Lipodystrophy is a disorder characterized by atrophy of adipose tissue. Lipodystrophy may be localized, partial, or total, depending on the location and degree of fat loss.
Localized lipodystrophy is usually manifested in the form of isolated or multiple, indentations, particularly in the extremities of the body in childhood. Occasionally, these may disappear all on a sudden. But in some, the lesions may expand. In some cases, secondary pigmentation can be seen on the skin. This form of lipodystrophy is not associated with any underlying disease at the time of presentation. Some patients present with panatrophy of muscle and fat.
Acquired partial lipodystrophy has the onset in childhood usually before 16 years. This is followed by viral infections like measles. Progression of the disease occurs slowly over a period of months to years. One fourth of the patients will have severe fat loss before 13 years of age. Loss of adipose tissue extends from face, neck, and shoulders to upper trunk and abdomen. The lower parts like hips and legs are not usually affected. Metabolic abnormalities are not seen associated with this form. About 60% of the patients may have hepatomegaly.
Extraordinary lack of subcutaneous fat from birth is characteristic of congenital generalized lipodystrophy. Visceral organs are often enlarged and toddlers may have severe pharyngeal tonsils and adenoids. One of the earliest symptoms of this condition include well-defined musculature with prominent superficial veins. Patients may also present with dermatologic manifestations like eruptive xanthomas, hirsutism, and thick, curled scalp hair. Children with this condition may attain more than 90% of adult growth within 10 years.
HIV-associated lipodystrophy is a progressive disease and the severity of symptoms is usually related to age, duration of disease and the duration of use of protease inhibitors or nucleoside reverse transcriptase inhibitors for treatment. It is characterized by an increase in the circumference of the neck, abdominal visceral fat accumulation, and symmetric and asymmetric lipomatoses.
Diagnosis of this disease is mainly based on clinical features. Laboratory studies are used to check for associated conditions like metabolic disorders, and autoimmune diseases. In many cases histopathological studies are the confirmatory diagnostic test. Histology depends on the type of lipodystrophy. The two main histopathological subsets are involutional type and inflammatory type. In involutional type small lipocytes are seen embedded in hyaline connective tissue, lobular accentuation in the periphery, and scarcity of inflammatory cells. In inflammatory type, normal lipocytes and vasculature are present. Focal lymphocytes, histiocytes and plasma cells are scattered. These forms are more commonly seen in localized lipodystrophy.
To rule out associated disorders, tests including fasting blood glucose and lipid profile, creatinine, and urinalysis may be useful. Tests may also be conducted for antinuclear antibodies, and anticardiolipin antibodies. For familial form of lipodystrophy, genetic workup may be needed. In progressive lipodystrophy, immunofluorescence studies may be helpful.
Just like the different types of the disease, the treatment options are also varied. Efficacy of the treatment modality also depends on the type of the disease and the clinical features in an individual. Generally, any treatment strategy focus on alleviating the metabolic and pathologic changes in the distribution of fat. A general approach includes lifestyle modification like diet, exercise, and nutritional therapy. Patients with this disease are recommended to have less than 30% of daily calories from fat. About 60-70% of the calories should be provided by monounsaturated fat and carbohydrates. Exercise may be helpful in improving the metabolic parameters. Resistance training is found to enhance total lean mass and to decrease total fat accumulation. Exercise is also helpful in increasing peripheral insulin sensitivity, and HDL cholesterol levels.
Patients with concurrent diabetes may be suggested metformin for managing associated condition. Thiazolidinediones also may be helpful in improving insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Treatment guidelines for dyslipidemia in lipodystrophy is similar to that of coronary artery disease. Lifestyle modification is the first step in this regard. Statins are given for hypercholesterolemia. Fibrates and extended release niacin may be used for controlling hypertriglyceridemia. Ezetimibe inhibitors may be opted for patients who cannot tolerate statins.
Mortality and morbidity associated with the disease depends on the organ involved and the extent of involvement. If no other organ systems are involved, prognosis of lipodystrophy is good. Most of the patients will have a normal life expectancy without many disabilities. Even a progressive form of the disease like acquired partial lipodystrophy has a good prognosis if associated complications like renal impairment and insulin resistance are absent. In congenital forms most of the patients survive to young adulthood or early middle age.
Most forms of localized lipodystrophy have idiopathic etiology. Occasionally it is seen associated with subcutaneous and intradermal injections. Trauma at the site of injection is implicated in the release of cytokines that enhance catabolism of fat. Contamination of animal insulin is also found to cause localized lipodystrophy by cross reaction with lipid tissues and insulin antibody. This form of lipid dystrophy is very rare compared to other forms . Similarly, no special etiology is known for partial dystrophy also. There are reports of progressive partial lipodystrophy being associated with a history of viral or bacterial infection.
Inherited forms of lipodystrophy are caused by mutations. Congenital generalized lipodystrophy (CGL), characterized by total absence of adipose tissue, is caused by an autosomal recessive mutation. There are four subtypes of CGL, caused by compound mutations in four genes, 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT2), Berardinelli-Seip congenital lipodystrophy 2 (BSCL2), caveolin 1 (CAV1), and polymerase I and transcript release factor (PTRF).
The incidence and prevalence of many forms of lipodystrophy are not known. Both acquired and inherited forms of this disease are rare. Localized lipodystrophies, including the cases secondary to injections are rare. Few of them are reported in literature. Information on racial association of the disease is lacking. In general, females are found to be more affected than males in case of localized lipodystrophy. Onset of this form usually occurs within 10 to 20 years of age, and may be present from infancy to adulthood.
Acquired partial lipodystrophy is more common than generalized form of the disease. A total of 250 cases have been reported in United States . As in the case of localized lipodystrophy, no specific association has been reported between race and occurrence of acquired lipodystrophy. The prevalence is found to be four times more among women when compared to men. The median age of onset for acquired partial lipodystrophy is around 7 years, and occasionally it is also noted in 40 to 50 years. The clinical manifestations are found to start at a later stage in women when compared to men. The estimated prevalence of this form of inherited lipodystrophy is around 1 in 15 million persons.
Incidence of congenital lipodystrophy is found to be equal in male and female. Highest frequency of congenital generalized lipodystrophy is reported from Brazil . Congenital generalized lipodystrophy is a rare autosomal recessive disorder and around 250 cases are reported world over in literature. No difference has been reported in the frequency of this disorder in different parts of the world .
Congenital generalized lipodystrophy is classified into type 1 to 4, depending on the clinical manifestations and the etiological mutations. Type 1 (CGL1) is caused by a mutation of 1-acylglycerol-3-phosphate-O-acyltransferase 2 gene (AGPAT2). AGPAT2 gene plays an important role in functioning of adipocyte tissue and also in the synthesis of triacylglycerol in adipose tissue . Mutation of this gene affects the metabolically important tissue like the fat tissue in subcutaneous region, bone marrow, intramuscular, intraabdominal and intrathoracic regions. Type 2 (CGL2) occurs due to mutations of Berardinelli-Seip Congenital Lipodystrophy 2 gene (BSCL2). BSCL2 gene is involved in the coding of the protein seipen, which is implicated in the differentiation of adipose tissue and lipid droplet formation . Caveolin 1 (CAV1) mutations, and Polymerase I and transcript release factor (PTRF) mutations are associated with CGL3, and CGL4, respectively.
Many genetic mutations have been implicated in the development of inherited partial lipodystrophy. The most prevalent form is familial partial lipodystrophy type 2 and is caused by a mutation in the gene LMNA . HAART-associated lipodystrophy syndrome is a side-effect of HAART. Lipodystrophy may be caused by nucleoside reverse transcriptase inhibitors. It may result in abnormal proliferation of mitochondria, known as mitochondrial toxicity . Protease inhibitors are also implicated in the disruption of adipocyte differentiation and also in increased production of cytokines. Drug-induced lipodystrophy may also include increased lipolysis. Enhanced lipolysis along with deficiency of subcutaneous fat, indirectly lead to metabolic disturbances like insulin resistance and dyslipidemia.
No known method of prevention exist for lipodystrophy. In most of the cases controlling the underlying condition would go a long way in preventing complications.
Lipodystrophy is a disorder characterized by atrophy of adipose tissue which may be localized, partial, or total, depending on the location and degree of fat loss . Total lipodystrophy can be congenital with complete loss of fat tissue in the body and is often associated with metabolic abnormalities like insulin resistance, hyperlipidemia, and hyperglycemia. Partial lipodystrophy is manifested by loss of adipose tissue, particularly from face. Similar atrophy may not be present in other parts of the body. Localized lipodystrophy is manifested by localized loss of fat tissue.
Complications of lipodystrophy are often associated with the extent of loss of adipose tissue . Loss of adipose tissue occurs from the subcutaneous region and sometimes from visceral region . Lipodystrophy disorders result in fat redistribution, including lipohypertrophy and lipoatrophy. These disorders may lead to cosmetic problems in some, while in others it may even lead to severe metabolic complications. Lipodystrophy may be inherited or secondary to other illnesses, called as acquired lipodystrophy.
Lipodystrophy refers to a heterogeneous group of disorders that result in fat loss. As more and more of fat is lost from the body, other organs and structures underneath the skin become more defined and fat loss may be noted as depressions on the skin. Lipodystrophy may be categorized as congenital or acquired. It may also be divided as generalized, where fat loss occurs all over the body, and partial where fat loss occurs only in some parts of the body. Loss of fat leads to metabolic complications, the severity of which depends on the extent of loss.
Location of fat loss may vary from one person to another. Some patients may have very thin face and arms, while others may have very less fat on the lower areas of the body like legs and buttocks. Some others may have very little fat and appear muscular. In most of these patients, fat may be present in unusual places like kidney, blood, heart, liver and pancreas. This may lead to serious problems like insulin resistance, high cholesterol, diabetes mellitus, fatty liver disease and heart disease.
Clinical features with a family history of lipodystrophy and associated conditions are often used in diagnosis of the disease. Associated conditions may include diabetes mellitus, high levels of triglycerides or cholesterol, fatty liver, dark, velvety patches of skin and polycystic ovary syndrome. Treatment strategy include alleviating the disturbances due to changes in fat distribution. Lifestyle modifications with diet, nutrition therapy and exercise are important steps in the treatment of the condition. Medications are given for controlling diabetes mellitus, high levels of cholesterol and triglycerides. If no organs are involved in the disease, lipodystrophy has a good prognosis.