What is Lipodystrophy?
Lipodystrophy syndromes are rare disorders marked by a lack of body fat just beneath the skin’s surface. Which type a person has is determined by the patterns of fat loss on the body and whether the disease is acquired or genetic. Due to the body’s inability to process fat, lipodystrophy leads to severe metabolic, hormonal, cardiovascular and fat storage disorders. Because the disease affects an individual’s outward appearance, it can also have deep psychological effects that may need to be addressed by a mental health care professional.
People who have lipodystrophy can end up with extra fat deposits in their legs, on the face, the back of the neck, or abdomen, and within the liver (called non-alcoholic fatty liver disease). This happens because the body is unable to maintain a layer of fat beneath the skin’s surface, so the fat he or she consumes concentrates elsewhere in the body.
Pathophysiology of Lipodystrophy
The metabolic alterations seen in patients with lipodystrophies result from an overall decrease in adipose tissue burden. Adipose is a metabolically active tissue that has many physiologic functions. Adipose tissue not only provides insulation but also serves to mediate inflammation and secrete many hormones involved in endocrine regulation. In patients with lipodystrophies, a reduction in adipose leads to a deficiency in certain hormones.
In particular, a decrease in leptin has been described in many lipodystrophy patients. Leptin is a proinflammatory adipokine secreted by adipose tissue. It is often referred to as the “satiety hormone” because it regulates mediators of appetite and energy expenditure. A decrease in leptin, whether in the setting of intrinsic leptin deficiency or lipodystrophy, leads to the downstream complications of hyperinsulinemia, insulin resistance with possible progression to diabetes, hypertriglyceridemia, and hepatic steatosis.
The prevalence in adults varies from 2-60% but for UK adults a recent paper quotes a prevalence of 17%. With increased awareness there are now fewer new cases of LDHIV. A prevalence of 33% has been quoted for highly active antiretroviral therapy (HAART) treated HIV children.
Types of Lipodystrophy
The first type of lipodystrophies includes those that are present at birth:
Congenital generalized lipodystrophy (CGL) is one of the most well-studied lipodystrophy syndromes with over 300 reported cases in the literature. Affected subjects have extreme paucity of adipose tissue from birth, leading to a muscular appearance with prominent veins and an acromegaloid appearance, along with severe acanthosis nigricans, hepatosplenomegaly, and early onset of diabetes, hypertriglyceridemia and steatohepatitis. Marked hypoleptinemia is a universal feature of this disease.
Patients with familial partial lipodystrophy (FPL) have normal fat distribution at birth but usually develop fat loss from the extremities after puberty. The well-studied type of FPL is the Dunnigan variety (FPLD) in which fat loss from the limbs and often the trunk, especially anteriorly and over the breasts, is usually accompanied by excess fat deposition over the face and neck. Metabolic abnormalities are similar to those seen in patients with CGL but may not be as severe in some patients. Since the extent of fat loss is not uniform, circulating leptin levels may also vary from low to normal in these patients.
The second type of this disease includes patients who acquire it during their lifetime:
Acquired lipodystrophies may occur in association with other autoimmune disorders or panniculitis, or may be idiopathic. Patients with acquired generalized lipodystrophy (AGL) may show severe metabolic complications similar to patients with CGL, while patients with acquired partial lipodystrophy (APL), also known as Barraquer-Simons syndrome, who invariably have well-preserved lower body fat, have lesser incidences of metabolic complications compared with other lipodystrophy syndromes. Rare forms of acquired partial lipodystrophy associated with autoinflammatory syndromes may however be associated with significant metabolic abnormalities.
Inherited lipodystrophy is a genetic disorder, meaning one or both parents typically pass the abnormal gene to their child. The type of lipodystrophy your child has depends on which genes she or he inherited.
Acquired lipodystrophy is not passed down from parent to child, but develops at some point in childhood, adolescence or adulthood. It can be caused by:
- An infection such as measles or pneumonia
- An autoimmune disease such as rheumatoid arthritis
The cause of an acquired lipodystrophy can also remain unknown.
Experts do not know the exact cause of many cases of acquired lipodystrophy. Certain medications and autoimmune conditions may increase a person’s risk.
Related autoimmune conditions, beyond those listed just above, and may include:
- Autoimmune thyroiditis
- Autoimmune hepatitis
- Autoimmune hemolytic anemia
- Rheumatoid arthritis
- Sjogren’s syndrome
- Sicca syndrome
The following infections may also increase the risk of developing acquired lipodystrophy:
- Infectious mononucleosis
- Diphther osteomyelitis
Lipodystrophy can affect all or part of the body. Signs and symptoms can include areas of the body that appear thin while other areas may appear to be enlarged. Children with the genetic form of lipodystrophy may have symptoms and signs including
- Prominent musculature
- Protruding belly
- Voracious appetite
- Early puberty
- Cognitive deficiencies
- Growth faster than their peers
- Increased bone age
Metabolic complications in lipodystrophy can be severe and life-threatening. They are more common in those with a greater extent of fat loss, especially the generalised lipodystrophies. CGL and AGL feature reduced levels of leptin, causing over-feeding which results in the abnormal deposition of fat in other organs with associated metabolic complications, such as:
- High insulin levels resulting in insulin-resistant diabetes
- Hypertriglyceridemia causing recurrent attacks of pancreatitis
- Polycystic ovarian syndrome, infertility, and masculinisation in females
- Fatty liver disease, which can progress to liver cirrhosis and eventual liver failure
- Enlargement of the liver and spleen
- Hypertension and cardiovascular disease.
Other complications include:
- Kidney disease
- Peripheral T-cell cutaneous lymphoma, occuring in 7% of AGL
- Significant psychological distress resulting from the appearance of fat loss
- Physical discomfort arising from the loss of fat pads from the buttocks and feet.
Doctors typically diagnose lipodystrophy by performing a physical exam and asking about symptoms. They may try to eliminate the possibility of other conditions, such as Cushing’s syndrome or anorexia.
The following diagnostic tests can help support the diagnosis and rule out other conditions:
- Genetic tests
- Tests to check blood chemical profiles
- Whole-body MRI to check for patterns of fat loss characteristic of acquired lipodystrophy
- Renal biopsy to check for kidney involvement in cases of suspected APL
Currently, there is no specific treatment that will permanently replace adipose tissue.
The reduced amount of adipose tissue and its impact on appearance is distressing to some people. In certain cases, cosmetic interventions and surgery have been used. The best approach to cosmetic surgery in lipodystrophy has not been formally studied.
The main treatment focus in lipodystrophy is on a low-fat or low energy diet. The aim of dietary therapy is to reduce the amount of ectopic fat in organs which contributes to insulin resistance and the development of metabolic complications of lipodystrophy. Dietary intervention can produce major improvements in many of the established complications that are associated with ectopic fat such as insulin resistance, high blood fat and liver inflammation.
In certain types of lipodystrophy Leptin replacement therapy may be prescribed. Leptin is a hormone which is made by adipocytes (fat cells). Leptin regulates appetite. In patients affected by lipodystrophy leptin levels can be low due to the reduced number of adipocytes and when this happens it may increase appetite. Increased appetite and excess food intake will have a negative effect on metabolism. In such cases Leptin therapy can reduce appetite and improve some of the metabolic complications of the condition. It is most often used in cases of generalised lipodystrophy where there is a near absence of fat.
As a chronic condition and one that is appearance-altering, lipodystrophy can be associated with psychological distress. Some patients may benefit from accessing a variety of psychological support services.
Where specific complications arise such as diabetes and high triglycerides in the blood, medical therapy specific to those conditions may be recommended. It is not uncommon for lipodystrophy patients with diabetes to require high doses of insulin, in that instance concentrated forms of insulin therapy or sometimes insulin pump therapy may be needed. All of these medical interventions are prescribed in conjunction with a low energy/low-fat diet.
Among patients with partial lipodystrophy and metabolic complications that are not adequately controlled using conventional therapy, metabolic surgery, specifically has been used effectively. Roux-en-Y gastric bypass reduces the size of the upper stomach and thus supports weight loss. In addition, it improves general metabolic problems like reduction of high blood sugar levels and amelioration of insulin sensitivity in muscles, liver and fat tissues.
Prevention of Lipodystrophy
It is important, having identified aetiological factors, to try to prevent LDHIV. Efforts in this direction are being targeted on:
- Increasing awareness amongst doctors and patients, together with regular assessment, may help early identification. Early identification may be assisted by techniques such as MRI.
- Choice of antiretroviral regimen, avoiding combinations of PIs and certain NRTIs.
- Early treatment and interventions for metabolic changes (as these may promote the LDHIV).
- General advice on diet and exercise. This may include the use of supplements, high fiber, and omega 3, etc.
- Earlier treatment of the HIV infection may help prevent LDHIV (before AIDS develops and before the CD4 count falls below 200/mm3).