The American Venous Forum, American Vein and Lymphatic Society and the Society for Vascular Medicine expert opinion consensus on lymphedema diagnosis and treatment.

BACKGROUND: Lymphedema imposes a significant economic and social burden in modern societies. Controversies about its risk factors, diagnosis, and treatment permeate the literature. The goal of this study was to assess experts' opinions on the available literature on lymphedema while following the Delphi methodology. METHODS: In December of 2019, the American Venous Forum created a working group tasked to develop a consensus statement regarding current practices for the diagnosis and treatment of lymphedema. A panel of experts was identified by the working group. The working group then compiled a list of clinical questions, risk factors, diagnosis and evaluation, and treatment of lymphedema. Fifteen questions that met the criteria for consensus were included in the list. Using a modified Delphi methodology, six questions that received between 60% and 80% of the votes were included in the list for the second round of analysis. Consensus was reached whenever >70% agreement was achieved. RESULTS: The panel of experts reached consensus that cancer, infection, chronic venous disease, and surgery are risk factors for secondary lymphedema. Consensus was also reached that clinical examination is adequate for diagnosing lymphedema and that all patients with chronic venous insufficiency (C3-C6) should be treated as lymphedema patients. No consensus was reached regarding routine clinical practice use of radionuclide lymphoscintigraphy as a mandatory diagnostic tool. However, the panel came to consensus regarding the importance of quantifying edema in all patients (93.6% in favor). In terms of treatment, consensus was reached favoring the regular use of compression garments to reduce lymphedema progression (89.4% in favor, 10.6% against; mean score of 79), but the use of Velcro devices as the first line of compression therapy did not reach consensus (59.6% in favor vs 40.4% against; total score of 15). There was agreement that sequential pneumatic compression should be considered as adjuvant therapy in the maintenance phase of treatment (91.5% in favor vs. 8.5% against; mean score of 85), but less so in its initial phases (61.7% in favor vs. 38.3% against; mean score of 27). Most of the panel agreed that manual lymphatic drainage should be a mandatory treatment modality (70.2% in favor), but the panel was split in half regarding the proposal that reductive surgery should be considered for patients with failed conservative treatment. CONCLUSION: This consensus process demonstrated that lymphedema experts agree on the majority of the statements related to risk factors for lymphedema, and the diagnostic workup for lymphedema patients. Less agreement was demonstrated on statements related to treatment of lymphedema. This consensus suggests that variability in lymphedema care is high even among the experts. Developers of future practice guidelines for lymphedema should consider this information, especially in cases of low-level evidence that supports practice patterns with which the majority of experts disagree.

Standard of care for lipedema in the United States.

BACKGROUND: Lipedema is a loose connective tissue disease predominantly in women identified by increased nodular and fibrotic adipose tissue on the buttocks, hips and limbs that develops at times of hormone, weight and shape change including puberty, pregnancy, and menopause. Lipedema tissue may be very painful and can severely impair mobility. Non-lipedema obesity, lymphedema, venous disease, and hypermobile joints are comorbidities. Lipedema tissue is difficult to reduce by diet, exercise, or bariatric surgery. METHODS: This paper is a consensus guideline on lipedema written by a US committee following the Delphi Method. Consensus statements are rated for strength using the GRADE system. RESULTS: Eighty-five consensus statements outline lipedema pathophysiology, and medical, surgical, vascular, and other therapeutic recommendations. Future research topics are suggested. CONCLUSION: These guidelines improve the understanding of the loose connective tissue disease, lipedema, to advance our understanding towards early diagnosis, treatments, and ultimately a cure for affected individuals.

In vitro diagnostics for the medical dermatologist. Part II: Hypercoagulability tests.

The skin often provides initial clues of hypercoagulability with features such as livedo reticularis, livedo racemosa, retiform purpura, necrosis, and ulcerations. Because these cutaneous manifestations are nonspecific, laboratory testing is often needed to evaluate for underlying causes of hypercoagulability. Importantly, these disorders are reported to be the most common mimicker, resulting in an erroneous diagnosis of pyoderma gangrenosum. Understanding inherent properties of, and indications for, available tests is necessary for appropriate ordering and interpretation of results. Additionally, ordering of these tests in an indiscriminate manner may lead to inaccurate results, complicating the interpretation and approach to management. This second article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of hypercoagulability and vasculopathic disease as it pertains to dermatologic disease.

The clinical characteristics of lower extremity lymphedema in 440 patients.

BACKGROUND: Lower extremity lymphedema is frequently encountered in the vascular clinic. Established dogma purports that cancer is the most common cause of lower extremity lymphedema in Western countries, whereas chronic venous insufficiency (CVI) is often overlooked as a potential cause. Moreover, lymphedema is typically ascribed to a single cause, yet multiple causes can coexist. METHODS: A 3-year retrospective analysis was conducted of demographic and clinical characteristics of 440 eligible patients with lower extremity lymphedema who presented for lymphatic physiotherapy to a university medical center's cancer-based physical therapy department. RESULTS: The four most common causes of lower extremity lymphedema were CVI (phlebolymphedema; 41.8%), cancer-related lymphedema (33.9%), primary lymphedema (12.5%), and lipedema with secondary lymphedema (11.8%). The collective cohort was more likely to be female (71.1%; P < .0001), to be white (78.9%; P < .0001), to demonstrate bilateral distribution (74.5%; P < .0001), and to have involvement of the left leg (bilateral, 69.1% [P < .0001]; unilateral, 58.9% [P = .0588]). Morbid obesity was pervasive (mean weight and body mass index, 115.8 kg and 40.2 kg/m2, respectively) and significantly correlated with a higher International Society of Lymphology lymphedema stage (stage III mean weight and body mass index, 169.2 kg and 57.3 kg/m2, respectively, vs stage II, 107.8 kg and 37.5 kg/m2, respectively; P < .0001). Approximately one in three (35.7%) of the population sustained one or more episodes of cellulitis, but patients with stage III lymphedema had roughly twice the rate of soft tissue infection as patients with stage II, 61.7% vs 31.8%, respectively (P < .001). Multifactorial lymphedema was present in 25%. Approximately half of the patients with lipedema with secondary lymphedema (48.1%) or primary lymphedema (45.5%) had a superimposed cause of swelling that was usually CVI. Total knee arthroplasty was the most common cause of noncancer surgery-mediated worsening of pre-existing lymphedema. CONCLUSIONS: In a large cohort of patients treated in a cancer-affiliated physical therapy department, CVI (phlebolymphedema), not cancer, was the predominant cause of lower extremity lymphedema. One in four patients had more than one cause of lymphedema. Notable clinical characteristics included a proclivity for female patients, bilateral distribution, left limb, cellulitis, and nearly universal morbid obesity.

Pseudocellulitis Need Not be Benign: Three Cases of Superficial Migratory Thrombophlebitis with "Negative" Venous Duplex Ultrasonography.

Trousseau syndrome is a rare phenomenon in cancer patients characterized by superficial migratory thrombophlebitis. In this brief report, the authors describe three recent case presentations of patients without a prior history of cancer who were treated for cellulitis prior to be admitted to the hospital. All three patients were found to have "negative" testing on venous duplex scanning. Communication with the technicians and additional clinical and laboratory evaluations confirmed Trousseau syndrome as well as an underlying hematologic cancer in each patient. Dermatologists should be aware of the diagnostic limitations in the venous duplex scanning, especially when evaluating superficial veins or areas overlying pain, and should recognize the importance of communicating with the technician performing the procedure.

Pharmacologic treatment to improve venous leg ulcer healing.

Pharmacologic treatment for venous leg ulcers (VLUs) is an adjuvant treatment to compression therapy. It encompasses a variety of plant-derived and synthetic compounds with properties that alter venous microcirculation, endothelial function, and leukocyte activity to promote VLU healing. These compounds are often referred to as venotonics or venoactive drugs but have also been referred to as edema-protective agents, phlebotonics, vasoprotectors, phlebotropics, and venotropics. The exact mechanism of their ability to heal VLUs is not known; however, clinical trials support their efficacy. This evidence-based review assesses randomized clinical trials and meta-analyses with the objective of determining the effectiveness of venotonics to promote VLU healing.

Bier spots are an under-recognized cutaneous manifestation of lower extremity lymphedema: a case series and brief review of the literature.

Bier spots represent a benign vascular mottling characterized by multiple irregular white macules along the extensor surfaces of the arms and legs. They have been reported in a variety of diverse conditions with no consistent disease association. We have identified a novel association between these physiologic anemic macules and lower extremity lymphedema. Eleven patients between 23 and 70 years of age (5 male and 6 female) were diagnosed with Bier spots as evidenced by reversible white macules ranging from 3 to 8 mm in diameter on the extensor portions of the feet, ankles, and calves. The thighs were affected as well in 2 morbidly obese subjects. We suspect that these lesions are not uncommon in lymphedema but are simply under-recognized.

An unusual case of familial lymphedema.

A 47-year-old man with stable stage II chronic kidney disease and episodic diarrhea presented with chronic, progressive bilateral lower extremity lymphedema. His mother and 2 brothers had similar acral swelling. Thus, a diagnosis of typical primary familial lymphedema was suspected. Approximately 1 year later, progressive azotemia and proteinuria ensued. A renal biopsy suggested Fabry disease, which was confirmed by enzymatic and genetic testing. In addition, Fabry disease was diagnosed in his mother and 2 male siblings with lower extremity lymphedema. As this case illustrates, Fabry disease is an underappreciated and often unrecognized cause of familial lymphedema.

Warfarin-induced Venous Limb Gangrene.

Warfarin is a commonly used anticoagulant that has been associated with several significant cutaneous side effects, most notably warfarin-induced skin necrosis. A lesser known adverse reaction to warfarin is warfarin-induced venous limb gangrene. Both cutaneous adverse effects share the same pathophysiology, but are clinically quite different. The majority of cases of warfarin-induced venous limb gangrene has been in patients with cancer or heparin-induced thrombocytopenia. However, other hypercoagulable disease states, such as the antiphospholipid antibody syndrome, can be associated with venous limb gangrene. In order to increase recognition of this important condition, the authors report a case of warfarin-induced venous limb gangrene in a patient with presumed antiphospholipid antibody syndrome and review the literature on warfarin-induced venous limb gangrene.

A Second Case of Sunitinib-associated Pyoderma Gangrenosum.

Pyoderma gangrenosum is a painful, noninfectious, ulcerative, cutaneous disorder that most commonly affects the lower extremities. The diagnosis is made by recognizing the characteristic clinical manifestations in the setting of a causative systemic disease and excluding other causes of similar-appearing ulcerations. Pyoderma gangrenosum often evolves in the setting of systemic illnesses, such as inflammatory bowel disease, rheumatological disorders, and hematological conditions. However, several medications have rarely been linked to pyoderma gangrenosum. The authors report the second case of sunitinib-associated pyoderma gangrenosum in a 61-year-old patient with recurrent renal cell carcinoma.

Superficial venous thrombosis of the lower extremities: analysis of risk factors, and recurrence and role of anticoagulation.

Superficial venous thrombosis (SVT) of the lower extremities is a common ailment seen in outpatient offices of vascular medicine and surgery practices. This study of 60 consecutive outpatients was carried out to examine the incidence of concomitant deep venous thrombosis (DVT), risk factors associated with SVT, recurrence of SVT and/or new DVT, and the role of anticoagulant therapy in the prevention of recurrence. Concomitant SVT and DVT (13%) were significantly less likely to be present in patients with varicose veins as compared to patients without varicose veins (p < 0.04) and more likely to be present in patients with a previous history of DVT (p < 0.02). Fifteen patients (25%) developed either recurrent SVT or new DVT, with two patients developing both SVT and DVT. The absence of varicose veins and the presence of a hypercoagulable condition (n = 12) appeared to influence the development of new DVT but not the recurrence of SVT. Recurrent SVT was much more likely in patients with thrombosis of the tributaries (p < 0.0008). New DVT was seen significantly less frequently in patients on anticoagulants (p < 0.02).