Case 1
A 47-year-old female was referred to our outpatient allergy clinic because of a generalized urticaria developed within minutes in the first week of an exenatide BID 5 mcg/20 mcl treatment. Urticaria was not accompanied by respiratory, cardiovascular or gastrointestinal symptoms and disappeared spontaneously after the drug administration had stopped.
To confirm the diagnosis of exenatide allergy, we performed skin tests with a stepwise approach. The skin prick tests were applied with dilutions of 1/10, 1/1 and were followed by the intradermal (ID) tests with 1/1000, 1/100 and 1/10 dilutions respectively until receiving a positive response. The ID test with 1/100 of exenatide was positive in the patient (shown in Fig. 1). Additionally, in order to exclude an irritation reaction that may cause false positivity, skin tests at increasing concentrations were applied to 4 patients who were using exenatide without any problem with the same indication and revealed no positivity (shown in Fig. 2).
We suggested to treat the patient with an alternative treatment. However, it was stated by her endocrinologist that an alternative GLP-1 analogue was not available. Since there was no previously published desensitization protocol with exenatide, we created a new protocol for the patient. The desensitization process was delivered in 7 consecutive steps of subcutaneous injections with 30 minutes intervals. The targeted daily dose was 10 mcg for the patient. We started with the dose of 0,1 mcg (1/100 of the targeted dose) than increased the doses with 30 minutes’ intervals. In the seventh step, the drug was administered with its own injector and desensitization was completed (Table 1). No allergic reaction developed during the desensitization procedure and the protocol was successfully completed. The patient has been using exenatide treatment for 3 months without any allergic reaction after the desensitization procedure.
Table 1
Exenatide desensitization protocol
Step
|
The amount of solution applied in each step (ml)
|
The dose administered at each step (mcg)
|
Cumulative dose (mcg)
|
1
|
0.04
|
0.1
|
0.1
|
2
|
0.08
|
0.2
|
0.3
|
3
|
0.16
|
0.4
|
0.7
|
4
|
0.32
|
0.8
|
1.5
|
5
|
0.64
|
1.6
|
3.1
|
6
|
0.76
|
1.9
|
5.0
|
7
|
Application with autoinjector
|
5.0
|
10.0
|
Each application was performed with an interval of 30 minutes and the total dose was determined as the daily therapeutic dose for the particular patient. In the first six steps, 5 mcg/2 ml dose of solution obtained by adding 1.98 ml of 0.9% NaCl to 5mcg/0.02 ml dose of drug was used. In the seventh step, the drug was administered with its own injector. ml: milliliter, mcg: microgram, NaCl: sodium chloride
Case 2
A 46-year-old female, diagnosed as type 2 diabetes and obesity, was referred to us because of having a large local immediate injection site reaction appeared in 15 minutes following an exenatide BID 5 mcg/20 mcl injection for a month. After the fourth injection, an itchy, edematous and hyperemic lesion had developed on the injection site (shown in Fig. 3.A). Skin prick and ID tests were applied on the patient with the same protocol and ID test with 1/100 dilution revealed positivity to exenatide (shown in Fig. 3.B).
Since the patient did not have a systemic reaction, a divided dose and local steroid therapy was initially administered. However, we decided to apply the same desensitization protocol on the patient who could not tolerate the splitted doses of the drug during long-term therapy. During the protocol, no lesion occurred on the injection area and the patient continued to use the drug in one injection per application in the following days without any reaction. Furthermore, the following skin tests performed in the first month of desensitization were interestingly found negative (shown in Fig. 3.C).