Necrobiosis Lipoidica

Necrobiosis Lipoidica

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Necrobiosis lipoidica is a disorder of collagen degeneration with a granulomatous response, thickening of blood vessel walls, and fat deposition. The main complication of the disease is ulceration, usually occurring after trauma. Infections can occur but are uncommon. There have been rare reported cases of squamous cell carcinomas developing in chronic lesions of necrobiosis lipoidica. [1, 2, 3]

The condition was first described in 1929, by Oppehhein, who called it dermatitis atrophicans lipoidica diabetica; in 1932, however, the disease was renamed necrobiosis lipoidica diabeticorum (NLD), by Urbach.

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 the disorder was suggested to exclude diabetes from the title. [4] Today, the term necrobiosis lipoidica is used to encompass all patients with the same clinical lesions, regardless of whether or not diabetes is present.

Despite extensive studies, the etiology of necrobiosis lipoidica is still uncertain. 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.

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 that 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. The pathogenesis of necrobiosis lipoidica has not been demonstrated to be linked to genetic factors.

Tumor necrosis factor (TNF)–alpha has a potentially critical role in conditions such as disseminated granuloma annulare and necrobiosis lipoidica. It is found in high concentrations in the sera and skin in patients with these conditions.

A study by Hammer et al of 64,133 patients with type 1 diabetes found that those with necrobiosis lipoidica tended to have worse metabolic control, a longer duration of diabetes, and a need for higher insulin doses than did the other patients. In addition, a correlation was found between necrobiosis lipoidica and celiac disease, and a greater percentage of patients with necrobiosis lipoidica had elevated thyroid antibodies. [5]

A retrospective study by Erfurt-Berge et al of 100 patients with necrobiosis lipoidica found female sex and middle age to be characteristic of patients with the disease. The investigators also reported that ulceration, seen in 33% of cases, was most prevalent in males and in patients with diabetes mellitus and that thyroid dysfunction occurred in 15% of all cases. [6]

A study by Jockenhöfer et al found that among 262 patients with necrobiosis lipoidica, comorbidities other than diabetes mellitus (34.4% of patients) included essential hypertension (9.2% of patients), obesity (4.6% of patients), chronic heart failure (4.1% of patients), and dyslipidemias (2.3% of patients). [7]

The average age of onset for necrobiosis lipoidica is 30 years, but it can occur at any age. The age of onset ranges from infancy to the eighth decade. The disease tends to develop at an earlier age in patients with diabetes. It also shows a sex predilection, being 3 times more common in women than in men.

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 diabetes is controlled.

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. [1]

From a cosmetic standpoint, the prognosis of necrobiosis lipoidica is poor. Treatment is helpful in halting the expansion of individual lesions, which tend to run a chronic course. Lesional ulcerations can cause significant morbidity, requiring prolonged wound care. These ulcerations can be painful, become infected, and heal with scarring.

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Rhodes EL. Necrobiosis lipoidica treated with ticlopidine. Acta Derm Venereol. 1986. 66(5):458. [Medline].

Handfield-Jones S, Jones S, Peachey R. High dose nicotinamide in the treatment of necrobiosis lipoidica. Br J Dermatol. 1988 May. 118(5):693-6. [Medline].

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

Marr TJ, Traisman HS, Griffith BH, Schafer MA. Necrobiosis lipoidica diabeticorum in a juvenile diabetic: treatment by excision and skin grafting. Cutis. 1977 Mar. 19(3):348-50. [Medline].

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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.

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

Zhang KS, Quan LT, Hsu S. Treatment of necrobiosis lipoidica with etanercept and adalimumab. Dermatol Online J. 2009 Dec 15. 15(12):12. [Medline].

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Barouti N, Cao AQ, Ferrara D, Prins C. Successful treatment of ulcerative and diabeticorum necrobiosis lipoidica with intravenous immunoglobulin in a patient with common variable immunodeficiency. JAMA Dermatol. 2013 Jul. 149(7):879-81. [Medline].

Bonura C, Frontino G, Rigamonti A, Battaglino R, Favalli V, Ferro G. Necrobiosis Lipoidica Diabeticorum: A pediatric case report. Dermatoendocrinol. 2014 Jan 1. 6(1):e27790. [Medline].

Grillo E, Rodriguez-Munoz D, Gonzalez-Garcia A, Jaen P. Necrobiosis Lipodica. Dermatology, Australian Family Physician. 2014. 43(3):129-30.

Lee SY, Shen L, Keimig EL. A solitary red patch. JAMA. 2014 Jun 11. 311(22):2328-9. [Medline].

Lesiak A. Impairment of Angiogenesis in Patients with Granuloma Annulare and Necrobiosis Lipoidica. J Am Acad Dermatol. November 2013. 69(5):783-91.

Lozanova P, Dourmishev L, Vassileva S, Miteva L, Balabanova M. Perforating disseminated necrobiosis lipoidica diabeticorum. Case Rep Dermatol Med. 2013. 2013:370361. [Medline].

Reid SD, Ladizinski B, Lee K, Baibergenova A, Alavi A. Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. J Am Acad Dermatol. 2013 Nov. 69(5):783-91. [Medline].

Tauveron V, Rosen A, Khashoggi M, Abdallah-Lotf M, Machet L. Long-term successful healing of ulcerated necrobiosis lipoidica after topical therapy with becaplermin. Clin Exp Dermatol. 2013 Oct. 38(7):745-7. [Medline].

Wood A, Hamilton SA, Wallace WA, Biswas A. Necrobiotic granulomatous tattoo reaction: report of an unusual case showing features of both necrobiosis lipoidica and granuloma annulare patterns. Am J Dermatopathol. 2014 Aug. 36(8):e152-5. [Medline].

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.

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.

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

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.

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.

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.

Necrobiosis Lipoidica

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