Is Lipedema an Autoimmune Disease?

Lipedema is a condition characterized by abnormal accumulation of adipose tissue, primarily in the limbs. This can lead to painful swelling and disfigurement, which often impair individuals’ mobility and quality of life. The causes of lipedema are not fully understood; however, the condition has been linked to inflammatory processes mediated by innate immune cells. Recent studies have reported a correlation between lipedema incidence and certain HLA class II alleles linked to autoimmune conditions, such as celiac. Another study found that tissue samples from patients with lipedema had elevated levels of a protein called macrophage migration inhibitory factor 1 (MIF-1), which has been implicated in several other diseases, including some autoimmune diseases. These findings suggest that autoreactive immune cells could play a role in the pathogenesis of lipedema; however, further studies are needed to reveal whether autoimmune mechanisms play a direct causal role in the development of lipedema.

Author - Faith Wershba

Postgraduate researcher at the University of Cambridge.

Faith used MediSearch to find sources for this blog.

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What is Lipedema?

Lipedema is a chronic, idiopathic disorder that primarily affects women post-puberty. The disorder is characterized by the symmetrical accumulation of adipose tissue, typically within the lower limbs and arms (although it can affect other areas of the body) [1]. The disease is frequently misdiagnosed as obesity or lymphedema: a condition in which the lymphatic fluid accumulates within body tissues [1]. Such misdiagnosis may lead to inappropriate management and medical stigma, which further contributes to the disease’s morbidity [5].

Symptoms of Lipedema

The accumulation of fat in lipedema results in swollen, painful, and enlarged limbs, which can significantly impact a person's self-esteem, mobility, and overall quality of life [1]. Individuals with lipedema may also experience increased bruising and tenderness [6]. If left untreated, lipedema can lead to more serious complications such as osteoarthritis and secondary lymphedema [6].

What Causes Lipedema?

Lipedema is considered an idiopathic condition: that is, the cause(s) of disease remain unknown [2]. The condition appears to have a strong genetic component, with 60% of lipedemic individuals having a first-degree relative with the condition [7]. Lipedema occurs more frequently in women and its onset often coincides with hormonal changes, such as puberty, pregnancy, or menopause. As such, some researchers have hypothesized that the pathogenesis of lipedema is estrogen-mediated [7]. Several studies have linked lipedema with inflammatory processes, suggesting that the disease’s pathogenesis may also have an immunological component [2, 4].

How to Treat Lipedema

There is currently no cure for lipedema, and so most treatments focus on pain management and symptom reduction [2]. Broadly speaking, there are two main treatment approaches: conservative treatment and surgical intervention.

Conservative Treatment of Lipedema

Conservative treatments for lipedema include [2]:

Complex decongestive therapy (CDT). CDT involves techniques such as manual lymph drainage (MLD), compression therapy, soft tissue mobilization, and skin care. The goal of such therapies is to reduce swelling and relieve pain.
Diet. Although diet cannot directly reduce the fat deposits characteristic of lipedema, certain foods that are considered anti-inflammatory or ketogenic may help diminish edema, tissue hypoxia, and inflammation.
Medications and supplements. Medications and supplements including amphetamines, phentermine, metformin, resveratrol, diosmin and selenium may be helpful in reducing inflammation and reducing swelling [8].

Surgical Treatment of Lipedema

The main surgical treatments used to treat lipedema are liposuction and lipectomy [2]. Liposuction is used to remove small masses of adipose deposits in order to reduce localized pain and improve quality of life [2]. Lipectomy, on the other hand, is used to remove larger masses of tissue.

Is Lipedema an Autoimmune Disorder?

Lipedema is officially characterized as a connective tissue disorder. It is not considered to be autoimmune in nature. This being said, some researchers have begun exploring potential links between autoimmune mechanisms and lipedema pathogenesis. For example, Amato et al. reported that the prevalence of HLA-DQ2 and HLA-DQ8 alleles was higher amongst women diagnosed with lipedema compared to the general population [3]. These alleles have been linked to celiac disease, an autoimmune condition triggered by gluten. Another study reported that the accumulation and skewed polarization of macrophages—which is often observed in patients with lipedema—is mediated by macrophage migration inhibitory factor 1 (MIF-1), helping clarify the link between immune processes and disease pathogenesis [4]. Further research is needed to confirm whether such associations are replicable across patients and/or biologically meaningful.

Conclusion

Lipedema is a connective tissue disorder characterized by abnormal accumulation of fat tissue at various body sites. The condition typically leads to progressive swelling and enlargement of the limbs, which can cause pain, immobility, psychological distress, and reduced quality of life. The causes of lipedema are unknown, and thus treatment aims primarily at reducing symptoms and preventing further progression. Lipedema is not an autoimmune condition, although some research suggests that the disorder may be linked to immune dysfunction and dysregulation. Further studies are needed to parse out the molecular mechanics of these associations and determine whether lipedema shares relevant features with other autoimmune conditions.