Diabetes Mellitus and the Skin: Recognition and Management of Cutaneous Manifestations

William B. Horton, MD; Patrick L. Boler, MD, PharmD; Angela R. Subauste, MD

Disclosures

South Med J. 2016;109(10):636-646. 

In This Article

Dermatologic Conditions Associated With T1DM

Vitiligo

Vitiligo is an acquired pigmentary disorder of the skin and mucous membranes that is characterized clinically by the development of well-circumscribed, depigmented macules, and patches of skin and hair with the absence of melanocytes microscopically.[32] Vitiligo affects 0.3% to 0.5% of the world's population, making it the most common depigmenting disorder.[4] The exact pathophysiology of vitiligo remains unclear. The most accepted theory involves the autoimmune destruction of melanocytes. The action of antibodies against melanocytes has been confirmed in vitiligo. The main antigen recognized is tyrosinase. Alterations in T cells and cytokines also have been described. The condition is frequently (20%–30% of cases) associated with disorders of autoimmune origin.[4] The most common associations are with Hashimoto thyroiditis, Graves disease, rheumatoid arthritis, psoriasis, T1DM, pernicious anemia, systemic lupus erythematosus, and Addison disease.[33] Approximately 2% to 10% of patients with T1DM also have vitiligo.[34]

In general, the diagnosis of vitiligo is made on the basis of clinical findings, although biopsy can be helpful in distinguishing vitiligo from other depigmentary disorders. Given the strong association with autoimmune diseases, patients should be made aware of signs and symptoms that suggest the onset of hypothyroidism, DM, or other autoimmune disorders. If signs or symptoms occur, then appropriate tests should be performed.[35]

Treatment attempts to reduce T-cell response and induce melanocyte migration and regeneration.[4] First-line treatments include corticosteroids (eg, clobetasol, betamethasone) with or without narrow-band ultraviolet B (UVB) phototherapy, calcineurin inhibitors (eg, tacrolimus), or systemic PUVA phototherapy.[4] Calcipotriol, topical PUVA, excimer laser, corticosteroid pulse therapy, and surgical melanocyte grafting are additional treatment options.[4] Use of sunscreen also is recommended but controversial because of the UVB stimulation of melanocytes and the possibility of repopulation, as well as the photoadaptation of vitiligo-affected skin.[4] Moderate exposure to sun is therefore recommended.[4]

Vitiligo is a chronic disease with a substantial psychosocial impact on patients.[36] Offering support to patients and their families is an important part of the treatment process. Numerous support groups are available.[4]

Necrobiosis Lipoidica

Necrobiosis lipoidica (NL) is a chronic inflammatory skin disorder of collagen degeneration with a granulomatous response, thickening of blood vessel walls, and fat deposition.[37] A small clinical study determined that patients with NL had a higher proportion of natural antibodies against antigens such as actin, myosin, keratin, desmin when compared with patients with T1DM and healthy control subjects.[38] Clinical appearance is characterized typically by irregular, painless ovoid plaques with a yellow atrophic center and a red-to-purple periphery, most commonly in girls and women and located on the pretibial skin (Fig. 3).[4] Lesions usually are multiple and bilateral[4] and may ulcerate spontaneously or following trauma.[39,40] NL has been associated repeatedly with T1DM in the medical literature. Studies have shown that anywhere from 11%[39] to 65%[41] of patients have T1DM at the time of NL diagnosis. Despite the high prevalence of DM in patients with NL, necrobiosis remains relatively uncommon in the overall DM population, with a reported prevalence of only 3 in 1000 patients.[40]

Figure 3.

Necrobiosis lipoidica, (A) oval yellow atrophic plaques with overlying telangectasias. (B) Ulcerative lesions in the same patient following trauma.

Diagnosis usually is made by the characteristic clinical appearance of lesions.[37] For cases in which diagnosis is not clear, biopsy can prove beneficial. NL is a benign condition and dermatology referral is usually unnecessary.[4] The exact cause of NL is unknown,[37] but proposed mechanisms include localized trauma, microangiopathy, immunoglobulin and fibrin deposition, and metabolic changes.[4,37,42] Although NL is benign, its appearance can be cosmetically distressing to patients.[4]

The treatment of NL rarely is completely effective and flare-ups occur frequently.[37] Treatment options consist mainly of steroids, either topical, intralesional, or rarely, systemic.[4] Steroids are cost-effective and have relatively low adverse effect profiles in comparison with other therapies.[4] Stockings are beneficial in helping with changes in stasis and protecting the patient from trauma.[4,42] Other treatments that have demonstrated varying degrees of success include cyclosporine, ticlopidine, infliximab, thalidomide, nicotinamide, clofazimine, chloroquine, and topical tretinoin.[4] Of note, the use of pentoxifylline has demonstrated great success in case reports, including the complete reversal of early-stage NL in one patient.[43] Glycemic control has no effect on the course of NL.[25]

Bullosis Diabeticorum

Bullosis diabeticorum (BD), or diabetic bullae, is a noninflammatory blistering condition that occurs in patients with DM.[44] BD classically presents as serous fluid-filled tense bullae that are large and asymmetrical in shape (Fig. 4A).[45,46] The bullae arise spontaneously and usually are located on acral and distal skin surfaces of the lower extremities.[4,44] Occasionally they are seen on the forearms and hands.[4] BD has been observed in 0.5% of patients with T1DM and is most frequently seen in men with long-standing poorly controlled DM with peripheral neuropathy.[4,47,48] The exact etiology of BD is unknown.[4,49]

Figure 4.

(A) Bullosis diabeticorum: noninflammatory, tense bulla of the lower extremity with erosions following unroofing of local bullae. Image appears with permission from DermNet NZ. Published online at: http://www.dermnetnz.org. (B) Diabetic dermopathy: tan-brown macules and patches on anterior leg. Image appears with permission from VisualDx © 2016.

The diagnosis of BD involves punch biopsy and subsequent histopathologic examination.[50] Histology typically reveals a noninflammatory blister with separation in an intraepidermal or subepidermal location; anchoring fibrils and hemidesmosomes tend to be decreased.[50] Caterpillar bodies, often seen in cases of porphyria, also can be seen.[50] Immunofluorescence staining typically is negative for immunoglobulin (Ig) M, IgG, IgA, and complement component 3; the diagnosis can be confirmed in the presence of characteristic presentation.[50]

The treatment of BD is focused on the prevention of infection.[51] If bullae become large and symptomatic, they may be aspirated, leaving the roof intact to protect the skin barrier.[25] Saline compresses may be applied for symptomatic relief.[4] Topical antibiotics and steroids are generally not necessary because lesions tend to resolve on their own in 2 to 5 weeks.[4]

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