Lipedema

Description

Lipedema is a disorder of adipose tissue characterized by fat legs and orthostatic edema. Characteristically, the buttocks and other parts of the lower extremities are symmetrically enlarged owing to accumulation of excess fat and fluid. The condition affects women almost exclusively and, in most instances, represents an exaggeration of the female form (summary by Hines, 1952).

Clinical Features

Wold et al. (1951) reviewed 119 cases of lipedema in patients examined at the Mayo Clinic between 1937 and 1946, 19 (16%) of whom reported a positive family history. There was 1 male patient who presented in the series. The majority of patients were overweight, with a preponderance of the excess fat being in the lower half of the body. Age at onset could not be accurately determined, but there was apparently no greater frequency of onset during the decades of menarche or menopause than other decades. Discomfort in the legs, consisting of diffuse pain, tenderness, and aching, was a prominent symptom in about half of the group. Chronic indurated cellulitis and stasis lesions did not occur unless there was an associated, coincidental chronic venous insufficiency. Basal metabolic rate was less than zero in 27 of the 30 patients assessed, but none of the group had clinical evidence of myxedema. Wold et al. (1951) noted that mild to marked anxiety about the appearance of their legs was common in these patients, and that approximately one-third presented evidence of neurosis.

Hines (1952) stated that in lipedema, the enlargement usually develops gradually and progresses slowly, may or may not be associated with generalized obesity, and in most instances, the upper part of the body is normal in shape and contour. He noted that the skin and subcutaneous tissues of the involved parts are soft and pliable, which distinguishes the condition from lymphedema (see 153100). The basic problem in lipedema is the subcutaneous deposition of fat, with edema becoming more prominent after the increased fat has been present for several years. Hines (1952) stated that the edema is related to the effects of gravity on the circulation in a tissue, which constitutes a poor supporting structure and consequently offers little resistance to the passage of fluid from the blood and lymph vessels into the surrounding tissue spaces. In lipedema there is no excess of fat or fluid in the feet, which the author attributed to pressure on the tissues from tightly fitting shoes. Hines (1952) stated that the diagnosis of lipedema could be made easily from observation of the characteristic symmetric distribution of fat in the lower half of the body, sparing the feet, and edema of varying degrees in the more dependent portions of the affected members.

Beninson and Edelglass (1984) described 2 cases of lipedema, noting that the disorder is not rare, but is often misdiagnosed as lymphedema. One patient was a 41-year-old woman who first noticed enlargement of her lower body from waist to ankles at the time of puberty, with gradual enlargement from that time. She had a daughter who also began to develop some enlargement of these areas beginning at puberty. The other patient was a 55-year-old woman in otherwise good health who developed enlargement of the legs and buttocks in her early forties. After a gradual onset, the enlargement progressed steadily over the next 10 years, then plateaued. On examination, both women had massive symmetric enlargement of the legs, thighs, and buttocks grossly out of proportion to the stature of the upper torso, with feet that were normal in size. There was no pitting edema, and the tissues had a soft, yet solid consistency. Laboratory values, including lipid profiles, were normal. Beninson and Edelglass (1984) noted that the characteristically normal size of the feet and ankles provides a diagnostic sine qua non. They stated that they had successfully treated the disorder using diet and properly measured and fitted Jobst compression garments, with patients reporting significant thinning of the legs and improvement in their emotional state and quality of life.

Rudkin and Miller (1994) reviewed 250 cases of lymphedema of the lower extremity and identified 9 patients who shared unique findings in their histories and physical examination that were atypical for lymphedema, but rather representative of lipedema. All 9 patients were women who had symmetric enlargement of both legs that began at the ankle and extended proximally to the upper thighs, with onset between 13 and 23 years of age; 4 of the patients reported a family history of a similar condition affecting 1 father, 2 mothers, and 1 maternal grandmother. Eight of the 9 patients reported an unusual discomfort in the plantar surface of the foot, often described as a 'tingling' or 'burning' sensation, not relieved by antiinflammatory medication. Rudkin and Miller (1994) noted that the physical findings in these patients were extraordinarily similar and always bilateral, with an abrupt increase in the thickness of the subcutaneous tissue presenting as a ring of fatty tissue just above the ankle. None of the patients had dermal thickening or induration as commonly seen in patients with lymphedema. A consistent fat pad was found just anterior to the lateral malleolus, with additional fatty tissue between the Achilles tendon and the medial malleolus. Distal to the ankle, no edema was present, and no abnormality of any kind could be identified in the foot. Seven patients underwent surgical treatment, with substantial improvement in contour and size of the extremities. Microscopic examination of the skin and subcutaneous tissue showed minimal perivascular fibrotic change in the subcutaneous compartment and no dermal thickening (features seen in lymphedema), and there was no histologic abnormality of the excess subcutaneous tissue. Rudkin and Miller (1994) stated that the constellation of findings described by Allen and Hines (1940) was strikingly similar to that of their 9 patients and likely represented the same entity.

Child et al. (2010) studied 67 propositi with lipedema, of whom 10 had at least 1 affected first-degree relative and 7 had at least 2 other affected first-degree relatives. All propositi and affected family members were female. Complete information was available for 38 of the 67 propositi who underwent examination, with an age range of 26 to 74 years and a mean age of 51 years. Onset of lipedema occurred during puberty in 21 (55%) of 38 cases. Twenty-seven (71%) of 38 propositi reported pain upon pressure in the swollen legs; 31 (82%) reported easy bruising, and 21 (55%) reported knee pain. BMIs ranged from 21.1 to 54.6, with 4% of patients classified as having a normal weight and 11% classified as overweight by WHO criteria; the remainder were in the obese range. Fifteen (39.5%) had associated varicose veins, whereas 20 (53%) had venous telangiectasia/reticular veins on their legs; 22 (58%) had fat pads around their knees. Child et al. (2010) also identified 4 unrelated isolated adult males with lipedema: 2 were testosterone-depleted, 1 had liver disease, gynecomastia, and signs of estrogen excess, and 1 had growth hormone deficiency and hypogonadism. None had syndromic features, and none had a family history of lipedema. The authors proposed that these males developed lipedema secondary to hormonal disturbances, with reduced testosterone levels being a common factor.

Mapping

In a 3-generation family with lipedema, in which the proband's mother, 3 sisters, and a niece were affected, Child et al. (2010) performed linkage analysis with X-chromosome markers and excluded all markers on the X chromosome.

Inheritance

Based on the exclusion of mapping to the X chromosome, Child et al. (2010) concluded that autosomal dominant inheritance was the more likely mode of inheritance.