eMedicine Specialties > Dermatology > Diseases of the Subcutaneous Tissue

Lipodystrophy, Progressive

Geover Fernandez, MD, FAAD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry New Jersey, New Jersey Medical School
Isabelle Thomas, MD, Associate Professor, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School; Chief of Dermatology Service, Veterans Affairs Medical Center of East Orange

Updated: Mar 28, 2007

Introduction

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

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.

Differential Diagnoses

Cockayne Syndrome
Lipodystrophy, HIV
Lipodystrophy, Localized

Workup

Laboratory 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

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

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

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.

Inpatient & Outpatient Medications

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

Medicolegal 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

Coessens BC, Van Geertruyden JP. Simultaneous bilateral facial reconstruction of a Barraquer-Simons lipodystrophy with free TRAM flaps. Plast Reconstr Surg. Apr 1995;95(5):911-5. [Medline].
Ferrarini A, Milani D, Bottigelli M. Two new cases of Barraquer-Simons syndrome. Am J Med Genet A. May 1 2004;126(4):427-9. [Medline].
Fitch N, Tulandi T. Progressive partial lipodystrophy and third-trimester intrauterine fetal death. Am J Obstet Gynecol. May 1987;156(5):1195-6. [Medline].
Font J, Herrero C, Bosch X, et al. Systemic lupus erythematosus in a patient with partial lipodystrophy. J Am Acad Dermatol. Feb 1990;22(2 Pt 2):337-40. [Medline].
Greene AK. Lluis Barraquer-Roviralta (1855-1928): Spanish neurologist described progressive lipodystrophy. Plast Reconstr Surg. Jan 2001;107(1):158-62. [Medline].
Hagari Y, Sasaoka R, Nishiura S, et al. Centrifugal lipodystrophy of the face mimicking progressive lipodystrophy. Br J Dermatol. Oct 1992;127(4):407-10. [Medline].
Halazonetis J. A case of progressive lipodystrophy. Barraquer-Simon''s disease. Br J Oral Surg. Nov 1968;6(2):130-3. [Medline].
Haxton MJ. Progressive partial lipodystrophy in association with intrauterine death and growth retardation. Am J Obstet Gynecol. Dec 1 1983;147(7):837-8. [Medline].
Hegele RA, Cao H, Liu DM, et al. Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet. Aug 2006;79(2):383-9.
Ketterings C. Lipodystrophy and its treatment. Ann Plast Surg. Dec 1988;21(6):536-43. [Medline].
Levy Y, George J, Yona E, Shoenfeld Y. Partial lipodystrophy, mesangiocapillary glomerulonephritis, and complement dysregulation. An autoimmune phenomenon. Immunol Res. Aug 1998;18(1):55-60. [Medline].
Mathieson PW, Wurzner R, Oliveria DB, et al. Complement-mediated adipocyte lysis by nephritic factor sera. J Exp Med. Jun 1 1993;177(6):1827-31. [Medline].
McNeill AD. Progressive lipodystrophy. Br J Surg. Mar 1966;53(3):216-8. [Medline].
Mitchell SW. Singular case of absence of adipose matter in the upper half of the body. Am J Med Sci. 1885;90:105-106.
Perrot H, Delaup JP, Chouvet B. [Barraquer and Simons lipodystrophy. Complement anomalies and cutaneous leukocytoclasic vasculitis]. Ann Dermatol Venereol. 1987;114(9):1083-91. [Medline].
Polsky B, Kotler D, Steinhart C. HIV-associated wasting in the HAART era: guidelines for assessment, diagnosis, and treatment. AIDS Patient Care STDS. Aug 2001;15(8):411-23. [Medline].
Pope E, Janson A, Khambalia A, Feldman B. Childhood acquired lipodystrophy: a retrospective study. J Am Acad Dermatol. Dec 2006;55(6):947-50. [Medline].
Quecedo E, Febrer I, Serrano G, et al. Partial lipodystrophy associated with juvenile dermatomyositis: report of two cases. Pediatr Dermatol. Nov-Dec 1996;13(6):477-82. [Medline].
Requena Caballero C, Angel Navarro Mira M, Bosch IF. Barraquer-Simons lipodystrophy associated with antiphospholipid syndrome. J Am Acad Dermatol. Oct 2003;49(4):768-9. [Medline].
Rifkind BM, Boyle JA, Gale M. Blood lipid levels, thyroid status, and glucose tolerance in progressive partial lipodystrophy. J Clin Pathol. Jan 1967;20(1):52-5. [Medline].
Serra JM, Ballesteros A, Mesa F, et al. Use of the temporal muscle flap in Barraquer-Simon''s progressive lipodystrophy. Ann Plast Surg. Feb 1993;30(2):180-2. [Medline].
Sissons JG, West RJ, Fallows J, et al. The complement abnormalities of lipodystrophy. N Engl J Med. Feb 26 1976;294(9):461-5. [Medline].
Smak Gregoor PJ, van Bommel EF, Ketterings C, et al. Progressive lipodystrophy, a diagnosis at a glance. Nephrol Dial Transplant. Feb 1998;13(2):507-9. [Medline].
Sonnino M, Ribuffo D, Piovano L, et al. [Nonprogressive, late-onset atrophy of the cheek]. Minerva Chir. Dec 2000;55(12):881-5. [Medline].
Spranger S, Spranger M, Tasman AJ, et al. Barraquer-Simons syndrome (with sensorineural deafness): a contribution to the differential diagnosis of lipodystrophy syndromes. Am J Med Genet. Sep 5 1997;71(4):397-400. [Medline].
Van Etten E, Branisteanu DD, Overbergh L, et al. Combination of a 1,25-dihydroxyvitamin D3 analog and a bisphosphonate prevents experimental autoimmune encephalomyelitis and preserves bone. Bone. Apr 2003;32(4):397-404. [Medline].
Walport MJ, Davies KA, Botto M, et al. C3 nephritic factor and SLE: report of four cases and review of the literature. QJM. Oct 1994;87(10):609-15. [Medline].
Williams DG. C3 nephritic factor and mesangiocapillary glomerulonephritis. Pediatr Nephrol. Feb 1997;11(1):96-8. [Medline].

Keywords

progressive partial lipodystrophy, Barraquer-Simons syndrome, acquired partial lipodystrophy, cephalothoracic dystrophy, acquired progressive lipodystrophy, Kobberling-Dunnigan syndrome, familial mandibuloacral dysplasia syndrome, generalized lipodystrophy, metabolic anomalies, glucose intolerance, hypertriglyceridemia, hypocomplementemia, glomerulonephritis, autoimmune disorders

Contributor Information and Disclosures

Author

Geover Fernandez, MD, FAAD, Staff Physician, Department of Dermatology, University of Medicine and Dentistry New Jersey, New Jersey Medical School
Geover Fernandez, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Society for MOHS Surgery
Disclosure: Nothing to disclose.

Coauthor(s)

Isabelle Thomas, MD, Associate Professor, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School; Chief of Dermatology Service, Veterans Affairs Medical Center of East Orange
Isabelle Thomas, MD is a member of the following medical societies: American Academy of Dermatology and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

David P Fivenson, MD, Director, Wound Care Service, Department of Dermatology, Henry Ford Health System
David P Fivenson, MD is a member of the following medical societies: American Academy of Dermatology, Medical Dermatology Society, Michigan Dermatological Society, Michigan State Medical Society, Photomedicine Society, Society for Investigative Dermatology, and Wound Healing Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory
Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, European Academy of Dermatology and Venereology, International Society of Dermatology, Massachusetts Medical Society, New York Academy of Sciences, Phi Beta Kappa, Society for Investigative Dermatology, and Texas Medical Association
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

Further Reading