Xerosis, or dry skin, is one of the earliest and most common signs of diabetes and is found in up to 22% of patients with DM1.8 Xerosis has been demonstrated by measuring transepidermal water loss and the high-frequency conductance of the forearm.9 Another finding of interest is that even in the absence of clinically evident xerosis, the skin of patients with diabetes exhibits abnormal desquamation and reduced elasticity10 as well as a greater than average thickness that may contribute to a reduction in elasticity.11 Skin thickening is classified clinically into 3 categories: a)benign thickening of the skin; b)scleroderma-like syndrome; and c)scleredema of Buschke. It is thought that skin thickening in this setting is caused by abnormal collagen glycation during episodes of hyperglycemia or by collagen proliferation promoted by excess insulin.12 The hands and feet are the most common sites of benign skin thickening in diabetic patients, and involvement of these sites is closely associated with joint limitation.13 Although the condition may be asymptomatic, increased skin thickness can be measured using cutaneous ultrasound.11

Keratosis pilaris is a common condition in diabetic children, with a prevalence of 11.7% in patients with DM1 over 10years of age.8 The etiology is unclear, but it appears that xerosis plays an important role.14 The clinical characteristics include rough follicular papules and variable erythema located predominantly on the extensor surfaces of the arms and legs and occasionally on the face, buttocks, and trunk (Fig. 1). Keratosis pilaris tends to flare up in winter and usually improves during the summer months.15 It is mainly associated with atopic dermatitis and an high body mass index.16 Treatment includes keratolytic agents, retinoids, and low potency topical corticosteroids.17

Fig. 1.

Follicular hyperkeratotic papules secondary to keratosis pilaris on the buttocks, accompanied by striae.

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Rubeosis faciei diabeticorum—the characteristic facial rash found in diabetic patients (Fig. 2)—is caused by the dilation of small vessels in the cheeks probably as a result of microangiopathy induced by hyperglycemia.18 The prevalence of this condition is higher in patients with DM2 (21%-59%)19 than in children with DM1 (7%),8 and it is directly related to the duration of the disease.

Fig. 2.

Rubeosis faciei in an overweight child with diabetes who also presented keratosis pilaris on the trunk.

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Limited joint mobility, also called diabetic cheiroarthropathy or limited joint mobility syndrome, is the earliest clinically apparent long-term complication of DM1 in childhood.20 It involves asymptomatic bilateral contracture of the joints of the digits and the large joints associated with waxy thickening of the skin and short stature. It appears to be the result of nonenzymatic glycation of collagen, which results in insoluble crosslinked collagen that produces rigidity in the dermis and joints.7 The frequency of this condition is variable; in some case series it has been found in 2.3% of patients with DM1,8 and in others it has been reported in 30% of diabetic patients aged under 21 who are short in stature.21 The incidence of this complication has decreased in recent years with improved glycemic control.

The first joints affected are the proximal interphalangeal joints of the fourth and fifth fingers, with a stiffness or flexion contracture that limits finger extension accompanied by scleroderma skin changes. This rigidity may spread to the other fingers and to the wrists, elbows, ankles, knees, toes, and cervical and thoracic spine. As the development of this complication is directly related to the duration of diabetes and glycemic control, cases in children under 10 years of age are rare.22 Patients with limited joint mobility have an increased risk of developing the other microvascular complications of diabetes, especially retinopathy, nephropathy, and neuropathy.23

It is well known that diabetic patients are susceptible to severe, recurrent, and atypical infections. The infections most often found in diabetic children are fungal and bacterial infections, especially with species of Candida, Staphylococcus, and Streptococcus.5No association with or predisposition to specific viral infections has been observed.

Changes related to the effects of diabetes on the vascular and nervous system occur later than those described above because they are associated with structural deterioration caused by chronic hyperglycemia and ischemia of the vasa nervorum in the case of peripheral nerves27 and a form of arteriosclerosis in the microvasculature associated with reduced elasticity and impaired endothelial vasomotor function in the peripheral arteries.28 Consequently, these effects occur more frequently during the second decade of life.

Findings in the lower limbs include decreased temperature, nail dystrophy, and mottled skin color on the feet, accompanied by skin atrophy and hair loss on the legs and feet. Other changes observed include anhidrosis—the result of severe vascular insufficiency or autonomic dysfunction—and poor wound healing due to vascular insufficiency and neuropathy. These changes are mainly found in older adolescents and young adults.4

Although more typical of the older diabetic patient, the structural and functional alterations that will predispose these patients to develop diabetic foot—including calluses, long nails, blisters, and dry skin—are also observed in younger patients.29 It is very important that these predisposing factors be identified so that preventive measures can be implemented. The physician should seek to reduce the incidence of diabetic foot and the prevalence of lower limb amputation in adult patients with diabetes.30

There is a group of disorders of unknown origin that are associated with diabetes or are found more frequently in diabetic patients. It includes necrobiosis lipoidica, granuloma annulare, diabetic dermopathy, bullosis diabeticorum, reactive collagenosis, scleroderma diabeticorum, pruritus, and yellow skin. In this article we will only discuss necrobiosis lipoidica, granuloma annulare, and diabetic dermopathy since the other manifestations are rare and very few pediatric cases have been reported in the literature.

Necrobiosis Lipoidica

Necrobiosis lipoidica is a rare disease, more common in women, with a prevalence of 0.3% in adult patients with diabetes; it is much less frequent in childhood, with a prevalence of only 0.06%.31,32 In diabetic patients, the presence of this disorder is associated with a higher frequency of retinopathy and nephropathy.33 Clinically, it appears as bilateral, asymptomatic, yellow-orange or red-brown plaques distributed symmetrical on the lower limbs, often on the anterior aspect of the tibia (Fig. 3); in isolated cases the lesions may be located on the upper limbs.34 The characteristic histologic features are neutrophilic necrotizing vasculitis in the early stages and amorphous degeneration and hyalinization of dermal collagen (necrobiosis) in the later stages. Treatment consists of good control of blood glucose levels. Numerous treatments have been tried with limited success, including topical or intralesional corticosteroids, pentoxifylline, topical retinoids, and calcineurin inhibitors.35

Fig. 3.

Necrobiosis lipoidica on the anterior aspect of the leg.

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Granuloma Annulare

Granuloma annulare is a benign inflammatory disorder of unknown origin characterized by degeneration of the connective tissue and a predominantly histiocytic inflammatory infiltrate. Although the origin of this condition remains poorly understood, in adults a marked association has been observed with certain systemic diseases, particularly diabetes and rheumatic diseases.36 No such association has been established in children, but isolated cases of granuloma annulare in childhood diabetes have been reported and in the presence of these conditions physicians should assess the risk factors for other comorbidities and order the pertinent tests or studies.37

Granuloma annulare can occur at any age, but is most frequently observed in children and adolescents.38 In childhood, the most common clinical variants are the localized and subcutaneous forms. Localized granuloma annulare presents as pale red or violaceous papules which are firm and smooth to the touch. The lesions fuse into single or multiple annular plaques organized around a slightly depressed and hyperpigmented center. Subcutaneous or deep granuloma annulare presents as a fixed nodule located on the legs (Fig. 4), scalp, palms, or buttocks.39 Other less common variants include disseminated granuloma annulare characterized by a diffuse papular eruption, and a perforating form that presents as umbilicated papules with a central crust or scale and transepidermal elimination of necrobiotic connective tissue from the center.

Fig. 4.

Granuloma annulare: slightly erythematous annular plaques around a pale center on the dorsum of the foot.

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In some patients, granuloma annulare may coexist with necrobiosis lipoidica. Owing to the histologic similarity, some authors have suggested that granuloma annulare is an early phase of necrobiosis lipoidica.40

Treatment is frequently unnecessary since most of these lesions resolve spontaneously within 2years of onset. The condition may be treated for cosmetic reasons,41 and in such cases the treatment options will depend on the clinical presentation. The localized forms can be managed with high-potency topical corticosteroids, calcineurin inhibitors, cryotherapy, or pulsed dye laser.42 Generalized forms may be treated with one of a variety of systemic therapies, including dapsone, retinoids, niacinamide, antibiotics, antimalarials, phototherapy, or photodynamic therapy, all with only relative therapeutic success.43–45

The incidence of autoimmune diseases is higher in children with DM1 and their families, apparently due to the presence of circulating autoantibodies against specific organs.20 It is important, therefore, when taking a medical history to ask the appropriate questions and to ensure early diagnosis of these diseases. The autoimmune diseases most closely linked to diabetes mellitus are thyroid diseases, celiac disease, and primary adrenal insufficiency.

Acanthosis nigricans is the most common dermatologic manifestation of pediatric obesity, occurring in 66% of overweight adolescents73 and in 56% to 92% of children and adolescents with DM2. It is considered to be an important clinical marker.74 The condition presents as pigmented velvety patches or plaques, sometimes with a hypertrophic and verrucous surface. Distribution is usually bilateral, symmetrical, and localized to the armpits (Fig. 5), the posterior neck fold, the flexures of the upper and lower limbs, the umbilicus and the inguinal and inframammary folds.75 Acanthosis nigricans is the most common early symptom observed in children who present obesity and/or insulin resistance syndrome. In most cases, treatment involves weight reduction and adequate control of blood sugar levels.

Fig. 5.

Acanthosis nigricans: velvety hyperpigmented plaque in the armpit of a teenager who also presented purple striae on the breast.

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Acanthosis nigricans also occurs in children with multisystem disorders and in such cases is a useful diagnostic indicator. In type A acanthosis nigricans or HAIR-AN syndrome (hyperandrogenism, insulin resistance and acanthosis nigricans), hyperandrogenism is associated with polycystic ovaries, signs of virilization, hirsutism, seborrhea, and episodes of acne. In type B acanthosis nigricans, more common in women and older patients (age range from 12 to 60 years),4 marked hyperandrogenism is found in association with other autoimmune diseases, primarily lupus erythematosus.76 In this setting, the acanthosis nigricans may be periorbital. Other more rare syndromic forms are the congenital Berardinelli-Seip syndrome and acquired generalized lipodystrophy or Lawrence syndrome, characterized by a complete absence of subcutaneous fat due to severe insulin resistance and hyperandrogenism.77

The detection of acanthosis nigricans is useful in that it can lead to early referral to a specialist, which in turn leads to advice on lifestyle modifications that can improve the patient's risk factors.78

Acrochorda, fibroepithelial polyps, or pedunculated fibroids are soft, coffee colored, pedunculated papules often located on the neck, in the axillae, (Fig. 6) or in the groin. They are associated with acanthosis nigricans. Few studies have been published on the incidence of this condition in children. The origin of these skin tags is unknown, but their appearance in adults is closely linked to excessive rubbing of the skin, hormonal imbalance, hypertension, metabolic syndrome, and obesity in adults.79 It has been observed that patients who have more than 10 acrochorda are usually obese16 and have elevated leptin levels.71 Treatment options are simple excision with cold scissors, electrodessication, or cryotherapy.

Fig. 6.

Skin tags: an uncountable number of flesh-colored pedunculated papules in the armpit of a patient who also presented acanthosis nigricans.

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In childhood, the presence of striae, like that of acrochorda, is directly related to excess weight,16 with an incidence of up to 40% in children with moderate to severe obesity.80 Striae are linear atrophic plaques distributed perpendicular to the force of greatest tension. They are found predominantly on the breasts, buttocks (Fig. 7), abdomen, and thighs.71 In the initial stages the marks are erythematous, but they later turn violet and finally become white depressed patches. Treatment options are numerous, and include tretinoin, alone or combined with glycolic acid, microdermabrasion, pulsed dye laser, and fractionated laser (CO2 and erbium). None of these treatment has been shown to be more successful than the others.81

Fig. 7.

Striae: linear atrophic violaceous plaques on the buttocks.

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In obese patients, the shape of the foot may be altered with the loss of the arch, a wider and more obvious footprint, and greater pressure evident when the patient is standing or walking.66 Plantar hyperkeratosis, a condition caused by physical pressure mechanisms, is associated with the duration and severity of obesity16 and is a precursor lesion to diabetic foot in patients with diabetes mellitus.30

Infections are the most frequent complications in obese patients. The risk factors are diverse, as mentioned above, and include impaired barrier function, humid and macerated microenvironments, as well as limitations in mobility and basic hygiene activities.

Intertrigo, the most common manifestation, presents as marked redness in the body folds accompanied by secretion and occasionally odor. The condition requires medical treatment with topical antibiotics. In some cases, low potency corticosteroids are used to reduce symptoms. Treatment also requires a high degree of cooperation from the patient, who must change hygiene routines and use a drying medication to reduce friction. A common complication of intertrigo is superinfection with yeasts, mainly Candida albicans; such infections require additional treatment with topical antifungals.

Other infections found in this setting include pachyonychia, furunculosis, and anthrax caused by staphylococci, and erythrasma caused by Corynebacterium minutisimi. Obese patients also exhibit a greater tendency to cellulitis in the extremities and vascular ulcers due to lymphedema and venous insufficiency.

The association of obesity and psoriasis was first described in 1986, when a higher prevalence of obesity was observed in a group of women with psoriasis than in a group of healthy women.86 It has now been shown that the two conditions share a common pathogenic substrate in the form of inflammation pathways and excess cytokines.87 It should be remembered that obesity is a chronic low-grade inflammatory disease. The elevation of proinflammatory cytokines—mainly tumor necrosis factor-α, IL-6, and acute phase proteins, such as C-reactive protein—could explain the association of obesity with psoriasis. Since obesity is associated with other diseases, it is therefore a component of metabolic syndrome.88

Worldwide, children with psoriasis tend to be overweight and carry the excess fat around the waistline, regardless of the severity of psoriasis.89 Early identification of this metabolic risk factor and education about modifiable factors (healthy eating, maintaining a healthy weight, and physical activity) are the cornerstone of the treatment of these patients and a key intervention in the prognosis of patients with psoriasis.90

There is a strong association between obesity, atopic dermatitis, and bronchial asthma, especially when the patient is obese and under 5 years of age and the condition is prolonged.91 While the physiological and pathogenic mechanisms involved are not yet entirely clear, they may be explained in part by the presence of an abnormal inflammatory response in obese patients and the synthesis by white adipose tissue of mast cells; the increase in mast cells correlates with increased leptin levels and greater sensitization to allergens.72 The most important aspect of this association is that atopic obese patients experience more severe flares of dermatitis and require more treatment.92

Hidradenitis suppurativa is a chronic and recurrent inflammatory skin disease. It begins at puberty and is characterized by deep and painful lesions located in the apocrine glands of hair-bearing parts of the body, especially the axillas and the inguinal and anogenital regions.93 The condition is rare, with a global prevalence of 1% and a male-to-female ratio of 1:3.3. It is now accepted that hidradenitis suppurativa is caused by a defect in the pilosebaceous unit and not in the sweat glands.94 The first event in the pathogenesis is hyperkeratosis of the infundibulum, which leads to follicular occlusion and bacterial superinfection with staphylococci, Escherichia coli, or streptococci. Tobacco consumption is an added risk factor, with a direct dose-effect relationship observed mainly in severe cases.82