4 Lymfoedeem

  • R.J. Damstra


Lymfoedeem is een veelvoorkomende aandoening die gedefinieerd wordt als zwelling van een gedeelte van het lichaam veroorzaakt door accumulatie van interstitieel vocht in het suprafasciale compartiment, als gevolg van insufficiëntie van het lymfesysteem. Lymfoedeem kan zich geleidelijk ontwikkelen en uiteindelijk leiden tot onherstelbare schade, zoals verharding in het bindweefsel en hyperkeratose van de huid. Klachten van lymfoedeem nemen in de loop van het leven toe door het van nature progressieve karakter van de ziekte. Onbehandeld kan lymfoedeem op den duur aanleiding geven tot ernstige en invaliderende complicaties.


  1. 1 Levick JR. Revision of the Starling principle: new views of tissue fluid balance. J Physiol (London) 2004;557:704.Google Scholar
  2. 2 Mortimer Ps, Levick JR. Chronic peripheral oedema: the critical role of the lymphatic system. Clinical medicine (London) 2004;4(5):448-453.Google Scholar
  3. 3 Levick JR. Circulation of fluid between plasma, interstitium and lymph. In: Levick JR ed. An introduction to cardiovascular physiology. Londen, Arnold 2003.Google Scholar
  4. 4 Aukland K, Reed RK. Interstitial-lymphatic mechanisms in the control of extracellular volume. Phys Reviews 1993;73:1-78.Google Scholar
  5. 5 Angeli V, Randolph G. Inflammation, lymphatic function and dendritic cell migration. Lymphat Res Biol 2006;4:217-228.PubMedCrossRefGoogle Scholar
  6. 6 Tso P, Balint JA. Formation and transport of chylomicrons by enterocytes to the lymphatics. Am J Physiol 1986;250:715-726.Google Scholar
  7. 7 Levick JR, Michell CC. Microvascular fluid exchange and the revised Starling principle. Cardiovascular Research 2010;87(2):198-210.PubMedCrossRefGoogle Scholar
  8. 8 Connell F, Brice G, Jeffery S, Keeley V, Mortimer PS, Mansour S. A new classification system for primary lymphatic dysplasias based on phenotype. Clin Genet 2010;77(5):438-452.PubMedCrossRefGoogle Scholar
  9. 9 Yamashita JK. Differentiation of arterial, venous and lymphatic endothelial cells from vascular progenitors. Trends Cardiovasc Med 2007;17:59-63.PubMedCrossRefGoogle Scholar
  10. 10 Petrova T, Karpanen T, Normen C et al. Mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med 2004;10:974-981.PubMedCrossRefGoogle Scholar
  11. 11 OMIM®, online Mendelian Inheritance of Man. Johns Hopkins University: Scholar
  12. 12 Browse N, Burnand K, Mortimer PS. Diseases of the lymphatics. Londen, Arnold 2003;Chap 5:102-108.Google Scholar
  13. 13 Damstra RJ. Diagnostic and therapeutical aspects of lymphedema. Bonn, Rabe Verlag Medical publishing 2010. ISBN 978-3-940654-11-3.Google Scholar
  14. 14 Ferrell RE, Kimak MA, Lawrence EC, Finegold DN. Candidate gene analysis in primary lympedema. Lymphat Res Biol 2008;6(2):69-76.PubMedCrossRefGoogle Scholar
  15. 15 Alders M, Hogan BM, Gjini E, Salehi F, Al-Gazali L, Hennekam RC et al. Mutations in CCBE1 cause generalized lymph vessel dysplsia in humans. Nat Genet 2009;41(12):1272-1274.PubMedCrossRefGoogle Scholar
  16. 16 Van Der Burgt. Review: Noonan syndrome. Orphanet J Rare Dis 2007;2:4-6.Google Scholar
  17. 17 Dupuis-Girod S, Corradini N, Hadj-Rabia S et al. Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia and immunodeficiency in a boy and incontinentia pigmenti in his mother. Pediatrics 2002;109:97.CrossRefGoogle Scholar
  18. 18 Van Steensel MAM, van Geel M, Schrander-Stumpel C et al. Lymphedema, Cardiac Septal Defects and Characteristic Facies: Possible New Case of Irons-Bianchi Syndrome. Am J Med Genet 2007;143A:2448-2451.PubMedCrossRefGoogle Scholar
  19. 19 Mansour S, Connell F, Steward C, Ostergaard P, Brice G et al. Emberger syndrome-primary lymphedema with myelodysplasia: report of seven new cases. Am J Med Genet 2010;152A(9):2287-2296.PubMedCrossRefGoogle Scholar
  20. 20 Damstra RJ, Jagtman EA, Steijlen PM. Cancer related secondary lymphedema due to cutaneous lymphangitis carcinomatosa: Clinical presentations and review of literature. Eur J Cancer Care 2010;19(5):669-675.CrossRefGoogle Scholar
  21. 21 Reading C. Secretan’s syndrome. Hard edema at the dorsum of the hand. Plast Reconstr Surg 1900;65:182-187.CrossRefGoogle Scholar
  22. 22 Consensus document of the International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema. Lymphology 2003;36:84-91.Google Scholar
  23. 23 Stemmer R. Ein klinisches Zeichen zur Fruh- und Differentialdiagnose des Lymphodems. VASA 1976;5:261-262.PubMedGoogle Scholar
  24. 24 Stemmer R. Stemmer”s sign: possibilities and limits of clinical diagnosis of Lymphedema. Wien Med Wochenschr 1999;149:85-86.Google Scholar
  25. 25 Irrthum A, Karkkainen MJ, Devriendt K et al. Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am J Hum Genet 2000;67:295-301.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26 Brice G, Child AH, Evans A et al. Milroy disease and the VEGFR3 mutation phenotype. J Med Genet 2005;42:98-102.Google Scholar
  27. 27 Connell FC, Ostergaard P, Carver C et al. Lymphoedema Consortium. Analysis of the coding regions of VEGFR3 and VEGFC in Milroy disease and other primary lymphoedemas. Hum Genet 2009;124:625-631.Google Scholar
  28. 28 Erickson RP, Dagenais SL, Caulder MS et al. Clinical heterogenity in lymphoema-distichiasis with FOXC@ truncating mutations. J Med Genet 2001;38:761-766.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29 Mellor RH, Brice G, Stanton AWB et al. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limbs. Circulation 2007;115:1912-1920.Google Scholar
  30. 30 Petrova TV, Karpanen T, Normen C et al. Defective valves and abnormal mural cell recruitment underlie lymphatic vascular failure in lymphedema distichiasis. Nat Med 2004;10:974-981.Google Scholar
  31. 31 Connell FC, Kalidas K, Ostergaard P et al. Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia. Hum Genet 2010;127(2):231-241.PubMedCrossRefGoogle Scholar
  32. 32 Hennekam RC, Geerdink RA, Hamel BC, Hennekam FA, Kraus P, Rammeloo JA, Tillemans AA. Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. Am J Med Genet 1989;34:593-600.Google Scholar
  33. 33 Irrthum A, Devriendt K, Chitayat D et al. Mutations in the Transcription Factor Gene SOX18 Underlie Recessive and Dominant Forms of Hypotrichosis-Lymphedema-Telangiectasia. Am J Hum Genet 2003;72:1470-1478.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34 Borroni G, Larizza D, Vignati G, Zaccone C, Zanetta R, Vignoli GP, Brazelli V, Bobba C, Rabbiosi G. The dermatological spectrum of the Turner syndrome. Dermatol Venereol 1994;3:334-340.Google Scholar
  35. 35 Minikin W, Frank SB, Wolman SR et al. Lymphedema in Noonan’s syndrome. Int J Dermatol 1974;13:179-183.Google Scholar
  36. 36 Bloom D. Hereditary lymphedema (Nonne-Milroy-Meige): Report of family with hereditary lymphedema associated with ptosis of the eyelids in several generations. New York Med J 1941;41:856-863.Google Scholar
  37. 37 Lee BB, Laredo J, Lee TS, Huh S, Neville R. Terminology and classification of congenital vascular malformations. Phlebology/Venous Forum of the Royal Society of Medicine 2007;22(6):249-252.Google Scholar
  38. 38 Goodman RM. Familial lymphedema of Meige’s type. Am J Med 1962;32:651-656.CrossRefGoogle Scholar
  39. 39 Stanton AWB, Modi S, Bennett Britton T et al. Lymphatic drainage in the muscle and subcutis of the arm after breast cancer treatment. Breast Cancer Res Treat 2008: Epub ahead:DOI 10.1007/s10549-008-0259-z.Google Scholar
  40. 40 Damstra RJ, van Steensel MAM, Boomsma H et al. Erysipelas as a sign of subclinical primary lymphedema: a prospective quantitative scintigraphic study of 40 patients with unilateral erysipelas of the leg. Br J dermatol 2008;158:1210-1215.Google Scholar
  41. 41 Padmasiri EA, Montresor A, Biswas G et al. Controlling lymphatic filariasis and solid-transmitted helminthiasis together in South Asia: opportunities and challenges. Trans R Soc Trop Med Hyg 2006;100:807-810.PubMedCrossRefGoogle Scholar
  42. 42 World Health Organisation Global Programme to Eliminate Lymphatic Filariasis. Weekly Epidemiological Record 2006;22:221-232.Google Scholar
  43. 43 Davey G, Tekola F. Newport MJ. Podoconiosis: non-infectious geochemical elephantiasis. Trans R Soc Trop Med Hyg 2007;101:1175-1180.PubMedCrossRefGoogle Scholar
  44. 44 Fife CE, Carter MJ. Lymphedema in the morbidly obese patient: unique challenges in a unique population. Ostomy Wound Manage 2008;54(1):44-56.Google Scholar
  45. 45 Vanelli A, Battaglia L, Poiasina E et al. Pelvic lymphedema: Truth or fiction? Med Hypotheses 2009;72:267-270.CrossRefGoogle Scholar
  46. 46 Neumann HAM, Veraart JCJM. Morphological and functional skin changes in postthrombotic syndrome. Wien Med Wochenschr 1994;144:204-206.Google Scholar
  47. 47 Milligan A, Graham-Brown RAC, Burns DA et al. Prolidase deficiency. A case report and literature review. Br J Dermatol 1989;121:405-409.Google Scholar
  48. 48 Camacho-Martinez F, Winkelmann RK. Solid facial edema as a manifestation of acne. J Am Acad Dermatol 1990;22:129-130.Google Scholar
  49. 49 Borrie P, Taylor GW. Lymphoedema presenting in the skin department. Br J Dermatol 1962;74:403-413.CrossRefGoogle Scholar
  50. 50 Holze E, Jansen T, Plewig G. Morbus Morbihan: Chronisch persistierendes Erythem und Odem des Gesichts. Hautarzt 1995;46:796-798.Google Scholar
  51. 51 Nozicka Z. Endovasal granulomatous lymphangitis as a pathogenic factor in cheilitis granulomatosa. J Oral Pathol 1985;14:363-365.PubMedCrossRefGoogle Scholar
  52. 52 White MI, Smart LM, MacGregor DM, Rayner CR, Smith FW. Recurrent facial edema associated with a siliconerubber implant. Br J Dermatol 1991;125:183-185.Google Scholar
  53. 53 Saha M, Edmonds E, Martin J, Bunker CB. Penile lymphoedema in association with asymptomatic Crohn’s disease. Clinical and Experimental Dermatology 2009;34(1):88-90.Google Scholar
  54. 54 Levick JR, Mortimer PS. Fluid ‘Balance’ between Microcirculation and Interstitium in Skin and Other Tissues: Revision of the Classical Filtration-Reabsorption Scheme. In: Messmer K ed. Microcirculation in Chronic Venous Insufficiency. Prog Appl Microcirc. Karger, Basel 1999;23:42-62.Google Scholar
  55. 55 Chamourard P, Nehme-Scuster H, Simler J-M, Finck G, Baumann R, Pasquali J-L. Videocapsule endoscopy is useful for the diagnosis of intestinal lymphangiectasia. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 2006;38(9):699-703.Google Scholar
  56. 56 Kitchen ND, Hocken DB, Greenhalgh RM, Kaplan DK. Use of the Denver pleuroperitoneal shunt in the treatment of chylothorax secondary to filariasis. Thorax 1991;46(2):144-145.Google Scholar
  57. 57 Makino Y, Shimanuki Y, Fujiwara N, Morio Y, Sato K, Yoshimoto J, Gunji Y, Suzuki T, Sasaki S, Iwase A, Kawasaki S, Takahashi K, Seyama K. Peritoneovenous shunting for intractable chylous ascites complicated with lymphangioleiomyomatosis. Intern Med 2008;47(4):281-285.Google Scholar
  58. 58 Barker DJP, Rose G. Epidemiology in Medical Pract 4th ed. Churchill Livingstone, Edinburgh 1990.Google Scholar
  59. 59 Smeltzer DM, Gunnar B, Schirger A. Primary lymphedema in children and adolescents: a follow-up study and review. Pediatrics 1985;76(2):206-218.Google Scholar
  60. 60 Greenlee R, Hoyme H, Witte M et al. Developmental disorders of the lymphatic system. Lymphology 1993;26:156-158.Google Scholar
  61. 61 Dale RF. The inheritance of primary lymphoedema. J Med Genet 1985;22(4):274-278.Google Scholar
  62. 62 Scharz U. Die Hauftigkeit des primairen Lymphodems. Eine epidemiologische Studie an uber 100 probanden. Med Lymphol 1990;1:29-34.Google Scholar
  63. 63 Pannier F, Hofmann B, Stang A et al. Prevalence of Stemmer’s sign in the general population. Results from the Bonn Vein Study. Phlebology 2007;36:289-292.Google Scholar
  64. 64 Moffath CJ, Franks PJ, Doherty DC et al. Lymphoedema: an underestimated health problem. Quarterly J Med 2003;96:731-738.CrossRefGoogle Scholar
  65. 65 Kwan W, Jackson J, Weir LM et al. Chronic Arm Morbidity After Curative Breast Cancer Treatment: Prevalence and Impact on Quality of Life. J Clin Oncol 2002;20:4242-4248.Google Scholar
  66. 66 Paskett ED, Naughton MJ, McCoy P et al. The epidemiology of arm and hand swelling in pre-menopausal breast cancer survivors. Cancer Epidemiol Biomarkers Prev 2007;16:775-782.Google Scholar
  67. 67 Meeske KA, Sullivan-Halley J, Smith AW et al. Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women. Breast Cancer Res Treat 2009;113:383-391.Google Scholar
  68. 68 Sener SF, Winchester DJ, Martz CH et al. Lymphedema after sentinel lymphadenectomie for breast carcinoma. Cancer 2001;92:748-752.Google Scholar
  69. 69 Wilke LG, Mccall LM, Posther E et al. Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol 2006;13:491-500.Google Scholar
  70. 70 Lee TS, Kilbreath SL, Refshauge KM et al. Prognosis of the upper limb following surgery and radiation for breast cancer. Breast Cancer Res Treat 2008;110:19-37.Google Scholar
  71. 71 Beesley V, Janda M, Eakin E et al. Lymphedema after gynecological cancer treatment: prevalence, correlates and supportive care needs. Cancer 2007;109:2607-2614.Google Scholar
  72. 72 Gaarenstroom KN, Kenter GG, Trimbos JB et al. Postoperative complications after vulvectomy and inguinofemoral lymphadectomy using separate groin incisions. Int J Gynecol Cancer 2003;13:522-527.PubMedCrossRefGoogle Scholar
  73. 73 Catalona W. Modified inguinal lymphadenectomy for carcinoma of the penis with preservation of saphenous veins: technique and preliminary results. J Urol 1988;140:306-310.Google Scholar
  74. 74 Rempelakos A, Bastas E, Lymperakis CH et al. Carcinoma of the penis: experience from 360 cases. J Buon 2004;9:51-55.Google Scholar
  75. 75 Lieskovsky G, Skinner DG Weisenburger T. Pelvic lymphadectomy in the management of carcinoma of the prostate. J Urol 1980;124:635-638.Google Scholar
  76. 76 Partsch. Practical aspects of indirect lymphography and lymphoscintigraphy. Lymphatic research and biology 2003;1(1):73-74.Google Scholar
  77. 77 Franzeck UK, Spiegell, Fischer M et al. Combined physical therapy for lymphoedema evaluated by fluorescence microlymphography and lymph capillary pressure measurements. J Vasc Res 1997;34(4):306-311.Google Scholar
  78. 78 Weissleder H, Weissleder R. Lymphedema: evaluation of qualitative and quantitative lymphoscintigraphy in 238 patients. Radiology 1988:167(3):729-735.Google Scholar
  79. 79 Szuba A, Shin WS, Strauss HW, Rockson S. The third circulation: radionuclide lymphoscintigraphy in the evaluation of lymphedema. J Nucl Med 2003;44(1):43-57.Google Scholar
  80. 80 Barrett T, Choyke PL, Kobayashi H. Imaging of the lymphatic system: new horizons. Contrast Media Mol Imaging 2006;1(6):230-245.PubMedCrossRefGoogle Scholar
  81. 81 Lohrmann C, Foeldi E, Speck O, Langer M. High-resolution MR Lymphangiography in patients with primary and secondary lymphedema. American journal of roentgenology 2006;187(2):556-561.Google Scholar
  82. 82 Sitzia J. Volume measurement in lymphedema treatment examination of formulae. Eur J Cancer Care 1995;4:11-16.Google Scholar
  83. 83 Stanton AWB, Northfield JW, Holroyd B, Mortimer PS, Levick JR. Validation of an optoelectric limb volumeter (Perometer). Lymphology 1997;30(2):77-97.Google Scholar
  84. 84 Ryttov N, Holm V, Qvist N, Blichert-Toft M. Influence of adjuvant irradiation on the development of late arm mastectomy for carcinoma of the breast. Acta Oncologica 1988;27:667-670.Google Scholar
  85. 85 Farncombe M, Daniels G, Cross L. Lymphedema: the seemingly forgotten complication. J Pain Sympt Manage 1994;9:269-276.CrossRefGoogle Scholar
  86. 86 Lin PP, Allison DC, Wainstock J, Miller KD, Dooley WC et al. Impact of axillary lymph node dissection on the therapy of breastcancer patients. J Clin Oncol 1993;11:1136-1144.Google Scholar
  87. 87 Herpertz U. Messung und Dokumentation von Odemen. Lymphology 1994;18:24-30.Google Scholar
  88. 88 Kettle JH, Ruindle FF, Oddie TH. Measurement of upper limb volumes: a clinical method. Aust N Z J Surg 1958;27:263-270.Google Scholar
  89. 89 Damstra RJ, Glazenburg E, Hol W. The validation of the inverse water volumetry: New gold standard for arm volume measurement. Breast Cancer Res Treat 2006;99(3):267-273.Google Scholar
  90. 90 Aaronson NK, Muller M, Cohen PD, Essink-Bot ML, Fekkes M, Sanderman R, Sprangers MA, te Velde A, Verrips E. Translation, validation and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations. J Clin Epidemiol 1998;51(11):1055-1068.Google Scholar
  91. 91 Rockson SG, Miller LT, Senie R, Brennan MJ et al. American Cancer Society Lymphedema Workshop. Workgroup III: Diagnosis and management of lymphedema. Cancer 1998;83(12 Suppl American);2882-2885.Google Scholar
  92. 92 Damstra RJ, Voesten HGJ, van Schelven D et al. Lymphatic Venous Anastosmosis (LVA) for Treatment of Secondary Arm Lymphedema. A Prospective Study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat 2009;113:199-206.Google Scholar
  93. 93 Loprinzi CL, Kugler JW, Sloan JA et al. Lack of effect of coumarin in women with lymphedema after treatment for breast cancer. N Engl J Med 1999;340:346-350.PubMedCrossRefGoogle Scholar
  94. 94 Mortimer PS, Badger C, Clarke I et al. A double blind randomized, parallel-group, placebo-controlled trial of O-(beta-hydroxyethyl)-rutosides in chronic arm edema resulting from breast cancer treatment. Phlebology 1995;10:51-55.Google Scholar
  95. 95 Casley-Smith JR. There are many benzopyrones for lymphedema. Lymphology 1997;30:38-39.Google Scholar
  96. 96 Carrati CJ, Anderson SN, Gannon BJ et al. Treatment of postmastectomy lymphedema with low-level laser therapy: a double blind, placebo-controlled trial. Cancer 2003;98:1114-1122.Google Scholar
  97. 97 Moseley AL, Esplin M, Piller NB et al. Endermologie® with and without compression therapy: a new treatment option for secondary arm lymphedema. Lymphology 2007;40:129-137.Google Scholar
  98. 98 Damstra RJ, Kaandorp CJE. CBO-richtlijn Lymfoedeem. Ned Tijdschr Geneesk 2003;147:648-652.Google Scholar
  99. 99 Morgan P, Doherty D, Moffatt C et al. The National Lymphoedema Framework Project. Nurs Times 2005;101:48.Google Scholar


  1. Afbeeldingen: dr. R.J. Damstra.Google Scholar

Copyright information

© Bohn Stafleu van Loghum, onderdeel van Springer Uitgeverij 2011

Authors and Affiliations

  • R.J. Damstra

There are no affiliations available

Personalised recommendations