Introduction

Rare adipose tissue disorders (RADs) are characterised by abnormal or persistent fat that is resistant to standard weight control techniques and frequently manifests as metabolic problems.¹ Dercum's disease (DD), also known as adiposis dolorosa, is a rare and complicated RAD that affects adipose (fatty) tissue. Its main characteristic is persistent, incapacitating pain in adipose tissue, which is sometimes accompanied by lipomas or subcutaneous masses.²

Understanding dercum’s disease

Dercum's disease classification can aid in comprehending its various forms:³

• Type one (generalised diffuse form): painful adipose tissue that is widespread and without obvious lipomas
• Type two (generalised nodular form): severe pain in and around several lipomas spread throughout the body, along with general adipose tissue pain
• Type three (localised nodular form): lipomas and pain are restricted to specific areas
• Type four (juxta-articular form): painful lipomas close to the joints, particularly significant ones like the elbow, hip, or knee

The World Health Organisation recognises DD as a rare disease. It meets the criteria of the Orphan Drug Act of 1983, which provides funding for the treatment of rare diseases, because estimates indicate that it affects fewer than 200,000 people in the United States.² People assigned female at birth (AFAB) are five to 30 times more likely than people assigned male at birth (AMAB) to develop the condition, which often manifests between the ages of 35 and 50.³

Common clinical features

The main feature is the chronic and debilitating pain in adipose tissue. Many people describe this pain as severe, scorching, and burning, and it lasts longer than three months.² It may range from palpable and constant discomfort to unexpected, intense episodes.⁴ Another main feature is the development of lipomas or subcutaneous masses. These fat deposits may be as small as a pea or as large as a fist.¹ They are typically found in the legs, arms, trunk, pelvis, and buttocks.² Less commonly, the face, scalp, and neck may also be impacted.¹

Associated symptoms:

• Weakness and fatigue²
• Depression, anxiety, and cognitive issues.² Other psychiatric symptoms include disorientation, seizures, and emotional instability⁵
• Increased vascular fragility and easy bruising⁴
• Sleep disturbances⁴
• Muscle stiffness and joint pain 
• Metabolic disorders like diabetes and high cholesterol²
• Gastrointestinal distress, which frequently includes constipation, bloating, stomach pain, and irritable bowel syndrome 
• Breathlessness and tachycardia (fast heartbeat/palpitations)⁴

Diagnostic challenges

Due to its acknowledged rarity, DD is not yet widely understood by the medical community, making diagnosis extremely difficult and could therefore result in detrimental effects on you as a patient. Additionally, the rare and diverse symptoms seen in DD often result in delayed or incorrect diagnoses. Furthermore, the lack of reliable laboratory markers and objective criteria means that doctors must rely on careful clinical evaluation of symptoms and the elimination of other possible causes, thereby increasing the risk of human-based errors.²

When DD is a component of a more complex medical condition, misdiagnosis becomes very likely. For example, neurological or psychiatric symptoms may take precedence over the other symptoms, leading to the painful lipomas going undetected and contributing to an underestimation of their occurrence. Additionally, in contrast to pain in muscles, bones, or tendons, many healthcare professionals do not consider pain in adipose tissue to be a credible complaint. This lack of acceptance contributes to DD being overlooked as a plausible diagnosis.⁶ 

Despite the growing pool of scientific research, the precise cause of DD remains unclear.² There is little evidence to support many of the suggested theories, which include trauma, inflammation, adipose tissue dysfunction, mechanical strain on nerves, and nervous system dysfunction.⁴ Imaging techniques like ultrasound, computed tomography, and magnetic resonance imaging can confirm subcutaneous lipomas but do not provide definitive diagnostic markers for DD, especially for the diffuse forms.²

Overlap with other conditions

DD is a diagnosis of exclusion; a final diagnosis cannot be determined until all other conditions have been ruled out.⁵ DD can be confused with obesity, fibromyalgia, lipoedema, Madelung’s disease, and familial multiple lipomatosis:

Obesity

Many people with DD generally appear overweight and are therefore incorrectly diagnosed with obesity.⁶ However, weight loss through traditional methods is typically ineffective in people with DD due to the aberrant fatty deposits.³

Fibromyalgia 

Fibromyalgia can be difficult to differentiate from DD, particularly in obese people. This is because both conditions entail widespread adipose and muscular pain, exhaustion, cognitive abnormalities, and mental symptoms.⁵

Lipoedema 

Lipoedema is the symmetrical expansion of both legs brought on by the deposition of subcutaneous adipose tissue, which feels sore to the touch.² It primarily impacts people who are AFAB.^{5, 4} Unlike DD, it usually appears as diffuse fat without lipomas.³

Madelung's disease

Madelung’s disease, also known as multiple symmetrical lipomatosis, is characterised by large, symmetrical subcutaneous fatty masses, usually around the neck, shoulders, and upper body. These fat accumulations are more common in people who are AMAB and are also frequently linked to alcohol abuse.⁴

Familial multiple lipomatosis

Familial multiple lipomatosis (FML) is an inherited condition characterised by numerous widespread, painless lipomas.⁴ Although mostly painless, some people with FML may experience painful lipomas similar to those of DD.¹

Consequences of diagnostic delays and errors

Due to its rarity and wide range of symptoms, DD is commonly misdiagnosed or diagnosed late, leaving you feeling uneasy and uncertain. Living alongside ongoing physical pain while waiting for the correct diagnosis can be emotionally exhausting.² As such, early identification and assessment are essential for starting the right kind of treatment, lowering unease, and eventually enhancing your quality of life.⁵ 

Additionally, misdiagnosing these disorders might result in improper or inefficient treatments being prescribed. For example, because of the abnormal subcutaneous adipose tissue in DD, traditional methods of treating similar conditions, such as exercise, caloric restriction, and bariatric surgery, may not work.¹ As a result, you may undergo multiple therapeutic interventions, such as using painkillers, muscle relaxants, and antidepressants, yet only experience minor relief in pain. This trial-and-error approach increases the emotional strain, overall cost, and use of healthcare facilities until suitable treatments are found.⁷ However, although fat recurrence is possible, liposuction is still a crucial management technique as it has been shown to reduce pain.² 

Without clear guidelines and criteria, diagnostic pathways can become lengthy, involving multiple assessments and investigations to reach a conclusion, which increases healthcare costs.⁵

Emerging approaches and future directions

There is growing interest in research for new DD treatments. For example, RZL-012 is a small molecular therapy currently in phase 2 of its clinical trials. It is recognised as an orphan drug and aims to replace painful adipose tissue with fibrotic tissue.⁵ Another example of an emerging treatment for DD is transcutaneous electrical stimulation therapy, which has been shown to result in pain reduction and changes to subcutaneous adipose tissue, resulting in the regaining of the tissue’s functional status.⁶

Additionally, developing a clear, validated, objective diagnostic criterion for DD is crucial because the current criteria lack standardisation. Research on the cause, prevalence, and underlying genetic pathways of DD is also necessary to further understand its risk factors and improve diagnosis.⁵ Current approaches often rely on individual case studies, so larger clinical studies are required to create standardised surgical and medical therapeutic options for DD.⁶ 

For RADs more broadly, academic studies into different diets, physiotherapies, surgery, medication, and vitamins are also required.¹ Equally, raising medical awareness amongst healthcare professionals and the general public is essential for effective treatment and enhancing your quality of life.² To receive the most effective care, finding multidisciplinary teams that specialise in chronic pain management would be best, as they can offer you tailored support depending on your needs and concerns.⁴⁴

Summary

Dercum’s disease (DD), also known as adiposis dolorosa, is a rare adipose tissue disorder characterised by chronic, debilitating pain in fatty tissue, often accompanied by lipomas. It primarily affects people who are AFAB between the ages of 35 and 50, and is classified into four types. Alongside pain, DD is associated with fatigue, depression, cognitive difficulties, metabolic disturbances, and gastrointestinal issues, significantly impairing quality of life. 

Diagnosing DD is challenging due to its rarity, lack of specific biomarkers, and symptom overlap with obesity, fibromyalgia, lipoedema, Madelung’s disease, and FML. Imaging may confirm lipomas, but cannot reliably distinguish DD. These factors contribute to frequent misdiagnoses, delayed treatment, and high healthcare costs. Current research explores pharmacological therapies, surgical interventions, and electrical stimulation; however, greater awareness, validated diagnostic criteria, and multidisciplinary care are equally needed for effective management.