Editing Lymphedema (section)

==Causes and risk factors==
Lymphedema may be inherited (primary) or caused by injury to the lymphatic vessels (secondary).<ref name="Visual Guide to Lymphedema">{{cite web|url=https://www.webmd.com/breast-cancer/ss/slideshow-lymphedema|title=A Visual Guide to Lymphedema|website=WebMD|access-date=7 July 2021|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709190953/https://www.webmd.com/breast-cancer/ss/slideshow-lymphedema|url-status=live}}</ref> There are also risk factors that may increase one's risk of developing lymphedema such as old age, being overweight or [[Obesity|obese]], and having [[Rheumatoid arthritis|rheumatic]] or [[psoriatic arthritis]].<ref>{{Cite web |title=Lymphedema – Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/lymphedema/symptoms-causes/syc-20374682 |access-date=2023-08-02 |website=Mayo Clinic |language=en |archive-date=2023-08-01 |archive-url=https://web.archive.org/web/20230801182000/https://www.mayoclinic.org/diseases-conditions/lymphedema/symptoms-causes/syc-20374682 |url-status=live }}</ref>

===Lymph node damage===
Lymphedema is most commonly seen after [[lymphadenectomy|lymph node dissection]], [[surgery]] or [[radiation therapy]] for the treatment of cancer, most notably [[breast cancer]]. In many patients the condition does not develop until months or even years after therapy has concluded.{{Medical citation needed|date=September 2023}} Lymphedema may also be associated with [[accident]]s or certain diseases or conditions that may inhibit the lymphatic system from functioning properly.<ref name="grada-2017" /> It can also be caused by damage to the lymphatic system from infections such as [[cellulitis]].<ref>{{Cite web |date=2017-10-20 |title=Lymphoedema – Causes |url=https://www.nhs.uk/conditions/lymphoedema/causes/ |access-date=2022-06-15 |website=nhs.uk |language=en |archive-date=2022-10-21 |archive-url=https://web.archive.org/web/20221021013232/https://www.nhs.uk/conditions/lymphoedema/causes/ |url-status=live }}</ref> In tropical areas of the world where parasitic filarial worms are endemic, a common cause of secondary lymphedema is [[filariasis]].<ref>{{Cite journal |last=Shenoy |first=R. K. |date=2008-09-20 |title=Clinical and Pathological Aspects of Filarial Lymphedema and Its Management |url=http://www.parasitol.kr/journal/view.php?number=166 |journal=The Korean Journal of Parasitology |language=English |volume=46 |issue=3 |pages=119–125 |doi=10.3347/kjp.2008.46.3.119 |pmid=18830049 |pmc=2553332 |issn=0023-4001 |access-date=2022-06-15 |archive-date=2021-12-02 |archive-url=https://web.archive.org/web/20211202121527/https://www.parasitol.kr/journal/view.php?number=166 |url-status=live }}</ref>

Primary lymphedema may be congenital or may arise sporadically. Multiple syndromes are associated with primary lymphedema, including [[Turner syndrome]], [[Milroy's disease]], and [[Klippel–Trénaunay syndrome]]. In these syndromes it may occur as a result of absent or malformed lymph nodes or lymphatic channels. Lymphedema can be present at birth, develop at the onset of puberty (praecox), or not become apparent for many years into adulthood (tarda). In men, lower-limb primary lymphedema is most common, occurring in one or both legs. Some cases of lymphedema may be associated with other vascular abnormalities.<ref name="grada-2017" />{{Citation needed|date=September 2023|reason=This paragraph needs more medical citations}}

Secondary lymphedema affects both men and women, and, in Western countries, is most commonly due to cancer treatment.<ref name="Brorson2008">{{cite journal | vauthors = Brorson H, Ohlin K, Olsson G, Svensson B, Svensson H | title = Controlled compression and liposuction treatment for lower extremity lymphedema | journal = Lymphology | volume = 41 | issue = 2 | pages = 52–63 | date = June 2008 | pmid = 18720912}}</ref> In women, it is most prevalent in an upper limb after breast cancer surgery, especially [[axillary lymph node]] dissection,<ref>{{cite book|author1=Jeannie Burt|author2=Gwen White|title=Lymphedema: A Breast Cancer Patient's Guide to Prevention and Healing|url=https://archive.org/details/lymphedemabreast00burt|url-access=registration|date=1 January 2005|publisher=Hunter House|isbn=978-0-89793-458-9|pages=[https://archive.org/details/lymphedemabreast00burt/page/9 9]}}</ref> and occurs on the same side of the body as the surgery. Breast and trunk lymphedema can also occur but go unrecognised as there is swelling in the area after surgery, and its symptoms ([[peau d'orange]] and an inverted nipple) can be confused with post surgery [[fat necrosis]].<ref>{{cite web|url=http://www.nhs.uk/ipgmedia/national/Lymphoedema+Support+Network/Assets/BreastandTruncalOedemaLSN8pages.pdf|title=IPS retired|first=NHS|last=Choices|website=nhs.uk|access-date=9 May 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828152826/https://www.nhs.uk/retired/pages/ips.aspx|url-status=dead}}</ref>  Between 38 and 89% of breast cancer patients have lymphedema due to axillary lymph node dissection or radiation.<ref name="Brorson2008" /><ref>{{cite journal | vauthors = Kissin MW, Querci della Rovere G, Easton D, Westbury G | title = Risk of lymphoedema following the treatment of breast cancer | journal = The British Journal of Surgery | volume = 73 | issue = 7 | pages = 580–584 | date = July 1986 | pmid = 3730795 | doi = 10.1002/bjs.1800730723 | s2cid = 25777064}}</ref><ref>{{cite journal | vauthors = Segerström K, Bjerle P, Graffman S, Nyström A | title = Factors that influence the incidence of brachial oedema after treatment of breast cancer | journal = Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery | volume = 26 | issue = 2 | pages = 223–227 | year = 1992 | pmid = 1411352 | doi = 10.3109/02844319209016016}}</ref> Unilateral lymphedema of a lower limb occurs in up to 41% of patients after gynecologic cancer.<ref name="Brorson2008" /><ref>{{cite journal | vauthors = Werngren-Elgström M, Lidman D | title = Lymphoedema of the lower extremities after surgery and radiotherapy for cancer of the cervix | journal = Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery | volume = 28 | issue = 4 | pages = 289–293 | date = December 1994 | pmid = 7899840 | doi = 10.3109/02844319409022014}}</ref> For men treated for prostate cancer, a 5-66% incidence has been reported, with the incidence rate depending on whether staging or radical removal of lymph glands was done in addition to radiotherapy.<ref name="Brorson2008" /><ref>{{cite journal | vauthors = Pilepich MV, Asbell SO, Mulholland GS, Pajak T | title = Surgical staging in carcinoma of the prostate: the RTOG experience. Radiation Therapy Oncology Group | journal = The Prostate | volume = 5 | issue = 5 | pages = 471–476 | year = 1984 | pmid = 6483687 | doi = 10.1002/pros.2990050502 | s2cid = 36177502}}</ref><ref>{{cite journal | vauthors = Pilepich MV, Krall J, George FW, Asbell SO, Plenk HD, Johnson RJ, Stetz J, Zinninger M, Walz BJ | title = Treatment-related morbidity in phase III RTOG studies of extended-field irradiation for carcinoma of the prostate | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 10 | issue = 10 | pages = 1861–1867 | date = October 1984 | pmid = 6386761 | doi = 10.1016/0360-3016(84)90263-3}}</ref>

Head and neck lymphedema can be caused by surgery or radiation therapy for tongue or throat cancer. It may also occur in the lower limbs or groin after surgery for colon, ovarian or uterine cancer, if removal of lymph nodes or radiation therapy is required. Surgery or treatment for prostate, colon and testicular cancers may result in secondary lymphedema, particularly when lymph nodes have been removed or damaged.{{medical citation needed|date=September 2023}}

The onset of secondary lymphedema in patients who have had cancer surgery has also been linked to aircraft flight (likely due to decreased cabin pressure or relative immobility). For cancer survivors wearing a prescribed and properly fitted compression garment may help decrease swelling during air travel.<ref>{{cite journal | vauthors = Lim CS, Davies AH | title = Graduated compression stockings | journal = CMAJ | volume = 186 | issue = 10 | pages = E391–E398 | date = July 2014 | pmid = 24591279 | pmc = 4081237 | doi = 10.1503/cmaj.131281}}</ref>

Some cases of lower-limb lymphedema have been associated with the use of [[tamoxifen]], due to blood clots and [[deep vein thrombosis]] (DVT) associated with this medication. Resolution of the blood clots or DVT is needed before lymphedema treatment can be initiated.{{medical citation needed|date=September 2023}}

===At birth===
'''Hereditary lymphedema''' is a primary lymphedema – swelling that results from abnormalities in the [[lymphatic system]] that are [[congenital|present from birth]]. Swelling may be present in a single limb, several limbs, genitalia, or the face. It is sometimes diagnosed prenatally by a [[nuchal scan]] or postnatally by [[:wikt:lymphoscintigraphy|lymphoscintigraphy]].{{medical citation needed|date=September 2023}}

The most common cause is [[Meige disease]] which usually presents at [[puberty]]. Another form of hereditary lymphedema is [[Milroy's disease]], caused by mutations in the [[VEGFR3]] gene.<ref name="grada-2017" /><ref>{{Cite book |chapter-url=http://accessmedicine.mhmedical.com/content.aspx?aid=5014541|title=Schwartz's Principles of Surgery |last1=Liem |first1=Timothy K. |last2=Moneta |first2=Gregory L. |date=2010 |publisher=The McGraw-Hill Companies |editor-last=Brunicardi |editor-first=F. Charle s|edition=9th |location=New York, NY|editor-last2=Andersen|editor-first2=Dana K.|editor-last3=Billiar|editor-first3=Timothy R.|editor-last4=Dunn|editor-first4=David L.|editor-last5=Hunter|editor-first5=John G.|editor-last6=Matthews|editor-first6=Jeffrey B.|editor-last7=Pollock|editor-first7=Raphael E.|chapter=Chapter 24. Venous and Lymphatic Disease}}{{Dead link|date=January 2019 |bot=InternetArchiveBot |fix-attempted=yes}}</ref> Hereditary lymphedema is frequently syndromic and is associated with [[Turner syndrome]], [[lymphedema–distichiasis syndrome]], [[yellow nail syndrome]], and [[Klippel–Trénaunay syndrome]].<ref>{{Cite book|chapter-url=http://accessmedicine.mhmedical.com/content.aspx?aid=56081150|title=Fitzpatrick's Dermatology in General Medicine|last1=Burkhart|first1=Craig N.|last2=Adigun|first2=Chris|last3=Burton|first3=Claude S. |date=2012|publisher=The McGraw-Hill Companies|editor-last=Goldsmith|editor-first=Lowell A.|edition=8|location=New York, NY|editor-last2=Katz|editor-first2=Stephen I.|editor-last3=Gilchrest|editor-first3=Barbara A.|editor-last4=Paller|editor-first4=Amy S.|editor-last5=Leffell|editor-first5=David J.|editor-last6=Wolff|editor-first6=Klaus|chapter=Chapter 174. Cutaneous Changes in Peripheral Venous and Lymphatic Insufficiency}}{{Dead link|date=January 2019 |bot=InternetArchiveBot |fix-attempted=yes}}</ref>

One defined genetic cause for hereditary lymphedema is [[GATA2 deficiency]]. This deficiency is a grouping of several disorders caused by a single defect: familial or sporadic [[Mutation#By effect on function|inactivating mutation]]s in one of the two parental ''[[GATA2]]'' [[gene]]s. These [[autosomal dominant]] mutations cause a reduction, i.e. a [[haploinsufficiency]], in the cellular levels of the gene's product, [[GATA2]]. The GATA2 [[protein]] is a [[transcription factor]] critical for the [[Embryogenesis|development]], maintenance, and functionality of [[blood|blood-forming]], [[Lymphatic system|lymphatic-forming]], and other tissue-forming [[stem cell]]s. Due to these mutations cellular levels of GATA2 are deficient and over time individuals develop hematological, immunological, lymphatic, and other disorders. GATA2 deficiency-induced defects in the lymphatic vessels and valves underlies the development of lymphedema, primarily in the lower extremities but may also occur in places such as the face or [[hydrocele testis|testes]]. This form of the deficiency, when coupled with [[sensorineural hearing loss]], which may also be due to faulty development of the lymphatic system, is sometimes termed [[Emberger syndrome]].<ref>{{cite journal | vauthors = Crispino JD, Horwitz MS | title = GATA factor mutations in hematologic disease | journal = Blood | volume = 129 | issue = 15 | pages = 2103–2110 | date = April 2017 | pmid = 28179280 | pmc = 5391620 | doi = 10.1182/blood-2016-09-687889}}</ref><ref>{{cite journal | vauthors = Hirabayashi S, Wlodarski MW, Kozyra E, Niemeyer CM | title = Heterogeneity of GATA2-related myeloid neoplasms | journal = International Journal of Hematology | volume = 106 | issue = 2 | pages = 175–182 | date = August 2017 | pmid = 28643018 | doi = 10.1007/s12185-017-2285-2 | doi-access = free}}</ref>

Primary lymphedema occurs in approximately one to three births out of every 10,000 births, with a female to male ratio of 3.5:1. In North America, the incidence of primary lymphedema is approximately 1.15 births out of every 100,000 births.{{Contradictory inline|date=September 2023}} Compared to secondary lymphedema, primary lymphedema is relatively rare.<ref>{{cite journal | vauthors = Kurland LT, Molgaard CA | title = The patient record in epidemiology | journal = Scientific American | volume = 245 | issue = 4 | pages = 54–63 | date = October 1981 | pmid = 7027437 | doi = 10.1038/scientificamerican1081-54 | bibcode = 1981SciAm.245d..54K}}</ref>

=== Inflammatory lymphedema ===
{{Main|Bilateral lower extremity inflammatory lymphedema}}
[[Bilateral lower extremity inflammatory lymphedema]] (BLEIL) is a distinct type of lymphedema occurring in a setting of acute and prolonged standing, such as in new recruits during [[basic training]].<ref>{{cite journal | vauthors = Fajardo KA, Keller P, Kobayashi T, Hivnor CM, Webber BJ, Federinko SP, Tchandja J | title = Bilateral lower extremity inflammatory lymphedema in Air Force basic trainees: clinical and epidemiologic study of a new disease entity | journal = JAMA Dermatology | volume = 151 | issue = 4 | pages = 395–400 | date = April 2015 | pmid = 25607253 | doi = 10.1001/jamadermatol.2014.3794 | doi-access = }}</ref> Possible underlying mechanisms may include venous congestion and inflammatory vasculitis.<ref>{{cite journal | vauthors = McCann SE, Dalton SR, Kobayashi TT | title = Histopathology of bilateral lower extremity inflammatory lymphedema in military basic trainees: A leukocytoclastic vasculitis of the deep vascular plexus | journal = Journal of Cutaneous Pathology | volume = 44 | issue = 5 | pages = 500–503 | date = May 2017 | pmid = 28195354 | doi = 10.1111/cup.12918 | s2cid = 6650610 | url = https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1168&context=usuhs | access-date = 2021-08-08 | archive-date = 2022-05-06 | archive-url = https://web.archive.org/web/20220506014202/https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1168&context=usuhs | url-status = live }}</ref>