A New Appraisal of Dermatologic Manifestations of Diabetes Mellitus

Bullosis Diabeticorum

Bullosis diabeticorum is a rare but well-described occurrence of self-resolving, nonscarring blisters that arise on the extremities of diabetic patients. This entity should be distinguished from other primary autoimmune blistering disorders and from simple mechanobullous lesions. Several types of bullosis diabeticorum have been described, with the most classic form showing an intraepidermal cleavage plane.¹⁵ These lesions tend to resolve in weeks but can be recurrent. The location of the pathology underlines its nonscarring nature, though similar lesions have been reported showing a cleavage plane in the lamina lucida of the dermoepidermal junction, which underlines the confusion in the literature surrounding diabetic bullae.¹⁶ Some may even use this term interchangeably with trauma or friction-induced blisters, which diabetics may be prone to develop due to peripheral neuropathy. Confounding reports have stated there is a correlation between bullosis diabeticorum and neuropathy as well as the acral location of these blisters. Although many authors cite the incidence of bullosis diabeticorum being 0.5%,¹⁷ no population-based studies have confirmed this figure and some have speculated that the actual incidence is higher.¹⁸ In the end, the term bullosis diabeticorum is probably best reserved for a rapidly appearing blister on the extremities of diabetic patients with at most minimal trauma, with a lesion containing sterile fluid and negative immunofluorescence. The mechanism for these blisters is thought to be microangiopathy, with scant blood supply to the skin causing it to be more prone to acantholysis and blister formation.¹⁹ This theory was reinforced in a study showing a reduced threshold for suction blister formation in diabetic patients.²⁰ Care should be taken to prevent secondary infections at these sites.

Acanthosis Nigricans

Acanthosis nigricans, which consists of dark brown plaques in the flexural areas, especially the posterior neck and axillae, is a common finding in diabetic patients and is no doubt familiar to clinicians. The pathophysiology of these lesions has been well studied and is a prototype for the effects of insulin resistance in the skin. In this model, high concentrations of insulin binding to insulinlike growth factor receptor in the skin stimulate keratinocyte proliferation,²¹ leading to the clinical appearance and the histologic finding of hyperkeratosis and papillomatosis, which in turn is responsible for the observed hyperpigmentation. It is an important finding, especially in those without a known history of diabetes, as it can also signal an underlying endocrinopathy (eg, Cushing syndrome, acromegaly, polycystic ovary syndrome) or malignancy (ie, adenocarcinoma of the gastrointestinal tract). Several distinct mechanisms of insulin resistance have been described, including insulin resistance due to receptor defects, such as those seen with insulin resistance in NIDDM; autoimmune processes; and postreceptor defects in insulin action.²² Keratolytics and topical retinoids have been used to ameliorate the appearance of these lesions.

Necrobiosis Lipoidica (Diabeticorum)

Necrobiosis lipoidica diabeticorum was first described by Urback²³ in 1932, but reports of similar lesions were described in nondiabetic patients soon after. The dermatologic community has since come to realize that perhaps a more accurate nomenclature is necrobiosis lipoidica to fully encompass this entity. Clinically, lesions appear as erythematous papules and plaques that expand into a larger well-circumscribed plaque with a waxy yellowish atrophic center, often with telangiectases, and usually presenting in the pretibial area. Lesions can become ulcerated in up to one-third of cases. Necrobiosis lipoidica also is defined by characteristic histologic findings, including important features such as palisaded granulomas arranged in a tierlike fashion, necrotizing vasculitis, collagen degradation, and panniculitis. Necrobiosis lipoidica is still relatively rare, developing in approximately 0.3% of patients with diabetes,²⁴ though its relationship with insulin resistance and diabetes is strong. Approximately two-thirds of patients with necrobiosis lipoidica have diabetes and an even higher number go on to develop diabetes or have a positive family history of diabetes.

Although these figures are interesting, the data are nearly a half-century-old, and it is unclear if these findings still hold true today. The etiology of necrobiosis lipoidica also remains elusive, with theories focusing on the role of microangiopathy, immunoglobulin deposition leading to vasculitis, structural abnormalities in collagen or fibroblasts, and trauma; however, the true nature of this condition is likely some combination of these factors.²⁵ These lesions are difficult to treat, especially at an advanced stage. Management with topical steroids to limit the inflammatory progression of the lesions is the mainstay of therapy.

Scleredema

Scleredema adultorum (Buschke disease) refers to indurated plaques over the posterior neck and upper back. It is usually thought of as 3 distinct forms. The form that is known to occur in diabetic patients is sometimes referred to as scleredema diabeticorum; the other 2 occur as postinfectious, usually Streptococcus, or malignancy-related forms. The prevalence of scleredema diabeticorum among diabetic individuals most frequently is reported as 2.5%²⁶; however, it is worth noting that other estimates have been as high as 14%.²⁷ Although there has been some correlation between poorly controlled NIDDM, treatment and tight glucose control does not seem to readily resolve these lesions with only few conflicting case studies serving as evidence for and against this premise.^28-30 The lesions often are recalcitrant toward a wide variety of treatment approaches. Histopathologic analysis generally reveals a thickened dermis with large collagen bundles, with clear spaces between the collagen representing mucin and increased numbers of mast cells. Proposed mechanisms include stimulation of collagen synthesis by fibroblasts and retarded collagen degradation, likely due to excess glucose.³¹