Non-infectious Granulomatous Diseases of the Skin and their Associated Systemic Diseases: An Evidence-based Update to Important Clinical Questions

Elena Balestreire Hawryluk; Leonid Izikson; Joseph C. English III


Am J Clin Dermatol. 2010;11(3):171-181. 

In This Article

2. is Necrobiosis Lipoidica Always Associated with Concurrent, Antecedent, or Subsequent Diabetes Mellitus?

NL is a necrotizing skin disease that often starts with a 'bruised' appearance, not necessarily corresponding to a known injury, often localized to the patient's anterior shins. The expanding border of the lesions is erythematous, while the central area turns yellow in color, with atrophy and prominent telangiectasias. The disorder was previously regarded as necrobiosis lipoidica dibeticorum, but the nomenclature was changed because a significant number of patients do not have concurrent diabetes. Skin lesions may precede, coincide with, or occur after onset with diabetes, or occur independently from glucose dysregulation.

NL is present in a small percentage of patients with diabetes (0.3%), although diabetes is present in most patients with NL.[25] According to a 1966 study of 19 patients who were non-diabetic at the time of diagnosis and had NL for an average of 10 years, 42% were ultimately diagnosed with diabetes, and many with normal glucose tolerance test results had a family history of diabetes.[25] However, a more recent retrospective review of patients from three hospitals in Dublin in 1999 suggests the association with glucose dysregulation is far less prominent: their pool of 65 NL patients included 11% with diabetes, 18% with a family history of diabetes, and only 11% with impaired glucose tolerance over a 15-year follow-up period.[26] Even if the magnitude is less strong than originally suggested, the data suggest that patients with NL may have a predisposition to abnormal glucose metabolism or subclinical endocrine dysfunction related to insulin action. Interestingly, when NL patients are compared with diabetic patients, NL patients have increased retinopathy and proteinuria in both adult and pediatric populations.[27,28] Accordingly,NL patients should be monitored for changes in glucose metabolism and possible end-organ damage.

NL is certainly more common among diabetic versus control populations. Even in young patients, a study comparing skin manifestations in young type 1 diabetic patients (mean age 12.5 years) with healthy control subjects found that NL occurred in 5 of 122 diabetic patients compared with 0 of 196 control subjects.[29] However, compared with other skin conditions that afflict diabetic patients, NL was much less prevalent than xerosis and rubeosis, and occurred at a similar frequency as skin changes of the hand (Huntley papules).[29]

The role of genetics in NL pathogenesis is unclear. Rare cases of familial NL, not associated with diabetes or impaired glucose tolerance, have been described in the literature.[30–32] A recent case report by Shimanovich et al.[33] describes NL in monozygotic twins with type 2 diabetes, suggesting that genetics may play an important role in disease pathogenesis. It is possible that diabetes, a family history of diabetes, and impaired glucose tolerance may be proxy phenotypes for other genes or physiologic processes involved in NL pathogenesis.

2.1 Summary and Recommendations

The pathophysiologic relationship between NL and diabetes is not mechanistically understood, although there is clearly an association between NL and impaired glucose tolerance in many patients, and genetics may play a role. Given the data, patients with NL should be screened for diabetes, and diabetic NLpatients should be monitored closely to evaluate for signs of end-organ damage.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: