Keywords

Introduction

Diabetes mellitus can cause alterations of skin homeostasis by both primary diabetes-induced changes of skin metabolism and by associated complications, such as vasculopathy and neuropathy resulting in various skin manifestations. Hyperglycemia-induced nonenzymatic glycation of structural and regulatory proteins plays a central role in the pathogenesis of diabetic complications. Chemical transformation of the proteins results in the formation and accumulation of advanced glycation end products (AGEs). Specific receptors for AGEs (RAGE) are expressed by many cell types including keratinocytes (Sakaguchi et al. 2014). The accumulation of AGEs and their interaction with RAGEs initiate different intracellular signaling cascades, which are assumed to contribute to the pathogenesis of various diabetic disorders (Nowotny et al. 2015). In addition, diabetic patients often exhibit altered keratinocyte functions due to the influence of insulin on keratinocyte proliferation, differentiation, and migration, resulting in impaired epidermal barrier function, delayed wound healing, and reduced stratum corneum hydration (Wertheimer et al. 2000). Moreover, a decreased sebum secretion and altered skin elasticity have been detected in diabetic patients (Seirafi et al. 2009). It has been estimated that at least one third of patients with diabetes develop any type of skin manifestations during the course of their disease (Perez and Kohn 1994). This review describes the clinical aspects of the most common dermatologic skin manifestations that could be observed in patients with diabetes, which can be distinguished into specific cutaneous markers of diabetes and non-specific skin conditions associated with diabetes (Table 1).

Table 1 Skin manifestations occurring in patients with diabetes
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Specific Cutaneous Markers of Diabetes Mellitus

Acanthosis Nigricans

Acanthosis nigricans (AN) is characterized by velvety hyperpigmentation and accentuation of skin markings of the intertriginous surfaces, particularly the axillae, groin, posterior neck, and, less often, extensor surfaces (Fig. 1a). AN is generally asymptomatic, but it may be painful, malodorous, or macerated in rare cases. Histologically, AN shows proliferation of epidermal keratinocytes and dermal fibroblasts and thickened stratum corneum. Probably one or more circulating factors stimulate keratinocyte proliferation, through insulin-like growth factor receptors. AN may be associated also to malignancies, in particular adenocarcinomas of the gastrointestinal tract. However, it is most frequently associated with insulin resistance and obesity (Behm et al. 2012; Murphy-Chutorian et al. 2013). In addition, AN has been reported as a rare, local, cutaneous side effect of repeated exogenous insulin injections. Rotating injection sites may help to prevent or reverse the reaction (Buzasi et al. 2011). Diagnosis of AN is usually clinical and warrants screening for diabetes and insulin resistance. New onset of AN should prompt an evaluation for underlying malignancy. AN is a chronic but reversible condition. Management focuses on treating the underlying cause. In the diabetic patient, weight control, dietary restrictions, and increased physical activity are of primary importance. Moreover, topical keratolytics (i.e., salicylic acid, retinoic acid, and ammonium lactate) and oral isotretinoin can reduce thicker plaques in areas of maceration, decreasing odor and discomfort (Murphy-Chutorian et al. 2013).

Fig. 1
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Specific cutaneous markers of diabetes mellitus: acanthosis nigricans (a), bullous disease of diabetes (b), necrobiosis lipoidica (c, e), and diabetic foot (d)

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Necrobiosis Lipoidica Diabeticorum

Necrobiosis lipoidica (NL) is a chronic granulomatous skin disease that occurs primarily in individuals with diabetes, although it may be observed also in nondiabetic patients. NL occurring in diabetic patients is called necrobiosis lipoidica diabeticorum (NLD). Typical lesions are well-demarcated, indurated, annular plaques that contain characteristic yellow brown atrophic centers studded with prominent vessels and delimited by narrow, reddish-brown, or violaceous margins (Fig. 1c, e). Solitary or multiple lesions are most commonly distributed bilaterally on the lower extremities, particularly the pretibial areas, but may occur on the face, scalp, trunk, and upper extremities. NLD can be asymptomatic or painful and/or pruritic, especially when ulcerated. Ulceration occurs in approximately one third of lesions, either spontaneously or secondary to trauma. Ulcerative lesions may be complicated by secondary infection and, more rarely, by squamous cell carcinoma. NLD occurs more frequently in type I diabetes but is associated also to type II diabetes (Shall et al. 1990). There is a female predominance with typical onset in the fourth decades of life. Distinctive necrobiosis surrounded by palisading granulomas is seen on histopathology. A retrospective review found that only 22% of 65 patients with NL had or developed diabetes over a 15-year period (O’Toole et al. 1999). Diabetes precedes the onset of NL by a mean of 10 years but can develop concurrently with or later than NL. Therefore, patients with NL with normal glucose metabolism should be closely monitored over time for diabetes or insulin resistance. The cause of NLD is unknown. Vasculopathy, collagen alterations, immune complex deposition, and inflammatory mechanisms have all been implicated in the pathogenesis of NLD. Treatment of NL is challenging. Topical and intralesional steroids, topical calcineurin inhibitors (i.e., tacrolimus and pimecrolimus), topical tretinoin, and phototherapy are the most commonly recommended therapeutic approaches (Erfurt-Berge et al. 2012). In addition, topical granulocyte colony-stimulating factor, intralesional tumor necrosis factor (TNF)-α inhibitors (infliximab and etanercept), intravenous infliximab, systemic steroids, and colchicine have demonstrated efficacy in severe refractory cases of ulcerative NLD (Evans and Atherton 2002; Hu et al. 2009).

Generalized Granuloma Annulare

Granuloma annulare is a relatively common disease that occurs in all age groups, but it is rare in infancy. Women are affected by granuloma annulare twice as often as men. Granuloma annulare is clinically characterized by many papules merging in annular plaques. The clinical variants of granuloma annulare classically described include localized, generalized, subcutaneous, and perforating type. Generalized granuloma annulare occurs predominantly in adults, and it is observed in 9–15% of all patients with granuloma annulare. Patients with generalized granuloma annulare characteristically present with a few to hundreds of 1- to 2-mm papules or nodules that range in color from flesh-toned to erythematous involving multiple body regions. Lesions may coalesce into annular plaques, which measure 3–6 cm in diameter and which may enlarge centrifugally over weeks to months. Although any part of the cutaneous surface may be involved, lesions tend to be symmetrically disposed over the trunk. Rarely, the head, palms, soles, and mucous membranes are involved. Proposed pathogenic mechanisms include primary degeneration of connective tissue leading to granulomatous inflammation, lymphocyte-mediated immune reaction with macrophage activation, and cytokine-mediated degradation of connective tissue. Granuloma annulare has been associated primarily with type I diabetes mellitus, but it is only rarely associated with type II diabetes mellitus and thyroid disease, based on an increased number of granuloma annulare patients with these diseases in small case series (Kakourou et al. 2005). Laboratory investigations are largely noncontributory in patients with granuloma annulare. With a classic history and unremarkable physical examination findings, no additional workup is necessary except for skin biopsy. Histological examination reveals foci of degenerative collagen associated with palisaded granulomatous inflammation. Macrophages surround acellular necrobiotic areas in which collagen bundles are thinned, or they sometimes have a pale, homogeneous, light-blue appearance, the latter of which is due to the presence of mucin. Treatment of the generalized disease is unfortunately fraught with a lack of consistently effective options. While the treatment of choice remains to be defined, the available literature supports the use of isotretinoin or phototherapy with oral psoralen and UV-A (PUVA) as first-line options for generalized granuloma annulare. Other anecdotal reports describe successful treatment with dapsone, narrow-band UVB, systemic steroids, pentoxifylline, hydroxychloroquine, cyclosporine, fumaric esters, interferon gamma, nicotinamide, etanercept, infliximab, adalimumab, and photodynamic therapy (Piaserico et al. 2009; Weisenseel et al. 2008; Rosmarin et al. 2009).

Bullous Disease of Diabetes

Bullous disease of diabetes (bullosis diabeticorum) is a distinct, spontaneous, noninflammatory, blistering condition of acral skin that is unique to patients with diabetes mellitus. Bullosis diabeticorum tends to arise in patients with long-standing diabetes mellitus or with multiple complications of the disease. Blisters typically heal spontaneously, within 2–6 weeks, but lesions often recur in the same or a different location. Common clinical findings of bullosis diabeticorum include tense blisters arising on non-erythematous skin. Blisters are generally quite large (from 0.5 to 17 cm in diameter), often with an irregular shape, simulating a burn (Fig. 1b). Some blisters may also be flaccid. Although blisters typically occur on the feet or lower legs, they also may occur on fingers, toes, hands, and arms. Major differential diagnosis includes bullous pemphigoid, chemical burns, epidermolysis bullosa acquisita, friction blisters, and porphyria cutanea tarda. The pathophysiology of bullous disease of diabetes is likely multifactorial. Patients with diabetes have been shown to have a lower threshold for suction-induced blister formation compared with nondiabetic controls (Bernstein et al. 1983), and because of the acral frequent localization of diabetic bullae, the role of trauma has been proposed. Electron microscopic evidence has also suggested an abnormality in anchoring fibrils. However, this alone does not explain the frequent spontaneous development of multiple lesions at several locations. In some patients, blisters are related to UV exposure, especially in those with nephropathy (Larsen et al. 2008). Poor blood glucose regulation has been associated with blister formation (Wilson et al. 2012). Approaches range from culture to skin biopsy in order to more clearly differentiate the condition from other clinically similar conditions and identify secondary infections that might require treatment. Cultures are only warranted if secondary bacterial infections are suspected. If bullous disease of diabetes blister fluid is cloudy instead of clear, the clinician should consider excluding secondary bacterial infection with culture of the blister fluid. If a patient presents with prominent involvement of the dorsal hands, evaluation of porphyrin levels is warranted. Porphyrin levels are normal in persons with bullous disease of diabetes but abnormal in case of porphyria cutanea tarda or another blistering porphyria. Individuals with end-stage renal disease may have mildly elevated plasma porphyrin levels, possibly contributing to the total pathogenesis of blister formation. Histologic features of bullous disease of diabetes are not entirely specific. Many of the reported cases describe a separation in the superficial epidermis within the superficial part of the spinous layer, but the blister plane may also appear in a subcorneal, intraepidermal, or subepidermal location. Surrounding epidermis is normal. Specific treatment of bullous disease of diabetes is unnecessary because the condition is self-limiting. The blister should be left intact whenever possible to serve as a sterile dressing and to avoid secondary infection. Antibiotics are only warranted when secondary staphylococcal infection is present.

Scleredema Diabeticorum

Scleredema adultorum was first described by Buschke et al. in 1900 (Buschke 1900). It may be triggered by infections or be associated with systemic diseases including paraproteinemia, malignancy, as well as poorly controlled type II diabetes mellitus. This subtype of scleredema (scleredema diabeticorum) tends to occur more often in middle-aged males (at a reported 10:1 ratio), often obese, with long-standing, often uncontrolled, type II diabetes mellitus. Subtle skin hardening of the upper back begins in an insidious manner, progressing slowly over many years, to involve the upper back, neck, and shoulders. Scleredema presents as woody, non-pitting, indurated plaques. Erythema, hyperpigmentation, and/or a “peau d’ orange” appearance of the affected areas may be present. The taut skin may be firm with wrinkling of overlying epidermis. Main differential diagnosis includes amyloidosis, scleromyxedema, eosinophilic fasciitis, morphea, and nephrogenic systemic fibrosis. Imaging studies with ultrasound and/or magnetic resonance have been proposed as a method to measure induration in the involved soft tissues and monitor the response to therapy (Kurihara et al. 2011). Diabetes-associated scleredema adultorum usually shows a slow and non-resolving progress. Hyperstimulation of collagen synthesis by fibroblasts as a response to altered glucose metabolism seems to be a possible pathogenic mechanism. The histopathology of scleredema is characterized by enlarged collagen bundles separated by spaces of mucin deposits (i.e., hyaluronic acid), which results in a thickening of the dermis. The epidermis remains unaffected (Lewerenz and Ruzicka 2007). Although the disorder is usually restricted to the skin, the tongue, pharynx, esophagus, skeletal muscle, and cardiac muscle may rarely be affected. Optimal control of the glycemia does not improve scleredema (Meguerditchian et al. 2006). There is no standard therapeutic protocol, as therapeutic success is limited to case reports. Psoralen plus ultraviolet A (PUVA) or ultraviolet A1 (UVA1) phototherapy is the most beneficial approach in scleredema adultorum (Eberlein-Konig et al. 2005). Systemic corticosteroids and immunosuppressive drugs should be reserved for patients with persistent, debilitating disease in whom phototherapy has failed or for patients with scleredema-associated multiple myeloma (Rongioletti et al. 2015).

Diabetic Foot

Diabetic foot occurs in 15–25% of diabetic patients (Singh et al. 2005) (Fig. 1d). In the development of the diabetic foot syndrome, micro- and macroangiopathy and peripheral neuropathy play crucial roles. Poor foot care, abnormal foot structure, or poorly fitting shoes are frequent trigger of diabetic ulcers. Diabetic foot ulcers can be divided into two groups: those in neuropathic feet (so-called neuropathic ulcers) and those in feet with ischemia often associated with neuropathy (so-called neuro-ischemic ulcers). The neuropathic foot is warm and well perfused with palpable pulses; sweating is diminished and the skin may be dry and prone to fissuring. The neuro-ischemic foot is a cool, pulseless foot; the skin is thin, shiny, and without hair. There is also atrophy of the subcutaneous tissue, and intermittent claudication and rest pain may be absent because of neuropathy (Consensus Development Conference on Diabetic Foot Wound Care 1999). The ulcers usually occur in areas of increased plantar pressure such as beneath the metatarsal heads (Pavicic and Korting 2006). In addition, diabetic patients suffer from impaired wound healing; therefore, diabetic ulcers often progress, become chronic, and are risk factors for gangrene (Falanga 2005). Dry gangrene commonly manifests in a toe due to poor tissue perfusion and normally drops off naturally. In contrast, wet gangrene occurs due to infection of ulcers and requires urgent surgical intervention. Treatment of diabetic ulcers includes the elimination of plantar pressure by protective shoes, debridement, regular foot care, and moist wound treatment (Edmonds and Foster 2006). In approximately a quarter of patients with diabetic foot, an amputation will be necessary in the course of disease.

Eruptive Xanthomas

Eruptive xanthomas manifest as multiple yellow papules, 1–4 mm in diameter, mainly on the extensor surfaces of the extremities and on the buttocks. The papules are surrounded by erythematous halos at their base and may be tender or pruritic (Ferringer and Miller 2002). The histopathology shows an accumulation of lipid-laden histiocytic foam cells with a mixed infiltrate of lymphocytes and neutrophils in the dermis. The prevalence of xanthomatosis among diabetic population is unclear (Parker 1985). The pathogenic mechanism for the increased frequency of eruptive xanthomatosis among individuals with diabetes has been proposed. Eruptive xanthomatosis is associated to hypertriglyceridemia. Because insulin is a stimulating factor critical to the normal activity of lipoprotein lipase, it plays an important role in the metabolism of serum triglycerides and triglyceride-rich lipoproteins. The insulin-deficient state of uncontrolled insulin-dependent diabetes results in the absence of lipoprotein lipase activity. The impaired clearance of very-low-density lipoproteins and chylomicrons leads to a hyperlipemic syndrome, which, if severe enough, can precipitate eruptive xanthomas. Diabetic hyperlipidemia may be accelerated by polyphagia caused by glycosuria. The diagnosis of eruptive xanthomatosis should prompt further investigation and treatment of hyperglycemia (Feingold and Elias 1987). Xanthomatosis resolves with control of carbohydrate and lipid metabolism; therefore the diabetic patient typically requires just optimized insulin therapy. Statins or fibrates can supplement treatment as tolerated (Wani et al. 2009).

Non-specific Skin Conditions Associated with Diabetes

Psoriasis

Chronic plaque psoriasis is a common inflammatory disease of the skin affecting 1–3% of the general population in the Western world (Parisi et al. 2013). Genetic and environmental factors play an integrated role in the pathogenesis of psoriasis. In psoriasis, the inflammatory cytokine network is deregulated, leading to the excessive release of pro-inflammatory mediators from immune cells and increase of keratinocyte proliferation (Lowes et al. 2014). In particular, Th1 and Th17 cell populations produce different cytokines (interleukin [IL]-6, IL-17, and IL-22, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α), causing abnormal differentiation and hyperproliferation of keratinocytes, blood vessel dilatation, and infiltration of leukocytes into the dermis and epidermis (Durham et al. 2015). The hallmarks of psoriasis are raised and clearly delimited erythematous lesions covered by silver scales. Psoriatic lesions are commonly localized on the elbows, knees, trunk, sacrum, and scalp; the involvement of the face, genitals, nails, and palm-plantar regions is associated with higher impact on quality of life. Psoriatic lesions are frequently symptomatic with pruritus, followed by scaling and flaking. Psoriasis may affect many facets of life including emotional, social, work, and leisure. Approximately, one third of patients present signs/symptoms of concomitant psoriatic arthritis. Patients with severe psoriasis are at increased risk of several metabolic diseases, such as obesity, diabetes, fatty liver disease, metabolic syndrome, and cardiovascular diseases. The association of psoriasis with insulin-resistance and diabetes has been investigated in several epidemiological studies and meta-analyses. The prevalence of diabetes in patients with psoriasis ranges from 4.4% to 54% (Armstrong et al. 2013). Most of the studies found that the prevalence of diabetes is higher in patients with moderate to severe psoriasis compared to mild disease (Al-Mutairi et al. 2010). In a meta-analysis of 44 studies by Coto-Segura P et al., the pooled odds ratio for the association between psoriasis and diabetes was 1.76 (95% CI 1.59–1.96). It was reported a “dose effect” in the risk of suffering from diabetes, as patients with severe psoriasis had higher risk compared with those with mild disease. The highest risk was for patients with psoriatic arthritis (OR 2.18, 95% CI 1.36–3.50) (Coto-Segura et al. 2013). In another meta-analyses of observational studies (n = 27), psoriasis was associated also with an increased incidence of diabetes, other than prevalence. The study found that patients with psoriasis have a 27% increased risk of developing diabetes compared to the general population. In particular, those aged below 60 years and with more severe psoriasis carry the higher risk of developing diabetes (Armstrong et al. 2013). Moreover, a Danish nationwide cohort study (study period 1997–2009) including 52,613 patients with psoriasis found that the incidence rate ratios of new-onset diabetes were increased in patients with psoriasis compared with the general population (Khalid et al. 2013). On the other hand, a case-control study by Wu et al. including 41,289 subjects found that diabetic patients are at risk of developing psoriasis. The incidence rates of first-time psoriasis in diabetic patients and nondiabetic subjects were 70.2 cases and 42.5 cases per 100,000 person-years, respectively (p <0.001). The more severe the diabetes is, the higher the risk for psoriasis. Furthermore, thiazolidinedione use has been associated with slightly lower risk of incident psoriasis (0.87, 95% CI 0.77–0.99) (Wu et al. 2015).

Acrochordons

Acrochordons or skin tags are benign, soft, usually flesh-colored, or hyperpigmented tumors, frequently localized on the neck, the eyelids, the axillae, and the groins (Behm et al. 2012). They can range from small papules to pedunculated polyps, typically 1 to 6 mm in diameter, with smooth or irregular surfaces. There is a slight female predilection, and prevalence increases with age (Murphy-Chutorian et al. 2013). Histologic features consist of a papillary-like dermis consisting of loose collagen fibers and thin-walled blood vessels. Multiple skin tags are associated with abnormal glucose metabolism, possibly due to insulin-induced keratinocyte proliferation. Approximately 66–75% of patients with multiple skin tags have diabetes, and more than 80% show impaired carbohydrate metabolism (Murphy-Chutorian et al. 2013). A correlation between the number of skin tags and the fasting plasma glucose value has been observed (Rasi et al. 2007). Treatment is only necessary due to cosmetic reasons. Acrochordons can be removed by excision or cryosurgery.

Yellow Skin and Nails

Yellowish skin and nails are more frequently observed in diabetic patients, compared with the general population. About 40% of diabetics show yellow nails. The yellow coloration is probably caused by the effect of nonenzymatic glycosylation of dermal collagen; however the exact mechanism is not clearly understood. Onychomycosis may be considered as differential diagnosis (Murphy-Chutorian et al. 2013), and performing nail culture for the isolation of the fungi may be appropriate.

Generalized Pruritus

Xerosis, drug therapy, pathogens, and the damage of sensory c-fibers in diabetic polyneuropathy may contribute to itch sensation in diabetic patients (Yamaoka et al. 2010); however generalized pruritus does not seem significantly more common in diabetic than in nondiabetic patients. Localized pruritus, especially in the genital and perianal areas, is significantly more common in diabetic women, and it is associated with poor glycemic control. In some patients, a predisposition to candidiasis may play a role. Diabetic neuropathy is characteristically associated with pain, burning, or prickling sensations, although pruritus has been described (Weisshaar et al. 2012). As pruritus often occurs in dry skin, the regular usage of emollients may partially prevent this skin complication in diabetics (Behm et al. 2012).

Rubeosis Faciei

Rubeosis faciei has long been described as a common manifestation of diabetes mellitus. The condition is characterized by a chronically flushed appearance of the face, neck, and upper extremities (Fig. 2d). It may result from microangiopathic alterations and superficial facial venous dilatation. Although rubeosis is a benign condition, it may serve as a clue to microangiopathy secondary to suboptimal glycemic control. Therefore, patient evaluation for serious complications such as retinopathy is recommended. Treatment of rubeosis faciei is strict diabetic control and avoidance of alcohol, caffeine, and other vasodilators (Murphy-Chutorian et al. 2013).

Fig. 2
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Non-specific skin conditions associated with diabetes mellitus: tinea pedis (a), onychomycosis of the first and second toes (b), candidal intertrigo of mammary fold (c), rubeosis faciei (d), and pigmented purpura of a leg (e)

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Diabetic Dermopathy and Pigmented Purpura

Diabetic dermopathy affects 10% of diabetic patients. It is a sign of microangiopathy, characterized by multiple asymptomatic, round, dull red to pink papules or plaques predominantly on the pretibial skin evolving in atrophic macules with fine scale. Sometimes they may be complicated by ulceration. An association with coronary artery disease, neuropathy, nephropathy, and retinopathy has been identified. Thus, diabetic dermopathy may be considered a clinical marker for the severity of systemic diabetic complications (Behm et al. 2012). Pigmented purpura coexists with diabetic dermopathy in about 50% of cases. In the absence of diabetic dermopathy, pigmented purpura is not considered a marker for diabetes. It is a wide group of uncommon, idiopathic, progressive skin conditions, being Schamberg’s disease the most common form. Pigmented purpura is characterized by asymptomatic, non-blanching, orange to brown patches, distributed mainly over the lower extremities, especially the pretibial leg (Fig. 2e). It is caused by erythrocyte extravasation from the superficial venous plexus (Murphy-Chutorian et al. 2013). No medical intervention is necessary, but ascorbic acid and rutoside may be helpful.

Skin Infections

The impaired microcirculation, sensory and autonomic neuropathy, acid-base imbalances, and impaired immune response of diabetes mellitus and its complications predispose diabetic patients to bacterial and fungal infections of the skin more frequently compared with general population. Recurrent skin infections such as impetigo contagiosa, abscesses, erythrasma, folliculitis, erysipelas, or severe fungal infections may be the presenting feature of diabetes. The most common bacterial infections in diabetic patients are staphylococcal and beta-hemolytic streptococcal infections. Skin swab for culture is recommended for the microbe identification. Depending on the severity of the infection, oral or intravenous antibiotics and diabetic control are mandatory. Pseudomonas infections of the toe web spaces and colonization of the toenails required topical and systemic antibiotics such as oral ciprofloxacin. Malignant otitis externa caused by Pseudomonas aeruginosa is a rare life-threatening skin infection of the external auditory canal, associated with high morbidity and mortality. Antibiotic therapy and necrotic tissue debridement should be initiated promptly. Candida infections are often seen in the setting of diabetes. They include angular stomatitis, paronychia, thrush, and intertrigo of the skin folds (Fig. 2c). Common female-specific Candida skin infections include pruritus vulvae (often accompanying vulvovaginitis) and inframammary fold infection. Candida infections should be managed with topical antifungals and/or oral fluconazole for more severe or refractory cases as well as glycemic control. Dermatophyte infections of the skin are most frequently caused by Trichophyton rubrum. Tinea pedis is the most prevalent dermatophytosis among diabetic patients (Fig. 2a). Skin scrapings for direct fungi microscopy and culture are indicated. Treatment of dermatophytosis includes topical and systemic antifungals and the management of potential superimposed bacterial infections. Onychomycosis (fungal infection of the nail) is common in diabetes, most often caused by Candida or Trichophyton. Signs of onychomycosis include yellow discoloration, subungual hyperkeratosis, distal onycholysis, and nail dystrophy (Fig. 2b). Nail culture for the isolation of the fungi is indicated. Nail infections can provide a portal of entry for secondary bacterial infection including erysipelas. Patients should be educated about the importance of proper foot and nail care for prevention of infections (Behm et al. 2012; Murphy-Chutorian et al. 2013).

Conclusions

The wide range of dermatologic conditions related to impaired glucose metabolism is important across multiple medical specialties to identify undiagnosed diabetes as early as possible and to better manage patients with known disease. Despite numerous investigations, the exact causes of many cutaneous complications of diabetes remain elusive.