Can insulin cause skin reactions such as redness and induration of the skin? Are these a general si

Fråga: Can insulin cause skin reactions such as redness and induration of the skin? Are these a general side effects of all types of insulin? Background: A woman born in 1942 has had type II diabetes mellitus for about 10 years. She has been treated with oral hypoglycaemic drugs. Last autumn subcutaneous insulin treatment was started (human insulin, Mixtard). After about two months she got redness and induration of the skin at the site of injection and she was switched back to oral hypoglycaemic drugs.

Sammanfattning: All types of insulin can cause local skin reactions at the site of injection. Conventional insulin causes these reactions more often than highly purified or human insulin.

Svar: Several types of dermal reactions to insulin have been reported. These are insulin allergy, lipodystrophy and idiosyncratic reactions. Insulin allergy may be local or systemic and occurs within one to four weeks after starting treatment. The local reactions are of three types. The most common is the late phase reaction, a biphasic IgE reaction characterised by immediate burning and itching with a wheal and flare at the injection site. It may resolve or become indurate, with pruritus continuing for hours or days. Two rare forms are the Arthus-type reaction, producing a pruritic, painful nodule 6 to 8 hours after injection, and the delayed hypersensitivity reaction, which is similar but appears 12 to 24 hours after injection (1, 2). Local reactions, characterised by erythema and pruritus at the injection site, usually disappear with continued treatment. Hypersensitivity reactions are observed less frequently with purified than with conventional insulins and porcine insulin is less immunogenic than bovine insulin. Although hypersensitivity reactions have been reported in patients receiving human insulin who were previously treated with animal insulins, there are only isolated reports of such reactions in patients treated exclusively with human insulin (3, 4).

Lipodystrophy, lipoatrophy or lipohypertrophy may be a consequence of chronic local insulin reactions which can be elicited by less pure as well as by highly purified preparations (1). Lipoatrophy occurs less frequently with purified insulins than with conventional insulins. Lipohypertrophy is usually associated with repeated injections at the same site and may usually be overcome by rotating the site of injection (3).

Pigmentation can occur at the injection site and, rarely, keloids may form (1). Localised amyloidosis at the sites of injection of porcine insulin has been reported (5).

It should be mentioned that allergic reactions may also be elicited by Surfen (aminoquinuride, a constituent of various insulin preparations, which delays the uptake of insulin), by zinc or by zinc and/or protamine, and by the preservative metacresol. Remnants of fluids used for cleansing the skin may be co-injected in micro-amounts and elicit allergic reaction (4). Some local reactions (initially pruritic lesions, later minimally elevated plaques) can be a consequence of an incorrect injection technique, generally the use of too short a needle or too superficial an injection (4, 6).

Twentyfive skin reactions have been reported to SADRAC (The Swedish Adverse Drug Reactions Advisory Committee) during the period from 1965 until 1998. Twelve of them were local skin reactions. Different types of insulin were suspected to cause these reactions (7).