Features of the skin of patients with diabetes mellitus

Svetlana Galnykina , MD, PhD, professor, member of the American Academy of Dermatology

In patients with diabetes mellitus, lesions of the skin and mucous membranes are often diagnosed; they are nonspecific manifestations of this disease and occur in approximately 30% of patients. Sometimes these changes can be the first to signal danger; they are characterized by a unique clinical picture and a severe course. It is generally accepted that about 55% of dermatoses appear in the first year of the disease, and 80% after 5 years.

Most of the dermatological pathology combined with diabetes mellitus is not caused by the degree of carbohydrate metabolism disorder, so the administration of insulin does not produce a special therapeutic effect on it. So, let's analyze this pathology.

Diabetes is the most common endocrine disease, affecting about 8.3% of the population. Skin manifestations are typically present in 79.2% of people with diabetes. A study of 750 patients with diabetes found that the most common skin manifestations were skin infections (47.5%), dryness (26.4%), and inflammatory skin diseases (20.7%). They were more common in patients with type 2 diabetes than in those with type 1 diabetes.

Skin diseases can be the first sign of diabetes or develop at any time during the course of the disease. In this review, we provide a short list of problems that doctors who practice in the field of dermatocosmetology may encounter when working with patients suffering from diabetes.

Conditions associated with insulin resistance

Acanthosis Nigricans (acanthosis nigricans)

Acanthosis nigricans is probably the most easily recognized cutaneous manifestation of diabetes. It is present in more than 74% of obese adults and may be a predictive marker for hyperinsulinemia and the development of type 2 diabetes. There may also be a genetic predisposition or increased skin sensitivity to hyperinsulinemia in different ethnic groups.

It manifests itself as hyperpigmented velvety thickenings of skin folds, mainly in the neck, axillary and groin areas. Additional manifestations in the form of hyperkeratosis are possible. Heredity, obesity, endocrine disorders, certain medications and malignant neoplasms can cause this pathology.

Acrochordons

Acrochordons, or fibroepithelial polyps, soft fibromas are outgrowths on a narrow stalk, most often appear on the skin of the eyelids, neck, armpits and inguinal folds. They are detected in approximately 25% of the adult population, and as a rule, their number and prevalence increase with age.

Acrochordons are benign in nature, but symptomatic irritation or necrosis may be observed. Redness or blackening of skin growths is the result of twisting of the base, resulting in impaired blood supply. The diagnosis of acrochordons is based on the clinical picture. In cases of suspected malignant process, histological examination is recommended.

Treatment is usually aimed at removing formations using various methods. Excision can be performed using tweezers and scissors, as well as using cryo- or radio wave therapy using the fulguration method.

Diabetic dermopathy

Large-scale studies conducted in Sweden indicate that diabetic dermopathy (DD) develops in 33% of patients with type 1 diabetes mellitus and in 39% of patients with type 2 diabetes mellitus. However, a more recent study found that DD is present in only 0.2% of people with well-controlled type 2 diabetes.

DD are small (less than 1 cm), well-demarcated spots or papules on the lower legs and are considered a sign of insulin resistance. The rash may disappear on its own within 1–2 years, leaving atrophic hypopigmentation in the affected areas. Little is known about the relationship between diabetic dermopathy and diabetes. There are studies indicating the presence of hemosiderin and melanin deposits in the epidermis of such patients.

Diabetic dermopathy does not require treatment, since it is asymptomatic and does not affect the general condition.

Eruptive xanthomas

Eruptive xanthomas (EC) are sudden onset rashes of yellow papules with an erythematous base on the buttocks, elbows, knees, etc. EC is rare and is more often found in patients with poorly controlled type 2 diabetes mellitus. The sudden appearance of EC can be an alarming symptom for patients, a kind of signal to visit a doctor.

Such rashes may also be the first sign of diabetes. A decrease in lipoprotein lipase activity in diabetes leads to the accumulation of triglycerides in the blood serum. At times, when serum triglyceride levels reach 2000 mg/dL, lipids will be deposited in the skin. Skin manifestations are associated with types I, III, IV, and V hypertriglyceridemia and depend on the presence of secondary hyperlipidemia. EC lesions tend to resolve spontaneously within 14 weeks.

The diagnosis can be made clinically and confirmed by biopsy of the lesions. It is important to monitor fasting lipid levels. People with EC have a higher risk of developing early coronary heart disease and pancreatitis. Treatment should be aimed at reducing triglyceride concentrations through dietary adjustments and systemic medications to reverse the condition and reduce complications.

Rubeose

Rubeosis, or facial redness, is a relatively common skin condition associated with diabetes and is a microangiopathic complication. This may go unnoticed by patients and doctors. However, its presence should alert clinicians to look for other microangiopathic complications, such as retinopathy.

Pathology is observed in 3-5% of people with diabetes. It often occurs in childhood and adolescence in patients with insulin-dependent diabetes on the skin of the forehead, cheeks (less often, chin), hyperemia in the form of a slight blush is observed, which is sometimes combined with thinning of the eyebrows. Diabetic erythema occurs as ephemeral erythematous spots, which are observed mainly in men over 40 years of age who have had diabetes for a short time. These spots are characterized by large sizes, sharp boundaries, rounded outlines and a rich pink-red color. They are localized mainly on open skin: face, neck, dorsum of the hand. Subjective sensations are either absent, or patients complain of a slight tingling sensation. The spots have a very short lifespan (2-3 days) and disappear spontaneously.

The appearance of rubeosis on the face is correlated with poor glucose control. No treatment is required. Strict glycemic control may improve appearance and prevent complications of microangiopathy in other organ systems. This pathology is especially important for the diagnosis of doctors practicing in the field of dermatocosmetology, since such patients can turn to them, regarding it, first of all, as a cosmetic defect.

Epidermal necrolysis/Stevens-Johnson syndrome

Stevens-Johnson syndrome is a rare disease, occurring in 1-6 cases per million people per year worldwide. The more severe form is called toxic epidermal necrolysis and is diagnosed in 0.4-1.2 cases per million people per year. Because of their similar etiology, pathogenesis, clinical and histological manifestations, it has been proposed to combine both pathologies under the name epidermal necrolysis (EN).

In most cases, the disease begins after exposure to the inciting drug within 8 weeks of the first dose. The dipeptidyl peptidase-4 inhibitor sitagliptin has been associated with cases of Stevens-Johnson syndrome. The condition may present with fever, headache, rhinitis, cough, general malaise and dysphagia. After 1-3 days, EN progresses to skin erosions, necrosis and detachment of the epidermis, severe stomatitis and eye damage.

Currently, the study of the pathophysiology of EN continues. No strong cellular immune response involving pathogen-specific natural killer cells and CD8 + T lymphocytes was observed. This reaction also involves monocytes and granulocytes. Other factors that enhance the response are still being investigated. The end result of hypersensitivity is damage by apoptosis to keratinocytes of the epidermis and mucous membranes. Although drugs and their compounds are often the most common etiological causes of EN, viruses, Mycoplasma pneumoniae and immunization can also lead to this condition. More than 100 drugs have been identified as causes of EN. If a patient develops EN while taking sitagliptin, the manufacturer of the drug recommends discontinuing therapy immediately after the onset of a hypersensitivity reaction.

EN is a life-threatening complication. Current treatments include stopping the medications that lead to this complication. Prompt elimination of medications started in the last 8 weeks is especially important. The benefit of immunosuppressants has not been proven. Patients with EN should be admitted to the intensive care unit as soon as possible.

Conditions associated with type 1 diabetes

Necrobiosis lipoidica

Necrobiosis lipoidica (NL) is rare, occurring in 0.3-1.6% of people with type 1 diabetes, more often in women than men. Typical NL lesions occur in young and middle-aged patients as painless oval plaques with a yellow atrophic center and a red to purple color at the periphery. Lesions are usually multiple and bilateral. They can ulcerate spontaneously or due to trauma. 11-65% of patients with NL are diagnosed with type 1 diabetes during skin testing. 90% of people with ND who do not have diabetes eventually develop it (mostly type 1 diabetes). Glucose level control has no effect on the course of NL.

The cause of the condition is currently unknown. Suspected causes include local trauma, microangiopathies, fibrin deposits, and metabolic changes. Despite the fact that NL is a benign disease, its cosmetic manifestations cause discomfort to patients.

The main treatment method for necrobiosis lipoidica currently is local or, less commonly, systemic use of glucocorticosteroids. Their use is effective in the early stages of the disease, but is not able to help in the presence of an atrophic component of the lesions and may worsen the atrophy. Other treatments that have been used include pentoxifylline, cyclosporine, ticlopidine, infliximab and thalidomide. Some authors point to the effectiveness of nicotinamide, clofazimine, chloroquine, etc.

Vitiligo

Vitiligo is diagnosed in 0.3-0.5% of the world's population, making it the most common pigmentation disorder. Patients typically have areas of skin and hair depigmentation.

A 2009 study of 50 patients with type 1 diabetes found that 4% of patients had vitiligo. Genetic vitiligo is most often a gradually progressive disease and does not respond to treatment. However, in some cases it is possible to stop progression.

Dermatological therapy aims to reduce the T-cell response and induce melanocyte migration and regeneration. Calcipotriol, excimer laser, pulse corticosteroid therapy and surgical treatment are used. These procedures are long and complex, with numerous side effects. Moderate exposure to sunlight is recommended.

The psychosocial component of the disease is significant and negatively affects the quality of life of such patients.

Diabetic pemphigus (diabetic bullae)

Diabetic pemphigus, or diabetic bullae, occurs in 0.5% of patients with type 1 diabetes. This condition occurs more often in men and in patients with long-standing peripheral neuropathy. The lesions occur spontaneously, primarily on the dorsum of the lower leg and foot. Sometimes they are visible on the forearms and arms. The lesions are present as transparent bullous elements on a non-inflamed base. They are painless and contain a sterile liquid. The size of the damage can vary from a few millimeters to several centimeters.

Diabetic pemphigus usually appears in people who have had type 1 diabetes for many years. However, it may also be the first sign of diabetes. The lesions resolve on their own within 2-5 weeks. The differential diagnosis includes bullous pemphigoid, which can be excluded by biopsy of the lesion followed by direct and indirect immunofluorescence. The lesions resemble porphyria cutanea tarda, autoimmune bullosis, erythema or toxicderma.

Treatment focuses on preventing infections. If the blisters become large, their contents are aspirated, leaving the tire intact to leave a protective skin barrier. Saline compresses can be used to relieve symptoms. Treatment with antibiotics or corticosteroids is usually not required.

Other diabetes-related complications

Psoriasis

Psoriasis is a chronic inflammatory polygenic skin disease with environmental triggers such as injury, medications, and infections. Psoriasis is characterized by erythematous scaly papules and plaques that occur most commonly in areas of friction such as the scalp, elbows, knees, arms, legs, torso, and nails. Histologically, psoriasis presents with epidermal growth changes, intermittent parakeratosis, and multiple biochemical, immunological, and vascular abnormalities. This disease can develop at any age, with the most common onset between 15 and 30 years of age; rarely - in children under 10 years of age. It affects 2-3% of the world's population. About 9% of people with diabetes (type 1 or 2) have psoriasis. Recent studies have shown that psoriasis may indicate a predisposition to the development of diabetes, as well as coronary heart disease and stroke. One study of 52,000 people concluded that people with psoriasis had a 49-56% higher risk of developing type 2 diabetes later in life.

Lichen planus

Lichen planus is a disease of the skin and mucous membranes that affects less than 1% of the total population. It often begins in middle age (30-60 years). However, the prevalence of lichen planus in people with type 1 or type 2 diabetes has been reported to be 2-4%. Lichen planus can affect the skin (called "cutaneous" with several variations), as well as the lining of the mouth, genitals, or esophagus.

Lichen planus appears as grouped, symmetrical, erythematous to violet, flat-surfaced polygonal papules, distributed mainly in the extremities, but may also have other localizations. Variants may include ulcerative and verrucous types.

Clinically, cutaneous lichen planus appears as a flat-topped, violet-like papular rash on the skin. Papules can be several millimeters in diameter or coalesce to form larger plaques. Fine white lines known as Wickham's grooves may be visible on the surface of the papules or plaques. Diagnosis can be made based on clinical findings. If it is in doubt, a biopsy is indicated. The etiology of the disease is unknown.

Lichen planus falls under the purview of a dermatologist. Its treatment is aimed at eliminating itching, using glucocorticosteroids in the form of ointments and creams. Injections of glucocorticosteroids are used for more extensive lesions.

Xerosis

Xerosis is the medical term for dry skin. It is the second most common skin manifestation in people with diabetes. In a study of 100 patients with diabetes mellitus and skin lesions, dry skin was present in 44% of patients. Healthcare providers should teach patients to maintain skin hygiene, including using creams or lotions to maintain skin moisture.

Diabetic scleroderma

Diabetic scleroderma occurs in approximately 2.5-14% of people with diabetes. It is more common in middle-aged men with obesity and type 2 diabetes. In patients with diabetic scleroderma, the disease is often asymptomatic; however, neck and back pain may be bothersome. Diagnosis is often made clinically, although definitive diagnosis is confirmed by skin biopsy.

The pathogenesis of diabetic scleroderma is believed to be associated with increased insulin stimulation and non-enzymatic glycosylation of collagen.

Treatment includes corticosteroids, methotrexate and phototherapy. Differential diagnosis is carried out with Buschke's scleroderma, also associated with type 1 diabetes. Buschke's scleroderma appears as thickening of the skin, mainly on the neck, shoulders and upper extremities. Goes away spontaneously over several months or years. Women are affected more often than men. Diabetic scleroderma affects the fingers, arms and torso.

Granuloma annulare

Granuloma annulare (GA) presents as erythematous, flesh-colored papules that coalesce to form an oval or annular lesion. HA is often asymptomatic, but may cause itching or burning. The relationship between granuloma annulare and diabetes is controversial. Skin lesions can often precede diabetes. Patients with recurrent manifestations of GC should undergo a glucose tolerance test.

The pathogenesis of GC is currently unknown. Treatment options include corticosteroids, isotretinoin, dapsone, antimalarials, and phototherapy. Sometimes the lesions may regress spontaneously. HC tends to be idiopathic, however, it can be associated with diabetes and with diseases such as autoimmune thyroiditis, HIV, hepatitis C, Epstein-Barr virus, sarcoidosis and internal malignancies.

Onychodystrophy

Onychodystrophies are excessive thickening of the nails and their deformation, which can cause subsequent infection of the feet, which should be considered diabetic ulcers. Poorly fitting shoes can lead to re-injury and worsening of the affected area. In patients with diabetes, onychodystrophies are the result of poor peripheral circulation and diabetic neuropathy. The condition itself can lead to diabetic foot ulcers. Proper nail care, well-fitting shoes, and immediate attention to nail infections are essential. Such patients should be the focus of attention of podiatrists.

Periungual telangiectasia

Periungual telangiectasias present as nail fold erythema, dilated blood vessels visible to the naked eye, and thick cuticles. They occur in people with diabetes after the loss of capillary loops and dilatation of the remaining capillaries. This pathology occurs in approximately 49% of people with diabetes. No treatment is required.

Infections associated with diabetes

Skin infections form the largest group of skin diseases that occur against the background of diabetes mellitus. Skin infections include candidiasis, dermatophytosis, and bacterial infections.

Candidiasis

Candidiasis of the skin and mucous membranes is most often caused by Candida Albicans and manifests itself in the form of red plaques with a characteristic white coating of exudate and pustules. The risk of infection increases with hyperglycemia, which promotes candida proliferation. Vulvovaginal candidiasis is the most common of all cases; perianal candidiasis also occurs in men and women. Other manifestations include stomatitis (infection of the oral mucosa) and jamming (angular cheilitis), diaper rash (infection of large skin folds and interdigital candidal erosion), paronychia (infection of the soft tissue around the nail plate) and onychomycosis.

Dermatophytosis

Dermatophytoses are superficial infections of the skin, hair and nails caused by a fungus. Ringworm, tinea pedis (athlete's foot), and onychomycosis are common dermatophytosis found in people with diabetes. In a study of 76 patients with ringworm, the main predisposing factor was xerosis. In a study of 171 patients with diabetes, compared with 276 control subjects, the most common infection diagnosed in people with diabetes was tinea pedis (athlete's foot), followed by distal subungual onychomycosis. This study showed no correlation between dermatophytosis and the duration or type of diabetes or its complications.

Bacterial infections

Skin bacterial infections in people with diabetes are more common and more severe. Diabetic foot ulcers are the main type of morbidity in patients with diabetes. They develop due to decreased sensitivity due to diabetic neuropathy, which leads to injury and subsequent infection. Dysfunction of blood white blood cells as a result of elevated glucose levels allows bacteria to multiply. Staphylococcal folliculitis, or skin abscesses, is one of the most common bacterial infections in uncontrolled diabetes. Treatment includes systemic antibiotics and surgical drainage.

External ear canal infection caused by Pseudomonas aeruginosa is also common in people with diabetes. Microscopically, pseudomonads were identified as gram-negative rods. Patients may complain of otalgia, otorrhea, hearing loss, as well as swelling and redness of the skin of the external auditory canal.

Treatment consists of topical antibacterial agents for uncomplicated infections. Malignant otitis externa requires immediate administration of systemic antibiotics such as fluoroquinolones, plus an antibiotic with antipseudomonal properties. Higher doses and surgical debridement are necessary to prevent the infection from spreading to the bones and nervous system. Prompt treatment of otitis externa is important because of its ability to quickly spread to the bones and cranial nerves, which can be fatal.

Summary

Diabetes is the most common endocrine disease and many skin disorders are usually associated with it. Knowing these features can help your healthcare provider diagnose diabetes and treat associated skin conditions.

Most manifestations can be managed with lifestyle modifications, and in some cases referral to a dermatologist may be warranted. As the incidence and prevalence of diabetes increases, skin manifestations associated with diabetes will become more common. Therefore, it is very important to familiarize practicing dermatocosmetologists with the principles of diagnosis and treatment of this pathology.