Editing Lymphedema

{{Short description|Swelling due to a compromised lymphatic system}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox medical condition
| name            = Lymphedema
| image           = Lymphödem.JPG
| caption         = Lower extremity lymphedema
| pronounce       =
| field           = [[Vascular medicine]], [[Rheumatology]],<ref>{{cite journal | vauthors = Joos E, Bourgeois P, Famaey JP | title = Lymphatic disorders in rheumatoid arthritis | journal = Seminars in Arthritis and Rheumatism | volume = 22 | issue = 6 | pages = 392–398 | date = June 1993 | pmid = 8342046 | doi = 10.1016/s0049-0172(05)80031-9 | publisher = Elsevier BV}}</ref> [[Physical medicine and rehabilitation]], [[General surgery]], [[Plastic surgery]]
| synonyms        = Lymphoedema, lymphatic obstruction, lymphatic insufficiency
| symptoms        =
| complications   =
| onset           =
| duration        =
| types           =
| causes          =
| risks           =
| diagnosis       = [[Clinical diagnosis|Based on symptoms]]<ref name="Lymphedema Diagnostic workup" />
| differential    = [[Lipodystrophy]], [[Chronic venous insufficiency|venous insufficiency]]<ref name="Lymphedema Diagnostic workup" />
| prevention      =
| treatment       =
| medication      =
| prognosis       =
| frequency       =
| deaths          =
}}
<!-- Diagnosis and symptoms-->

'''Lymphedema''', also known as '''lymphoedema''' and '''lymphatic edema''', is a condition of localized [[edema|swelling]] caused by a compromised [[lymphatic system]].<ref name="Lymphedema Diagnostic workup" /> The lymphatic system functions as a critical portion of the body's [[immune system]] and returns [[interstitial fluid]] to the [[bloodstream]].

Lymphedema is most frequently a complication of cancer treatment or [[parasitic infection]]s, but it can also be seen in a number of [[genetic disorder]]s. Tissues with lymphedema are at high risk of [[infection]] because the lymphatic system has been compromised.<ref>{{cite book | vauthors = Sleigh BC, Manna B | chapter = Lymphedema | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | date = January 2020 | pmid = 30725924}}</ref>

<!-- Treatment -->
Though incurable and progressive, a number of treatments may improve symptoms.<ref name="Lymphedema Diagnostic workup" /> This commonly includes compression therapy, good skin care, [[exercise]], and [[manual lymphatic drainage]] (MLD), which together are known as combined decongestive therapy.<ref name="Lymphedema Diagnostic workup" /> [[Diuretics]] are not useful.<ref name="Lymphedema Diagnostic workup" />
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==Signs and symptoms==
[[File:Dr. Ming-Huei Cheng's lymphedema Sample.png|thumb|upright=1.3|Lymphedema seen on CT scan]]

The most common manifestation of lymphedema is soft tissue swelling ([[edema]]). As the disorder progresses, worsening edema and skin changes including discoloration, verrucous (wart-like) [[hyperplasia]], [[hyperkeratosis]], [[papillomatosis]], dermal thickening, and [[Ulcer (dermatology)|ulcers]] may be seen. Additionally, there is increased risk of infection of the skin, known as [[erysipelas]].{{citation needed|date=April 2023}}

===Complications===
When lymphatic impairment becomes so great that the collected lymph fluid exceeds the lymphatic system's ability to transport it, an abnormal amount of protein-rich fluid collects in the tissues. Left untreated, this stagnant, protein-rich fluid causes tissue channels to increase in size and number, reducing oxygen availability. This interferes with wound healing and provides a rich medium for bacterial growth which can result in [[infections|skin infections]], [[lymphangitis]], [[lymphadenitis]], and, in severe cases, [[Ulcer (dermatology)|skin ulcers]].<ref name="grada-2017" /> It is vital for lymphedema patients to be aware of the symptoms of infection and to seek immediate treatment, since recurrent infections or cellulitis, in addition to their inherent danger, further damage the lymphatic system and set up a vicious circle.{{citation needed|date=February 2021}}

In rare cases, lymphedema may lead to a form of cancer called [[lymphangiosarcoma]], although the mechanism of carcinogenesis is not understood. Lymphedema-associated lymphangiosarcoma is called [[Stewart–Treves syndrome]].<ref name="grada-2017" /> Lymphangiosarcoma most frequently occurs in cases of long-standing lymphedema. The incidence of angiosarcoma five years after radical mastectomy is estimated to be 0.45% in surviving patients.<ref>{{cite journal | vauthors = Martin MB, Kon ND, Kawamoto EH, Myers RT, Sterchi JM | title = Postmastectomy angiosarcoma | journal = The American Surgeon | volume = 50 | issue = 10 | pages = 541–545 | date = October 1984 | pmid = 6541442}}</ref><ref>{{cite journal | vauthors = Chopra S, Ors F, Bergin D | title = MRI of angiosarcoma associated with chronic lymphoedema: Stewart Treves syndrome | journal = The British Journal of Radiology | volume = 80 | issue = 960 | pages = e310–e313 | date = December 2007 | pmid = 18065640 | doi = 10.1259/bjr/19441948}}</ref> Lymphedema is also associated with a low [[Grading (tumors)|grade]] form of cancer called [[retiform hemangioendothelioma]] (a low grade angiosarcoma).<ref>{{cite journal | vauthors = Requena L, Sangueza OP | title = Cutaneous vascular proliferations. Part III. Malignant neoplasms, other cutaneous neoplasms with significant vascular component, and disorders erroneously considered as vascular neoplasms | journal = Journal of the American Academy of Dermatology | volume = 38 | issue = 2 Pt 1 | pages = 143–75; quiz 176–8 | date = February 1998 | pmid = 9486670 | doi = 10.1016/S0190-9622(98)70237-3}}</ref>

Lymphedema can be disfiguring, and may result in a poor body image and psychological distress.<ref>{{Cite web|url=https://www.phlebolymphology.org/body-image-and-quality-of-life-in-secondary-lymphedema-of-the-upper-limb/|title=Body image and quality of life in secondary lymphedema of the upper limb|last=Publishing|first=Licorn|date=2009-10-28|website=Servier – Phlebolymphology|language=en-US|access-date=2019-09-03|archive-url=https://web.archive.org/web/20190903201452/https://www.phlebolymphology.org/body-image-and-quality-of-life-in-secondary-lymphedema-of-the-upper-limb/|archive-date=2019-09-03|url-status=dead}}</ref> Complications of lymphedema can cause difficulties in activities of daily living.<ref>{{Cite web|url=https://www.aota.org/~/media/Corporate/Files/AboutOT/Professionals/WhatIsOT/RDP/Facts/Oncology%20fact%20sheet.pdf|title=Oncology Fact Sheet|website=aota.org|access-date=2019-09-03|archive-date=2020-09-20|archive-url=https://web.archive.org/web/20200920235641/https://www.aota.org/~/media/Corporate/Files/AboutOT/Professionals/WhatIsOT/RDP/Facts/Oncology%20fact%20sheet.pdf|url-status=live}}</ref>

==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>

==Physiology==
[[Lymph]] is formed from the fluid that filters out of blood and contains proteins, cellular debris, bacteria, etc. This fluid is collected by the initial lymph collectors that are blind-ended [[Epithelium|endothelial]]-lined vessels with fenestrated openings that allow fluids and particles as large as cells to enter. Once inside the [[lumen (anatomy)|lumen]] of the lymphatic vessels, the fluid is guided along increasingly larger vessels, first with rudimentary valves to prevent backflow, later with complete valves similar to the venous valve. Once the lymph enters the fully valved lymphatic vessels, it is pumped by a rhythmic [[Peristalsis|peristaltic]]-like action by smooth muscle cells within the lymphatic vessel walls. This peristaltic action is the primary driving force moving lymph within its vessel walls. The [[sympathetic nervous system]] regulates the frequency and power of the contractions. Lymph movement can be influenced by the pressure of nearby muscle contraction, arterial pulse pressure and the vacuum created in the chest cavity during respiration, but these passive forces contribute only a minor percentage of lymph transport. The fluids collected are pumped into continually larger vessels and through lymph nodes, which remove debris and police the fluid for dangerous microbes. The lymph ends its journey in the thoracic duct or right lymphatic duct, which drain into the blood circulation.<ref name="Visual Guide to Lymphedema" />

Several research groups have hypothesized that chronic inflammation is a key regulator in the development of lymphedema. Th cells, particularly Th2 differentiation, play a crucial role in the pathophysiology of lymphedema. Research has shown that increased expression of Th2-inducing cytokines in the epidermal cells of the lymphoedematous limb. Treatment with QBX258 has been found to decrease hyperkeratosis and fibrosis, reduce the number of CD4+ cells, and normalize the expression of Th2-inducing cytokines and IL13R by keratinocytes. These findings suggest that epidermal cells may initiate or coordinate chronic Th2 responses in lymphedema.<ref name=":1">{{Cite journal |last1=Mehrara |first1=Babak J. |last2=Park |first2=Hyeung Ju |last3=Kataru |first3=Raghu P. |last4=Bromberg |first4=Jacqueline |last5=Coriddi |first5=Michelle |last6=Baik |first6=Jung Eun |last7=Shin |first7=Jinyeon |last8=Li |first8=Claire |last9=Cavalli |first9=Michele R. |last10=Encarnacion |first10=Elizabeth M. |last11=Lee |first11=Meghan |last12=Van Zee |first12=Kimberly J. |last13=Riedel |first13=Elyn |last14=Dayan |first14=Joseph H. |date=2021-09-18 |title=Pilot Study of Anti-Th2 Immunotherapy for the Treatment of Breast Cancer-Related Upper Extremity Lymphedema |journal=Biology |volume=10 |issue=9 |pages=934 |doi=10.3390/biology10090934 |doi-access=free |issn=2079-7737 |pmc=8466465 |pmid=34571811}}</ref>

=== Role of T-Cell inflammation and Th2 response ===
Lymphedema involves a complex interplay of inflammatory processes. Recent research has shed light on the role of T-cell inflammation and the Th2 immune response in the initiation of lymphedema.<ref name=":0">{{Cite journal |last1=Avraham |first1=Tomer |last2=Zampell |first2=Jamie C. |last3=Yan |first3=Alan |last4=Elhadad |first4=Sonia |last5=Weitman |first5=Evan S. |last6=Rockson |first6=Stanley G. |last7=Bromberg |first7=Jacqueline |last8=Mehrara |first8=Babak J. |date=March 2013 |title=Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema |journal=FASEB Journal|volume=27 |issue=3 |pages=1114–1126 |doi=10.1096/fj.12-222695 |doi-access=free |issn=1530-6860 |pmc=3574290 |pmid=23193171}}</ref>

==== T-Cell inflammation and fibrosis ====
Studies have revealed that sustained lymphatic stasis results in the infiltration of CD4+ T-cells, leading to inflammation and fibrosis within affected tissues.<ref name=":0" />

==Diagnosis==
Diagnosis is generally based on signs and symptoms, with testing used to rule out other potential causes.<ref name="Lymphedema Diagnostic workup" /> An accurate diagnosis and staging may help with management.<ref name="Lymphedema Diagnostic workup">{{cite journal | vauthors = Grada AA, Phillips TJ | title = Lymphedema: Diagnostic workup and management | journal = Journal of the American Academy of Dermatology | volume = 77 | issue = 6 | pages = 995–1006 | date = December 2017 | pmid = 29132859 | doi = 10.1016/j.jaad.2017.03.021}}</ref> A swollen limb can result from different conditions that require different treatments. Diagnosis of lymphedema is currently based on history, physical exam, and limb measurements. Imaging studies such as lymphoscintigraphy and indocyanine green lymphography are only required when surgery is being considered.<ref name="Lymphedema Diagnostic workup" /> However, the ideal method of staging to guide treatment is controversial because of several different proposed protocols.<ref>{{cite journal | vauthors = Burnand KM, Glass DM, Mortimer PS, Peters AM | title = Lymphatic dysfunction in the apparently clinically normal contralateral limbs of patients with unilateral lower limb swelling | journal = Clinical Nuclear Medicine | volume = 37 | issue = 1 | pages = 9–13 | date = January 2012 | pmid = 22157021 | doi = 10.1097/RLU.0b013e31823931f5 | s2cid = 34921176}}</ref><ref>{{cite journal | vauthors = Tiwari A, Cheng KS, Button M, Myint F, Hamilton G | title = Differential diagnosis, investigation, and current treatment of lower limb lymphedema | journal = Archives of Surgery | volume = 138 | issue = 2 | pages = 152–161 | date = February 2003 | pmid = 12578410 | doi = 10.1001/archsurg.138.2.152 | doi-access = free}}</ref>

Lymphedema can occur in both the upper and lower extremities, and in some cases, the head and neck. Assessment of the extremities first begins with a visual inspection; color, presence of hair, visible veins, size and any sores or ulcerations are noted. Lack of hair may indicate an arterial circulation problem.<ref name="Jarvis2004">{{Cite book|url=https://books.google.com/books?id=aDiJoAEACAAJ&pg=PA530|title=Physical Examination and Health Assessment|author=Jarvis, C.|publisher=Saunders Elsevier|year=2004|isbn=978-1-4160-5188-6|edition=5th|pages=530–553|access-date=2018-03-14|archive-date=2023-01-13|archive-url=https://web.archive.org/web/20230113000219/https://books.google.com/books?id=aDiJoAEACAAJ&pg=PA530|url-status=live}}</ref> In cases of swelling, the extremities' circumference is measured over time for reference. In early stages of lymphedema, elevating the limb may reduce or eliminate the swelling. Palpation of the wrist or ankle can determine the degree of swelling; assessment includes a check of the pulses. The axillary or inguinal lymph nodes may be enlarged due to the swelling. Enlargement of the nodes lasting more than three weeks may indicate infection or other illnesses (such as sequela from breast cancer surgery) requiring further medical attention.<ref name="Jarvis2004" />

Diagnosis or early detection of lymphedema is difficult. The first signs may be subjective observations such as a feeling of heaviness in the affected extremity. These may be symptomatic of early-stage lymphedema where accumulation of lymph is mild and not detectable by changes in volume or circumference. As lymphedema progresses, definitive diagnosis is commonly based upon an objective measurement of differences between the affected or at-risk limb and the opposite unaffected limb, e.g. in volume or circumference. No generally accepted criterion is definitively diagnostic, although a volume difference of 200&nbsp;ml between limbs or a {{Convert|4|cm|abbr=on}} difference (at a single measurement site or set intervals along the limb) is often used. [[Bioelectrical impedance analysis|Bioimpedance]] measurement (which measures the amount of fluid in a limb) offers greater sensitivity than other methods.<ref>{{cite journal | vauthors = Ward LC | title = Bioelectrical impedance analysis: proven utility in lymphedema risk assessment and therapeutic monitoring | journal = Lymphatic Research and Biology | volume = 4 | issue = 1 | pages = 51–56 | year = 2006 | pmid = 16569209 | doi = 10.1089/lrb.2006.4.51}}</ref> Devices like SOZO <ref>{{Cite web |date=2019-06-05 |title=SOZO® Digital Health Platform {{!}} ImpediMed |url=https://www.impedimed.com/products/sozo/ |access-date=2024-03-20 |website=www.impedimed.com |language=en-US |archive-date=2024-03-20 |archive-url=https://web.archive.org/web/20240320163547/https://www.impedimed.com/products/sozo/ |url-status=live }}</ref> utilize Bioimpedence Analysis (BIA) by sending a current through the body and measuring the resultant impedance. Another approach involves Tissue Dielectric Constant (TDC) measurement, used by devices such as Delfin Technology's MoistureMeterD and LymphScanner,<ref>{{Cite web |title=Delfin Technologies - Skin research instruments |url=https://delfintech.com/ |access-date=2024-03-20 |website=Delfin Technologies |language=en-US |archive-date=2024-03-20 |archive-url=https://web.archive.org/web/20240320163549/https://delfintech.com/ |url-status=live }}</ref> which employ microwaves to detect changes in the dielectric properties of tissue.  These innovative techniques have become integral to official protocols for lymphedema detection.<ref>{{Cite journal |last1=Shah |first1=Chirag |last2=Whitworth |first2=Pat |last3=Valente |first3=Stephanie |last4=Schwarz |first4=Graham S. |last5=Kruse |first5=Megan |last6=Kohli |first6=Manpreet |last7=Brownson |first7=Kirstyn |last8=Lawson |first8=Laura |last9=Dupree |first9=Beth |last10=Vicini |first10=Frank A. |date=2023 |title=Bioimpedance spectroscopy for breast cancer-related lymphedema assessment: clinical practice guidelines |journal=Breast Cancer Research and Treatment |volume=198 |issue=1 |pages=1–9 |doi=10.1007/s10549-022-06850-7 |issn=0167-6806 |pmc=9883343 |pmid=36566297}}</ref>

Chronic venous stasis changes can mimic early lymphedema, but are more often bilateral and symmetric. [[Lipedema]] can also mimic lymphedema, however lipedema characteristically spares the feet beginning abruptly at the [[malleolus]] (ankle).<ref name="Lymphedema Diagnostic workup" /> As a part of the initial work-up before diagnosing lymphedema, it may be necessary to exclude other potential causes of lower extremity swelling such as [[kidney failure]], [[hypoalbuminemia]], [[Heart failure|congestive heart-failure]], protein-losing [[kidney disease]], [[pulmonary hypertension]], obesity, pregnancy and drug-induced [[edema]].{{citation needed|date=November 2021}}

===Classification===
[[File:Cheng's Lymphedema Grading.png|thumb|upright=1.6|Cheng's Lymphedema Grading]]
The International Society of Lymphology (ISL) Staging System is based solely on subjective symptoms, making it prone to substantial observer bias. Imaging modalities have been suggested as useful adjuncts to the ISL staging to clarify the diagnosis, such as Cheng's Lymphedema Grading tool, which assesses the severity of extremity lymphedema based on objective limb measurements and provides appropriate options for management.<ref>{{cite journal | title = The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology | journal = Lymphology | volume = 46 | issue = 1 | pages = 1–11 | date = March 2013 | pmid = 23930436 | author1 = International Society of Lymphology}}</ref><ref>{{cite journal | vauthors = Patel KM, Lin CY, Cheng MH | title = A Prospective Evaluation of Lymphedema-Specific Quality-of-Life Outcomes Following Vascularized Lymph Node Transfer | journal = Annals of Surgical Oncology | volume = 22 | issue = 7 | pages = 2424–2430 | date = July 2015 | pmid = 25515196 | doi = 10.1245/s10434-014-4276-3 | s2cid = 13376881}}</ref><ref>{{cite book|url=https://books.google.com/books?id=0_JwCgAAQBAJ|title=Principles and Practice of Lymphedema Surgery|last1=Cheng|first1=Ming-Huei|last2=Chang|first2=David W.|last3=Patel|first3=Ketan M.|date=13 July 2015|publisher=Elsevier Health Sciences|isbn=978-0-323-29897-1|access-date=14 March 2018|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113000234/https://books.google.com/books?id=0_JwCgAAQBAJ|url-status=live}}</ref>

==== I. Grading ====
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* '''Grade 1''': Spontaneously reversible on elevation. Mostly pitting edema.
* '''Grade 2''': Non-spontaneously reversible on elevation. Mostly non-pitting edema.
* '''Grade 3''': Gross increase in volume and circumference of Grade 2 lymphedema, with eight stages of severity given below based on clinical assessments.

===== II. Staging =====
As described by the Fifth [[World Health Organization|WHO]] Expert Committee on [[Filariasis]],<ref>{{cite web|url=http://whqlibdoc.who.int/hq/2001/WHO_CDS_CPE_CEE_2001.26a.pdf|title=Treatment and Prevention of Problems Associated with Lymphatic Filariasis|publisher=World Health Organization|access-date=2014-05-16|url-status=live|archive-url=https://web.archive.org/web/20120418030537/http://whqlibdoc.who.int/hq/2001/WHO_CDS_CPE_CEE_2001.26a.pdf|archive-date=2012-04-18}}</ref><ref>{{cite journal | vauthors = | title = Lymphatic filariasis: the disease and its control. Fifth report of the WHO Expert Committee on Filariasis | journal = World Health Organization Technical Report Series | volume = 821 | pages = 1–71 | year = 1992 | pmid = 1441569}}</ref>  and endorsed by the [[American Society of Lymphology]],<ref>{{cite book|url={{google books |plainurl=y |id=a4ZtTzIWBjUC}}|title=Lymphedema: Diagnosis and Treatment|last1=Tretbar|first1=Lawrence L|last2=Morgan|first2=Cheryl L.|last3=Lee|first3=Byung-Boong |date=6 May 2010|publisher=Springer Science & Business Media|isbn=978-1-84628-793-0|first4=Simon J. |last4=Simonian |first5=Benoit |last5=Blondeau}}{{Page needed|date=September 2011}}</ref>{{Citation needed|date=September 2011}} the staging system helps to identify the severity of lymphedema. With the assistance of medical imaging, such as [[Magnetic resonance imaging|MRI]] or [[CT scan|CT]], staging can be established by the physician, and therapeutic or medical interventions may be applied:{{citation needed|date=February 2021}}
* '''Stage 0''': The lymphatic vessels have sustained some damage that is not yet apparent. Transport capacity is sufficient for the amount of lymph being removed. Lymphedema is not present.
* '''Stage 1''' : Swelling increases during the day and disappears overnight as the patient lies flat in bed. Tissue is still at the pitting stage: when pressed by the fingertips, the affected area indents and reverses with elevation. Usually, upon waking in the morning, the limb or affected area is normal or almost normal in size. Treatment is not necessarily required at this point.
* '''Stage 2''': Swelling is not reversible overnight, and does not disappear without proper management. The tissue now has a spongy consistency and is considered non-pitting: when pressed by the fingertips, the affected area bounces back without indentation. [[Fibrosis]] found in Stage 2 lymphedema marks the beginning of the hardening of the limbs and increasing size.
* '''Stage 3''': Swelling is irreversible and usually the limb(s) or affected area becomes increasingly large. The tissue is hard (fibrotic) and unresponsive; some patients consider undergoing reconstructive surgery, called "debulking". This remains controversial, however, since the risks may outweigh the benefits and further damage done to the lymphatic system may make the lymphedema worse.
* '''Stage 4''': The size and circumference of the affected limb(s) become noticeably larger. Bumps, lumps, or protrusions (also called knobs) on the skin begin to appear.
* '''Stage 5''': The affected limb(s) become grossly large; one or more deep skin folds is present.
* '''Stage 6''': Knobs of small elongated or rounded sizes cluster together, giving mossy-like shapes on the limb. Mobility of the patient becomes increasingly impaired.
* '''Stage 7''': The person becomes "handicapped", and is unable to independently perform daily routine activities such as walking, bathing and cooking. Assistance from the family and health care system is needed.

====Grades====
Lymphedema can also be categorized by its severity (usually compared to a healthy extremity):<ref>{{cite journal | vauthors = Lee TS, Morris CM, Czerniec SA, Mangion AJ | title = Does Lymphedema Severity Affect Quality of Life? Simple Question. Challenging Answers | journal = Lymphatic Research and Biology | volume = 16 | issue = 1 | pages = 85–91 | date = February 2018 | pmid = 28453410 | doi = 10.1089/lrb.2016.0049}}</ref>
* '''Grade 1''' (mild edema): Involves the distal parts such as a forearm and hand or a lower leg and foot. The difference in circumference is less than {{Convert|4|cm|abbr=on}} and no other tissue changes are present.
* '''Grade 2''' (moderate edema): Involves an entire limb or corresponding quadrant of the trunk. Difference in circumference is {{Convert|4|-|6|cm|abbr=on}}. Tissue changes, such as pitting, are apparent. The patient may experience [[erysipelas]].
* '''Grade 3a''' (severe edema): Lymphedema is present in one limb and its associated trunk quadrant. Circumferential difference is greater than {{Convert|6|cm|abbr=on}}. Significant skin alterations, such as [[Keratin#Cornification|cornification]], [[keratosis]], [[cysts]] or [[fistulae]], are present. Additionally, the patient may experience repeated attacks of [[erysipelas]].
* '''Grade 3b''' (massive edema): The same symptoms as grade 3a, except that two or more extremities are affected.
* '''Grade 4''' (gigantic edema): In this stage of lymphedema, the affected extremities are huge, due to almost complete blockage of the lymph channels.

===Differential===
Lymphedema should not be confused with edema arising from [[chronic venous insufficiency]], which is caused by compromise of venous drainage rather than lymphatic drainage. However, untreated venous insufficiency can progress into a combined venous/lymphatic disorder known as [[Edema#Veins|phlebetic lymphedema]] (or phlebolymphedema).<ref>{{Cite journal |title=Sequelae of Untreated Venous Insufficiency |year=2005 |pmc=3036289 |last1=Nicholls |first1=S. C. |journal=Seminars in Interventional Radiology |volume=22 |issue=3 |pages=162–168 |doi=10.1055/s-2005-921960 |pmid=21326689}}</ref><ref>{{Cite journal |last=Farrow |first=Wade |date=2010 |title=Phlebolymphedema-a common underdiagnosed and undertreated problem in the wound care clinic |journal=The Journal of the American College of Certified Wound Specialists |volume=2 |issue=1 |pages=14–23 |doi=10.1016/j.jcws.2010.04.004 |issn=1876-4983 |pmc=3601853 |pmid=24527138}}</ref><ref>{{Cite web |last1=Publishing |first1=Licorn |last2=Guiboles |date=2009-11-24 |title=The causes of edema in chronic venous insufficiency |url=https://www.phlebolymphology.org/the-causes-of-edema-in-chronic-venous/ |access-date=2023-09-01 |website=Servier – Phlebolymphology |language=en-US |archive-date=2023-09-01 |archive-url=https://web.archive.org/web/20230901182645/https://www.phlebolymphology.org/the-causes-of-edema-in-chronic-venous/ |url-status=live }}</ref>

==Treatment==
While there is no cure, treatment may improve outcomes.<ref name="Lymphedema Diagnostic workup" /> This commonly include compression therapy, good skin care, exercise, [[manual lymphatic drainage]] (MLD) and the use of an intermittent pneumatic compression pump, which together is known as combined decongestive therapy.<ref name="Lymphedema Diagnostic workup" /> MLD is most effective in mild to moderate disease.<ref name="Ezzo2015">{{cite journal | vauthors = Ezzo J, Manheimer E, McNeely ML, Howell DM, Weiss R, Johansson KI, Bao T, Bily L, Tuppo CM, Williams AF, Karadibak D | title = Manual lymphatic drainage for lymphedema following breast cancer treatment | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD003475 | date = May 2015 | volume = 2015 | pmid = 25994425 | pmc = 4966288 | doi = 10.1002/14651858.CD003475.pub2}}</ref> In breast cancer-related lymphedema, MLD is safe and may offer added benefit to compression bandages for reducing swelling.<ref name="Ezzo2015" /> Most people with lymphedema can be medically managed with conservative treatment.<ref>{{cite journal | vauthors = Koul R, Dufan T, Russell C, Guenther W, Nugent Z, Sun X, Cooke AL | title = Efficacy of complete decongestive therapy and manual lymphatic drainage on treatment-related lymphedema in breast cancer | journal = International Journal of Radiation Oncology, Biology, Physics | volume = 67 | issue = 3 | pages = 841–846 | date = March 2007 | pmid = 17175115 | doi = 10.1016/j.ijrobp.2006.09.024}}</ref> Diuretics are not useful.<ref name="Lymphedema Diagnostic workup" /> Surgery is generally only used if symptoms are not improved by other measures.<ref name="Lymphedema Diagnostic workup" /><ref>{{Cite web |last=Rajaee Rizi |first=Farid |date=2022 |title=Towards Better Lymphedema Rehabilitation by Interdisciplinary Approach in the Elderly |url=https://en.civilica.com/doc/1858250/ |website=Civilica}}</ref>

===Compression===

====Garments====
[[File:Lymphedema Compression sleeve November 2106 Second Skin 016.jpg|thumb|right|200px|Lymphedema compression sleeve on a mannequin]]

Once a person is diagnosed with lymphedema, compression becomes imperative in the management of the condition. Garments are often intended to be worn all day but may be taken off for sleep, unless otherwise prescribed. [[Compression stockings|Elastic compression garments]] are worn on the affected limb following complete de-congestive therapy to maintain edema reduction. Inelastic garments provide containment and reduction.<ref name="Lymphedema Diagnostic workup" /> Available styles, options, and prices vary widely. A professional garment fitter or certified lymphedema therapist can help determine the best option for the patient.<ref>{{Cite web |title=Lymphoedema |url=https://www.physio-pedia.com/Lymphoedema |access-date=2025-03-17 |website=Physiopedia |language=en}}</ref>

====Bandaging====
Compression bandaging, also called wrapping, is the application of layers of padding and short-stretch bandages to the involved areas. Short-stretch bandages are preferred over long-stretch bandages (such as those normally used to treat sprains), as the long-stretch bandages cannot produce the proper therapeutic tension necessary to safely reduce lymphedema and may produce a [[tourniquet]] effect. Compression bandages provide resistance that assists in pumping fluid out of the affected area during exercise. This counter-force results in increased lymphatic drainage and therefore a decrease in size of the swollen area.<ref name="tan-2019">{{cite journal | vauthors = Tan C, Wilson CM | title = Clinical Outcomes After Physical Therapy Treatment for Secondary Lymphedema After Breast Cancer | journal = Cureus | volume = 11 | issue = 5 | pages = e4779 | date = May 2019 | pmid = 31367497 | pmc = 6666846 | doi = 10.7759/cureus.4779| doi-access = free }}</ref>

====Intermittent pneumatic compression therapy====
Intermittent pneumatic compression therapy (IPC) utilizes a multi-chambered pneumatic sleeve with overlapping cells to promote movement of lymph fluid.<ref name="Lymphedema Diagnostic workup" /> Pump therapy should only be used in addition to other treatments such as compression bandaging and manual lymph drainage. Pump therapy has been used in the past to help with controlling lymphedema. In some cases, pump therapy helps soften fibrotic tissue and therefore potentially enable more efficient lymphatic drainage.<ref>{{cite journal | vauthors = Cheville AL, McGarvey CL, Petrek JA, Russo SA, Taylor ME, Thiadens SR | title = Lymphedema management | journal = Seminars in Radiation Oncology | volume = 13 | issue = 3 | pages = 290–301 | date = July 2003 | pmid = 12903017 | doi = 10.1016/S1053-4296(03)00035-3}}</ref> However, reports link pump therapy to increased incidence of edema proximal to the affected limb, such as genital edema arising after pump therapy in the lower limb.<ref>{{cite journal | vauthors = Boris M, Weindorf S, Lasinski BB | title = The risk of genital edema after external pump compression for lower limb lymphedema | journal = Lymphology | volume = 31 | issue = 1 | pages = 15–20 | date = March 1998 | pmid = 9561507}}</ref> Current literature has suggested the use of IPC treatment in conjunction with an [[elastic therapeutic tape]] is more effective in the overall reduction of lymphedema as well as increasing shoulder [[range of motion]] than the traditional treatment of IPC paired with complete decongestive therapy. The tape is an elastic cotton strip with an acrylic adhesive that is used commonly used to relieve the discomfort and disability associated with sports injuries, but in the context of lymphedema, this increases the space between the dermis and the muscle which increases the opportunity for lymphatic fluid to flow out naturally.<ref>{{Cite web |last=Robinson |first=Lauren |date=2024-04-22 |title=Lymphedema - Symptoms, Treatment, & Care at VIC Chattanooga |url=https://vascularinstituteofchattanooga.com/vein-clinic/venous-conditions/lymphedema/ |access-date=2025-04-21 |website=vascularinstituteofchattanooga.com |language=en-US |archive-date=2025-02-21 |archive-url=https://web.archive.org/web/20250221211040/https://vascularinstituteofchattanooga.com/vein-clinic/venous-conditions/lymphedema/ |url-status=live }}</ref><ref name="Effects of Kinesio Taping">{{cite journal | vauthors = Kasawara KT, Mapa JM, Ferreira V, Added MA, Shiwa SR, Carvas N, Batista PA | title = Effects of Kinesio Taping on breast cancer-related lymphedema: A meta-analysis in clinical trials | journal = Physiotherapy Theory and Practice | volume = 34 | issue = 5 | pages = 337–345 | date = May 2018 | pmid = 29308967 | doi = 10.1080/09593985.2017.1419522 | s2cid = 3351415}}</ref> The use of IPC treatments with tape, as well as subsequent lymphatic drainage, has proven to significantly reduce the circumference of lymphatic limbs in patients experiencing lymphedema secondary to breast cancer post-mastectomy.<ref name="Effects of Kinesio Taping" />

===Exercise===
In those with lymphedema or at risk of developing lymphedema, such as following breast cancer treatment, resistance training did not increase swelling and led to decreases in some, in addition to other potential beneficial effects on cardiovascular health.<ref>{{cite journal | vauthors = Furmaniak AC, Menig M, Markes MH | title = Exercise for women receiving adjuvant therapy for breast cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 9 | pages = CD005001 | date = September 2016 | pmid = 27650122 | pmc = 6457768 | doi = 10.1002/14651858.CD005001.pub3}}</ref><ref>{{cite journal | vauthors = Schmitz KH, Ahmed RL, [[Andrea Troxel|Troxel A]], Cheville A, Smith R, Lewis-Grant L, Bryan CJ, Williams-Smith CT, Greene QP | title = Weight lifting in women with breast-cancer-related lymphedema | journal = The New England Journal of Medicine | volume = 361 | issue = 7 | pages = 664–673 | date = August 2009 | pmid = 19675330 | doi = 10.1056/NEJMoa0810118 | s2cid = 3125299 | doi-access = free}}</ref> Moreover, resistance training and other forms of exercise were not associated with an increased risk of developing lymphedema in people who previously received breast cancer-related treatment. Compression garments should be worn during exercise.<ref>{{cite web |url=http://www.lymphnet.org/resources/position-paper-exercise |title=Position Paper: Exercise &#124; National Lymphedema Network |publisher=Lymphnet.org |access-date=2014-05-16 |url-status=dead |archive-url=https://web.archive.org/web/20140508025721/http://www.lymphnet.org/resources/position-paper-exercise |archive-date=2014-05-08}}</ref>

Physical therapy for patients with lymphedema may include [[Myofascial trigger point|trigger point]] release, soft tissue massage, postural improvement, patient education on condition management, strengthening, and stretching exercises. Exercises may increase in intensity and difficulty over time, beginning with passive movements to increase range of motion and progressing towards using external weights and resistance in various postures.<ref name="tan-2019" />

=== Surgery ===
The treatment of lymphedema is usually conservative, however the use of surgery is proposed for some cases.<ref>{{cite journal | vauthors = Carl HM, Walia G, Bello R, Clarke-Pearson E, Hassanein AH, Cho B, Pedreira R, Sacks JM | title = Systematic Review of the Surgical Treatment of Extremity Lymphedema | journal = Journal of Reconstructive Microsurgery | volume = 33 | issue = 6 | pages = 412–425 | date = July 2017 | pmid = 28235214 | doi = 10.1055/s-0037-1599100 | s2cid = 7791985}}</ref>

Suction assisted lipectomy (SAL), also known as [[liposuction]] for lymphedema, may help improve chronic non pitting edema.<ref name="Granzow2013" /> The procedure removes fat and protein and is done alongside continued compression therapy.<ref name="Granzow2013">{{cite journal | vauthors = Granzow JW, Soderberg JM, Kaji AH, Dauphine C | title = Review of current surgical treatments for lymphedema | journal = Annals of Surgical Oncology | volume = 21 | issue = 4 | pages = 1195–1201 | date = April 2014 | pmid = 24558061 | doi = 10.1245/s10434-014-3518-8 | doi-access = free}}</ref>

Vascularized lymph node transfers (VLNT) and lymphovenous bypass are supported by tentative evidence {{as of|2017|lc=y}} but are associated with a number of complications.<ref name="Lymphedema Diagnostic workup" />{{Example needed|date=September 2023}}

===Laser therapy===
[[Low-level laser therapy]] (LLLT) was cleared by the [[Food and Drug Administration (United States)|US Food and Drug Administration]] (FDA) for the treatment of lymphedema in November 2006.<ref>[http://www.dotmed.com/news/story/3067/ dotmed.com December 27, 2006] {{webarchive|url=https://web.archive.org/web/20100107145043/http://www.dotmed.com/news/story/3067 |date=January 7, 2010}} ''Low Level Laser FDA Cleared for the Treatment of Lymphedema''. (accessed 9 November 09)</ref> According to the US [[National Cancer Institute]], LLLT may be effective in reducing lymphedema in some women. Two cycles of laser treatment were found to reduce the volume of the affected arm in approximately one-third of people with post-mastectomy lymphedema at three months post-treatment.<ref>[http://www.cancer.gov/cancertopics/pdq/supportivecare/lymphedema/HealthProfessional/page3#Section_68 National Cancer Institute: Low-level laser therapy] {{webarchive|url=https://web.archive.org/web/20090924235935/http://www.cancer.gov/cancertopics/pdq/supportivecare/lymphedema/HealthProfessional/page3 |date=2009-09-24}} accessed 9 November 09</ref><ref>{{cite journal | vauthors = Carati CJ, Anderson SN, Gannon BJ, Piller NB | title = Treatment of postmastectomy lymphedema with low-level laser therapy: a double blind, placebo-controlled trial | journal = Cancer | volume = 98 | issue = 6 | pages = 1114–1122 | date = September 2003 | pmid = 12973834 | doi = 10.1002/cncr.11641 | s2cid = 7043788 | doi-access = free}}</ref>

A new therapeutic approach involving the drug QBX258 has shown promising results in the treatment of lymphedema. Although it did not reach statistical significance, QBX258 treatment modestly decreased periostin expression and the number of CD4+ and CD4+IL4+ cells in lymphoedematous skin. Notably, QBX258 significantly reduced the expression of Th2-inducing cytokines, improving physical and social quality-of-life measures for patients. However, psychological improvements were not observed.<ref name=":1" />

==Epidemiology==
Lymphedema affects approximately 200 million people worldwide.<ref name="grada-2017">{{cite journal | vauthors = Grada AA, Phillips TJ | title = Lymphedema: Pathophysiology and clinical manifestations | journal = Journal of the American Academy of Dermatology | volume = 77 | issue = 6 | pages = 1009–1020 | date = December 2017 | pmid = 29132848 | doi = 10.1016/j.jaad.2017.03.022}}</ref>

== References ==
{{reflist}}

== External links ==
{{Commons category}}

{{Medical resources
|  DiseasesDB     = 7679
|  ICD11          = {{ICD11|BD93}}, {{ICD11|BE1B.0}}
|  ICD10          = {{ICD10|Q82.0}}, {{ICD10|I97.2}}, {{ICD10|I89.0}}
|  ICD9           = {{ICD9|457.0}}, {{ICD9|457.1}}, {{ICD9|757.0}}
|  ICDO           =
|  OMIM           = 153100
|  MedlinePlus    =
|  eMedicineSubj  = article
|  eMedicineTopic = 1087313
|  MeshID         = D008209
}}
{{Congenital malformations and deformations of integument}}
{{Lymphatic disease}}
{{Disorders of volume state}}

[[Category:Diseases of veins, lymphatic vessels and lymph nodes]]
[[Category:Lymphatic vessel diseases]]