Investigation of Central Sensitization and Associated Factors in Patients With Lipedema

Official title

Investigation of the Prevalence of Central Sensitization and Associated Factors in Patients With Lipedema

Overview

This study aims to investigate the presence of central sensitization and its associated parameters in patients with lipedema. Lipedema is a chronic and hereditary condition that primarily affects the lower extremities in women and is often associated with hormonal changes. Symptoms such as pain, swelling, and tenderness are common in lipedema, and these symptoms may be related to central sensitization. Additionally, the ultrasonographic findings and pain sensitivity in lipedema will be compared with those of healthy individuals. This study seeks to contribute to the diagnosis and treatment process of lipedema.

Detailed description

Lipedema is a chronic and hereditary condition that affects the subcutaneous fat tissue, particularly in the lower extremities of women. Although its prevalence is not clearly known, it is estimated to be common in the general population. It typically begins during periods of weight gain associated with hormonal changes such as puberty, pregnancy, and menopause. It is characterized by persistent swelling in the lower extremities, especially in the upper thighs, which does not improve with elevation, and is painful to touch. Patients often report easy bruising even with minor trauma or touch. The hips and gluteal region are the most commonly affected areas, and the hands and feet are typically spared. On examination, the affected extremities feel soft and doughy due to fat hypertrophy, and there is an increased sensitivity across the area. During follow-up, patients' weight and body mass index (BMI) should be monitored, and the circumferences and volumes of the affected extremities should be measured and recorded.

The diagnosis is usually made clinically after ruling out other differential diagnoses. Among the auxiliary imaging methods, ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) can be used to evaluate the skin and subcutaneous fat tissue. US is frequently preferred in the diagnosis of lipedema as it allows differentiation from lymphedema. Common ultrasonographic findings of lipedema include normal skin thickness, increased thickness of the subcutaneous layer, homogeneous expansion of this layer, and a decrease in echogenicity. A key issue in the diagnosis of lipedema is its confusion with obesity, a prevalent health issue in the general population.

Pain is a significant symptom in patients with lipedema. Studies have shown that pain and increased sensitivity in the swollen extremities of lipedema patients negatively affect their quality of life. Patients frequently complain of nonspecific pain and tenderness, thought to be transmitted by A beta and C fibers, a phenomenon known as allodynia. These complaints are believed to be associated with an increase in pain sensitivity.

Central sensitization is the increased sensitivity of the central nervous system to pain. This condition is associated with exaggerated pain responses to stimuli from specific areas of the body, especially in patients with chronic pain. The pain experienced in lipedema, which worsens even with mild stimuli like touch, raises the possibility of central sensitization. These findings suggest that pain in lipedema is not merely a localized fat tissue issue, but rather a complex process that also affects the nervous system. Therefore, although the presence of central sensitization in lipedema has not been conclusively proven, it is believed that central sensitization may occur in lipedema, considering the role of chronic pain and neurogenic mechanisms. This study aims to investigate the presence of central sensitization and its associated parameters in patients with lipedema. Additionally, the study will examine the differences and similarities in ultrasonographic and pain sensitivity findings between individuals with lipedema and healthy controls.

Interventions

• Other Pain-Pressure Threshold Measurement With an Algometer
  The measurement will be performed 2 times with 3 min intervals for each region and the average of these applications will be recorded. Before the test, a trial test will be applied to the patient. With the pressure algometer, pressure will be applied to the selected points until it causes pain and the test will be terminated for that region when the patient feels pain. The measurement includes bilateral thigh, pretibial region and left forearm as remote site and Wagner manual pressure algometer
• Other Central Sensitization Inventory
  The central sensitization scale was developed primarily to detect central sensitization findings in patients with chronic pain and consists of two parts, A and B. In part A, 25 somatic and psychosocial symptoms frequently found in patients with central sensitization.
• Other Numeric Rating Scale
  Leg pain, feeling of tension and heaviness on the affected arm will be evaluated separately by numerical scale.
• Other Lower Extremity Functional Scale
  The lower extremity functional scale is a valid patient-rated outcome measure for the measurement of lower extremity function. The scale consist of 4 groups with 20 questions. The questions in these group focus on activities with increasing physical demands like questions from walking between rooms to running on uneven ground. The scoring of this scale varies from 0 (extreme difficulty/unable to perform activity) to 4 (no difficulty). The total score can be obtained by summing the scores of the
• Other Short form 12
  The Short form 12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. It is often used as a quality of life measure.The scoring yields two summary measures: the Physical Component Summary (PCS) and the Mental Component Summary (MCS).Utilize the norm-based scoring system to interpret PCS and MCS scores, with a mean of 50 and a standard deviation of 10 in the general population.Scores above 50 indicate a better-than-average health-related quality of
• Other lower extremity volumetric measurement
  It is calculated by converting the circumference measurements taken at 4 cm intervals from the ankle to the proximal thigh into lower extremity volume with Excel.
• Other lower extremity circumference measurement
  bilateral tuberosity tibia, 20 cm proximal tuberosity tibia, tuberosity tibia 10 cm distal and ankle level
• Other Bioelectrical Impedance Analysis
  With Bioelectrical Impedance Analysis, fat, muscle and water ratio and lean mass are calculated in addition to the patient's body weight.
• Diagnostic test Ultrasound
  Measurement of subcutaneous fat tissue thickness from mid-thigh, pretibial, lateral leg and supramalleolar regions with ultrasound.The average of two measurements taken from the same area will be recorded.According to these measurements; 12-15 mm = mild lipedema or lipohyperplasia, 15-20 mm = moderate lipedema, \>20 mm = significant lipedema, \>30 mm = severe lipedema.

Primary outcome measures

• Central Sensitization Inventory [Time frame: 3 months]
• Pressure Pain Threshold [Time frame: 3 months]

Secondary outcome measures (6)

• Short Form-12 [Time frame: 3 months]
• Lower Extremity Functional Scale, LEFS [Time frame: 3 months]
• Bioelectrical Impedance Analysis [Time frame: 3 months]
• Evaluation with ultrasonography [Time frame: 3 months]
• Lower extremity measurements [Time frame: 3 months]
• Lower extremity volumetric measurements [Time frame: 3 months]

Eligibility criteria

Inclusion criteria

• Lipedema; Diagnosis of lipedema Aged between 18 and 65 years Literate Willing to participate in the study
• control group; Being completely healthy (no internal/metabolic issues such as diabetes, obesity, or hypothyroidism, and no diagnosis of lipedema) BMI ≤ 30 Aged between 18 and 65 years Literate Willing to participate in the study

Exclusion criteria

• Lipedema group; Under 18 or over 65 years of age Presence of concurrent lymphedema, chronic venous insufficiency, deep vein thrombosis, polyneuropathy, or fibromyalgia Illiterate Not willing to participate in the study
• Control group; Under 18 or over 65 years of age Presence of concurrent lymphedema, chronic venous insufficiency, deep vein thrombosis, polyneuropathy, fibromyalgia, systemic rheumatic diseases, active cancer, infections, or pregnancy Illiterate Not willing to participate in the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Turkey (Türkiye) · 1 center

• Sultan 2. Abdülhamid Han Eğitim ve Araştırma Hastanesi, İstanbul, Üsküdar 34000 — Istanbul

Publications

• Chakraborty A, Crescenzi R, Usman TA, Reyna AJ, Garza ME, Al-Ghadban S, Herbst KL, Donahue PMC, Rutkowski JM. Indications of Peripheral Pain, Dermal Hypersensitivity, and Neurogenic Inflammation in Patients with Lipedema. Int J Mol Sci. 2022 Sep 7;23(18):10313. doi: 10.3390/ijms231810313. PMID 36142221
• Dinnendahl R, Tschimmel D, Low V, Cornely M, Hucho T. Non-obese lipedema patients show a distinctly altered quantitative sensory testing profile with high diagnostic potential. Pain Rep. 2024 Apr 11;9(3):e1155. doi: 10.1097/PR9.0000000000001155. eCollection 2024 Jun. PMID 38617100
• Soylu C, Kutuk B. Reliability and Validity of the Turkish Version of SF-12 Health Survey. Turk Psikiyatri Derg. 2022 Summer;33(2):108-117. doi: 10.5080/u25700. English, Turkish. PMID 35730511
• Jebb SA, Cole TJ, Doman D, Murgatroyd PR, Prentice AM. Evaluation of the novel Tanita body-fat analyser to measure body composition by comparison with a four-compartment model. Br J Nutr. 2000 Feb;83(2):115-22. doi: 10.1017/s0007114500000155. PMID 10743490
• Duzce Keles E, Birtane M, Ekuklu G, Kilincer C, Caliyurt O, Tastekin N, Is EE, Ketenci A, Neblett R. Validity and reliability of the Turkish version of the central sensitization inventory. Arch Rheumatol. 2021 Oct 18;36(4):518-526. doi: 10.46497/ArchRheumatol.2022.8665. eCollection 2021 Dec. PMID 35382371
• Binkley JM, Stratford PW, Lott SA, Riddle DL. The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network. Phys Ther. 1999 Apr;79(4):371-83. PMID 10201543
• Amato ACM, Saucedo DZ, Santos KDS, Benitti DA. Ultrasound criteria for lipedema diagnosis. Phlebology. 2021 Sep;36(8):651-658. doi: 10.1177/02683555211002340. Epub 2021 Apr 15. PMID 33853452

Identifiers

NCT: NCT06770634 · 2024/14/14/10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗