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Lymphedema, also known as lymphoedema and lymphatic edema, is a condition of localized swelling caused by a compromised
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid ...
. The lymphatic system functions as a critical portion of the body's
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
and returns
interstitial fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower ...
to the
bloodstream The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
. Lymphedema is most frequently a complication of cancer treatment or parasitic infections, but it can also be seen in a number of
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s. Though incurable and progressive, a number of treatments may improve symptoms. Tissues with lymphedema are at high risk of
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
because the lymphatic system has been compromised. While there is no cure, treatment may improve outcomes. This commonly include compression therapy, good skin care,
exercise Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic ...
, and
manual lymphatic drainage Manual lymphatic drainage (MLD) is a type of massage based on the hypothesis that it will encourage the natural drainage of the lymph, which carries waste products away from the tissues back toward the heart. The lymph system depends on intrinsic c ...
(MLD), which together are known as combined decongestive therapy.
Diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics i ...
are not useful.


Signs and symptoms

The most common manifestation of lymphedema is soft tissue swelling,
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
. As the disorder progresses, worsening edema and skin changes including discoloration, verrucous (wart-like)
hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferatio ...
,
hyperkeratosis Hyperkeratosis is thickening of the stratum corneum (the outermost layer of the epidermis, or skin), often associated with the presence of an abnormal quantity of keratin,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologi ...
,
papillomatosis Papillomatosis of skin is skin surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae.Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathologic Basis of Disease'' (7th ed.). Saunders. Page 1230. . ...
, dermal thickening, and
ulcers An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
may be seen. Additionally, there is increased risk of infection of the skin, known as
Erysipelas Erysipelas () is a relatively common bacterial infection of the superficial layer of the skin ( upper dermis), extending to the superficial lymphatic vessels within the skin, characterized by a raised, well-defined, tender, bright red rash, ...
.


Complications

When lymphatic impairment becomes so great that the 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 culture medium for bacterial growth that can result in
infections An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
,
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
,
lymphangitis Lymphangitis is an inflammation or an infection of the lymphatic channels that occurs as a result of infection at a site distal to the channel. The most common cause of lymphangitis in humans is '' Streptococcus pyogenes'' (Group A strep), hemoly ...
,
lymphadenitis Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...
, and, in severe cases,
skin ulcers An ulcer is a sore on the skin or a mucous membrane, accompanied by the disintegration of tissue. Ulcers can result in complete loss of the epidermis and often portions of the dermis and even subcutaneous fat. Ulcers are most common on the skin ...
. 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. In rare cases, lymphedema may lead to a form of cancer called
lymphangiosarcoma Lymphangiosarcoma is a rare cancer which occurs in long-standing cases of primary or secondary lymphedema. It involves either the upper or lower lymphedematous extremities but is most common in upper extremities. Although its name implies lymphat ...
, although the mechanism of carcinogenesis is not understood. Lymphedema-associated lymphangiosarcoma is called
Stewart–Treves syndrome Stewart–Treves syndrome refers to a lymphangiosarcoma, a rare disorder marked by the presence of an angiosarcoma (a malignant tumor of blood or lymph vessels) in a person with chronic (long-term) lymphedema. Although it most commonly refers to ...
. Lymphangiosarcoma most frequently occurs in cases of long-standing lymphedema. The incidence of angiosarcoma is estimated to be 0.45% in patients living five years after radical mastectomy. Lymphedema is also associated with a low grade form of cancer called
retiform hemangioendothelioma Hemangioendotheliomas are a family of vascular neoplasms of intermediate malignancy. Signs and symptoms They have been described as masses that fall between a hemangioma and angiosarcoma. They are vascular tumors that commonly present with an en ...
(a low grade angiosarcoma). Lymphedema can be disfiguring, and may result in a poor body image, which can cause psychological distress. Complications of lymphedema can cause difficulties in activities of daily living.


Causes

Lymphedema may be inherited (primary) or caused by injury to the lymphatic vessels (secondary).


Lymph node damage

It is most frequently seen after lymph node dissection,
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pa ...
and/or
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
, in which damage to the lymphatic system is caused during the treatment of cancer, most notably
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
. In many patients with
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, this condition does not develop until months or even years after therapy has concluded. Lymphedema may also be associated with
accident An accident is an unintended, normally unwanted event that was not directly caused by humans. The term ''accident'' implies that nobody should be blamed, but the event may have been caused by unrecognized or unaddressed risks. Most researche ...
s or certain diseases or problems that may inhibit the lymphatic system from functioning properly. In tropical endemic areas of the world, a common cause of secondary lymphedema is
filariasis Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type. These are spread by blood-feeding insects such as black flies and mosquitoes. They belong to the group of diseases called helminthiases. These ...
, a parasitic infection. It can also be caused by damage to the lymphatic system from infections such as
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
. Primary lymphedema may be congenital or arise sporadically. Multiple syndromes are associated with primary lymphedema, including
Turner syndrome Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low h ...
, Milroy's disease, and
Klippel–Trénaunay syndrome Klippel–Trénaunay syndrome, formerly Klippel–Trénaunay–Weber syndrome and sometimes angioosteohypertrophy syndrome and hemangiectatic hypertrophy, is a rare congenital medical condition in which blood vessels and/or lymph vessels fail t ...
. It is generally thought to occur as a result of absent or malformed lymph nodes and/or lymphatic channels. Lymphedema may 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. Secondary lymphedema affects both men and women. In women, it is most prevalent in the upper limbs after breast cancer surgery, in particular after axillary lymph node dissection, occurring in the arm on the side of the body in which the surgery is performed. 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/or an inverted nipple) can be confused with post surgery fat necrosis. In Western countries, secondary lymphedema is most commonly due to cancer treatment. Between 38 and 89% of breast cancer patients have lymphedema due to axillary lymph node dissection and/or radiation. Unilateral lymphedema occurs in up to 41% of patients after gynecologic cancer. For men, a 5-66% incidence of lymphedema has been reported in patients treated with incidence depending on whether staging or radical removal of lymph glands was done in addition to radiotherapy. 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, in which 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. 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, therefore, wearing a prescribed and properly fitted compression garment may help decrease swelling during air travel. Some cases of lower-limb lymphedema have been associated with the use of
tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
, due to the blood clots and
deep vein thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...
(DVT) that can be associated with this medication. Resolution of the blood clots or DVT is needed before lymphedema treatment can be initiated. Infectious causes include lymphatic filariasis.


At birth

Hereditary lymphedema is a primary lymphedema – swelling that results from abnormalities in the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid ...
that are present from birth. Swelling may be present in a single affected limb, several limbs, genitalia, or the face. It is sometimes diagnosed prenatally by a nuchal scan or post-natally by lymphoscintigraphy. The most common form is Meige disease that usually presents at
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a ...
. Another form of hereditary lymphedema is Milroy's disease caused by mutations in the
VEGFR3 Fms-related tyrosine kinase 4, also known as FLT4, is a protein which in humans is encoded by the ''FLT4'' gene. This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involve ...
gene. Hereditary lymphedema is frequently syndromic and is associated with
Turner syndrome Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low h ...
, lymphedema–distichiasis syndrome,
yellow nail syndrome Yellow nail syndrome, also known as "primary lymphedema associated with yellow nails and pleural effusion", is a very rare medical syndrome that includes pleural effusions, lymphedema (due to under development of the lymphatic vessels) and yellow d ...
, and
Klippel–Trénaunay syndrome Klippel–Trénaunay syndrome, formerly Klippel–Trénaunay–Weber syndrome and sometimes angioosteohypertrophy syndrome and hemangiectatic hypertrophy, is a rare congenital medical condition in which blood vessels and/or lymph vessels fail t ...
. One defined genetic cause for hereditary lymphedema is
GATA2 deficiency GATA2 deficiency is a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental ''GATA2'' genes. Being the gene haploinsufficient, mutations that cause a reduction in the ce ...
. This deficiency is a grouping of several disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental ''
GATA2 GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of bl ...
''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s. These
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
mutations cause a reduction, i.e. a haploinsufficiency, in the cellular levels of the gene's product,
GATA2 GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of bl ...
. The GATA2
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
is a
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
critical for the
embryonic development An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...
, maintenance, and functionality of
blood-forming Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the ...
, lympathic-forming, and other tissue-forming
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of ...
s. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, and/or other disorders. GATA2 deficiency-induced defects in the lymphatic vessels and valves underlies the development of lymphedema which is primarily located in the lower extremities but may also occur in other places such as the face or testes (i.e.
hydrocele A hydrocele is an accumulation of serous fluid in a body cavity. A hydrocele testis, the most common form of hydrocele, is the accumulation of fluids around a testicle. It is often caused by fluid collecting within a layer wrapped around the tes ...
). This form of the deficiency, when coupled with
sensorineural hearing loss Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve (cranial nerve VIII). SNHL accounts for about 90% of re ...
which may also be due to faulty development of the lymphatic system, is sometimes termed the Emberger syndrome. Primary lymphedema has a quoted incidence of approximately 1-3 births out of every 10,000 births, with a particular female preponderance 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 Compared to secondary lymphedema, primary lymphedema is relatively rare.


Inflammatory lymphedema

Bilateral lower extremity inflammatory lymphedema Bilateral lower extremity inflammatory lymphedema (BLEIL) is a distinct clinical entity characterized by acute lymphedema in both ankles and lower legs after being exposed to prolonged standing, such as during military basic training. Presenta ...
(BLEIL) is a distinct type of lymphedema occurring in a setting of acute and prolonged standing, such as in new recruits during
basic training Military recruit training, commonly known as basic training or boot camp, refers to the initial instruction of new military personnel. It is a physically and psychologically intensive process, which resocializes its subjects for the unique deman ...
. The possible underlying mechanisms are thought to be venous congestion and inflammatory vasculitis.


Physiology

Lymph Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues ...
is formed from the fluid that filters out of the blood circulation and contains proteins, cellular debris, bacteria, etc. The collection of this fluid is carried out by the initial lymph collectors that are blind-ended
endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...
-lined vessels with fenestrated openings that allow fluids and particles as large as cells to enter. Once inside the lumen of the lymphatic vessels, the fluid is guided along increasingly larger vessels, first with rudimentary valves to prevent backflow, which later develops into complete valves similar to the venous valve. Once the lymph enters the fully valved lymphatic vessels, it is pumped by a rhythmic 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 regulation of the frequency and power of contraction is regulated by the
sympathetic nervous system The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of t ...
. 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.


Diagnosis

Diagnosis is generally based on signs and symptoms, with testing used to rule out other potential causes. An accurate diagnosis and staging may help with management. 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. However, the ideal method for lymphedema staging to guide the most appropriate treatment is controversial because of several different proposed protocols. 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. Given swelling, the extremities' circumference is measured for reference as time continues. 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 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. 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 at the opposite unaffected limb, e.g. in volume or circumference. No generally accepted criterion is definitively diagnostic, although a volume difference of 200 ml between limbs or a 4-cm difference (at a single measurement site or set intervals along the limb) is often used.
Bioimpedance Bioelectrical impedance analysis (BIA) is a method for estimating body composition, in particular body fat and muscle mass, where a weak electric current flows through the body and the voltage is measured in order to calculate impedance (resista ...
measurement (which measures the amount of fluid in a limb) offers greater sensitivity than existing methods. Chronic venous stasis changes can mimic early lymphedema, but the changes in venous stasis are more often bilateral and symmetric.
Lipedema Lipedema is a condition that is almost exclusively found in women and results in enlargement of both legs due to deposits of fat under the skin. Women of any weight may develop lipedema and the fat associated with lipedema is resistant to traditi ...
can also mimic lymphedema, however lipedema characteristically spares the feet beginning abruptly at the medial malleoli (ankle level). 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 Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
,
hypoalbuminemia Hypoalbuminemia (or hypoalbuminaemia) is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or ...
, congestive heart-failure, protein-losing nephropathy, pulmonary hypertension, obesity, pregnancy and drug-induced
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
.


Classification

According to the Fifth
WHO Who or WHO may refer to: * Who (pronoun), an interrogative or relative pronoun * Who?, one of the Five Ws in journalism * World Health Organization Arts and entertainment Fictional characters * Who, a creature in the Dr. Seuss book '' Horton He ...
Expert Committee on
Filariasis Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type. These are spread by blood-feeding insects such as black flies and mosquitoes. They belong to the group of diseases called helminthiases. These ...
the most common method of classification of lymphedema is as follows: (The same classification method can be used for both primary and secondary lymphedema) 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. The lymphedema expert Dr. Ming-Huei Cheng developed a Cheng's Lymphedema Grading tool to assess the severity of extremity lymphedema based on objective limb measurements and providing appropriate options for management.


I. Grading

* 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
WHO Who or WHO may refer to: * Who (pronoun), an interrogative or relative pronoun * Who?, one of the Five Ws in journalism * World Health Organization Arts and entertainment Fictional characters * Who, a creature in the Dr. Seuss book '' Horton He ...
Expert Committee on
Filariasis Filariasis is a parasitic disease caused by an infection with roundworms of the Filarioidea type. These are spread by blood-feeding insects such as black flies and mosquitoes. They belong to the group of diseases called helminthiases. These ...
, and endorsed by the
American Society of Lymphology The Lymphology Association of North America, formerly known as the American Society of Lymphology, is a non-profit organization based in Kansas City, Missouri, Kansas City, Missouri. The society provides current information and resources for profess ...
., the staging system helps to identify the severity of lymphedema. With the assistance of medical imaging apparatus, such as MRI or CT, staging can be established by the physician, and therapeutic or medical interventions may be applied: * 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 Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
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 the further damage done to the lymphatic system may in fact make the lymphedema worse. * Stage 4: The size and circumference of the affected limb(s) become noticeably large. 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 prevalent among patients in this stage. * Stage 6: Knobs of small elongated or small rounded sizes cluster together, giving mossy-like shapes on the limb. Mobility of the patient becomes increasingly difficult. * 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 referenced to a healthy extremity): * 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 4 cm and other tissue changes are not yet present. * Grade 2 (moderate edema): Involves an entire limb or corresponding quadrant of the trunk. Difference in circumference is 4–6 cm. Tissue changes, such as pitting, are apparent. The patient may experience
erysipelas Erysipelas () is a relatively common bacterial infection of the superficial layer of the skin ( upper dermis), extending to the superficial lymphatic vessels within the skin, characterized by a raised, well-defined, tender, bright red rash, ...
. * Grade 3a (severe edema): Lymphedema is present in one limb and its associated trunk quadrant. Circumferential difference is greater than 6 centimeters. Significant skin alterations, such as
cornification Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, hor ...
or
keratosis Keratosis (from '' kerat-'' + '' -osis'') is a growth of keratin on the skin or on mucous membranes stemming from keratinocytes, the prominent cell type in the epidermis. More specifically, it can refer to: * actinic keratosis (also known as solar ...
,
cysts A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubble) ...
and/or fistulae, are present. Additionally, the patient may experience repeated attacks of
erysipelas Erysipelas () is a relatively common bacterial infection of the superficial layer of the skin ( upper dermis), extending to the superficial lymphatic vessels within the skin, characterized by a raised, well-defined, tender, bright red rash, ...
. * 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 venous insufficiency, which is caused by compromise of the venous drainage rather than lymphatic drainage. However, untreated venous insufficiency can progress into a combined venous/lymphatic disorder.


Treatment

While there is no cure, treatment may improve outcomes. This commonly include compression therapy, good skin care, exercise, and
manual lymphatic drainage Manual lymphatic drainage (MLD) is a type of massage based on the hypothesis that it will encourage the natural drainage of the lymph, which carries waste products away from the tissues back toward the heart. The lymph system depends on intrinsic c ...
(MLD), which together is known as combined decongestive therapy. MLD is most effective in mild to moderate disease. In breast cancer-related lymphedema, MLD is safe and may offer added benefit to compression bandages for reducing swelling. Most people with lymphedema can be medically managed with conservative treatment. Diuretics are not useful. Surgery is generally only used in those who are not improved with other measures.


Compression


Garments

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 sleeping unless otherwise prescribed. Elastic compression garments are worn on the affected limb following complete de-congestive therapy to maintain edema reduction. Inelastic garments provide containment and reduction. Available styles, options, and prices vary widely. A professional garment fitter or certified lymphedema therapist can help determine the best option for the patient.


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 in fact end up producing 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.


Intermittent pneumatic compression therapy

Intermittent pneumatic compression therapy (IPC) utilizes a multi-chambered pneumatic sleeve with overlapping cells to promote movement of lymph fluid. Pump therapy should be used in addition to other treatments such as compression bandaging and manual lymph drainage. Pump therapy has been used a lot 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. 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. Current literature has suggested the use of IPC treatment in conjunction with Kinesiotape (KT) is more effective in the overall reduction of lymphedema as well as increasing shoulder ROM than the traditional treatment of IPC paired with complete decongestive therapy. Kinesiotape (KT) 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. The use of IPC treatments with KT 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 postmastectomy.


Exercise

In those with lymphedema or at risk of developing lymphedema, following breast cancer treatment, resistance training did not increase swelling and decreases in some, in addition to other potential beneficial effects on cardiovascular health. 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 (with the possible exception of swimming). Physical therapy treatment of patients with lymphedema may include 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.


Surgery

The treatment of lymphedema is usually conservative, however the use of surgery is proposed for some cases. Suction assisted lipectomy (SAL), also known as
liposuction Liposuction, or simply lipo, is a type of fat-removal procedure used in plastic surgery. Evidence does not support an effect on weight beyond a couple of months and does not appear to affect obesity-related problems. In the United States, lipo ...
for lymphedema, may help improve chronic non pitting edema if present. The procedure removes fat and protein and is done along with continued compression therapy. Vascularized lymph node transfers (VLNT) and lymphovenous bypass are supported by tentative evidence but is associated with a number of complications.


Laser therapy

Low-level laser therapy Low-level laser therapy (LLLT), cold laser therapy, or photobiomodulation (PBM) is a form of medicine that applies low-level (low-power) lasers or light-emitting diodes (LEDs) to the surface of the body. Whereas high-power lasers are used in la ...
(LLLT) was cleared by the
US Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) for the treatment of lymphedema in November 2006. According to the US
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. T ...
, LLLT may be effective in reducing lymphedema in some women. Two cycles of laser treatment were found to be reduce the volume of the affected arm in approximately one-third of people with postmastectomy lymphedema at three months post-treatment.


Epidemiology

Lymphedema affects approximately 200 million people worldwide.


References


External links

{{Disorders of volume state Diseases of veins, lymphatic vessels and lymph nodes Lymphatic vessel diseases