associate Professor of Medicine
- Harvard Medical School
Lymphedema is defined as the abnormal accumulation of interstitial fluid and fibroadipose tissues resulting from injury, infection, or congenital abnormality of the lymphatic system. Lymphedema is classified as primary or secondary depending on etiology and presentation.
The etiology, risk factors, clinical manifestations, classification, diagnosis, and differential diagnosis of lymphedema will be reviewed here. The prevention and treatment of lymphedema, the operative management of primary and secondary lymphedema, and an overview of the pathophysiology and etiology of generalized edema are presented separately. (See "Clinical staging and conservative management of peripheral lymphedema" and "Surgical treatment of primary and secondary lymphedema" and "Pathophysiology and etiology of edema in adults" and "Pathophysiology and etiology of edema in children".)
NORMAL LYMPHATIC SYSTEM AND LYMPHEDEMA
Lymph flow takes place in a low pressure system. Uptake of interstitial fluid begins in lymphatic capillaries and precollectors that abut the interstitial space. The process is facilitated by local arterial pulsation, skeletal muscle contraction, and unidirectional valves that prevent retrograde flow. The initial lymphatics merge into vessels of increasing caliber partially surrounded by a specialized smooth muscle layer that, upon contraction, promotes peristaltic movement of the lymph fluid toward the systemic circulation.
The lymph draining from both lower extremities, the gastrointestinal tract, and the left upper body (upper extremity, chest wall, upper back, shoulder, and breast) enter the venous circulation through the thoracic duct, which opens into the venous angle between the left subclavian vein and left internal jugular vein (figure 1) . The lymph draining from the right upper body drains into the right lymphatic duct via a similar right-sided venous angle.
In the extremities, the superficial lymphatic system drains the skin and subcutaneous tissue and drains into the deep system that then drains into the lymph nodes in the axilla or pelvis. [1,2]
- Lawenda BD, Mondry TE, Johnstone PA. Lymphedema: a primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin 2009; 59:8.
- Szuba A, Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med 2003; 44:43.
- International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. Lymphology 2013; 46:1.
- Kerchner K, Fleischer A, Yosipovitch G. Lower extremity lymphedema update: pathophysiology, diagnosis, and treatment guidelines. J Am Acad Dermatol 2008; 59:324.
- Vignes S, Arrault M, Yannoutsos A, Blanchard M. Primary upper-limb lymphoedema. Br J Dermatol 2013; 168:272.
- Moffatt CJ, Franks PJ, Doherty DC, et al. Lymphoedema: an underestimated health problem. QJM 2003; 96:731.
- Dale RF. The inheritance of primary lymphoedema. J Med Genet 1985; 22:274.
- Brayton KM, Hirsch AT, O Brien PJ, et al. Lymphedema prevalence and treatment benefits in cancer: impact of a therapeutic intervention on health outcomes and costs. PLoS One 2014; 9:e114597.
- Ramaiah KD, Ottesen EA. Progress and impact of 13 years of the global programme to eliminate lymphatic filariasis on reducing the burden of filarial disease. PLoS Negl Trop Dis 2014; 8:e3319.
- Yost KJ, Cheville AL, Al-Hilli MM, et al. Lymphedema after surgery for endometrial cancer: prevalence, risk factors, and quality of life. Obstet Gynecol 2014; 124:307.
- Cormier JN, Askew RL, Mungovan KS, et al. Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema. Cancer 2010; 116:5138.
- Meric F, Buchholz TA, Mirza NQ, et al. Long-term complications associated with breast-conservation surgery and radiotherapy. Ann Surg Oncol 2002; 9:543.
- Warren AG, Brorson H, Borud LJ, Slavin SA. Lymphedema: a comprehensive review. Ann Plast Surg 2007; 59:464.
- Hayes SC, Janda M, Cornish B, et al. Lymphedema after breast cancer: incidence, risk factors, and effect on upper body function. J Clin Oncol 2008; 26:3536.
- Deutsch M, Land S, Begovic M, Sharif S. The incidence of arm edema in women with breast cancer randomized on the National Surgical Adjuvant Breast and Bowel Project study B-04 to radical mastectomy versus total mastectomy and radiotherapy versus total mastectomy alone. Int J Radiat Oncol Biol Phys 2008; 70:1020.
- Bar Ad V, Cheville A, Solin LJ, et al. Time course of mild arm lymphedema after breast conservation treatment for early-stage breast cancer. Int J Radiat Oncol Biol Phys 2010; 76:85.
- Cariati M, Bains SK, Grootendorst MR, et al. Adjuvant taxanes and the development of breast cancer-related arm lymphoedema. Br J Surg 2015; 102:1071.
- Ozaslan C, Kuru B. Lymphedema after treatment of breast cancer. Am J Surg 2004; 187:69.
- DiSipio T, Rye S, Newman B, Hayes S. Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. Lancet Oncol 2013; 14:500.
- Williams SK, Rabbani F. Complications of lymphadenectomy in urologic surgery. Urol Clin North Am 2011; 38:507.
- Abu-Rustum NR, Alektiar K, Iasonos A, et al. The incidence of symptomatic lower-extremity lymphedema following treatment of uterine corpus malignancies: a 12-year experience at Memorial Sloan-Kettering Cancer Center. Gynecol Oncol 2006; 103:714.
- Rockson SG, Rivera KK. Estimating the population burden of lymphedema. Ann N Y Acad Sci 2008; 1131:147.
- Purushotham AD, Upponi S, Klevesath MB, et al. Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial. J Clin Oncol 2005; 23:4312.
- Erickson VS, Pearson ML, Ganz PA, et al. Arm edema in breast cancer patients. J Natl Cancer Inst 2001; 93:96.
- Borup Christensen S, Lundgren E. Sequelae of axillary dissection vs. axillary sampling with or without irradiation for breast cancer. A randomized trial. Acta Chir Scand 1989; 155:515.
- Kissin MW, Querci della Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg 1986; 73:580.
- Shah C, Wilkinson JB, Baschnagel A, et al. Factors associated with the development of breast cancer-related lymphedema after whole-breast irradiation. Int J Radiat Oncol Biol Phys 2012; 83:1095.
- Proske S, Uter W, Schwanitz HJ. [Secondary lymphedema of the hand as a complication of recurrent erysipelas in irritant contact dermatitis]. Hautarzt 2001; 52:888.
- Joos E, Bourgeois P, Famaey JP. Lymphatic disorders in rheumatoid arthritis. Semin Arthritis Rheum 1993; 22:392.
- Sant SM, Tormey VJ, Freyne P, Casey EB. Lymphatic obstruction in rheumatoid arthritis. Clin Rheumatol 1995; 14:445.
- Kiely PD, Joseph AE, Mortimer PS, Bourke BE. Upper limb lymphedema associated with polyarthritis of rheumatoid type. J Rheumatol 1994; 21:1043.
- Mulherin DM, FitzGerald O, Bresnihan B. Lymphedema of the upper limb in patients with psoriatic arthritis. Semin Arthritis Rheum 1993; 22:350.
- Salvarani C, Cantini F, Olivieri I, et al. Distal extremity swelling with pitting edema in psoriatic arthritis: evidence of 2 pathological mechanisms. J Rheumatol 1999; 26:1831.
- Lekpa FK, Economu-Dubosc A, Fevre C, et al. Efficacy of etanercept in lymphedema associated with psoriatic arthritis. J Rheumatol 2009; 36:207.
- Böhm M, Riemann B, Luger TA, Bonsmann G. Bilateral upper limb lymphoedema associated with psoriatic arthritis: a case report and review of the literature. Br J Dermatol 2000; 143:1297.
- Ostrov BE. Beneficial effect of etanercept on rheumatoid lymphedema. Arthritis Rheum 2001; 44:240.
- Helyer LK, Varnic M, Le LW, et al. Obesity is a risk factor for developing postoperative lymphedema in breast cancer patients. Breast J 2010; 16:48.
- Farshid G, Weiss SW. Massive localized lymphedema in the morbidly obese: a histologically distinct reactive lesion simulating liposarcoma. Am J Surg Pathol 1998; 22:1277.
- Asch S, James WD, Castelo-Soccio L. Massive localized lymphedema: an emerging dermatologic complication of obesity. J Am Acad Dermatol 2008; 59:S109.
- Modolin ML, Cintra W Jr, Paggiaro AO, et al. Massive localized lymphedema (MLL) in bariatric candidates. Obes Surg 2006; 16:1126.
- Manduch M, Oliveira AM, Nascimento AG, Folpe AL. Massive localised lymphoedema: a clinicopathological study of 22 cases and review of the literature. J Clin Pathol 2009; 62:808.
- Greene AK, Grant FD, Slavin SA. Lower-extremity lymphedema and elevated body-mass index. N Engl J Med 2012; 366:2136.
- Yen TW, Laud PW, Sparapani RA, et al. An algorithm to identify the development of lymphedema after breast cancer treatment. J Cancer Surviv 2015; 9:161.
- Tiwari A, Cheng KS, Button M, et al. Differential diagnosis, investigation, and current treatment of lower limb lymphedema. Arch Surg 2003; 138:152.
- Weissleder H, Schuchhardt C. Lymphedema diagnosis and therapy, 2nd, Kagerer Kommunikation, Bonn, Germany 1997.
- Rockson SG. Diagnosis and management of lymphatic vascular disease. J Am Coll Cardiol 2008; 52:799.
- Beaulac SM, McNair LA, Scott TE, et al. Lymphedema and quality of life in survivors of early-stage breast cancer. Arch Surg 2002; 137:1253.
- Casley-Smith JR. Measuring and representing peripheral oedema and its alterations. Lymphology 1994; 27:56.
- Boland R, Adams R. Development and evaluation of a precision forearm and hand volumeter and measuring cylinder. J Hand Ther 1996; 9:349.
- The diagnosis and treatment of peripheral lymphedema: 2003 consensus of the International Society of Lymphology Executive Committee www.u.arizona.edu/%7Ewitte/ISL.htm (Accessed on April 19, 2011).
- Morgan PA, Moffat CJ. International consensus on managing lymphoedema. Nurs Times 2006; 102:42, 44.
- Lette J. A simple and innovative device to measure arm volume at home for patients with lymphedema after breast cancer. J Clin Oncol 2006; 24:5434.
- Deltombe T, Jamart J, Recloux S, et al. Reliability and limits of agreement of circumferential, water displacement, and optoelectronic volumetry in the measurement of upper limb lymphedema. Lymphology 2007; 40:26.
- Ancukiewicz M, Russell TA, Otoole J, et al. Standardized method for quantification of developing lymphedema in patients treated for breast cancer. Int J Radiat Oncol Biol Phys 2011; 79:1436.
- Brorson H, Höijer P. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. J Plast Surg Hand Surg 2012; 46:410.
- Okhovat JP, Alavi A. Lipedema: A Review of the Literature. Int J Low Extrem Wounds 2015; 14:262.
- Cohen MM Jr. Proteus syndrome: an update. Am J Med Genet C Semin Med Genet 2005; 137C:38.
- 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; 127:1571.
- Herbst KL. Rare adipose disorders (RADs) masquerading as obesity. Acta Pharmacol Sin 2012; 33:155.
- Child AH, Gordon KD, Sharpe P, et al. Lipedema: an inherited condition. Am J Med Genet A 2010; 152A:970.
- Stewart FW, Treves N. Classics in oncology: lymphangiosarcoma in postmastectomy lymphedema: a report of six cases in elephantiasis chirurgica. CA Cancer J Clin 1981; 31:284.
- Tomita K, Yokogawa A, Oda Y, Terahata S. Lymphangiosarcoma in postmastectomy lymphedema (Stewart-Treves syndrome): ultrastructural and immunohistologic characteristics. J Surg Oncol 1988; 38:275.
- Cozen W, Bernstein L, Wang F, et al. The risk of angiosarcoma following primary breast cancer. Br J Cancer 1999; 81:532.
- Weissleder H, Weissleder R. Lymphedema: evaluation of qualitative and quantitative lymphoscintigraphy in 238 patients. Radiology 1988; 167:729.
- Monnin-Delhom ED, Gallix BP, Achard C, et al. High resolution unenhanced computed tomography in patients with swollen legs. Lymphology 2002; 35:121.
- Position Statement of the National Lymphedema Network: The Diagnosis and Treatment of Lymphedema. http://www.lymphnet.org/pdfDocs/nlntreatment.pdf (Accessed on May 10, 2012).
- NORMAL LYMPHATIC SYSTEM AND LYMPHEDEMA
- - Primary
- - Secondary
- EPIDEMIOLOGY AND RISK FACTORS
- Cancer and cancer treatment
- - Lymphadenectomy
- - Radiation therapy
- Inflammatory disorders
- Hereditary syndromes
- CLINICAL FEATURES
- History and physical
- Extremity measurements
- - Limb circumference
- - Limb volume
- Clinical severity
- Differential diagnosis
- FURTHER EVALUATION
- Imaging the lymphatic system
- Genetic testing
- INFORMATION FOR PATIENTS