PRACTICAL POINTERS

Cutaneous Manifestations of Mellitus Michelle Duff,1 Olga Demidova,2 Stephanie Blackburn,1 and Jay Shubrook2

iabetes is the most common endocrine disorder, affect- Ding 8.3% of the population (1). Skin disorders will be present in 79.2% of people with diabetes (2). A study of 750 patients with diabetes found that the most common skin manifestations were cutaneous infec- tions (47.5%), xerosis (26.4%), and inflammatory skin diseases (20.7%) (2). Individuals with type 2 diabe- ■ FIGURE 1. Acanthosis nigricans tes are more likely than those with and acrochordans. to develop cutaneous manifestations. Cutaneous disease can AN is a hyperpigmented velvety appear as the first sign of diabetes or thickening of skin folds, presenting may develop at any time in the course predominantly in the neck, axilla, of the disease. This review provides and groin areas (Fig. 1). Possible a brief overview of skin conditions additional presentations could that primary care providers (PCPs) include skin tags and hyperkeratosis. may encounter when treating patients Heredity, obesity, endocrine disor- with diabetes. ders, certain drugs, and malignancy Conditions Associated With are associated with AN. Benign AN Resistance type 2 is related to , and pseudo-AN type 3 is associated Acanthosis Nigricans with the metabolic syndrome. Type Acanthosis nigricans (AN) is likely 2 diabetes–related AN has an insid- the most readily recognized skin man- ious onset and initially presents as ifestation of diabetes (3). It is present hyperpigmentation. Both underly- in up to 74% of obese adult patients ing conditions present with insulin 1OhioHealth O’Bleness Hospital, Athens, and can be predictive of the existence resistance (3). Children aged 8–14 OH of hyperinsulinemia (4). The presence years who had AN were found to 2Ohio University Heritage College of of AN is a prognostic indicator for have , and 25% had Osteopathic Medicine, Athens, OH developing type 2 diabetes. There is disturbed glucose metabolism at the Corresponding author: Jay Shubrook, also a possible genetic predisposition time of the study (6). Microscopically, [email protected] or increased sensitivity of the skin to AN presents as papillomatosis and DOI: 10.2337/diaclin.33.1.40 hyperinsulinemia in different ethnic hyperkeratosis (epidermis in irregu- groups. At the same obesity rates, lar folds, exhibiting various degrees ©2015 by the American Diabetes Association. Readers may use this article as long as the work prevalence of AN is lowest in whites of acanthosis). is properly cited, the use is educational and not (0.5%), higher in Hispanics (5%), Treatment consists of treating the for profit, and the work is not altered. See http:// creativecommons.org/licenses/by-nc-nd/3.0 and even higher in African Americans underlying cause. Significant weight for details. (13%) (5). loss resolves AN type 2 and type 3.

40 CLINICAL.DIABETESJOURNALS.ORG d u f f e t a l .

Topical or systemic retinoids and hyperlipidemias. Types I, III, IV, topical retinolytics may be used to and V show high concentrations of manage symptoms (7). very-low-density lipoprotein and chy- Acrochordrons lomicrons. EX lesions tend to resolve spontaneously within weeks (14). Acrochordons, or fibroepithelial pol- Diagnosis can be made clinically yps, skin tags, and soft fibromas, are and confirmed with a biopsy of the pedunculated outgrowths of normal lesions. It is important to obtain skin on a narrow stalk, most com- fasting lipid levels at presentation. monly located on the eyelids, neck, People with EX are at higher risk axillae, and groin (Fig. 1). They are ■ FIGURE 2. Diabetic dermopathy. from hypertriglyceridemia of early found in ~25% of adults, and their arterial wall thickening, and 11 of 14 coronary artery disease and pancre- number and prevalence increases samples demonstrated mild basement atitis (13). Treatment should aim to with age (6). Familial history, obesity membrane thickening. Stain findings lower the triglyceride concentration and AN have been related to acro- suggested the presence of hemosid- with diet modification and systemic chordons; the relationship between erin and melanin depositions in the medications to reverse this condition hyperinsulinemia and skin tags has epidermis of affected patients (11). and decrease complications (15,16). been well established (8). No current treatment exists Acrochordons are benign lesions, or is necessary for DD, which is Rubeosis Facei but may become symptomatic with asymptomatic and does not lead Rubeosis facei (RF), a relatively com- abrasion or necrosis. Red or black to morbidity (3). mon skin manifestation associated skin tags are the result of twisting with diabetes, is a microangiopathic of the base, which cuts off the blood Eruptive Xanthoma . It may go unnoticed by supply. The diagnosis of acrochor- Eruptive xanthoma (EX) presents patients and physicians. However, if dons is made by clinical appearance. on the buttocks, elbows, and knees recognized, it should alert physicians Rarely, they may look suspicious for as sudden onset crops of yellow pap- to look for other microangiopathic malignancy and should be sent for ules with an erythematous base (Fig. complications such as retinopathy histological testing. 3) (12). EX is rare and occurs more (17). RF presents as a flushing to the Treatment is usually cosmetic or often in patients with poorly con- face. This condition is seen in 3–5% for cases involving irritation. Excision trolled type 2 diabetes. The sudden of people with diabetes. In a study may be performed with forceps, fine- appearance of EX can be worrisome of 150 participants comparing facial grade scissors, cryosurgery with liquid to patients and may prompt a visit to redness association with diabetes, nitrogen, or electrodesiccation (9). the physician. Gitelson et al. (18) showed that 59% These lesions can be the first Diabetic Dermopathy of patients with diabetes had marked- sign of diabetes. The decrease in ly red faces compared to slightly red Population studies from Sweden lipoprotein lipase activity seen in or not red (21 and 20%, respectively). demonstrate that diabetic dermopa- insulin-dependent diabetes results The appearance of RF correlates thy (DD) affects 33% of patients with in an accumulation of serum tri- with poor glucose control. No treat- type 1 diabetes, 39% of patients with glycerides. Occasionally, when the ment is needed. Strict glycemic type 2 diabetes, and 2% of control serum triglyceride level reaches 2,000 control can improve the appear- subjects (9). However, a more recent mg/dL, lipids will deposit in the skin ance and prevent complications of study found that DD is present in (13). Cutaneous presentation is asso- microangiopathy in other organ sys- only 0.2% of people with well-con- ciated with hypertriglyceridemia tems (12,19). trolled type 2 diabetes (10). types I, III, IV, and V or secondary This condition presents as small Epidermal Necrolysis/Stevens- (<1 cm), well-demarcated, atrophic Johnson Syndrome depressions, macules, or papules on Stevens-Johnson syndrome is a rare the pretibia and is considered to be mucocutaneous necrotizing condition a sign of insulin resistance (Fig. 2). diagnosed in 1–6 cases per million Lesions heal and disappear within people annually worldwide (20). A 1–2 years on their own, leaving atro- more severe form called toxic epider- phic hypopigmentation at the site of mal necrolysis is diagnosed at a rate of origin (3). Little is known about the 0.4–1.2 cases per million people per relationship of DD to diabetes. On year (21). Because of their similar eti- cadaveric skin biopsy, 4 of 14 sam- ■ FIGURE 3. Eruptive xanthomas. ology, pathogenesis, and clinical and ples demonstrated moderate to severe histological presentation, it has been

VOLUME 33, NUMBER 1, WINTER 2015 41 PRACTICAL POINTERS proposed to refer to both conditions ticularly important. EN is treated as epidermal necrolysis (EN) (22). supportively as a massive burn, with In most cases, EN begins on first emphasis on preservation of intact exposure to an inciting drug, within skin and supportive symptomatic 8 weeks of the first dose. The dipep- measures. Patients presenting with tidyl peptidase-4 inhibitor sitagliptin EN should be transferred to a qual- has been associated with cases of ified intensive care unit as soon as Stevens-Johnson Syndrome (23). It possible (31). Immunosuppressive could present with fever, headache, drugs have not proven to be rhinitis, cough, malaise, burning helpful (24). eyes, and dysphagia (24). In 1–3 days, Conditions Associated With EN progresses to mucocutaneous Type 1 Diabetes ulcerations, necrosis and detachment of epidermis, severe stomatitis, and Necrobiosis Lipoidica ■ FIGURE 4. Necrobiosis lipoidica. ocular involvement (25). Initial dusky Necrobiosis lipoidica (NL) is rare, ap- red, pruritic macules are distributed pearing in 0.3–1.6% of people with trauma (35). Other treatments that symmetrically over the face, upper type 1 diabetes, more often in women have been used include pentoxifyllin, trunk, and proximal limbs, with dis- than men (12,32). Typical lesions of cyclosporine, ticlopidine infliximab, tal limbs relatively spared (26). These NL occur in young and middle-aged and thalidomide. Some case reports lesions progressively coalesce and patients and present most common- have shown benefit from nicotin- develop dark necrotic centers as they ly on the pretibial skin as irregular, amide, clofazimine, cloroquine, and spread down the trunk. Nickolsky’s painless ovoid plaques with a yellow topical tretanoin. These later treat- sign—displacement of epidermis atrophic center and a red to purple ments do require dermatology referral with lateral pressure—is positive over periphery. The lesions are usually to manage medications and potential the blistering epidermis. multiple and bilateral. Lesions may The pathophysiology of EN is ulcerate spontaneously or from trau- side effects (32,36). under-investigated. Presence of a ma (33,34). Of the patients with NL, Vitiligo strong cell-mediated immunologi- 11–65% have type 1 diabetes at the Vitiligo affects 0.3–0.5% of world cal response involving natural killer time of cutaneous diagnosis (34). + population, making it the most com- cells and CD8 T lymphocytes spe- Ninety percent of people with NL mon depigmenting disorder. Patients cific for the causative agent has been who do not have diabetes eventually present with patches of depigmenta- noted. This reaction also involves develop diabetes (mostly type 1 dia- tion of skin and hair (Fig. 5). monocytes and granulocytes (27). betes) (12). Glycemic control has no Other factors that amplify the reac- effect on the course of NL (16). Possible etiologies are both envi- tion are still being investigated. The NL is a benign condition, and ronmental and polygenetic. This end result of hypersensitivity is a dermatology referral is not usually condition affects males and females full-thickness keratinocyte apoptosis necessary. The cause of NL is cur- equally (37). Out of several subtypes, of the epidermis and mucous mem- rently unknown. Proposed causes generalized vitiligo is most common. branes (28). Although drugs and are localized trauma, microangiop- It is associated with autoimmune their components are the most com- athy, immunoglobulins and fibrin diseases in 20–30% of cases. The mon etiologies, viruses, Mycoplasma deposition, and metabolic changes most common associations are with pneumoniae, and immunizations are (32,35). Although NL is benign, its Hashimoto’s thyroiditis, Grave’s dis- also suspected. More than 100 medi- appearance is cosmetically distressing ease, rheumatoid arthritis, psoriasis, cations have been identified as causes to patients (Fig. 4). type 1 diabetes (usually adult-on- of EN (29). If a person develops EN The mainstay of treatment is set), pernicious anemia, systemic while on sitagliptin, the drug’s man- currently steroids, either topical, lupus erythematosus, and Addison’s ufacturer recommends discontinuing intralesional, or, rarely, systemic. disease (38). A 2009 study of 50 therapy as soon as a hypersensitivity Steroids are cost-effective and have reaction is noted (30). low side-effect profiles. Steroid use patients with type 1 diabetes reported EN is a life-threatening emer- is beneficial to control the initial that 4% of subjects had vitiligo (39). gency. Current treatments include erythema in early lesions but fails to Genetic vitiligo (GV) is most often a withdrawal of all medications that help with the atrophic component gradually progressive disorder and is would not be life-threatening. of the lesions and can worsen atro- unresponsive to treatment. However, Discontinuation of medications phy. Stockings are advised to help some cases do stop progressing. GV started in the past 8 weeks is par- with stasis changes and protect from complications are long duration,

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the forearms and hands. The lesions vessels, thinned suprapapillary plate, present as clear bulla on non-inflamed and differentiation), intermittent par- bases. They are painless and contain akeratosis, and multiple biochemical, sterile fluid. Lesion size can range immunological, and vascular abnor- from a few millimeters to a few cen- malities (e.g., lymphocyte and neu- timeters (16). trophil infiltration). Blister pathology is currently This condition can develop at any unknown. Diabetic bullae typically age, with the most common onset appear in individuals who have had between 15 and 30 years of age; it is type 1 diabetes for many years. uncommon in people <10 years of However, this condition may be the age. It affects 2–3% of the U.S. pop- first sign of diabetes (41). Lesions ulation. Approximately 9% of people resolve on their own in 2–5 weeks. with diabetes (type 1 or type 2) has ■ FIGURE 5. Vitiligo. Differential diagnosis includes bul- psoriasis (42). Recent research shows lous pemphigoid, which can be that psoriasis may raise predisposition Koebner phenomenon, leukotrichia, ruled out by submitting a biopsy for developing diabetes mellitus, just and mucosal involvement (37). of the lesion for direct and indirect as it does for heart attack and stroke. Dermatological therapy attempts immunofluorescence. The lesions A 13-year study with 52,000 partic- to reduce T-cell response and resemble those in acquired epider- ipants concluded that people with induce melanocyte migration and molytic bullosa, porphyria cutanea psoriasis have a 49–56% greater risk regeneration. Corticosteroids with tarda, autoimmune or impetiginous of developing type 2 diabetes later in ultraviolet B or calcineurin inhibitors bullae, erythema multiforme, or drug life (43). or systemic psoralen and ultraviolet A eruption (42). Dermatologists often Most people with psoriasis (PUVA) light are first-line treatments. make the diagnosis of diabetic bulla; will be treated by a dermatologist. Calcipotriol, topical PUVA, excimer after diagnosis, this condition can be Treatment consists of topical and laser, corticosteroid pulse therapy, managed by PCPs. systemic immunomodulators, as and surgical melanocyte grafting are The treatment is focused on well as ultraviolet light and laser some of the treatment options. These infection prevention (19). If the bul- application. Topical treatments are treatments are long and complicated lae become large and symptomatic, effective in most cases; however, they by numerous side effects. Use of they can be aspirated, leaving the carry a 40% adherence rate because sunscreen is recommended but also roof intact to protect the skin bar- of time-consuming application and controversial because of ultraviolet B rier (16). Individuals may use saline cosmetic inappropriateness (44). stimulation of melanocytes and the compresses for symptomatic relief. Both cream and ointment should be possibility of repopulation, as well as Topical antibiotics or steroids are prescribed. Phototherapy with ultra- photo-adaptation of vitiligo-affected generally not necessary (41). violet A, ultraviolet B, and psoralein skin. Moderate exposure to sun Other Diabetes-Related has been used for several decades is recommended. Conditions and has shown good response in The psychosocial impact of vitiligo mild cases (45). can be substantial, and patient sup- Psoriasis Lichen Planus port groups are available. Numerous Psoriasis is a chronic, inflammatory, nontraditional treatments are polygenic skin disorder with envi- Lichen planus is an uncommon disor- < attempted by patients but should be ronmental triggers such as trauma, der affecting 1% of the general pop- investigated for safety before admin- medications, and infection. Psoriasis ulation. Onset is common in middle istration (40). is characterized by erythematous age (30–60 years of age). However, scaly papules and plaques with pus- the prevalence of lichen planus in Bullosis Diabeticorum tular and erythrodermic eruptions people with type 1 or type 2 diabetes Bullosis diabeticorum, or diabetic occurring most commonly in areas of has been noted to be 2–4% (39,46). bullae, are seen in 0.5% of individ- friction such as scalp, elbows, knees, Lichen planus may affect the skin uals with type 1 diabetes. This con- hands, feet, trunk, and nails. Koebner (termed “cutaneous,” with several dition is seen more often in men and phenomenon is a well-documented variants), the oral cavity (“oral”), the in those with longstanding peripheral factor, in which a plaque develops on genitalia (“vulvar” or “penile”), the neuropathy. The lesions arise sponta- the site of the injury. Histologically, scalp (“lichen planopilaris”), the nails, neously and are primarily on the dor- Koebner phenomenon presents with or the esophagus (47,48). sa and the sides of the lower legs and alterations in epidermal growth (elon- Lichen planus presents as grouped, feet. Occasionally, they are seen on gated rete ridges with dilated blood symmetric, erythematous to viola-

VOLUME 33, NUMBER 1, WINTER 2015 43 PRACTICAL POINTERS ceous, flat-topped, polygonal papules because of the typical spontaneous clears spontaneously in a period of distributed mainly in flexural aspects remission of lichen planus (47,48). months or years. Women are affected of arms and legs and rarely can Xerosis more often than men. Sclerederma diabeticorum involves the fingers, appear on the trunk (“Blaschkoid” Xerosis is another name for dry skin. hands, and trunk. It is in the family or “zosteriform”) and inverse (“inter- It is the second most common skin of diabetic thick skin called mor- triginous”) (48). Variants may include manifestation in people with diabe- phea and is the most severe, systemic ulcerative and perforating types. tes. In a study of 100 patients with sclerederma (53). Koebner phenomenon is common, diabetes and skin lesions, xerosis was and pruritus associated with lichen present in 44% of the patients (50). Granuloma Annulare planus is intense and heals with post- Patients with renal disease also fre- Granuloma annulare (GA) presents inflammatory hyperpigmentation. quently suffer from xerosis. as erythematous to flesh-colored Clinically, cutaneous lichen pla- No referral to a dermatologist is papules coalescing to form an oval or nus presents as flat-topped, violaceous necessary for xerosis. PCPs should ring lesion. GA often presents asymp- papulosqamous eruptions on the skin. educate patients about the impor- tomatically but can cause pruritus or It is classically described as the “four tance of skin hygiene, including a burning sensation (54). The asso- Ps”: pruritic, purple (violaceous), applying fragrance-free creams or ciation between granuloma annulare polygonal, and papules or plaques. lotions within 3 minutes of bathing and diabetes is controversial. One Papules may be isolated and a few mil- to trap moisture within the skin. retrospective study showed a 12% limeters in diameter or may coalesce Sclerederma Diabeticorum association between GA and diabetes (55). Another study reported diabetes to form larger plaques (48). Fine white Sclerederma diabeticorum is a con- in 21% of 100 cases of generalized lines may be visible on the surface of dition of thick, indurated, erythem- granuloma annulare (GGA) and in papules or plaques and are known as atous plaques occurring on the upper 9.7% of 1,350 cases of localized GA “Wickham’s striae.” Diagnosis can back and neck. Lesions may have (56). Skin lesions may often precede be made based on clinical findings. erythema. This condition is seen in diabetes. Struder et al. (55) suggest If clinical recognition is questionable, ~2.5–14% of individuals with di- that patients with recurrent localized a biopsy is indicated. Etiology of the abetes (51). The condition is more granuloma annulare or the dissemi- condition is unknown. It is suspected common in obese middle-aged men nated form be given a glucose toler- that CD8+ T cells and a Th1 immune with type 2 diabetes. Patients with ance test. scleroderma diabeticorum are often response (cell-mediated mechanism The pathogenesis of GA is cur- asymptomatic; however, neck and against keratinocytes) is involved (49). rently unknown. Treatment options back pain may occur. The diagnosis Most cases of lichen planus will are topical steroids, intralesional is often made clinically, although a be managed by a dermatologist. steroids, isotretinoin, dapsone, definitive diagnosis is confirmed by Treatment of cutaneous lichen pla- antimalarials, and phototherapy. skin biopsy. nus is focused on pruritus control Untreated lesions may spontaneously The pathogenesis of scleroderma (47). The potency of topical steroids regress; this is more common in the diabeticorum is thought to be linked used depends on the site involved. On localized form of GA than in the dis- to increased stimulation of insulin the trunk and extremities, high-po- seminated form (57). Localized forms and nonenzymatic glycosylation of tency corticosteroids are indicated, can be treated easily and followed by collagen. This causes increased col- whereas on the face and intertrigi- PCPs. Recurrent GA or disseminated lagen cross-linking, rendering the nous areas, medium- to low-potency GA can be worked up by PCPs and collagen fibers resistant to degrada- ointments are used. This is because referred to a dermatologist. GGA tion by collagenase and leading to tends to be idiopathic. However, it of steroid-induced atrophy. Treatment increased amounts of collagen. has been associated with diabetes efficacy should to be checked in 3 Treatments have showed limited and with diseases such as autoim- weeks. With generalized involvement, benefits. Some treatment options mune thyroiditis, HIV, hepatitis C, light therapy may be added to the include steroids, methotrexate, and Epstein-Barr virus infection, sarcoid- treatment plan. Intralesional cortico- ultraviolet light phototherapy (15,52). osis, and internal malignancies (58). steroids are applied to thicker lesions Differential diagnosis includes (49). Systemic glucocorticoids, pho- Sclerederma Buschke, also associated Acquired Perforating totherapy with PUVA and ultraviolet with type 1 diabetes. Sclerederma Dermatosis B, and oral acitretin can be beneficial Buschke presents as thickening Acquired perforating dermatosis in people who are not candidates for mainly on the neck, shoulders, and presents as dome-shaped papules and topical steroid therapy. Few studies upper limbs, often after an upper-re- nodules with hyperkeratotic plugs. have been conducted on treatments spiratory infection. This condition This condition is characterized by

44 CLINICAL.DIABETESJOURNALS.ORG d u f f e t a l . the transepidermal elimination of and . The con- tion is increased with , some component of the dermis. The dition itself may cause which favors Candida proliferation. cutaneous perforating disorders have ulcers (62). Proper nail care, well-fit- Candidal vulvovaginitis is the most classically been divided into four ting shoes, and immediate attention common of all cases, and perianal types: elastosis perforans serpiginosa, to nail infections are important. candidiasis is also common in both reactive perforating collagenosis, per- males and females. Other presen- Periungual Telangectasias forating folliculitis, and Kyrle’s dis- tations include thrush (infection of ease. Perforating disorders have been Periungual telangectasias present as oral mucosa and perleche), angular associated with chronic renal failure, nail fold erythema, dilated blood cheilitis, intertrigo (infection of skin- dialysis, and diabetes. Acquired perfo- vessels visible to the naked eye, fin- folds and erosio interdigitalis blasto- rating dermatitis is seen in both type gertip tenderness, and thick cuticles. mysetica chronica), finger web space 1 and type 2 diabetes (15,16,59). Telangectasias arise in the nail beds of infection, paronychia (infection of In most cases, the renal disease is a people with diabetes after loss of cap- soft tissue around the nailplate), and complication of illary loops and dilation of remaining onichomycosis (infection of the nail) (60). The lesions of acquired perfo- capillaries. The condition is present (3). Common cutaneous fungal infec- rating dermatosis are most commonly in up to 49% of people with diabetes tions are summarized in Table 1. seen on the trunk and extremities and (63). Some patients also experience Rarely, critically ill patients with tend to be pruritic. fingertip tenderness. No treatment is (DKA) may It has been thought that the mech- necessary for this condition. be diagnosed with mucormycosis, anism of action may be derived from Infections Associated With an acute, severe, soft-tissue infec- epidermal trauma, a foreign-body Diabetes tion caused by Mucor, Rhizopus, and reaction to the collagen in the dermis, Absidia species. Saprophytic fungi or metabolic products from uremia Cutaneous Infections prefer the low pH environments seen (59,61). Dialysis has not shown ther- Infections form the largest group of during DKA and thrive in hyper- apeutic value, but renal transplant has cutaneous conditions affecting people glycemia. Some fungi also utilize been shown to be effective in clearing with diabetes. In a 2009 study of 50 ketones as nutritional substance (3). the lesions (60). Treatment options patients, 55% of those with diabetes An estimated 50–75% of cases of include avoidance of scratching, topi- had infectious skin manifestations at rhinocerebral mucormycosis occur cal or systemic steroids, phototherapy, some time (39). Another study re- in patients with diabetes (65). retinoid, and antihistamines. ported a 61% prevalence rate in skin Mucormycosis is progressive and infections in people with diabetes Onychodystrophy poorly responds to systemic anti- (64). Cutaneous infections include fungals. Treatment options include Onychodystrophy presents as exces- candidiasis, dermatophytosis, and itraconazole, fluconazole, ampho- sive nail thickening and deformity, bacterial infections. These are de- tericine B, and voriconazole. This which may cause accumulation of scribed in more detail below. condition is often fatal. debris and subsequent infection of the toe that should be treated as a di- Candidiasis Dermatophytosis abetic ulcer. Poorly fitting shoes may Mucocutaneous candidiasis is caused Tinea or dermatophytoses are super- cause repeated trauma and worsening most commonly by Candida albicans ficial infections of the skin, hair, and of the injured site (61). In patients and presents as red plaques with char- nails by fungus. Tinea corporis, tinea with diabetes, onychodystrophy is the acteristic white adherent exudate and pedis (Fig. 6), and onychomycosis result of poor peripheral circulation satellite pustules. The risk of infec- (Fig. 7) are common dermatophyte

TABLE 1. Common Cutaneous Fungal Infections Infection Definition Candidal vulvovaginitis Infection of vaginal mucosa Perianal candidiasis Infection of perineum and perianal area Thrush Infection of the oral mucosa Perleche Infection of labial commissures of mouth angles Intertrigo Infection of skinfolds Erosion interdigitalis blastomysetica chronica Infection of finger web space Paronychia Infection of the soft tissue around the nail plate Onichomycosis Infection of the nail

VOLUME 33, NUMBER 1, WINTER 2015 45 PRACTICAL POINTERS

TABLE 2. Treatment Options for Common Fungal Infections Cutaneous Fungal Treatment Options Infections Candidal vulvovaginitis Butoconazole vaginal 2% cream Clotrimazole vaginal 1% cream, 100 mg vaginal tablet Miconazole 2% cream, 100 mg vaginal suppository, 200 mg vaginal suppository, 1,200 mg vaginal suppository Ticonazole vaginal 6.5% ointment ■ FIGURE 6. Tinea pedis. Fluconazole 150 mg × 1 dose Nystatin vaginal 100,000-unit vaginal tablet Perianal candidiasis Miconazole topical 2% cream, 4% cream Miconazole insert 100 mg, 200 mg, 1,200 mg Diflucan 150 mg by mouth× 1 Thrush Nystatin 100,000 U/mL Clotrimazole 10 mg Miconazole 50 mg Gentian violet topical 1% Perleche Nystatin/triamcinolone topical 100,000 U/0.1% ■ FIGURE 7. Onchiomycosis. Clotrimazole topical 1% Miconazole topical 2% infections encountered in people with Ketoconazole topical 2% diabetes. In a 2013 study of 76 pa- Intertrigo Fluconazole 200 mg daily × 2–4 weeks tients with tinea corporis, the main predisposing factor was xerosis (66). Itraconazole 200 mg daily × 2–4 weeks In a 2001 study of 171 people with Ketoconazole 200 mg daily × 2–4 weeks diabetes compared with 276 control Terbinafine 500 mg by mouth twice subjects, the most common infection daily × 6–8 weeks in people with diabetes was tinea Nystatin topical 100,000 units/g ointment, pedis, followed by distal subungual powder, cream onychomycosis (65). This study did Erosion interdigitalis Clotrimazole 1% cream or solution not show a correlation between der- blastomysetica chronica matophytosis and duration or type of Paronychia Fluconazole 200 mg daily × 2–4 weeks diabetes or its complications. Itraconazole 200 mg daily × 2–4 weeks Trichophyton rubrum Trichophy­ , Ketoconazole 200 mg daily × 2–4 weeks ton mentagrophytes, and Trichophyton Terbinafine 500 mg by mouth twice tonsurans are the most common der- daily × 6–8 weeks matophytes. Because dermatophyte infections are so common in the Onichomycosis Terbinafine 250 mg general population, no dermatology in people with diabetes. Diabetic foot the most common bacterial infections referral is necessary. Treatment con- ulcers are the leading type of morbid- in uncontrolled diabetes. They re- sists of topical antifungals or systemic ity in diabetes. They develop because spond well to antibiotics and surgical antifungal medication. Table 2 sum- of decreased sensation from diabetic drainage. Pseudomonas aeruginosa is marizes common fungal infections neuropathy and unrecognized inju- another common and the topical and oral antifungal ry, with subsequent infection. White organism. therapies used to treat them. blood cell dysfunction resulting from External ear canal infection Bacterial Infections increased glucose levels allows bacte- caused by Pseudomonas aeruginosa Cutaneous bacterial infections are ria to proliferate. Staphylococcal fol- is also frequent in people with dia- more common, as well as more severe, liculitis or skin abscesses are among betes. Pseudomonads thrive in moist

46 CLINICAL.DIABETESJOURNALS.ORG d u f f e t a l . environments full of oxygen. Lesions gov/DIABETES//pubs/factsheet11.htm. 16. Ferringer T, Miller F 3rd. Cutaneous Accessed 25 August 2013 can be recognized by characteristic manifestations of diabetes mellitus. 2. Demirseren DD, Emre S, Akoglu G, et Dermatol Clin 2002;20:483–492 green-blue pigment, as well as fluores- al. Relationship between skin diseases and 17. Namazi MR, Jorizzo JL, Fallahzadeh cence with Wood’s lamp application. extracutaneous complications of diabetes MK. Rubeosis faciei diabeticorum: a Microscopically, pseudomonads are mellitus: clinical analysis of 750 patients. common, but often unnoticed, clini- identified as gram-negative rods. Am J Clin Dermatol 2014;15:65–70 cal manifestation of diabetes mellitus. ScientificWorldJournal 2010;10:70–71 Patients may present with otalgia, 3. Kalus AA, Chien AJ, Olerud JE. Chapter 151: Diabetes mellitus and other endocrine 18. 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Accessed 11 Available from http://accessmedicine. to a dermatologist may be warranted November 2014 mhmedical.com/content.aspx?book- in some cases. As the incidence and 10. Ragunatha S, Anitha B, Inamadar id=392§ionid=41138737. Accessed 11 AC, Palit A, Devarmani SS. Cutaneous November 2014 prevalence of diabetes increases, skin disorders in 500 diabetic patients attend- 25. Stevens AM, Johnson FC. A new erup- manifestations associated with diabe- ing diabetic clinic. Indian J Dermatol tive fever associated with stomatitis and tes will become more common. Thus, 2011;56:160–164 ophthalmia: report of two cases in children. PCPs should familiarize themselves 11. McCash S, Emanuel PO. Defining Am J Dis Child 1922;24:526–533 diabetic dermopathy. J Dermatol 26. Mockenhaupt M. Severe drug-induced with their presentation and treatment. 2011;38:988–992 skin reactions: clinical pattern, diagnos- 12. Paron NG, Lambert PW. Cutaneous tics and therapy. J Dtsch Dermatol Ges Duality of Interest manifestations of diabetes mellitus. Prim 2009;7:142–160 Care 2000;27:371–383 Jay. Shubrook has received research grant 27. Paquet P, Nikkels A, Arrese JE, support from Sanofi Aventis and serves 13. Martínez DP, Díaz JÓF, Bobes CM. Vanderkelen A, Piérard GE. Macrophages on the Global Primary Care Diabetes Eruptive xanthomas and acute pancreatitis and tumor necrosis factor alpha in toxic Board of Eli Lilly. No other potential in a patient with hypertriglyceridemia. Int epidermal necrolysis. Arch Dermatol conflicts of interest relevant to this article Arch Med 2008;1:6 1994;130:605–608 were reported. 14. Binic´ I, Jankovic´ A. Eruptive xanthomas 28. Sassolas B, Haddad C, Mockenhaupt M, associated with diabetes mellitus. Chin Med et al. ALDEN, an algorithm for assess- References J 2009;122:2074–2075 ment of drug causality in Stevens-Johnson 1. Centers for Disease Control and 15. Levy L, Zeichner JA. 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