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ANGIOEDEMA

Edema and Angioedema

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Angioedema

Related Terms:  angioneutrotic edema, chronic recurrent angioedema, idiopathic angioedema, hereditary angioedema, oedema, allergic reactions, AAE, HAE, hereditary angioneutrotic edema,  swelling, allergic angioedema, hives, urticaria, laryngoedema, anaphylaxis, chronic recurrent angioedema, idiopathic angioedema, hereditary angioedema, hereditary angioedema I, hereditary angioedema II, urticaria

Discussion:

Inflammatory condition or response that is characterized by localized swelling (welts) under the surface of the skin, the mucous membranes or  an internal organ.   Often associated with urticaria, except that the swelling (edema) is below the surface of the skin rather than on top.  The swelling can be life threatening as if often occurs in the throat causing airway obstruction thus preventing respiration. 

Angioedema and urticaria are varying manifestation of the same pathaoloagical process. Both are described as a post capillary inflammation that results in fluid leakage and edema. The differamce is that angioedema involves vessels in the layers of the indodermal regions whereas uticaria is localized superficial to the dermis. (2)

Classifications:

There are three classifications of angioedema.

Allergic - Also referred to as Chronic Recurrent, this is a response to an allergen such as a food groups (often nuts, certain seafoods), medicines (aspirin being the most common), reaction to latex , pet dander, insect bites (bees, yellow jackets), pollen and can even be triggered by emotional stress.  The bodies response meechanism to an allergen is called anaphylaxis.  The most common body systems involved with this response are  the cutaneous dermal organ (skin), respiratory, cariovascular and gastrointestinal systems.

Unknown etiology - Also referred to as idiopathic angioedema.  This is perhaps the most frequent class and can be extremely frustrating as the cause or source of the edema is unknown.  Individuals experiencing this form may be referred to an immunologist.

Hereditary - This is the  rarest form of angioedema and often runs in families which indicates a possible genetic cause.  Individuals with this form exhibit a deficiency of the C1 esterase inhibitor blood protein. Hereditary angioedema may be diagnosed through hematologic workup and has two classifications. Type one, which is the most common is called Hereditary Angioedema I.   This type is the result of abnormally low levels of certain complex proteins in the blood (C1 esterase inhibitors) known as complements. They help regulate various body functions (flow of body fluids in and out of cells).

Hereditary Angioedema Type II  is a rarer form of the disorder.  This type occurs as the result of the production of abnormal complement proteins. (1)          

Symptoms:

Localized swelling or edema involving the face, lips, or eyes, or tongue; the sudden devlopment of welts, which may be red, itchy or painful; problems with breathing (due to neck or throat edema) and possible abdominal cramping,, which may cause nausea or vomiting.

The edema experienced in angioedema is referred to as localized non-pitting edema .

Other symptoms may include dizziness, nasal congestion, syncope, diarrhea, swollen conjunctiva.  All symptoms may occur within five to thirty minutes of exposure to or ingestion of a given allergen.

Diagnosis:

The diagnosis on angioedema is generally done of the basis of the appearance of the skin and observation of the expression of symptoms.  Allergen testing may also be done to determine causative factors. 

Pathophysiology:

The response results in the release of  histamines, serotonin and kinis with the result that vascular leakage occurs in the dermis and subcutis.

Complications:

In an acute episode af angioedema, the most serious complication may be laryngoedema, which is the sudden constriction or closure of the larynx.  Should this occur, immediate action must be taken to clear the breathing passageway.  Other complications that could affect breathing are bronchospams, and swelling of the tongue.

Treatment:

The treatment involved depends on the classification of angioedema.  In acute episode, it is imperative that the airway be kept clear.  Medications used include steroids, H1 and H2 blockers, epinephrine and antihistimines. Other medications may include Doxepin, Terbutaline, Colchicine, and Danazol.

Hereditary angioedema patients are given aminocaproic acid for maintenance replacement of C1INH to prevent attacks.

For the edema associated with angioedema, decongestive therapy may be prescribed

Prognosis:

Patient expectations are excellent, especially upon immediate attention and treatment of episodes.   The focus on long term prognosis rests in identifying the causative factors and avoiding them.

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Urticaria and Angioedema

What is urticaria?
Urticaria, also known as hives, is an outbreak of swollen, pale red bumps or patches (wheals) on the skin that appear suddenly as a result of the body's adverse reaction to certain allergens or for unknown reasons. Hives usually cause itching but may also burn or sting. They can appear anywhere on the body including the face, lips, tongue, throat or ears. Hives vary in size (from a pencil eraser to a dinner plate) and may join together to form larger areas known as plaques. They can last for hours or up to 3 to 4 days before fading.

What is angioedema?
Angioedema is tissue swelling similar to urticaria, but the swelling occurs beneath the skin instead of on the surface. Angioedema is characterized by deep swelling around the eyes and lips and sometimes of the genitals, hands and feet. Angioedema generally lasts longer than urticaria, but the swelling usually goes away in less than 24 hours.

Occasionally, severe, prolonged tissue swelling can be disfiguring. Rarely, angioedema of the throat, tongue or the lungs can block the airways, causing difficulty breathing and become life-threatening.

What causes hives and angioedema?
Hives and angioedema form when blood plasma leaks out of small blood vessels in the skin because a chemical called histamine is released. Histamine is released from mast cells along the blood vessels in the skin. Allergic reactions, chemicals in foods, insect stings, sunlight exposure or medications can cause histamine release. Sometimes it's impossible to find out why hives have formed.

Types of urticaria and angioedema

Acute Urticaria: hives lasting less than six weeks. The most common causes are foods, medications, latex or infections. Insect bites and internal disease may also be responsible. The most common foods that cause hives are nuts, chocolate, fish, tomatoes, eggs, fresh berries and milk. Fresh foods cause hives more often than cooked foods. Food additives and preservatives may also be the cause. Medications that can cause hives and angioedema include aspirin and other nonsteroidal anti-inflammatory medications such as ibuprofen, high blood pressure medications (ACE inhibitors) or pain-killers such as codeine.

Chronic Urticaria and Angioedema: hives lasting more than six weeks. The cause of this type of hives is usually more difficult to identify than that of acute urticaria. In patients with chronic urticaria, the cause is found in only a small number of patients and is unknown for more than 80 percent of patients. Chronic urticaria and angioedema can effect other internal organs (such as the lungs and gastrointestinal tract), and can cause symptoms of shortness of breath, vomiting, and diarrhea.

Physical Urticaria: hives caused by direct physical stimulation of the skin such as cold, heat, sun exposure, vibration, pressure, sweating, exercise and others. The hives usually occur at the site of direct stimulation and rarely, appear on other skin areas. Most of the hives appear within one hour after exposure.

Dermatographism: hives that form after firmly stroking or scratching the skin. These hives can also occur along with other forms of urticaria. This type of hives is considered a normal variant of the skin.

How are hives and angioedema diagnosed?
Your doctor will need to ask many questions in an attempt to find the possible cause. Since there are no specific tests for hives or the associated swelling of angioedema, testing will depend on your medical history and a thorough examination by your dermatologist. Skin tests may be performed to determine the substance that you are allergic to. Routine blood tests are done to determine if a systemic illness is present.

How are hives and angioedema treated?
The best treatment for hives and associated swelling is to identify and remove the trigger. This is not an easy task. Antihistamines are usually prescribed by your dermatologist to provide relief from symptoms. Antihistamines work best if taken on a regular schedule to prevent hives from forming.

Chronic hives may be treated with antihistamines or combination medications. When antihistamines do not provide relief, oral corticosteroids may be prescribed. For severe hive or angioedema outbreaks, an injection of epinephrine (adrenaline) or a cortisone medication may be needed.

How can hives be managed?
While you’re waiting for the hives and swelling to disappear, here are some tips:

When should I call the doctor? 
If hives or angioedema occur with any of the following symptoms, please contact your doctor right away:

Also contact your doctor if your hives have lasted longer than a few days, if they continue to recur over a month or longer, or if you have symptoms of angioedema or anaphylaxis

The Cleveland Clinic

http://www.clevelandclinic.org/health/health-info/docs/1900/1960.asp?index=8630

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Unusual Presentations of Hereditary Angioedema and Acquired Angioedema

Abstract

Two cases of hereditary angioedema and one of acquired angioedema are reported because of their unusual emergency department presentations. Case one is a 27-year-old man of Italian descent who visited the ED because of severe abdominal pain. He subsequently underwent an unnecessary appendectomy. Case two is a 56-year-old Caucasian man who presented to the ED because of shortness of breath, and, subsequently, he developed severe airway obstruction and was intubated. Case three is a 68-year-old black women with a history of chronic lymphocytic leukemia in remission. She was brought into the ED because of severe shortness of breath and had an emergent cricothyrotomy was performed in the ED because of upper airway obstruction and an inability to be intubated.

Source Information

Introduction

Hereditary angioedema has been known to exist for over a century. It is only within the last 30 years, however, that the disease has been attributed to a C1 esterase inhibitor deficiency, transmitted as an autosomal dominant condition. Hereditary angioedema is episodic and asymptomatic in most patients. Recently, an acquired form of angioedema has been described in patients with underlying malignancies (such as lymphocytic leukemia), collagen vascular disease, or who have developed C1 esterase inhibitor autoantibodies.

Hereditary and acquired angioedema are characterized by recurrent episodes of angioedema involving any part of the body. Laryngeal edema is common, and it is the major cause of death. Angioedema of the gastrointestinal tract frequently may mimic an acute abdomen, resulting in unnecessary surgery. The emergency physician should be aware of these conditions and should initiate prompt treatment in order to avoid unnecessary morbidity and death.

Case Study I

A 28-year-old Italian man was brought to the ED because of abdominal pain. The pain had a sudden onset and had been present for approximately one hour. He had five episodes of vomiting and loss of appetite. There was no fever, diarrhea, melena, hematochezia, or hematemesis. He denied chest pain, and he had no history of dysuria, frequency, urgency, or hematuria. He reported a past medical history of frequent episodes of abdominal pain, especially after aggressive exercise or stress. He denied alcohol or recent aspirin use. The patient's father died after the sudden onset of abdominal pain of unknown cause at age 52, and he also had frequent episodes of acute abdominal pain.

The patient's vital signs consisted of a blood pressure of 120/60 mmHg (without orthostatic changes), pulse 95, respirations 12, and oral temperature 37.5°C. His skin was warm and dry without cyanosis, rash, or decreased turgor. His head was atraumatic, external auditory canals were clear, and tympanic membranes were intact. The lungs were clear to auscultation, and breath sounds were equal bilaterally. The cardiac examination demonstrated a regular rate and rhythm without murmurs. The abdomen was moderately distended with decreased bowel sounds, and diffuse abdominal tenderness associated with slight rebound and guarding. No flank tenderness or ecchymoses were present. Stool was guaiac negative, and the rest of the physical exam was within normal limits.

The CBC, Chemistry 20, and urinalysis were all within normal limits. Chest and abdominal radiography revealed no abnormalities. General surgery was consulted and a diagnosis of an acute abdomen was made. The patient underwent exploratory laparotomy which revealed swollen bowel. An appendectomy was performed, however, the pathology report revealed that the appendix was normal. The patient had an unremarkable recovery and he was later referred to an allergist who diagnosed hereditary angioedema. Subsequently, the patient was started on androgen hormone maintenance therapy.

Case Study II

A 56-year-old Caucasian man was brought into the ED because of shortness of breath and a swollen throat. He had a non-productive cough without congestion or fever. There were no known precipitating events. On presentation he had severe shortness of breath and denied palpitations, chest pain, vomiting, or diarrhea. The patient had a history of episodes of swollen hands while in the armed services, and several years prior, he frequently visited the ED for throat swelling, and had been treated with epinephrine and diphenhydramine. He eventually was referred to an allergist/immunologist and diagnosed with hereditary angioedema. Androgen hormone therapy were initiated, which had controlled his laryngeal edema for the previous five years.

His physical examination revealed that his head, ears, and nose were normal. His tongue was swollen. His neck was supple, nontender, and without lymphadenopathy. Stridor was noted. The cardiac examination demonstrated tachycardia and a regular rhythm. The abdomen was soft and nontender, with normoactive bowel sounds. Extremities were without edema. The skin was warm, dry and without rash, and he was neurologically intact.

Laryngoscopy revealed severe upper airway obstruction, and he was intubated in the ED. Diagnostic chest radiography revealed no abnormalities. The patient was admitted to the ICU and treated with IV fluids, methylprednisolone 125 mg IV and diphenhydramine 50 mg IV every 6 hours. After 12 hours he had complete resolution of his upper airway obstruction and was extubated. He was discharged from the hospital after being cleared by an allergist/immunologist, and androgen hormone therapy was resumed at an increased dosage

Case Study III

Discussion

Early recognition of hereditary and acquired angioedema in the ED is important because significant iatrogenic morbidity may result if the diagnosis is not established. The diagnosis of these disorders is aided by a detailed past medical and family history. Hereditary and acquired angioedema are clinically characterized by recurrent episodes of angioedema involving any part of the body. Urticaria is not a feature of these diseases; however, laryngioedema is common, and the major cause of death. Angioedema involving the GI tract may mimic an acute abdomen, resulting in unnecessary surgery and increased morbidity. Hereditary angioedema is inherited as an autosomal dominant condition for which there are two forms. One form is manifest by the absence of C1 esterase inhibitor, and the other form is manifest by normal levels of C1 esterase inhibitor, but the enzyme is dysfunctional. The absence of, or dysfunction of, C1 esterase inhibitor allows uncontrolled activation of the complement cascade, resulting in angioedema. The diagnosis is usually established by a family history of angioedema in a symptomatic patient, and the diagnosis is confirmed by biochemical C 1 esterase inhibitor deficiency or functional deficiency.

Acquired forms of angioedema are associated with an underlying hematologic malignancy or immune complex disease, resulting in activation of C1Q in the complement cascade. The acquired and hereditary forms can be differentiated from each other by quantification of C1Q levels. The C1Q level in the hereditary form is normal, and the level is low in the acquired form. Life-threatening acute attacks of angioedema do not generally respond to epinephrine, antihistamines, or steroids. Treatments of hereditary and acquired angioedema in the ED consist of supportive therapy with IV fluids, analgesics, and airway management. A purified inhibitor preparation of C1 esterase inhibitor is not yet available in the United States. Fresh frozen plasma is an alternative therapy which is generally effective, but it has the potential disadvantage of causing temporary aggravation of symptoms because C2 and C4 levels transiently increase before the angioedema is brought under control. Therapy with fresh frozen plasma or purified inhibitor preparation should be administered early on in an attempt to avoid unnecessary intubation, cricothyrotomy, or surgery. Patients recognized as having hereditary angioedema may be placed on androgen hormone therapy in order to increase hepatic synthesis of C1 esterase inhibitor. Other effective maintenance therapies include epsilon amino caproic acid and tranexamic acid, which inhibit plasmin activation for long-term prophylactic management

http://www.medical-library.org/journals/derm/angioede.htm

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For further Information:

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Angioedema

http://www.users.globalnet.co.uk/~aair/angioedema.htm

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Angioedema

Author: Nedra Dodds, MD, Staff Physician, Department of Emergency Medicine, Northside Hospital - Cherokee

http://knowledge.emedicine.com/cgi-bin/knijavascript.htm?va=angioedema

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Angioedema

http://www.hon.ch/Library/Theme/Allergy/Glossary/angioedema.html

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Hereditary Angioedema (1)

Copyright 1986, 1987, 1989, 1991, 1992, 1993, 1996, 1997, 1999, 2002

Synonyms of Angioedema, Hereditary

Disorder Subdivisions

General Discussion

Hereditary Angioedema is a rare inherited disorder characterized by an accumulation of fluids outside of the blood vessels, blocking the normal flow of blood or lymphatic fluid and causing rapid swelling of tissues in the hands, feet, limbs, face, intestinal tract, or airway. Usually, this swelling is not accompanied by itching, as it might be with an allergic reaction. Swelling of the gastrointestinal tract leads to cramping. Swelling of the airway may lead to obstruction, a potentially very serious complication. These symptoms develop as the result of deficiency or improper functioning of certain proteins that help to maintain the normal flow of fluids through very small blood vessels (capillaries). In some cases, fluid may accumulate in other internal organs. The severity of the disease varies greatly among affected individuals.

The most common form of the disorder is Hereditary Angioedema Type I, which is the result of abnormally low levels of certain complex proteins in the blood (C1 esterase inhibitors), known as complements. They help to regulate various body functions (e.g., flow of body fluids in and out of cells). Hereditary Angioedema Type II, a rarer form of the disorder, occurs as the result of the production of abnormal complement proteins..

Organizations related to Angioedema, Hereditary

http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Angioedema%2C%20Hereditary

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Anaphylaxis (2)

eMedicine

Last Updated: March 7, 2003

Synonyms and related keywords: systemic allergic reaction, anaphylactic reaction, anaphylactoid reaction, allergic reaction, allergies, peanut allergy, latex allergy, shellfish allergy, hypersensitivity reaction, food allergy, insect sting, Hymenoptera venom, wasp sting, bee sting, yellow jacket sting, hornet sting, penicillin allergy, radiocontrast medium allergy, contrast allergy, RCM allergy, cardiovascular collapse, laryngeal edema, atopy, atopic disease, fire ant bite, fire ant sting, immunotherapy

http://www.emedicine.com/MED/topic128.htm

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Hereditary Angioedema Support Group

http://www.hereditaryangioedema.com/

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Medline Plus

Medical Encyclopedia

National Institutes of Health

Angioedema

Alternative names  

Angioneurotic edema; Swelling - eyes

Definition

Angioedema is the development of large welts below the surface of the skin, especially around the eyes and lips. The welts may also affect the hands, feet, and throat. The condition can be associated with allergies and histamine release.

Causes, incidence, and risk factors   

Angioedema is a swelling similar to urticaria (hives), but the swelling is beneath the skin rather than on the surface. There seems to be a hereditary tendency toward the development of both angioedema and hives (see hereditary angioedema). Angioedema is associated with the release of histamine and other chemicals into the bloodstream, which is part of the allergic response.

Common allergens include:
Hives and angioedema may also occur after infections or illness (including autoimmune disorders, leukemia, and others).

Symptoms 

Signs and tests  

The diagnosis is primarily based on the appearance of the skin and a history of exposure to an irritant/allergen. There may be stridor (crowing sound when inhaling) if the throat is affected. Rarely, allergy testing may be performed to determine the causative allergen.

Treatment 

Mild symptoms may not need treatment. Moderate to severe symptoms may need treatment. Difficulty breathing or stridor indicates an emergency condition.

Self-care includes cool compresses or soaks to the area to provide pain relief and reduce symptoms.

Medications to reduce the allergic response and associated symptoms include antihistamines, adrenaline (epinephrine), terbutaline, cimetidine, corticosteroids, sedatives, and tranquilizers.

For an emergency condition, protect the airway (see breathing difficulties - first aid). At the hospital, there may be a need for intubation (placement of a tube in the throat to keep the airway open).

To prevent recurrence of angioedema avoid irritating the affected area, avoid known allergens, and avoid temperature extremes. See also allergic reactions.

Expectations (prognosis)

Angioedema that does not affect the breathing may be uncomfortable, but it generally is harmless and resolves itself in a few days.

Complications 

Calling your health care provider  

Call your health care provider if angioedema is severe and does not respond to treatment.

Go to the emergency room or call the local emergency number (such as 911) if difficulty breathing, wheezing, stridor, or fainting occurs with an episode of angioedema.

Prevention

Avoid known allergens and don't take medications that are not prescribed for you.

Update Date: 10/30/2003

Updated by: Donald Accetta, MD, MPH. President, Allergy & Asthma Care, PC, Taunton, MA. Review provided by VeriMed Healthcare Network.

http://www.nlm.nih.gov/medlineplus/ency/article/000846.htm

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See also:

Comparison of Edema versus Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=edema

Edema and Chronic Venous Insufficiency

http://www.lymphedemapeople.com/thesite/edema_chronic_venous_insufficiency.htm

Edema and Deep Venous Thrombosis

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Edema and Reflex Sympathetic Dystrophy/Complex Regional Pain Syndrome

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Edema and Venous Pooling

http://www.lymphedemapeople.com/thesite/edema_and_venous_pooling.htm

Edema of the Neck

http://www.lymphedemapeople.com/thesite/lymphedema_of_the_neck.htm

Edema and Nephrotic Syndrome

http://www.lymphedemapeople.com/thesite/edema_nephrotic_syndrome.htm

Edema of the Face

http://www.lymphedemapeople.com/thesite/edema_of_the_face.htm

Edema and Thrombophlebitis

http://www.lymphedemapeople.com/wiki/doku.php?id=thrombophlebitis

Edema and Diabetes

http://www.lymphedemapeople.com/thesite/lymphedema_and_diabetes.htm

Edema and Congestive Heart Failure

http://www.lymphedemapeople.com/thesite/lymphedema_and_congestive_heart_failure.htm

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Children with Lymphedema

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Lipedema Lipodema Lipoedema

No matter how you spell it, this is another very little understood and totally frustrating conditions out there. This will be a support group for those suffering with lipedema/lipodema. A place for information, sharing experiences, exploring treatment options and coping.

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MEN WITH LYMPHEDEMA

If you are a man with lymphedema; a man with a loved one with lymphedema who you are trying to help and understand come join us and discover what it is to be the master instead of the sufferer of lymphedema.

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All About Lymphangiectasia

Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.

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Lymphatic Disorders Support Group @ Yahoo Groups

While we have a number of support groups for lymphedema... there is nothing out there for other lymphatic disorders. Because we have one of the most comprehensive information sites on all lymphatic disorders, I thought perhaps, it is time that one be offered.

DISCRIPTION

Information and support for rare and unusual disorders affecting the lymph system. Includes lymphangiomas, lymphatic malformations, telangiectasia, hennekam's syndrome, distichiasis, Figueroa
syndrome, ptosis syndrome, plus many more. Extensive database of information available through sister site Lymphedema People.

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Lymphedema People Online Support Groups 

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Lymphedema and Pain Management 

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Infections Associated with Lymphedema 

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How to Treat a Lymphedema Wound 

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Fungal Infections Associated with Lymphedema 

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Lymphedema in Children 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children 

Lymphoscintigraphy 

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Extraperitoneal para-aortic lymph node dissection (EPLND) 

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Magnetic Resonance Imaging 

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 http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_foxc2

 Lymphedema Gene VEGFC

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_vegfc

 Lymphedema Gene SOX18

 http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18

 Lymphedema and Pregnancy

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pregnancy

Home page: Lymphedema People

http://www.lymphedemapeople.com

Updated: Jan. 13, 2012