Dermatology Online Journal

Necrobiosis lipoidica
Kathryn O’Reilly MD PhD, Julie Chu MD, Shane Meehan MD, Patricia Heller MD, Robin Ashinoff MD, Lisa Gruson MD
Dermatology Online Journal 17 (10): 18

Department of Dermatology, New York University, New York, New York

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Abstract

A 58-year-old woman presented with a seven-year history of an eruption on her lower legs that was associated with edema, weeping, pruritus, and a burning sensation. Past medical history included Hashimoto thyroiditis, which was diagnosed eight years prior to presentation. Histopathologic examination was consistent with necrobiosis lipoidica (NL). To our knowledge, NL that is associated with Hashimoto thyroiditis has been described in only one prior report. NL is a chronic, cutaneous, granulomatous condition with degenerative connective-tissue changes of unknown etiology. Our patient responded well to a potent topical glucocorticoid and topical tretinoin. Although our patient did not have diabetes mellitus, 75 percent of patients with NL have diabetes mellitus at the time of diagnosis or will subsequently develop diabetes mellitus. This association with diabetes mellitus mandates screening for glucose intolerance in all patients with NL.

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History

A 58-year-old woman presented to the dermatology clinic at the Veterans Affairs New York Harbor Healthcare System in April, 2010, for evaluation of a seven-year history of an eruption on her lower legs that was associated with edema, weeping, pruritus, and a burning sensation. Hashimoto thyroiditis was diagnosed in 2002 and she developed these lesions about one year later. The patient used topical almond oil, olive oil, and zinc oxide paste on the affected areas without improvement.

The patient reported a history of Hashimoto thyroiditis, which was diagnosed in 2002. Laboratory investigation at that time showed an elevated thyroid stimulating hormone (TSH) level as well as elevated anti-thyroglobulin and anti-thyroid peroxidase antibodies. The TSH has since become normal with daily 0.075 mg levothyroxine. In addition to levothyroxine, her medications included fluoxetine and hypromellose eye drops. Medical history also included peripheral venous disease and depression. She reported a drug allergy to diphenhydramine and denied both alcohol consumption and tobacco use. Her family history was non-contributory and the review of systems was negative.

Physical examination

Figure 1	Figure 2

Erythematous and yellow, sharply demarcated, indurated plaques were present on the pretibial aspects of the lower extremities.

Laboratory data

A complete blood count, metabolic panel, liver function tests, and lipid panel were normal. A hemoglobin A1C, thyroid stimulating hormone, T3, and T4 were normal.

Histopathology

Figure 3

There is extensive fibrosis of the reticular dermis with palisaded necrobiosis. The inflammatory infiltrate is superficial and deep and is comprised of lymphocytes, plasma cells, and multinucleated giant cells.

Discussion

Necrobiosis lipoidica (NL) is a chronic, cutaneous, granulomatous condition with degenerative connective tissue changes of unknown etiology. NL usually presents as small papules or nodules that expand into well-demarcated, red-brown-to-yellow plaques, which are typically located on the pretibial portion of the lower extremities [1]. These plaques may grow peripherally and become atrophic and yellow centrally with an elevated erythematous edge. Ulceration of the plaques occurs in up to 25 percent [2]. Although classically localized on the pretibial shins, NL has been described on the penis, trunk, and in a diffuse form [3, 4, 5]. This entity usually appears in young adults and is three times more common in women than it is in men [6]. In 75 percent of patients with NL, diabetes mellitus is present at the time of diagnosis or the patient will subsequently develop diabetes mellitus. NL is, however, only present in 0.03 percent of all diabetic patients [7]. Treatment of comorbid diabetes mellitus does not result in improvement in NL. In addition to diabetes mellitus, NL has been reported in association with sarcoidosis, inflammatory bowel disease, and, as in our case, autoimmune thyroiditis [8, 9]. To our knowledge, this is only the second report of NL associated with Hashimoto thyroiditis [9]. Rare familial cases of NL also have been described and are not associated with glucose dysregulation [10, 11].

The pathophysiology of NL remains unknown. Immune-complex-mediated vascular disease and microangiopathic vessel changes in diabetic patients have been hypothesized as putative causes of collagen degeneration in this condition [6, 12]. IgM and C3 have been reported in the walls of blood vessels in NL lesions, but an extensive histopathologic review showed only mild vascular involvement in just 30 percent of NL lesions [13]. Histopathologic features of NL include layered tiers of necrobiotic granulomatous inflammation in the dermis that are oriented parallel to the skin surface and extend into the subcutaneous fat [1]. Palisaded histiocytes surround degenerated collagen and the epidermis may be normal or atrophic. A superficial and deep, perivascular, lymphocytic infiltrate is present with occasional plasma cells and rare eosinophils. Prominent endothelial-cell swelling, as well as fibrosis and hyalinization of blood-vessel walls, also may be observed [14].

Various NL treatment modalities have been described, but there is no single universally effective modality; no double-blind, randomized, controlled trials have been conducted. Mainstays of treatment include potent topical or intralesional glucocorticoids. Antiplatelet agents such as aspirin and agents that decrease blood viscosity, such as pentoxifylline, also have been used. Topical tretinoin and tacrolimus have been used, as have systemic agents, which include mycophenolate mofetil, cyclosporin, niacinamide, thalidomide, and etanercept [6, 15]. Successful treatment of NL also has been described with PUVA photochemotherapy [16]. Our patient responded well to one month of clobetasol 0.05 percent ointment twice daily and tretinoin cream nightly, with improvement in the induration of the plaques and pruritus. As is recommended for all patients diagnosed with NL, our patient underwent diabetes screening with a serum hemoglobin A1C and fasting serum glucose, which were normal upon diagnosis. A hemoglobin A1C and fasting serum glucose were repeated by the patient’s primary care physician six months later and also were normal.

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