July-Sept 2005: LE-related complications

LymphLink Question Corner - Archived from July-Sept 2005
Andrea Cheville, MD

Q:  How is lymphedema related to obesity?

A:  Currently, we lack definitive epidemiological data regarding the association between obesity and lymphedema. We do not know the degree to which LE risk and severity increase as body mass index increases. We further lack insight into the pathophysiological mechanisms through which lymphedema and obesity may relate.

Morbid obesity appears capable of producing lymphedema in the absence of any iatrogenic or traumatic compromise of the lymphatic system. This may occur because as the arteriovenous system proliferates in response to the oxygen requirements of increasing fatty tissue, the lymphatic system fails to proliferate comparably, if at all. Progressive disequilibrium between interstitial fluid delivery and removal may produce an increase in net ultrafiltration. Ultimately, lymphatic overload and valvular incompetence may result.

Alternatively, changes in the interstitial space may develop in morbid obesity that undermine lymphatic function. The fact that obesity, even when extreme, does not consistently produce lymphedema suggests that some individuals are inherently vulnerable, presumably due to less redundancy and functional research in their lymphatic systems. Metaplastic transformation of fibroblasts into adipocytes (fat cells) has been reported in animal models. It has been suggested that the disproportionate fatty tissue in lymphedematous tissue reflects this type of conversion of alternate cell types into fat cells. At present, all proposed mechanisms remain purely speculative.

An interesting finding noted by the author, as well as other lymphologists, is the disproportionate loss of adipose tissue from lymphedematous areas when patients lose weight. Conversely, lymphedematous tissue seems to have a greater propensity to deposit fat when patients gain weight. A well-designed prospective cohort study demonstrated that weight gain after primary breast cancer therapy is second only to the extent of axillary dissection in predicting which patients will develop LE (Petrek). While obesity at the time of diagnosis also increased patients' LE risk, it was not nearly as influential as weight gain subsequent to breast cancer treatment.

Q:  Why does lymphedema cause pain?

A:  In several cross sectional studies, breast cancer survivors with lymphedema reported experiencing abnormal "sensations" in the territory affected by lymphedema. A range of sensations has been described: heaviness, tingling, aching, etc. Presumably, the sensations are produced by distention of neurons and sensory receptors in the skin and subdermal tissue. Traction on the nerve axons may cause them to fire spontaneously or to respond abnormally to sensory input. This phenomenon has been well characterized in other pain states. Generally, the sensations diminish or cease entirely with successful decongestion. If they persist, workup for an alternate etiology should be considered.

Lymphedema does not cause intense, focal pain. Incorrect attribution of focal pain to lymphedema may delay diagnosis of a potentially harmful problem. Recurrent cancer must always be considered. The level of suspicion and diagnostic work up should be dictated by the type and stage of each patient's malignancy. Tendonopathies (e.g. lateral epicondylitis, DeQuervaine's tenosynovitis, bicipital tendonitis, etc.) may develop as a result of abnormal biomechanical patterns adopted because of increased limb size and weight. Tendonopathies produce local inflammation which increases lymph load. They may trigger the initial development of lymphedema. Severe focal pain may result. Tendonopathies should be promptly diagnosed and treated to avoid reinforcement of abnormal movement patterns, accumulation of inflammatory mediators, and worsening lymphedema.

Focal pain may also arise from inflammatory and infectious arthropathies. If appropriately diagnosed, these conditions generally respond rapidly to medical management. Similar to tendonopathies, they can increase lymph load, thereby triggering or aggravating LE.

Decongestive therapy may inadvertently produce musculoskeletal overuse syndromes and inflammation in the affected limb. Compressive bandaging restricts joint excursion, increases limb weight and bulk, and forces patients to alter limb usage patterns. If patients show signs of developing a tendonopathy or arthropathy during decongestive therapy, it is critical to reevaluate the bandaging strategy, study patients' limb usage patterns and educate them in compensatory strategies to avoid stressing the inflamed structure(s).

Q:  Does lymphedema produce neurological deficits?

A:  Lymphedema does not cause focal sensory or motor deficits. When weakness, numbness, loss of dexterity, or paresthesias parallels the onset and progression of lymphedema, a unifying diagnosis should be sought. Recurrent cancer, particularly lung or breast cancer in the upper thorax, can infiltrate or exogenously compress nerves and lymph vessels/nodes. Workup should include either an MRI or CT scan with contrast. Electrodiagnostic evaluation allows identification of the precise nerves affected. In this way, plexopathies can be distinguished from radiculopathies and peripheral mononeuropathies.

As mentioned previously, patients may report "tingling" in the distribution of their lymphedema. With close questioning, patients generally can distinguish this "tingling" from the numbness and paresthesias ("pins and needles" sensation) associated with nerve compromise. Pinprick and light touch testing on neurological examination may be globally diminished throughout the territory affected by lymphedema. Currently, no pathophysiological explanation for this finding has been proposed. In Stage III lymphedema of the lower extremities, it is presumably due, in part, to dermal keratinification. Before attributing diminished sensation to lymphedema, it is critical to ascertain that the deficits do not conform to a radicular or peripheral nerve distribution.

Certain nerves are commonly injured during dissection of specific lymph node beds. During history taking, it is important to establish the temporal relationship between surgery and the onset of neurological deficits. Patients should be encouraged to differentiate post-operative deficits from those with later onset, and static from progressive deficits. The spinal accessory nerve is commonly injured during cervical and supraclavicular lymph node dissections. It provides innervation to the trapezius muscle. Injury produces scapular depression and protraction. The intercostal brachial nerve, commonly sacrificed during axillary lymph node dissections, is a purely sensory nerve. It variably innervates the proximal, medial upper arm, superior flank, and axilla. Femoral cutaneous nerves, also purely sensory, are frequently injured during inguinal lymph node dissections. They innervate the anterior and lateral thigh.

Many patients with secondary lymphedema related to cancer have received neurotoxic chemotherapy agents. Taxanes (docetaxel, paclitaxel), vincaalkyloids (vincristine, vinblastine), and platinum based compounds (cis-platin, carboplatin, oxaliplatin) produce peripheral neuropathy. In addition to the stockingglove numbness and paresthesias characteristic of chemotherapy-induced neuropathies, patients may experience greater sensitivity to mild compression along the neural axis. Compression occurs at sites common in non-cancer populations, e.g. neural foramina, thoracic outlet, ulnar groove, carpal tunnel, etc. Focal neurological deficits in patients who have received neurotoxic chemotherapy mandates careful neurological evaluation with attention paid to potential sites of compression. Electrodiagnostic testing may be required for a definitive diagnosis.


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