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Lipedema is a disease with high prevalence but low recognition. It is often misdiagnosed and underdiagnosed. Obesity and lymphoedema are the most common differential diagnoses and can also coexist in patient with lipedema. Its broad range of presentation and fat distribution types contribute to this confusion. It is likely that lipedema symptom variations and presentation forms are often associated with hormonal variations, chronic low-grade systemic inflammation, and wide polygenic variations. This paper presents a theory regarding the clinical evolution of lipedema clinical and its involvement with other diseases, suggesting a three-phase approach for treatment.

This Letter to the Editor documents several verifiable internal inconsistencies in the article by Bruno and D’Antimi, including contradictory statements on study design, a level-of-evidence rating incompatible with the stated methods, contradictory informed-consent statements, and references to a procedure and outcome domain that do not correspond to the study performed. A correction or clarification is requested.

BACKGROUND: Lipedema is characterized as an abnormal deposition of fat in the buttocks and legs bilaterally that may be accompanied by swelling, pain, and tenderness. It is still often confused with more frequent conditions such as obesity and lymphedema. The estimated prevalence in Europe varies between 0.06% and 39%. OBJECTIVES: To evaluate the prevalence of lipedema and identify health factors related to it in the Brazilian population. METHODS: Administration of a previously validated online screening questionnaire to a representative sample of the general population. The questionnaire was distributed and administered to anonymous volunteers representing the general Brazilian population using software designed for population analyses. RESULTS: 253 women answered the questionnaire, 12.3 ± 4% (Confidence Interval [CI] 95%) of whom presented symptoms compatible with a high probability of being diagnosed with lipedema. Furthermore, anxiety, depression, hypertension, and anemia were also correlated with a high probability of the diagnosis. CONCLUSIONS: The estimated prevalence of lipedema in the population of Brazilian women is 12.3%.

Background  The Questionário de avaliação sintomática do lipedema (QuASiL – Lipedema Symptom Assessment Questionnaire) assesses 13 distinct inflammatory symptoms of lipedema, but whether these symptoms resolve and recur simultaneously or follow a consistent order remains unknown. Objectives  To characterize the persistence hierarchy of the 13 QuASiL inflammatory symptoms in a retrospective lipedema cohort under heterogeneous conservative treatment, using 6 complementary rank-order analyses and testing the null hypothesis that symptoms resolve with equal magnitude. Methods  This retrospective longitudinal study included 1,300 patients who were clinically diagnosed with lipedema by a vascular surgeon and who completed the QuASiL on at least 2 occasions (minimum 14-day interval; median follow-up 181 days, IQR 92–380, maximum 1,787 days). A consensus ranking was computed across all analyses. A sensitivity analysis was conducted using the conventional T0 = first visit, T1 = last visit convention, and a Kaplan-Meier survival analysis estimated the time (in absolute days) to ≥ 50% reduction from baseline per symptom. Results  The symptoms did not resolve simultaneously (Friedman χ2 (12) = 168.08, p < 0.001). All 13 symptoms improved during follow-up, showing a consistent order across the 6 analyses. A slower-resolving core was identified: bruising (consensus rank 1.7), swelling (2.0), touch sensitivity (4.3), leg heaviness (4.7), and fatigue (4.7). A rapidly-responding group comprised skin irritation (66.4% proportional reduction), itching (62.0%), and walking difficulty (62.6%). Even the most resistant symptom (bruising) achieved a mean 39.1% proportional reduction, with half of patients reaching ≥ 50% improvement. During worsening, swelling and pressure/tension re-emerged first. The sensitivity analysis (T0 = first, T1 = last) produced an essentially identical ranking (Spearman ρ = 0.945, p < 10−5). The Kaplan-Meier analysis estimated a median of 546 days for bruising vs 207 days for itching to reach ≥ 50% reduction from baseline (log-rank χ2 = 44.6, p < 10−10); the fastest-resolving symptom was heat/burning at 203 days. Conclusions  In this retrospective cohort of patients under heterogeneous conservative treatment, the 13 QuASiL inflammatory symptoms improved following a consistent order across 6 independent analyses, with bruising and swelling as the most persistent symptoms. Keywords: lipedema; inflammatory symptoms; resolution order; bruising; patient-reported outcomes; longitudinal study

SUMMARY OBJECTIVE: The aim of this study was to characterize global scientific output on lipedema from 2000 to 2025 and identify emerging thematic trends, with emphasis on the emergence of immunological research. METHODS: Publications indexed in Google Scholar, PubMed, Crossref, OpenAlex, and Scopus were retrieved using the terms "lipedema" OR "lipoedema." Records were deduplicated by normalized title matching and DOI cross-referencing. Bibliometric indicators computed included publication volume, citation metrics, field h-index, exponential growth rate, geographic distribution, author metrics, specialty classification (journal-name keyword matching supplemented by OpenAlex concept tags), and immunological content (regular-expression pattern matching against a predefined term list). RESULTS: A total of 942 unique publications were identified, accumulating 13,688 citations (field h-index=60; mean 14.5 citations per article; median 2 citations per article). Annual output grew from below 12 per year through 2009 to 145 in 2025, with a doubling time of 3.6 years (R2=0.90; p<0.001). The United States, Germany, and Brazil were the most productive countries. Karen Lynn Herbst (USA) was the most influential researcher (46 papers; h-index=20; 1,586 citations). Lymphology and phlebology formed the dominant classifiable domain (17.1%), with 69.3% of publications spanning multiple disciplines. Publications with immunological content totaled 30 (3.2%), grew from essentially zero before 2019 to 4.8% of annual output in 2025, and received higher mean citations than non-immunological articles (16.6 vs. 14.5). CONCLUSION: Lipedema research is undergoing rapid exponential expansion driven by growing global recognition of a historically neglected condition. The accelerating immunological trend, with consistently higher citation impact, indicates an accelerating paradigm shift toward chronic adipose tissue inflammation as a unifying pathophysiological framework.

Lipedema is characterized by fat accumulation in the limbs, sparing the trunk, hands, and feet. Its etiology remains uncertain, but may be related to genetic and female hormones. Several theories suggest an association with chronic inflammation and fibrosis. Pain, spontaneous bruising, and increased diameter of the affected areas are the most frequent signs and symptoms. Diagnosis is primarily clinical, but frequently supported by imaging techniques, including ultrasound, magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DEXA), and lymphoscintigraphy to differentiate lipedema from other similar conditions. This study retrospectively analyzed ultrasonographic images of 34 female patients, clinically diagnosed with lipedema and correlated structural patterns with different stages of inflammation and fibrosis in the dermis and subcutaneous tissue. The images were obtained in 2024 using high-frequency linear transducers (12 - 15 MHz). The findings enabled the identification of potentially characteristic changes for the development of a classification that may assist in diagnosis, treatment, and monitoring of this condition. However, while ultrasonography has already been incorporated into routine medical practice to investigate lipedema, prospective and comparative multicenter studies that correlate ultrasound findings with the clinical stage of the disease are necessary to validate the applicability of this approach.

Lipedema is characterized by symmetrical accumulation of subcutaneous fat in the lower and upper limbs, sparing the trunk, feet and hands. Although diagnosis is primarily clinical, ultrasound has proven to be a valuable, non-invasive, reproducible, and cost-effective tool for the assessment of lipedema. Ultrasound (US) facilitates diagnosis through quantitative evaluation of subcutaneous tissue thickness and enables qualitative Lipedema Dermal and Hypodermal Classification (LDHC), with morphological changes. The presence of hyperechoic nodules in patients with lipedema has been previously described and classified as LDHC 3; recently, a case report analyzing the microscopic features of such nodules demonstrated hemorrhagic areas and steatonecrosis, resulting from disorganized hypodermal expansion leading to increased pressure within the subcutaneous compartment—causing hypoxia and stimulating immature neovascularization (fragile wall, predisposing to hemorrhage). However, these nodules are not uniform and exhibit different morphologies, enabling subclassification. The first type presents with poorly defined margins; the second is well-defined margins; the third has an anechoic area, and the fourth shows a faint posterior shadow. These different nodule presentations in lipedema may be correlated with evolutionary stages or previously described clinical presentations, requiring future correlation with pathological anatomy or other diagnostic methods.

Lipedema is a chronic and progressive condition characterized by the disproportionate accumulation of subcutaneous adipose tissue predominantly in the upper and lower limbs, sparing the trunk, hands, and feet. It affects approximately 12.3% of the female population in Brazil. Clinically diagnosed, its most common symptoms include tenderness upon palpation and spontaneous bruising. During the development of a qualitative ultrasonographic classification for lipedema, termed Lipedema Dermis and Hypodermis Classification (LDHC), an echogenic nodule was identified in the superficial hypodermis. This nodule was painful upon superficial palpation and lacked ultrasonographic features of a lipoma. The patient presented with a nodule in the distal posterior region of the right thigh and another on the distal posterior of the right arm. Given the possible differential diagnoses, including neoplasia and angiodysplasia, an ultrasound-guided biopsy was performed. Macroscopic analysis revealed an oval-shaped, reddish nodule, suggestive of blood content. Histological analysis revealed areas of steatonecrosis, hemorrhagic foci, and neoangiogenesis with irregular architecture and fragile vessel walls. Complementary analysis of the resistance index (RI) of superficial hypodermal arteries demonstrated an increased RI in the lipedema patient compared to the control. All these findings suggest that the tissue is hypoxic and characterized by chronic inflammation, supporting the hypothesis of increased subcutaneous compartment pressure in lipedema. This case report elucidates the ultrasonographic findings of nodules classified by LDHC through microscopic anatomical correlation and aids in understanding the pathophysiological mechanisms underlying lipedema.