ABSTRACT

Diabetes mellitus is a common and debilitating disease that affects a variety of organs including the skin. Between thirty and seventy percent of patients with diabetes mellitus, both type 1 and type 2, will present with a cutaneous complication of diabetes mellitus at some point during their lifetime. A variety of dermatologic manifestations have been linked with diabetes mellitus; these conditions vary in severity and can be benign, deforming, and even life-threatening. Such skin changes can offer insight into patients’ glycemic control and may be the first sign of metabolic derangement in undiagnosed patients with diabetes. Recognition and management of these conditions is important in maximizing the quality of life and in avoiding serious adverse effects in patients with diabetes mellitus. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

INTRODUCTION

The changes associated with diabetes mellitus can affect multiple organ systems. Between thirty and seventy percent of patients with diabetes mellitus, both type 1 and type 2, will present with a cutaneous complication of diabetes mellitus at some point during their lifetime (1). Dermatologic manifestations of diabetes mellitus have various health implications ranging from those that are aesthetically concerning to those that may be life-threatening. Awareness of cutaneous manifestations of diabetes mellitus can provide insight into the present or prior metabolic status of patients. The recognition of such findings may aid in the diagnosis of diabetes or may be followed as a marker of glycemic control. The text that follows describes the relationship between diabetes mellitus and the skin, more specifically: (1) skin manifestations strongly associated with diabetes, (2) non-specific dermatologic signs and symptoms associated with diabetes, (3) dermatologic diseases associated with diabetes, (4) common skin infections in diabetes, and (5) cutaneous changes associated with diabetes medications.

SKIN MANIFESTATIONS STRONGLY ASSOCIATED WITH DIABETES MELLITUS

Acanthosis Nigricans

EPIDEMIOLOGY

Acanthosis nigricans (AN) is a classic dermatologic manifestation of diabetes mellitus that affects men and women of all ages. AN is more common in type 2 diabetes mellitus (2) and is more prevalent in those with darker skin color. AN occurs more frequently in African Americans, Hispanics, and Native Americans (3). AN is observed in a variety of endocrinopathies associated with resistance to insulin such as acromegaly, Cushing syndrome, obesity, polycystic ovarian syndrome, and thyroid dysfunction. Unrelated to insulin resistance, AN can also be associated with malignancies such as gastric adenocarcinomas and genitourinary cancers, as well as with autoimmune disorders, various medications, and familial disorders (4, 4a-f).

PRESENTATION

AN presents chronically as multiple poorly demarcated plaques with grey to dark brown hyperpigmentation and a thickened velvety to verrucous texture (figure 1). Classically, AN has a symmetrical distribution and is located in intertriginous or flexural surfaces such as the back of the neck, axilla, elbows, palmar hands (also known as “tripe palms”), inframammary creases, umbilicus, or groin. Affected areas are asymptomatic; however, extensive involvement may cause discomfort or fetor. Microscopy shows hyperkeratosis and epidermal papillomatosis with acanthosis. The changes in skin pigmentation are primarily a consequence of hyperkeratosis, not changes in melanin. AN can present prior to the clinical diagnosis of diabetes; the presence of AN should prompt evaluation for diabetes mellitus and for other signs of insulin resistance.

Figure 1.

Acanthosis nigricans. From Wikipedia.

PATHOGENESIS

The pathogenesis of AN in diabetes is multifactorial. It is well-established that a hyperinsulin state directly activates insulin growth factor receptors (IGF), specifically IGF-1, on keratinocytes and fibroblasts, provoking cell proliferation, resulting in the aforementioned cutaneous manifestations of AN (5,6). Hyperinsulinemia also decreases circulating levels of IGF binding protein 1 and 2, increasing IGF-1 blood levels for the same effect (6a).

TREATMENT

Treatment of AN may improve current lesions and prevent future cutaneous manifestations. AN is best managed with lifestyle changes such as dietary modifications, increased physical activity, and weight reduction. In patients with diabetes, pharmacologic adjuvants, such as metformin, that improve glycemic control and reduce insulin resistance are also beneficial (7). One case report demonstrated the effectiveness of the glucagon peptide receptor 1 (GLP-1) receptor agonist liraglutide in improving the clinical appearance of AN (7a). Primary dermatologic therapies are usually ineffective especially in patients with generalized involvement. However, in those with thickened or macerated areas of skin, topical retinoids, topical vitamin D analogs such as calciprotriol, or topical keratolytics such as ammonium lactate and salicylic acid are the primary treatments used for localized lesions (8-10). Systemic retinoids such as isotretinoin and acitretin have been associated with improvement in patients with extensive involvement but are not often used due to risk of systemic adverse effects and relapse upon discontinuation (10a). Topical urea, trichloroacetic acid, glycolic acid peels, and laser therapy have also been suggested as localized treatment modalities, though addressing the underlying disorder remains the most effective intervention.

Diabetic Dermopathy

EPIDEMIOLOGY

Diabetic dermopathy (DD), also known as pigmented pretibial patches or diabetic shin spots, is the most common dermatologic manifestations of diabetes, occurring in as many as one-half of those with diabetes (11). Although disputed, some consider the presence of DD to be pathognomonic for diabetes. DD has a strong predilection for men and those older than 50 years of age, with the number of lesions increasing with the duration of diabetes, increasing age, and HbA1C levels (12, 12a). Although DD may antecede the onset of diabetes, it occurs more frequently as a late complication of diabetes and in those with microvascular disease. DD often occurs prior to the onset of neuropathy and retinopathy; nephropathy is also regularly present in patients with DD (12a). An association with cardiovascular disease has also been identified, with one study showing 53% of non- insulin-dependent diabetes mellitus with DD had coexisting coronary artery disease (13).

PRESENTATION

DD initially presents with rounded, dull, red papules that progressively evolve over one-to-two weeks into well-circumscribed, atrophic, brown macules with a fine scale (figure 2). Normally after about eighteen to twenty-four months, lesions dissipate and leave behind an area of concavity and hyperpigmentation. At any time, different lesions can present at different stages of evolution. The lesions are normally distributed bilaterally and localized over bony prominences. The pretibial area is most commonly involved, although other bony prominences such as the forearms, lateral malleoli, or thighs may also be involved. Aside from the aforementioned changes, patients are otherwise asymptomatic. DD is a clinical diagnosis that should not require a skin biopsy, which should be especially avoided in patients with poor wound healing (12a). Histologically, DD is rather nonspecific; it is characterized by lymphocytic infiltrates surrounding vasculature, engorged blood vessels in the papillary dermis, and dispersed hemosiderin deposits. Moreover, the histology varies based on the stage of the lesion. Immature lesions present with epidermal edema as opposed to epidermal atrophy which is representative of older lesions (14).

Figure 2.

Diabetic dermopathy.

PATHOGENESIS

The origin of DD remains unclear, however, mild trauma to affected areas (15), hemosiderin and melanin deposition (16), microangiopathic changes (12A, 17), and destruction of subcutaneous nerves (18) have all been suggested.

TREATMENT

Treatment is typically avoided given the asymptomatic and self-resolving nature of DD as well as the ineffectiveness of available treatments. However, DD often occurs in the context of microvascular complications and neuropathies (12); hence, patients need to be examined and followed more rigorously for these complications. Although improvement of DD lesions is variable with glycemic control, managing blood glucose can help prevent progression of microvascular complications (18a).

Diabetic Thick Skin

Skin thickening is frequently observed in patients with diabetes. Affected areas of skin can appear thickened, waxy, or edematous. These patients are often asymptomatic but can have a reduction in sensation and pain. Although different parts of the body can be involved, the hands and feet are most frequently involved. Ultrasound evaluation of the skin can be diagnostic and exhibit thickened skin. Subclinical generalized skin thickening is the most common type of skin thickening. Diabetic thick skin may represent another manifestation of scleroderma-like skin changes, limited joint mobility, or scleredema diabeticorum, which are each described in more detail below.

SCLERODERMA-LIKE SKIN CHANGES

Epidemiology

Scleroderma-like skin changes are a distinct and easily overlooked group of findings that are commonly observed in patients with diabetes. Ten to fifty percent of patients with diabetes present with the associated skin findings (32). Scleroderma-like skin changes occur more commonly in those with type 1 diabetes and in those with longstanding disease (33). There is no known variation in prevalence between males and females, or between racial groups.

Presentation

Scleroderma-like skin changes develop slowly and present with painless, indurated, occasionally waxy appearing, thickened skin. These changes occur symmetrically and bilaterally in acral areas. In patients with scleroderma-like skin changes the acral areas are involved, specifically the dorsum of the fingers (sclerodactyly), proximal interphalangeal, and metacarpophalangeal joints. Severe disease may extend centrally from the hands to the arms or back. A small number of patients with diabetes may develop more extensive disease, which presents earlier and with truncal involvement. The risk of developing nephropathy and retinopathy is increased in those with scleroderma-like skin changes who also have type 1 diabetes (33,34). The aforementioned symptoms are also associated with diabetic hand syndrome which may present with limited joint mobility, palmar fibromatosis (Dupuytren's contracture), and stenosing tenosynovitis (“trigger finger”) (35). The physical exam finding known as the “prayer sign” (inability to flushly press palmar surfaces on each hand together) may be present in patients with diabetic hand syndrome and scleroderma-like skin changes (36). On histology, scleroderma-like skin changes reveal thickening of the dermis, minimal-to-absent mucin, and increased interlinking of collagen. Although on physical exam scleroderma may be difficult to distinguish from these skin changes, scleroderma-like skin changes are not associated with atrophy of the dermis, Raynaud’s syndrome, pain, or telangiectasias.

Pathogenesis

Although not fully understood, the pathogenesis is believed to involve the strengthening of collagen as a result of reactions associated with advanced glycosylation end products or a buildup of sugar alcohols in the upper dermis (37,38).

Treatment

Scleroderma-like skin changes is a chronic condition that is also associated with joint and microvascular complication. Therapeutic options are extremely limited. One observational report has suggested that very tight blood glucose control may result in the narrowing of thickened skin (39). In addition, aldose reductase inhibitors, which limit increases in sugar alcohols, may be efficacious (38). In patients with restricted ranges of motions, physical therapy can help to maintain and improve joint mobility.

LIMITED JOINT MOBILITY

Epidemiology

Limited Joint Mobility (LJM), also known as diabetic cheiroarthropathy, is a relatively common complication of long-standing diabetes mellitus. The majority of patients with LJM also present with scleroderma-like skin changes (38,40). The prevalence of LJM is 4% to 26% in patients without diabetes and 8% to 58% in patients with diabetes (41).

Presentation

LJM presents with progressive flexed contractures and hindered joint extension, most commonly involving the metacarpophalangeal and interphalangeal joints of the hand. The earliest changes often begin in the joints of the fifth finger before then spreading to involve the other joints of the hand (38). Patients may present with an inability to flushly press the palmar surfaces of each of their hands together (“prayer sign”) (figure 3) or against the surface of a table when their forearms are perpendicular to the surface of the table (“tabletop sign”) (42).

Pathogenesis

These changes occur as a result of periarticular enlargement of connective tissue. Pathogenesis likely involves hyperglycemia induced formation of advanced glycation end-products, which accumulate to promote inflammation and the formation of stiffening cross-links between collagen (43). LJM is strongly associated with microvascular and macrovascular changes and diagnosis of LJM should prompt a workup for related sequela (44). Patients with LJM may also be at an increased risk for falls (45).

Treatment

There are no curative treatments. Symptomatic patients may benefit from non-steroidal anti-inflammatory drugs or targeted injection of corticosteroids (43). LJM is best managed with improved glycemic control (46), as well as regular stretching to maintain and minimize further limitations in joint mobility.

Figure 3.

Limited joint mobility.

SCLEREDEMA DIABETOCORUM

Epidemiology

Scleredema is a chronic and slowly progressive sclerotic skin disorder that is often seen in the context of diabetes, in which case it is classified as scleredema diabeticorum (SD). Whereas 2.5% to 14% of all patients with diabetes have scleredema, over 50% of those with scleredema present with concomitant diabetes (47). SD has a proclivity for men with a long history of diabetes (47a). It remains unclear whether there is a predilection for SD in those with type 1 diabetes (48) compared to those with type 2 diabetes (48).

Presentation

SD presents with gradually worsening indurated and thickened skin. These skin changes occur symmetrically and diffusely. The most commonly involved areas are the upper back, shoulders, and back of the neck. The face, chest, abdomen, buttocks, and thighs may also be involved; however, the distal extremities are classically spared. The affected areas are normally asymptomatic but there can be reduced sensation. Patients with severe longstanding disease may develop a reduced range of motion, most often affecting the trunk. In extreme cases, this can lead to restrictive respiratory problems. A full-thickness skin biopsy may be useful in supporting a clinical presentation. The histology of SD differentiates it from the autoimmune disease scleroderma, displaying increased collagen and a thickened reticular dermis, with a surrounding mucinous infiltrate, without edema or sclerosis.

Pathogenesis

Although many theories center on abnormalities in collagen, there is no consensus regarding the pathogenesis of SD. The pathogenesis of SD may involve an interplay between non-enzymatic glycosylation of collagen, increased fibroblast production of collagen and mucin, or decreases in collagen breakdown (50-51a).

Treatment

SD is normally unresolving and slowly progressive over years. Improved glycemic control may be an important means of prevention but evidence has not shown clinical improvements in those already affected by SD. A variety of therapeutic options have been proposed with variable efficacy. The 2024 European Dermatology Forum Guidelines (51a) recommend medium-to-high dose phototherapy with UVA1 or PUVA as first-line therapy, methotrexate as second-line therapy, and other treatments including immunosuppressants, corticosteroids, intravenous immunoglobulin, and electron-beam therapy as advanced therapies (52). Independent of other treatments, physical therapy is an important therapeutic modality for patients with SD and reduced mobility (51A, 53).

Necrobiosis Lipoidica

EPIDEMIOLOGY

Necrobiosis lipoidica (NL) is a rare chronic granulomatous dermatologic disease that is seen most frequently in patients with diabetes. Although nearly one in four patients presenting with NL will also have diabetes, only 0.3% to 1.6% of patients with diabetes will develop NL (47A,54). For unknown reasons, NL expresses a strong predilection for women compared to men (55). NL generally occurs in type 1 diabetes during the third decade of life, as opposed to type 2 diabetes in which it commonly presents in the fourth or fifth decades of life (54). The majority of cases of NL presents years after a diagnosis of diabetes mellitus; however, NL may precede diabetes, with 7% to 42% of patients with initial NL going on to develop impaired glucose tolerance or diabetes (47A,56). One study evaluating comorbidities and diabetic complications in patients with NL found high rates of smoking, hypertension, hyperlipidemia, obesity, coronary artery disease, myocardial infarction, thyroid disease, poor kidney function, and poor glucose control (56A). The highest comorbidity rates in patients with NL were patients with type 2 diabetes.

PRESENTATION

NL begins as a single or group of firm well-demarcated rounded erythematous papules (figure 4). The papules then expand and aggregate into plaques characterized by circumferential red-brown borders and a firm yellow-brown waxen atrophic center containing telangiectasias. NL occurs bilaterally and exhibits Koebnerization. Lesions are almost always found on the pretibial areas of the lower extremities. Additional involvement of the forearm, scalp, distal upper extremities, face, or abdomen may be present on occasion, and the heel of the foot or glans penis even more infrequently. If left untreated, only about 15% of lesions will resolve within twelve years. Despite the pronounced appearance of the lesions, NL is often asymptomatic. However, there may be pruritus and hypoesthesia of affected areas, and pain may be present in the context of ulceration. Ulceration occurs in about one-third of lesions and has been associated with secondary infections and squamous cell carcinoma. The histology of NL primarily involves the dermis and is marked by palisading granulomatous inflammation, necrobiotic collagen, a mixed inflammatory infiltrate, blood vessel wall thickening, and reduced mucin.

Figure 4.

Necrobiosis Lipoidica.

PATHOGENESIS

The pathogenesis of NL is not well understood. The relationship between diabetes and NL has led some to theorize that diabetes-related microangiopathy is related to the development of NL (54). Other theories focus on irregularities in collagen, autoimmune disease, neutrophil chemotaxis, or blood vessels (57).

TREATMENT

NL is a chronic, disfiguring condition that can be debilitating for patients and difficult for clinicians to manage. Differing degrees of success have been reported with a variety of treatments; however, the majority of such reports are limited by inconsistent treatment responses in patients and a lack of large, controlled studies. Corticosteroids are often used in the management of NL and may be administered topically, intralesionally, or orally. Corticosteroids can be used to manage active lesions but is best not used in areas that are atrophic. Success has also been reported with calcineurin inhibitors (e.g., cyclosporine), anti-tumor necrosis factor inhibitors (e.g., infliximab), pentoxifylline, antimalarials (e.g., hydroxychloroquine), PUVA, granulocyte colony stimulating factor, dipyridamole, and low-dose aspirin (54). Appropriate wound care is important for ulcerated lesions; this often includes topical antibiotics, protecting areas vulnerable to injury, emollients, and compression bandaging. Surgical excision of ulcers typically has poor results. Some ulcerated lesion may improve with split-skin grafting. Although still recommended, improved control of diabetes has not been found to lead to an improvement in skin lesions. Patients with newly diagnosed NL should be screened for hypertension, hyperlipidemia, and thyroid disease (56a).

NONSPECIFIC DERMATOLOGIC SIGNS AND SYMPTOMS

Ichthyosiform Changes of the Shins

Ichthyosiform changes of the shins presents with large bilateral areas of dryness and scaling (sometimes described as “fish scale” skin) (figure 5). Although cutaneous changes may occur on the hands or feet, the anterior shin is most classically involved. These cutaneous changes are related to rapid skin aging and adhesion defects in the stratum corneum (61). The prevalence of ichthyosiform changes of the shins in those with type 1 diabetes has been reported to be between 22% to 48% (33,62). These changes present relatively early in the disease course of diabetes. There is no known difference in prevalence between males and females (33). The development of ichthyosiform changes of the shins is related to production of advanced glycosylation end products and microangiopathic changes. Treatment is limited but topical emollients or keratolytic agents may be beneficial (61).

Figure 5.

Acquired ichthyosiform changes.

Eruptive Xanthomas

EPIDEMIOLOGY

Eruptive xanthomas (EX) are a clinical presentation of hypertriglyceridemia, generally associated with serum triglycerides above 2,000 mg/dL (73). However, in patients with diabetes, lower levels of triglycerides may be associated with EX. The prevalence of EX is around one percent in type 1 diabetes and two percent in type 2 diabetes (74,75). Serum lipid abnormalities are present in about seventy-five percent of patients with diabetes (76). For a detailed discussion of lipid abnormalities in patients with diabetes see the Endotext chapter entitled “Dyslipidemia in Patients with Diabetes” (76a).

PRESENTATION

EX has been reported as the first presenting sign of diabetes mellitus, granting it can present at any time in the disease course. EX presents as eruptions of clusters of glossy pink-to-yellow papules, ranging in diameter from 1 mm to 4 mm, overlying an erythematous area (figure 6). The lesions can be found on extensor surfaces of the extremities, the buttocks, and in areas susceptible in Koebnerization. EX is usually asymptomatic but may be pruritic or tender. Histology reveals a mixed inflammatory infiltrate of the dermis which includes triglyceride containing macrophages, also referred to as foam cells.

Figure 6.

Eruptive xanthomas.

PATHOGENESIS

Lipoprotein lipase, a key enzyme in the metabolism of triglyceride rich lipoproteins, is stimulated by insulin. In an insulin deficient state, such as poorly controlled diabetes, there is decreased lipoprotein lipase activity resulting in the accumulation of chylomicrons and other triglyceride rich lipoproteins (77). Increased levels of these substances are scavenged by macrophages (78). These lipid-laden macrophages then collect in the dermis of the skin where they can lead to eruptive xanthomas.

TREATMENT

EX can resolve with improved glycemic control and a reduction in serum triglyceride levels (79). This may be achieved with fibrates or omega-3-fatty acids in addition to an appropriate insulin regimen (80). A more comprehensive review of the treatment of hypertriglyceridemia can be found in the Endotext chapter entitled “Triglyceride Lowering Drugs” (80a).

Acrochordons

Acrochordons (also known as soft benign fibromas, fibroepithelial polyps, or skin tags) are benign, soft, pedunculated growths that vary in size and can occur singularly or in groups (figure 7). The neck, axilla, and periorbital area are most frequently involved, although other intertriginous areas can also be affected. Skin tags are common in the general population but are more prevalent in those with increased weight or age, and in women. It has been reported that as many as three out of four patients presenting with acrochordons also have diabetes mellitus (81). Patients with acanthosis nigricans may have acrochordons overlying the affected areas of skin. Although disputed, some studies have suggested that the amount of skin tags on an individual may correspond with an individual's risk of diabetes or insulin resistance (82). Excision or cryotherapy is not medically indicated but may be considered in those with symptomatic or cosmetically displeasing lesions.

Figure 7.

Acrochordons.

Keratosis Pilaris

Keratosis pilaris is a very common benign keratotic disorder. Patients with keratosis pilaris classically present with areas of keratotic perifollicular papules with surrounding erythema or hyperpigmentation (figure 8). The posterior surfaces of the upper arms are often affected but involvement of the thighs, face, and buttocks can also be seen. Compared to the general population, keratosis pilaris occurs more frequently and with more extensive involvement of the skin in those with diabetes (33,62). Keratosis pilaris can be treated with various topical therapies, including salicylic acid, moisturizers, and emollients.

Figure 8.

Keratosis pilaris.

Palmar Erythema

Palmar erythema is a benign finding that presents with symmetric redness and warmth involving the palms (figure 9). The erythema is asymptomatic and often most heavily affects the hypothenar and thenar eminences of the palms. The microvascular complications of diabetes are thought to be involved in the pathogenesis of palmar erythema (91). Although diabetes associated palmar erythema is distinct from physiologic mottled skin, it is similar to other types of palmar erythema such as those related to pregnancy and rheumatoid arthritis.

Figure 9.

Palmar erythema. From Wikipedia.

DERMATOLOGIC DISEASES ASSOCIATED WITH DIABETES

Generalized Granuloma Annulare

EPIDEMIOLOGY

Although various forms of granuloma annulare exist, only generalized granuloma annulare (GGA) is thought to be associated with diabetes. It is estimated that between ten and fifteen percent of cases of GGA occur in patients with diabetes (96). Meanwhile, less than one percent of patients with diabetes present with GGA. GGA occurs around the average age of 50 years. It occurs more frequently in women than in men, and in those with type 1 diabetes (97).

PRESENTATION

GGA initially presents with groups of skin-colored or reddish, firm papules which slowly grow and centrally involute to then form hypo- or hyper-pigmented annular rings with elevated circumferential borders (figure 10). The lesions can range in size from 0.5 cm to 5.0 cm. The trunk and extremities are classically involved in a bilateral distribution. GGA is normally asymptomatic but can present with pruritus. The histology shows dermal granulomatous inflammation surrounding foci of necrotic collagen and mucin. Necrobiosis lipoidica can present similarly to GGA; GGA is distinguished from necrobiosis lipoidica by its red color, the absence of an atrophic epidermis, and on histopathology: the presence of mucin and lack of plasma cells.

Figure 10.

Generalized granuloma annulare. From Wikipedia.

PATHOGENESIS

The pathogenesis of GGA is incompletely understood. It is believed to involve an unknown stimulus that leads to the activation of lymphocytes through a delayed- type hypersensitivity reaction, ultimately initiating a proinflammatory cascade and granuloma formation (98). Recent studies have identified Th1, JAK-STAT, and perhaps also Th2 pathway dysregulation in GA lesional skin (97a).

TREATMENT

GGA has a prolonged often unresolving disease course and multiple treatments have been suggested to better manage GGA. However, much of the information stems from small studies and case reports. Several large retrospective studies suggest the efficacy of intralesional and topical corticosteroids in some patients, with phototherapy being an option for GA refractory to corticosteroids (97a). Antimalarials, retinoids, dapsone, methotrexate, cyclosporine, and calcineurin inhibitors have also been suggested as therapies (97a,98).

Vitiligo

Vitiligo is an acquired autoimmune disorder involving melanocyte destruction. Patients with vitiligo present with scattered well-demarcated areas of depigmentation that can occur anywhere on the body but frequently involves the acral surfaces and the face (figure 11). Whereas about 1% of the general population is affected by vitiligo, vitiligo is much more prevalent in those with diabetes mellitus. Vitiligo occurs more frequently in women and is also more common in type 1 than in type 2 diabetes mellitus (96,98). Coinciding vitiligo and type 1 diabetes mellitus may be associated with endocrine autoimmune abnormalities of the gastric parietal cells, adrenal, or thyroid (102). A more comprehensive review of polyglandular autoimmune disorders can be found in the Autoimmune Polyglandular Syndromes section of Endotext (102a).

Figure 11.

Vitiligo. From Wikipedia.

Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory condition characterized by inflamed nodules and abscesses located in intertriginous areas such as the axilla or groin (figure 12). These lesions are often painful and malodorous. HS is frequently complicated by sinus formation and the development of disfiguring scars. HS occurs more often in women than men and usually presents in patients beginning in their twenties (103). The prevalence of HS is 0.095% in White populations, increasing more than 3-fold in Black populations (103a). Compared to the general population, diabetes mellitus is three times more common in patients with HS; HS has also been associated with cigarette smoking, diabetes, and low socioeconomic status (103a,104). It is recommended that patients with HS be screened for diabetes mellitus. Although there is no standardized approach to the treatment of HS, a multimodal approach may address underlying follicular occlusion, inflammation, bacterial overgrowth, hormonal and metabolic dysregulation and lifestyle modifications (103a). Some benefits have been reported with the use of antibiotics, retinoids, antiandrogens, or immunomodulators such as tumor necrosis factor (TNF) inhibitors (105).

Figure 12.

Hidradenitis suppurativa. From Wikipedia.

Glucagonoma

Glucagonoma is a rare neuroendocrine tumor that most frequently affects patients in their sixth decade of life (106). Patients with glucagonoma may present with a variety of non-specific symptoms. However, necrolytic migratory erythema (NME) is classically associated with glucagonoma and presents in 70% to 83% of patients (106) (107). NME is characterized by erythematous erosive crusted or vesicular eruptions of papules or plaques with irregular borders (figure 13). The lesions may become bullous or blistered and may be painful or pruritic. The abdomen, groin, genitals, or buttocks are frequently involved, although cheilitis or glossitis may also be present. Biopsy at the edge of the lesion may demonstrate epidermal pallor, necrolytic edema, and a perivascular inflammatory infiltrate (108). Patients with glucagonoma may also present with diabetes mellitus. In patients with glucagonoma, diabetes mellitus frequently presents prior to NME (107). Approximately 20% to 40% of patients will present with diabetes mellitus before the diagnosis of glucagonoma (107,109). Of those patients diagnosed with glucagonoma but not diabetes mellitus, 76% to 94% will eventually develop diabetes mellitus (110). A more comprehensive review of glucagonoma can be found in the Glucagonoma section of Endotext (110a).

Figure 13.

Necrolytic migratory erythema. From Endotext chapter entitled Glucagon & Glucagonoma Syndrome.

CUTANEOUS CHANGES ASSOCIATED WITH DIABETES MEDICATIONS

CONCLUSION

Diabetes mellitus is associated with a broad array of dermatologic conditions (Table 1). Many of the sources describing dermatologic changes associated with diabetes mellitus are antiquated; larger research studies utilizing modern analytic tools are needed to better understand the underlying pathophysiology and treatment efficacy. Although each condition may respond to a variety of specific treatments, many will improve with improved glycemic control. Hence, patient education and lifestyle changes are key in improving the health and quality of life of patients with diabetes mellitus.

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