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Diagnosing And Treating Necrobiosis Lipoidica

Necrobiosis lipoidica is a skin disorder characterized by collagen degradation, granulomatous reaction, blood vessel thickening and lipid deposition. Authors first identified this disorder in patients with diabetes and initially termed it necrobiosis lipoidica diabeticorum but subsequent identification of this condition in non-diabetic patients led to renaming by excluding diabetes from the term.1  

Numerous theories exist regarding the etiology of necrobiosis lipoidica but the exact cause has not been identified. Given this disorder’s frequent occurrence in patients with diabetes, several studies have examined whether pathologic processes (including microangiopathy and abnormal collagen formation) associated with diabetes contribute to the pathogenesis of this disorder. Studies have shown that microvascular changes in the eye and kidney in patients with diabetes are similar to the vascular changes in necrobiosis lipoidica.2-4 Additionally, glycoprotein deposition, the causative agent of diabetic microangiopathy, similarly occurs in necrobiosis lipoidica.3,4

Diabetes has numerous effects on collagen synthesis including increased collagen cross-linking and formation of abnormal collagen fibrils leading to end-organ damage and accelerated aging. Abnormal collagen formation similarly arises in necrobiosis lipoidica and increased collagen cross-linking may contribute to basement membrane thickening in this disorder.4 Other theories to explain the etiology of necrobiosis lipoidica include immunoglobulin deposition, antibody-mediated vasculitis, impaired neutrophil migration and increased tumor necrosis factor-alpha.5

Necrobiosis lipoidica has a 3:1 predilection for females.6 Sixty-five percent of patients with necrobiosis lipoidica have diabetes mellitus but necrobiosis lipoidica is a relatively rare complication of diabetes, occurring in 0.3 percent of the diabetic population.7,8 Research has shown the level of glycemic control in patients with diabetes has no effect on which patients develop necrobiosis lipoidica and improved glycemic control has no effect on the resolution of necrobiosis lipoidica skin lesions.9

Necrobiosis lipoidica skin lesions most commonly arise on the pretibial area. They begin as brown papules that coalesce to form flat, yellow-brown, waxy, atrophic plaques with telangiectasia and surrounding erythema. The skin lesions are typically asymptomatic but can be pruritic or painful. The lesions may ulcerate secondary to trauma.

One commonly makes the diagnosis of necrobiosis lipoidica clinically as the lesions have a distinct appearance. Skin biopsy can confirm diagnosis and is recommended for any atypical lesions. Histopathology of these lesions shows a characteristic granulomatous inflammatory reaction surrounding destroyed collagen, thickened blood vessel walls and endothelial swelling.10  

Established necrobiosis lipoidica skin lesions have a very characteristic appearance but early and atypical lesions can be more difficult to diagnose. Differential diagnoses for necrobiosis lipoidica include granuloma annulare, xanthomas, sarcoidosis, erythema nodosum and venous stasis dermatitis. Rheumatoid nodules have a similar histologic appearance to that of necrobiosis lipoidica skin lesions but a different clinical presentation, appearing as subcutaneous plaques rather than atrophic skin plaques.

How To Treat Necrobiosis Lipoidica

Numerous treatment modalities are available for necrobiosis lipoidica. Topical and intralesional steroid injections can slow the progression of early active lesions and the active borders of chronic lesions. However, careful monitoring is necessary as steroid treatment can increase atrophy and risk of ulceration.6 Authors have used immunomodulating drugs, including ciclosporin, tacrolimus and anti-tumor necrosis factor alpha therapies, to treat necrobiosis lipoidica with variable success rates.11-13 Given the microangiopathy component of necrobiosis lipoidica skin lesions, antiplatelet therapy is another possible treatment modality.

Treatment with aspirin, dipyridamole (Persantine, Boehringer-Ingelheim) or pentoxifylline can have some benefit in the treatment of necrobiosis lipoidica.14,15 Phototherapy and laser therapy have additionally shown benefit in the stabilization and treatment of necrobiosis lipoidica skin lesions.16,17 Clinician have employed surgical excision and grafting but recurrence and poor healing of the graft site is common.18

Necrobiosis lipoidica lesions tend to be chronic in nature with a very poor response to treatment. Ulceration secondary to trauma is a potential complication of these skin lesions and can lead to significant morbidity including pain, delayed healing, infection and scarring. Researchers have reported squamous cell carcinoma in chronic necrobiosis lipoidica skin lesions with ulceration.19

In Summary

Necrobiosis lipoidica is a skin disorder characterized by flat, yellow, atrophic plaques on the shin. While occurring commonly in patients with diabetes, this disorder is not isolated to patients with diabetes. Treatment options for necrobiosis lipoidica are poor and the disorder frequently has a chronic course that can be complicated by ulceration and infection.

References

1.    Rollins TG, Winkelmann RK. Necrobiosis lipoidica granulomatosis. Necrobiosis lipoidica diabeticorum in the nondiabetic. Arch Dermatol. 1960;82:537-543.
2.    Reid SD, Ladizinski B, Lee K, Baibergenova A, Alavi A. Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options. J Am Acad Dermatol. 2013;69(5):783-791.
3.    Thomas M, Khopkar US. Necrobiosis lipoidica: A clinicopathological study in the Indian scenario. Ind Dermatol Online J. 2013;4(4):288-291.
4.    Engel MF, Smith JG, Jr. The pathogenesis of necrobiosis lipoidica. Necrobiosis lipoidica, a form fruste of diabetes mellitus. Arch Dermatol. 1960;82:791-797.
5.    Imtiaz KE, Khaleeli AA. Squamous cell carcinoma developing in necrobiosis lipoidica. Diab Med. 2001;18(4):325-328.
6.    Erfurt-Berge C, Seitz AT, Rehse C, Wollina U, Schwede K, Renner R. Update on clinical and laboratory features in necrobiosis lipoidica: a retrospective multicentre study of 52 patients. Eur J Dermatol. 2012;22(6):770-775.
7.    Lowitt MH, Dover JS. Necrobiosis lipoidica. J Am Acad Dermatol. 1991;25(5 Pt 1):735-748.
8.    Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum. A clinical and pathological investigation of 171 cases. Arch Dermatol. 1966;93(3):272-281.
9.    Cohen O, Yaniv R, Karasik A, Trau H. Necrobiosis lipoidica and diabetic control revisited. Med Hypotheses. 1996;46(4):348-350.
10.    Muller SA, Winkelmann RK. Necrobiosis lipoidica diabeticorum histopathologic study of 98 cases. Arch Dermatol. 1966;94(1):1-10.
11.    Stanway A, Rademaker M, Newman P. Healing of severe ulcerative necrobiosis lipoidica with cyclosporin. Australas J Dermatol. 2004;45(2):119-122.
12.    Rallis E, Korfitis C, Gregoriou S, Rigopoulos D. Assigning new roles to topical tacrolimus. Expert Opin Investig Drugs. 2007;16(8):1267-1276.
13.    Suarez-Amor O, Perez-Bustillo A, Ruiz-Gonzalez I, Rodriguez-Prieto MA. Necrobiosis lipoidica therapy with biologicals: an ulcerated case responding to etanercept and a review of the literature. Dermatology. 2010;221(2):117-121.
14.    Eldor A, Diaz EG, Naparstek E. Treatment of diabetic necrobiosis with aspirin and dipyridamole. N Engl J Med. 1978;298(18):1033.
15.    Littler CM, Tschen EH. Pentoxifylline for necrobiosis lipoidica diabeticorum. J Am Acad Dermatol. 1987;17(2 Pt 1):314-316.
16.    Heidenheim M, Jemec GB. Successful treatment of necrobiosis lipoidica diabeticorum with photodynamic therapy. Arch Dermatol. 2006;142(12):1548-1550.
17.    Moreno-Arias GA, Camps-Fresneda A. Necrobiosis lipoidica diabeticorum treated with the pulsed dye laser. J Cosmet Laser Ther. 2001;3(3):143-146.
18.    Marr TJ, Traisman HS, Griffith BH, Schafer MA. Necrobiosis lipoidica diabeticorum in a juvenile diabetic: treatment by excision and skin grafting. Cutis. 1977;19(3):348-350.
19.    Lim C, Tschuchnigg M, Lim J. Squamous cell carcinoma arising in an area of long-standing necrobiosis lipoidica. J Cutaneous Pathol. 2006;33(8):581-583.

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