Impact of Hypermobile Ehlers-Danlos Syndrome on Adipose Tissue
Hypermobile Ehlers-Danlos Syndrome (hEDS) affects adipose tissue through connective tissue abnormalities that alter mechanical stiffness and may lead to mast cell activation and inflammatory responses in fat tissue. 1
Connective Tissue Abnormalities in Adipose Tissue
- Skin biopsies in hEDS patients show altered collagen fibril structure that triggers fibroblast dysfunction within connective tissue, affecting adhesion and cytoskeletal response 1
- Evidence indicates that in hEDS, connective tissue is softer and less stiff than in control subjects, which likely extends to adipose tissue that contains significant amounts of connective tissue 1
- Proteome profiling of hEDS patients' dermal myofibroblasts reveals dysregulation of proteins involved in cytoskeleton organization, energy metabolism, redox balance, and intracellular trafficking 2
Mast Cell Activation and Adipose Tissue
- Mast cells migrate into connective tissue and mucosa, including adipose tissue, where they can proliferate and potentially cause inflammatory responses 1
- In hEDS, there is evidence of early or excessive mast cell degranulation leading to mast cell activation disorders that can affect multiple tissue systems including adipose tissue 1
- When Mast Cell Activation Syndrome (MCAS) is suspected in hEDS patients, treatment with histamine receptor antagonists and mast cell stabilizers may benefit adipose tissue function 1
- MCAS symptoms can be triggered by mechanical stimuli (e.g., friction), which may explain why adipose tissue in hypermobile areas could experience increased inflammation 1
Unique Adipose Tissue Manifestations
- Case reports have documented "mobile encapsulated lipomas" in hEDS patients, characterized by highly mobile nodules within subcutaneous adipose tissue that consist of mature or degenerative lipocytes encapsulated by fibrous tissue 3
- The altered connective tissue structure in hEDS may contribute to abnormal adipose tissue distribution or encapsulation 3, 4
- Proteostasis and intracellular trafficking abnormalities identified in hEDS may affect adipocyte function and lipid metabolism 2
Clinical Implications for Adipose Tissue Management
- Dietary interventions may be necessary for hEDS patients with adipose tissue abnormalities, particularly when MCAS is present, including low-histamine diets 1
- Mechanical stimuli that trigger mast cell activation should be minimized to reduce inflammation in adipose tissue 1
- The connective tissue abnormalities in hEDS may require special consideration when evaluating adipose tissue-related conditions 4, 5
- Genetic testing should be considered in patients with joint hypermobility and adipose tissue abnormalities to exclude alternative diagnoses that may require different management approaches 6
Diagnostic Considerations
- The Beighton scale is essential for diagnosing hEDS, with age-specific thresholds: ≥6/9 points in children before puberty, ≥5/9 points for adults up to age 50, and ≥4/9 points for adults over 50 7
- Up to 60% of hEDS patients experience gastrointestinal symptoms, which may be related to altered connective tissue affecting both the GI tract and surrounding adipose tissue 7
- The diagnosis of hEDS remains clinical as its molecular basis is still unknown, making it challenging to definitively characterize its effects on adipose tissue 5
Management Approaches
- Treatment should focus on the most prominent symptoms, including those that may be related to adipose tissue abnormalities 1
- For patients with suspected MCAS affecting adipose tissue, avoiding triggers such as certain foods, alcohol, strong smells, temperature changes, and mechanical stimuli is recommended 1
- Special diets including low-histamine approaches may be beneficial but should be delivered with appropriate nutritional counseling to avoid restrictive eating 1
- Integrated care involving multiple specialties may be necessary for comprehensive management of hEDS patients with adipose tissue abnormalities 1