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Systemic causes of leg edema include idiopathic cyclic edema, heart failure, cirrhosis, nephrosis and other hypoproteinemic states. Lymphedema may be primary, or secondary to neoplasm, lymphangitis, retroperitoneal fibrosis and, rarely (in the U.S.), filariasis. Thrombophlebitis and chronic venous insufficiency are not uncommon causes. Finally, infection, ischemia, lipedema, vascular anomalies, tumors and trauma can be responsible for the swollen leg.
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1. Lipoedema is described with an illustration of a recent case. 2. This condition should be distinguished from lymphoedema of the legs. 3. The differential diagnosis is discussed. 4. Comment is made on treatment.
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Background: Lipedema is characterized by disproportionate gluteofemoral adiposity, often regarded as a metabolic sink, yet its relationship with systemic autoimmunity, specifically celiac disease (CD), remains unexplored. Objective: We investigated the immunometabolic profiles and body composition patterns distinguishing lipedema phenotypes from celiac disease autoimmunity. Methods: This cross-sectional analysis included 3,833 women from NHANES 2011–2014. Celiac disease was defined by strict serology (tTG-IgA+ and EMA-IgA+), while the lipedema phenotype was defined as a leg-to-trunk fat ratio >90th percentile via dual-energy X-ray absorptiometry (DXA). We assessed gynoid fat mass, HOMA-IR, and neutrophil-to-lymphocyte ratio (NLR) compared to controls. Results: CD prevalence was 0.56% (n=11). Women with CD exhibited significantly lower gynoid region percent fat compared to non-celiacs (39.5% vs. 42.6%, p=0.0007). Conversely, the lipedema phenotype was associated with a distinct anti-inflammatory and insulin-sensitive profile, characterized by 44.2% lower HOMA-IR (p<0.001) and 7.6% lower NLR (p=0.012) compared to controls. While broad lipedema criteria did not reach statistical significance for CD exclusion due to low case numbers (p=0.570), no celiac cases were observed in the highest tier of gynoid adiposity. Conclusions: Although prevalence differences did not reach statistical significance, this study of US women demonstrates a phenotypic divergence where celiac disease is associated with reduced gynoid adiposity, contrasting with the superior immunometabolic profile observed in the lipedema phenotype. These findings suggest that these conditions represent opposing physiological states regarding gynoid adipose tissue function.
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Lipedema is a chronic, progressive disorder of adipose tissue that predominantly affects women, characterized by symmetrical fat accumulation in the extremities, pain, and resistance to caloric restriction. Recent insights suggest that lipedema represents a hormone-driven gynecological fat disorder, in which estrogen receptor (ER) imbalance plays a central role. The predominance of ERβ activity and suppression of ERα signaling are hypothesized to drive adipose hypertrophy, fibrosis, and inflammation, particularly in the context of intracrine estradiol excess. This model aligns lipedema with other estrogen-sensitive conditions, such as endometriosis and uterine fibroids, and provides a novel framework for understanding its pathophysiology. Therapeutically, this reframing opens new perspectives for hormonal modulation using selective progestins (drospirenone, gestrinone) and metabolic adjuncts such as tirzepatide, beyond the current symptomatic or surgical approaches.
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Lipoedema is a chronic disease with various manifestation of symptoms, related to excessive deposition of subcutaneous adipose tissue in the legs, hips and buttocks. The scale of the problem is enormous and may affect up to one in five women. Lipoedema is often underdiagnosed and misdiagnosed with lymphedema, obesity or lipohypertrophy. In recent years, lipoedema has been diagnosed in an increasing number of younger women, and its first symptoms may manifest already in puberty. Even though it is often perceived as only an aesthetic problem, it has a huge impact on the quality of life, mental health, self-esteem or self-confidence. Moreover, lipoedema causes stigmatization, unfortunately also in healthcare professionals. Nevertheless, recently, diagnostic criteria (also ultrasound) have been created, and lipoedema has been classified in ICD-10 (E88.2). There are also more and more treatment options, with emphasis on the role of psychological care. Awareness and knowledge of lipoedema have also increased despite its underestimation but still is not enough. The multidimensional nature of lipoedema and its impact on many aspects of life highlights the essential role of comprehensive support to patients. Nowadays, in times of caring for mental health, it is crucial to increase public awareness and spread knowledge about lipoedema.
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