AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Subcutaneous loss of fat can occur as generalized or partial lipodystrophy; the latter is more common. Progressive lipodystrophy is the most common type of partial lipodystrophy. The other types, such as the Kobberling-Dunnigan variety or the familial mandibuloacral dysplasia syndrome, may be familial and tend to be associated with metabolic anomalies such as glucose intolerance and hypertriglyceridemia.

Progressive lipodystrophy is a rare condition that typically affects children and young adults. The first case was described by Mitchell in 1886, and later cases were described by Barraquer in 1907 and Simons in 1911. The onset is usually insidious with the slow, progressive disappearance of subcutaneous fat involving the upper half of the body. The predictive progression of the disease from the face to the neck, upper extremities, and trunk (sparing the buttocks and lower limbs) is characteristic. Associated hypocomplementemia, glomerulonephritis, and autoimmune disorders are frequently present in some patients.

Pathophysiology

The etiology of this condition is obscure. Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3.

C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations.

Frequency

International

This condition is rare, with fewer than 200 cases reported in the world literature since the first case was reported in 1885.

Mortality/Morbidity

Acquired progressive lipodystrophy is a nonfatal condition, but it is frequently associated with mesangiocapillary glomerulonephritis, which can lead to renal insufficiency.

• In pregnancy, more severe renal disease is associated with a risk of intrauterine growth retardation, prematurity, and fetal death.
• Associated autoimmune disorders are also present in some patients, including systemic lupus erythematosus and dermatomyositis.

Race

No racial predilection is reported.

Sex

This condition is 4-5 times more common in women than in men. Of patients with progressive lipodystrophy, 80% are females.

• The accumulation of fat in the buttocks and lower limbs occurs almost exclusively in females.
• Males who are affected usually have lipoatrophy without lower body hypertrophy.

Age

• Progressive lipodystrophy typically starts in individuals aged 0-20 years, with most cases starting before individuals are aged 15 years.
• This condition tends to develop earlier in most male patients compared with female patients.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients are born healthy with a normal appearance and fat distribution.
• In individuals aged 0-20 years, progressive loss of fat, which first involves the face, spreads distally to the neck, arms, and trunk; the lower part of the body is usually spared.

Physical

Because of the insidious onset and slow progression of this condition, most patients present when the disease is in an advanced stage. Advanced cases have a characteristic physical appearance.

• The face appears cachectic.
• • Buccal fat pads are absent, resulting in a prominent zygoma and chin.
  • The temples and cheeks are hollowed, causing a cadaverous appearance.
  • The eyes are deeply sunken due to the loss of periorbital fat.
  • The face is heavily lined, creating numerous wrinkles lying over the cheeks, which causes the appearance of premature senility.
  • The scalp, hair, and other facial areas are unaffected.
• Frequently, the breasts are underdeveloped, with a firm, nodular feel.
• The arms and shoulders have a clear, well-demarcated outline of muscles below the skin, which gives the false impression of increased muscularity.
• The area of fat loss is sharply demarcated at a level above the thighs; the lower extremities are spared.
• • The uninvolved lower part of the body appears obese when contrasted with the upper, thin area.
  • In female patients, excessive fat may develop on the legs and buttocks after puberty.
• The overlying skin itself is normal in color, elasticity, and texture.
• No muscular hypertrophy is noted.

Causes

• No specific cause or risk factor has been elucidated.
• Some reports have shown a correlation with prior acute viral or bacterial infection.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Generalized lipodystrophies such as Berardinelli-Seip syndrome (associated with acanthosis nigricans)
Other types of partial lipodystrophy
Centrifugal lipodystrophy
Facial hemiatrophy
Short, hyperextensibility or hernia, ocular depression, Rieger anomaly, and teething (SHORT) syndrome
Werner syndrome
Anterior hypothalamus tumor

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Urinalysis may be helpful.
• • Approximately one third of patients with this condition have some degree of glomerulonephritis, and, if hypocomplementemia is present, the risk is higher.
  • Manifestations of glomerulonephritis range from asymptomatic proteinuria to a nephrotic syndrome and renal insufficiency.
• Baseline creatinine and blood urea nitrogen studies, as well as urine studies, should be performed to detect proteinuria and hematuria.
• A CBC count should be obtained. Normochromic normocytic anemia is often present.
• Immune studies can be ordered.
• • Immune studies may be needed to identify patients with associated immune disorders, particularly if the diagnosis of partial lipodystrophy is made at a younger age.
  • The presence of serum antinuclear antibodies and anti–double-stranded DNA antibodies has been reported in some patients.
• Complement levels may be determined.
• • The most common laboratory abnormality in patients with progressive lipodystrophy is a low complement level.
  • Hypocomplementemia is characterized by a low C3 complement level, a normal C4 level, and the presence of C3 nephritic factor.
• Lipid studies may be performed. Hypertriglyceridemia secondary to nephrotic syndrome may be present in some patients.

Imaging Studies

• Head MRIs show evidence of fat loss.

Other Tests

• Immunofluorescence studies show deposits of C3 in a granular pattern in the basement membranes.

Procedures

• Skin biopsy findings confirm the diagnosis.
• Kidney biopsy is required if a glomerulonephritis is associated.

Histologic Findings

Cutaneous biopsy reveals a reduction or absence of subcutaneous fat in affected areas. Subcutaneous fat cells are decreased in number.

Traces of adipose tissue may be found around hair follicles and sebaceous glands. The dermis and epidermis are normal.

Renal biopsy findings are characterized by a membranoproliferative glomerulonephritis with a proliferation of mesangial cells and matrix, as well as thickening of the basement membranes by amorphous electron-dense deposits.

Immunofluorescence studies show deposits of C3 in a granular pattern in the basement membranes.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• No specific treatment for progressive lipodystrophy is effective.
• Symptomatic therapy should be prescribed as necessary for the treatment of renal complications and associated autoimmune disorders.

Surgical Care

• Various surgical techniques have been adopted through the years in an effort to improve the patient's facial appearance.
• Dermal-fat grafts from the gluteal region, temporal muscle flaps, silicone-filling material, and subcutaneous injections of fat from unaffected areas have been used with variable results.

Consultations

Referral to a nephrologist or an internist may be warranted for patients with severe nephropathy and those with associated autoimmune diseases.

Diet

Hyperalimentation can result in the excessive accumulation of fat in an unaffected area with no improvement on dystrophic areas.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No medical treatment for progressive partial lipodystrophy is effective.

Symptomatic therapy may be indicated in patients with severe nephropathy or associated immune disorders.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Renal and immunologic disturbances may warrant inpatient care at times.
• During pregnancy, the health status of the fetus should be ascertained with modalities such as an electronic fetal monitor. Fetal health assessment is particularly important during the third trimester to reduce the risk of intrauterine fetal death associated with progressive lipodystrophy.

Further Outpatient Care

• Renal status
• • Patients should be monitored regularly for evidence of glomerulonephritis.
  • Glomerulonephritis can develop more than 10 years after the onset of progressive lipodystrophy.
• Autoimmune disorders
• Patients should be monitored for the development of systemic lupus erythematosus because it was reported in a few patients 2-28 years after the onset of progressive lipodystrophy.
• Other autoimmune disorders have also been associated with this disease.

In/Out Patient Meds

• No inpatient or outpatient medications are specific for lipodystrophy.
• Symptomatic therapy may be required for patients with nephropathy or associated immune disorders.

Complications

• Renal disease
• • Mesangioproliferative glomerulonephritis occurs in 50% of patients with lipodystrophy and a low C3 complement level.
  • Mesangioproliferative glomerulonephritis often follows an aggressive course and may lead to renal insufficiency.
• Immune disorders
• Systemic lupus may develop in a few patients.
• Other autoimmune diseases include dermatomyositis, rheumatoid arthritis, leukocytoclastic vasculitis, hypothyroidism, and pernicious anemia.

Prognosis

• The prognosis is correlated with the renal complications and the onset of renal failure.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to monitor for glomerulonephritis and its complications
• Failure to closely monitor a high-risk pregnancy

Special Concerns

• Underlying renal disease
• Associated autoimmune disorder in some cases
• High-risk pregnancy with a risk of fetal death

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Mar 28, 2007