Lipodystrophy

Classification

Important types and clinical clues

• Usually autosomal recessive; fat loss apparent at birth/early infancy.
• Generalized muscular or acromegaloid appearance, prominent veins, hepatomegaly.
• Mechanical fat over palms, soles, and orbits may be spared.
• Hyperphagia, accelerated growth, hypertrichosis, acanthosis nigricans.
• Genes: AGPAT2, BSCL2, CAV1, CAVIN1.
• Complications: diabetes, severe hypertriglyceridemia, pancreatitis, fatty liver/cirrhosis, cardiomyopathy.

• Usually autosomal dominant, commonly LMNA mutation.
• Onset around puberty, more obvious in females.
• Loss of fat from limbs, buttocks, and trunk, with relative excess fat over face, neck, and supraclavicular region.
• Muscular limbs, acanthosis nigricans, PCOS/hirsutism may occur.
• Severe insulin resistance, diabetes, hypertriglyceridemia, fatty liver.

• Progressive generalized fat loss beginning in childhood/adolescence.
• Often autoimmune; may follow panniculitis.
• Marked metabolic complications if extensive fat loss.

• Symmetrical fat loss from face, neck, arms, and upper trunk.
• Lower body usually spared or relatively obese.
• Often follows viral illness; associated with low C3 and membranoproliferative glomerulonephritis.

• Lipoatrophy of face, limbs, and buttocks with central fat accumulation: dorsocervical fat pad, abdomen, breasts.
• Associated particularly with older protease inhibitor-based HAART. Fitzpatrick’s Dermatology, p. 1324.

• Local depressed plaques at sites of repeated insulin, corticosteroid, or vaccine injections, trauma, pressure, or panniculitis.

Clinical manifestations

• Visible loss of subcutaneous fat, muscular appearance, prominent veins.
• Acanthosis nigricans, hypertrichosis.
• Xanthomas in severe hypertriglyceridemia.
• Hepatomegaly due to steatosis.

• Insulin resistance and early diabetes mellitus.
• Hypertriglyceridemia, risk of acute pancreatitis.
• Hepatic steatosis, steatohepatitis, cirrhosis.
• PCOS, irregular menses, infertility.
• Hypertension, cardiovascular disease, cardiomyopathy.

Diagnosis

• History: age at onset, family history, HIV/ART, injections, panniculitis, autoimmune disease.
• Examination: distribution of lipoatrophy/lipohypertrophy; acanthosis; hepatomegaly.
• Metabolic work-up: fasting glucose/HbA1c, lipid profile, liver enzymes, urine protein.
• Serum leptin is often low, especially in generalized disease.
• Body-fat assessment: skinfold thickness, DEXA or MRI where required.
• Genetic testing in suspected inherited forms.
• In acquired partial disease: serum complement C3 and renal assessment.

Management

1. Lifestyle
   • Diet, weight/metabolic control, exercise if no cardiomyopathy.
   • Avoid alcohol, especially with hypertriglyceridemia/fatty liver.
2. Treat complications aggressively
   • Diabetes: metformin, insulin, other antidiabetic therapy as indicated.
   • Hypertriglyceridemia: diet, fibrates/omega-3 fatty acids; urgent treatment if pancreatitis risk.
   • Treat hypertension, dyslipidemia, fatty liver, renal and cardiac disease.
3. Metreleptin
   • Recombinant leptin.
   • First-line adjunct to diet for metabolic/endocrine abnormalities in generalized lipodystrophy with hypoleptinemia.
   • May be considered in selected partial lipodystrophy with severe metabolic disease. Guideline recommendations
4. Cosmetic and psychological care
   • Facial fillers, fat grafting, reconstructive/cosmetic procedures.
   • Counsel regarding body-image distress.
5. Cause-specific measures
   • Review/modify offending ART where feasible in HIV-associated disease.
   • Stop/re-site causative injections in localized lipoatrophy.

One-line conclusion