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

Lipodystrophy or lipoatrophy is primary idiopathic atrophy of adipose tissue. Lipodystrophy is a very rare disorder with no known etiology. Lipodystrophy can be total, partial, or localized. Total lipodystrophy consists of congenital or acquired complete loss of adipose tissue usually associated with hepatomegaly, hyperglycemia, insulin resistance, hyperlipidemia, and hypermetabolism. Partial lipodystrophy is manifested as symmetric loss of facial fat tissue with or without similar atrophy of the arms and upper part of the trunk. This syndrome has been associated with renal disease, glomerulonephritis, diabetes, hirsutism, hyperlipidemia, hypocomplementemia, and immunological disorders. Localized lipodystrophy is localized loss of adipose tissue usually involving multiple areas. This article focuses on localized lipodystrophy; total and partial lipodystrophy are not discussed further in this article.

Pathophysiology

Localized lipodystrophy or atrophy is localized loss of adipose tissue. Patients with localized lipodystrophy usually have single or multifocal, well-demarcated, atrophic lesions. Some patients have local panatrophy involving muscle, fat, and morphealike changes. Localized lipodystrophy can present as panatrophy that includes the manifestation of hemifacial atrophy.

Associations with localized scleroderma and lichen sclerosus et atrophicus have been noted. One subset group has annular atrophy of the ankles and semicircular lipoatrophy of the anterolateral region of the thighs. Annular lipodystrophy is another form of lipoatrophy in which underlying inflammation has been described. Lipoatrophy can be a common sequela of panniculitis in patients with connective tissue diseases (eg, systemic lupus erythematosus, subcutaneous morphea, the syndrome of lobular lymphocytic connective tissue panniculitis of Winkelmann and Padilha-Goncalves). Lipoatrophy can be associated with nephritis, hypocomplementemia, scleroderma, Sjögren syndrome, recurrent pyogenic infections, immune thrombocytopenic purpura (ITP), and thyroiditis.

The etiology of lipodystrophy is believed to be either inflammatory or noninflammatory. Patients with serologic and immunologic abnormalities tend to have inflammatory patterns on histopathologic examinations, although these changes are not diagnostic of a particular connective tissue disease. These histopathologic abnormalities can be a manifestation of an immunologic disease. Patients with inflammatory patterns tend to have multiple lesions, as opposed to single areas of lipoatrophy. Patients with no inflammatory features have a more benign form of the disease.

Localized lipodystrophy can also be observed in patients having intradermal or subcutaneous injections (eg, insulin, corticosteroids, IM penicillin G, iron dextran, diphtheria/pertussis/tetanus vaccine, acupuncture, recombinant growth hormone). In a 2002 Japanese study by Hisamichi et al, 2 patients with localized involutional lipoatrophy were reported. These patients received intramuscular steroid injections and in the immunohistochemical studies with the antibody against macrophage (anti-CD68 antigen) showed that positive cells were scattered around blood vessels and shrunken lipocytes in the subcutaneous tissues. Most of these cells in the fat lobules were also positive for mucin stains such as Alcian blue.¹ In a 2002 report by Yamamoto et al, 6 patients were reported with localized involutional lipoatrophy who presented with a depressive plaque on the lateral part of their upper arms after receiving injections for allergic rhinitis.²

Lipodystrophy is also a common complication in patients who are infected with HIV and are taking protease inhibitors. This form of lipodystrophy is more of a generalized lipodystrophy and is not discussed in this article. Localized lipoatrophy has also been observed with subcutaneous glatiramer acetate (Copaxone) injection used for the treatment of multiple sclerosis.³

Frequency

United States

Localized lipodystrophy is extremely rare. Other than localized lipodystrophy secondary to injections, only a few case series of lipodystrophic syndromes are reported in the literature.

International

Because localized lipodystrophy is extremely rare, only a few case series of lipodystrophic syndromes are reported in the literature.

Mortality/Morbidity

• The natural course of lipodystrophy is benign. Mortality and morbidity usually depend on associated organ system involvement and comorbid conditions.
• Patients without other organ system involvement experience no disability and are anticipated to have a normal life expectancy.
• Cosmetically, lipodystrophy can be disturbing; in extreme cases, the patient's body self-image can be impaired significantly.

Race

No studies addressing the racial distribution in localized lipodystrophy syndromes exist.

Sex

Females seem to be affected more often than are males, but the ratio is not known.

Age

Lipodystrophy can present at any age, from early infancy through adulthood. Onset usually occurs during the first or second decade of life.

CLINICAL

Section 3 of 10  

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

History

Localized lipodystrophy usually presents as isolated or multiple, atrophic, depressed areas with induration and indentations typically found in the extremities and other parts of the body in early childhood. These lesions may expand and, sometimes, spontaneously disappear. Lesions usually have no overlying skin changes and might have secondary skin pigmentations. Patients generally do not have any underlying diseases or associated symptoms at the time of presentation.

Physical

• Localized lipodystrophy typically presents as depressions of the skin in various areas; lesions are multifocal, well-demarcated, and atrophic.
• • Lesions can be pigmented or nonpigmented, and they usually are painless.
  • Lesions can be as big as 15 cm in diameter.
  • Lesions tend to be located proximally, ie, buttocks, thighs, and upper arms are involved more frequently than lower legs are. The face, scalp, breasts, distal aspects of the extremities, and mucous membranes tend to be spared.
• Some patients have local panatrophy involving muscle, fat, and morphealike changes.
• • Local panatrophy can present as panatrophy that includes the manifestation of hemifacial atrophy.
  • One subset group has annular atrophy of the ankles and semicircular lipoatrophy of the anterolateral region of the thighs. These signs can be observed in subcutaneous and intradermal injection sites.

Causes

The cause of lipodystrophic syndromes is unknown. One subset of the lipodystrophic syndromes is associated with subcutaneous and intradermal injection sites. In this group, trauma may induce the release of macrophage cytokines (eg, tumour necrosis factor, interleukin-1) that might enhance lipocyte catabolism. Impure animal insulin might lead to localized lipodystrophy, possibly because of a cross-reaction with lipid tissues and insulin antibody. Localized lipodystrophy caused by a cross-reaction is very rare with synthetic insulin.

DIFFERENTIALS

Section 4 of 10  

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

Other Problems to be Considered

Congenital partial lipodystrophy
Congenital generalized lipodystrophy
Acquired partial lipodystrophy
Acquired generalized lipodystrophy
Lipodystrophy secondary to protease inhibitor usage in patients infected with HIV
Progressive lipodystrophy
Lipodystrophia progressiva
Barraquer Simons disease (progressive lipodystrophy)
Lipodystrophia facialis
Cephalothoracic brachial form of lipodystrophy
Progressive cephalothoracic lipodystrophy
Lipoatrophic diabetes

WORKUP

Section 5 of 10  

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

Lab Studies

• No specific laboratory blood tests exist to diagnose lipodystrophy.
• Serological markers of systemic connective tissue diseases can be present with the inflammatory type of lipodystrophies.

Imaging Studies

No specific imaging study to diagnose localized lipodystrophy exists.

Other Tests

Histopathological examination is the hallmark of diagnosis.

Procedures

Obtaining a biopsy of lesions is the diagnostic procedure of choice, and performing a histopathological examination might be helpful to diagnose and guide the treatment.

Histologic Findings

Histology depends on the type of lipodystrophy. According to one study, 2 main histopathological subsets exist.⁴ One form, termed involutional fat, is a distinctive picture characterized by lobules of small lipocytes embedded in hyaline connective tissue, peripheral lobular accentuation, absence or scarcity of inflammatory cells, and myxoid stroma with numerous capillaries. Most of the patients with this type of histology have a single lesion, usually of the upper arm. Results of serological studies are normal. Of 3 cases in which direct immunofluorescence was performed, only one patient showed immunoreactants in the blood vessels.

The other type of histology is more of an inflammatory type, with inflammation of the fat. Normal-appearing lipocytes and normal vasculature are present, as well as scattered focal lymphocytes, histiocytes, and plasma cells. This histology involves multiple areas of localized lipoatrophy. In the early biopsy specimens of a series of 4 patients, lymphocytic panniculitis was observed, emphasizing the inflammatory basis for this disorder.⁵

Staging

Classification of partial or localized lipodystrophy involves association with the following:

• Nephritis with low complement levels (membranoproliferative glomerulonephritis)
• Scleroderma
• Sjögren syndrome
• Systemic lupus erythematosus
• Recurrent pyogenic infections
• Thyroiditis secondary to intradermal or subcutaneous injections
• Injection of insulin, corticosteroids, and other medications (eg, IM penicillin G, iron dextrans, diphtheria/pertussis/tetanus vaccine, acupuncture, recombinant growth hormone injections)
• Lipoatrophy secondary to panniculitis of connective tissue disease
• Lupus panniculitis/profundus
• Lymphocytic connective tissue panniculitis
• Localized lipoatrophy
• Annular lipoatrophy
• Abdominal lipoatrophy
• Atrophic panniculitis

TREATMENT

Section 6 of 10  

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

Medical Care

• No specific medical treatment exists.
• Treatment of insulin lipodystrophy consists of reassuring the patient that the condition is benign, switching to purified insulin (pork or human), and having the patient inject insulin in noninvolved areas and rotate the injection sites. This regimen is effective in more than 95% of patients. Improvement begins in 2-4 weeks, and normal consistency generally is restored within 2 months.
• Treatment of underlying immunological disorders might prevent progression of the disease.

Surgical Care

Surgical treatment with adipofascial flaps has been successful in some cases.

Consultations

Dermatological, medical, and surgical consultations are appropriate.

Diet

No specific dietary recommendations or restriction of diet has been recommended.

Activity

No specific activity or restriction of activity has been proposed.

MEDICATION

Section 7 of 10  

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

No specific medical therapy has proven to be beneficial.

FOLLOW-UP

Section 8 of 10  

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

Further Inpatient Care

No specific inpatient care is necessary.

Further Outpatient Care

Follow-up of lesions with biopsies to determine disease activity and obtaining serological markers for immunological disorders might be helpful to guide the treatment.

Deterrence/Prevention

No known method for prevention exists. Controlling the underlying immunological disorder might be preventative.

Complications

• Loss of subcutaneous tissue
• Cosmetic complications

Prognosis

• Prognosis is usually benign. Mortality and morbidity depends on associated organ system involvement and comorbid conditions.
• Patients without other organ system involvement experience no disability and are anticipated to have a normal life expectancy.

Patient Education

• No specific care is required.
• Patients can be taught to change insulin injection sites if lipodystrophy is related to insulin injections.

MISCELLANEOUS

Section 9 of 10  

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

Medical/Legal Pitfalls

• Patients with localized lipodystrophy can have underlying immunological disorders and connective tissue diseases, such as systemic lupus erythematosus, nephritis, Sjögren syndrome, scleroderma, morphea, nephritis, hypocomplementemia, recurrent pyogenic infections, thyroiditis, and ITP. Therefore, localized lipodystrophy should alert physicians to these diseases and disorders. Prompt and appropriate workup is necessary where clinically indicated.
• Recognize localized lipodystrophy at intramuscular, intradermal, and subcutaneous injection sites early and avoid injections in these sites. Insulin lipodystrophy usually occurs at the injection sites, but, sometimes, it occurs elsewhere.
• • Insulin lipodystrophy is more prevalent in females and in patients younger than 20 years.
  • Insulin lipodystrophy usually occurs 3-6 months after initiation of insulin therapy.
  • Before the availability of highly purified insulin, this complication occurred in about 20% of patients.
  • The precise mechanism of insulin lipodystrophy is not understood; however, the mechanism probably is due to an immunologic reaction to impurities in insulin.
  • Insulin lipodystrophy is rare in patients using purified insulin.
  • The absorption of insulin from such areas is unpredictable and may cause erratic or poor glucose control.
  • Although patients usually respond to purified insulin, occasionally, no response to purified insulin occurs. If no response occurs, the addition of dexamethasone to the insulin may be helpful (4 mcg/U).

Special Concerns

• Cosmetically, lipodystrophy can be disturbing. In extreme cases, body self-image can be significantly impaired.

REFERENCES

Section 10 of 10

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

1. Hisamichi K, Suga Y, Hashimoto Y, Matsuba S, Mizoguchi M, Ogawa H. Two Japanese cases of localized involutional lipoatrophy. Int J Dermatol. Mar 2002;41(3):176-7. [Medline].
2. Yamamoto T, Yokozeki H, Nishioka K. Localized involutional lipoatrophy: report of six cases. J Dermatol. Oct 2002;29(10):638-43. [Medline].
3. Soos N, Shakery K, Mrowietz U. Localized panniculitis and subsequent lipoatrophy with subcutaneous glatiramer acetate (Copaxone) injection for the treatment of multiple sclerosis. Am J Clin Dermatol. 2004;5(5):357-9. [Medline].
4. Winkelmann RK, Frigas E. Eosinophilic panniculitis: a clinicopathologic study. J Cutan Pathol. Feb 1986;13(1):1-12. [Medline].
5. Winkelmann RK. [Panniculitis with cellular phagocytosis. Chronic form of histiocytic panniculitis with fever, pancytopenia, polyserositis and lethal hemorrhagic diathesis]. Hautarzt. Nov 1980;31(11):588-94. [Medline].
6. Buyukgebiz A, Aydin A, Dundar B, Yorukoglu K. Localized lipoatrophy due to recombinant growth hormone therapy in a child with 6.7 kilobase gene deletion isolated growth hormone deficiency. J Pediatr Endocrinol Metab. Jan-Feb 1999;12(1):95-7. [Medline].
7. Capanni C, Mattioli E, Columbaro M, Lucarelli E, Parnaik VK, Novelli G, et al. Altered pre-lamin A processing is a common mechanism leading to lipodystrophy. Hum Mol Genet. Jun 1 2005;14(11):1489-502. [Medline].
8. Drago F, Rongioletti F, Battifoglio ML, Rebora A. Localised lipoatrophy after acupuncture. Lancet. May 25 1996;347(9013):1484. [Medline].
9. Koshy CE, Evans J. Facial contour reconstruction in localised lipodystrophy using free radial forearm adipofascial flaps. Br J Plast Surg. Oct 1998;51(7):499-502. [Medline].
10. Peters MS, Winkelmann RK. Localized lipoatrophy (atrophic connective tissue disease panniculitis). Arch Dermatol. Dec 1980;116(12):1363-8. [Medline].
11. Peters MS, Winkelmann RK. The histopathology of localized lipoatrophy. Br J Dermatol. Jan 1986;114(1):27-36. [Medline].

Article Last Updated: Oct 19, 2007