History
Patients with progressive lipodystrophy are born healthy with a normal appearance and fat distribution. In individuals aged 0-20 years, progressive loss of fat, which first involves the face, spreads distally to the neck, arms, and trunk; the lower part of the body is usually spared.
Physical Examination
Because of the insidious onset and slow progression of progressive lipodystrophy, most patients present when the disease is in an advanced stage. Advanced cases have a characteristic physical appearance.
The face appears cachectic. Buccal fat pads are absent, resulting in a prominent zygoma and chin. The temples and cheeks are hollowed, causing a cadaverous appearance. The eyes are deeply sunken due to the loss of periorbital fat. The face is heavily lined, creating numerous wrinkles lying over the cheeks, which causes the appearance of premature senility. The scalp, hair, and other facial areas are generally unaffected. However, centrifugal lipodystrophy has been described in a child with progressive arch–form alopecia. The alopecia continuously extended for a decade, after which expansion ceased, leaving a linear nonhairy patch. [18]
Frequently, the breasts are underdeveloped, with a firm, nodular feel. The arms and shoulders have a clear, well-demarcated outline of muscles below the skin, which gives the false impression of increased muscularity.
The area of fat loss is sharply demarcated at a level above the thighs; the lower extremities are spared. The uninvolved lower part of the body appears obese when contrasted with the upper, thin area. In female patients, excessive fat may develop on the legs and buttocks after puberty. A form of familial partial lipodystrophy with a highly selective partial fat loss pattern and proteinuria has been described. [19]
The overlying skin itself is normal in color, elasticity, and texture. No muscular hypertrophy is noted.
A patient with acquired partial lipodystrophy (Barraquer-Simons syndrome) was described with localized scleroderma. [20]
Complications
Renal disease
Mesangioproliferative glomerulonephritis occurs in 50% of patients with lipodystrophy and a low C3 complement level. Mesangioproliferative glomerulonephritis often follows an aggressive course and may lead to renal insufficiency.
Immune disorders
Systemic lupus may develop in a few patients. Other autoimmune diseases include dermatomyositis, [21] rheumatoid arthritis, leukocytoclastic vasculitis, hypothyroidism, and pernicious anemia.
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Model of the adipocyte destruction in acquired partial lipodystrophy showing complement activation at the adipocyte surface resulting in adipocyte lysis. Adipocytes synthesize C3, factor B, and factor D (adipsin), which allows C3bBb to be formed locally, but which usually does not result in the activation of the terminal lytic part of the complement pathway (C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B to its active enzymatic form. Factor D is expressed to a higher extent in the fat cells of the upper half of the body compared with the lower half, and it is possibly this regional difference that accounts for the restriction of fat loss to the head, arms, and trunk. C3Nef is also associated with type II, dense-deposit membranoproliferative glomerulonephritis in which subendothelial deposits of immunoglobulin and C3 are probably due to a deregulated alternative complement pathway.
