Lipodystrophy or lipoatrophy is primary idiopathic atrophy of adipose tissue. Lipodystrophy is a very rare disorder with no known etiology. Lipodystrophy can be total, partial, or localized.[1] Total lipodystrophy consists of congenital or acquired complete loss of adipose tissue usually associated with hepatomegaly, hyperglycemia, insulin resistance, hyperlipidemia, and hypermetabolism.
Partial lipodystrophy is manifested as symmetrical loss of facial fat tissue with or without similar atrophy of the arms and upper part of the trunk. This syndrome has been associated with renal disease, glomerulonephritis, diabetes, hirsutism, hyperlipidemia, hypocomplementemia, and immunologic disorders. Localized lipodystrophy is localized loss of adipose tissue, usually involving multiple areas.[2] This article focuses on localized lipodystrophy; total and partial lipodystrophy are not discussed further in this article.
Localized lipodystrophy or atrophy is localized loss of adipose tissue. Patients with localized lipodystrophy usually have single or multifocal, well-demarcated, atrophic lesions. Some patients have local panatrophy involving muscle, fat, and morphealike changes. Localized lipodystrophy can present as panatrophy that includes the manifestation of hemifacial atrophy.
Associations with localized scleroderma and lichen sclerosus et atrophicus have been noted. One subset group has annular atrophy of the ankles and semicircular lipoatrophy of the anterolateral region of the thighs. Annular lipodystrophy is another form of lipoatrophy in which underlying inflammation has been described. Lipoatrophy can be a common sequela of panniculitis in patients with connective tissue diseases (eg, systemic lupus erythematosus, subcutaneous morphea, the syndrome of lobular lymphocytic connective tissue panniculitis of Winkelmann and Padilha-Goncalves[3] ). Lipoatrophy can be associated with nephritis, hypocomplementemia, scleroderma, Sjögren syndrome, recurrent pyogenic infections, immune thrombocytopenic purpura (ITP), and thyroiditis.[4, 5]
The etiology of lipodystrophy is believed to be either inflammatory or noninflammatory. Patients with serologic and immunologic abnormalities tend to have inflammatory patterns on histopathologic examinations, although these changes are not diagnostic of a particular connective tissue disease. These histopathologic abnormalities can be a manifestation of an immunologic disease. Patients with inflammatory patterns tend to have multiple lesions, as opposed to single areas of lipoatrophy. Patients with no inflammatory features have a more benign form of the disease.
Localized lipodystrophy can also be observed in patients having intradermal or subcutaneous injections (eg, insulin, corticosteroids, IM penicillin G, iron dextran, diphtheria/pertussis/tetanus vaccine, acupuncture, recombinant growth hormone). In a 2002 Japanese study by Hisamichi et al, 2 patients with localized involutional lipoatrophy were reported. These patients received intramuscular steroid injections and in the immunohistochemical studies with the antibody against macrophage (anti-CD68 antigen) showed that positive cells were scattered around blood vessels and shrunken lipocytes in the subcutaneous tissues. Most of these cells in the fat lobules were also positive for mucin stains such as Alcian blue.[6] In a 2002 report by Yamamoto et al, 6 patients were reported with localized involutional lipoatrophy who presented with a depressive plaque on the lateral part of their upper arms after receiving injections for allergic rhinitis.[7] Tanrıkulu et al report a case of localized lipoatrophy following intramuscular steroid injection to both buttocks.[8]
Lipodystrophy is also a common complication in patients who are infected with HIV and are taking protease inhibitors. This form of lipodystrophy is more of a generalized lipodystrophy and is not discussed in this article. Localized lipoatrophy has also been observed with subcutaneous glatiramer acetate (Copaxone) injection used for the treatment of multiple sclerosis.[9]
Touraine et al conducted a randomized, double-blind, placebo-controlled study on 105 patients with growth hormone (GH) deficiency to test the safety and efficacy of a long-acting GH molecule. The molecule, which requires weekly subcutaneous injections, rather than daily injections, was produced by covalent binding of polyethylene glycol with recombinant human GH. The study was terminated, however, after 13 patients developed injection-site lipodystrophy; in 3 patients, the atrophy occurred after the first injection. The investigators concluded that this side effect may limit the development of this long-acting GH molecule.[10]
United States
Localized lipodystrophy is extremely rare. Other than localized lipodystrophy secondary to injections, only a few case series of lipodystrophic syndromes are reported in the literature.
International
Because localized lipodystrophy is extremely rare, only a few case series of lipodystrophic syndromes are reported in the literature.
The natural course of lipodystrophy is benign. Mortality and morbidity usually depend on associated organ system involvement and comorbid conditions.
Patients without other organ system involvement experience no disability and are anticipated to have a normal life expectancy.
Cosmetically, lipodystrophy can be disturbing; in extreme cases, the patient's body self-image can be impaired significantly.
No studies addressing the racial distribution in localized lipodystrophy syndromes exist.
Females seem to be affected more often than are males, but the ratio is not known.
Lipodystrophy can present at any age, from early infancy through adulthood. Onset usually occurs during the first or second decade of life.
Localized lipodystrophy usually presents as isolated or multiple, atrophic, depressed areas with induration and indentations typically found in the extremities and other parts of the body in early childhood. These lesions may expand and, sometimes, spontaneously disappear. Lesions usually have no overlying skin changes and might have secondary skin pigmentations. Patients generally do not have any underlying diseases or associated symptoms at the time of presentation.
Localized lipodystrophy typically presents as depressions of the skin in various areas; lesions are multifocal, well-demarcated, and atrophic.
Some patients have local panatrophy involving muscle, fat, and morphealike changes.
The cause of lipodystrophic syndromes is unknown. One subset of the lipodystrophic syndromes is associated with subcutaneous and intradermal injection sites. In this group, trauma may induce the release of macrophage cytokines (eg, tumor necrosis factor, interleukin-1) that might enhance lipocyte catabolism. Impure animal insulin might lead to localized lipodystrophy, possibly because of a cross-reaction with lipid tissues and insulin antibody. Localized lipodystrophy caused by a cross-reaction is very rare with synthetic insulin.[11]
No specific laboratory blood tests exist to diagnose lipodystrophy.
Serological markers of systemic connective tissue diseases can be present with the inflammatory type of lipodystrophies.
Obtaining a biopsy of lesions is the diagnostic procedure of choice, and performing a histopathological examination might be helpful to diagnose and guide the treatment.
Histology depends on the type of lipodystrophy. According to one study, 2 main histopathological subsets exist.[12] One form, termed involutional fat, is a distinctive picture characterized by lobules of small lipocytes embedded in hyaline connective tissue, peripheral lobular accentuation, absence or scarcity of inflammatory cells, and myxoid stroma with numerous capillaries. Most of the patients with this type of histology have a single lesion, usually of the upper arm. Results of serological studies are normal. Of 3 cases in which direct immunofluorescence was performed, only one patient showed immunoreactants in the blood vessels.
The other type of histology is more of an inflammatory type, with inflammation of the fat. Normal-appearing lipocytes and normal vasculature are present, as well as scattered focal lymphocytes, histiocytes, and plasma cells. This histology involves multiple areas of localized lipoatrophy. In the early biopsy specimens of a series of 4 patients, lymphocytic panniculitis was observed, emphasizing the inflammatory basis for this disorder.[13]
Classification of partial or localized lipodystrophy involves association with the following:
No specific medical treatment exists.[14]
Treatment of insulin lipodystrophy consists of reassuring the patient that the condition is benign, switching to purified insulin (pork or human), and having the patient inject insulin in noninvolved areas and rotate the injection sites. This regimen is effective in more than 95% of patients. Improvement begins in 2-4 weeks, and normal consistency generally is restored within 2 months.
Treatment of underlying immunological disorders might prevent progression of the disease.
Surgical treatment with adipofascial flaps has been successful in some cases.
Follow-up of lesions with biopsies to determine disease activity and obtaining serological markers for immunological disorders might be helpful to guide the treatment.
No known method for prevention exists. Controlling the underlying immunological disorder might be preventative.
Complications include the following:
Prognosis is usually benign. Mortality and morbidity depends on associated organ system involvement and comorbid conditions.
Patients without other organ system involvement experience no disability and are anticipated to have a normal life expectancy.
Patients can be taught to change insulin injection sites if lipodystrophy is related to insulin injections.