Transcutaneous electrical stimulation therapy and genetic analysis in Dercum's disease: A pilot study.

ABSTRACT: Dercum's disease (DD), or adiposis dolorosa, is a rare condition of unknown etiology characterized by growth of painful subcutaneous adipose tissue. No specific treatment exists. Pain is often invalidating and resistant to analgesic drugs. We tested the efficacy of Frequency Rhythmic Electrical Modulation System (FREMS) therapy on pain relief. Subcutaneous biopsies were performed for genetic analysis.Nine DD patients were enrolled. Five cycles of FREMS at 3-month intervals during 1 year were administered. Visual analogue scale (VAS), Bartel Index Questionnaire and Short Form 36 questionnaire were used to measure pain and general health status at baseline, 6 and 12 months. Dual-energy X-ray absorptiometry (DEXA) quantified fat mass. Next-Generation Sequencing (NGS) was performed on adipose tissue biopsies and peripheral blood sample to search for somatic variants and specific protein pathway mutation.Seven patients were included in the final analysis. FREMS induced a reduction in VAS score (from 92 to 52.5, P = .0597) and a significant improvement in SF-36 domains (Physical functioning, Role limitation due to physical health, Body pain, Vitality, Social functioning, P < .05). No modification in anthropometrics and DEXA values was observed. The analysis of the mitochondrial Displacement loop (D-loop) region confirmed the clonality of all lipomatous lesions. The presence of the mitochondrially encoded tRNA-Lysine (MT-TK) m.8344A>G variant, occasionally identified in patients with multiple symmetric lipomatosis, was excluded in all subjects. On the other hand, we observed variants in genes belonging to signaling pathways involved in cell cycle and proliferation (Phosphoinositide 3-kinase/AKT/mTOR, MAPK/ERK, and Hippo).FREMS can be a useful tool to alleviate pain and improve overall quality of life in patients with DD. Genetic analysis highlighted the molecular heterogeneity of lipomas.

[Dercum's disease].

Dercum's disease is a rare disease, which mainly affects women and has an unknown prevalence and aetiology. The disease is characterised by generalised obesity and more than three-month painful subcutaneous adipose tissue not responding to usual pain treatment. A suggested classi-fication of the disease includes four types: generalised diffuse, generalised nodular, localised nodular and juxta-articular. Diagnosis is one of exclusion, and treatment includes medical and surgical options with the aim of pain palliation and increased mobility and function.

Subcutaneous adipose tissue therapy reduces fat by dual X-ray absorptiometry scan and improves tissue structure by ultrasound in women with lipoedema and Dercum disease.

Lipoedema is painful nodular subcutaneous adipose tissue (SAT) on legs and arms of women sparing the trunk. People with Dercum disease (DD) have painful SAT masses. Lipoedema and DD fat resists loss by diet and exercise. Treatments other than surgery are needed. Six women with lipoedema and one with DD underwent twelve 90-min sessions over 4 weeks. Body composition by dual X-ray absorptiometry scan, leg volume, weight, pain, bioimpedance, tissue size by caliper and ultrasound were analysed before and after SAT therapy by paired t-tests. There was a significant decrease from baseline to end of treatment in weight, 87.6 ± 21 to 86.1 ± 20.5 kg (P = 0.03), leg fat mass 17.8 ± 7.7 to 17.4 ± 7.6 kg (P = 0.008), total leg volume 12.9 ± 4 to 12 ± 3.5 L (P = 0.007), six of 20 calliper sites and tissue oedema. Pain scores did not change significantly. By ultrasound, six women had 22 hyperechoic masses in leg fat that resolved after treatment; five women developed seven new masses. Fascia improved by ultrasound after treatment. SAT therapy reduced amount and structure of fat in women with lipoedema and Dercum disease; studies are needed to compare SAT therapy to other therapies.

Lipomatoses.

Lipomatoses are benign proliferations of adipose tissue, often with typical distribution patterns, which usually occur without clear causes. In contrast to circumscribed lipomas, they develop diffusely and symmetrically and are not surrounded by a fibrous pseudocapsule. The most common form is benign symmetric lipomatosis (BSL; Launois-Bensaude syndrome), of which four types are distinguished based on the distribution pattern of hyperplastic adipose tissue. The etiology and pathogenesis of the disease are still largely unknown, although some forms appear to have a hereditary basis or to be associated with increased alcohol consumption. In some cases, mitochondrial dysfunctions have been detected. Lipomatoses may be solitary, but may also be associated with other symptoms or illnesses (comorbidity). Effective drug therapies are not known, but surgical procedures can alleviate the symptoms. Lipomatosis dolorosa, which can be distinguished from BSL, occurs predominantly in middle-aged women and is characterized by proliferation of adipose tissue and severe pain in the affected areas. Various differential diagnoses and concomitant illnesses need to be considered, in particular depression. There are no evidence-based recommendations for therapy. Repetitive lidocaine infusions can achieve temporary improvement. Recurrence after surgical intervention is not uncommon, but long-term success is also possible.

Successful Treatment of Dercum's Disease by Transcutaneous Electrical Stimulation: A Case Report.

Dercum's disease is a rare condition of painful subcutaneous growth of adipose tissue. Etiology is unknown and pain is difficult to control. We report the case of a 57-year-old man with generalized diffuse Dercum's disease, who improved after the treatment with transcutaneous frequency rhythmic electrical modulation system (FREMS). Treatment consisted in 4 cycles of 30 minutes FREMS sessions over a 6-month period. Measures of efficacy included pain assessment (visual analogue scale, VAS), adipose tissue thickness by magnetic resonance imaging, total body composition and regional fat mass by dual-energy X-ray absorptiometry, physical disability (Barthel index), and health status (Short Form-36 questionnaire). After FREMS treatment the patient's clinical conditions significantly improved, with reduction of pain on the VAS scale from 64 to 17 points, improvement of daily life abilities (the Barthel index increased from 12 to 18) and amelioration of health status (higher scores than baseline in all Short Form-36 domains). Furthermore, we documented a 12 mm reduction in subcutaneous adipose tissue thickness at the abdominal wall and a 7040 g decrease in total body fat mass. FREMS therapy proved to be effective and safe in the treatment of this rare and disabling condition.

Review of Dercum's disease and proposal of diagnostic criteria, diagnostic methods, classification and management.

UNLABELLED: DEFINITION AND CLINICAL PICTURE: We propose the minimal definition of Dercum's disease to be generalised overweight or obesity in combination with painful adipose tissue. The associated symptoms in Dercum's disease include fatty deposits, easy bruisability, sleep disturbances, impaired memory, depression, difficulty concentrating, anxiety, rapid heartbeat, shortness of breath, diabetes, bloating, constipation, fatigue, weakness and joint aches. CLASSIFICATION: We suggest that Dercum's disease is classified into: I. Generalised diffuse form A form with diffusely widespread painful adipose tissue without clear lipomas, II. Generalised nodular form - a form with general pain in adipose tissue and intense pain in and around multiple lipomas, and III. Localised nodular form - a form with pain in and around multiple lipomas IV. Juxtaarticular form - a form with solitary deposits of excess fat for example at the medial aspect of the knee. EPIDEMIOLOGY: Dercum's disease most commonly appears between the ages of 35 and 50 years and is five to thirty times more common in women than in men. The prevalence of Dercum's disease has not yet been exactly established. AETIOLOGY: Proposed, but unconfirmed aetiologies include: nervous system dysfunction, mechanical pressure on nerves, adipose tissue dysfunction and trauma. DIAGNOSIS AND DIAGNOSTIC METHODS: Diagnosis is based on clinical criteria and should be made by systematic physical examination and thorough exclusion of differential diagnoses. Advisably, the diagnosis should be made by a physician with a broad experience of patients with painful conditions and knowledge of family medicine, internal medicine or pain management. The diagnosis should only be made when the differential diagnoses have been excluded. DIFFERENTIAL DIAGNOSIS: Differential diagnoses include: fibromyalgia, lipoedema, panniculitis, endocrine disorders, primary psychiatric disorders, multiple symmetric lipomatosis, familial multiple lipomatosis, and adipose tissue tumours. GENETIC COUNSELLING: The majority of the cases of Dercum's disease occur sporadically. A to G mutation at position A8344 of mitochondrial DNA cannot be detected in patients with Dercum's disease. HLA (human leukocyte antigen) typing has not revealed any correlation between typical antigens and the presence of the condition. MANAGEMENT AND TREATMENT: The following treatments have lead to some pain reduction in patients with Dercum's disease: Liposuction, analgesics, lidocaine, methotrexate and infliximab, interferon α-2b, corticosteroids, calcium-channel modulators and rapid cycling hypobaric pressure. As none of the treatments have led to long lasting complete pain reduction and revolutionary results, we propose that Dercum's disease should be treated in multidisciplinary teams specialised in chronic pain. PROGNOSIS: The pain in Dercum's disease seems to be relatively constant over time.

[Fatter through lipids or water. Lipohyperplasia dolorosa versus lymphedema]. / Dicker durch Fett oder Wasser. Lipohyperplasia dolorosa vs. Lymphödem.

Lipohyperplasia dolorosa and lymphedema are completely different disease entities, which are both, however, classified under lymphology. While in lipohyperplasia dolorosa a congenital lipid distribution disorder leads to a high volume insufficiency and the corresponding clinical symptoms, lymphedema is characterized by a congenital transport incompetence of the vessels or acquired disorders of transport capacity. Both lymphedemas of different genesis are familial volume alterations of the affected regions and the increase in volume is irreversible if not exclusively still in stage I or II. According to current knowledge the solid increase in volume by lymphedema is due to a malfunctioning biomechanism by which the release of additional proteoglycans in the homeostasis system of the fluid in the interstital space plays an important role. Removal of this tissue and the sponge-like substance of proteoglycans is the aim of therapeutic approaches. Manual lymph drainage and compression can evacuate the sponge but not remove it. Lymphological liposculpture is a successful dermatosurgical measure even for secondary lymphedema. Reduction of the necessity of complex hemostasis therapy to 20% of the initial value and an adjustment of the affected extremity on the healthy side, represent a clear improvement in quality of life of patients. The same dermatosurgical method, lymphological liposculpture, has been known for many years to fulfil the successfully proven purpose for the treatment of lipohyperplasia dolorosa by the removal of subcutaneous fatty tissue, present as hyperplasia and not hypertrophy. Tenderness and the necessity for complex hemostasis therapy are no longer present or no longer necessary after lymphological liposculpture for lipohyperplasia dolorosa. This condition is permanent because the congenital fatty masses do not reoccur following surgical removal. Lipohyperplasia dolorosa is therefore curable by lymphological liposculpture. For secondary lymphedema a drastic improvement in quality of life of the patient can be achieved by this method which is demonstrated by the adjustment of symmetry of the extremities and reduction or even avoidance of complex hemostasis therapy.

Dercum's disease: an unusual presentation.

Dercum's disease, also known as adiposis dolorosa, is a rare disease characterized by the accumulation of painful subcutaneous deposits of mature adult fatty tissue around the thighs, trunk, and upper arms and usually in a multifocal distribution. We are reporting an unusual presentation of Dercum's disease, presenting as a single painful, erythematous lesion around the left hip in a 71-year old postmenopausal woman. This report emphasizes the unusual presentation of adiposa dolorosa with a new modality for therapy. A summary of the major clinical associations, diagnostic challenges, and treatment modalities are also included in this manuscript.

Microcannular tumescent liposuction in advanced lipedema and Dercum's disease.

AIM: We evaluated the outcome and risks of tumescence liposuction in patients with advanced lipedema or Dercum's disease. METHODS: Six patients treated at a single center during the years 2004 to 2008 have been included. All patients were female and obese (body mass index 34 to 41.9; mean 38.2+/-3.8) with an age range from 29 to 78 years (mean 55.7+/-20.5 years), five of them had co-morbidities. RESULTS: The total amount of lipoaspirates varied between 1500 mL and 4800 mL. Pain could be reduced in all four patients with Dercum's disease. Large adipose tissue removing implies a better the outcome for pain. Patient's satisfaction was "high" or "very high" in 5 and "medium" in one. The most common adverse effect was met-hemoglobulinemia (N.=4). CONCLUSION: Tumescence liposuction is a treatment option for lipedema and Dercum's disease. With careful monitoring the procedure is safe even for patients in advanced stages, higher age and with co-morbidities.

[Skin manifestations, treatment and rehabilitation in overweight and obesity]. / A túlsúly és az elhízás bortünetei, kezelés, rehabilitáció

Overweight and obesity is a public health problem in Hungary and in the Western world. It is important to underline that obesity is an illness and an important risk factor for several skin and other diseases. An overview of skin diseases caused or aggravated by obesity (acanthosis nigricans, acrochordons, keratosis pilaris, hyperandrogenism, stria, adiposis dolorosa, lymphoedema, chronic venous insufficiency, plantar hyperkeratosis, lipoedema, skin infections, acne inversa, psoriasis, tophi) helps us to look and see as well. Look for the possibility of skin infections as it helps the early diagnosis and to avoid complications. Draw patients' attention to the preventive importance of skin care. In case of an obese patient the usual dosage of most local and systemic drugs should be modified. It must be kept in mind that obesity directly or indirectly starts unfavorable processes in almost all organ systems. Therefore, only a multidisciplinary care may secure treatment and rehabilitation of obese patients. Dermatological and lymphological care is often part of the rehabilitation.

Dercum's disease (Lipomatosis dolorosa): successful therapy with pregabalin and manual lymphatic drainage and a current overview.

Dercum's disease which is also termed lipomatosis dolorosa is a rare and relatively unknown disease. In this entity the upper arms, elbows, stomach wall, buttocks, thighs and knees are predominantly affected showing painful subcutaneous adipose tissue deposits. In addition severe hyperalgesia can be triggered by light pressure and touch. Analgesic and/or nonsteroidal antirheumatic drugs have usually only a minor or no effect. Here, we report a patient with Dercum's disease who was successfully treated with pregabalin and manual lymphatic drainage, and present a current overview of the literature.

Dercum's disease.

Dercum's disease (adiposis dolorosa, lipomatosis dolorosa morbus Dercum), is a rare disorder resulting in painful fatty deposits around the upper legs, trunk, and upper arms. The portrait painted of Dercum's disease is very complicated, with many other disorders seen associated with the disease. There are no clear pathological mechanisms known, although it is suspected that there is either a metabolic or autoimmune component involved. Here, the authors review the literature to date, including some information from their own studies. In particular, the authors will look at the different strands of evidence pointing to the pathological mechanism of the disorder.

[Liposuction in children: clinical utility]. / Liposucción en niños: utilidad clínica.

Liposuction has become one of the most frequent aesthetic procedures. The "typical" patient is a young female with fat deposits in the trochanteric region. Gradually the safety of the technique together with the high satisfaction rate of the patients have contributed to the widening of its indications to other pathologies of the adipose tissue in different age populations. However, there is scarce literature regarding liposuction in childhood. The authors present their experience with liposuction as the treatment of congenital as well as acquired lipodystrophies in the paediatric age. Some particular details of the technique are described and the advantages of liposuction versus open surgery in these cases are analyzed.

[Lipomatosis dolorosa--a frequently overlooked disease picture]. / Lipomatosis dolorosa--ein häufig übersehenes Krankheitsbild.

Dercum's disease (lipomatosis dolorosa) is a relatively unknown illness. The disorder usually affects middle-aged females. Subcutaneous fatty tissue deposits may occur in many parts of the body. The upper arms, elbows, stomach wall, buttocks, thighs, or knees are most commonly affected. Severe hyperalgesia is found on light pressure and touch. Analgesics or pain-modulating drugs usually have little or no effect. The following case report demonstrates successful symptomatic treatment of the otherwise nearly unbearable complaints: intravenous infusions of 5 mg/kg body weight of lidocaine over 30-90 min may give pain relief lasting several weeks or even months. Alternatively, patients are treated with 150-750 mg orally administered mexiletine daily. Surgical excision or liposuction of these fatty tissue deposits have shown significant reduction of pain. However, this effect reduces over time and recurrences often develop.

Lipomatosis: a propósito de nuestras observaciones / Lipomatosis: for the purpose our observations

Los lipomas son tumores únicos o múltiples, desarrollados a partir del tejido adiposo. En sus formas múltiples constituyen las "lipomatosis", dando origen a cuadros clínicos raros y complejos. Se reconocen los siguientes cuadros: 1) Enfermedad de Dercum, afecta fundamentalmente a mujeres perimenopáusicas obesas, con disendocrinias, presentando tumores dolorosos en tronco y miembros; 2) Adenolipomatosis o Enfermedad de Launois-Bensaude, con afectación de hombres, disponiéndose en cuello, ingle y axilas, remedando adenopatías, 3) Lipomatosis mesosomática de Roch-Lery, con compromiso exclusivo de tronco y 4) Enfermedad de Touraine-Renault, disponiéndose en forma segmentaria o zoniforme