Hereditary Lymphedema, Type I Congenital Hereditary Lymphedema Milroy Disease Nonne-Milroy-Meige Syndrome Hereditary Lymphedema, Type II Meige's Lymphedema Familial Lymphedema Praecox Hereditary Lymphedema Tarda Hereditary Lymphedema Type III
Form of primary hereditary lymphedema that expresses itself during middle age (generally onset 35+ years). Swelling generally occurs in the legs and may involve either one or both limbs. There is a higher incidence of [lymphedema tarda among females than males.
This form of inherited lymphedema accounts for approximately 10% of those with primary lymphedema.
Basic diagnosis can be made by the fact that swelling (generally of the legs) unexpectedly and there is a family history of similar swelling. Currently the most precise diagnosis can be made by a lymphoscintigraphy test. In this test a radioactive substance is injected into the limb and is traced on a computer screen. Through this method the exact location of the lymphatic blockages can be identified.
It is suspected that the cause of lymphedema tarda is a break in the FOXC2 gene.
The usual complications involved with the condition include fibrosis of the limb tissues, cellulitis (and or lymphangitis and erysipelas infections). Other complications made include involvement of the genitalia, pain, skin conditions and in very rare situations lymphangiosarcoma.
Long term prognosis is excellent is the condition is identified early and treatment begins so after the diagnosis is made.
It is important as well to be aware that when you have lymphedema, even in one limb there is always the possibility of another limb being affected at some later time. This “inactive” period referred to as the latency stage. It is associated with hereditary forms of lymphedema.
Lymphatic transport capacity is reduced No visible/palpable edema Subjective complaints are possible
(Spontaneously Irreversible Lymphedema) Accumulation of protein rich edema fluid Pitting becomes progressively more difficult Connective tissue proliferation (fibrosis)
Treatment of Leg Lymphedema
1. Infections such as cellulitis, lymphangitis, erysipelas. This is due not only to the large accumulation of fluid, but it is well documented that lymphodemous limbs are localized immunodeficient and the proein rich fluid provides an excellent nurturing invironment for bacteria.
2. Draining wounds that leak lymphorrea which is very caustic to surrounding skin tissue and acts as a port of entry for infections.
4. Loss of Function due to the swelling and limb changes.
5. Depression - Psychological coping as a result of the disfigurement and debilitating effect of lymphedema.
6. Deep venous thrombosis again as a result of the pressure of the swelling and fibrosis against the vascular system. Also, can happen as a result of cellulitis, lymphangitis and infections.
7. Sepsis, Gangrene are possibilities as a result of the infections.
8. Possible amputation of the limb.
11. Chronic localized inflammations.
12. Pain ranging from mild in early lymphedema to severe in late stage lymphedema.
13. Lymphatic cancers which can include angiosarcoma, lymphoma; Kaposi's Sarcoma; lymphangiosarcoma (Stewart_treves Syndrome); Cutaneous T-Cell lymphoma; Cutaneous B-Cell lymphoma; Pseudolymphomatous Cutaneous Angiosarcoma. See also: Primary Lymphedema and Cancer for a discussion and Lymphatic Cancers Secondary to Lymphedema.
Note: These cancers are rare and are usually associated with long term, untreated or improperply treated lymphedema. Typically occuring in stage three or four; quite rare in stage two.
14. Skin complications possible in stages 3 and 4 include papillomatosis; placques including “cobblestone” appearing placque; dermatofibroma; Skin Tags; Warts and Verrucas; Mycetoma skin fungus; dermatitis and many lymphedema patients report increased problems with psoriasis; eczema and shingles. I would suspect this may be due to again, the immunocompromised condition of the arm or leg afflicted with lymphedema.
16. Debilitating joint problems. This is caused by a combination of the excess fluid weight and the constant inflammatory process that accompanies lymphedema. As we have gotten older, many lymphedemapatients are having total knee replacement, total hip replacement, or total shoulder replacement while others are experiencing carpal tunnel syndrome and are having carpal tunnel surgery or experiencing shoulder problems associated with lymphedema and must haverotator cuff surgery
Long standing lymphedema causes a condition known as fibrosis. As the fluid continually collects in a limb, it becomes hard and dense. With each stage of lymphedema there is also a change in the tissue texture of a limb.
With stage one the tissue is still much like normal tissue, its just satiated with fluid. As the swelling continues and as he fluid changes to that protein-rich fluid referred to a lymphorrea, you enter into stage two. In this stage, the tissue become very similar to a grape (best image I can think of). Already it is becoming much more difficult for antibiotics to reach bacteria and it becomes less response to the decongestive therapy.
At stage three, the tissue become similar to one of those old synthetic kitchen sponges, the ones that become rock hard when they are dry.
This is the very real serious side affect of stage three lymphedema. This type of tissue increases potential of persistent and very hard to treat cellulitis or lymphangitis.
The denseness of the limb prohibits antibiotics from reaching the infecting bacterium and it is often able to survive in pockets of fibrotic tissue. These pockets act as a septic foci and after antibiotic treatment is completed, the infections will reappear.
Generally at this stage it is going to take IV antibiotics to deal with any infection because oral antibiotics just are not able to penetrate this mass of hard tissue.
Also, as the fibrosis intensifies you become more susceptible to deep venous thrombosis (DVT) and other circulatory problems. You may also start to experience neuropathy as the pressure of this tissue compresses nerves within the limb.
Acute Cellulitis is one of the complications of lymphedema. The patient may not be aware of the source of the etiology. Sometimes it may be a cut, mosquito bite, open wound or other infection in the body.
The first sign is increased or different quality of PAIN involving the lymphedema limb. The patients often describe this as a “flu like symptom or an ache” involving the Lymphedema arm or leg. This is usually followed by sudden onset of ERYTHEMA(redness, red streaks or blotches) on the involved limb. The HYPERTHERMIA(lymphedema limb becomes warm, hot) will follow and the patient may experience the CHILLS and even HIGH FEVER.
The early intervention and treatment with antibiotics will resolve this condition (it usually takes one week of antibiotics). Only a Medical Doctor will be able to prescribe the Antibiotics, thus a consultation with a Doctor is necessary. Severe Cellulitis may require Inter venous Antibiotic treatment and hospitalization. Again, elevation of the affected limb is important.
During that phase the patient should NOT massage the Lymphedema limb, bandage, apply the pump, wear tight elastic sleeve or exercise excessively. Avoid the blood pressure and blood to be drawn from the involved arm. Keep the limb elevated as much as possible while resting. Once the symptoms dissipate the treatment MLD/CDP should be initiated.
How do we prevent this infection? The patient should be careful with daily activities and take all precautions to protect the skin (wear gloves when gardening, cleaning with detergents, etc… ). If an injury to skin occurs on the Lymphedema limb it is necessary to clean the wound with alcohol or hydrogen peroxide and apply Neosporin/Polysporin antibiotic ointment. If the symptoms progress seek the attention of a physician immediately.
Manual Lymphatic Drainage (MLD) is a unique, therapeutic method of stimulating the movement of fluids in the tissues. The gentle, rhythmic, pumping, massage movements follow the direction of lymph flow and produce rapid results. It assists the cutaneous lymphatics in picking up and removing not just fluids, but all the waste products, protein particles and debris from our system. It also is successful in breaking fibrosis and fibrotic areas of a lymphodemous limb.
This treatment was created and developed Danish therapists Dr. Emil Vodder and his wife, Estrid, in the 1930's and was introduced in Paris in 1936. They are also credit with creating a specialty of medicine called Lymphology.
First brought to North America in 1982, the school is located in Victoria, British Columbia, Canada. Before it was introduced the standard treatment course in North American was either a surgery called debulking or the use of compression machines wherein the limb was literally squeezed by pneumatic air pressure.
Comprehensive Decongestive Therapy (CDT) is used primarily in the treatment of lymphedema and venous insufficiency edema. It is a combination of MLD, bandaging, exercises and skin care. CDT may also involve breathing exercises, compressive garments and dietary measures. A frequent indication for CDT is lymphedema caused by irradiation or surgery due to cancer. It can relieve edema, fibrosis and the accompanying pain and discomfort.
Also known as Complete Decongestive Physiotherapy (CDP), this treatment therapy was pioneered in the United States by Dr. Robert Lerner.
The treatment for leg lymphedema is much the same as treatment for arm lymphedema. The preferred treatment is decongestive therapy. See also manual lymphatic drainage mld complex decongestive therapy cdt.
There is one final and critical area pertaining to the treatment, control and management of lymphedema, and that is exercise. Not only is it vital for our over all health, it helps in weight control and is important for the movement of lymph fluid through our body. No matter the stage of lymphedema, underlying medical conditions or age, everyone of us should have a plan for exercises for lymphedema.
Sometimes too, the process we must go through to get our treatment covered is maddening to say the least. You made need to learn how_to_file_a_health_insurance_appeal to reverse a coverage or treatment denial and you may even have to learn the process how to file a complaint against your insurance company with your state commissioner.
Clin Exp Dermatol. 2009 Dec
Localized bullous pemphigoid in a patient with primary lymphoedema tarda. Perez A, Clements SE, Benton E, Robson A, Bhogal B, Stefanato CM, McGibbon D.
St John's Institute of Dermatology, St Thomas' Hospital, London, UK. firstname.lastname@example.org
Correspondence to Dr A Perez, St John's Institute of Dermatology, St Thomas' Hospital, London, SE1 7EH, UK E-mail: email@example.com
Conflict of interest: none declared.
We report a case of localized bullous pemphigoid (BP) in a woman patient with primary lymphoedema tarda. There is only one previous case reported of localized pemphigoid in an area of lymphoedema, this being of the cicatricial variant. Slow circulation in the lymphatic vessels, increased capillary permeability with preferential localization of antibodies in the area, and potential cleavage of the epidermal junction due to increased hydrostatic pressure leading to autoimmunity, have all been advocated as possible pathogenic mechanisms. Nevertheless, we consider that the mechanism by which localized pemphigoid arises on lymphoedema remains elusive, based on a previous case of generalized BP sparing an area of postsurgical lymphoedema.
J Pediatr. 2003 Jun;
Levinson KL,Feingold E, Ferrell RE, Glover TW, Traboulsi EI, Finegold DN. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
OBJECTIVE: To characterize age of onset patterns and penetrance in hereditary lymphedema, including differences caused by sex and genetic heterogeneity.
STUDY DESIGN: Kaplan-Meier analysis of three family cohorts with autosomal dominant lymphedema: (1) five families with unique mutations in FLT4, (2) 16 families with unique mutations in FOXC2, and (3) 77 families with no mutations yet identified in any gene (the heterogeneous group). RESULTS: Age of onset was typically congenital among FLT4 mutation families and pubertal among FOXC2 mutation families, with similar male and female penetrance in both groups. Age of onset was highly variable in the families with no identified mutation, with substantially higher penetrance among female patients than male patients. In addition, male patients and female patients in the heterogeneous group had very different overall age of onset profiles.
CONCLUSIONS: The two genes identified to date that cause hereditary lymphedema have equal male and female effects, but each displays a different pattern of onset age and penetrance. The heterogeneous group represents a genetically heterogeneous population and has phenotypic overlaps with the FLT4 and FOXC2 mutation families.
Exp Clin Transplant. 2006 Dec
Saab S, Nguyen S, Collins J, Kunder G, Busuttil RW. Department of Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, Los Angeles, California 90095-7302, USA. Ssaab@mednet.ucla.edu
We present a patient with lymphedema that developed after orthotopic liver transplantation. The cause of the posttransplant lymphedema was likely related to a developmental abnormality of the lymphatic system that was exaggerated by refractory chylous ascites. A peritoneal fluid with a milky appearance, chylous ascites is rich in triglycerides and is caused by the obstruction or disruption of abdominal lymphatic channels. It is a rare complication that may develop after trauma or abdominal surgery or as a result of a malignant disease, and it is even more uncommon after liver transplantation. Therapy for chylous ascites involves treating its underlying cause. In the patient we describe, lymphedema tarda, which was diagnosed 6 months after liver transplantation, was likely caused by chylous ascites and a developmental abnormality of the lymphatic system.
In June 2004, a 49-year-old man underwent orthotopic liver transplantation (OLT) without venovenous bypass for decompensated liver disease caused by hepatitis C and alcohol abuse. The manifestations of his liver disease included hepatic encephalopathy, refractory ascites, extreme fatigue, lower-extremity edema, and hepatocellular carcinoma. The ascitic fluid was clear and the color of straw. The serum ascites gradient was greater than 1.1 g/dL. After surgery, this patient was discharged with instructions to continue treatment with mycophenolate mofetil, prednisone, tacrolimus, trimethoprim/sulfamethoxazole, and ganciclovir. At discharge, his aspartate amino transferase (AST) and amino alanine transferase (ALT) values were 39 U/L and 78 U/L, respectively.
One month after the transplantation, the patient underwent a liver biopsy to determine the cause of newly elevated values of AST (284 U/L) and ALT (596 U/L). The results of a percutaneous liver biopsy were consistent with recurrent mildly active chronic hepatitis C and portal fibrosis. Two months after his surgery, straw-colored ascites developed, and the following results of liver testing revealed worsening hepatic function: serum total bilirubin, 9.0 mg/dL; serum creatinine, 1.8 mg/dL; alkaline phosphatase, 286 U/L; ALT, 397 U/L; and AST, 508 U/L. The hepatitis C viral load at that time was 2,840,000 IU/mL. A 10-cm 10-Fr biliary stent was placed during endoscopic retrograde cholangiopancreatography in the common bile duct to ensure a smooth anastomotic stricture. A repeat liver biopsy revealed chronic hepatitis C with mild lymphocytic infiltrates and periportal fibrosis. Treatment with pegylated interferon and ribavirin for recurrent hepatitis C was initiated.
In March 2005, 9 months after the transplantation, bilateral nonpitting lower-extremity edema and diuretic-refractory ascites developed and were treated with large-volume paracentesis every 2 weeks (± 0.66 week). During each paracentesis treatment, a mean (± SD) volume of 9 L (± 2.5 L) was removed. The ascitic fluid was milky, and the patient’s triglyceride value was 173 mg/dL (± 46.2 mg/dL). The ascitic fluid albumin value was < 1 g/dL, and the mean serum albumin value was 2 g/dL (± 0.22 g/dL). The mean serum creatinine value was 1.7 mg/dL (± 0.2 mg/dL), and the serum triglyceride value ranged from 248 to 255 mg/dL. The results of bacterial and fungal cultures and cytologic studies were consistently negative. Magnetic resonance imaging (MRI), including MRI angiography and venography of the abdomen and pelvis, revealed marked ascites and patent blood vessels. The results of the hepatic venogram and pressure measurements showed no peritoneal abnormality, portal hypertension, or hepatic vein thrombosis. The results of a transjugular liver biopsy indicated mild lymphocytic infiltration and periportal fibrosis
Because of the patient’s persistent chylous ascites, a lymphangiogram was performed to determine whether the thoracic duct was intact. The diagnosis of lymphedema tarda (Meige disease) was based on the results of the bipedal lymphangiogram, which demonstrated insufficient lymphatic drainage from the left lower extremity and lymph nodes within the femoral triangle as well as mild fibrosis over the dorsal fascial planes (Figures 1, A and B; and 2, A and B) . Fluoroscopically guided cannulation of a single lymphatic vessel over the dorsum of the right foot revealed impedance to the flow of ethiodized oil (Ethiodol) contrast medium. Fluoroscopically guided cannulation of the lymphatic vessel over the left foot showed the flow of Ethiodol into a single dilated lymphatic vessel (as opposed to the usual 6 to 10 such vessels) over the medial left thigh and into a single superficial inguinal lymph node (Figure 1, A and B). Ethiodol contrast medium was noted in the superficial inguinal, hypogastric, and iliac divisions. Eventually, the contrast medium advanced into the left lumbar lymphatic vessels and crossed over to the right of midline, partially outlining the periaortic lymphatic vessels up to the level of the second to the third lumbar vertebra of the cisterna chyli. The contrast medium was contained within the thoracic duct at the middle of the twelfth thoracic vertebra. A fluoroscopically guided study showed the extravasation of Ethiodol from the thoracic duct at the level of the twelfth thoracic vertebra. A metal wire was placed over the site to mark the level of extravasation of the contrast medium (Figure 3, A and B). Initial and delayed 24-hour follow-up radiographs documented the swelling of both feet as well as the circumvention of residual Ethiodol contrast medium into the superficial and dermal lymphatic vessels of the left foot and leg (Figure 2, A and B). The images featured in this report best display the causes of the patient’s lymphedema tarda and the extravasation of Ethiodol as previously described.
In July 2005, treatment with pegylated interferon and ribavirin was discontinued. The following month, therapy with a low-fat medium-chain triglyceride and orlistat was begun. Although the frequency of paracentesis was not altered, the ascitic fluid triglyceride level decreased from a mean of 173 mg/dL to 75 mg/dL. The patient underwent the placement of a peritoneovenous shunt in October 2005. From October to February 2006, he required 3 paracentesis treatments. The mean (± SD) ascitic fluid triglyceride value on the day of each paracentesis treatment was 75 mg/dL (± 10.6 mg/dL), and the mean (± SD) serum albumin value was 3.7 g/dL (± 0.33 g/dL). Furthermore, the appearance of the ascitic fluid changed from milky to clear and straw-colored. Since February 2006, this patient has not required further paracentesis, and his lymphedema has resolved. Abdominal ultrasonography in March 2006 revealed no ascites, and his hepatitis C viral load was undetectable.
Discussion Chylous ascites is a rare finding that was shown in a study by Press and colleagues to occur with an incidence of approximately 1 in 20,000 admissions to a large university-based hospital over a 20-year period . However, it is widely believed that the incidence of chylous ascites has increased because of more aggressive cardiothoracic and abdominal surgery as well as the longer survival of patients with cancer . Chylous ascites can be caused by any of 3 mechanisms: obstruction of the major lymphatic channels at the base of the mesentery or the cisterna chyli, which causes leakage of chyle from dilated mesenteric lymphatic vessels; direct leakage of chyle through a lymphoperitoneal fistula created by abnormal or injured retroperitoneal lymphatic vessels; or the exudation of chyle through the retroperitoneal megalymphatic vessels without a visible fistula or obstruction of the thoracic duct .
Chylous ascites is caused by an abdominal malignacy or cirrhosis in more than two-thirds of all patients . As many as half of those malignancies are lymphomas [1, 5]. Injury during abdominal aortic surgery, which is the most common cause of postoperative chylous ascites, results in 81% of all chylous complications . Nevertheless, chylous ascites accounts for fewer than 1% of all complications after vascular surgery involving the abdominal aorta . Warren shunts are an uncommon cause of chylous ascites , and chylous ascites rarely develops after liver transplantation [2, 10, 11]. We presumed that the development of chylous ascites after OLT in our patient (who did not exhibit ascites before his liver transplant) was caused by the disruption of lymphatic vessels near the porta hepatis or the retrohepatic area during the dissection and removal of the native liver.
Primary lymphedema, which results from aplasia or hypoplasia of the lymphatics, is thought to be a genetically determined disease, the expression of which varies by the patient’s age at onset . There are several primary causes for lymphedema: Milroy disease, a rare disorder in which the patient demonstrates a lymphatic malformation at birth; lymphedema praecox, which has an onset at or near puberty; and lymphedema tarda (Meige disease). Lymphedema tarda is the rarest developmental abnormality of the lymphatic system and is not clinically evident until the patient is 35 years of age or older. The manifestation of lymphedema tarda usually follows a precipitating event such as trauma or an inflammatory reaction .
The time of onset of lymphedema may be associated with the relative number of functioning lymphatic vessels. It is generally thought that the fewer the lymphatic vessels, the earlier the onset of lymphedema. Patients with lymphedema often exhibit absent or incompetent lymphatic valves. The results of a lymphangiogram revealed lymphedema tarda in our patient. In our opinion, our patient’s lymphedema was clinically manifested only after a secondary insult (in his case, the development of chylous ascites that was likely caused by a leaking lymphatic vessel, located in the area of surgical dissection, that impeded lymph return).
Chylous ascites frequently causes painless abdominal distension . Abdominal paracentesis is the most important diagnostic tool in evaluating and managing patients with ascites. In contrast to the straw-colored and transparent appearance of ascites caused by cirrhosis and portal hypertension, chylous ascites usually has a cloudy and turbid appearance. The triglyceride value in ascitic fluid (which is typically higher than 200 mg/dL, although some clinicians use a cutoff value of 110 mg/dL [14, 15]) is very important in identifying chylous ascites. Radiographic studies useful in the diagnosis and management of chylous ascites include computed tomography (which reveals pathologic intra-abdominal lymph nodes and masses) and lymphangiography and lymphoscintigraphy (which show abnormal retroperitoneal nodes, leakage from dilated lymphatic vessels, fistulization, and the patency of the thoracic duct) [16, 17]. Lymphangiography, which is the gold standard for identifying obstructions, may result in complications such as reactions to the contrast medium, transient lymphedema, tissue necrosis, or fat embolism [5, 16].
The management of chylous ascites remains controversial, but current treatments include repeated therapeutic paracentesis; a high-protein, low-fat, medium-chain–triglyceride diet; total parenteral nutrition (TPN); diuretics; the placement of a transjugular intrahepatic portosystemic shunt; peritoneovenous shunting; percutaneous coiling of the thoracic duct; or surgical ligation of the disrupted lymphatic channel [1, 18, 19]. The use of TPN in combination with octreotide has been reported to result in the rapid resolution of chylous ascites after liver transplantation . It has been speculated that somatostatin improves chylous ascites by inhibiting lymph fluid excretion through specific receptors found in the normal intestinal wall of lymphatic vessels . In a retrospective review of 156 patients with chylous ascites from various causes, 51 patients were successfully treated surgically (41% with the ligation of a leak, 39% with a peritoneovenous shunt, 10% with resection, and 10% with another surgical technique such as a peritoneal fluid filtration circuit) . Of the 105 remaining patients who were treated conservatively, 67% were treated successfully. Forty-three percent of those individuals achieved success by dietary modification alone; a combination of diet, TPN, and paracentesis was successful in 26%; TPN alone produced resolution in 14%; and paracentesis alone was successful in 7% .
Our patient was initially treated with orlistat (which was recently reported to have benefitted a patient with chylous ascites ) and a high-protein, low-fat, medium-chain–triglyceride diet. When those measures were unsuccessful, he underwent the placement of a peritoneovenous shunt. Eventually, he experienced the resolution of both his chylous ascites and the edema caused by abnormal lymphatic drainage. Our case report should increase the awareness that congenital anomalies of the lymphatic system, when exacerbated by surgical procedures such as OLT, are often indicated by edema of the lower extremities
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2230.2009.03722.x/abstract|Wiley Online Library]]
Med Sci Monit. 2006 Oct
J Natl Med Assoc. 2005 Jul
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