A 63-year-old woman sought evaluation of asymptomatic, nontender, gradually progressing bilateral plaques on her shins. The lesions had arisen 8 months earlier as small, firm, red papules that spread peripherally. The papules had enlarged and developed atrophic centers. The patient had no history of glucose intolerance or diabetes.
Biopsy of the lesions revealed diffuse palisaded and interstitial granulomatous dermatitis that was structured with linear tiers of granulomatous inflammation, which consisted of multinucleated histiocytes aligned parallel to the epidermis. The tiers extended into the deep subcutis. The epidermis was atrophic. There was a superficial and deep perivascular infiltrate predominantly composed of lymphocytes and some plasma cells. Necrobiosis lipoidica (NL) was diagnosed.
Allison Cashman, MD, of Minneapolis notes that NL is 3 times more likely to develop in women than in men.1 About 60% of patients have concurrent diabetes mellitus; 20% have glucose intolerance. The average age of onset is 34 years, although it is earlier in patients with type 1 diabetes mellitus and later in patients with type 2 diabetes mellitus.1
NL may precede the onset of frank diabetes by an average of 2 years in 15% of patients.2 There is no proven connection between the level of glycemic control and the likelihood of lesions developing. In patients with diabetes, NL is associated with a higher rate of diabetic complications, such as peripheral neuropathy, retinopathy, and limited joint mobility.3
In most patients, NL begins as small, firm, erythematous papules with or without slight scale. The papules gradually enlarge and have a center with a "glazed-porcelain" sheen that becomes depressed and atrophic. Mature, or "classic," NL lesions are yellowish brown, waxy, atrophic telangiectatic plaques surrounded by a well-circumscribed, raised, violaceous rim. Ulceration occurs in 13% to 35% of patients.1,4,5
The anterior tibia is most commonly affected. The face, neck, trunk, and forearms also can be involved. The lesions may be accompanied by decreased sensation to pinprick and fine touch, hypohidrosis, and partial alopecia. Squamous cell carcinoma arising within chronic NL lesions has been reported.6,7
The cause of NL is unknown. The finding of immunoreactants deposited in vessel walls of affected sites suggests that NL may be an immunologically mediated vascular disease.8 However, other mechanisms, such as abnormal platelet adhesion, increased thromboxane A2 production, and increased blood viscosity, may be involved.9
The differential diagnosis of NL includes:
- Granuloma annulare.
- Necrobiotic xanthogranuloma.
- Diabetic dermopathy.
- Stasis dermatitis.
- Panniculitis (erythema nodosum, subacute migratory panniculitis, erythema induratum).
- Infectious lipogranuloma (leprosy, tertiary syphilis, dimorphic fungal infections).
- Sclerosing lipogranuloma.
Effective treatments are available, although none have been studied in randomized controlled trials. High-potency topical corticosteroids are considered first-line treatment. Injections of triamcinolone suspension and short courses of systemic corticosteroids may reduce the progression of NL.10 Other therapies include stanozolol, aspirin, dipyridamole, inositol, ticlopidine, pentoxifylline, niacinamide (nicotinamide), topical tretinoin (0.025% gel), topical psoralen UV-A, granulocyte-macrophage colony-stimulating factor bovine collagen, mycophenolate mofetil, and cyclosporine. Spontaneous resolution may occur in 13% to 19% of patients after 6 to 12 years.2
1. Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum. A clinical and pathological investigation of 171 cases. Arch Dermatol. 1966;93:272-281.
2. Odom RB, James WD, Berger TG. Andrews' Diseases of the Skin: Clinical Dermatology. 9th ed. St Louis: WB Saunders Co; 2000.
3. Boulton AJ, Cutfield RG, Abouganem D, et al. Necrobiosis lipoidica diabeticorum: a clinicopathologic study. J Am Acad Dermatol. 1988;18:530-537.
4. Lowitt MH, Dover JS. Necrobiosis lipoidica. J Am Acad Dermatol. 1991;25 (5, pt 1):735-748.
5. Dwyer CM, Dick D. Ulceration in necrobiosis lipoidica--a case report and study. Clin Exp Dermatol. 1993;18:366-369.
6. Clement M, Guy R, Pembroke AC. Squamous cell carcinoma arising in long-standing necrobiosis lipoidica. Arch Dermatol. 1985;121:24-25.
7. Imtiaz KE, Khaleeli AA. Squamous cell carcinoma developing in necrobiosis lipoidica. Diabet Med. 2001;18:325-328.
8. Quimby SR, Muller SA, Schroeter AL. The cutaneous immunopathology of necrobiosis lipoidica diabeticorum. Arch Dermatol. 1988;124:1364-1371.
9. Howard A, White CR. Dermatology. St Louis: Mosby; 2003.
10. Petzelbauer P, Wolff K, Tappeiner G. Necrobiosis lipoidica: treatment with systemic corticosteroids. Br J Dermatol. 1992;126:542-545.