eMedicine Specialties > Dermatology > Metabolic Diseases

Necrobiosis Lipoidica

Author: Cheryl J Barnes, MD, Dermatologist, McIntosh Clinic, PC
Coauthor(s): Loretta Davis, MD, Professor, Department of Internal Medicine, Division of Dermatology, Medical College of Georgia
Contributor Information and Disclosures

Updated: Jul 31, 2009

Introduction

Background

In 1929, Oppehhein first described necrobiosis lipoidica diabeticorum and called it dermatitis atrophicans lipoidica diabetica, but it was later renamed necrobiosis lipoidica diabeticorum (NLD) by Urbach in 1932. In 1935, Goldsmith reported the first case in a nondiabetic patient. Other cases of necrobiosis lipoidica diabeticorum in nondiabetic patients were described by Meischer and Leder in 1948. Rollins and Winkelmann in 1960 also described this condition in nondiabetic patients, and a renaming of this disorder was suggested to exclude diabetes from the title.1 Today, the term necrobiosis lipoidica (NL) is used to encompass all patients with the same clinical lesions regardless of whether or not diabetes is present.

Pathophysiology

Necrobiosis lipoidica is a disorder of collagen degeneration with a granulomatous response, thickening of blood vessel walls, and fat deposition. The exact cause of necrobiosis lipoidica is unknown, but the leading theory of necrobiosis lipoidica has focused on diabetic microangiopathy. Other theories suggest trauma or inflammatory or metabolic changes. Still other theories suggest that an antibody-mediated vasculitis may cause the changes seen in necrobiosis lipoidica.

Frequency

United States

Necrobiosis lipoidica has been described in about 0.3% of diabetic patients. In one study, necrobiosis lipoidica was shown to precede the onset of diabetes mellitus in 15% of patients. In addition, 60% of patients had the diagnosis of diabetes mellitus prior to the onset of necrobiosis lipoidica, while 25% of patients had lesions that appeared with the onset of diabetes mellitus. The presence or progression of necrobiosis lipoidica does not correlate with how well the diabetes is controlled.

Mortality/Morbidity

Treatment for necrobiosis lipoidica is not very satisfactory. The disease is typically chronic with variable progression and scarring. Squamous cell cancers have been reported in older lesions of necrobiosis lipoidica related to previous trauma and ulceration.2

Race

Necrobiosis lipoidica has been reported to occur in all races with no predilection.

Sex

Necrobiosis lipoidica is 3 times more common in women than in men.

Age

The average age of onset is 30 years, but it can occur at any age. The age of onset ranges from infancy to the eighth decade. Necrobiosis lipoidica tends to develop at an earlier age in patients with diabetes.

Clinical

History

  • Patients usually present with asymptomatic shiny patches that slowly enlarge over months to years. The patches are initially red-brown and progress to yellow, depressed atrophic plaques.
  • Ulcerations can occur typically after trauma and occasionally with associated pain.
  • The patient's main complaint is the unsightly cosmetic appearance of the lesions.
  • The clinical appearance of necrobiosis lipoidica is distinctive, yet there are many atypical presentations and early forms can be hard to recognize.
    • Superficial annular lesions can resemble granuloma annulare.
    • Yellow annular lesions of necrobiosis lipoidica with a fatty infiltration can resemble xanthomas.
    • Necrobiotic xanthogranuloma (NXG) is a rare disease that can mimic necrobiosis lipoidica clinically and histologically. NXG has been associated with paraproteinemia and some hematologic malignancies, which is not the case with necrobiosis lipoidica.
    • Sarcoidosis of the skin can appear like necrobiosis lipoidica both clinically and histologically.
    • Rheumatoid nodules also have a histologic appearance similar to necrobiosis lipoidica but clinically appear like subcutaneous nodules rather than atrophic plaques.
    • Ulcerated necrobiotic lesions also have been described in patients with rheumatoid arthritis.

Physical

  • Skin lesions of classic necrobiosis lipoidica begin as 1- to 3-mm well-circumscribed papules or nodules that expand with an active border to become waxy, atrophic, round plaques centrally. Initially, these plaques are red-brown in color but progressively become more yellow and atrophic in appearance.


Typical presentation of necrobiosis lipoidica on ...

Typical presentation of necrobiosis lipoidica on the lower pretibial legs.

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Typical presentation of necrobiosis lipoidica on ...

Typical presentation of necrobiosis lipoidica on the lower pretibial legs.



Red-brown plaque with yellow atrophic center on ...

Red-brown plaque with yellow atrophic center on lower leg.

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Red-brown plaque with yellow atrophic center on ...

Red-brown plaque with yellow atrophic center on lower leg.

  • Most cases of necrobiosis lipoidica occur on the pretibial area but cases have been reported on the face, scalp, trunk, and upper extremities where the diagnosis is more likely to be missed.
    • Multiple telangiectatic vessels can be seen on the surface of the thinning epidermis.
    • Ulceration at the site of trauma and subsequent infection are occasional complications of necrobiosis lipoidica.
  • The Koebner phenomenon has been well established in patients with necrobiosis lipoidica, especially in patients with vasculitis at the site of trauma.3
  • Miller reported a case of a woman with known type 1 diabetes mellitus who developed biopsy-proven necrobiosis lipoidica in a cholecystectomy scar and also on her abdomen at insulin injection sites.
  • In most patients, the lesions of necrobiosis lipoidica are typically multiple and bilateral. The lesions may become painless because of cutaneous nerve damage in 75% of the cases, or they can be extremely painful in 25% of the cases.

Causes

Necrobiosis lipoidica remains a disease of questionable etiology despite extensive studies. The pathogenesis has not been demonstrated to be linked to genetic factors.

  • Because of the strong relationship between diabetes and necrobiosis lipoidica diabeticorum, many studies have focused on diabetic microangiopathy as the leading etiologic theory. Diabetic alterations of the kidney and eye vasculature are similar to the vascular changes seen in necrobiosis lipoidica. A deposition of glycoprotein in blood vessel walls may be the cause of diabetic microangiopathy. A similar glycoprotein deposition is seen in necrobiosis lipoidica. Also see Bullous Disease of Diabetes.
  • Another theory is based on the deposition of immunoglobulins, the third component of complement and fibrinogen in the blood vessel walls of patients with necrobiosis lipoidica. Some believe an antibody-mediated vasculitis may initiate the blood vessel changes and subsequent necrobiosis in necrobiosis lipoidica.
  • An additional etiologic theory focuses on the abnormal collagen in necrobiosis lipoidica. It is well established that abnormal and defective collagen fibrils have been responsible for diabetic end-organ damage and accelerated aging. Lysyl oxidase levels have been found in some diabetic persons to be elevated and are responsible for increased collagen cross-linking. Increased collagen cross-linking could explain basement membrane thickening in necrobiosis lipoidica.
  • Other theories link trauma and inflammatory and metabolic changes as a possible etiology. It also has been found that there may be impaired neutrophil migration leading to an increased number of macrophages possibly explaining the granuloma formation in necrobiosis lipoidica.

More on Necrobiosis Lipoidica

Overview: Necrobiosis Lipoidica
Differential Diagnoses & Workup: Necrobiosis Lipoidica
Treatment & Medication: Necrobiosis Lipoidica
Follow-up: Necrobiosis Lipoidica
Multimedia: Necrobiosis Lipoidica
References
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References

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  2. Lim C, Tschuchnigg M, Lim J. Squamous cell carcinoma arising in an area of long-standing necrobiosis lipoidica. J Cutan Pathol. Aug 2006;33(8):581-3. [Medline].

  3. Miller RA. The Koebner phenomenon. Int J Dermatol. May 1982;21(4):192-7. [Medline].

  4. Ullman S, Dahl MV. Necrobiosis lipoidica. An immunofluorescence study. Arch Dermatol. Dec 1977;113(12):1671-3. [Medline].

  5. Clayton TH, Harrison PV. Successful treatment of chronic ulcerated necrobiosis lipoidica with 0.1% topical tacrolimus ointment. Br J Dermatol. Mar 2005;152(3):581-2. [Medline].

  6. Stanway A, Rademaker M, Newman P. Healing of severe ulcerative necrobiosis lipoidica with cyclosporin. Australas J Dermatol. May 2004;45(2):119-22. [Medline].

  7. Eldor A, Diaz EG, Naparstek E. Treatment of diabetic necrobiosis with aspirin and dipyridamole. N Engl J Med. May 4 1978;298(18):1033. [Medline].

  8. Littler CM, Tschen EH. Pentoxifylline for necrobiosis lipoidica diabeticorum. J Am Acad Dermatol. Aug 1987;17(2 Pt 1):314-6. [Medline].

  9. Zeichner JA, Stern DW, Lebwohl M. Treatment of necrobiosis lipoidica with the tumor necrosis factor antagonist etanercept. J Am Acad Dermatol. Mar 2006;54(3 Suppl 2):S120-1. [Medline].

  10. Kolde G, Muche JM, Schulze P, Fischer P, Lichey J. Infliximab: a promising new treatment option for ulcerated necrobiosis lipoidica. Dermatology. 2003;206(2):180-1. [Medline].

  11. Kukreja T, Petersen J. Thalidomide for the treatment of refractory necrobiosis lipoidica. Arch Dermatol. Jan 2006;142(1):20-2. [Medline].

  12. Spenceri EA, Nahass GT. Topically applied bovine collagen in the treatment of ulcerative necrobiosis lipoidica diabeticorum. Arch Dermatol. Jul 1997;133(7):817-8. [Medline].

  13. De Rie MA, Sommer A, Hoekzema R, Neumann HA. Treatment of necrobiosis lipoidica with topical psoralen plus ultraviolet A. Br J Dermatol. Oct 2002;147(4):743-7. [Medline].

  14. Beattie PE, Dawe RS, Ibbotson SH, Ferguson J. UVA1 phototherapy for treatment of necrobiosis lipoidica. Clin Exp Dermatol. Mar 2006;31(2):235-8. [Medline].

  15. Heidenheim M, Jemec GB. Successful treatment of necrobiosis lipoidica diabeticorum with photodynamic therapy. Arch Dermatol. Dec 2006;142(12):1548-50. [Medline].

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  20. Heymann WR. Necrobiosis lipoidica treated with topical tretinoin. Cutis. Jul 1996;58(1):53-4. [Medline].

  21. Durupt F, Dalle S, Debarbieux S, Balme B, Ronger S, Thomas L. Successful treatment of necrobiosis lipoidica with antimalarial agents. Arch Dermatol. Jan 2008;144(1):118-9. [Medline].

  22. Boyd AS. Treatment of necrobiosis lipoidica with pioglitazone. J Am Acad Dermatol. Nov 2007;57(5 Suppl):S120-1. [Medline].

  23. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med. Sep 9 2004;351(11):1106-18. [Medline].

  24. Ellis CN, Varani J, Fischer GJ, Zeigler ME, Pershadsingh HA, Benson SC, et al. Troglitazone improves psorasis and normalizes models of proliferative skin disease:ligand for perioxisome proliferators-activated receptor - gamma inhibit keratinocyte proliferation. Arch Dermatol. May/2000;136:609-616.

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  33. Soler NG, McConnachie PR. HLA antigens and necrobiosis lipoidica diabeticorum--a comparison between insulin-dependent diabetics with and without necrobiosis. Postgrad Med J. Dec 1983;59(698):759-62. [Medline].

  34. Stawiski MA, Voorhees JJ. Cutaneous signs of diabetes mellitus. Cutis. Sep 1976;18(3):415-21. [Medline].

  35. Wake N, Fang JC. Images in clinical medicine. Necrobiosis lipoidica diabeticorum. N Engl J Med. Nov 2 2006;355(18):e20. [Medline].

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Further Reading

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Keywords

necrobiosis lipoidica, necrobiosis lipoidica diabeticorum, NLD, dermatitis atrophicans lipoidica diabetica, collagen degeneration, diabetic microangiopathy, vasculitis

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Contributor Information and Disclosures

Author

Cheryl J Barnes, MD, Dermatologist, McIntosh Clinic, PC
Cheryl J Barnes, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Loretta Davis, MD, Professor, Department of Internal Medicine, Division of Dermatology, Medical College of Georgia
Loretta Davis, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
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

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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