Erythema insulin

Allergic reactions to insulin include erythema, pruritus, and indurations,22 which usually are transient. For the more troublesome reactions, treatment options include dexamethasone, desensitization, or change in delivery system (i.e., insulin pump or inhaled insulin). 

A pulsed depolarizing iontophoretic system has been developed by Advance Co. [26] that delivers a current of frequency 40 Hz and an on-off duty of 30% to deliver a significant amount of metoprolol into the blood without any observed skin irritation or erythema at the site of application. Okabe et al. [26] hypothesized that the high-frequency pulses provided low skin impedance in addition, the capacitance of the skin was restored to its initial state at the start of each pulse cycle. Chien et al. [89] reported that a sine waveform induced a faster hypoglycemic effect with insulin, with the peak at approximately 2 hours, than either a trapezoidal (7 hours) or a square waveform (12 hours) however, the duration of the hypoglycemia was also shorter (11 hours) compared with the other two waveforms [89]. 

One of the inherent features of iontophoresis—in fact, one that is embodied in the definition of iontophoresis—is the ability to deliver a drug through the skin without prior preparation of the skin. An iontophoretic system for dehvery of insulin would be a skin patch. Insulin passes through the skin and into the systemic circulation by action of a weak electric current. This current is barely perceptible as it passes through the skin and has been shown to not alter the barrier function of the skin (Ledger, 1992). The only apparent effect that iontophoresis has on the skin is a blushlike erythema of the skin under the patch, which resolves in a few hours. 

An iontophoretic dosage form for the delivery of insulin would be of little benefit if diabetics could not wear it. Recently, the skin response to a 24-hr iontophoresis dosage form was measured in human volunteers (Maibach, 1994). In terms of comparisons of iontophoretic patches at 200 /A/cm2 and similar patches without current, no significant changes were measured for transepithelial water loss (TEWL), skin capacitance, and skin temperature. The only effect was modest transient erythema. For a 24-hr application, this establishes a well-tolerated current density. In order to determine a well-tolerated total current, we need only know the skin contact area. Experience with passive patches has shown that a total area of SOcm for a system worn all day, every day, may be close to a maximum. Allowing 20 cm2 for si-in adhesion and 30 cm for the anode and cathode, a IS-cm electrode area is estimated. For a current density of 20Q A/cm2, this yields an estimate of 3 mA as well tolerated for a system worn aU day, every day. 

The skin manifestations of continuous subcutaneous insulin infusion have been studied in 40 children aged under 6 years (mean age 2.3 years) compared with 38 children over 6 years (mean age 8.4 years) [10 ]. Small scars of less than 3 mm were the most commonly reported events, and there were slightly fewer in the younger children 20 (50%) compared with 27 (71%). Lipohypertrophy was also common at the insertion sites 18 (45%) and 18 (47%) respectively. Erythema and blisters were less common, but occurred more often in those who had reported an allergic predisposition before starting subcutaneous... 

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