The prevalence of skin disorders in 387 million people diagnosed with diabetes worldwide range from 51.1% to 97%, depending on the region, according to an epidemiologic review published in 2016.1 Cutaneous symptoms are well established consequences of diabetes, but the relationship of these conditions may actually reflect different expressions of a continuum of systemic dysfunction. Current thinking suggests that many common skin disorders may not simply be independent symptoms, but they may represent the first clinical signs of diabetes.2-4 In addition, benign conditions, such as an excess of skin tags or the perpetually flushed look of rubeosis faciei, are commonly predictive of diabetes.2

According to John Barbieri MD, MBA, a practicing dermatologist in Mason, Ohio, and a dermatology research fellow at the University of Pennsylvania in Philadelphia, “There are multiple specific cutaneous symptoms that should be recognized by dermatologists as suggestive of underlying diabetes.” The American Academy of Dermatology (AAD) has identified conditions such as acanthosis nigricans, skin tags, diabetic dermopathy, rubeosis faciei, pruritus, granuloma an­nulare, necrobiosis lipoidica, scleroderma diabeti­corum, and bullosis diabeticorumas possible precursors to diabetes.2-4 The correlation is so striking that the AAD has recommended that patients receive glucose metabolism testing for diabetes whenever these conditions are detected.2 This association is supported in part by a 2017 review that concluded that screening was definitely warranted in the presence of acanthosis nigricans, skin tags, or bullosis diabeticorum , and possibly in the presence of other disorders, too.4

Highly Predictive Disorders

“Most predominantly, Acanthosis nigricans, characterized by dark, velvety thickening of the skin in the skin folds, often around the neck and armpits, is an important sign that could suggest insulin resistance or diabetes,” Dr Barbieri told us. When first identified in 1889, acanthosis nigricans was linked to obesity. The PRIME study found that patients with acanthosis nigricans were nearly twice as likely as healthy individuals to have markers of type 2 diabetes, including elevated fasting glucose, insulin, and insulin resistance.5

Sometimes called “shin spots” because of the round or oval hyperpigmented macules observed on the lower limbs, diabetic dermopathy has also been pathogenomically linked to diabetes and other microvascular complications of diabetes, such as retinopathy and peripheral neuropathy.4 Dr Barbieri explained that diabetic dermopathy  is typically “characterized by small, asymptomatic dull red to pink papules on the shins that can evolve to become well-demarcated atrophic brown macules and patches with fine scale, and may affect up to half of patients with diabetes.” 


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Treating Skin Disorders That Are Comorbid With Diabetes

Although cutaneous symptoms are treated in patients with diabetes in the same manner as in the nondiabetic population, Dr Barbieri suggested that conditions such as dermatophytosis might warrant more aggressive treatment in those with diabetes to reduce the risk for cellulitis and other complications. “Diabetic dermopathy is one of the most common skin findings in patients with existing diabetes,” he noted, adding that, “There is no clearly effective treatment for diabetic dermopathy and some lesions may resolve spontaneously over time.”

Infections

“Individuals with diabetes are more prone to cutaneous infections, such as cellulitis, dermatophytosis, and candidiasis, which may be more challenging to treat,” Dr Barbieri explained. Infection has been reported in about 20% of patients diagnosed with diabetes.1 Most infections are fungal in origin, due to Candida albicans, causing fungal overgrowth (appearing as reddened rashes surrounded by tiny blisters or scales) in areas of the body where excess skin moisture can develop, such as the armpits, under the breasts, between the thighs, the groin area, and between the fingers and toes.6 Fungal infections are often chronic, and although they may cause discomfort, are not considered serious or life threatening.

Although less common, bacterial infections such as styes, boils, folliculitis, nail infections, and carbuncles that occur in the deeper layers of the skin and the subdermal tissues are of particular concern in patients diagnosed with diabetes. These infections are most often caused by Staphylococcus aureus and tend to promote painful inflammations that make the skin become hot, swollen, and reddened.6

Shared Pathologic Mechanisms

Both diabetes and skin dysfunction have been linked to insulin resistance. Chronic hyperglycemia because of poor glycemic control induces oxidative stress at the cellular level, and in turn, promotes endothelial dysfunction and vascular inflammation. Left to develop, these processes contribute to the rapid aging of the skin and promote the development of multiple skin disorders.7

Insulin resistance occurring in the early stages of diabetes contributes to a systemic imbalance of growth factors, cytokines and hormones, setting the stage for skin conditions such as acanthosis nigricans .4,7 “The pathologic mechanisms underlying acanthosis nigricans are poorly understood, but proposed mechanisms include abnormalities involving insulin-like growth factor receptor-1, fibroblast growth factor receptor, and epidermal growth factor receptor signaling pathways,” Dr Barbieri said.

Other less severe skin signs, such as yellowed skin and nails, thickened skin, and generalized pruritus are commonly seen in patients who have been diagnosed with diabetes, and can be used as markers of active disease. Likewise, an accumulation of skin tags in 1 or more regions of the body often points to poor glycemic control and suggests attention to strict management of diabetes.2-4

Management of Cutaneous Symptoms

Careful monitoring and outpatient follow-up of cutaneous symptoms can be a very useful practice in the management diabetes. In addition to indicating the need for testing in undiagnosed individuals, skin manifestations can provide markers of therapeutic lack of adherence or suboptimal response to current therapy in patients who are already diagnosed with diabetes. Early detection and dermatologic management of skin symptoms are important to the maintenance of general health and the prevention of complications in patients with diabetes.1

References

1.  de Macedo GMC, Nunes S, Barreto T. Skin disorders in diabetes mellitus: an epidemiology and physiopathology review. Diabetol Metab Syndr. 2016;8:63 doi: 10.1186/s13098-016-0176-y

2. Diabetes: 12 warning signs that appear on your skin. American Academy of Dermatology https://www.aad.org/public/diseases/a-z/diabetes-warning-signs. Accessed August 3, 2020.

3. Karadag AS, Ozlu E, Lavery MJ. Cutaneous manifestations of diabetes mellitus and the metabolic syndrome.

Clin Dermatol. 2018 Jan-Feb;36(1):89-93. doi: 10.1016/j.clindermatol.2017.09.015. Abstract

4. Bustan RS, Wasim D, Yderstræde KB, Bygum A. Specific skin signs as a cutaneous marker of diabetes mellitus and the prediabetic state – a systematic review. Dan Med J. 2017;64(1):A5316.

5. Kong AS, Williams RL, Rhyne R et al. Acanthosis nigricans: high prevalence and association with diabetes in a practice­based research network consortium – a primary care multi­ethnic network (PRIME Net) study. J Am Board Fam Med.2010;23:476­85.

6. American Diabetes Association website. https://www.diabetes.org/diabetes/complications/skin-complications. Accessed August 6, 2020.

7. Kochet K, Lytus I, Svistunov I, Sulaieva O. Skin pathology in diabetes mellitus: clinical and pathophysiological correlations (review). Georgian Med News. 2017 Dec;(273):41-46.PMID: 29328028 Review. Russian. Abstract.

This article originally appeared on Dermatology Advisor