Skin manifestations of diabetes

Bacterial infections

Pyodermic infections such as impetigo, folliculitis, carbuncles, furunculosis, ecthyma, and erysipelas can be more severe and widespread in diabetic patients. Therapy consists of adequate diabetic control and, if necessary, adequate systemic antibiotic therapy; deeper infections require intravenous antibiotics.

Erythrasma, caused by Corynebacterium minutissimum, occurs with increased frequency in obese diabetic patients, but it is often missed. Intertriginous areas are the main affected site. Sweat, friction, and maceration play a role in the development. Erythrasma presents as shiny, hyperpigmented patches with an active border. With the Wood’s lamp, a characteristic coral fluorescence is seen. Treatment consists of topical or systemic erythromycin, or both. Prevention of sweating, friction, and maceration can limit the chances of developing this infection.^5,6,37

Rare infections

Poor metabolic control and ketoacidosis may set the stage for severe infections by otherwise nonpathogenic microorganisms, such as mucormycosis by Phycomycetes and anaerobic cellulitis by Clostridium species. Treatment consists of metabolic control, aggressive debride ment of devitalized tissue, and intravenous antimicrobial therapy.³⁷

In older diabetic patients, malignant otitis externa, often caused by Pseudomonas aeruginosa, can be fatal. This invasive infection may spread from the external auditory canal to the base of the skull, the meninges, and the brain itself. Treatment consists of irrigation and drainage of the ear canal, antibiotics, and sometimes debridement. A cure rate of more than 90% can be achieved using parenteral or oral quinolones.³

CUTANEOUS REACTIONS TO INSULIN

Impurities in insulin preparations, the presence of cow or pig proteins, the insulin molecule itself, preservatives, or additives cause allergic reactions. The use of human recombinant insulin has decreased the incidence of insulin allergy, so that now it is reported in fewer than 1% of diabetic patients treated with insulin.⁶

Allergic reactions to insulin can be classified as immediate-local, generalized, delayed, or biphasic.

Immediate-local reactions reach maximum intensity in 15 to 30 minutes and usually subside within 1 hour. Clinically, one finds erythema, which may become urticarial. This reaction probably is mediated by immunoglobulin E (IgE).

Generalized reactions. Immediate reactions may progress to generalized erythema and urticaria. Anaphylaxis is unusual.

Delayed hypersensitivity reactions are the most common. They usually appear about 2 weeks after the start of insulin therapy as an itchy nodule at the site of injection, 4 to 24 hours after injection.

Biphasic, or dual, reactions are rare events and consist of an immediate and a delayed local reaction, often with a generalized illness resembling serum sickness. They are considered Arthus-immune complex reactions.⁶

Other complications of insulin injections

Other local cutaneous complications include keloids, hyperkeratotic papules, purpura, and localized pigmentation.

The treatment of choice for localized immediate allergic reactions is a change of insulin to a more purified product.¹⁷ Other tools to manage allergic reactions are antihistamines, the addition of glucocorticoids to insulin, discontinuation of therapy, desensitization therapy, or a change in the insulin delivery system.^5,6

The most important immunologic problem is IgE-mediated anaphylaxis, which can be managed by temporary reduction in dose or by insulin desensitization. Serum sickness responds to corticosteroid therapy.³⁸

Insulin therapy may also cause lipoatrophy and lipohypertrophy that can coexist in the same patient. Lipoatrophy presents as circumscribed, depressed areas of skin at the insulin injection site 6 to 24 months after the start of therapy. Children and obese women are affected most often. It may be caused by lipolytic components in the insulin preparation or by an inflammatory process mediated by the immune complex. Other theories involve cryotrauma from refrigerated insulin, mechanical trauma due to the angle of injection, surface alcohol contamination, or local hyperproduction of tumor necrosis factor alpha from macrophages induced by injected insulin. Since the introduction of purified recombinant human insulin, lipoatrophy has become rare.^37,39 Duration of the presence of an insulin depot has been implicated as well. That is why Murao et al⁴⁰ suggested substituting rapid-acting insulin.

Lipohypertrophy clinically resembles lipoma and presents as soft dermal nodules at the site of frequent injections. Lipohypertrophy is regarded as a local response to the lipogenic action of insulin and can be prevented by rotation of the injection site.^5,17,37

SKIN EFFECTS OF INSULIN ANALOGUES

Cutaneous side effects are not often described in insulin analogues, but there have been case reports. A case of IgE-mediated anaphylaxis⁴¹ and one case of vitiligo⁴² were described with insulin lispro. One case of allergy was described with insulin glargine.⁴³ Although insulin detemir is well tolerated in general, several cases of local injection site reactions have been reported.^44,45 Treatment depends on the extent of the reaction and can include desensitization, changing the type of insulin, rotating the injection site, or a combination of these.^41–45