COMPARISON OF THE DIAGNOSTIC VALUE OF TWO ASSAYS FOR SPECIFIC IMMUNOGLOBULIN E IN SUSPECTED BETA LACTAM ALLERGY/PORE[ETH]ENJE DIJAGNOSTICKE VREDNOSTI DVA TESTA ZA SPECIFICNI IMUNOGLOBULIN E KOD PACIJENTA SA SUSPEKTNOM ALERGIJOM NA BETA LAKTAME.
Introduction. The aim of this study was to compare the diagnostic value of two imunoglobulin E assays for penicillin in a group of patients with a history compatible with hypersensitivity reaction during penicillin treatment who exhibited positive skin testing and/or a drug provocation testing.
Material and Methods. In the first part of the study, penicillin G, V and/or amoxicillin specific immunoglobulin E, positive with ImmunoCAP system (Termo Fisher, Waltham, Massachusetts, USA), were selected from our biobank sera, and measured specific immunoglobulin E with Immulite system (Siemens, Munich, Germany). The second part of the study included skin testing, and if negative, drug provocation testing was done with the culprit penicillin in patients with a history compatible with hypersensitivity reaction during penicillin treatment. To check the impact of high values of total immunoglobulin E on performance of specific immunoglobulin E, we examined the specific immunoglobulin E to penicillin using both methods in sera of penicillin tolerant patients with total immunoglobulin E over 700 kIU/L. Results. Out of 2.521 in vitro specific immunoglobulin E penicillin tests, 58 were positive with ImmunoCAP. Of these tests, 52 were tested by the Immulite and they were all negative. Among 114 patients with a history compatible with hypersensitivity reaction during penicillin treatment, hypersensitivity was confirmed in 36 (31.6%). In 11 patients with positive immediate skin or drug provocation tests, ImmunoCAP was positive in 3 patients and Immulite in 1 patient. Sensitivity of ImmunoCAP and Immulite were 27.1% and 9.1%, respectively. Specificity of ImmunoCAP and Immulite were 96.1% and 100%, respectively. Specific immunoglobulin E to penicillins was detected with ImmunoCAP in 8/22 sera with total immunoglobulin E over 700 kIU/L. All sera were negative by the Immulite. Conclusion. Both the Immuno-CAP and Immulite specific immunoglobulin E assays have low sensitivity when assessing patients with a history of immediate hypersensitivity to penicillin, positive immediate skin, or drug provocation tests.
Key words: beta-Lactams; Hypersensitivity; Immunoglobulin E; Penicillins; Diagnosis; Skin Tests; Drug Hypersensitivity; False Negative Reactions; False Positive Reactions
Uvod. Nas cilj je bio da uporedimo dijagnosticke vrednosti dva IgE testa prema penicilinu u grupi pacijenata sa anamnezom hipersenzitivne reakcije tokom primanja penicilna, koji su imali pozitivan kozni test i/ili provokativni test. Materijal i metode. U prvom delu studije izabrali smo serume iz nase biobanke, gde su bila specificna IgE (sIge) pozitivna sa ImmunoCAP sistemom (Termo Fisher, Waltham, Massachusetts, USA) prema penicilinu G, V i/ili amoksicilinu. U drugom delu studije uradili smo kozni test i ukoliko je bio negativan, izvrsili smo provokativni test sa penicilinom koji je prouzrokovao hipersenzitivnu reakciju tokom primanja. Da bi proverili uticaj visokih vrednosti ukupnog imunoglobulina E na uspesnost testiranja specificnog imunoglobulina E, izmerili smo specificni imunoglobulin E prema penicilinu sa obe metode u serumu pacijenata koji su tolerantni na penicillin, i koji su imali ukupni imunoglobulin E iznad 700 kIU/L. Rezultati. Od 2521 in vitro specificni imunoglobulin penicilinskih testova, 58 je bilo pozitivno na ImmunoCAP sistem. 52 od tih je bilo podvrgnuto testiranju sa Immulit sistemom, svi su bili negativni. Kod 114 pacijenata sa anamnezom hipersenzitivne reakcije za vreme primanja penicilina, hipersenzitivnost je bila dokazana kod 36 (31,6%). Kod 11 pacijenata sa ranom koznom reakcijom ili provokativnim testom, ImmunoCAP je dao pozitivan rezultat kod troje pacijenata, a Immulite kod jednog pacijenta. Senzitivnost ImmunoCAP-a i Immulite 27,1% odnosno 9,1%. Specificnost ImmunoCAP-a i Immulite-a je bila 96,1 odnosno 100%. sIgE prema penicilinu bila je otkrivena Immuno-CAP-om kod 8/22 seruma sa ukupnim IgE preko 700 kIU/L. Svi serumi su bili negativni na Immulite aparatu. Zakljucak. Oba, ImmunoCAP i Immulite sIgE testa su imala malu senzitivnost tokom testiranja pacijenata sa anamnezom rane hipersenzitivne reakcije na penicillin, pozitivne rane kozne ili provokativne reakcije.
Kljucne reci: beta laktami; hipersensitivnost; imunoglobulin E; penicilini; dijagnoza; kozni testovi; preosetljivost na lekove; lazno negativne reakcije; lazno pozitivne reakcije
Suspected beta lactam allergy is quite common referral to allergy departments, but the diagnosis is confirmed in less than 20% of suspected patients . The cost of treatment of infections in patients with real or perceived diagnosis of beta lactam allergy is significantly higher than in beta lactam tolerant individuals .
Abbreviations IgE -- immunoglobulin E sIgE -- specific immunoglobulin E DPT -- drug provocation test ST -- skin test SPT -- skin prick test IDT -- intradermal test tIgE -- total IgE DST -- delayed skin test PPL -- benzylpenicilloyl poly-L-lysine MDM -- minor determinant mix
Determination of specific immunoglobulin E (sIgE) is a part of the diagnostic protocol in suspected penicillin allergy. The in-vitro testing penicillin allergy sensitivity is known to be low, and negative tests are not sufficient for allergy exclusion . On the other hand, there is evidence in the literature, that ImmunoCAP sIgE assay, which is most often used in the diagnosis of drug allergy, often gives false positive results . There is only scarce data on performance of other invitro test systems for sIgE to penicillin. The aim of this study was to compare the diagnostic value of two commonly used immunoglobulin E (IgE) assays in a group of well-defined patients with skin tests (ST) and/or drug provocation tests (DPTs) with confirmed or excluded penicillin allergy.
Material and Methods
The study was performed in a tertiary institution as a part of a research program, P3-0360 financed by a Slovenian Research Agency. The State Ethics Committee has approved the experiments (approval No 77/09/14). All patients gave their written informed consent. In the first part of the study, sera obtained in the period of 2010-2012, during routine diagnostic workup of patients referred to the clinic due to suspected penicillin allergy, were retrospectively analyzed. In the majority of patients with a history of penicillin allergy, the diagnostic procedure started with determination of sIgE against penicillin G, V and/or amoxicillin (allergens were selected from the medical history) with ImmunoCAP system (Termo Fisher, Waltham, Massachusetts, USA). In 2013, in all available ImmunoCAP positive sera, stored at--20 [degrees] C, sIgE against the same antibiotics were determined by Immulite system (Siemens, Munich, Germany). To check the stability of sIgE in frozen sera, the measurement of frozen sera was repeated with ImmunoCAP as well.
The second part of the study was conducted in 2014, and it prospectively included patients with a history compatible with IgE mediated penicillin allergy, namely a history of urticaria/angioedema, anaphylaxis or rash during penicillin, amoxicillin or amoxicillin-clavulanic acid treatment. Patients gave written informed consent with the procedures. The diagnostic procedure started with STs with culprit penicillin. Prick tests were considered positive if the wheal diameter after 20 minutes was at least half of that of histamine, and if the diameter of wheal increased by at least 3 mm and was surrounded by erythema . When STs were negative, DPT with the culprit antibiotic was performed . The blood samples were taken before testing, and sIgE-antibodies against penicillin antibiotics were measured after diagnostic work-ups were completed. The sIgE was considered truly positive if immediate STs, or DPT were positive.
Skin prick tests (SPTs) were performed with commercially available intravenous penicillin G (10,000 IU/ml) (Fagron, Belgium) and amoxicillin (20 mg/ml) (Lek, Slovenia). In case of negative SPT, intradermal tests (IDTs) with the same substance were performed with dilution of 1:10 and undiluted suspected antibiotic. If negative, tests were read 2 or 3 days latter, for possible late reaction. If IDTs were negative, oral DPT was performed . An increasing amount of drug was administered at 1-hour intervals. Doses for phenoxymethylpenicillin (Ospen 1000, Lek, Slovenia) were 50 mg, 150 mg, 300 mg, and 500 mg (cumulative dose 1,000 mg) . Doses for amoxicillin (Hiconcil 500, Krka, Slovenia) were 5 mg, 50 mg, 250 mg, and 500 mg (cumulative dose 805 mg). If immediate DPT was negative, patients continued taking 2 x 1000 mg of the antibiotic for 3 days, unless reaction occurred earlier. Patients were observed for possible delayed reactions .
To check the impact of high total IgE (tIgE) on performance of sIgE testing, sera of patients with tIgE over 700 kIU/L were taken from our biobank. Sera of patients with a history of penicillin allergy and sera of patients sensitized to molds were excluded.
The differences between groups of patients were calculated by Mann--Whitney U test. The difference between diagnostic performances of both tests was calculated by Chi-square test. The p < 0.05 was regarded as a statistically significant difference.
In a 3-year period (2010 - 2012), 2.521 in-vitro determinations of sIgE against penicillin antibiotics were performed in 1.233 patients using ImmunoCAP. A total of 57 patients were positive (> 0.35 kIU/L). We retested 51 of these positive sera with Immulite (6 sera were not available), and all turned out negative (< 0.35 kIU/L). Out of 45 sera retested with Immuno-CAP, 33 remained positive and 12 turned out negative (9 class I positive (0.36 - 0.55 kIU/L) in fresh sample turned to borderline negative (0.14-0.33 kIU/L) in stored samples, and 3 strongly positive in fresh sample turned completely negative (< 0.1 kIU/L) in stored samples. The difference between tests was statistically significant (p < 0.05; Chi-square).
A total of 114 adult patients with a history compatible with hypersensitivity reaction during penicillin treatment were included into a prospective analysis. Of them, 60 reported hypersensitivity to amoxicillin with (39) or without (21) clavulanic acid, 51 to penicillin V and 3 to penicillin G.
According to patients' history, 35 developed reaction during the first hour of treatment (early reactors), 67 after 1 hour (range - 2 hours to 21 days, median 4 days) after beginning of treatment (late reactors), and 12 patients were not able to recall the time course of the reaction. Among 114 patients with a history compatible with hypersensitivity reaction during penicillin treatment, hypersensitivity was confirmed in 36 (31.6%) (Table 1).
Among 35 early reactors, hypersensitivity was proven in 13 patients (37.1%). The hypersensitivity reaction occurred 54.7 [+ or -] 97.1 months before testing in patients with confirmed allergy, and 125.0 [+ or -] 170.0 months before testing in patients with negative diagnostic work-up, and the difference was not statistically significant (p > 0.05, t-test). As shown in Table 1, there were 5 with SPT, 2 with IDT, 3 with delayed skin tests (DSTs) and 3 with DPT (all immediate DPT reactions). Only in 2 of these patients (number 8 and 14) sIgE ImmunoCAP was positive (1 amoxicillin, 1 penicillin V, G and amoxicillin). One of the patients was SPT posi tive to the corresponding penicillin. The other patient with a negative ST and positive DPT had positive sIgE measured by ImmunoCAP and Immulite. The other patients were Immulite negative. It is noteworthy that all 5 patients with a history of anaphylaxis were ST positive (Table 1).
Among 67 delayed reactors, hypersensitivity was confirmed in 22 patients (32.8%). The hypersensitivity reaction occurred 55.0 [+ or -] 103.5 months before testing in patients with confirmed allergy and 100.2 [+ or -] 137.6 months before testing in patients with negative diagnostic work-up; the difference was not statistically significant (p > 0.05, t-test). As shown in Table 1, there was 1 patient with SPT (a patient with a history of anaphylaxis 3 hours after taking penicillin V), 8 with DST, and 13 with DPT. The ImmunoCAP sIgE was positive in 5 patients, (2 amoxicillin, 3 penicillin V). One of these patients was SPT positive, 2 were negative to DPT, and 1 was ST negative but reacted to prolonged DPT. All 5 ImmunoCAP sIgE positive patients were Immulite negative (Table 1).
In 12 patients, who were not able to recall the time course of the reaction, one patient was delayed ST positive (Table 1). All the others were ST and DPT negative. All patients were sIgE negative by both methods.
The diagnostic value of both sIgE assays is shown in Table 2. In 11 patients with positive immediate ST or DPTs, ImmunoCAP was truly positive in 3 patients and Immulite in 1 patient. Sensitivity of ImmunoCAP and Immulite were 27.2% and 9.1%, respectively. Specificity of ImmunoCAP and Immulite were 96.1% and 100%, respectively. Out of 6 positive ImmunoCAP sIgE with culprit antibiotic, 3 were truly positive, 2 were false positive and 1 was probably false positive (a patient with high tIgE), namely the patient had negative ST, but positive delayed DPT. As shown in Table 1, all three truly positive sIgE results (patients 8, 14, 23) were tested not more than 3 months after reaction (Table 1). The sIgE was false negative in 5 patients with immediate ST positivity, and the additional 3 patients were with negative ST and immediate DPT reaction. In Immulite, 1 patient was truly positive and 10 false negative. The difference in sensitivity and specificity between tests was not statistically significant (p > 0.05, chi-square).
As shown in Table 3, sIgE against penicillin and/or amoxicillin were detected with ImmunoCAP in 0/9 penicillin tolerant subjects with tIgE between 700 and 1000 kIU/L, 3/8 with tIgE between 1000 and 2000, and 5/5 with tIgE over 2000 kIU/L. Six were positive to penicillin and 2 to amoxicillin. The concentration of sIgE was between 0.37 and 0.76 kIU/L. All sera were negative with Immulite (p < 0.05, chi-square).
This prospective study was designed to compare the diagnostic efficacy of two commercially available tests for detection of sIgE in the sera of patients with suspected allergy to penicillin antibiotics (penicillin G, V and/or amoxicillin). The well known disadvantages of commercially available in vitro tests, radio allegro sorbent test (RAST) and enzyme-linked immunosorbent assay (ELISA) include their low sensitivity and ability to detect only sIgE to major but not minor penicillin (penicillin G, V and/or amoxicillin) determinants .
This study showed that compared to Immuno-CAP, Immulite assay has lower sensitivity, but the difference did not reach statistical significance. To our knowledge, there are no reports comparing both widely used diagnostic in-vitro assays for beta lactam allergy. There are few reports comparing assays in respiratory, food and venom allergies . In a study of predominantly inhalant allergen allergy, Lee and colleagues found close association and significant correlation between both assays. Intermethod agreement based on sIgE detection was 74.1 - 100% . In food allergic patients (chicken egg white, cow's milk and/or peanut) sIgE levels obtained by both methods were highly correlated regarding positivity/negativity rating, but the values obtained by Immulite were 2- to 5-fold higher than those obtained by ImmunoCAP [10, 11].
On the other side, it has been reported, that IgE sensitization does not automatically mean the presence of allergic disease [12, 13]. In ImmunoCAP penicillin sIgE assay, two technical problems were identified which may have resulted in false positive results. High tIgE sometimes resulted in low level positive result of sIgE to beta lactams in UniCAP assay [14, 15]. In as says used before 2005, positive sIgE results were found in nearly half of sera with tIgE between 500 and 600 kIU/L, and 75% in patients with tIgE over 1000 kIU/L. In a retrospective analysis of 606 patients with a history of penicillin allergy, 49 patients (8%) were sIgE positive . About one third of these had tIgE over 500 kIU/L. Four of such patients were subjected to DPT and turned out negative. In the current study, an improved ImmunoCAP assay was used , and false positive sIgE results were found only in sera with tIgE over 1000 kIU/L. Some other studies have also shown high rate of false positivity of sIgE against penicillin antibiotics. Silva  challenged patients with positive UniCAP sIgE to penicillin. Only 2 out of 7 patients were DPT positive. Macy  challenged SPT negative patients with a remote history of penicillin allergy regardless of the result of in-vitro tests. Six out of 150 patients were sIgE (UniCAP) positive to penicillins, and all of them were DPT negative. Johanson and colleagues found that 26% of patients with suspected IgE-mediated reaction to penicillin and positive penicillin ImmunoCAP actually might have clinically irrelevant IgE, which makes, as they stated, Immuno-CAP a poor choice for the diagnosis of penicillin allergy . Unfortunately, they did not test other commercial penicillin sIgE tests for that flaw. Hjortlund and colleagues made a diagnosis of beta lactam allergy in 28.7% of tested subjects . They also noticed a considerable lack of correlation between IgE and ST-positivity. They performed STs in sIgE positive patients and found that only 6 of 19 IgE-positive patients were also IDT positive. Unfortunately, DPT was not performed in sIgE positive ST negative patients. They also reported that intradermal ST might be false negative. They performed duplicate tests and showed that reproducibility of penicillin ST is only 83%. That might be one of the reasons why some patients with convincing history have negative ST and positive DPT.
There are some limitations of our study that should be considered when evaluating the results. In the retrospective part, ImmunoCAP results obtained from fresh sera were compared with Immulite results obtained from frozen sera. Thus, after testing frozen sera with ImmunoCAP, 12 out of 45 samples turned negative. We cannot explain the reason for the negativization of the ImmunoCAP results. One possibility, which is less likely, is the decrease of sIgE concentration over time in stored frozen samples. The more likely explanation is the improvement in the reagents used for sIgE determination . However, in the prospective part of the study, both methods were tested simultaneously using frozen sera. A pitfall was also a selection of allergens for ST. The two main allergenic determinants currently used in the diagnosis of type I or immediate hypersensitivity to benzylpenicillin and related antibiotics (beta-lactam), by means of SPT and IDTs are classified as major benzylpenicilloyl poly-L-lysine (PPL) formed by the bonding of the primary determinant to lysine chains and minor determinant mix (MDM), mixture of sodium benzylpenicillin, benzylpenicilloic acid, and sodium benzylpenicilloate. Both PPL and MDM are recommended standard reagents for penicillin ST. However, penicillin G is commonly suggested as an alternative source of minor determinants . In this study, penicillin G (10,000 IU/ml) was used, since PPL and MDM are not available in our market. Penicillin G was also used in ST in patients with positive history following penicillin V treatment. That might be the reason for ST negativity in patients with positive DPT with penicillin
Both ImmunoCAP and Immulite sIgE assays showed low sensitivity when assessing patients with a history of hypersensitivity reactions during penicillin treatment, as well as positive immediate skin or immediate drug provocation tests. In addition, Immuno-CAP is nonspecific in patients with high total immunoglobulin E levels.
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Mitja KOSNIK (1,2), Mira SILAR (2), Mihaela ZIDARN (2) and Petar KOROSEC (2)
University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia (1)
University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia (2)
The study was performed as a part of research program P3-0360 financed by Slovenian Research Agency
Nissera Bajrovic, MD, Renato Erzen, MD, Peter Kopac, MD, Nika Lalek, MD; Katja Adamic, MD performed diagnostic workup. Vesna [ETH]ordevic, MD has performed the translation to Serbian language
Table 1. Clinical data on patients with positive penicillin allergy tests Tabela 1. Klinicki podaci pacijenata sa pozitivnim alergoloskim testovima na peniciline Patient History number Anamneza Broj pacijenta 1 Type Culprit drug/Lek Clinical Tip koji je prouzrokovao presentation hipersenzitivnu Klinicka reakciju prezentacija 2 immediate amoxi/clav, itch rana pen V/amoxiclav svrab V, pen V 3 immediate amoxicillin urticaria rana amoksicilin urtikarija 4 immediate amoxi/clav urticaria rana amoksi/klav urtikarija 5 immediate amoxi/clav angioedema rana amoksi/klav angioedem 6 immediate amoxi/clav anaphylaxis rana amoxi/clav anafilaksa 7 immediate amoxi/clav anaphylaxis rana amoksi/klav anafilaksa 8 immediate amoxi/clav anaphylaxis rana amoksi/klav anafilaksa 9 immediate amoxi/clav anaphylaxis rana amoksi/klav anafilaksa 10 immediate amoxi/clav urticaria rana amoksi/klav urtikarija 11 immediate amoxicillin urticaria rana amoksicilin urtikarija 12 immediate amoxi/clav MPE rana amoksi/klav MPE 13 immediate pen V dyspnea rana pen V dispnea 14 immediate pen V MPE rana pen V MPE 15 delayed amoxi/clav MPE kasna amoksi/klav MPE 16 delayed amoxicillin urticaria kasna amoksicilin urtikarija 17 delayed amoxi/clav urticaria kasna amoksi/klav urtikarija 18 delayed amoxi/clav MPE kasna amoksi/klav MPE 19 delayed amoxi/clav urticaria kasna amoksi/klav MPE 20 delayed pen V MPE kasna pen V MPE 21 delayed pen V MPE kasna pen V MPE 22 delayed amoxi/clav MPE kasna amoksi/klav MPE 23 delayed pen V anaphylaxis kasna pen V anafilaksa 24 delayed amoxicillin urticaria kasna amoksicilin urtikarija 25 delayed pen V angioedema kasna pen V angioedem 26 delayed pen V urticaria kasna pen V urtikarija 27 delayed pen V MPE kasna pen V MPE 28 delayed amoxicillin MPE kasna amoksicilin MPE 29 delayed pen V urticaria kasna pen V urtikarija 30 delayed pen V urticaria kasna pen V urtikarija 31 delayed amoxicillin erythema kasna amoksicilin eritem 32 delayed amoxi/clav urticaria kasna amoksi/klav urtikarija 33 delayed pen V urticaria kasna pen V urtikarija 34 delayed pen V angioedema kasna pen V angioedem 35 delayed pen V angioedema kasna pen V angioedem 36 delayed amoxi/clav urticaria kasna amoksi/klav urtikarija 37 delayed amoxicillin urticaria kasna amoksicilin urtikarija 38 delayed pen V Dress kasna pen V Dress 39 unknown amoxicillin urticaria nepoznata amoksicillin urtikarija Patient History Delay to testing number Anamneza (months) Broj Vreme do testiranja pacijenta (meseci) 1 Type Treatment duration Tip till reaction Trajanje terapije do pojave eakcije 2 immediate 1 hour 14 rana 1 cas 3 immediate 1 hour 100 rana 1 cas 4 immediate 1 hour 3 rana 1 cas 5 immediate 1 hour 24 rana 1 cas 6 immediate 20 minutes 6 rana 20 minuta 7 immediate 20 minutes 120 rana 20 minuta 8 immediate 10 minutes 3 rana 10 minuta 9 immediate 5 minutes 2 rana 5 minuta 10 immediate 1 hour 350 rana 1 cas 11 immediate 10 minutes 4 rana 10 minuta 12 immediate 1 hour 60 rana 1 cas 13 immediate 1 hour 24 rana 1 cas 14 immediate 1 hour 1 rana 1 cas 15 delayed 3 days 90 kasna 3 dana 16 delayed 4 days 7 kasna 4 dana 17 delayed 3 days 17 kasna 3 dana 18 delayed 4 days 9 kasna 4 dana 19 delayed 4 days 40 kasna 4 dana 20 delayed 4 days 10 kasna 4 dana 21 delayed 4 days 400 kasna 4 dana 22 delayed 9 days 5 kasna 9 dana 23 delayed 3 hours 3 kasna 3 casa 24 delayed 7 days 140 kasna 7 dana 25 delayed 3 days 300 kasna 3 dana 26 delayed 5 days 3 kasna 5 dana 27 delayed 3 days 6 kasna 3 dana 28 delayed 8 days 3 kasna 8 dana 29 delayed 10 days 6 kasna 10 dana 30 delayed 12 days 4 kasna 12 dana 31 delayed 2 days 36 kasna 2 dana 32 delayed 7 days 12 kasna 7 dana 33 delayed 7 days 7 kasna 7 dana 34 delayed 8 hours 100 kasna 8 casova 35 delayed 3 days 10 kasna 3 dana 36 delayed 5 days 3 kasna 5 dana 37 delayed 10 days 9 kasna 10 dana 38 delayed 10 days 400 kasna 10 dana 39 unknown 3 days 240 nepoznata 3 dana Patient sIgE Immuno sIgE Immulite Total IgE number CAP kIU/L kIU/L kIU/L Broj sIgE Immuno sIgE Immulite Ukupan IgE pacijenta CAP kIU/L kIU/L kIU/L 1 Type pen pen amox pen pen amox Tip V G V G 2 immediate < < < < < < NA rana 3 immediate ND ND < ND ND < NA rana 4 immediate ND ND < ND ND < NA rana 5 immediate < ND < < ND < NA rana 6 immediate < < < < < < NA rana 7 immediate < ND < ND ND < NA rana 8 immediate < < 3,58 < < < 80,7 rana 9 immediate ND ND < ND ND < NA rana 10 immediate ND ND < ND ND < NA rana 11 immediate ND ND < ND ND < NA rana 12 immediate ND ND < ND ND < NA rana 13 immediate < < < < < < NA rana 14 immediate 7,42 0,78 1,26 0,41 0,48 0,44 >2000 rana 15 delayed ND ND < ND ND < NA kasna 16 delayed ND ND < ND ND < NA kasna 17 delayed ND ND < ND ND < NA kasna 18 delayed ND ND < ND ND < NA kasna 19 delayed < < < < < < NA kasna 20 delayed < < < < < < NA kasna 21 delayed < < ND < < ND NA kasna 22 delayed < < ND < < ND NA kasna 23 delayed 19,8 < ND < < ND 71,1 kasna 24 delayed ND ND < ND ND < NA kasna 25 delayed < < ND < < ND NA kasna 26 delayed 0,5 0,54 ND < < ND 2733 kasna 27 delayed < < < < < < NA kasna 28 delayed < < NA kasna 29 delayed < < ND < < ND NA kasna 30 delayed < < ND < < ND NA kasna 31 delayed ND ND < ND ND < NA kasna 32 delayed ND ND < ND ND < NA kasna 33 delayed < < ND < < < NA kasna 34 delayed < ND ND < < ND NA kasna 35 delayed < ND 0,51 ND ND < 2375 kasna 36 delayed ND ND < ND ND < NA kasna 37 delayed ND < 7,83 ND < < 421 kasna 38 delayed 1,05 0,62 ND < < ND 803 kasna 39 unknown < ND < << ND ND NA nepoznata Patient Skin tests OPT number Kozni OPT Broj testovi pacijenta 1 Type Drug Tip Lek 2 immediate ID amoxi/clav late ND rana positive/ID amoksi/klav kasno pozitvna 3 immediate ID amoxi/clav late ND rana positive/ ID amoksi/klav kasno pozitvna 4 immediate ID amoxi/clav late ND rana positive/ID amoksi/klav kasno pozitvna 5 immediate ID pen V, amox/clav ND rana positive/ID pen V, amoksi/klav pozitivno 6 immediate ID amox/clav positive/ID ND rana amoksi/klav pozitivno 7 immediate prick amox/clav positive/prik ND rana amoks/klav pozitivno 8 immediate prick amoxicillin ND rana positive/prik moksicillin pozitivno 9 immediate prick amoxicillin ND rana positive/prik amoksicillin pozitivno 10 immediate prick amox/clav positive/prik ND rana amoks/klav pozitivno 11 immediate prick amoxicillin and ND rana ID pen V positive/prik amoksicillin i ID pen V pozitivno 12 immediate negative amoxi/clav rana negativno amoksi/klav 13 immediate negative pen V rana negativno 14 immediate negative pen V rana negativno 15 delayed ID amoxi/clav late positive/ID ND kasna amoksi/klav kasno pozitivno 16 delayed ID amoxi/clav late positive/ID ND kasna amoksi/klav kasno pozitivno 17 delayed ID amoxi/clav late ND kasna positive/ID amoksi/klav kasno pozitivno 18 delayed ID amoxi/clav late ND kasna positive/ID amoksi/klav kasno pozitivno 19 delayed ID amoxi/clav late ND kasna positive/ID amoksi/klav kasno pozitivno 20 delayed ID amoxi/clav late ND kasna positive/ID amoksi/klavkasno pozitivno 21 delayed ID penicillin late positive/ID ND kasna penicillin kasno pozitivno 22 delayed ID penicillin late positive/ID ND kasna penicillin kasno pozitivno 23 delayed prick penicilline G ND kasna positive/prik penicillin G pozitivno 24 delayed negative amoxicillin kasna negativno amoksicilin 25 delayed negative pen V kasna negativno 26 delayed negative pen V kasna negativno 27 delayed negative pen V kasna negativno 28 delayed negative amoxicillin kasna negativno amoksicilin 29 delayed negative pen V kasna negativno 30 delayed negative pen V kasna negativno 31 delayed negative amoxicillin kasna negativno amoksicilin 32 delayed negative amoxicillin kasna negativno amoksicilin 33 delayed negative pen V kasna negativno 34 delayed negative pen V kasna negativno 35 delayed negative pen V kasna negativno 36 delayed negative amoxi/clav kasna negativno amoksi/klav 37 delayed amoxicillin amoxicillin kasna amoksicillin amoksicilin 38 delayed pen V pen V kasna pen V 39 unknown ID amoxi/clav late positive/ID ND nepoznata amoksi/klav kasno pozitivno Patient OPT number OPT Broj pacijenta 1 Type Reaction Tip Reakcija 2 immediate ND rana 3 immediate ND rana 4 immediate ND rana 5 immediate ND rana 6 immediate ND rana 7 immediate ND rana 8 immediate ND rana 9 immediate ND rana 10 immediate ND rana 11 immediate ND rana 12 immediate erythema rana eritem 13 immediate anaphylaxis rana anafilaksa 14 immediate urticaria rana urtikarija 15 delayed ND kasna 16 delayed ND kasna 17 delayed ND kasna 18 delayed ND kasna 19 delayed ND kasna 20 delayed ND kasna 21 delayed ND kasna 22 delayed ND kasna 23 delayed ND kasna 24 delayed urticaria kasna urtikarija 25 delayed MPE kasna 26 delayed MPE kasna 27 delayed MPE kasna 28 delayed erithema kasna eritem 29 delayed MPE kasna 30 delayed MPE kasna 31 delayed erithema kasna eritem 32 delayed MPE kasna 33 delayed urticaria kasna urtikarija 34 delayed urticaria kasna urtikarija 35 delayed angioedema kasna angioedem 36 delayed urticaria kasna urtikarija 37 delayed negative kasna negativno 38 delayed negative kasna negativno 39 unknown ND nepoznata Legend: Delay to testing: interval between hypersensitivity reaction and diagnostics; amoxi/clav - amoxicillin plus clavulanic acid; ID - intradermal test; OPT - oral provocation test; ND - test not performed; MPE - maculopapular exantema Legenda: Vreme do testiranja: interval izmedu hipersenzitivne reakcije i dijagnoze; amoksi/klav - amoksicilin plus klavulanska kiselina; ID - intradermalni test; OPT - oralni provokativni test; ND - test nije bio izveden; MPE - makulo-papularni osip, sIgE - specificni imunoglobulin E Table 2. ImmunoCAP and Immulite sIgE assays in patients with a history compatible with hypersensitivity reaction during penicillin treatment, with immediate positive skin reaction or immediate drug provocation tests Table 2. ImmunoCAP i Immulite testovi za specificni imunoglobulin E kod pacijaneta sa anamnezom hipersenzitvne rekacije za vreme primanja penicilina, koji su imali rane pozitvne kozne testove ili provokativno testiranje Immuno CAP Immulite True positive (patients)/Pozitivni (pacijenti) 3 1 False positive (patients)/Lazno pozitivni 4 0 (pacijenti) False negative (patients)/Lazno negativni 8 10 (pacijenti) True negative (patients)/Negativni (pacijenti) 99 103 Sensitivity (%)/Senzitivnost (%) 27.2 9.1 Specificity (%)/Specificnost (%) 96.1 100 Positive predictive value (%)/Pozitivna 42.9 100 prognosticka vrednost (%) Negative predictive value (%)/Negativna 92.5 91.2 prognosticka vrednost (%) Table 3. ImmunoCAP and Immulite sIgE assays in penicillin tolerant patients with high levels of total IgE Table 3. ImmunoCAP i Immulite testovi za specificni imunoglobulin E kod pacijenta tolerantnih na penicillin sa visokim ukupnim imunoglobulinom E Subject number Immulite (kIU/l) ImmunoCAP (kIU/l) a Broj Immulite (kIU/l) ImmunoCAP (kIU/l) a pen G pen V amoxicillin pen V amoxicillin 1 < < < < < 2 < < < < < 3 < < < < < 4 < < < < < 5 < < < < < 6 < < < < < 7 < < < < < 8 < < < < < 9 < < < < < 10 < < < < < 11 < < < 0,76 < 12 < < < < < 13 < < < < < 14 < < < 0,38 < 15 < < < < < 16 < < < < 0,49 17 < < < < < 18 < < < 0,43 < 19 < < < 0,55 < 20 < < < 0,65 < 21 < < < 0,67 < 22 < < < < 0,35 Subject number Total IgE kIU/L Broj Ukupan IgE kIU/L 1 733 2 785 3 799 4 804 5 823 6 853 7 873 8 916 9 922 10 1040 11 1173 12 1221 13 1381 14 1424 15 1634 16 1813 17 1977 18 2001 19 2001 20 2001 21 2001 22 2001
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|Author:||Kosnik, Mitja; Silar, Mira; Zidarn, Mihaela; Korosec, Petar|
|Date:||Jul 1, 2017|
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