Review
Update on necrobiosis lipoidica: A review of etiology, diagnosis, and treatment options

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Necrobiosis lipoidica (NL) is a rare chronic granulomatous disease that has historically been associated with diabetes mellitus. Debate exists regarding the etiology and pathogenesis of NL with a widely accepted theory that microangiopathy plays a significant role. NL typically presents clinically as erythematous papules on the front of the lower extremities that can coalesce to form atrophic telangiectatic plaques. NL is usually a clinical diagnosis, but if the clinical suspicion is uncertain, skin biopsy specimen can help differentiate it from sarcoidosis, necrobiotic xanthogranuloma, and granuloma annulare. NL is a difficult disease to manage despite a large armamentarium of treatment options that include topical and intralesional corticosteroids, immunomodulators, biologics, platelet inhibitors, phototherapy, and surgery. Randomized control trials are lacking to evaluate the many treatment methods and establish a standard regimen of care. Disease complications such as ulceration are common, and lesions should also be monitored for transition to squamous cell carcinoma, a less common sequelae.

Section snippets

Epidemiology

NL is a rare disorder with a female predominance (female to male ratio of 3:1). Age of onset is typically around the third decade of life in patients with type 1 diabetes and fourth decade in patients with type 2 diabetes and in nondiabetics.6, 7 The incidence of NL in people with diabetes is only 0.3% to 1.2%.7 NL precedes a diagnosis of diabetes in up to 14% of patients, is diagnosed simultaneously in up to 24%, and appears after a diagnosis of diabetes in up to 62%.6, 7 Up to half of these

Etiology and pathogenesis

The origin and pathogenesis of NL remains unclear with the leading theory involving microangiopathy as a result of glycoprotein deposition in the vasculature resulting in thickening of blood vessels.9 Boateng et al9 demonstrated lower oxygen tension of blood vessels at the site of NL lesions using Doppler analysis, suggesting that hypoxia is a part of the pathogenesis.9 Ngo et al10 later refuted this study, demonstrating that blood flow was higher in NL lesions as compared with unaffected skin.

Clinical presentation and complications

NL lesions typically present as 1 to 3 asymptomatic, well-circumscribed papules and nodules with active erythematous borders that slowly coalesce into plaques. The plaques appear violaceous and contain a central area that initially appears red-brown, but later progresses to a yellow-brown discoloration (Fig 1). The central area often contains atrophic, waxy, and eroded skin. Telangiectasis can develop as a direct result of collagen degeneration occurring beneath the epidermis. NL lesions can

NL and diabetes

There is much debate regarding the nature of the correlation between NL and diabetes. Studies from the 1960s established the precedent that over 60% of patients with NL had diabetes or abnormal glucose metabolism. This has been challenged by later studies that were unable to reproduce such a definitive correlation. A study of 65 patients with NL by O'Toole et al15 found that diabetes was present in only 11%, with an additional 5% being given a diagnosis of diabetes later in life. Sampling

Treatment options

NL has historically been a difficult disease to treat, with current therapeutic options producing minimal and inconsistent results. A multitude of case reports have described the use of several treatments (Table I), but large randomized placebo-controlled trials are lacking.

Lifestyle modifications are important to minimize risk of NL complications, primarily the avoidance of trauma. Once ulcerated, healing may be difficult. A palpable dorsalis pedis or posterior tibialis pulse indicates

Conclusion

Despite years of research, the origin of NL remains unknown. The relationship between NL and diabetes continues to be investigated, with more current literature suggesting a lesser correlation. Further, no effective treatment regimens have been established. Currently, there are several off-label treatment options with varying results that can be offered to patients. The condition may also resolve spontaneously without treatment, although few epidemiologic studies have examined the rates of

References (72)

  • J. Peyri et al.

    Necrobiosis lipoidica

    Semin Cutan Med Surg

    (2007)
  • S.K. Kota et al.

    Necrobiosis lipoidica diabeticorum: a case-based review of literature

    Indian J Endocrinol Metab

    (2012)
  • B. Boateng et al.

    Cutaneous microcirculation in pretibial necrobiosis lipoidica: comparative laser Doppler flowmetry and oxygen partial pressure determinations in patients and healthy probands

    Hautarzt

    (1993)
  • B. Ngo et al.

    Skin Blood flow in necrobiosis lipoidica diabeticorum

    Int J Dermatol

    (2008)
  • S.A. Muller et al.

    Necrobiosis lipoidica diabeticorum histopathologic study of 98 cases

    Arch Dermatol

    (1966)
  • S.R. Quimby et al.

    The cutaneous immunopathology of necrobiosis lipoidica diabeticorum

    Arch Dermatol

    (1988)
  • C. Lim et al.

    Squamous cell carcinoma arising in an area of long-standing necrobiosis lipoidica

    J Cutan Pathol

    (2006)
  • J. Santos-Juanes et al.

    Squamous cell carcinoma arising in long-standing necrobiosis lipoidica

    J Eur Acad Dermatol Venereol

    (2004)
  • M. Clement et al.

    Squamous cell carcinoma arising in long-standing necrobiosis lipoidica

    Arch Dermatol

    (1985)
  • E.A. O'Toole et al.

    Necrobiosis lipoidica: only a minority of patients have diabetes mellitus

    Br J Dermatol

    (1999)
  • J.E. Jelinek

    Cutaneous manifestation of diabetes mellitus

    Int J Dermatol

    (1994)
  • N.G. Soler et al.

    HLA antigens and necrobiosis lipoidica diabeticorum–a comparison between insulin-dependent diabetics with and without necrobiosis

    Postgrad Med J

    (1983)
  • A.D. Souza et al.

    Does pancreas transplant in diabetic patients affect the evolution of necrobiosis lipoidica?

    Int J Dermatol

    (2009)
  • C.E. Attinger et al.

    Angiosomes of the foot and ankle and clinical implications for limb salvage: reconstruction, incisions, and revascularization

    Plast Reconstr Surg

    (2006)
  • S.C. Wu et al.

    Foot ulcers in the diabetic patient, prevention and treatment

    Vasc Health Risk Manag

    (2007)
  • R.G. Sibbald et al.

    Special considerations in wound bed preparation 2011: an update

    Adv Skin Wound Care

    (2011)
  • C. Barde et al.

    Intralesional infliximab in noninfectious cutaneous granulomas: three cases of necrobiosis lipoidica

    Dermatology

    (2011)
  • O. Suarez-Amor et al.

    Necrobiosis lipoidica therapy with biologicals: an ulcerated case responding to etanercept and a review of the literature

    Dermatology

    (2010)
  • B. Bouhanick et al.

    Necrobiosis lipoidica: treatment by hyperbaric oxygen and local corticosteroids

    Diabetes Metab

    (1998)
  • W.R. Heymann

    Necrobiosis lipoidica treated with topical tretinoin

    Cutis

    (1996)
  • A. Patsatsi et al.

    Necrobiosis lipoidica: early diagnosis and treatment with tacrolimus

    Case Rep Dermatol

    (2011)
  • Y. Binamer et al.

    Treatment of ulcerative necrobiosis lipoidica with topical calcineurin inhibitor: case report and literature review

    J Cutan Med Surg

    (2012)
  • E.A. Spenceri et al.

    Topically applied bovine collagen in the treatment of ulcerative necrobiosis lipoidica diabeticorum

    Arch Dermatol

    (1997)
  • H.I. Beck et al.

    Treatment of necrobiosis lipoidica with low-dose acetylsalicylic acid: a randomized double-blind trial

    Acta Derm Venereol

    (1985)
  • H.I. Beck et al.

    Skin blood flow in necrobiosis lipoidica during treatment with low-dose acetylsalicylic acid

    Acta Derm Venereol

    (1988)
  • M.C. Heng et al.

    Healing of necrobiotic ulcers with antiplatelet therapy: correlation with plasma thromboxane levels

    Int J Dermatol

    (1989)
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    Conflicts of interest: None declared.

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