eMedicine Specialties > Dermatology > Diseases of the Subcutaneous Tissue
Lipodystrophy, Localized
Updated: Apr 29, 2008
Introduction
Background
Lipodystrophies are a heterogeneous group of diseases clinically characterized by a congenital or acquired loss of fat in circumscribed, partial, or diffuse areas of the body. As a rule, localized lipodystrophies are not associated with metabolic or systemic disorders, they tend to resolve spontaneously, and they have an excellent prognosis. The main concern is cosmetic when the lesions persist. Controversy exists in their classification, but 3 subsets can be identified based on the presence or the absence of preceding inflammation and the histologic findings.
Centrifugal lipodystrophy or lipodystrophia centrifugalis abdominalis infantilis is the best-characterized subset. It affects children at a young age. It begins on the trunk, spreads for a few years to the neighboring abdomen or chest, and eventually resolves spontaneously in most patients.
The second group is defined by a lack of preceding inflammation and a common histologic pattern of involutional lipoatrophy. It includes such entities as lipoatrophia semicircularis; semicircular or annular dystrophy; and lipoatrophies linked to repeated trauma, pressure, or drug injections. A number of cases are idiopathic.
The third type represents a sequela from various types of panniculitis and is associated with preceding inflammation. It includes lipophagic granulomatous panniculitis and other types of panniculitis, primarily associated with connective-tissue disease.
Some other eMedicine articles on lipodystrophy include the following:
A related Medscape CME course is A Randomized, Multicenter, Open-Label Study of Poly-L-Lactic Acid for HIV-1 Facial Lipoatrophy.
Pathophysiology
The pathophysiology of localized lipodystrophy is unknown. The pathogenetic mechanism of inherited lipodystrophies at the molecular level has been linked to mutations of lamin A/C, peroxisome proliferator-activated receptor (PPAR-gamma), and other seemingly unrelated proteins.1 In cases linked to injections of insulin, an immune response mediated by tumor necrosis factor-alpha has been hypothesized.
Familial partial lipodystrophy (FPLD) usually results from coding sequence mutations either in LMNA, encoding nuclear lamin A/C, or in peroxisome proliferator-activated receptor-gamma (PPARG), encoding PPAR-gamma. The LMNA form is called FPLD2 (Mendelian Inheritance in Man [MIM] 151660) and the PPARG form is called FPLD3 (MIM 604367). FPLD phenotype may be due to a single-base mutation in the DNA-binding domain of peroxisome PPAR-gamma.2 Impaired PPARG function through a mutation of a conserved salt bridge (R425C) producing FPLD has also been described.3
Frequency
International
Few cases have been reported internationally. Centrifugal lipodystrophy and the involutional type are rare. Lipoatrophy secondary to panniculitis is more frequent.
Mortality/Morbidity
Localized lipodystrophies usually have little or no associated morbidity or mortality. They are circumscribed and tend to resolve spontaneously, although panniculitis may be chronic and relapsing. Usually, no associated systemic disorder is present, except in some cases of panniculitis induced by an underlying connective-tissue disorder. Even then, symptoms tend to be mild with an excellent overall outcome.
Race
No racial predilection exists except for centrifugal lipodystrophy, which has been described mainly in Asian children.
Sex
No difference in sex has been established, except for a female predominance in the involutional type. A female predominance is also observed in connective-tissue disorder–associated lipoatrophic panniculitis.
Age
No specific age of onset exists except for centrifugal lipodystrophy. In these cases, lesions appear before age 3 years, they stop spreading by age 8 years, and they tend to resolve by age 13 years.
Connective-tissue disorder–associated lipoatrophic panniculitis may be observed at any age, but it occurs most frequently in adults aged 20-60 years. Lupus erythematosus is the most common underlying disease.
Clinical
History
- Lipodystrophia centrifugalis is defined by the appearance of cutaneous lesions surrounded by a peripheral erythematous border before age 3 years. They may progress centrifugally for as long as 10 years and tend to regress thereafter. Children who are affected are healthy.
- Involutional lipoatrophy is characterized by one or a few circumscribed depressions of the skin affecting any part of the body in persons of any age, with or without a history of previous trauma, pressure, or previous injections in the area.4 Clinically, it usually appears as a solitary, asymptomatic, well-demarcated, atrophic depression and often involves areas of antecedent intramuscular or intra-articular injections.5,6,7 Overlying hypopigmentation and atrophy with morphealike changes may be noted with histology studies.
- Panniculitis precedes the onset of lipoatrophy in the inflammatory subsets but may be asymptomatic clinically.
Physical
- Lipodystrophia centrifugalis abdominalis infantilis, as originally described by Imamura et al8 in 1971, presents as a round or oval depression in the skin, often in the groin or the axilla. The overlying skin is of normal texture and color except for the periphery, which may be erythematous and a little scaly. Lesions tend to spread centrifugally to adjacent areas, such as the chest and the abdomen, for several years. The face and the sacral area can also be involved. Regional enlarged lymph nodes can often be palpated. No other abnormal finding is present clinically.
- Involutional lipoatrophy is characterized by one or a few circumscribed depressions or indentations in the skin. The lesions are round, oval, bandlike, horizontal, annular, or semicircular in configuration. They are flesh colored and barely visible with normal overlying skin. The anterior parts of the thighs, the buttocks, or the lower parts of the limbs, including the ankles in some cases, as well as the arms, the neck, and the scalp may be involved, unilaterally or bilaterally. The lesions may be mildly tender at first. No associated finding and no preceding sign of inflammation are present.
- Localized lipoatrophy may represent the late stage of panniculitis. Indurated, tender, erythematous, purplish or hyperpigmented subcutaneous nodules or plaques usually involving the extremities precede the onset of lipoatrophy at the same sites.
- Fever and systemic signs may be present depending on the type of associated panniculitis.
- Lipophagic panniculitis of childhood, first described by Winkelmann et al in children and later in adults, is characterized by its benign self-limited course. It presents with multiple, slightly tender, erythematous subcutaneous nodules and plaques, which precede the onset of lipoatrophy. The lesions mainly occur on the extremities. It may recur several times, and it may be associated with intermittent fever.
- Localized lipoatrophy may be the only presenting feature in patients with an underlying or evolving connective-tissue disorder, such as lupus erythematosus, morphea profunda, dermatomyositis,9 or overlap disease. In patients with lupus panniculitis, multiple, often painful subcutaneous nodules or plaques, with a predilection for the proximal extremities, may be observed in association with irregular, indurated depressions in the same areas. The overlying skin is often normal, or changes, such as atrophy, hyperkeratosis, telangiectasias, and/or ulceration, seen in discoid lupus erythematosus may be present. Arthralgias or Raynaud syndrome may be observed, but most patients show no evidence of severe systemic involvement, such as glomerulonephritis or neurologic complications.
Causes
- The cause of centrifugal lipodystrophy is unknown.
- In many cases, involutional lipodystrophy is idiopathic. In other cases, repeated trauma, chronic pressure or compression, or local injections may be the cause. It has been reported to develop at the site of injection or in the surrounding area of injection with insulin, intralesional or intra-articular steroids, antibiotics (eg, intramuscular benzathine penicillin), vasopressin, and human growth hormone.
- Localized lipoatrophy may represent the late or end stage of a preceding or concomitant panniculitis, which may be triggered by various underlying conditions. Connective-tissue disease–induced panniculitis is one of the main causes and may not be symptomatic at the time of presentation. Other causes of lipoatrophic panniculitis may include alpha-1-antitrypsin deficiency or cytophagic, factitial, and infectious panniculitides.
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| References |
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References
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Further Reading
Keywords
localized lipoatrophy, lipodystrophia centrifugalis abdominalis infantilis, centrifugal lipoatrophy, annular lipoatrophy, semicircular lipoatrophy, lipoatrophia semicircularis, involutional lipoatrophy, lipophagic granulomatous panniculitis, lipoatrophic panniculitis
