What causes necrobiosis lipoidica, and what are the comorbidities?

Updated: Mar 06, 2020
  • Author: Cheryl J Barnes, MD; Chief Editor: George T Griffing, MD  more...
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Answer

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 (C3), 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. [8]

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. [9]

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). [10]

A multicenter, retrospective study by Hashemi et al of patients with necrobiosis lipoidica found that 58.5% had diabetes. The prevalence of other comorbidities were also higher than in the Jockenhöfer study and included the following [11] :

  • Obesity - 51.6%
  • Hypertension - 45.2%
  • Dyslipidemia - 43.6%
  • Thyroid disease - 24.5%

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