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Both lipedema and juxta-articular adiposis dolorsa are painful disorders of subcutaneous adipose tissue. We investigated 297 female patients with lipedema treated at our department for the presence of juxta-articular adiposis dolorsa. Occurrence of both disorders was identified in 4.4% of lipedema patients. The common presence of both disorders was observed only in more advanced lipedema (grade II and III). Juxta-articular adiposis dolorosa of the knees is seen exclusively on the inner knees, and it presents neither bruising nor creases or hypothermia. Choices of surgical treatment are either microcannula liposuction or dermolipectomy. Recurrences have not been observed.

OBJECTIVES: The association between serum Vitamin D (Vit. D) and mood disorders in lipedema patients has not been investigated. Therefore, the main aim of this study is to investigate the correlation between serum Vit. D, depression and anxiety risk. METHODS: A cross-sectional cohort of lipedema patients were investigated by collecting the clinical and demographic data. The Hamilton Depression Scale (HAM-D) and the Hamilton of Anxiety Scale (HAM-A) were used to evaluating the risk of depression and anxiety. Serum concentrations of Vit. D were measured. The association between Vit. D levels and both HAM-A and HAM-D scores were statistically examined by bivariate and partial correlations. RESULTS: Forty lipedema patients were enrolled in this study. Around two-thirds of them had a higher depression or anxiety risk, and 77.5% were under the normal serum Vit. D levels. A significant and inverse correlation was observed between serum Vit. D levels and both HAM-D (r=-0.661, p<0.001), and HAM-A (r=-0.496, p=0.001) scores. This strong association was sustained after the statistical model adjusted for the main potential confounding factors (age, body mass index (BMI), disease duration, and lipedema stages). Additionally, serum Vit. D correlated significantly and inversely with BMI (r=-0.647, p<0.001). Moreover, BMI significantly correlated with HAM-D: r=0.560, p<0.001, and HAM-A: r=0.511, p=0.00. CONCLUSIONS: This study suggests a strong correlation between Vit. D levels, depression scores, and anxiety scores in lipedema patients. Our results also demonstrate a strong and direct relationship between BMI, Vit. D levels, depression, and anxiety.

Lipedema is a chronic, progressive disease marked by abnormal fat distribution in the limbs, resulting in disproportionately sized and painful limbs. It primarily affects women and causes significant disability, functional impairment, and psychological distress. Despite its clinical significance in women’s health, lipedema is largely unknown, underdiagnosed, and misdiagnosed with other diseases with similar symptoms including obesity. It is difficult to distinguish between obesity and lipedema since these two conditions often coexist. Since the precise etiology of lipedema is yet to be determined, there is no treatment that targets the underlying cause. The most basic conservative treatment is decongestive physical therapy, which is normally needed life-long. In some cases, surgical procedures such as liposuction and excisional lipectomy are the therapeutic alternatives. Lipedematous scalp is a rare, dermatological condition with no known cause, characterized by increased subcutaneous tissue thickness and a smooth and boggy scalp. When it occurs in conjunction with alopecia, it is known as lipedematous alopecia, often mistaken as androgenetic alopecia. The goals of this article are to explain the etiology, clinical features, and treatment options for lipedema and lipedematous scalp (two relatively less known conditions), as well as to highlight their diagnostic features.

Introduction Lipoedema is a chronic and progressive fat distribution disorder characterised by a symmetrical disproportional increase of adipose tissue on the extremities. The disorder is most commonly associated with pain, oedemas, increased tendency of bruising, as well as sensory dysfunctions on the affected limbs, resulting in severely reduced quality of life (QoL) for exclusively female patients. According to current clinical guidelines, conservative treatment of lipoedema consists of manual lymphatic drainage, compression garments, or both combined as complex decongestive therapy (CDT). If conservative therapy does not result in sufficient improvement of symptoms, a surgical intervention, in the form of liposuction under tumescence anaesthesia, may be indicated. This systematic review aims to assess the clinical effectiveness and safety of liposuction in patients with lipoedema (stage I-III) in comparison to any conservative treatment, concerning patient-relevant outcomes, as reduction of pain, reduction in the size of extremities, improvement of QoL, and procedure-related adverse events. Methods A systematic literature search was conducted in December 2020 in five databases to answer customised research questions on clinical effectiveness and safety-related outcomes, yielding in overall 294 potentially relevant hits. One additional hit was identified by hand search. The study selection, data extraction, and assessment of the methodological quality of the studies were performed by two independent researchers. Results A total of six prospective and one retrospective single-arm before/after studies were eligible for inclusion in the current report. Overall, data on safety and clinical effectiveness were evaluated in 492 and 467 female patients of all three lipoedema stages, respectively. The post-operative follow-up ranged from six months to twelve years. Clinical effectiveness Due to the lack of controlled trials, no conclusions on the comparative clinical effectiveness of liposuction for lipoedema could be made. Therefore, data from the prospective single-arm studies comparing patient-reported complaints before and after the liposuction were analysed. All six prospective studies reported statistically significant improvements in pain outcomes pre- vs post-liposuction. These effects were reported beginning at a six-month follow-up but also up to twelve years after the intervention. Reduced sizes of patients’ extremities before-and-after liposuction were reported in three of the included studies, in terms of reduced leg volume and circumference of lower extremities. Statistically significant changes in lipoedema-related QoL outcomes were reported by four studies. Further, reduction in complaints about oedema/swelling, bruising and sensory dysfunctions were reported in some of the included studies.

Lipedema is a chronic, progressive disease that almost exclusively affects women and often misdiagnosed as obesity or primary lymphedema. Research concerning lipedema is sparse, and there is a lack of studies focusing on women's experiences of living with the illness. We interviewed fourteen women with lipedema with the aim of describing their experiences of living with lipedema. Our results show that women felt controlled by their body, and were fat-shamed and viewed by others as a person who lacked character. They received unsupportive advice on how to manage from healthcare, and blamed themselves while striving to take responsibility.

Williams syndrome (WS) is a relatively rare microdeletion disorder that occurs in as many as 1:7,500 individuals. WS arises due to the mispairing of low-copy DNA repetitive elements at meiosis. The deletion size is similar across most individuals with WS and leads to the loss of one copy of 25–27 genes on chromosome 7q11.23. The resulting unique disorder affects multiple systems, with cardinal features including but not limited to cardiovascular disease (characteristically stenosis of the great arteries and most notably supravalvar aortic stenosis), a distinctive craniofacial appearance, and a specific cognitive and behavioural profile that includes intellectual disability and hypersociability. Genotype–phenotype evidence is strongest for ELN, the gene encoding elastin, which is responsible for the vascular and connective tissue features of WS, and for the transcription factor genes GTF2I and GTF2IRD1, which are known to affect intellectual ability, social functioning and anxiety. Mounting evidence also ascribes phenotypic consequences to the deletion of BAZ1B, LIMK1, STX1A and MLXIPL, but more work is needed to understand the mechanism by which these deletions contribute to clinical outcomes. The age of diagnosis has fallen in regions of the world where technological advances, such as chromosomal microarray, enable clinicians to make the diagnosis of WS without formally suspecting it, allowing earlier intervention by medical and developmental specialists. Phenotypic variability is considerable for all cardinal features of WS but the specific sources of this variability remain unknown. Further investigation to identify the factors responsible for these differences may lead to mechanism-based rather than symptom-based therapies and should therefore be a high research priority.

Patient: Female, 31-year-old, Final Diagnosis: Lipedema, Symptoms: Bruising • leg edema • leg pain, Medication: —, Clinical Procedure: —, Specialty: Endocrinology and Metabolic • Family Medicine • Medicine, General and Internal • Metabolic Disorders and Diabetics • Plastic Surgery • Psychiatry

Background Reduced diffusion along perivascular spaces in adults with Alzheimer’s-disease-related-dementias has been reported and attributed to reduced glymphatic flow. Objectives To apply quantitative measures of diffusion along, and orthogonal to, perivascular spaces in a cohort of older adults with and without clinical symptoms of alpha-synuclein related neurodegeneration. Methods 181 adults with Parkinson disease (PD) or essential tremor (ET) additionally sub-classified by the presence of cognitive impairment underwent 3 Tesla MRI. Diffusion-tensor-imaging (spatial resolution=2x2x2 mm; b-value=1000 s/mm2; directions=33) measures of diffusion (mm2/s) parallel and orthogonal to perivascular spaces at the level of the medullary veins, and the ratio of these measures (DTI-ALPS), were calculated. Regions were identified by a board-certified neuroradiologist from T1-weighted and T2-weighted MRI. Evaluations of motor impairment and mild cognitive impairment (MCI) were interpreted by a board-certified neurologist and neuropsychologist, respectively. Multiple regression with false discovery rate correction was applied to understand how diffusion metrics related to (i) disease category (PD vs. ET), (ii) cognition (MCI status), and (iii) white matter disease severity from the Fazekas score. Results The DTI-ALPS score was reduced in PD compared to ET participants (p=0.037). No association between DTI-ALPS score and MCI status, but an inverse association between DTI-ALPS and Fazekas score (p=0.002), was observed. DTI-ALPS scores were inversely associated with age (p=0.007). Conclusion Diffusion aberrations near perivascular spaces are evident in patients with alpha-synuclein related neurodegenerative disorders, and are related to age and white matter disease severity.

The Western diet is rich in salt, and a high salt diet (HSD) is suspected to be a risk factor for cardiovascular diseases. It is now widely accepted that an experimental HSD can stimulate components of the immune system, potentially exacerbating certain autoimmune diseases, or alternatively, improving defenses against certain infections, such as cutaneous leishmaniasis. However, recent findings show that an experimental HSD may also aggravate other infections (e.g., pyelonephritis or systemic listeriosis). Here, we discuss the modulatory effects of a HSD on the microbiota, metabolic signaling, hormonal responses, local sodium concentrations, and their effects on various immune cell types in different tissues. We describe how these factors are integrated, resulting either in immune stimulation or suppression in various tissues and disease settings.

BackgroundLipedema 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.MethodsThis 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.ResultsEighty-five consensus statements outline lipedema pathophysiology, and medical, surgical, vascular, and other therapeutic recommendations. Future research topics are suggested.ConclusionThese 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.

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Patient: Female, 41-year-old, Final Diagnosis: Malnutrition, Symptoms: Leg edema • weakness, Medication: —, Clinical Procedure: Lymphatic mapping, Specialty: Dermatology • Endocrinology and Metabolic • Surgery

Lipedema is a chronic feminine disease that causes abnormal fat deposition in lower limbs and occasionally upper limbs. Easy bruising and pain are common. Lipedema patients suffer from both physical and psychological disability. Despite the relatively high prevalence and the impact on the quality of life, little is known about the disease. The majority of patients are misdiagnosed as lymphedema or obesity. The objective was to perform a non-systematic review on lipedema literature, related to diagnosis and therapy. Regarding pathophysiology, alterations are not exclusively confined to adipose tissue. Lymphatic dysfunction, cardiovascular variations, blood capillary fragility and increased permeability are common. Patients often present with neurological alterations and hormonal malfunction. Elevated cutaneous sodium has been documented. Due to the absence of a defined etiology, evidence-based research is difficult in the management of lipedema. The setting of realistic expectations is important for both patient and medical care provider. The major aims of the management are multimodal for improvements in the quality of life; reduction in heaviness and pain, reshaping the affected limbs, weight control, improvements in mobility. Compression garments, physical therapy, exercise regimens, diet and psychological counseling are necessities. For selected patients, surgical treatment is an added option.

BACKGROUND: Lipedema is characterized by the deposition of abnormal fat in the lower and upper limbs bilaterally. It is a disease with high prevalence and genetic characteristics. Non-specific and non-quantified increases in the thickness of the subcutaneous tissue have previously been demonstrated using magnetic resonance imaging and computed tomography. OBJECTIVES: To evaluate the thickness of the dermis and subcutaneous tissue in predetermined areas as a distinguishing feature between individuals with and without lipedema using ultrasound. METHODS: Ultrasound images of 89 female patients were analyzed, including patients undergoing clinical investigation for venous insufficiency or lipedema who underwent ultrasound evaluations at our institution. Patients were divided in two groups: with lipedema clinically diagnosed and those without lipedema. They underwent a common Doppler protocol for venous mapping to assess venous insufficiency associated with the evaluation of dermis and subcutaneous thickness at pre-defined points of the lower limbs. RESULTS: There were 63 patients with lipedema. Anterior thigh, pre-tibial and lateral aspect of the leg and supra-just medial malleolar region were significantly different. Supra-just medial malleolar region was significantly different with BMI above 25. An optimal cutoff value was calculated for the ultrasound diagnosis of lipedema using thickness of the dermis and subcutaneous tissues. CONCLUSIONS: Studied criteria allow use of simple and reproducible ultrasound cutoff values to diagnose lipedema in the lower limbs. Pre-tibial region thickness measurement, followed by thigh and lateral leg thickness are recommended for the ultrasound diagnosis of lipedema.

This study examined the disease-specific quality of life (QoL) in lipoedema patients undergoing treatment for the condition with liposuction. We conducted a retrospective analysis of all patients (n = 69) who underwent liposuction for treatment of lipoedema between 2004 and 2019, and gathered data on patient age, body mass index, the number of liposuction sessions, and the amount of fat removed per side. The study also prospectively evaluated the QoL in 20 lipoedema patients before and after liposuction using the Freiburg Life Quality Assessment for lymphatic diseases questionnaire. The mean age was 50.6 ± 12.8 years, and the average number of liposuction sessions performed was 2.9 ± 1.9, with a mean volume of 1868 ± 885.5 mL of fat removed per side. Before treatment with liposuction, disease-specific QoL in patients with lipoedema was low on every single subscale as well as on the global score and showed a significant improvement in all aspects after liposuction. There was a significant correlation between a higher number of liposuction treatment sessions and general health status in lipoedema patients (P = .007). Liposuction greatly improves the QoL in lipoedema patients. A higher number of liposuction treatment sessions seem to have a positive effect on general health status in these patients.

Objective: The aim of this study is to investigate the effect of complex decongestive physiotherapy (CDP) plus intermittent pneumatic compression (IPC) applications on upper extremity circumference and volume in patients with lipedema. Methods and Results: All participants included in the study were included in a treatment protocol consisting of CDP and IPC. The Perometer 400 NT was used in the measurement of upper extremity volume and circumference before and after treatment. The measurements were performed in four reference points. According to the Perometer results before and after CDP, statistically significant reduction was found in the circumference of 3 of the 4 points of measurements performed in each of the left and right upper extremities. When the volume assessments were compared, it was seen that statistically significant reduction was found in the volume of both limbs. Conclusion: A treatment program consisting of CDP and IPC can be effective in reducing the circumference and volume of the arm in patients with upper extremity lipedema. So, CDP applications can help prevent the development of complications such as lipolymphedema, hypertension, and heart failure.

AIM: Fluid and macromolecule transport from the interstitium into and through lymphatic vessels is necessary for tissue homeostasis. While lymphatic capillary structure suggests that passive, paracellular transport would be the predominant route of macromolecule entry, active caveolae-mediated transcellular transport has been identified in lymphatic endothelial cells (LECs) in vitro. Caveolae also mediate a wide array of endothelial cell processes, including nitric oxide regulation. Thus, how does the lack of caveolae impact "lymphatic function"? METHODS: Various aspects of lymphatic transport were measured in mice constitutively lacking caveolin-1 ("CavKO"), the protein required for caveolae formation in endothelial cells, and in mice with a LEC-specific Cav1 gene deletion (Lyve1-Cre x Cav1flox/flox ; "LyCav") and ex vivo in their vessels and cells. RESULTS: In each model, lymphatic architecture was largely unchanged. The lymphatic conductance, or initial tissue uptake, was significantly higher in both CavKO mice and LyCav mice by quantitative microlymphangiography and the permeability to 70 kDa dextran was significantly increased in monolayers of LECs isolated from CavKO mice. Conversely, transport within the lymphatic system to the sentinel node was significantly reduced in anaesthetized CavKO and LyCav mice. Isolated, cannulated collecting vessel studies identified significantly reduced phasic contractility when lymphatic endothelium lacks caveolae. Inhibition of nitric oxide synthase was able to partially restore ex vivo vessel contractility. CONCLUSION: Macromolecule transport across lymphatics is increased with loss of caveolae, yet phasic contractility reduced, resulting in reduced overall lymphatic transport function. These studies identify lymphatic caveolar biology as a key regulator of active lymphatic transport functions.