Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about, or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Lipodystrophy

What is Lipodystrophy?

• Lipodystrophy is a pathological condition in which there abnormal loss of fat from the body. The layer of fat is present subcutaneously that is just underneath the skin. As the body loses fat from the body the structures lying underneath the layer of fat which are the muscles and bone to become more prominent in such a way that the appearance of the skin resembles that of crests and troughs.​
• Lipodystrophies are a group of heterogeneous disorders characterized by varying degrees of body fat loss and predisposition to insulin resistance and its metabolic complications. ​
• Generalized lipodystrophy is a rare, complex, and clinically heterogeneous disorder characterized by the widespread lack or loss of adipose tissue, leading to relative leptin deficiency and associated metabolic abnormalities​
• Generalized lipodystrophy (whether inherited or acquired) is estimated to affect less than one out of every one million people.​
• HIV-associated lipodystrophy is more common, but it is difficult to estimate how common it actually is. Estimates of lipodystrophy associated with HIV have ranged from 10% to over 80% of patients infected with HIV.​

How Do You Get It?

• Loss of adipose tissue can occur either due to genetic or acquired causes, and can involve either the entire body or be restricted to certain areas like the extremities, often with excess fat deposition in the unaffected areas.​
• Lipodystrophies should be suspected in differential diagnosis of “lean or non-obese” patients presenting with early diabetes, severe hypertriglyceridemia, hepatic steatosis, hepatosplenomegaly, acanthosis nigricans, and polycystic ovarian syndrome.​
• If inherited it may be present at birth (congenital).​
  • Congenital generalized lipodystrophy is a result of specific genetic mutations that are passed from one generation to the next (inherited). Mutations in the genes known as AGPAT2 and BSCL2 account for the majority (about 95%) of cases of CGL. Mutations in other genes, including CAV1 and PTRF, have also been associated with this form of the disease​
• You can get the acquired form after an infection, autoimmune illness, trauma, or repeated pressure or injury on a specific area of the body. (For example, if you have diabetes and you give yourself insulin shots in the same spot every day, you may get lipodystrophy at the injection site.) Acquired lipodystrophies are caused by medications, autoimmune mechanisms or other unknown mechanisms. These include highly active antiretroviral therapy (HAART) induced lipodystrophy in HIV-infected patients (LD-HIV), acquired generalized lipodystrophy (AGL), acquired partial lipodystrophy (APL) and localized lipodystrophy. Acquired lipodystrophies do not have a direct genetic basis. Rather, many mechanisms may be involved.​
  •  Lipodystrophy is most common at injection sites. This may be the site of a steroid injection or while injecting insulin in diabetics. For prevention it should be made sure that the injection is placed inside the muscles and not in the subcutaneous fat. Lipodystrophy can also be caused due to injections for vaccinations, hormone injections, or during acupuncture.
• You’re more likely to have lipodystrophy if you’re:​
  • Older​
  • White​
  • Obese or have had significant weight changes​
  • Fat loss might also be from AIDS wasting syndrome.​

What Are The Symptoms?

• Loss of fat tissue
  • In the buttocks​
  • In the face​
  • A person with HIV can have fat loss or fat buildup or both. Whether the changes are noticeable or not depends on the degree of fat loss or fat buildup. ​
• Leptin deficiency
• High HbA1c
• Increased fasting glucose
• Abnormal fat deposits in muscle or liver
• Hypertriglyceridemia
• Insulin resistance
• Diabetes
• Heart disease
• Some patients with generalized lipodystrophies are predisposed to developing extreme hypertriglyceridemia and chylomicronemia, which result in acute pancreatitis and even death. ​
• Many patients with FPL (familial partial lipodystrophy) develop coronary heart disease and other atherosclerotic vascular complications. Hepatic steatosis can lead to cirrhosis, necessitating liver transplantation. ​
• Fat buildup (also called lipohypertrophy) can occur:​
  • Around the organs in the belly.  ​
  • On the back of the neck between the shoulders (called a buffalo hump).​
  • In the breasts.​
  • Just under the skin. (The fatty bumps are called lipomas.)​

How Is It Treated?

• The treatment of lipodystrophy aims to ameliorate both the metabolic disturbances and pathological changes in fat distribution.​
• Treatment of various types of lipodystrophies is quite challenging. Proper counseling of parents is critical for preventing unwanted stress and psychological sequelae in children affected with lipodystrophy. ​
• The treatment for lipodystrophy depends on the underlying cause of the condition. They may include:​
  • Surgical procedure in which fat from one part of the body is moved to another part of the body.​
    • Because reversal of the lost adipose tissue is not possible, cosmetic surgery to improve appearance and management of metabolic complications are the only therapeutic options. Unwanted excess adipose tissue can be surgically excised or removed by liposuction.
    • Cosmetic implants
    • Those with severe facial lipodystrophy can undergo reconstructive facial surgery including fascial grafts from thighs, free flaps from anterolateral thigh, anterior abdomen, or temporalis muscle.​
  • Monitoring diabetes and high cholesterol ​
    • Tesamorelin (Egrifta), a daily shot that can lessen belly fat but may raise your blood sugar​
    • Metformin (Glucophage) for high blood sugar and insulin resistance
    • Atorvastatin (Lipitor) for high cholesterol​
  • Medication like steroids can be used for treatment of lipodystrophy.​
  • Hormone treatments, such as testosterone and human growth hormone
  • Injections to build up skin thickness and fill out sunken cheeks
• In 2014, the U.S. Food and Drug Administration approved Myalept (metreleptin for injection) as replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy. 
• Reduction of energy intake and increased physical activity is important in patients with familial partial lipodystrophy (FPL) to avoid excess fat deposition in nonlipodystrophic regions. ​
• Many patients with FPL have increased risk of coronary heart disease and they should limit intake of saturated and trans-unsaturated fats and dietary cholesterol. However, whether such diet will be beneficial in the long term to reduce hepatic steatosis, serum triglycerides and improve glycemic control remains unclear.​
  • Dietary guidelines for lipodystrophy have not been established. However, given their elevated risk for cardiovascular disease and diabetes, patients with lipodystrophy should adhere to the guidelines of the American Heart Association, which recommends that less than 30% of daily calories come from fat, and the America Diabetes Association, which recommends that carbohydrate and monounsaturated fat should provide 60–70% of daily calories.​

Where Can I Learn More???

• Check out our cornerstone on this disease here.