The pathogenesis of DD remains uncertain, but one proposed mechanism is through microvascular damage caused by hyperglycemia-induced, nonenzymatic glycation, possibly in conjunction with mild trauma, that leads to the deposition of hemosiderin and melanin in the skin.20,23 A recent study identified increased vascularization of dermopathy lesions when compared with surrounding tissue.24 Subcutaneous nerve ischemia and degeneration secondary to diabetic neuropathy also have been postulated as causative.20,23 Given the lack of effective therapies and the asymptomatic nature of DD, treatment typically is not pursued. However, DD is associated with other diabetic microvascular complications, including diabetic nephropathy, retinopathy, and neuropathy. For this reason, identification of DD warrants further characterization and management of a patient’s underlying diabetes.19,20
Scleredema Diabeticorum
Scleredema diabeticorum (SD) refers to the slowly progressive, painless thickening and woody induration of the neck, shoulders, and upper back in individuals with long-standing, poorly controlled diabetes. The condition is almost exclusively seen in the diabetic population, with prevalence rates reported to be as high as 14%.25-27 Although SD generally is asymptomatic, some individuals may experience restricted mobility and decreased sensation in affected areas.25,27,28 The diagnosis of SD frequently is missed or ignored clinically. Biopsy can provide diagnostic confirmation of this entity, as histopathology reveals a thickened reticular dermis with an accumulation of collagen and adjacent mucinous infiltrate with no edema or sclerosis.28,29
Although the pathogenesis of SD is not well established, it is theorized that the binding of advanced glycation end products (AGEs) to collagen fibers impairs proper cross-linking and degradation by collagenase.29-31 It is well known that hyperglycemic conditions can promote endogenous formation of AGEs, which occur when reducing sugar molecules become glycated through a nonenzymatic reaction.30-32 The Western diet also is high in preformed AGEs, which are created primarily through certain high-heat cooking methods such as frying and grilling.31,32 Hyperglycemia-induced stimulation of fibroblasts also has been proposed as a driver of increased collagen deposition observed histologically in SD.28,29,33 Treatment of SD can be difficult, as there are no consistently reported therapies, and even improvement in glycemic control does not appear to reverse this condition.29 Case reports have demonstrated some efficacy with various phototherapeutic modalities, including psoralen plus UVA and narrowband UVB phototherapy.34-36
Ichthyosiform Skin Changes
Ichthyosiform skin changes refer to areas of xerosis and scaling that classically present on the anterior distal lower extremities. Although ichthyosiform alterations have been associated with numerous systemic diseases, they often represent an early finding in diabetic patients.27,37 The development of ichthyosiform skin changes has been linked to the formation and accumulation of AGEs, which can cause defective cell adhesion in the stratum corneum.37,38 Treatment with topical emollients and keratolytics may prove beneficial for the skin but do not improve the underlying systemic condition.39
Acrochordons
Acrochordons (skin tags) are common benign fibroepithelial polyps that classically present on the face, neck, and trunk. The underlying mechanism responsible for the development of acrochordons is uncertain, but the association with insulin resistance and impaired carbohydrate metabolism is well validated.40-46 Several large cross-sectional and case-control studies have reported rates of T2DM ranging from 23% to 72% in patients with acrochordons.41,42,47 The pathophysiology may involve an increase in tissue and epidermal growth factors driven by elevated serum insulin levels, stimulation of IGF-1 receptors, and a localized proliferation of cutaneous tissue in elastin-poor areas.45,48,49 Interestingly, the quantity of acrochordons has been positively correlated with fasting blood glucose levels. Additionally, the presence of 30 or more acrochordons was found to increase the risk of developing T2DM.41 Therefore, the presence and number of acrochordons may serve as a convenient indicator of systemic glycemic control and insulin resistance. Screening for T2DM is warranted in individuals without a prior diagnosis who present with multiple acrochordons.
Keratosis Pilaris
Keratosis pilaris (KP) is a benign skin condition characterized by pink-red, erythematous, monomorphic, follicular papules often seen on the extensor arms, thighs, buttocks, and cheeks. Keratosis pilaris is exceedingly common in the general population but occurs more frequently and with more extensive involvement in those with atopic dermatitis and T2DM.27,50,51 The mechanism underlying the hyperkeratosis and inflammatory change observed in KP is not well understood and is likely multifactorial.52,53 Hyperandrogenism, as a consequence of hyperinsulinemia, may play an important role in KP, as elevated circulating androgens are known drivers of keratinocyte proliferation of the pilosebaceous unit of hair follicles.52,54 Support for this theory includes the clinical exaggeration of KP frequently encountered around puberty when androgen levels peak.55,56 Moreover, one study found a higher incidence of KP among adolescent patients with type 1 diabetes mellitus than among healthy age-matched controls.27 The most effective treatment of KP appears to be laser therapy, particularly the Q-switched Nd:YAG laser. Numerous topical modalities have been employed to treat KP but exhibit limited efficacy, including mineral oil, tacrolimus, azelaic acid, and salicylic acid, among others.57