Adiposis Dolorosa 

Updated: Dec 15, 2017
Author: Laura F McGevna, MD; Chief Editor: Dirk M Elston, MD 

Overview

Background

First described in 1892 by the American neurologist Francis Xavier Dercum at Jefferson Medical College in Philadelphia, Pennsylvania, Dercum disease (adiposis dolorosa) is an unusual progressive syndrome of unknown etiology characterized by multiple painful lipomas (see image below) that arise in adult life, most often affecting obese postmenopausal women.[1]

Multiple painful lipomas. Courtesy of Waikato Dist Multiple painful lipomas. Courtesy of Waikato District Health Board and DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/dermal-infiltrative/w/dercum-1.jpg).

The onset of Dercum disease (adiposis dolorosa) is insidious, but it has been described in at least one patient as having occurred after puerperal weight gain.[2] The pain is out of proportion to the physical findings and is often described by patients as "painful fat.” The pain increases with increases in fatty tissue and in connection with menstruation. Estrogen replacement at menopause has not been shown to reduce the pain.

Since the original description of Dercum disease (adiposis dolorosa), the clinical spectrum has changed to include, in addition to the painful nodular fatty deposits (which are often unaffected by weight loss), other components of Dercum disease (adiposis dolorosa) to various degrees.[3] General obesity, easy fatigability and weakness (asthenia), and a wide variety of unexplained emotional disturbances, such as depression, confusion, and dementia, are reported. This observation is why Dercum disease (adiposis dolorosa) has been proposed to be relabeled as Dercum syndrome.[4]

Dercum disease (adiposis dolorosa) has been classified by the World Health Organization (WHO) as a distinct entity. The National Organization of Rare Diseases (NORD) notes, "Dercum Disease is a rare disorder in which there are fatty deposits which apply pressure to the nerves, resulting in weakness and pain. Various areas of the body may swell for no apparent reason. The swelling may disappear without treatment, leaving hardened tissue or pendulous skin folds."

Criteria for diagnosis

In 1901, Roux and Vitaut first proposed the following four cardinal symptoms of Dercum disease (adiposis dolorosa), and these remain the standard for diagnosis of classic disease[5, 6, 7] :

  • Multiple, painful, fatty masses

  • Generalized obesity, usually in menopausal age

  • Asthenia

  • Neuropsychiatric disturbances, including emotional instability, depression, epilepsy, confusion, and dementia

As early as 1910, Stern noted that neuropsychiatric disturbances and asthenia did not accompany every case, and numerous case reports were subsequently described without all four cardinal features.[8] Therefore, some have lobbied for a “minimal definition” of adiposis dolorosa, which was recently proposed to include the following[9] :

  • Generalized obesity

  • Chronic pain (>3 mo) in the adipose tissue

Associated conditions

Associated conditions include sleep disturbances and pickwickian syndrome; slight-to-moderate dryness of the eyes and the mouth, with a gritty feeling in the eyes in spite of normal tear production (the criteria for Sjögren syndrome are not completely satisfied); an irritable bowel; coccygodynia; vulvovaginitis; vulvodynia; carpal tunnel syndrome; Tietze syndrome; chondromalacia patellae; thyroid malfunction, mainly hypothyreosis; trochanteritis; localized tendonitis; and onset of fibromyalgia (sometimes).[10, 11]

Mode of inheritance

Dercum disease (adiposis dolorosa) is believed to be transmitted in an autosomal dominant manner with incomplete penetrance[12, 13] ; it is particularly strong in the line of great grandmother-mother-daughter; however, most reported cases of adiposis dolorosa appear to be sporadic.[14]

Pathophysiology

The understanding of the pathogenesis and mechanism of Dercum disease (adiposis dolorosa) remains unknown. The origin of the pain is obscure, and the disease is better known as a clinical entity rather than as a physiologic or metabolic process. Fatty deposits are thought to cause nerve compression and result in weakness and pain.

A review of the histopathologic findings of Dercum disease (adiposis dolorosa) showed no consistent histologic abnormality in the adipose tissue that might distinguish these tumors from common sporadic lipomas.[14] In theory, the sudden appearance of the disease together with the incidence of a slight increase in the number of inflammatory cells in the fat could point toward the disease being, in part, an immune defense reaction.[11, 15] Some authors believe that the sympathetic nervous system may play a role in the origin and development of the pain.

The report of a case of Dercum disease (adiposis dolorosa) developing in association with the use of high-dose corticosteroids and its resolution upon reducing the dose suggests a causal relationship. Therefore, alterations of fat metabolism induced by corticosteroid excess may play a role in the development of this syndrome.[10] An earlier study suggested that a defect in the synthesis of monounsaturated fatty acids may play a role in its development. Further studies are needed to support this hypothesis and to identify a specific biochemical defect.[16]

Dercum disease (adiposis dolorosa) has been suggested to be an expression of familial multiple lipomas, which is an autosomal dominant disease characterized by multiple asymptomatic lipomas. This observation was derived by studying the family patterns of 2 siblings with adiposis Dercum disease (adiposis dolorosa); findings suggested that the disease segregates in an autosomal dominant fashion with variable phenotypic expressivity, ranging from totally asymptomatic to extremely painful lipomas.[17]

Mutational analysis excluded the 8344A→G mitochondrial mutation seen in other patients with multiple lipomas.[14, 17] The A→G transition at position 8344 in the tRNAlys gene of mitochondrial DNA has been described in the syndrome myoclonic epilepsy and ragged-red fibers (MERRF). A number of reports described the presence of multiple lipomas resembling those of multiple symmetrical lipomatosis in some members of pedigrees with MERRF harboring the 8344 tRNA mutation.[18]

Gamez et al described an unusual syndrome characterized by maternally inherited multiple symmetrical lipomatosis in a pedigree harboring the 8344 mutation in the tRNAlys gene of mitochondrial DNA.[17] Although the probands in their study harbored this mutation and had sensory polyneuropathy, they lacked the typical neuromuscular manifestations of MERRF.

Recently, an abnormal lymphatic phenotype was discovered in three patients with the disease compared with four female controls using near-infrared fluorescence (NIRF) lymphatic imaging.[19] The lymphatics in the participants with Dercum disease (adiposis dolorosa) were intact and dilated but could not readily clear lymph when compared with lymphatics in four control patients. Further NIRF imaging revealed masses of fluorescent tissue within the painful nodules, suggesting a lymphovascular etiology.

Etiology

The cause of this poorly understood disorder is unknown, although multiple candidate theories have been proposed, including endocrine dysfunction, mechanical pressure, and inflammation, among others. No theory has been consistently substantiated.

High-dose corticosteroids were the suspected cause in a reported case.[10]

Epidemiology

Frequency

Dercum disease (adiposis dolorosa) is rare and the prevalence has not been established.

Sex

Dercum disease (adiposis dolorosa) is 20 times more common in females who are postmenopausal, obese, or overweight than in other people. It can occur in individuals who are not obese. Sixteen percent are males.

Age

Dercum disease (adiposis dolorosa) is most commonly seen in persons aged 45-60 years. It may occur in women younger than 45 years. A survey of patients with the disease concluded that 85% of patients developed symptoms before the onset of menopause.[3] Adiposis dolorosa is almost never seen in children.

Prognosis

The course is of Dercum disease (adiposis dolorosa) chronic and progressive.

Patient Education

Educating patients about the chronicity of Dercum disease (adiposis dolorosa) and the available limited treatment modalities is important. Proper education about the aggravating and relieving factors should be explained.

Patient education about Dercum disease (adiposis dolorosa) is crucial. Addressing any possible needs of those persons with disabilities is important, preferably with the assistance of an occupational therapist and a social worker. Various aids may be needed in the home and at work.

The Dercum Group was formed in 1990 in Lund, Sweden. The group, which is a part of the Association for Rheumatics, is nationwide and has approximately 300 members. It works to provide support and information to both individual members and other interested parties.

 

Presentation

History

Previously healthy women notice lumps or previously present lumps start growing. They describe pain and discomfort in the region of the lumps, associated with weakness. Before the onset of the disease, the patient is usually only slightly overweight, but, in a short time, obesity ensues. The pain increases with the subsequent increase in fatty tissue and in connection to menstruation.

The painful lipomas have been reported to occur in any location.[20] It was previously thought that the head and the neck were excluded, but it is now suspected that retrobulbar fat deposits may cause facial pain in some patients.

The first classification system for the disease was developed in 1900 by Giudiceandrea and was subsequently amended by Roux and Viteat, among others.[7, 21] Most recently, a 2012 review proposed the following classification system[9] :

  • Type I: Generalized diffuse form; generalized, widespread painful adipose in the absence of discreet lipomas

  • Type II: Generalized nodular form; widespread painful adipose with concomitant intense pain in and around multiple discreet lipomas

  • Type III: Localized nodular form; pain in and around multiple discreet lipomas

  • Type IV: Juxta-articular form; discreet deposits of excess fat in specific locations, including at the medial aspect of the knee, the hips, and, rarely, the upper arm

The pain varies from discomfort on palpation to excruciating, paroxysmal spontaneous attacks.[5] The pain can be aching, burning, or stabbing, often described by the patient as "it hurts everywhere." The pain is usually symmetrical; however, it can become localized to the thighs, the knees, or the upper extremities. Pain can be felt in the skeletal system and in the fat.

Hyperalgesia is found by light pressure and touch in the fatty tissue below the skin and is made worse by tightly fitting clothes or showering. The pain is temperature and weather dependent; it decreases in dry heat and when pressure is high. Hot baths can have a positive but short-term effect in the relief of pain, but some patients do not tolerate heat.

Other symptoms, with variable incidence, include the following:

  • The fingers have a tendency to swell up, fumble, and tingle, and they can be numb (paresthesias), in addition to secondary median nerve compression.

  • General tiredness similar to the symptoms of chronic fatigue syndrome may be present. Light physical activity and poor sleep aggravate the tiredness.

  • A tendency to bruise, possibly secondary to the formation of delicate vessels in fat deposits, may be present. Coagulation test results are normal.

  • Morning stiffness and stiffness after resting may occur.

  • Headaches (eg, tension headaches, classic migraine, neck headaches) may occur. Also, pain in the jaw and the eyes due to retrobulbar fatty tissue may be present.

  • Cognitive dysfunction, with concentration and memory problems, may be present.

  • Bouts of depression (atypical depression, possibly latent) may occur; this finding is not associated with the onset of the disease. This association, among others, has been challenged given the prevalence of depression among obese individuals. However, a 2012 study of 111 patients with Dercum disease (adiposis dolorosa) compared with obese controls revealed a statistically significant greater prevalence of depression among patients with disease.[6]

  • Feeling hot affects a small number of patients, with recurring high temperatures of 37.5-39°C for weeks at a time associated with worsening of pain.

  • Patients may become susceptible to infection, as with one patient who developed sepsis secondary to steatonecrosis.[22] Pain is exacerbated with infections.

Physical Examination

Dercum disease (adiposis dolorosa) symptoms are almost always out of proportion to the physical findings, which include the following:

  • Dercum disease (adiposis dolorosa) patients are usually 50% over the normal weight for their age. In some patients, only localized fat, without general obesity, is present.

  • Lipomas are multiple, painful, symmetrically distributed, fatty deposits that are either diffuse or localized. The abdominal region and the lower extremities are common sites, especially around the knees. The ankle is an uncommon site of involvement.[23]

  • Hyperalgesia is found in the fatty tissue below the skin on light pressure and touch.

  • Other findings include acral swelling, bruises, and telangiectasias.

Complications

Dercum disease (adiposis dolorosa) can be debilitating and can lead to incapacitation. Also, because Dercum disease (adiposis dolorosa) symptoms are nonspecific, unnecessary medical procedures, tests, and operations can result in several complications.

Although rare, septicemia leading to septic shock, following necrosis of a fatty tumor, has been reported.[24]

 

DDx

Diagnostic Considerations

Like fibromyalgia, the diagnosis of Dercum disease (adiposis dolorosa) is made clinically, and both diseases include symptoms of a number of associated diseases. However, in Dercum disease (adiposis dolorosa), a relationship exists between pain and body weight, with pain in the fatty tissue and obesity being fundamental criteria for the diagnosis of Dercum disease (adiposis dolorosa). In addition, the pain is often more general and more severe than in fibromyalgia.

Madelung syndrome, also known as multiple symmetrical lipomatosis or benign symmetrical lipomatosis, is characterized by numerous, symmetrically distributed, nontender, poorly circumscribed lipomas, mainly around the neck, in the suboccipital region, on the proximal extremities, and on the upper part of the trunk. It is an idiopathic disease that affects middle-aged, nonobese men who are alcoholics. Neurologic involvement, particularly peripheral neuropathy, is considered a constitutive manifestation of this disease.[25]

Familial multiple lipomatosis belongs to the multiple lipoma syndromes. It is transmitted in an autosomal dominant fashion and often becomes apparent by the third decade of life. Patients may have up to hundreds of slowly growing, usually asymptomatic, subcutaneous lipomas of various sizes in widespread distribution. Patients with familial multiple lipomatosis are distinguished from patients with Dercum disease (adiposis dolorosa) by their lack of disabling pain.[25]

Proteus syndrome is characterized by lipomas, partial gigantism of the hands or the feet, hemihypertrophy, pigmented nevi, and other subcutaneous neoplasms (eg, hemangiomas, lymphangiomas, mesenchymomas).

Weber-Christian disease (nonspecific panniculitis), neurofibromatosis, Fröhlich syndrome, adenolipomatosis, lipodystrophia progressiva, Cushing syndrome, and osteoarthritis should be ruled out when evaluating patients with multiple subcutaneous tumors. Also, in a patient who is obese, myasthenia gravis should be considered.

A patient with increasingly painful nodules resembling adiposis dolorosa was found to have calciphylaxis, and it is noted that the diseases may present similarly.[26]

Differential Diagnoses

 

Workup

Laboratory Studies

Results of hormonal studies to rule out Cushing syndrome, thyroid abnormalities, and other endocrinologic abnormalities are characteristically normal.

Dercum disease (adiposis dolorosa) Patients might have associated slight-to-moderate rises of cholesterol levels.

Erythrocyte sedimentation rate results may be slightly elevated.

Coagulation test results are normal.

In spite of obesity, hypertension and type 2 diabetes mellitus seldom occur.

An increase in certain active parameters is seen in the following: sedimentation rate; alpha-1-antitrypsin; orosomucoid (alpha-1-acid glycoprotein, an acute phase reactant); haptoglobin; and complement factors C3, C4, Clq, and Cls.[10, 11]

The heat produced by the fat cells when measured with a microcalorie meter is approximately twice as high as that taken from people who are extremely overweight.

The ratio of monounsaturated fatty acid (16:1, 18:1) in the fatty tissue is greater than that of saturated fatty acid (14:1, 18:0) shown by a comparison with healthy people in controls.[25, 27]

The levels of substance P in the cerebrospinal fluid is significantly lower compared with healthy weight-matched controls. However, the average in both cases is above the normal level.[28] The level of the neuropeptide Y is on the lower side of normal, and B-endorphin is on the higher side (H. Brorson, B. Fagher, R. Ekman; unpublished data).

Imaging Studies

Ultrasonography and magnetic resonance imaging (MRI) may aid in the diagnosis of Dercum disease (adiposis dolorosa).[23, 29, 30]

On MRI, the lesions appear oblong, and this may be due to septal distortion that is seen on histopathological evaluation. In a study by Tins et al of 13 patients with Dercum disease (adiposis dolorosa), lesions of the condition were found to be markedly hyperechoic on ultrasound, superficial in location, and distinct from characteristic lipomas.[31] Further, when validated on more than 6000 MRIs, they appeared as ill-defined, nodular, “blush-like” subcutaneous fat on unenhanced MRI with a decreased T1-weighted signal. No case of Dercum’s disease was without these features in the study, and the authors concluded that these findings, along with multiple subcutaneous fatty lesions, is “very suggestive and possibly pathognomonic” for the condition.

Histologic Findings

A review of histopathologic findings did not reveal any significant features that might distinguish Dercum disease (adiposis dolorosa) tumors from the common sporadic lipomas. Minor features that were detected include a slight accumulation of perivascular lymphocytes and plasma cells and extremely large fat cells compared with those of healthy controls of similar weight. The tumors can be encapsulated, or the fatty deposits can be diffuse.

 

Treatment

Medical Care

Traditional management of Dercum disease (adiposis dolorosa) has been largely unsatisfactory relying on weight reduction and surgical excision of particularly troublesome lesions. Even at the present time, no known drug can change the course of the disease, and available treatments are only symptomatic.

Nonpharmacological approaches for Dercum disease (adiposis dolorosa) may be used as adjuncts to pharmacologic treatments. Some of these include acupuncture, cognitive behavioral therapy, hypnosis, and biofeedback.[32, 33]

Pharmacological treatments

Prednisone, 20 mg daily, has been reported to provide some pain relief.[4] However, in one case, the induction of disease was associated with high-dose corticosteroids.[10]

Intravenous lidocaine, 400 mg over 15 minutes every other day, has been reported to provide pain relief for 10 hours to several months.[34, 35] The exact mechanism of action is uncertain and remains to be elucidated as to whether it is a central effect or due to its effect on blood flow. Long-term intravenous lidocaine therapy has been associated with neurotoxicity.

Traditional analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDs), have traditionally been thought to have a poor effect. However, a large 2007 series by Herbst concluded that 89% achieved relief when treated with an NSAID, as did 97% when treated with an opiate.[3]  Acetaminophen combined with an opioid analgesic is the first choice. Localized pain may sometimes be treated with a cortisone/anesthetic injection, alternatively with sterile water given intracutaneously or more deeply.

Other medications

Because of troublesome swelling of the fingers, some patients may require diuretics.

In 2 reported cases of Dercum disease (adiposis dolorosa), interferon (INF) alfa-2b induced long-term relief of pain in 2 patients with adiposis dolorosa and chronic hepatitis C. The analgesic effect of IFN therapy was unexpected and occurred 3 weeks after treatment with 3 million units, 3 times per week, for 6 months. Whether the mechanism of pain relief with IFN is related to its antiviral effect, to the production of endogenous substances (eg, endorphins produced by IFN), or to the interference of INF with interleukin 1 and tumor necrosis factor-alpha cytokine production, which are involved in cutaneous hyperalgesias, remains unclear.[36]

Two Dercum disease (adiposis dolorosa) case reports have described pain relief with daily intake of oral mexiletine, an antiarrhythmic.[35, 37]

Singal et al reported improvement of a patient's Dercum disease (adiposis dolorosa) while on infliximab, with and without methotrexate, for ankylosing spondylitis. The patient experienced recurrent weight gain and lipoma pain with discontinuation of these medications.[38]

Desai et al reported on treatment with a lidocaine (5%) patch,[39] and Lange et al reported on successful therapy with pregabalin with manual lymphatic drainage.[40]

Metformin has been used with success in a patient with adiposis dolorosa and associated pain.[41] It is thought that the drug may have the capacity to favorably alter the cytokine milieu, impacting such mediators as tumor necrosis factor, interleukin (IL)–1, and leptin.[2, 41] In the report by Labuzek et al, each variable was affected moderately by the drug, and it was concluded that the effect of reduction of the inflammatory mediators is additive. Nonetheless, they concluded that other phenomena must contribute to the effects (eg, modulation of synaptic plasticity, activation of microglia).[41]

It should be noted that a study on cytokines in patients with adiposis dolorosa revealed there is no significant difference between these patients and controls with regard to tumor necrosis factor (TNF), leptin, IL-1, and most other mediators. However, patients with disease did demonstrate significantly lower levels of macrophage inhibitory protein-1 beta and higher levels of IL-13 and lower levels of fractalkine, an adipokine whose receptors are characteristically up-regulated in prolonged neuropathic pain.[9, 42]

Surgical Care

Liposuction[43]

Liposuction is regarded as a supportive treatment for Dercum disease (adiposis dolorosa). Any skeletal pain is not affected. A significant initial reduction of pain and an improved quality of life is seen; these effects decrease over time.[44]

Liposuction is indicated for patients with general lower-body fat or more localized large deposits of fat at the knees, on the arms, on the thighs, or on the stomach as opposed to those with general diffuse pain. In those patients, liposuction is considered a risky operation, requiring about a week of care in the plastic surgery department.

Surgical operation

Excision of isolated painful lipomas that are pressing and causing numbness and tingling, while not preventive, is useful in ameliorating local symptoms of pain.

Consultations

The following consultations may be warranted:

  • Psychiatrist: Depression and other psychosomatic symptoms are associated with Dercum disease (adiposis dolorosa). Many patients find they are misjudged and require psychological support.

  • Rheumatologist: A rheumatologic consultation is warranted to rule out osteoarthritis and fibromyalgia.

  • Endocrinologist: An endocrinologic etiology, such as hypothyroidism and Cushing syndrome, should be ruled out.

Diet

Experience shows that lasting weight reduction by changing the diet is difficult to achieve and does not appreciably affect the pain.

Activity

Light physical activity may worsen symptoms because of the stiffness experienced after periods of rest and minimal activity. Patients should avoid monotonous, static work and physical and psychological stress.

 

Medication

Medication Summary

Traditional management of Dercum disease (adiposis dolorosa) has been largely unsatisfactory relying on weight reduction and surgical excision of particularly troublesome lesions. Even at the present time, no known drug can change the course of the disease, and available treatments are only symptomatic. However, in two reported cases, INF alfa-2b induced long-term relief of pain in 2 patients with Dercum disease (adiposis dolorosa) and chronic hepatitis C (see Medical Care).

Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone (Meticorten, Orasone, Deltasone, Sterapred)

Prednisone may provide pain relief. Caution should be used because the adverse effects may outweigh the benefits. Prednisone is an immunosuppressant for treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Anesthetics

Class Summary

Lidocaine is reported to provide pain relief for 10 hours to several months. The exact mechanism of action is uncertain, and whether it is a central effect or due to its effect on blood flow remains to be elucidated. Cardiac monitoring is required. This should be considered an investigational therapy.

Lidocaine anesthetic (Dilocaine, Xylocaine)

Lidocaine anesthetic decreases permeability to sodium ions in neuronal membranes. This results in inhibition of depolarization, blocking transmission of nerve impulses.

Analgesics

Class Summary

Pain control is essential for quality patient care, and it ensures patient comfort.

Propoxyphene products were withdrawn from the United States market on November 19th, 2010. The withdrawal was based on new data showing QT prolongation at therapeutic doses. For more information, see the FDA MedWatch safety information.

Acetaminophen (FeverAll, Tempra, Aspirin Free Anacin, Tylenol)

Acetaminophen is the drug of choice for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI tract disease, or who are taking oral anticoagulants.