Diabetes Mellitus and the Skin: Recognition and Management of Cutaneous Manifestations

William B. Horton, MD; Patrick L. Boler, MD, PharmD; Angela R. Subauste, MD

Disclosures

South Med J. 2016;109(10):636-646. 

In This Article

Dermatologic Conditions Associated With T2DM

Acrochordons

Acrochordons, often referred to as skin tags, are pedunculated outgrowths of normal skin on a narrow stalk, commonly located on the neck, axillae, eyelids, and groin.[4] They consist of hyperplastic soft dermis and epidermis and are usually skin colored or brownish (Fig. 1A).[8] Acrochordons are relatively common and can be found in approximately 25% to 46% of the adult population, and their number and prevalence increase with advancing age and pregnancy.[9] The link between acrochordons and the metabolic syndrome (obesity, dyslipidemia, hypertension, insulin resistance, and elevated C-reactive protein levels) has been well established.[10,11]

Figure 1.

(A) Acrochordons: skin-colored to pink, fleshy, peduculated papules. (B) Acanthosis nigricans: hyperpigmented, velvety plaques on the neck. Images appear with permission from DermNet NZ. Published online at: http://www.dermnetnz.org.

The diagnosis of acrochordons is based on the clinical appearance and location of the lesions.[4,8] In rare cases they may look suspicious for malignancy and should be sent for histological testing.[4] The presence of acrochordons should be an indicator for the evaluation of possible DM by the PCP, if not previously diagnosed. These lesions often are asymptomatic and do not need to be removed unless desired by the patient for cosmetic reasons or in cases that involve irritation.[4] The treatment of acrochordons consists of excision and can be performed with forceps, fine-grade scissors, cryosurgery with liquid nitrogen, or electrodesiccation.[4,8]

Acanthosis Nigricans

Acanthosis nigricans (AN) is the most widely recognized cutaneous manifestation of DM.[4,12] AN is present in up to 74% of obese adults and can be predictive of hyperinsulinemia; one study found that patients with AN demonstrated higher fasting plasma insulin levels than their nonacanthotic counterparts.[13] It is postulated that in hyperinsulinemic states, excess insulin binds to insulin-like growth factor-1 receptors on keratinocytes and fibroblasts, stimulating hyperproliferation and leading to the development of AN.[14] The presence of AN also is an independent prognostic indicator for the development of T2DM.[4] AN is particularly common in African Americans and the incidence is equal between men and women. Insulin resistance is not the only underlying etiology for AN because it also can be associated with cancer as a result of tumor cell expression of the peptides that enhance the cellular proliferation. AN also has been described in other endocrine disorders (eg, polycystic ovary syndrome, Cushing syndrome, thyroid disease, acromegaly) and with the use of certain drugs (eg, insulin, oral contraceptives, nicotinic acid, corticosteroids, diethylstilbestrol, heroin, fusidic acid, methyltestosterone).[4]

AN is a dermatosis characterized by velvety, papillomatous, brownish-black, hyperkeratotic plaques, located typically on the intertriginous surfaces and neck (Fig. 1B).[15] Diagnosis is largely clinical, with histopathology needed only for the confirmation of unclear cases.[12] The primary treatment consists of managing the underlying cause.[4] Significant weight loss effectively resolves most forms of AN.[4] Topical or systemic retinoids and topical keratinolytics (eg, tretinoin and ammonium lactate creams) can be used to manage cutaneous disease.[4,16]

Eruptive Xanthomatosis

Eruptive xanthomatosis (EX) is a dermatosis characterized by the sudden appearance of yellow papules with an erythematous base on the buttocks, shoulders, and extensor surfaces of the extremities (Fig. 2).[17,18] The sudden appearance of these lesions can be worrisome to patients and may prompt a visit to their PCP for further evaluation.[4] EX is associated with the markedly elevated serum triglyceride levels that occur with hyperlipidemia syndromes (eg, Fredrickson-Levy types I, IV, and V) or with poorly controlled T2DM, hypothyroidism, obesity, pancreatitis, nephrotic syndrome, cholestatic liver disease, dysglobulinemia, and as an adverse effect of certain medications (eg, estrogens, corticosteroids, systemic retinoid agents).[19–22] EX can be the first sign of DM.[4]

Figure 2.

Eruptive xanthomatosis: yellow to erythematous papules on the extensor arm. Image appears with permission from DermNet NZ. Published online at: http://www.dermnetnz.org.

The diagnosis of EX can be made clinically and confirmed with a biopsy of the lesions.[4] Fasting lipid levels should be obtained once the diagnosis is made[4] because patients with EX are at a higher risk of early coronary artery disease and pancreatitis caused by hypertriglyceridemia.[23] The treatment of EX involves management of the underlying condition, and the PCP should aim to lower triglyceride levels with dietary modifications and systemic medications.[20,21,24,25] EX lesions resolve usually within 6 to 8 weeks with appropriate treatment.[20,21]

Scleredema Diabeticorum

Scleredema diabeticorum (SD) is a rare chronic connective tissue disorder that is associated primarily with T2DM.[26] The condition is seen in 2.5% to 14% of patients with DM[27,28] and is most common in obese middle-aged men with T2DM.[4] SD is characterized by thick, indurated, and sometimes erythematous skin on the upper back, neck, and shoulders.[4,26] The skin with SD may have a peau d'orange appearance.[26] Pathogenesis of SD is believed to be linked to increased stimulation of insulin and nonenzymatic glycosylation of collagen,[4] which leads to increased collagen cross-linking, rendering the collagen fibers resistant to degradation by collagenase and leading to increased amounts of collagen overall.[4]

Patients with SD often are asymptomatic, but pain and decreased mobility (especially of the neck and back) may be present in severe cases.[4,26] The diagnosis of SD usually is made based on clinical appearance.[4,26] A definitive diagnosis requires a full-thickness excisional biopsy along with histologic examination of the dermis.[27] Treatments for SD have shown limited benefit.[4,26] Psoralen + ultraviolet A (PUVA) light seems to be the most effective treatment, but others that have demonstrated therapeutic efficacy include potent topical and intralesional steroids (eg, triamcinolone, betamethasone), penicillamine, intralesional insulin, low-dose methotrexate, prostaglandin E1, and pentoxifylline.[26,29–31] Combination therapy with PUVA and physical therapy may help improve mobility in patients with severe SD.[29] Although strict glycemic control has not shown consistent therapeutic benefit for SD, it is proposed to be an effective preventive measure.[26]

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