6.2.a. Skin Tests
In the earliest reports the diagnosis of PPI allergy was based on clinical data or drug provocation test (DPT) tests results,3,48-52but, several large studies showed that skin tests are useful for the diagnosis of immediate HSRs due to PPIs and non-irritating skin test concentrations have been defined.3,17,18 Two main studies3,17have analyzed the accuracy of skin tests vs DPTs. Bonadonna et al.3 evaluated the diagnostic performance of skin tests vs DPT with the suspected PPI in 53 patients with grade 1 and 2 immediate HSRs. The authors report a high specificity and a positive predictive value (PPV) both of 100%, whereas sensitivity was lower (61.3%) and the negative predictive value (NPV) was 91.9%. In the study, 4/12 patients who exhibited positive skin tests with the suspected PPI underwent a DPT, and the positivity was confirmed in all cases. Additionally, there are several case reports showing confirmation of skin test positivity by DPT.34,53 These results are in agreement with data from another multicenter study by Kepil Ă–zdemir et al.17 on 38 patients who had experienced immediate HSRs to PPIs. The authors confirm the high specificity and PPV, 100% both, with lower values of sensitivity (58.8%) and NPV (70.8%). Based on the previous data from the literature, they did not perform a confirmatory DPT in patients with skin test positivity to the culprit. The same group further confirmed their data in a following retrospective study18 where they managed a definitive diagnosis throughout skin testing and/or DPTs with the suspected and/or alternative PPIs in 27 patients. Skin testing was positive in 13/14 patients with confirmed PPI hypersensitivity, while all 5 patients who had a negative DPT result with the suspected PPI, also had a negative skin test result. Performing diagnostic tests within 6 months from a reaction has been shown to increase the likelihood of positivity of skin tests.45
The recommended non-irritating concentrations of SPTs29 are shown in Table 2. If the SPT is negative, IDT should be pursued.29 IDT can be performed with 1:1000, 1:100 and 1:10 concentrations of the medication (Table 2). It is not recommended to perform IDTs with solutions obtained from oral preparations due to the risk of false positive results.2 Skin tests are overall safe; no adverse reactions performing skin tests with PPIs have been reported so far.2
Based on an extensive literature review, we highlight skin testing as first step in the evaluation of patients who experienced mild to moderate HSRs to PPIs. Due to the high PPV, in case of a positive skin test plus a corresponding clinical history, the patient should be advised to avoid the implicated PPI and the related ones. On the other hand, due to the low NPV, a negative skin test alone is not reliable in ruling out a drug allergy suspicion and the physician should consider proceeding with DPT after carefully evaluating the risk/benefit ratio in each patient.54