Drug Reactions To Insulin

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Injection Site Reaction Bovine Insulin
Fig. 7. Widespread cutaneous candidiasis in a patient with diabetes mellitus who had recently completed a course of broad-spectrum antibiotics.

There are two major types of localized reactions to subcutaneous injections of insulin: allergic and lipodystrophic. The latter group is then subdivided into either lipo-hypertrophy or lipoatrophy (16). Localized allergic reactions are characterized by pruritus in addition to erythema and induration; less often, the skin changes are those of dermatitis. These reactions may be immediate or delayed. As with systemic reactions, the "allergen" may be a component of the insulin preparation (e.g., zinc, protamine, or diluent) rather than the insulin itself. An even more elusive cause of allergic reactions is the presence of small quantities of natural latex rubber antigens in insulin injection materials (56,57). Finally, sterile abscesses can occur at the sites of injections.

Localized areas of lipoatrophy as a result of subcutaneous injections of insulin are fairly easy to recognize. The frequency of this side effect has decreased as the use of monocomponent and human insulin has increased. In fact, treatment of localized lipo-atrophy consists of switching to human insulin, injection of human insulin into the sites of lipoatrophy (beginning at the periphery and progressing toward the center), and rotation of sites over a 30-d cycle (24). In patients already receiving human insulin, the use of a jet injector may prove beneficial (58).

In contrast to lipoatrophy, lipohypertrophy results in an elevation or thickening of the skin (see Fig. 8) rather than an indentation due to loss of subcutaneous tissue. The clinical appearance is not the only problem, for the presence of lipohypertrophy can lead to delayed absorption of insulin. Unfortunately, the incidence of this side effect has not been decreasing. Other than rotation of injection sites, treatment options are rather limited. Recently, however, there have been reports of clinical improvement following liposuction (59) and use of the insulin analog lispro (60). Finally, continuous subcutaneous insulin infusions are associated with the reactions just outlined as well as a second set of cutaneous side effects ranging from bacterial infections at the injection

Insulin Injection Lipohypertrophy
Fig. 8. Lipohypertrophy of the midportions of both upper extremities at the sites of insulin injections.

site to contact dermatitis from components of the infusion system (e.g., components of the glue used in the infusion pump sets) (61).

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