Necrobiosis lipoidica – an old but challenging dermatosis

Introduction

Necrobiosis lipoidica (NL) is chronic granulomatous disease involving both dermis and subcutaneous tissue, first described in 1929 by Oppenheim [1]. Necrobiosis lipoidica presents as indolent shiny plaques in most cases localized on lower extremities. Usually, the disease progresses from red-brown telangiectatic lesions to atrophic, depressed and sclerotic plaques. It is considered that NL occurs mainly in diabetic patients, but there is increasing evidence about its concomitance with sarcoidosis, connective tissue diseases (CTD) and inflammatory bowel diseases (IBD) [2–4]. Based on data from the literature, about 75% of NL patients also suffer from diabetes mellitus (DM) [5], but NL occurs in only 0.3–1% of diabetic patients [6]. The association between NL and DM remains equivocal; there are still patients who develop these lesions in absence of DM. The histopathological picture of NL demonstrates an inflammatory process with granuloma formation, degeneration of collagen and thickening of endothelium. Granulomas, composed predominantly of lymphocytes and histiocytes with occasional plasma cells and eosinophils, are arranged in a layered fashion. Reduction of intradermal nerves and perivascular lymphocyte concentration is a supplementary feature of NL [7]. The pathogenesis of NL remains unknown, although many investigators have considered diabetic microangiopathy. Other conceptions about development of NL include immunoglobulin deposition in the endothelium and platelet aggregation dysfunction [7, 8]. Słowik-Kwiatkowska et al. [9] demonstrated that increased tumor necrosis factor (TNF)-α production in NL leads to impaired angiogenesis, which results in microangiopathy. There are also no guidelines about treatment of NL; immunosuppressive drugs such as cyclosporine, corticosteroids and antimalarials are not always effective, but there is increasing evidence that phototherapy combined with psoralen administration (PUVA) is efficient [10].

Objective

In this article we present a case of NL which was very challenging in both diagnosis and treatment.

Case report

The 44-year-old woman was admitted to our hospital with a 3-year history of skin lesions (fig. 1). Six months before admission, the diagnosis of deep tuberculoides chronic granulomatous infiltrate based on histopathological findings, was established, and in that time she was treated with isoniazid and rifampicin without the expected improvement. During the first hospitalization clinical examination revealed slightly painful red-brown atrophic plaques with visible blood vessels located on both shanks. Some small areas showed crusting and superficial ulceration. The histopathological analysis suggested the diagnosis of necrobiosis lipoidica. We decided to administer phototherapy combined with psoralen, but 72 cycles of PUVA bath did not bring a satisfactory effect. The next pathological examination revealed the presence of granulomas and fibrosis in the dermis, accompanied by an inflammatory infiltrate. The diagnosis suggested chronic granulomatous dermatitis, which could be observed in sarcoidosis, tuberculosis or necrobiosis lipoidica; nevertheless, the chest X-ray did not indicate any disorder. We performed polymerase chain reaction, but mycobacterial DNA was not detected in biopsy specimens. Then, we started dapsone therapy (100 mg per day), which resulted in blanching and flattening of skin lesions and healing of minor ulcerations (fig. 2). After 2 months of dapsone therapy, side effects from the gastrointestinal tract (nausea, mucous erosion and oral dryness) and paresthesias on both legs were observed, so it was discontinued. Additionally, atrophic plaques were enlarged again and new skin changes were noticed. The third pathological examination revealed perivascular macrophage infiltration and focal necrobiosis, with the suggestion of polyarteritis nodosa, necrobiosis lipoidica or granuloma annulare. We decided to include cyclosporine therapy in a dose of 300 mg per day. The performed venereal disease research laboratory test (VDRL) and anti-nuclear antibody levels were both negative, and other laboratory examination results were within normal limits. Skin changes were still painful and without any signs of clinical remission. Lack of improvement in the patient’s condition resulted in the fourth biopsy, which clearly suggested necrobiosis lipoidica. Cyclosporine therapy was replaced by methylprednisolone and pentoxifylline, but no significant remission of skin lesions was observed, although the patient reported reduction of pain. The patient remains under observation in an outpatient clinic, but after various therapies we did not achieve clinical remission (fig. 3).

Discussion

Necrobiosis lipoidica is an idiopathic dermatological condition, and very few studies have been conducted in order to establish its pathogenesis. The age of onset varies between infancy and late adulthood, and in most cases NL occurs in the third decade [11]. Necrobiosis lipoidica also has a sex predilection, being three times more common in women than in men [11]. One of the main problems with NL is its clinical similarity to other skin conditions: morphea, sarcoidosis and granuloma annulare [12]. Both morphea and NL can present as isolated yellow patches on sclerotic skin, but NL can be distinguished from morphea by telangiectasias around the lesions. In the case of sarcoidosis, cutaneous symptoms range from nodules and rashes to erythema nodosum. Skin atrophy occurs rather rarely, but in our case the absence of radiological abnormalities excluded sarcoidosis from the differential diagnosis. In the early form of necrobiosis lipoidica, superficial annular lesions can resemble granuloma annulare, as in our case [12]. These data indicate that the diagnosis of NL is time consuming. In our case the final diagnosis was established after four biopsies.
Treatment of necrobiosis lipoidica is challenging and usually marginally effective. Previously, we reported effectiveness of PUVA therapy in NL [10]. After a series of sessions we observed remission of skin lesions in some cases. Despite our promising results, in the reported case long-term photochemotherapy did not bring any improvement. The presence of inflammatory infiltrate in examined skin specimens was the reason why dapsone was introduced as a new treatment modality. Anti-inflammatory properties of dapsone could explain some regression of the lesions in our case, but this therapy should be discontinued because of side effects. Literature data indicate effectiveness of cyclosporine A in the treatment of NL [13]. In the present case 3 months of treatment with cyclosporine A did not bring sufficient improvement or even slight pain reduction.
Systemic and topical treatment with corticosteroids is one of the most widely used therapies in the treatment of NL, but in our case long-term therapy with methylprednisolone has not brought detectable clinical improvement. Nevertheless, Petzelbauer et al. [14] described successful 5-week systemic corticosteroid therapy with complete regression of skin lesions and no recurrence within 7 months after treatment. Also, vascular drugs are widely used in therapy of NL. Basaria and Braga-Basaria [15] and Littler and Tschen [16] reported successful treatment of NL with pentoxifylline, but in our case it was ineffective.

Conclusions

Despite a thorough diagnostic process including numerous histopathological examinations and laboratory tests, the diagnosis of NL was significantly delayed. Lack of treatment guidelines is also another problem, so the applied therapy is mainly based on dermatologists’ clinical experience. Good outcomes achieved by other doctors were not confirmed in our case. We present this case report as it was challenging both in differential diagnosis and treatment.

Conflict of interest

The authors declare no conflict of interest.

References

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Received: 3 VIII 2015
Accepted: 6 X 2015