necrobiosis lipoidica

WKP

Definition: Necrobiosis lipoidica is a necrotising skin condition that usually occurs in patients with diabetes mellitus but can also be associated with rheumatoid arthritis.

Necrobiosis lipoidica and granuloma annulare have palisading histiocytes surrounding degenerating collagen, but necrobiosis lipoidica also has thick walled vessels, and many more plasma cells. Plasma cells are much more commonly found in necrobiosis lipoidica.

Mucin stains such as alcian blue and colloidal iron are negative. It is more strongly associated with diabetes mellitus and grossly presents with yellow depressed plaques.

Digital case

 JRC:10727 : Necrobiosis lipoidica

Image

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Localization

The legs, particularly the shins, are overwhelmingly the commonest site of involvement, but lesions may also occur on the forearms, hands, and trunk.

Unusual sites include the nipple, penis, surgical scars, and a lymphedematous arm.

Three-quarters of cases are bilateral at presentation and many more become bilateral later. Lesions may be single but are more often multiple.

Diffuse disease is rare.

Clinical synopsis

Females are affected more than males in a ratio of 3 to 1. The average age of onset in one series was 34 years, but the condition may be seen in children.

It has occurred in monozygotic twins, but not until adult life.

The earliest lesions are red papules which enlarge radially to become patches or plaques with an atrophic, slightly depressed, shiny yellow-brown center and a well-defined raised red to purplish edge. Nodules are uncommon.

Some lesions resolve spontaneously but many are persistent and chronic and may ulcerate; this occurred in 13% of cases in one series.

Rarely, squamous cell carcinoma may arise in long-standing lesions.

Microscopy

The histopathological changes in necrobiosis lipoidica involve the full thickness of the dermis and often the subcutis. Early lesions are not often biopsied. They are said to show a superficial and deep perivascular and interstitial mixed inflammatory cell infiltrate in the dermis. Similar changes are present in septa of adipose tissue. A necrotizing vasculitis with adjacent areas of necrobiosis and necrosis of adnexal structures has also been seen.

In active chronic lesions there is some variability between cases. The characteristic changes are seen at the edge of the lesions. These changes involve most of the dermis but particularly its lower two-thirds.

Areas of necrobiosis may be extensive or slight: they are often more extensive and less well defined than in granuloma annulare. The intervening areas of the dermis are also abnormal.

Histiocytes, including variable numbers of multinucleate Langhans or foreign body giant cells, outline the areas of necrobiosis.

The necrobiosis tends to be irregular and less complete than in granuloma annulare. There is a variable amount of dermal fibrosis and a superficial and deep perivascular inflammatory reaction which, in contrast to the usual picture in granuloma annulare, includes plasma cells.

Occasional eosinophils may be present.

In some cases necrobiotic areas are less frequent and there are collections of epithelioid histiocytes and multinucleate cells, particularly about dermal vessels.

The dermal changes extend into the underlying septa of the subcutis and into the periphery of fat lobules.

This septal panniculitis may resemble erythema nodosum but in that condition there are no significant dermal changes.

Lymphoid cell aggregates, containing germinal centers, are present in the deep dermis or subcutis in approximately 10% of cases of necrobiosis lipoidica.

In old atrophic lesions and in the center of plaques, there is little necrobiosis and much dermal fibrosis.

The underlying subcutis is also fibrotic. Elastic tissue stains demonstrate considerable loss of elastic tissue. Scattered histiocytes may be present.

The presence of lipid in necrobiotic areas (demonstrated by Sudan stains) has been used in the past to distinguish necrobiosis lipoidica from granuloma annulare, but subsequent studies have also shown lipid droplets in granuloma annulare.

Cholesterol clefts may be present, uncommonly, in areas of necrobiosis.[448,490] Rarely they are a conspicuous feature.

Fibrin can also be demonstrated in necrobiotic areas.

There may be small amounts of mucin in the affected dermis but the presence of large amounts in areas of necrobiosis favors a diagnosis of granuloma annulare.

Vascular changes are more prominent in necrobiosis lipoidica, particularly in the deeper vessels.

These range from endothelial swelling to a lymphocytic vasculitis and perivasculitis. Epithelioid granulomas may be present in the vessel wall or adjacent to it.

In old lesions the wall may show fibrous thickening. The smaller, more superficial vessels are increased in number and telangiectatic.

Apart from atrophy and ulceration, epidermal changes are unremarkable in necrobiosis lipoidica. Transepidermal elimination of degenerate collagen has been reported; it may be associated with focal acanthosis or pseudoepitheliomatous hyperplasia. Transfollicular elimination also occurs.

Although in most cases it is possible to distinguish necrobiosis lipoidica from granuloma annulare, there are cases in which this is difficult both clinically and histologically.

There may also be difficulties distinguishing between necrobiosis lipoidica and necrobiotic xanthogranuloma.

Cholesterol clefts and transepidermal elimination may occur in both these conditions.

Clinical features are usually distinctive in necrobiotic xanthogranuloma but not all cases are associated with paraproteinemia or a periorbital distribution of lesions.

Associations

Necrobiosis lipoidica was originally called ‘necrobiosis lipoidica diabeticorum’ but, although some cases are associated with diabetes mellitus, it is not peculiar to diabetes.

In one series only 11% of patients with necrobiosis lipoidica had diabetes mellitus at presentation, while a further 11% developed impaired glucose tolerance/diabetes in the succeeding 15 years.

The incidence in diabetics is low – approximately 3 cases per 1000. It is even lower in childhood diabetes.

The simultaneous occurrence of necrobiosis lipoidica with granuloma annulare and with sarcoidosis has been reported.

It has also been associated with autoimmune thyroid disease, scleroderma, rheumatoid arthritis, and jejunoileal bypass surgery.

The case reported in association with light-chain-restricted plasma cellular infiltrates has been questioned by others as not representing necrobiosis lipoidica.

The association of these lesions with diabetes has already been referred to but the role of this metabolic disorder in the development of the cutaneous lesions is not understood.

Diabetic vascular changes may be important: in some early lesions a necrotizing vasculitis has been described.

Lesions show increased blood flow, refuting the hypothesis that the disease is a manifestation of ischemic disease.

The finding in areas of sclerotic collagen of Glut-1, a protein responsible for glucose transport across epithelial and endothelial barrier tissue, raises the possibility that a disturbance in glucose transport by fibroblasts may contribute to the histological findings.

Adults and children with insulin-dependent diabetes mellitus and necrobiosis lipoidica are at high risk for diabetic nephropathy and retinopathy.

The recent detection of spirochetal organisms in patients with this disease from central Europe, by focus floating microscopy, points to an involvement of B. burgdorferi or other strains in the development of this disease.

A study has shown a decreased number of S100-positive nerves in plaques, in conformity with the cutaneous anesthesia that may be a feature of these lesions.

Immunofluorescence

Immunofluorescence studies have demonstrated IgM and C3 in the walls of blood vessels in the involved skin. Fibrin is seen in necrobiotic areas. IgM, C3, and fibrinogen may be present at the dermoepidermal junction.

Ultrastructure

Ultrastructural studies have shown degeneration of collagen and elastin in the lesions.