Continuing Education Activity

Adiposis dolorosa is a rare disorder of multiple painful subcutaneous growths of adipose tissue most commonly affecting the proximal extremities, trunk, and buttocks. This activity outlines the evaluation and management of adiposis dolorosa and highlights the role of the interprofessional team in treating patients with this condition.

Objectives:

• Review the typical presentation of adiposis dolorosa.
• Describe how to properly evaluate a patient for adiposis dolorosa.
• Outline the differential diagnosis of adiposis dolorosa.
• Summarize the importance of collaboration and communication amongst interprofessional team members to enhance care coordination for patients with adiposis dolorosa.

Introduction

Adiposis dolorosa is a rare disorder of multiple painful subcutaneous growths of adipose tissue. It is also known as Dercum disease, Ander syndrome, morbus Dercum, adipose tissue rheumatism, adiposalgia, or lipomatosis dolorosa. This disease was first discovered in the late 1800s by American neurologist Francis Xavier Dercum. It is classified into 4 types which include generalized diffuse, generalized nodular, localized nodular, and juxta-articular forms. The generalized diffuse type presents with widespread painful adipose tissue with no apparent lipomas. The generalized nodular type presents with widespread, painful adipose tissue that is more painful in the vicinity of lipomas. In the localized nodular type, the pain is restricted to areas within and around lipomas. Lastly, the juxta-articular type presents as painful solitary adipose tissue near large joints.[1][2]

The diagnosis of adiposis dolorosa is made clinically and is a diagnosis of exclusion. The proposed criteria for the diagnosis includes chronic pain of the subcutaneous tissue for over 3 months in overweight patients or patients with obesity, though the criteria still need to be validated. The pain is often disabling and resistant to treatment. The disease is associated with weakness and psychiatric symptoms such as depression. Other associated symptoms include fatty deposits, easy bruising, sleep disturbances, impaired memory, difficulty concentrating, anxiety, rapid heartbeat, shortness of breath, diabetes, bloating, constipation, fatigue, and joint pain.

Etiology

The etiology of this disease is unknown. Current hypotheses include nervous system dysfunction, endocrine dysfunction, lymphovascular disorder, adipose tissue dysfunction, mechanical pressure on nerves, and trauma-induced. Although few case reports of patients diagnosed with adiposis dolorosa have been considered to be autosomal dominant with variable phenotypic expression, this is not the standard. Most cases of the disease are found to be sporadic with no specific genetic mutations.[3][4][5]

Epidemiology

No significant epidemiologic data is available but based on case reports adiposis dolorosa is found more frequently in obese females ages 35 to 50 years. Previously, it was thought that the disease was more common in post-menopausal females, but more recent studies have rejected this claim.

Pathophysiology

The pathogenesis and mechanism of adiposis dolorosa remain unknown.

Histopathology

The histopathology of biopsies taken from patients diagnosed with adiposis dolorosa shows an inflammatory response with lymphocytes and macrophages. The inflammation in this disease may not be any more pronounced than that of a healthy patient with obesity without adiposis dolorosa.

History and Physical

Patients typically first notice painful growing nodules. The pain of their condition is classically described as aching, stabbing, or burning in quality and it is generally symmetric. Typically, pain worsens with palpation. The most common areas of painful adipose tissue include the proximal extremities, trunk, and buttocks.

On physical exam, patients with adiposis dolorosa are commonly overweight or obese, and pain symptoms are out of proportion to what is found on the exam.

Evaluation

There are no laboratory markers for the condition, but lab work should be done to exclude other conditions. Hormonal studies should be ordered to rule out Cushing syndrome, thyroid abnormalities, or endocrinologic abnormalities. Patients with adiposis dolorosa are found to have a slight to moderate increase in cholesterol levels. Erythrocyte sedimentation rate (ESR) may be slightly elevated in this disease as well.

Ultrasound and magnetic resonance imaging (MRI) may be helpful in making the diagnosis. Ultrasound may demonstrate multiple, small, oblong hyperechoic nodules. MRI of patients with adiposis dolorosa may show multiple, oblong superficial subcutaneous fatty lesions with a nodular increased fluid signal that appears “blush-like.”

Treatment / Management

While many therapeutic options have been used, there is no standard treatment of choice for this disease. Therapies are individualized to specific symptoms in each patient with the goal to relieve symptoms and create support. The lipomas are found to be unaffected by weight loss and in a few cases have exacerbated symptoms. Pain may be debilitating and intermittent necessitating the need for a pain management specialist. Treatment options for pain suggested by case reports include analgesics, liposuction, lipectomy, and manual lymphatic drainage. The pain in adiposis dolorosa has not been found to be adequately controlled by traditional analgesics, though non-steroidal anti-inflammatory drugs (NSAIDs) and narcotics have shown some benefit in the diminishment of pain. Other medications and treatment modalities with mixed results of potential benefit include lidocaine, ketamine, methotrexate, infliximab, interferon alpha-2b, corticosteroids, calcium-channel modulators, transcutaneous electrical stimulation, and rapid cycling hypobaric pressure. Liposuction and lipectomy may be effective for pain reduction short term, but the pain typically returns and does not significantly increase the quality of life.[6][7]

Differential Diagnosis

The diagnosis of adiposis dolorosa should only be made when other diagnoses have been excluded. Differential diagnoses include fibromyalgia, panniculitis, endocrine disorders, primary psychiatric disorders, multiple symmetric lipomatosis (Madelung syndrome), multiple familial lipomatosis, Proteus syndrome, and benign adipose tissue tumors.

Fibromyalgia is a common chronic syndrome of widespread musculoskeletal pain and tenderness, fatigue, and cognitive difficulties that can be easily confused with adiposis dolorosa especially in overweight or obese females. These patients also have an unremarkable physical exam and lab work. The diagnosis of fibromyalgia is based on widespread pain & tender points typically in specific locations in muscle and joints as well as fatigue and cognitive and psychiatric disturbances which is also a diagnosis of exclusion.

Panniculitis presents with painful inflammatory nodules of the subcutaneous fat. The history, location, and associated findings of erythema, ulceration, and atrophic scarring help to differentiate the type of panniculitis. A biopsy is diagnostic.

Endocrine disorders that may be confused with adiposis dolorosa include Cushing syndrome and hypothyroidism. Both of these diseases present with weight gain and generalized pain not localized to the subcutaneous tissue, which helps differentiate them from adiposis dolorosa.

Depression can present similarly to Dercum disease in that it is often associated with chronic pain conditions.

Madelung syndrome presents with large, symmetric, nonpainful fat accumulation around the neck, upper extremities, and trunk typically in non-overweight, alcoholic males which help distinguish it from adiposis dolorosa.

Familial multiple lipomatosis similarly presents with multiple lipomas, though often multiple family members are affected because it is genetic with a mutation in the 12q13–15 region which contains the HMGA2 gene.

Proteus syndrome is a genetic disease with lipomatosis from an activating mutation in the AKT1 oncogene. This syndrome also presents with overgrowth of other various tissues.  

Lastly, benign adipose tissue tumors generally are not ordinarily painful but can present as multiple lesions on a single patient.

Prognosis

Adiposis dolorosa tends to be a chronic disease that does not abate over time and may progress to become more debilitating as time goes on. Though, there have been case reports showing variable results in prognosis.[8]

Consultations

This disease is best treated as a multidisciplinary approach with teams specialized in chronic pain.

Enhancing Healthcare Team Outcomes

Adiposis dolorosa is a rare disorder of multiple painful subcutaneous growths of adipose tissue. The diagnosis of adiposis dolorosa is made clinically and is a diagnosis of exclusion. The proposed criteria for the diagnosis includes chronic pain of the subcutaneous tissue for over 3 months in overweight patient or patient with obesity, though the criteria still need to be validated. The pain is often disabling and resistant to treatment. The disease is associated with weakness and psychiatric symptoms such as depression. Because of its rarity, the disorder is best managed by an interprofessional team of clinicians including specialists and specialty-trained nurses and pharmacists. If the diagnosis is delayed, it is associated with high morbidity. As such the clinical team should confirm the diagnosis as quickly as possible. The pharmacist should assist in considering treatment options and assuring compliance, and the specialty-trained nurse should assist with monitoring, coordinating follow up and with patient and family education. [Level 5]