1st Latin American Consensus on the management of lymphedema

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José L. CIUCCI
and the Consensus Group*

Central Military Hospital,
Buenos Aires, Argentina

SUMMARY

From 21 to 23 March 2003, the First Latin American Consensus Conference on the management of lymphedema was held in Buenos Aires, Argentina. The panel was composed of distinguished Latin American experts* in the area of lymphology, who discussed the following topics: definition and classification of lymphedema; diagnostic methods including lymphoscintigraphy, colour Doppler ultrasonography, direct or contrast capillaroscopy, and magnetic resonance imaging. Treatments: manual lymphatic drainage, sequential pneumatic compression, elastic compression, and benzopyrones. Multidisciplinary management: the nervous system and lymphedema, lymphedema and pain, the musculoskeletal system and lymphedema, cutaneous manifestations associated with lymphedema, lymph flow-enhancing exercises, nutrition and lymphedema, psychotherapy,and preventive recommendations. Lymphangitis: erysipelatoid lymphangitis, prophylactic treatment of lymphangitis, and immunotherapy in the treatment of lymphangitis. Surgical treatment: indications and advances in the surgical treatment of lymphedema, lymphatic-vein anastomosis with zero venous pressure, resection procedures, complications of surgery and their treatment, and informed consent.

INTRODUCTION

The desirability of a consensus conference on lymphedema had long been recognized when the Argentinian School of Lymphology was finally able to bring this project to fruition. From March 21 to 23, 2003, the First Latin American Consensus Conference on the management of lymphedema was held, in the province of Buenos Aires, Argentina. With the participation of distinguished lymphologists from across Latin America, the conference reviewed topics ranging from the classification of lymphedema to various aspects of the diagnosis and treatment. The conference proceedings will be reported in a special publication within the course of the year. The importance of this event stems, among other things, from the fact that for the first time the most renowned experts from Latin America were brought together to express their opinions, describe their practice, and present their ideas, the ultimate goal being to allow patients with lymphedema to achieve reintegration within their communities. Experts from many countries on our continent honored us with their presence, representing Brazil, Colombia, Cuba, Ecuador, Mexico, Uruguay, Venezuela, and various provinces of Argentina.

DEFINITION AND CLASSIFICATION OF LYMPHEDEMA

The definition of lymphedema was discussed and determined by consensus among the panel members as follows: lymphedema is an accumulation of water, salt, electrolytes, high-molecular-weight proteins, and other compounds within the interstitial compartment as a result of a dynamic or mechanical disturbance in the lymphatic system, the consequence being gradual and progressive enlargement of the affected extremity or other region of the body, accompanied with declines in functional and immunological capabilities, increased weight, and morphological changes.
A staging and classification scheme for lymphedema was developed on the basis of correlations linking pathophysiology, imaging study findings, and the morphology of the affected extremities. Using these correlations, various stages were defined for the classification of lymphedema. This classification system will serve as a tool for drawing a detailed picture of the condition, its natural history, and its course, while at the same time allowing physicians to determine the stage in each individual patient and, therefore, to select the appropriate treatment.

DIAGNOSTIC METHODS

The importance of lymphoscintigraphy in the diagnosis of lymphedema was discussed. This minimally invasive method has replaced, in some cases, contrast lymphography and can detect functional changes in the lymphatic system. The main advantage of lymphoscintigraphy is its ability to visualize the lymphatic flow without requiring catheterization of a lymphatic vessel, thereby eliminating the risk of injury to the lymphatic system. Although the anatomic resolution is low, new radiopharmaceuticals provide excellent contrast between the lymphatic system and the surrounding tissues. This reproducible diagnostic investigation carries no risk of allergic reactions or adverse effects. Lymphoscintigraphy is ascending and indirect; it provides information on both the transport function of the lymphatics (dynamic lymphography) and the function of lymph nodes (static lymphography). Acquisition can be static, dynamic, or by whole body scanning. The lymphatic system can be stimulated by active or passive mobilization of the limb under investigation. Examination of both sides for comparative purposes and comparison of images before and after treatment are recommended.
The role for ultrasonography and Doppler studies in the diagnosis of edema and lymphedema was discussed. When evaluating edema of the extremities, color ultrasonography is particularly useful, as it is both cost-effective and noninvasive. However, this technique provides only limited information on the anatomy and physiology of the lymphatic system and may be viewed as an ancillary method for the differential diagnosis of edema of the extremities and, in some specific cases, of lymphedema. The diagnosis of lymphedema is one of exclusion: other causes of edema of the extremities must be ruled out. The clinical picture and a number of ultrasonography findings assist in the diagnosis. *Lymph nodes may be visible when they are hypertrophic. *Obstructive lymphedema: matted metastatic nodes characterized by increased cortical echogenicity and unevenness of the capsule contours. With venous Doppler, compression may result in absence of color and loss of the spontaneous phasic flow. In primary lymphedema, distal ectasia of the vessels is visible, as well as absence of collecting lymphatics.
The panel agreed that capillaroscopy, whether direct or with fluorescein as a contrast agent, is not reliable for evaluating the lymphatic capillaries. Fluorescent agents such as Dextran 150 000 labeled with fl Na must be used to assess the lymphatic capillary networks, collecting ducts, and precollecting ducts. The fluorescent agent is injected under the dermis. Microscopic examination using a contrast capillaroscope can show normal images, with intact networks seen as ring-shaped spots and subepidermal spots. Abnormal aspects include blockage of the contrast agent, absence of spot development, dilation or unevenness of the rings, and leakage of the contrast agent through breached capillaries. One of the most important contributions of capillaroscopy to the diagnosis of lymphedema is dermal backflow after injection of the contrast agent. This has not been observed in normal patients. Today, microlymphography is extremely useful both for establishing the diagnosis and for classifying lymphedema.
Magnetic resonance imaging (MRI) is a noninvasive diagnostic method that is sensitive for differentiating lymphedema from other types of edema. In a few cases, MRI can indicate the cause of the lymphedema.

TREATMENT

Manual lymphatic drainage
Manual lymphatic drainage (MLD) is a treatment modality involving gentle maneuvers with pressures that do not exceed 40 mm Hg. MLD promotes the penetration of high-molecular-weight proteins into the initial lymphatic capillary and simultaneously stimulates contraction of the lymphatic vessel, thereby increasing the flow of lymph through the subdermal plexus and through the collaterals of the affected limbs. The patient is recumbent and the skin uncovered, with no substances interposed between the hands of the therapist and the patient. The manoeuvers performed during MLD follow the direction of the lymph flow. The rhythm should be slow, about 10 to 12 per minute. The duration of each session varies from 15 to 50 minutes.
Contraindications include acute infections, superficial and deep venous thrombosis, active neoplastic disease, and decompensated systemic conditions.

Sequential pneumatic compression
Sequential pneumatic compression is among the components of the conservative treatment of lymphedema. Current data indicate that 90% of cases of lymphedema respond favorably to conservative treatment. Sequential intermittent pneumatic compression (SIPC) should always be performed after a session of MLD. It increases the interstitial pressure, thereby promoting drainage of the fluid trapped in the interstitial compartment and promoting reduction of the edema. SIPC relies on pneumatic pumps comprising multiple chambers, which fill and empty independently from one another. The chambers work intermittently and sequentially in the distal-to-proximal direction.
The latest-generation pumps have 10 to 12 overlapping chambers designed to fragment the sequential pressures.
The pressure applied to the limb varies from 20 to 40 mm Hg in order to avoid injury to the lymphatic system; each session may last from 30 minutes to several hours. Before applying the pump, MLD must be performed to relieve obstruction in the body sectors proximal to the site of action of the pump. SIPC is contraindicated in patients with active erysipeloid lymphangitis, thrombophlebitis, heart failure, pulmonary edema, or venous thrombosis.

Compression with elastic bandages
Elastic bandage compression is at the core of every treatment program for lymphedema of the limbs. This modality should be used during the first treatment phase. Multilayered bandages ensure a high level of compression by combining a passive-protective layer and several active layers of very low-or low-stretch bandages, applied in a superimposed or overlapping arrangement, with sufficient tension to fit snugly around the limb. These bandages have a low resting pressure, of 10 mm Hg, contrasting with a high working pressure ranging from 25 to 50 mm Hg. Their effects are ascribable to reabsorption of protein and water; they increase the effectiveness of the soleusgastrocnemius pump and protect the diseased limb. Contraindications include local infection, significant arterial disease, and in situ neoplastic lesions. The orthopedic industry has developed a series of graduated elastic compression garments; thus, for upper-limb lymphedema, elastic sleeves with or without gloves are available, whereas for the lower limbs hosiery reaching up to the knee, thigh, or waist can be used. These garments apply graduated compression that decreases from the distal to the proximal limb, usually from 20 to 40 mm Hg, and exhibit medium to high elasticity. These orthopedic devices should be made of hypoallergenic material, easy to put on and take off, well tolerated, and durable. Elastic garments are indicated when the patient moves from the induction or aggressive treatment phase to the maintenance phase of physical therapy. Given the high resting pressure, they should be put on when the patient awakens in the morning and kept on until bedtime or until signs of intolerance develop.

Pharmacotherapy
It has been demonstrated that benzopyrones act via several distinct mechanisms and are extremely effective in the treatment of edema characterized by a high concentration of proteins, in particular primary and secondary lymphedema. The most widely used are the gamma benzopyrones, and among these micronized diosmin/hesperidin, which is indicated at individually tailored dosages. The dosage should be titrated, starting with 1500 mg and increasing the amount each week, to no more than 3000 mg. These agents are extremely effective and have few side effects. In follow-up studies, no evidence of nephrotoxicity or hepatotoxicity developed, even with prolonged treatment at effective therapeutic dosages.

MULTIDISCIPLINARY TREATMENT

Dr José Luis Ciucci presented an introduction on the multidisciplinary treatment of lymphedema, pointing out that close collaboration among team members working in a single facility plays a key role in reintegrating lymphedema patients in the community. The composition of the team, as well as the role of each team member, was discussed.
A number of disease states, including lymphedema, affect the nervous system. The clinical presentation is variable; stretching of the nerves manifests mainly as motor deficits followed by sensory disturbances, whereas compression predominantly induces sensory deficits. A less common presentation is hypoesthesia/dysesthesia without motor loss after radiation therapy to the axillary region. A variety of diagnostic investigations should be used to determine the severity of the nerve damage. The treatment varies according to the severity and nature of the nerve lesions; the diagnosis should be established as early as possible to ensure optimal treatment results.

Lymphedema and pain
Another topic discussed at the conference was lymphedema and pain. Special attention was directed to pain caused by lymphedema after treatment for breast cancer. The pain may be somatic or neuropathic. The first-line treatment of somatic pain is nonsteroidal anti-inflammatory drug (NSAID) therapy, with or without adjuvant medications. Weak opiates are used as second-line therapy; when this fails, strong opiates are given in combination with NSAID therapy, with or without adjuvant medications. Neuropathic pain requires treatment with adjuvant analgesic agents such as anticonvulsant medications, antidepressants, topical anesthetics, etc, either alone or in combination with other analgesics. It is worth pointing out that psychotherapeutic support should be provided concomitantly.

Functional impairment
The presentation on the musculoskeletal system and lymphedema highlighted the problems raised by functional impairment in limbs affected with lymphedema. Alterations in the epifascial structures are the main cause of functional impairment, rather than alterations in the subfascial structures. Computed tomography (CT) and MRI studies of the extremities have shown changes in the cellular subcutaneous tissue caused by fluid accumulation or fibrosis, with the characteristic honeycomb appearance and skin thickening and fibrosis; the bone and muscle structures, in contrast, remain normal.

Cutaneous manifestations and postmastectomy lymphedema
The cutaneous manifestations associated with postmastectomy lymphedema were discussed. The clinical manifestations depend on the number of lymph nodes removed and on the effects of radiation therapy. The nails, as well as the hair, are highly sensitive to various stimuli. These insults can produce an abrupt arrest in nail and hair growth. Thus, in patients with lymphedema, the nails may become yellow, opaque, and dystrophic. *Infectious skin diseases: lymphangitis, erysipelas, interdigital mycotic infections. *Traumatic lesions: excoriations, manicureinduced lesions. *Paraneoplastic skin diseases: malignant neoplasms may be associated with dermatological lesions that have no malignant characteristics per se but are directly related to the presence of the tumor. Thus, their course runs parallel to that of the malignancy: they resolve after surgical removal of the tumor and recur if the tumor recurs. Examples include paraneoplastic acrokeratosis (Bazex syndrome), erythema gyratum repens, acquired acanthosis nigricans, and paraneoplastic pemphigus (Cowden syndrome). *Skin metastases: a variety of clinical patterns exist. Carapace cancer: tumor spread to the subepidermal lymphatic spaces leads to the development of nodules in an erythematous-edematous area, usually located over the anterior chest wall in patients with breast cancer. Malignant erythema (Hutchinson syndrome) related to tumor cell spread via the deep dermal veins. Telengiectatic carcinoma produced by dissemination of tumour cells through small and superficial vessels. Stewart Treves syndrome (lymphangiosarcoma), in which nodular metastases develop on slightly erythematous and painful skin.
Lymph flow-enhancing exercises rely on muscle contractions to improve the flow of lymph; they constitute a training program that provides the patient with the gains needed to achieve reintegration into the community. When designing a training program, the location of the lymphedema and the extent of damage to muscle masses or nerves should be taken into consideration. All exercises that cause pain should be eliminated: thus, pain serves as a limiting signal. Exercises requiring maximum force should also be avoided. The focus should be on improving flexibility of the muscles and dermis, in order to optimize drainage through the veins and lymphatics. Integrated activity is of the utmost importance and should always be conducted under continuous medical supervision.

Nutrition and lymphedema
Links between nutrition and lymphedema were discussed. Lymphedema influences the nutritional status via a number of mechanisms. The chronic nature of lymphedema induces an emotional imbalance that modifies the patient’s quantitative and qualitative choice of foods, thereby directly influencing the nutritional status, causing either overnutrition or undernutrition. These nutritional disorders alter the immune responses, increase the existing edema by inducing hypoproteinemia, induce further trophic abnormalities in the skin and appendages, and hamper the healing of wounds, should any occur. Failure to recover a satisfactory nutritional balance leads to increased emotional distress, generating a vicious circle that can have devastating effects. Conversely, a satisfactory nutritional status increases the chances of a favorable outcome and diminishes the risk of intercurrent diseases.
For each individual patient, a nutritional program should be designed according to the underlying comorbidities and to their negative effects. To this end, after an evaluation of the patient’s nutritional status, the indications for nutritional therapy should be determined. Immune status improvement should be achieved by supplementation with arginine, glutamine, omega n-3 fatty acids, and antioxidants, as the underlying diseases in these patients generate an increased susceptibility to infections. Lymphedema may be associated with nutritional disorders such as overweight, obesity, dyslipidemia, protein-calorie malnutrition, and anemia; thus, special care should be taken when determining the appropriate nutritional program to ensure that there will be no negative impact on concomitant diseases.

Psychotherapy in lymphedema
Psychotherapy was incorporated into treatment programs for lymphedema when lymphedema specialists became aware of a need among their patients to discuss topics that fell outside the province of lymphology and phlebology but were within the realm of ethical and humanistic concerns shared by all physicians. Psychotherapy provides the patient with an opportunity to express unmet needs, pain, anxiety, etc. In addition, psychotherapists develop a close relationship with the patients in order to determine the meaning of the disease, which is not immediately obvious. The psychotherapist attempts to give this meaning a place in the life history of the patient, going beyond the effect of the condition on the body. Psychotherapists collaborate directly with the patient, striving to work through the psychological aspects present in the cause of the disease and evident in the physical deformity produced by the lymphedema. They work in collaboration with the other members of the management team in an effort to broaden the vision of the healthcare professionals involved in treating the patient, by integrating the role of psychological factors into the explanation of the symptom and its time course, as well as by analyzing distubances in the patient-physician or patient-health care team relationships.
The family members are also included, most notably when the patient is a child. Taking these aspects into account facilitates the work of all the team members. By offering the patients an opportunity to speak about their experience at the same time as they receive medical and surgical treatment, medications, physiotherapy, and nutritional therapy, psychotherapy maximizes the efficacy of each of these components of the management program.
Preventive measures for patients with lymphatic system disorders: patients with latent or clinically patent lymphedema, as well as their family, must receive information on the importance of preventing further damage to their lymphatic system, which might promote the development of lymphedema or worsen existing lymphedema. Effective prevention involves maintaining the trophism and humidity of the skin and appendages; avoiding injuries, such as cuts or contact with skin irritants that might cause contact dermatitis; early treatment of skin lesions such as eczema, folliculitis, or mycotic infections; elimination of intradermal, subcutaneous, and intramuscular injections; avoiding burns related to hot water or exposure to sunlight; and avoidance of muscular effort, carrying heavy loads, and wearing tight garments.

LYMPHANGITIS

The panel considered a protocol for the treatment of erysipelatoid lymphangitis designed to optimize outcomes while shortening hospital stay times and expediting the return to work. The initial induction phase involves antibiotic therapy, anti-inflammatory agents, analgesics, micronized diosmin/hesperidin, and lymphokinetic agents, selected based on the severity of the condition. Once the infectious process is under control, the second phase consists in initiation of multidisciplinary treatment combining drainage, pump therapy, lymph flow-enhancing exercises, skin care, etc, in conjunction with psychotherapy. Finally, the third phase consists of supportive therapy in those patients whose lymphedema fails to respond satisfactorily to the previous treatments. The drainage and pump therapy are continued, and specialists ensure direct control of comorbidities.
Another focus of discussion was the prophylactic treatment of lymphangitis: a number of prophylactic measures should be recommended in every patient, including proper hygiene and nutrition and avoidance of contact with pointed or cutting instruments. An additional measure is administration of a vaccine consisting of a suspension of dead cells, called Inmunoparvum, manufactured by the pharmaceutical company of Pernambuco state (LAFEPE). This vaccine has produced good results.
Another topic discussed at the conference was immunotherapy in the treatment of lymphedema. The panel examined the results of sublingual or subcutaneous immunotherapy in the prevention of recurrent lymphangitis. A comparison of the sublingual and subcutaneous vaccines showed that the sublingual route had no disadvantages as compared to the subcutaneous route. Sublingual immunotherapy with bacterial extracts (streptococci and staphylococci) was deemed a valid alternative in the treatment of recurrent lymphangitis. Results in the patients proved very good, as 80% had good outcomes and 20% fair outcomes. The antistreptolysin O test detected the production of antibacterial antibodies that may be stimulated by the vaccine. Although no relation has been found between antistreptolysin O test results and outcomes, the results after 3 years of treatment indicate that vaccination may have ensured the development of defense mechanisms against these organisms, which are susceptible to the effects of antibodies.

SURGICAL TREATMENT

The indications and limitations of surgical treatment for lymphedema were discussed. A surgical procedure performed appropriately optimizes the benefits produced by medical and physiotherapeutic means or allows these means to become effective by restoring drainage of the lymph through anatomically and physiologically intact lymphatic vessels; in this situation, lymphatic-venous anastomoses may be beneficial. In patients with chronic lymphedema, the goal is initial or residual reduction of the existing “lymphedema mass” or resection of the irreducible collagen mass (which may promote recurrences of infectious episodes), thereby improving the course of the disease.
A technical innovation in the area of lymphatic venous anastomoses was presented, namely, lymphatic-venous anastomosis with zero venous pressure in patients with lower limb lymphedema and an intact greater saphenous vein. The greater saphenous vein, whose ostial valve is competent, is converted to a cavity with no venous flow via ligation of the opening of the anastomosis and section of all the collaterals; this creates a substitute for the thoracic canal. The lymphatic-venous anastomoses are then performed with this nonfunctional venous segment.
The panel agreed that the resection surgical procedures used today in the management of lymphedema include: dermolipectomy, which consists merely in focal excision of the excess skin and subcutaneous cellular tissue followed by edge-to-edge suture and closed suction drainage. Liposuction: used mainly in postmastectomy lymphedema. Penoscrotal reconstructive surgery: using the Cordeiro technique. If the lymphedema is secondary to chylous reflux due to incompetence of the valves in the ileolumbar lymphatic vessels, the ileolumbar lymphatic chains should be ligated before the penoscrotal reconstructive procedure. Amputation is used in patients with malignant lymphedema and extensive lymph node destruction. A number of complications can occur. After bypass surgical procedures: damage to afferent lymphatic vessels, development of clots, suture dehiscence, absence or loss of union among endothelia, surgical infection, lymphocele, loss of contractility of the lymphatic vessel, and fibrotic changes in the distal lymphatics and in the lymph nodes. After surgical resection procedures: hemorrhage, surgical wound infection, skin necrosis, nerve lesions, venous thrombosis, and lymphorrhea. After surgery for penoscrotal lymphedema: infection, tissue necrosis, nerve lesions, abnormal scar formation, skin implant rejection, and impotence. Given the huge risk of complications, caution is required, and care should be taken to select the appropriate treatment; should complications occur, they must be treated as promptly as possible.
The physician should always be the coauthor of the informed consent document signed with the patient, failing which the physician is vulnerable to malpractice litigation. Consequently, the vital importance of this document as a medical act should be borne in mind, as well as the specific limitations and circumstances that make this act complex and difficult.

Servier – Phlebolymphology

Phlebolymphology is an international scientific journal entirely devoted to venous and lymphatic diseases