Dercum's disease (DD) is a rare condition characterized by intense, asymmetrical, chronic burning pain localized in adipose tissue, often accompanied by subcutaneous fat nodules, leading to a significant reduction in quality of life. It typically affects overweight or obese adults between 35 and 50 years of age, with a marked female predominance. Despite numerous hypotheses proposed over time, the pathophysiology of DD remains poorly understood. Diagnosis is particularly challenging, as it relies solely on clinical evaluation. Given the overlapping features with other conditions, including symptoms, clinical course and inheritance pattern, a differential, accurate, and timely diagnosis is essential for the effective management of DD. Current treatment strategies focus primarily on pain relief, reflecting the still uncomplete understanding of DD etiopathogenesis. This review provides an updated overview of the current knowledge on DD, with particular emphasis on recent advances in pharmacological treatment strategies.

Dercum's disease (DD) is a rare connective tissue disorder characterized by multiple painful progressive adipose deposits. No definitive treatment for DD exists; therefore, the purpose of this study was to aggregate the current treatment options and outcomes in the literature to guide clinical decision-making regarding intervention. A comprehensive search was conducted across the selected databases, PubMed, Web of Science, and clinicaltrials.gov , for studies including at least 3 patients with DD without concurrent lipedema. Given the rarity of the pathology, descriptive analysis was primarily utilized if there were no homogenous endpoints. A total of 837 studies were extracted from the databases, of which 10 met the inclusion criteria. The majority of studied interventions included liposuction (4 studies), followed by dermolipectomy, transcutaneous electrical stimulation, cyclic pneumatic compression, and injections with either Tapencarium (RZL-012) or deoxycholic acid, and prostigmine and aminoacetic acid. One hundred ninety patients underwent these intervention types, of which 95.3% were female, with a mean age of 51.7 years and an average body mass index of 34.0 kg/m 2 . Four intervention types (liposuction, pneumatic compression, dermolipectomy, and electrical stimulation) included pain assessments utilizing a visual analog scale. All interventions demonstrated a decrease in pain scores, although the effect of electrical stimulation did not reach significance. Of the 2 studies assessing liposuction, there were significantly decreased visual analog scale scores at the following time points: 3 and 6 months, and 3 and 5 years, with nonsignificant reductions at 1 and 2 years. Dercum's disease is a rare pathology that continues to cause pain and distress in a primarily middle-aged, obese female population. Our systematic review calls for further investigation for optimal management of an often debilitating disease.

Obesity is increasingly recognized not only as a metabolic disorder, but also as a state of chronic low-grade inflammation that predisposes to systemic complications. Within this context, Dercum's disease (DD), or adiposis dolorosa, emerges as a rare yet debilitating disorder characterized by painful subcutaneous lipomas, most commonly affecting middle-aged women. Despite its clinical impact, DD remains underdiagnosed and is often misclassified as lipedema, fibromyalgia, or lipomatosis, complicating prevalence estimates and hindering the development of targeted interventions. Current evidence suggests that DD represents a distinctive model of inflammatory obesity, where adipose tissue actively contributes to pain generation rather than serving as a passive fat reservoir. Histological and molecular findings point to adipose tissue dysfunction, immune cell infiltration, and elevated secretion of pro-inflammatory adipokines, signals which appear to fuel systemic low-grade inflammation, perineural immune interactions, and nociceptor sensitization. Peripheral mechanisms further shape the clinical phenotype. While familial clustering suggests possible genetic contributions, no definitive markers have been identified, and the role of obesity-induced epigenetic modifications remains unexplored. Therapeutic strategies remain largely symptomatic, including analgesics, antidepressants, physical rehabilitation, and surgical excision of lipomas, whereas molecularly targeted and diet-based interventions are still experimental. This article discusses the pathophysiology of DD, current treatments, and future perspectives, emphasizing that advancing patient registries, omics-based analyses, and interdisciplinary clinical trials will be crucial to elucidate disease mechanisms and guide novel therapies. Improved understanding of DD may not only enhance patient care, but also provide broader insights into the interplay between obesity, inflammation, and chronic pain. Adiposis dolorosa, also known as Dercum disease, Ander syndrome, morbus Dercum, adipose tissue rheumatism, adiposalgia, or lipomatosis dolorosa, is a rare chronic disorder characterized by multiple painful subcutaneous growths of adipose tissue. First described in the late 1800s by American neurologist Francis Xavier Dercum, this condition is classified into 4 types: generalized diffuse (widespread painful adiposity without discrete lipomas), generalized nodular (diffuse pain accentuated around lipomas), localized nodular (pain localized to discrete lipomas), and juxta-articular (painful, solitary adipose tissue near large joints). The diagnosis is clinical and one of exclusion, with proposed criteria including chronic pain of subcutaneous tissue for over 3 months in individuals who are overweight or obese, although these criteria require further validation. Pain is often disabling, resistant to standard analgesics, and accompanied by systemic manifestations such as weakness, depression, anxiety, cognitive impairment, sleep disturbances, palpitations, dyspnea, gastrointestinal complaints, fatigue, and joint pain. Pathologically, the disorder primarily affects subcutaneous adipose tissue, most commonly on the trunk, proximal extremities, and upper arms, with lesions that may be discrete or diffuse. Histology may reveal normal adipocytes, mild fibrosis, or inflammatory infiltrates, but no pathognomonic finding exists. The natural history is progressive, characterized by the gradual enlargement of lesions and worsening pain over time. Spontaneous remission is rare; symptoms tend to fluctuate but persist without intervention. While liposuction and surgical excision may temporarily reduce bulk and alleviate pain, recurrence is common, underscoring the importance of long-term, multidisciplinary management.

Adiposis dolorosa (Dercum disease) is a rare condition characterized by diffuse and recurring painful lipomas on the trunk and extremities. Patients are typically middle-aged females with an elevated BMI presenting with chronic pain. Physical examination reveals soft subcutaneous nodules and masses, tender to palpation. The associated pain significantly impacts quality of life and requires therapeutic intervention. The most common treatment option is surgical excision. Alternative options should be considered for patients with numerous lipomas where surgical management is not practical or is not desired. Deoxycholic acid injections are a viable alternative non-surgical technique. We present a case of a 55-year-old woman who presented with a history of Dercum disease and worsening pain associated with multiple lipomas. The patient desired a non-surgical intervention. She was subsequently treated with three rounds of deoxycholic acid injections with reduction in pain and improved mobility. Intralesional deoxycholic acid injections are a safe and effective nonsurgical alternative for patients with multiple lipomas.