Necrobiosis Lipoidica

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

Practice Essentials

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.

Signs and symptoms of necrobiosis lipoidica

Patients usually present with shiny, asymptomatic 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.

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.

Workup in necrobiosis lipoidica

At low magnification, lesions of necrobiosis lipoidica have a very characteristic appearance. The granulomas are arranged in a tierlike (layered) fashion and are admixed with areas of collagen degeneration.

The main findings on histopathology are thickening of the blood vessel walls and endothelial cell swelling found in the middle to deep dermis, characteristics shared with diabetic microangiopathy.

Direct immunofluorescence microscopy of necrobiosis lipoidica has demonstrated immunoglobulin M (IgM), IgA, the third component of complement (C3), and fibrinogen in the blood vessels, which cause the vascular thickening. [5] In nondiabetic patients with necrobiosis lipoidica, the vascular changes are not as prominent.

Management

Treatment for necrobiosis lipoidica is not very effective, partially because the exact etiology remains unknown. Because localized trauma can cause necrobiosis lipoidica to ulcerate, protection of the legs with elastic support stockings and leg rest may be helpful.

Topical and intralesional corticosteroids can lessen the inflammation of early active lesions and the active borders of enlarging lesions but have little beneficial effect on so-called “burned out” atrophic lesions. In fact, with atrophic lesions, corticosteroid use may cause further atrophy.

Excision and grafting have been successful, but recurrence may take place secondary to the underlying vascular damage. Poor healing of the graft site is not uncommon. [6]

Antiplatelet aggregation therapy with aspirin and dipyridamole has been tried owing to a belief that necrobiosis lipoidica results from platelet-mediated vascular occlusion or immune mechanisms that alter platelet survival. [7] These drugs are thought to prolong platelet survival time and, hence, prevent further worsening of necrobiosis lipoidica. The results of double-blind studies with aspirin and dipyridamole have varied but overall have shown some beneficial effects from the therapy.

Next:

Etiology

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%
Previous
Next:

Epidemiology

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. The aforementioned study by Hashemi et al found that in patients with necrobiosis lipoidica, the median age of those with diabetes was 45.0 years, versus 52.0 years in patients without diabetes. [11]

Necrobiosis lipoidica also shows a sex predilection, being three times more common in women than in men.

Occurrence in the 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 diabetes is controlled.

Previous
Next:

Prognosis

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.

Previous