Adiposis dolorosa (ORPHA:36397)
A rare disorder of subcutaneous tissue characterized by the development of painful, adipose tissue with multiple subcutaneous lipomas, in association with overweight or obesity.
Epidemiology
Prevalence is unknown. It is 5-30 times more common in women.
Clinical description
The onset may be abrupt or indolent and most commonly occurs between 35 and 50 years of age. The main symptoms are obesity and painful adipose tissue. The most common locations for lipomas are the extremities, the trunk, the pelvic area, and the buttocks. The pain is often described as burning or aching but the pain experience varies between different individuals. A number of associate symptoms have been described. Some of them can be induced by obesity per se, such as weakness and susceptibility to fatigue. Others, such as depression and psychiatric manifestations, are common in all diseases involving pain. Therefore, such symptoms should not be seen as diagnostic for the disease. Other symptoms, such as easy bruisability, rapid heartbeat, shortness of breath, thyroid disease, diabetes and constipation have only been described in case reports and in a questionnaire study; however there is no evidence to support the association with adiposis dolorosa. Adiposis dolorosa can clinically be classified into: i) generalised diffuse form with diffusely widespread painful adipose tissue without clear lipomas ii) generalised nodular form with general pain in the adipose tissue as well as in and around lipomas iii) localised nodular form with pain in and around lipomas iv) juxta-articular form with solitary deposits of excess fat around one or several joints.
Etiology
The etiology remains unknown but several hypotheses have been proposed including endocrine dysfunction, nervous system dysfunction, mechanical pressure on the nerves, adipose tissue dysfunction, inflammation, infection and induced by trauma or medications. Most of the hypotheses are based on case reports and there is no convincing evidence for any of the etiologies.
Diagnostic methods
The basic diagnostic criteria for adiposis dolorosa are i) generalised overweight or obesity and ii) chronic pain (for greater than 3 months) in the adipose tissue. The diagnosis should be based on systemic physical examination and thorough exclusion of differential diagnoses. There are no laboratory markers for the disease. The pathohistological picture of adipose biopsies is generally indistinguishable from that of lipomas. Radiological findings overlap with other lipodystrophies, although lymphovascular anomalies and MRI patterns with fatty lesions in the subcutaneous fat have been described in single cases. Laboratory tests, biopsies, and radiology can be useful to exclude differential diagnoses.
Differential diagnosis
In cases of general diffuse forms of adiposis dolorosa, the differential diagnosis should include other conditions with general pain, such as fibromyalgia, lipoedema, panniculitits, endocrine disorders comprising pain and obesity, and psychiatric conditions comprising pain, especially in combination with obesity. In nodular forms of adiposis dolorosa, the differential diagnosis should include other multiple lipoma syndromes such as familial multiple lipomatosis, multiple symmetric lipomatosis, myoclonic epilepsy with red ragged fibres (MERRF) syndrome, neurofibromatosis type 1, and multiple endocrine neoplasia type 1 (MEN1). In case of single lesions, adipose tissue tumors, such as sarcoma, have to be excluded.
Genetic counseling
The majority of reported cases are sporadic. Autosomal dominant inheritance has been suggested in several case reports; however, there are no described mutations.
Management and treatment
Treatment is symptomatic. Few convincing larger studies have been conducted. Methods that have been described for pain relief include liposuction or surgical resection of lipomas and traditional analgesics (NSAIDs). The following treatments have only been described in case reports or case series: lidocaine, corticosteroids, combinations of mexiletine and amitriptyline, or infliximab, calcium-channel modulators, D-thyroxine interferon alfa-2b, methotrexate, metformin, deoxycholic acid, rapid cycling hypobaric pressure, and transcutaneous electrical stimulations. Only one case of treatment with bariatric surgery in adiposis dolorosa has been described. There are no studies on the effect of weight loss in adiposis dolorosa.
Prognosis
The disease course is chronic. Case reports have suggested that pain increases with time. A study with a five-year follow-up has suggested that the average pain is relatively constant over time.

                            Last update: 
                            April 2020


                            - Expert reviewer(s): 
                            Pr Håkan BRORSON  - Pr Emma HANSSON