Wednesday, November 12, 2008

Do Bone Fractures Cause Lymphedema?

Do Bone Fractures Cause Lymphedema?
Over the past few years, there have been several members of my various groups who have reported lymphedema triggered by bone breaks. These cases involve both arm lymphedema and leg lymphedema.

This is highly unusual and even many lymphedema experts are unaware this can occur.

If we start with the premise that some people are born with an already “at risk” lymph system and then understand the exact mechanisms of the lymphatic system response to trauma and the changes within the lymph nodes, then it becomes clear that this is in fact a possibility.

I need to remind readers that I am not a medical professional nor have I ever had formal medical training and/or education. What is presented is a combination of my fifty-five years of living with lymphedema and from the research that I have undertaken.


Effect of lymphedema on the recovery of fractures

J Orthop Sci. 2007 Nov;
Arslan H, Uludağ A, Kapukaya A, Gezici A, Bekler HI, Ketani A. Department of Orthopedic and Trauma Surgery, University of Dicle, School of Medicine, Diyarbakir, Turkey.

BACKGROUND: Lymphedema delays the healing of any wound by negatively affecting its inflammatory period. Whether it affects bone healing in a similar negative manner is unknown. Therefore, we experimentally investigated the effect of lymphedema on fracture recovery.

METHODS: We used thirty 200- to 250-g Sprague-Dawley rats for the experiment. The rats were randomly divided into two groups of 15 rats each for the experimental lymphedema and control groups. Lymphedema development was confirmed by measuring the circumference and diameter of the extremities together with lymphoscintigraphy. Twenty days after the development of lymphedema, a fracture model was created in both groups in the right tibia with mid-diaphyseal osteotomy and fixing with an intramedullary Kirschner wire. After 6 weeks, all rats were sacrificed and the callus tissue that formed along the osteotomy was compared between groups with respect to radiographic, histological, and biomechanical characteristics.

RESULTS: The three-point bending test yielded an average stiffness value of 1227 N/mm (n = 6) in the control group and 284 N/mm (n = 7) in the experimental lymphedema group (P <>

CONCLUSIONS: Lymphedema negatively affected bone healing in rats. However, the mechanism of this negative effect and its occurrence in humans are still unknown. Further experimental and clinical studies are needed to support and extend our findings.


The healing of tibial fracture and response of the local lymphatic system

Szczesny G, Olszewski WL, Gewartowska M, Zaleska M, Górecki A. Department of Surgical Research and Transplantology, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.

BACKGROUND: Damage of tissues by mechanical injury and inflammation is followed by reaction of the regional lymphoid tissue, lymphatics, and lymph nodes. In our previous lymphoscintigraphic studies, we showed that closed fractures of a lower limb cause reaction of the local lymphoid tissue. There was dilation of lymphatics draining the site of the fracture and enlargement of inguinal lymph nodes. These changes persisted even after clinical healing of the fracture. In the long-lasting nonhealing fractures, the lymphoscintigraphic pictures were different. The draining lymphatics became obliterated, and the lymph nodes disappeared.

METHODS: In this study, we tried to correlate the lymphoscintigraphic images, reflecting the immune events at the fracture site, with the immunohistochemical observations of the biopsy specimens obtained during corrective operations from the healing and nonhealing fracture gaps. Thirty-eight patients with closed fracture of the tibia without traumatic skin changes were studied.

RESULTS: We confirmed that closed tibial fracture evokes response of the regional lymphatic system. Normal fracture healing with immune cell infiltrates and foci of ossification was accompanied by dilated lymphatics and enlarged lymph nodes. Prolonged nonhealing fracture with lack of cellular reaction in the gap proceeded with decreased mass of lymph nodes.

CONCLUSION: This study provides evidence for existence of a functional axis between wound of bone and surrounding soft tissue and the local lymphatic (immune) system. We hypothesize that the fast healing is regulated by influx into the wound of lymph node regulatory cells, whereas prolonged healing causes gradual exhaustion of the regional lymph node functional elements, and reciprocally impairment in sending regulatory cells to the fracture gap.

Journal of Trauma

Limb lymph node response to bone fracture.

Lymphat Res Biol. 2004;
Szczesny G, Olszewski WL, Zaleska M. Department of Surgical Research and Transplantology, Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland.

In previous clinical studies, dilation of afferent lymphatics and enlargement of inguinal lymph nodes (LN) were observed in lymphoscintigrams from patients with persistent posttraumatic edema of lower extremities after fractures and trauma of soft tissues. In this study, changes in rat popliteal and iliac lymph nodes draining lymph from the site of tibial fracture and adjacent soft tissue injury were investigated. The observed parameters were lymph node weight, cell number, phenotype frequency, cell cytokine expression, and reactivity to mitogens. The key observations included: a) increase in the weight and total cell number of the lymph nodes; b) increased autotransformation rate and responsiveness of lymph node cells to mitogen; c) decreased frequency of ED1 macrophages and activated OX8 cytotoxic cells in flow cytometry analysis; d) high expression of OX6 class II-positive, OX7 (stem cells), OX62 (migrating dendritic cells), ED1 (macrophages), and OX12 (B cells) on immunohistochemical sections of LNs with some few HIS48 (granulocytes); e) high expression of NOS3 and TGF beta by lymph node lymphocytes and endothelial cells.

In summary, local lymph nodes reacted to internal wounds, such as bone fracture and injury to adjacent tissues, through mobilization of cells from the blood circulation, along with activation of cellular subsets. The molecular mechanism that provides the signal for this reaction remains unknown. The absence of major changes in the frequency of lymph node cell subpopulations indicates that lymph nodes are constitutively prepared for influx of antigens from damaged tissues and react only with increase in cell number and cell activation. The nature of the reaction, including lack of immunization against autoantigens, remains unclear. Further elucidation will require studies on the mechanism of cross-tolerance to self-antigens during wound healing.


Lymphedema of the Hand and Forearm Following Fracture of the Distal Radius

By David A. Kasper, DO, MBA; Menachem M. Meller, MD, PhD ORTHOPEDICS 2008; 31:172

February 2008

Lymphedema of the hand following a fracture of the distal radius is a rare complication resulting from abnormal protein-rich fluid accumulation in the affected area. Although lymphedema affects approximately 2.5 million Americans and frequently is associated with breast cancer treatment, its occurrence in the context of a commonplace injury to the wrist is virtually nonexistent.1

The etiology of lymphedema development following fracture care is poorly understood and has been attributed to psychogenic causes. Only one case of lymphedema following a Colles fracture has been reported in the literature.2 In that report, the patient was a 42-year old man who presented with lymphedema after a fall while accidentally being pulled by a chain. After closed reduction of the fracture and immobilization, the patient reported intense pain without swelling. Immediately after removal of the patient’s final cast, his hand began to swell, and he underwent intense physiotherapy, numerous sympathetic nerve blocks, and hospitalization with no improvement. The authors suggested the pathogenesis of the patient’s lymphedema after his fracture was self-induced and psychogenic in nature.

This article presents a case of Colles fracture complicated by nonpitting edema in a 62-year-old woman in whom psychogenic causes were not identified.

Case Report

A 62-year-old right hand-dominant woman fell down a few steps at work onto her outstretched right hand. Evaluation in the emergency room indicated a fracture of the distal radius, and the patient underwent closed reduction (Figure 1) under general anesthesia without a tourniquet.
This resulted in excellent restoration of the skeletal alignment. She was placed in a well-padded short arm cast.

At a routine follow-up visit 10 days later, the patient had complete loss of position, with the fracture reverting to the presurgical misalignment sustained immediately following the injury. She subsequently underwent open reduction and internal fixation using a dorsal plate. Both the surgery and postoperative course were uneventful.

The patient’s history included controlled hypertension, mitral valve prolapse, gastroesophageal reflux disease, rheumatic fever, scarlet fever, and a prior arthroscopic knee procedure. She reported no prior malignancies, and she was compliant with routine general medical care.
Psychological profiling was normal.

Following cast removal, the patient began occupational and physical therapy. Two months postoperatively, the swelling persisted, and she developed increasing asymmetry. She also had progressive nonpitting edema. The patient reported having no pain, hypersensitivity, or other symptoms. She also reported she did not develop any other illnesses or malignancies during this time.

The patient underwent an extensive workup that included electrodiagnostic studies and radiographs of the cervical spine, right shoulder, and right wrist (Figure 2). Computed tomography and magnetic resonance imaging revealed prominent edema adjacent to the capsule (Figure 3). An intravenous Doppler study ruled out deep vein thrombosis of the right upper extremity. A Duplex arterial scan and technetium bone scan revealed no pathological findings other than the fractured wrist.

Her fracture healed satisfactorily without additional loss of position. However, the function of her right hand was limited by the edema (Figure 4). Traditional treatments, such as a Jobst gauntlet (BSN-Jobst, Inc, Charlotte, North Carolina), Kinesio taping (Kinesio, Albuquerque, New Mexico), massage, elevation, and Isotoner gloves (Totes Isotoner Corp, Cincinnati, Ohio) supplemented by home exercises failed to relieve her symptoms.

Treatment subsequently was prescribed with the NormaTec PCD (pneumatic compression device; NormaTec, Newton Center, Massachusetts), and the patient initially used it at home for 4 hours daily. Within 2 weeks, her massive forearm edema dramatically diminished, and her wrist and hand motion normalized. She was able to bring her fingertips down to the proximal palmar crease with good grip, pinch, and opposition.

To inhibit the recurrence of the edema and hand stiffness, the patient has continued to use the device at home approximately 1 hour per week. She requires no compression garments and has not had any episodes of cellulitis (Figure 5).


Although lymphedema is a common and severely disabling medical condition, it has not been described following orthopedic injuries such as a Colles fracture. The only previously published case report describing this injury combination attributed the lymphedema to psychogenic causes.2 In our patient, psychogenic causes were not identified.

Lymphedema results when the lymphatic volume in tissue exceeds the lymphatic transport system’s capabilities to clear the fluid. Increased hydrostatic pressure or decreased plasma oncotic pressure creates gradients across the capillary membranes, which causes the excess fluid to spill and accumulate in the interstitial space. Possible causes of this excess fluid production include local inflammation, surgery, infection, cancer, lymphatic obstruction (ie, due to scarring), and trauma.3 Although all body tissues are bathed in interstitial fluid, the lymph circulation still remains a complex, dynamic, and incompletely understood process.4

Lymphedema can be classified into two types: primary and secondary. Primary lymphedema is associated with hypoplastic, hyperplastic, missing, or impaired lymph vessels. Other presentations are classified further by age of onset. However, causes of primary lymphedema are generally unknown and cannot be linked to any specific traumatic event. The most common cause of primary lymphedema is lymphangiodysplasia.

Secondary lymphedema can be attributed to trauma to the lymph nodes or the lymphatic vessels themselves. Secondary lymphedema frequently is seen in surgical patients and is attributed to lymphatic obstruction.3 Speculations suggest secondary lymphedema associated with trauma is a consequence of an infectious or inflammatory process.3

Mechanical injury of the soft tissues and bones of the extremities usually is followed by edema distal to the site and at the site itself but not proximal to it. Patients usually present with a sensation of fullness and pain in the affected area, induration, edema, hyperkeratosis, and xerosis. Functional limitations include decreased range of motion, joint inflexibility, decreased mobility (if the lower limb is affected), and decreased activities of daily living (eg, grooming and dressing).3

For several decades, treatments to relieve lymphedema and traumatic or postoperative edema included manual massage, gradient compression stockings and sleeves, bandaging, taping, and pneumatic compression devices previously referred to as lymphedema pumps. All of these treatments used external compression, but none produced consistently good clinical outcomes.

Additionally, these treatments used static compression strategies, with compression applied and held constant for varying lengths of time. Most of the lymphedema pumps were poorly bioengineered, and their designs lacked understanding of the optimum parameters for noninvasive compression.

Recently, the concept of pneumatic medicine was developed to more clearly characterize and advance the science of external compression strategies. As defined by Avery et al,5 pneumatic medicine is the use of noninvasive, dynamic compression to treat the array of peripheral vascular disorders, including arterial insufficiency, chronic wounds, venous insufficiency, and lymphedema.

The NormaTec PCD uses a multi-cell sleeve or boot that is placed on the affected limb and pneumatically inflated and deflated via a unique Peristalic Pulse dynamic compression strategy. The patented Peristalic Pulse pneumatic waveform consists of a “pulse, gradient hold, release” compression cycle, simulating normal physiology. It incorporates three major physiological concepts: dynamic pulsing compression as seen in the muscle pump of a normal limb, directionality of flow similar to the venous and lymphatic one-way valves, and the effective movement of fluids created by peristalsis. The parameters of the NormaTec PCD are programmed by the physician, and the patient then uses the device independently at home.
A full functional outcome for our patient, who had chronic, clinically significant symptoms, was achieved in a brief period of time after numerous other treatments failed. The Peristalic Pulse compression strategy dynamically decongested the edematous tissues, and her hand and wrist range of motion improved markedly. Our patient has continued to use the device approximately 1 hour per week as maintenance therapy to prevent the return of edema and upper extremity stiffness. No compression garment is required, and compliance with the treatment program has been excellent.

A pathological anomaly that may have been a causative agent in our patient’s proximal edema following reduction of her Colles fracture is complex regional pain syndrome. According to the literature, the incidence of patients with Colles fractures who develop complex regional pain syndrome, albeit controversial, ranges between 2% and 37%.6 Although the pathogenesis is poorly understood, complex regional pain syndrome commonly is triggered by minor injuries such as fractures, crush injuries, peripheral nerve injuries, and other precipitating events that involve abnormal sympathetic nervous system activity.

Complex regional pain syndrome is characterized by pain and tenderness that is described as burning or aching in nature and usually occurring at a distal extremity. Patients with complex regional pain syndrome may develop rapid bony demineralization, trophic skin changes, and vasomotor instability that also are disproportionate to the underlying injury.

Complex regional pain syndrome progresses through three clinical phases. The first phase is characterized by an intense burning pain, edema, warmth, and tenderness of a distal extremity, especially noted around the joints. The joints become stiff, and pain is reproduced on passive and active motion of the joint. During the second phase (3 to 6 months), the patient’s skin becomes thin, cool, and shiny. In the third phase (another 3 to 6 months), the skin becomes atrophic and dry, with progression to flexion contractures and palmar fibromatosis.3

To aid in the diagnosis of complex regional pain syndrome, plain radiographs of patients with fractures may exhibit spotty rarefaction (Sudeck atrophy). Other tests used to substantiate this diagnosis include thermography, bone scan, and sympathetic blockade.

The key component to successful conservative treatment is early diagnosis within 6 to 8 weeks. Conservative treatment modalities include heat, elevation, and desensitization. Chronic disability occurs when the diagnosis and subsequent treatment is delayed. However, some authors have suggested there is no correlation among age, adequacy or number of reductions, or severity of fracture in patients who present with complex regional pain syndrome.3 In our patient, we ruled out complex regional pain syndrome because electromyography, nerve conduction study, radiographs, intravenous Doppler study, duplex arterial scan, and technetium bone scan revealed no pathologic findings other than the fractured wrist.

Some patients present with this syndrome after age 40 years, with the highest incidence in the sixth decade of life. Some patients also present with this anomaly after requiring repeated fracture reductions. Itzchaki et al2 suggested there may be a psychogenic component to this syndrome. Emotional instability was identified in one third of patients with this syndrome.2
Other causes of lymphedema were evaluated extensively in our patient. Local, regional, and metastatic causes such as breast cancer and Pancoast tumor were ruled out as were mechanical dysfunctions such as thoracic outlet syndrome and Milroy disease. Neurological involvement also was ruled out based on normal electroencephalographic readings and nonpathological clinical and physical findings.

The surgical procedure in our patient was uncomplicated and thus lymphedema secondary to any vascular injury was ruled out. Questions that need to be addressed are whether the lymphedema was locally or systemically mediated, or whether the onset of the fracture induced an avascular anastomosis that led to the lymphedema. Our conclusions led us to believe the development of lymphedema of the distal radius following Colles fracture was idiopathic in our patient.


Norton S. Managing lymphedema. Advance. 2000; 11(10):1-6. Itzchaki M, Ben-Hur N, Ashur H. Lymphedema of the hand following a fracture of the distal radius. Int Surg. 1978; 63(1):29-30. Patel AT. Lymphedema. In: Frontera WR, Silver JK, eds. Essentials of Physical Medicine and Rehabilitation. 1st ed. Philadelphia, PA: Hanley and Belfus; 2002:575-577. St Louis JD, McCann RL. Lymphatic System. In: Townsend CM, ed. Sabiston Textbook of Surgery. 16th ed. Philadelphia, PA: WB Saunders Co; 2001:1446-1450. Avery KB, Solomon AD, Weber RB, Jacobs LF. Treatment of congenital lymphoedema with sequential intermittent pneumatic compression therapy. The Foot. 2000; 10(4):210-215. Stern PJ, Derr RG. Non-osseous complications following distal radius fractures. Iowa Orthop J. 1993; 13:63-69. Authors Drs Kasper and Meller are from the Department of Orthopedic Surgery, Veterans Hospital, University of Pennsylvania, Philadelphia, Pennsylvania.

Drs Kasper and Meller have no relevant financial relationships to disclose.

Correspondence should be addressed to: Menachem M. Meller, MD, PhD, Department of Orthopedic Surgery, Veterans Hospital, University of Pennsylvania, 424 Stemmler Hall, Philadelphia, PA 19104-6081.