AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

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

INTRODUCTION

Section 2 of 12  

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

Background

Acquired partial lipodystrophy, also known as Barraquer-Simons syndrome or cephalothoracic lipodystrophy, is one of the rare forms of lipodystrophy. Mitchell initially reported this variety in 1885.¹ Barraquer and Simons further characterized the syndrome at the beginning of the 20th century. Since then, approximately 250 cases have been reported in English literature.

Acquired partial lipodystrophy usually begins in childhood, at a median age of 7 years.² It predominantly affects females and often follows an acute febrile illness. Fat loss is usually limited to the face, trunk, and upper extremities. Simultaneously, fat hypertrophy occurs in the lower extremities. These patients may develop nephropathies. Activation of alternate complement pathway has been demonstrated in most patients.

Compared with other types of lipodystrophy, acquired partial lipodystrophy is seldom associated with insulin resistance and its related metabolic derangements. This may be related to the fact that in this syndrome, patients have limited fat loss.

Disorders associated with acquired partial lipodystrophy include the following:

• Membranoproliferative glomerulonephritis -  This condition has been reported in about 20% of cases, and proteinuria, in 45% of cases. However, it is possible that other concomitant diseases (eg, urinary tract infection, diabetes) contribute to the rates of proteinuria.² Patients with membranoproliferative glomerulonephritis are more likely to have low C3 levels and the presence of C3 nephritic factor (C3NeF).^{3, 4, 5}
• Autoimmune diseases - Systemic lupus erythematosus is the most common of these^{3, 4}; other reported autoimmune diseases include, but are not limited to, the following:
  
  
  • Dermatomyositis
  • Pernicious anemia
  • Celiac disease
  • Dermatitis herpetiformis
  • Rheumatoid arthritis
  • Temporal arteritis
  • Leukocytoclastic vasculitis
• Propensity to bacterial infections
• Other - POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal component, skin changes) syndrome,⁶ mental retardation, and retinal disease are among the syndromes that also are associated with acquired partial lipodystrophy.
• Diabetes and impaired glucose tolerance - In contrast with their occurrence in most other lipodystrophies, diabetes and impaired glucose tolerance are found only rarely in acquired partial lipodystrophy, being reported in 6.7% and 8.9% of patients, respectively.²

Pathophysiology

The precise pathophysiology of fat loss is unclear. Activation of an alternate complement pathway, C3 hypocomplementemia with lysis of adipocytes induced by C3NeF, has been implicated.⁷ C3 hypocomplementemia likely contributes to the association of this syndrome with autoimmune diseases and with a propensity for patients to acquire bacterial infections.² Other proposed mechanisms include an autoimmune process and genetic associations.^{8, 9}

Frequency

United States

Approximately 250 cases have been reported since the recognition of this syndrome. It is a rare syndrome with no known prevalence, although it is more common than the generalized form of acquired lipodystrophy (Lawrence syndrome).²

International

Several case reports, coming from different parts of the world, have been made. However, the international incidence and prevalence of this disease are not known.

Mortality/Morbidity

Estimating the mortality rate based on the available literature is difficult. Several case reports have revealed an association between acquired partial lipodystrophy and other diseases (see the list of disorders associated with acquired partial lipodystrophy).

• Nephropathy, in the form of membranoproliferative glomerulonephritis, occurs in approximately 20% of patients.²
• Usually, patients do not have clinically evident renal disease or abnormalities in renal function until they have had the disease for 8 or more years.
  
  
  • Membranoproliferative glomerulonephritis usually presents with asymptomatic proteinuria or hematuria.
  • The disease may gradually progress. About 40-50% of patients develop end-stage renal disease over the course of 10 years. This condition is responsible for most recurrent hospital admissions in patients with acquired partial lipodystrophy.²
  • Rapid progression of renal disease in a pregnant patient was reported.¹⁰ 
  • Recurrent disease in transplanted kidneys is common, although there have been reports of successful transplantations.^{11, 12}
• Associated autoimmune diseases (eg, systemic lupus erythematosus, thyroiditis) contribute significantly to increased morbidity in these patients compared with the general population.
• Although uncommon, insulin resistance increases cardiovascular risk.
• Susceptibility to bacterial infections probably results from a C3 deficiency (due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial killing.

Race

No clear relationship exists between incidence and race in this syndrome; however, most reported patients have been of European descent.

Sex

Women are affected approximately 4 times more often than men.²

Age

The median age of onset of lipodystrophy has been reported to be around 7 years; however, onset occurring as late as the 4th or 5th decade of life also has been reported.²

The median age at presentation has been about 25 years, and women have been found to present later than men (age 28 y vs 18 y).

CLINICAL

Section 3 of 12  

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

History

• The problem usually begins in childhood. In most reports, disease onset occurs when patients are younger than 16 years.
• The onset usually follows an acute, febrile viral illness, most commonly measles. Minor surgical procedures and psychological stress have also been reported before the onset of fat loss.
• Lipodystrophy progresses slowly and occurs over a period of a few months to 2 years. Seventy-five percent of patients have been found to have significant fat loss when younger than 13 years.
• Acquired partial lipodystrophy is characterized by a fat loss that spreads through the cephalocaudal distribution from the face, neck, shoulders, arms, and forearms and that extends to the thoracic region and upper abdomen. Occasionally, fat loss may involve the groin or thighs. The hips and legs are usually spared (see Image 1). After puberty, women have a tendency to accumulate fat (lipohypertrophy) disproportionately in the hips and legs.¹³
• The process does not affect patient growth, and children usually experience developmental milestones with no difficulties. No pain is associated, but patients may occasionally complain of muscle weakness.
• Patients with acquired partial lipodystrophy do not usually experience the metabolic abnormalities observed in persons with other forms of lipodystrophy. However, inquiring about a history of menstrual irregularities, hirsutism, diabetes mellitus, and dyslipidemia is important, because metabolic abnormalities have been reported in these patients, and therapeutic interventions are available for these diseases. In addition, looking for evidence of renal disease, which occurs in approximately 20% of patients, is essential. Most patients are asymptomatic until the development of advanced renal impairment or acute decompensation.²
• Hepatomegaly has been reported in over 60% of patients. However, this finding might be due to associated autoimmune diseases.
• Patients with acquired partial lipodystrophy may present with a history that is suggestive of autoimmune or rheumatologic disease.

Physical

Patients usually have normal growth and secondary sexual characteristics. No specific bony abnormalities are present. 

• General inspection may reveal features of one of the associated autoimmune diseases (see the list of disorders associated with acquired partial lipodystrophy). Hepatomegaly might be present. Acanthosis nigricans and increased skin tags are very rare; they indicate the presence of insulin resistance.
• Exposing the patient properly for examination is very important; otherwise, the diagnosis can be easily missed. The best exposure during examination is achieved when the patient wears a gown exposing the extremities and trunk.
• These patients usually have characteristic body changes, including loss of fat and deposition of fat.
• • Loss of fat occurs in the face (around the cheeks and temples; eg, sunken cheeks), neck, shoulders and upper extremities, and upper abdomen. Breasts may lose fat and consist only of firm glandular tissue. Prominent veins in the arms with a muscular appearance (not associated with heavy exercise or muscle-building routines) are very characteristic of this syndrome.
  • Fat deposits can occur in the hips, lower extremities, breasts (in men and women), or other scattered areas around the body. These patients do not have cushingoid features.

Diagnostic criteria

• Gradual loss of subcutaneous fat in face, neck, trunk, and upper extremities occurring during childhood or adolescence (essential)
• Normal or excess subcutaneous fat in the hips and lower extremities
• Proteinuria or biopsy-proven membranoproliferative glomerulonephritis
• Low C3 level, reported in about 70% of patients (the C3 level might be normal with an elevated C3 degradation product, C3d)
• Presence of C3NeF, a polyclonal immunoglobulin G (IgG), able to break down C3 in normal human serum (it is reported to be present in about 80% of patients)
• Absence of other metabolic derangement
• Characteristic fat distribution, as measured by skinfold thickness or images from magnetic resonance imaging (MRI) studies^{9, 14}
• Presence of autoimmune disease

Causes

Proposed mechanisms include the activation of an alternate complement pathway, autoimmune diseases, genetic associations, and idiopathic disease.

DIFFERENTIALS

Section 4 of 12  

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

Other Problems to Be Considered

Because of the variable patterns of lipodystrophy in these patients, several other syndromes should be considered in the differential diagnoses of acquired partial lipodystrophy, including the following:

• Idiopathic localized lipodystrophy
• Familial partial lipodystrophy
• Drug-induced lipodystrophy
• Human immunodeficiency virus 1 (HIV-1)–related lipodystrophy^{9, 15}
• Acute panniculitis
• SHORT syndrome (short stature, hyperextensibility of joints, ocular depression, Reiger [ocular and dental] anomaly, teething delay)⁹
• Werner syndrome
• Neonatal progeroid syndrome (Wiedemann-Rautenstrauch syndrome)
• Leprechaunism (Donohue syndrome)
• Mandibuloacral dysplasia

WORKUP

Section 5 of 12  

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

Lab Studies

The diagnosis of the disease is mainly clinical (see the list of diagnostic criteria). The laboratory workup is needed primarily to investigate for the presence of associated disorders (metabolic, autoimmune, and renal diseases).

• Every patient should have a fasting blood glucose and lipid profile, creatinine evaluation, and urinalysis for protein content at the first visit, after which he/she should have these tests on a regular basis.
• Although uncommon, lipid abnormalities can occur in the form of raised triglyceride levels and low high-density lipoprotein (HDL) cholesterol levels. 
• Patients usually have decreased serum C3 levels, normal levels of C1 and C4, and high levels of C3NeF (autoantibody), which may indicate the presence of renal involvement.
• Antinuclear antibodies (ANA) and anti–double-stranded deoxyribonucleic acid (DNA) antibodies have reportedly been observed in some patients with acquired partial lipodystrophy.
• A genetic workup should be performed if the familial form of lipodystrophy is suggested.

Laboratory work for associated diseases includes the following:

• Metabolic disease - Fasting glucose, glucose tolerance test, lipid profile, and fasting insulin to characterize the insulin resistance state; free testosterone (in women) to look for polycystic ovary syndrome
• Autoimmune disease - ANA, anti–double-stranded DNA, rheumatoid factor, thyroid antibodies, C3, and C3NeF

Imaging Studies

As a confirmatory test, whole-body MRI usually clearly demonstrates the extent of lipodystrophy. MRI is not recommended on a routine basis.

Procedures

Renal biopsy is the test of choice to help diagnose the type of renal impairment in these patients. A transcutaneous procedure performed under ultrasonographic guidance, it is used to obtain renal tissue using a fine needle. Nephrologists should direct this procedure.

Histologic Findings

Under light microscopy, biopsy specimens of affected areas show a loss of subcutaneous fat; relative adipocyte volume is reduced to 65% of baseline. Lipocytes are usually atrophic or are reduced in number. No infiltrates with lymphocytes have been reported.

TREATMENT

Section 6 of 12  

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

Medical Care

• In general, treatment for acquired partial lipodystrophy is limited to cosmetic, dietary, or medical options.
• Currently, no effective treatment exists to halt the progression of lipodystrophy.
• Thiazolidinediones have been used in the management of various types of lipodystrophies. They bind to peroxisome proliferator-activator receptor gamma (PPAR-gamma), which stimulates the transcription of genes responsible for growth and differentiation of adipocytes.¹⁶ A single report has suggested a beneficial effect from treatment with rosiglitazone on fat distribution in acquired partial lipodystrophy¹⁷; however, preferential fat gain was in the lower body.
• Following the online publication of a meta-analysis,¹⁸ the Food and Drug Administration issued an alert on May 21, 2007, to patients and health care professionals warning that rosiglitazone could potentially cause an increased risk of myocardial infarction (MI) and heart-related deaths. A thiazolidinedione derivative, rosiglitazone is an antidiabetic agent that improves glycemic control by improving insulin sensitivity. The drug is highly selective and is a potent agonist for PPAR-gamma. Activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and utilization, thereby reducing blood glucose concentrations and hyperinsulinemia. Potent PPAR-gamma agonists have been shown to increase the incidence of edema. A large-scale phase III trial (RECORD) has been underway to study the cardiovascular outcomes of rosiglitazone.
   
  For more information, see the FDA's Safety Alert on Avandia. Additionally, responses to the controversy, including the following articles, can be viewed at Heartwire news (the heart.org, from WebMD): 1) Rosiglitazone increases MI and CV death in meta-analysis, 2) The rosiglitazone aftermath: Legitimate concerns or hype?, and 3) RECORD interim analysis of rosiglitazone safety: No clear-cut answers.
  
• Direct drug therapy is administered according to the associated condition.
  
  
  • Membranoproliferative glomerulonephritis and the presence of renal dysfunction largely determine the prognosis of acquired partial lipodystrophy. Standard guidelines for the management of renal disease should be followed.
  • The course of membranoproliferative glomerulonephritis in acquired partial lipodystrophy has not been significantly altered by treatment with corticosteroids or cytotoxic medications.
  • Recurrent bacterial infections, if severe, might be managed with prophylactic antibiotics.

Surgical Care

• The purpose of surgery is mainly cosmetic. According to guidelines from the American Academy of Dermatology, lipodystrophy is one of the indications for fat transplant.
• Several facial reconstruction techniques have been used, with variable success, to restore facial contour. However, surgical intervention cannot restore adipose tissue distribution in other affected areas.
• The literature is controversial regarding these procedures. The best approach is to individualize the treatment options based on the patient's condition and requirements. These procedures are not recommended for prepubertal children.
• Procedures may include the transposition of facial muscles, adipose tissue transplantation (liposuction), and the insertion of silicone or other implants.

Consultations

Early consultation with a nephrologist or an endocrinologist is very important if renal or metabolic complications are suggested.

Diet

No evidence in the literature favors any specific diets in this group of patients. A low-fat, high-carbohydrate diet can be detrimental with regard to triglyceride levels, and weight gain should be avoided to reduce the risk of worsening metabolic status. However, children with this syndrome should be permitted normal food intake to allow for normal growth.

Activity

Regular exercise should be encouraged to help improve metabolic status.

MEDICATION

Section 7 of 12  

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

Pharmacologic intervention is limited in this syndrome.^{17, 18, 16} Biguanides and thiazolidinediones have been used in the treatment of the insulin-resistant state (which includes type 2 diabetes and polycystic ovary disease) and in cases of HIV-related glucose intolerance. Although not studied in this group of patients, these drugs should be the first line of treatment if diabetes occurs. Fibrates are the drug of choice for the treatment of hypertriglyceridemia and low HDL cholesterol syndrome.

Drug Category: Hypoglycemic agents

These medications would be started if the patient has developed diabetes that is not being controlled through diet. Insulin sensitizers (biguanides and thiazolidinediones) can be used to reduce insulin levels in women with polycystic ovarian syndrome and with irregular periods.

FOLLOW-UP

Section 8 of 12  

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

Complications

The most significant complications are disfigurement in severe facial involvement, renal disease, and, rarely, insulin resistance state.

Prognosis

Acquired partial lipodystrophy is a slowly progressive disease. In the absence of associated renal impairment or insulin resistance, the prognosis is excellent.

Patient Education

• Educating patients about the disease and its associated complications is very important.
• Parents should be notified about facial changes that may occur in their child; they should also be told about the importance of balancing dietary intake in order to avoid metabolic complications and to ensure healthy development.

MISCELLANEOUS

Section 9 of 12  

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

Medical/Legal Pitfalls

These can result from failure to educate patients about the disease and its associated complications.

ACKNOWLEDGMENTS

Section 10 of 12  

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

eMedicine extends its thanks to Irina Lendel, MD, Clinical Instructor in Endocrinology, Division of Endocrinology, Diabetes, and Metabolism, Milton S Hershey Medical Center and Waleed Aldhahi, MD, FRCPC, Clinical Research Fellow, Department of Endocrinology, Joslin Diabetes Center, Harvard University for previous versions of this article.

MULTIMEDIA

Section 11 of 12  

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

Media file 1:  Fat distribution in acquired partial lipodystrophy.
	View Full Size Image
Media type:  Image

REFERENCES

Section 12 of 12

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

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3. Cronin CC, Higgins TJ, Molloy M. Lupus, C3 nephritic factor and partial lipodystrophy. QJM. Apr 1995;88(4):298-9. [Medline].
4. 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].
5. Walker PD. Dense deposit disease: new insights. Curr Opin Nephrol Hypertens. May 2007;16(3):204-12. [Medline].
6. Caramaschi P, Biasi D, Lestani M, et al. A case of acquired partial lipodystrophy associated with POEMS syndrome. Rheumatology (Oxford). Mar 2003;42(3):488-90. [Medline]. [Full Text].
7. 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].
8. 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. [Medline]. [Full Text].
9. Hegele RA, Joy TR, Al-Attar SA, et al. Thematic review series: adipocyte biology. Lipodystrophies: windows on adipose biology and metabolism. J Lipid Res. Jul 2007;48(7):1433-44. [Medline]. [Full Text].
10. Demetriou K, Kallikas I, Zouvani I, et al. The pregnant patient with partial lipodystrophy developing acute renal failure--onset of de novo membranoproliferative glomerulonephritis. Nephrol Dial Transplant. Aug 1998;13(8):2121-4. [Medline]. [Full Text].
11. Meyrier A. The patient with glomerulonephritis and lipodystrophy. Nephrol Dial Transplant. Jan 1997;12(1):226-7. [Medline]. [Full Text].
12. Chopra S, Isaacs R, Mammen K, et al. Renal transplantation in a patient with Barraquer-Simons disease and mesangiocapillary glomerulonephritis type II. Nephrol Dial Transplant. Oct 2000;15(10):1723-4. [Medline]. [Full Text].
13. Garg A. Lipodystrophies. Am J Med. Feb 2000;108(2):143-52. [Medline].
14. Al-Attar SA, Pollex RL, Robinson JF, et al. Quantitative and qualitative differences in subcutaneous adipose tissue stores across lipodystrophy types shown by magnetic resonance imaging. BMC Med Imaging. 2007;7:3. [Medline]. [Full Text].
15. Pujol RM, Domingo P, Xavier-Matias-Guiu, et al. HIV-1 protease inhibitor-associated partial lipodystrophy: clinicopathologic review of 14 cases. J Am Acad Dermatol. Feb 2000;42(2 Pt 1):193-8. [Medline].
16. Guettier JM, Park JY, Cochran EK, et al. Leptin therapy for partial lipodystrophy linked to a PPAR-gamma mutation. Clin Endocrinol (Oxf). Apr 2008;68(4):547-54. [Medline].
17. Walker UA, Kirschfink M, Peter HH. Improvement of acquired partial lipodystrophy with rosiglitazone despite ongoing complement activation. Rheumatology (Oxford). Feb 2003;42(2):393-4. [Medline]. [Full Text].
18. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. Jun 14 2007;356(24):2457-71. [Medline]. [Full Text].
19. Aragona P, Quattrocchi P, Trombetta CJ, et al. Retinal alterations in acquired partial lipodystrophy: a case report. Arch Ophthalmol. Feb 2002;120(2):218-20. [Medline].
20. Biasi D, Caramaschi P, Carletto A, et al. A case of acquired partial lipodystrophy associated with localized scleroderma and undifferentiated connective tissue disease. Rheumatol Int. 1999;19(1-2):75-6. [Medline].
21. Dupéré A, Poulin Y. Facial lipoatrophy following systemic lupus erythematosus. J Cutan Med Surg. May-Jun 2003;7(3):232-5. [Medline].
22. Haque WA, Shimomura I, Matsuzawa Y, et al. Serum adiponectin and leptin levels in patients with lipodystrophies. J Clin Endocrinol Metab. May 2002;87(5):2395. [Medline]. [Full Text].
23. Hisamichi K, Suga Y, Hashimoto Y, et al. Two Japanese cases of localized involutional lipoatrophy. Int J Dermatol. Mar 2002;41(3):176-7. [Medline].
24. Orrell RW, Peatfield RC, Collins CE, et al. Myopathy in acquired partial lipodystrophy. Clin Neurol Neurosurg. May 1995;97(2):181-6. [Medline].
25. Patel D, Page B. Ocular complications in acquired partial lipodystrophy. Postgrad Med J. Nov 2006;82(973):774. [Medline].
26. Poley JR, Stickler GB. Progressive lipodystrophy. A clinical study of 50 patients. Am J Dis Child. Oct 1963;106:356-63. [Medline].
27. Porter WM, O'Gorman-Lalor O, Lane RJ, et al. Barraquer-Simons lipodystrophy, Raynaud's phenomenon and cutaneous vasculitis. Clin Exp Dermatol. Jun 2000;25(4):277-80. [Medline].
28. Winhoven SM, Hafejee A, Coulson IH. An unusual case of an acquired acral partial lipodystrophy (Barraquer-Simons syndrome) in a patient with extrinsic allergic alveolitis. Clin Exp Dermatol. Jul 2006;31(4):594-6. [Medline].

Article Last Updated: Jun 18, 2008