Dermatologic Manifestations of Lymphedema 

  • Author: Kathleen M Rossy, MD; Chief Editor: William D James, MD   more...
 
Updated: Aug 2, 2011
 

Background

Lymphedema is an abnormal collection of protein-rich fluid in the interstitium due to a defect in the lymphatic drainage network. Lymphedema most commonly affects the extremities, but it can involve the face, genitalia, or trunk. Numerous causes, both primary and secondary in nature, have been identified for this condition.

The primary causes are due to abnormalities in the lymphatic system that are present at birth, although not always clinically evident until later in life. The 3 primary categories of lymphedema (due to genetic factors) are congenital lymphedema (Milroy disease), lymphedema praecox (Meige disease), and lymphedema tarda. Primary lymphedema can also be associated with various cutaneous syndromes. Sheng et al identified a VEGFR3 gene mutation in a Chinese family with Milroy disease.[1]

Secondary lymphedema is due to an acquired obstruction or infiltration of the lymphatic system. Secondary lymphedema has a number of causes, which include malignancy, infection, obesity, trauma, congestive heart failure, portal hypertension, and therapeutic intervention. Despite the fact that the underlying etiologies of secondary lymphedema vary, clinical progression is similar and difficult to control.

Filariasis is a type of lymphedema that is the result of infection with parasites and occurs most commonly in Africa.[2]

Lymphedema is a progressive, deforming condition that is both physically and psychologically debilitating.

Angiosarcoma arising in an area of long-standing lymphedema is termed Stewart-Treves syndrome. Most cases of Stewart-Treves syndrome occur in the arm after surgery for breast cancer; however, sometimes angiosarcomas can arise in a chronically lymphedematous leg.

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Pathophysiology

Lymphedema is caused by a compromised lymphatic system that impedes and diminishes lymphatic return. In primary lymphedema, the failure is caused by congenital hypoplasia or aplasia of the peripheral lymphatics or by valvular incompetence. In secondary lymphedema, the lymphatic drainage is altered by an acquired blockade of the lymph nodes or by disruption of the local lymphatic channels because of (1) recurrent attacks of lymphangitis (a key type of this is cellulitis), (2) malignancy, (3) obesity, or (4) surgery. Whether the cause is acquired blockade of the lymph nodes or disruption of the local lymphatic channels, the result is a failure to drain protein-rich lymphatic fluid from the tissue, causing interstitial edema with swelling of the affected site.

Chronic lymphedema causes fissuring and impairment of the epidermis, allowing bacteria to enter and grow. With chronic lymphedema, the development of verrucous, cobblestone plaques, known as elephantiasis nostra verrucosa (ENV), can occur.

A theory has also been proposed that chronic lymphedema changes the protein composition of lymph in affected areas. A decrease in alpha-2 globulin levels and an increase in the albumin-to-globulin ratio have been reported. This change in proteins and the resultant slowing of transport to the lymphoid tissue has been suggested to play a role in diminishing the effectiveness of immune surveillance and prevents early detection of tumor-specific antigens. Additionally, repeat episodes of chronic ulceration and healing may stimulate the proliferation of keratinocytes, which may contribute to neoplastic transformation.

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Epidemiology

Frequency

United States

A common cause of lymphedema reported in the United States is surgical therapeutic intervention (postsurgical complication), most commonly following mastectomy with axillary dissection and radiation therapy for breast cancer. Although not reported as often as postmastectomy induced–lymphedema, obesity is one of the most common causes of lymphedema seen in practice today.

Among the primary causes of lymphedema, lymphedema praecox is the most commonly reported.

International

Worldwide, the most common cause of lymphedema is filariasis infection. More than 100 million people are affected in endemic areas worldwide.[3]

Mortality/Morbidity

The outcome for persons with lymphedema depends on its chronicity, the complications that result, and the underlying disease state that caused the lymphedema.

The development of angiosarcoma (ie, Stewart-Treves syndrome) in the setting of lymphedema is the most serious complication of secondary lymphedema. The mean survival rate, after treatment, is approximately 24 months. The 5-year survival rate is 10%.

Other complications that increase morbidity are the development of recurrent cellulitis, bacterial or fungal infections, and lymphangioadenitis.

Sex

Primary lymphedema is most common in females. Lymphedema praecox is the most common form and affects 1 in 100,000 girls and 1 in 400,000 boys.

Age

Secondary lymphedema can affect persons of any age group, and its onset is determined by the primary cause. Hereditary (primary) lymphedema can be divided into 3 groups based on the age of onset of clinical lymphedema, as follows:

  • Milroy disease is the familial form of lymphedema that usually manifests from birth to age 1 year.
  • Lymphedema praecox (ie, Meige disease) occurs from age 1-35 years. It most commonly occurs around menarche.
  • Lymphedema tarda manifests after age 35 years.
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Contributor Information and Disclosures
Author

Kathleen M Rossy, MD  Staff Physician, Department of Dermatology, New York Medical College, Metropolitan Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Noah S Scheinfeld, MD, JD, FAAD  Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, and New York Eye and Ear Infirmary; Private Practice

Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Optigenex Consulting fee Independent contractor

Specialty Editor Board

Abby S Van Voorhees, MD  Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania

Abby S Van Voorhees, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, National Psoriasis Foundation, Phi Beta Kappa, Sigma Xi, and Women's Dermatologic Society

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Merck Salary Management position; Abbott Honoraria Speaking and teaching; Amgen Honoraria Review panel membership; Centocor Honoraria Consulting; Leo Consulting; Merck None Other

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD  Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology

Disclosure: Lippincott Williams Wilkins Royalty Textbook editor; DLA Piper Consulting fee Consulting

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

References

  1. Sheng J, Zeng F, Li C, Liu J, Wang Q, Liu M. [Identification of VEGFR3 gene mutation in a Chinese family with autosomal dominant primary congenital lymphoedema.]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. Aug 2010;27(4):371-5. [Medline].

  2. Hoerauf A, Pfarr K, Mand S, Debrah AY, Specht S. Filariasis in Africa-treatment challenges and prospects. Clin Microbiol Infect. Jul 2011;7:977-85. [Medline].

  3. McPherson T, Persaud S, Singh S, et al. Interdigital lesions and frequency of acute dermatolymphangioadenitis in lymphoedema in a filariasis-endemic area. Br J Dermatol. May 2006;154(5):933-41. [Medline].

  4. Karg E, Bereczki C, Kovacs J, et al. Primary lymphoedema associated with xanthomatosis, vaginal lymphorrhoea and intestinal lymphangiectasia. Br J Dermatol. Jan 2002;146(1):134-7. [Medline].

  5. Johnson SM, Kincannon JM, Horn TD. Lymphedema-distichiasis syndrome: report of a case and review. Arch Dermatol. Mar 1999;135(3):347-8. [Medline].

  6. Samlaska CP. Congenital lymphedema and distichiasis. Pediatr Dermatol. Mar-Apr 2002;19(2):139-41. [Medline].

  7. Berry FB, Tamimi Y, Carle MV, Lehmann OJ, Walter MA. The establishment of a predictive mutational model of the forkhead domain through the analyses of FOXC2 missense mutations identified in patients with hereditary lymphedema with distichiasis. Hum Mol Genet. Sep 15 2005;14(18):2619-27. [Medline].

  8. Lu S, Tran TA, Jones DM, et al. Localized lymphedema (elephantiasis): a case series and review of the literature. J Cutan Pathol. Jan 2009;36(1):1-20. [Medline].

  9. Fukuda H, Saito R. Verruciform xanthoma in close association with isolated epidermolytic acanthoma: a case report and review of the Japanese dermatological literature. J Dermatol. Jun 2005;32(6):464-8. [Medline].

  10. Wu JJ, Wagner AM. Verruciform xanthoma in association with milroy disease and leaky capillary syndrome. Pediatr Dermatol. Jan-Feb 2003;20(1):44-7. [Medline].

  11. Wu YH, Hsiao PF, Lin YC. Verruciform xanthoma-like phenomenon in seborrheic keratosis. J Cutan Pathol. May 2006;33(5):373-7. [Medline].

  12. Chavda LK, Vaidya RA, Vaidya AD. Yellow nail syndrome: missed diagnosis of a rare syndrome. J Assoc Physicians India. Apr 2011;59:258-60. [Medline].

  13. Irrthum A, Karkkainen MJ, Devriendt K, Alitalo K, Vikkula M. Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am J Hum Genet. Aug 2000;67(2):295-301. [Medline].

  14. Karkkainen MJ, Ferrell RE, Lawrence EC, et al. Missense mutations interfere with VEGFR-3 signalling in primary lymphoedema. Nat Genet. Jun 2000;25(2):153-9. [Medline].

  15. Salim A, Pike M, Turner R, Mortimer P. Lymphedema: an additional finding in the charge association. Pediatr Dermatol. Nov-Dec 2003;20(6):547-8. [Medline].

  16. Butler DF, Malouf PJ, Batz RC, Stetson CL. Acquired lymphedema of the hand due to herpes simplex virus type 2. Arch Dermatol. Sep 1999;135(9):1125-6. [Medline].

  17. Pereira de Godoy JM, Azoubel LM, de Fatima Guerreiro de Godoy M. Intensive treatment of leg lymphedema. Indian J Dermatol. Apr-Jun 2010;55(2):144-7. [Medline]. [Full Text].

  18. Beninson J, Redmond MJ. Mossy leg--an unusual therapeutic success. Angiology. Sep 1986;37(9):642-6. [Medline].

  19. Lerner R. What's New in Lymphedema Therapy in America?. Int J Angiol. May 1998;7(3):191-6. [Medline].

  20. Olszewski WL, Jamal S, Manokaran G, Tripathi FM, Zaleska M, Stelmach E. The effectiveness of long-acting penicillin (penidur) in preventing recurrences of dermatolymphangioadenitis(DLA) and controlling skin, deep tissues, and lymph bacterial flora in patients with "filarial" lymphedema. Lymphology. Jun 2005;38(2):66-80. [Medline].

  21. Debrah AY, Mand S, Marfo-Debrekyei Y, et al. Macrofilaricidal effect of 4 weeks of treatment with doxycycline on Wuchereria bancrofti. Trop Med Int Health. Dec 2007;12(12):1433-41. [Medline].

  22. Yongyuth P, Koyadun S, Jaturabundit N, Sampuch A, Bhumiratana A. Efficacy of a single-dose treatment with 300 mg diethylcarbamazine and a combination of 400 mg albendazole in reduction of Wuchereria bancrofti antigenemia and concomitant geohelminths in Myanmar migrants in Southern Thailand. J Med Assoc Thai. Aug 2006;89(8):1237-48. [Medline].

  23. Feind-Koopmans A, van de Kerkhof PC. Successful treatment of papillomatosis cutis lymphostatica with acitretin. Acta Derm Venereol. Sep 1995;75(5):411. [Medline].

  24. Boyd J, Sloan S, Meffert J. Elephantiasis nostrum verrucosa of the abdomen: clinical results with tazarotene. J Drugs Dermatol. Jul-Aug 2004;3(4):446-8. [Medline].

  25. Warren AG, Brorson H, Borud LJ, Slavin SA. Lymphedema: a comprehensive review. Ann Plast Surg. Oct 2007;59(4):464-72. [Medline].

  26. King B. Toe bandaging to prevent and manage oedema. Nurs Times. Oct 23-29 2007;103(43):44, 47. [Medline].

  27. Dürr HR, Pellengahr C, Nerlich A, Baur A, Maier M, Jansson V. Stewart-Treves syndrome as a rare complication of a hereditary lymphedema. Vasa. Feb 2004;33(1):42-5. [Medline].

  28. Chopra S, Ors F, Bergin D. MRI of angiosarcoma associated with chronic lymphoedema: Stewart Treves syndrome. Br J Radiol. Dec 2007;80(960):e310-3. [Medline].

  29. Aguiar Bujanda D, Camacho Galan R, Bastida Inarrea J, et al. Angiosarcoma of the abdominal wall after dermolipectomy in a morbidly obese man. A rare form of presentation of Stewart-Treves syndrome. Eur J Dermatol. May-Jun 2006;16(3):290-2. [Medline].

  30. Azurdia RM, Guerin DM, Verbov JL. Chronic lymphoedema and angiosarcoma. Clin Exp Dermatol. Jul 1999;24(4):270-2. [Medline].

  31. Komorowski AL, Wysocki WM, Mitus J. Angiosarcoma in a chronically lymphedematous leg: an unusual presentation of Stewart-Treves syndrome. South Med J. Aug 2003;96(8):807-8. [Medline].

  32. Shehan JM, Ahmed I. Angiosarcoma arising in a lymphedematous abdominal pannus with histologic features reminiscent of Kaposis sarcoma: report of a case and review of the literature. Int J Dermatol. May 2006;45(5):499-503. [Medline].

  33. Atillasoy ES, Santoro A, Weinberg JM. Lymphoedema associated with Kaposi sarcoma. J Eur Acad Dermatol Venereol. Jul 2001;15(4):364-5. [Medline].

  34. Torres-Paoli D, Sanchez JL. Primary cutaneous B-cell lymphoma of the leg in a chronic lymphedematous extremity. Am J Dermatopathol. Jun 2000;22(3):257-60. [Medline].

  35. 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. Nov 2006;103(2):714-8. [Medline].

  36. Bilen BT, Gurlek A, Alaybeyoglu N, Celik M, Aydin NE. Epidermoid carcinoma arising in chronic lymphedema. Eur J Surg Oncol. Oct 2003;29(8):697-8. [Medline].

  37. Devillers C, Vanhooteghem O, de la Brassinne M. [Lymphedema and cutaneous diseases]. Rev Med Suisse. Dec 5 2007;3(136):2802-5. [Medline].

  38. Goshtasby P, Dawson J, Agarwal N. Pseudosarcoma: massive localized lymphedema of the morbidly obese. Obes Surg. Jan 2006;16(1):88-93. [Medline].

  39. Hanna D, Cloutier R, Lapointe R, Desgagne A. Abdominal elephantiasis: a case report. J Cutan Med Surg. Jul-Aug 2004;8(4):229-32. [Medline].

  40. Iwao F, Sato-Matsumura KC, Sawamura D, Shimizu H. Elephantiasis nostras verrucosa successfully treated by surgical debridement. Dermatol Surg. Jun 2004;30(6):939-41. [Medline].

  41. Perera M, Whitehead M, Molyneux D, Weerasooriya M, Gunatilleke G. Neglected patients with a neglected disease? A qualitative study of lymphatic filariasis. PLoS Negl Trop Dis. Nov 21 2007;1(2):e128. [Medline].

  42. Rongioletti F, Gambini C, Parodi A, Cannata G, Rebora A. Mossy leg with eccrine syringofibroadenomatous hyperplasia resembling multiple eccrine syringofibroadenoma. Clin Exp Dermatol. Nov 1996;21(6):454-6. [Medline].

  43. Sanders LJ, Slomsky JM, Burger-Caplan C. Elephantiasis nostras: an eight-year observation of progressive nonfilarial elephantiasis of the lower extremity. Cutis. Nov 1988;42(5):406-11. [Medline].

  44. Scheinfeld NS. Obesity and dermatology. Clin Dermatol. Jul-Aug 2004;22(4):303-9. [Medline].

  45. Schissel DJ, Hivnor C, Elston DM. Elephantiasis nostras verrucosa. Cutis. Aug 1998;62(2):77-80. [Medline].

  46. Tiwari A, Cheng KS, Button M, Myint F, Hamilton G. Differential diagnosis, investigation, and current treatment of lower limb lymphedema. Arch Surg. Feb 2003;138(2):152-61. [Medline].

  47. Tiwari A, Myint F, Hamilton G. Management of lower limb lymphoedema in the United Kingdom. Eur J Vasc Endovasc Surg. Mar 2006;31(3):311-5. [Medline].

 
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Lymphedema in a patient with hypertension, diabetes, and impaired cardiac function.
Morbidly obese patient with lymphedema.
 
 
 
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