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.

https://www.jaad.org/article/S0190-9622(13)00653-1/pdf

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

https://www.derm.theclinics.com/article/S0733-8635(02)00018-9/pdf

Cutaneous manifestations of diabetes mellitus

Diabetes is the most common endocrine disorder, affecting 8.3% of the population (1). Skin disorders will be present in 79.2% of people with diabetes (2). A study of 750 patients with diabetes found that the most common skin manifestations were cutaneous infections (47.5%), xerosis (26.4%), and inflammatory skin diseases (20.7%) (2). Individuals with type 2 diabetes are more likely than those with type 1 diabetes to develop cutaneous manifestations. Cutaneous disease can appear as the first sign of diabetes or may develop at any time in the course of the disease. This review provides a brief overview of skin conditions that primary care providers (PCPs) may encounter when treating patients with diabetes.

### Acanthosis Nigricans

Acanthosis nigricans (AN) is likely the most readily recognized skin manifestation of diabetes (3). It is present in up to 74% of obese adult patients and can be predictive of the existence of hyperinsulinemia (4). The presence of AN is a prognostic indicator for developing type 2 diabetes. There is also a possible genetic predisposition or increased sensitivity of the skin to hyperinsulinemia in different ethnic groups. At the same obesity rates, prevalence of AN is lowest in whites (0.5%), higher in Hispanics (5%), and even higher in African Americans (13%) (5).

AN is a hyperpigmented velvety thickening of skin folds, presenting predominantly in the neck, axilla, and groin areas (Fig. 1). Possible additional presentations could include skin tags and hyperkeratosis. Heredity, obesity, endocrine disorders, certain drugs, and malignancy are associated with AN. Benign AN type 2 is related to type 2 diabetes, and pseudo-AN type 3 is associated with the metabolic syndrome. Type 2 diabetes–related AN has an insidious onset and initially presents as hyperpigmentation. Both underlying conditions present with insulin resistance (3). Children aged 8–14 years who had AN were found to have insulin resistance, …

https://clinical.diabetesjournals.org/content/diaclin/33/1/40.full.pdf

Cutaneous Manifestations of Diabetes Mellitus

Non-infectious granulomatous diseases of the skin are a broad group of distinct reactive inflammatory conditions that share important similarities. As a group, they are relatively difficult to diagnose and distinguish both clinically as well as histologically. Many of these disorders have significant associations with systemic diseases that impact the patient’s overall prognosis. In this update, we offer a discussion of emerging concepts and controversies in this field, as presented through evidence-based answers to seven important clinical questions regarding palisading and epithelioid granulomata. These questions offer an opportunity to review ten non-infectious granulomatous conditions that have implications for systemic disease: granuloma annulare, annular elastolytic giant cell granuloma, necrobiosis lipoidica, methotrexate-induced accelerated rheumatoid nodulosis, necrobiotic xanthogranuloma, interstitial granulomatous dermatitis, interstitial granulomatous drug reaction, palisaded neutrophilic granulomatous dermatitis, sarcoidosis, and metastatic Crohn disease. Recent clinical, epidemiologic, and laboratory studies have shed some light on these diseases, the association of these conditions with systemic disorders, and their overall prognoses.

Non-infectious granulomatous diseases of the skin and their associated systemic diseases: an evidence-based update to important clinical questions.

Cutaneous granulomatosis is a heterogeneous group of diseases, characterized by a skin inflammatory reaction triggered by a wide variety of stimuli, including infections, foreign bodies, malignancy, metabolites, and chemicals. From a pathogenic point of view, they are divided into non-infectious and infectious granulomas. Pathophysiological mechanisms are still poorly understood. Non-infectious granulomatous skin diseases include granuloma annulare, necrobiosis lipoidica, rheumatic nodules, foreign body granulomas, cutaneous sarcoidosis, and interstitial granulomatous dermatitis. Necrobiosis lipoidica is more frequent in diabetic patients. Infectious granulomas of the skin are caused by mycobacteria, in particular Mycobacterium tuberculosis or atypical mycobacteria; parasites, such as Leishmania; or fungi. Pathogenic mechanisms of M. tuberculosis-related granuloma are discussed. From a clinical point of view, it is useful to divide cutaneous granulomatosis into localized and more disseminated forms, although this distinction can be sometimes artificial. Three types of localized granulomatous lesions can be distinguished: palisaded granulomas (granuloma annulare, necrobiosis lipoidica, and rheumatoid nodules), foreign body granulomas, and infectious granulomas, which are generally associated with localized infections. Disseminated cutaneous granulomas can be divided into infectious, in particular tuberculosis, and non-infectious forms, among which sarcoidosis and interstitial granulomatous dermatitis. From a histological point of view, the common denominator is the presence of a granulomatous inflammatory infiltrate in the dermis and/or hypodermis; this infiltrate is mainly composed of macrophages grouped into nodules having a nodular, palisaded or interstitial architecture. Finally, we propose which diagnostic procedure should be performed when facing a patient with a suspected cutaneous granulomatosis.

Cutaneous Granulomatosis: a Comprehensive Review

Although it is commonly accepted that necrobiosis lipoidica (NL) is associated with diabetes mellitus (DM), there is some controversy regarding the degree of this association. In a retrospective review of 65 patients with NL attending our dermatology out-patient clinics we found that just seven (11%) were known to have DM at the time of presentation. Seven further patients (11%) were diagnosed as having impaired glucose tolerance/DM at presentation and over a 15-year follow-up period. Thus, only a minority of our patients with NL had DM.

Necrobiosis lipoidica: only a minority of patients have diabetes mellitus.

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Necrobiosis lipoidica: only a minority of patients have diabetes mellitus.