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.

Superficial Vein Thrombosis After Intra-articular Particulate Steroid Injection for Knee Osteoarthritis.

ABSTRACT: Intra-articular steroid injections for knee osteoarthritis are a routine procedure in musculoskeletal clinics. While their role in osteoarthritis care is debatable, they serve as an important therapeutic option to relieve osteoarthritis-associated pain. Potential risks are self-limited (increased pain flare, local skin irritation, flushing, insomnia) or severe (septic arthritis, intravascular medication placement, and the deleterious effect on cartilage and bone). In our experience, more serious adverse events are rare. In this case, we present a complication secondary to intra-articular steroid administration that has not previously been reported in the literature: superficial vein thrombosis. This will raise awareness among clinicians, improve the informed consent process, and provide an approach for the management of subsequent injections.

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.

Elephantiasis nostras verrucosa: an institutional analysis of 21 cases.

BACKGROUND: Previous reports regarding elephantiasis nostras verrucosa (ENV) have been typically limited to 3 or fewer patients. OBJECTIVES: We sought to statistically ascertain what demographic features and clinical variables are associated with ENV. METHODS: A retrospective chart review of 21 patients with ENV from 2006 to 2008 was performed and statistically analyzed. RESULTS: All 21 patients were obese (morbid obesity in 91%) with a mean body mass index of 55.8. The average maximal calf circumference was 63.7 cm. Concurrent chronic venous insufficiency was identified in 15 patients (71%). ENV was predominantly bilateral (86%) and typically involved the calves (81%). Proximal cutaneous involvement (thighs 19%/abdomen 9.5%) was less common. Eighteen (86%) related a history of lower extremity cellulitis/lymphangitis and/or manifested soft-tissue infection upon presentation. Multisegmental ENV was statistically more likely in setting of a higher body mass index (P = .02), larger calf circumference (P = .01), multiple lymphedema risk factors (P = .05), ulcerations (P < .001), and nodules (P < .001). Calf circumference was significantly and proportionally linked to developing lower extremity ulcerations (P = .02). Ulcerations and nodules were significantly prone to occur concomitantly (P = .05). Nodules appeared more likely to exist in the presence of a higher body mass index (P = .06) and multiple lymphedema risk factors (P = .06). LIMITATIONS: The statistical conclusions were potentially inhibited by the relatively small cohort. The study was retrospective. CONCLUSIONS: Our data confirm the association among obesity, soft-tissue infection, and ENV. Chronic venous insufficiency may be an underappreciated risk factor in the genesis of ENV.

Livedo reticularis and related disorders.

OPINION STATEMENT: Livedo reticularis is a violaceous mottling of the skin with a "fishnet" reticular appearance. Primary and secondary etiologies exist, including a pathologic variant termed livedo racemosa. No evidence-based medicine exists to guide therapy for this disorder, but most patients with primary and secondary livedo reticularis are asymptomatic and do not require treatment. In the rare instance that a patient with primary livedo reticularis experiences mild symptoms such as episodic numbness and tingling, avoidance of cold and vasoconstricting substances should be encouraged. Lastly, judicious dosing of a vasodilator such as a calcium channel blocker can be prescribed. Patients with secondary livedo reticularis or livedo racemosa may benefit from these same therapeutic suggestions; however, treating the proximate cause of livedo with a systemic association is encouraged and is most likely to yield cutaneous improvement. Although antiplatelet and/or anticoagulant therapy is often required when treating a patient with the antiphospholipid antibody syndrome or Sneddon's syndrome, the attendant livedo racemosa typically remains unchanged or progresses despite this treatment.

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.

Diagnostic approach to lower limb edema.

Patients with lower limb edema are frequently referred to vascular specialists for evaluation. Multiple etiologies must be considered and often more than one cause may be present. Notably, the role of lymphatic system regardless of the underlying pathology has been underestimated. A thorough history and physical examination and a carefully considered laboratory and imaging evaluation are critical in differentiating causes. In this opinion article, we propose a diagnostic algorithm that incorporates a systematic approach to the patient with leg swelling and provides an efficient pathway for the differential diagnosis for this problem.

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.

Cutaneous Manifestations of Chronic Vascular Disease.

In the contemporary era of medical diagnosis via sophisticated radiographic imaging and/or comprehensive serological testing, a focused physical examination remains paramount in recognizing the cutaneous manifestations of chronic vascular disease. Recognition of the unique cutaneous signs of lymphatic and venous hypertension assists in the diagnosis as well as the staging and classification of both lymphedema and chronic venous insufficiency. Awareness of explicit dermatologic vasomotor manifestations aids not only in the identification of acrocyanosis, Raynaud phenomenon, pernio, and erythromelalgia but also mitigates confusion related to their clinical overlap. Although the clinical signs of peripheral artery disease are not necessarily specific or sensitive, a knowledge of suggestive dermatologic findings is helpful in recognition of severe limb ischemia. A brief review of the epidemiology, etiology, pathogenesis, and therapy of cutaneous related chronic vascular disease follows including an emphasis on characteristic clinical features supported by illustrative photographs.

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.