Observational Study on a Large Italian Population with Lipedema: Biochemical and Hormonal Profile, Anatomical and Clinical Evaluation, Self-Reported History

Abstract

We analyzed the medical condition of 360 women affected by lipedema of the lower limbs in stages 1, 2, and 3. The data were assessed for the whole population and compared between different clinical stages, distinguishing between obese and non-obese patients. The most frequent clinical signs were pain when pinching the skin, subcutaneous nodules, and patellar fat pads. The most frequently painful site of the lower limbs was the medial lower third of the thigh. The pain score obtained on lower limb points increased progressively with the clinical stage. In all points evaluated, the thickness of the subcutaneous tissue increased with the clinical stage. Analyzing the data on the lower medial third of the leg and considering only patients with type 3 lipedema, the difference between stages was statistically significant after correction for age and BMI. We found higher levels of C-reactive protein at more severe clinical stages, and the difference was significant after correction for age and BMI between the stages. Overall, the prevalence of alterations of glucose metabolism was 34%, with a progressive increase in prevalence with the clinical stage. The most frequent comorbidities were vitamin D insufficiency, chronic venous disease, allergies, dyslipidemia, headache, and depression of mood. Interestingly, in comparison with the general population, we found higher prevalence of chronic autoimmune thyroiditis and polycystic ovary syndrome. Finally, the clinical stage and the involvement of the upper limbs or obesity suggest a worse clinical, anthropometric, and endocrine-metabolic profile.

Keywords: adipose tissue; hormonal impairment; inflammation; lipedema; obesity; pain; ultrasound.

Figure 1

Staging of lipedema. The figure shows the three clinical stages of lipedema: stage 1 (A), stage 2 (B), and stage 3 (C).

Figure 2

Pain score in the clinical stages. Figure 2 shows the mean of the lower limb pain score, upper limb pain score, and total pain score in the three stages. Pain was quantified using a Verbal Rating Scale with values from 0 to 4 (0 = no pain, 4 = maximum pain), applied to each specific site (as described in the text), evaluating three different scores: a lower limb pain score, an upper limb pain score, and a total pain score. The mean of all three pain scores increased with the severity of the clinical stage (p < 0.001 for all). For the lower pain score, the difference was significant when comparing stage 1 with stages 2 (p < 0.001) and 3 (p < 0.001); it was not significant when comparing stage 2 with stage 3 (p = 0.0125). The difference was always significant in the comparison of each stage for the upper limb and total pain scores (p < 0.001 for each comparison).

Figure 3

Clinical signs of lipedema. The figure shows some of the characteristic clinical signs of lipedema: ankle cuff (A,B), malleolar dimple (C,D), suprapatellar fat pad (E,F), malleolar fat pad (G,H).

Figure 4

(A,B) Points of pain detection (A) and adipose tissue thickness evaluation via ultrasound (B). (A) The figure shows the points of pain detection of lower and upper limbs: posterior middle third of the leg (1), medial upper third of the leg (2), medial and lateral lower third of the thigh (3 and 4), lateral upper third of the thigh (5), medial upper third of the thigh (6) and lower abdomen (7), lower edge of the subscapularis muscle (8), arm and forearm (9 and 10). (B) The figure shows the adipose tissue points where the thickness was assessed by ultrasound; some of these are in common with the pain detection points: medial upper third of the leg (2), medial and lateral lower third of the thigh (3 and 4), lateral upper third of the thigh (5), medial upper third of the thigh (6). Furthermore, the thickness of the adipose tissue was measured at four other points: lower medial third of the leg (11), lower lateral third of the leg (13), upper lateral third of the leg (12), upper anterior third of the thigh (14).

Figure 5

Ultrasound measurement of skin (dashed line 1) and adipose tissue thickness (dashed line 2): the thickness of the skin was measured from the skin surface to the lower edge of the epidermis and dermis complex, and the thickness of the suprafascial superficial adipose tissue was measured from the skin surface to the subcutaneous transition structure (fascia). This image is related to the lower medial third of the right leg, performed using a high-frequency linear probe (8–14 MHz), keeping the probe perpendicular to the skin and without applying pressure to the underlying tissue.