Printer Friendly

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.

Summary

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

Sazetak

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

Introduction

Suspected beta lactam allergy is quite common referral to allergy departments, but the diagnosis is confirmed in less than 20% of suspected patients [1]. 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 [2].
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 [3]. 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 [4]. 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 [3]. When STs were negative, DPT with the culprit antibiotic was performed [6]. 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 [5]. 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) [5]. 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 [5].

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.

Results

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).

Discussion

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 [7].

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 [8]. 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% [9]. 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 [16]. 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 [4], 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 [17] challenged patients with positive UniCAP sIgE to penicillin. Only 2 out of 7 patients were DPT positive. Macy [18] 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 [4]. 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 [3]. 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 [4]. 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 [20]. 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

Conclusion

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.

References

(1.) Trubiano J, Phillips E. Antimicrobial stewardship's new weapon? A review of antibiotic allergy and pathways to 'delabeling'. Curr Opin Infect Dis. 2013;26(6):526-37.

(2.) MacLaughlin EJ, Saseen JJ, Malone DC. Costs of betalactam allergies: selection and costs of antibiotics for patients with a reported beta-lactam allergy. Arch Fam Med. 2000;9(8): 722-6.

(3.) Hjortlund J, Mortz CG, Skov PS, Bindslev-Jensen C. Diagnosis of penicillin allergy revisited: the value of case history, skin testing, specific IgE and prolonged challenge. Allergy. 2013:68(8): 1057-64.

(4.) Johansson SG, Adedoyin J, van Hage M, Gronneberg R, Nopp A. False-positive penicillin immunoassay: an unnoticed common problem. J Allergy Clin Immunol. 2013;132(1):235-7.

(5.) Fransson S, Mosbech H, Kappel M, Hjortlund J, Poulsen LK, Kvisselgaard AD, et al. The importance of prolonged provocation in drug allergy - results from a Danish Allergy Clinic. J Allergy Clin Immunol Pract. In press. doi: 10.1016/j.jaip.2017.02.024.

(6.) Blanca M, Romano A, Torres MJ, Fernandez J, Mayorga C, Rodriguez J, et al. Update on the evaluation of hypersensitivity reactions to betalactams. Allergy. 2009;64(2):183-93.

(7.) Torres MJ, Blanca M, Fernandez J, Romano A, Weck A, Aberer W, et al. Diagnosis of immediate allergic reactions to beta-lactam antibiotics. Allergy. 2003;58(10):961-72.

(8.) Selb J, Kogovsek R, Silar M, Kosnik M, Korosec P. Improved recombinant Api m1 - and Ves v 5-based IgE testing to dissect bee and yellow jacket allergy and their correlation with the severity of the sting reaction. Clin Exp Allergy. 2016;46(4):621-30.

(9.) Lee YW, Sohn JH, Lee JH, Hong CS, Park JW. Allergen-specific IgE measurement with the IMMULITE 2000 system: intermethod comparison of detection performance for allergen-specific IgE antibodies from Korean allergic patients. Clin Chim Acta. 2009;401(1-2):25-32.

(10.) Hamilton RG, Mudd K, White MA, Wood RA. Extension of food allergen specific IgE ranges from the ImmunoCAP

to the IMMULITE systems. Ann Allergy Asthma Immunol. 2011;107(2):139-44.

(11.) Wang J, Godbold JH, Sampson HA. Correlation of serum allergy (IgE) tests performed by different assay systems. J Allergy Clin Immunol. 2008;121(5):1219-24.

(12.) Bodtger U. Prognostic value of asymptomatic skin sensitization to aeroallergens. Curr Opin Allergy Clin Immunol. 2004;4(1):5-10.

(13.) Bousquet J, Anto JM, Bachert C, Bousquet PJ, Colombo P, Crameri R, et al. Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitization to allergens. A GA2LEN project. Allergy. 2006;61(6):671-80.

(14.) Zidarn M, Silar M, Vegnuti M, Korosec P, Kosnik M. The specificity of tests for anti-beta-lactam IgE antibodies declines progressively with increase of total serum IgE. Wien Klin Wochenschr. 2009;121(9-10):353-6.

(15.) Aberer W, Zidarn M, Kranke B. IgE antibodies to penicillin are indicative for but not conclusive proof of penicillin allergy. Br J Dermatol. 2006;154(6):1209-10.

(16.) Kopac P, Zidarn M, Kosnik M. Epidemiology of hypersensitivity reactions to penicillin in Slovenia. Acta Dermatovenerol Alp Pannonica Adriat. 2012;21(4):65-7.

(17.) Silva R, Cruz L, Botelho C, Castro E, Cadinha S, Castel-Branco MG, et al. Immediate hypersensitivity to penicillins with negative skin tests--the value of specific IgE. Eur Ann Allergy Clin Immunol. 2009;41(4):117-9.

(18.) Macy E, Goldberg B, Poon KYT. Use of commercial anti--penicillin IgE fluorometric enzyme immunoassays to diagnose penicillin allergy. Ann Allergy Asthma Immunol. 2010;105(2):136-41.

(19.) Wangrattanasopon P, Ruxrungtham K, Chantaphakul H, Buranapraditkun S, Klaewsongkram J. Alkali-treated penicillin G solution is a better option than penicillin G as an alternative source of minor determinants for penicillin skin test. Allergy Asthma Proc. 2012;33(3):152-9.

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)

Acknowledgements

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
COPYRIGHT 2017 Drustvo Lekara Vojvodine
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2017 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Kosnik, Mitja; Silar, Mira; Zidarn, Mihaela; Korosec, Petar
Publication:Medicinski Pregled
Article Type:Report
Date:Jul 1, 2017
Words:5743
Previous Article:OUTCOME OF INTRAVENOUS THROMBOLYSIS FOR ACUTE ISCHEMIC STROKE IN PATIENTS WITH AND WITHOUT ATRIAL FIBRILLATION/ISHOD NAKON AKUTNOG ISHEMIJSKOG...
Next Article:WORK STATUS AND FACTORS AFFECTING WORK ENGAGEMENT OF PEOPLE WITH MULTIPLE SCLEROSIS./RADNI STATUS I FAKTORI KOJI UTICU NA RADNO ANGAZOVANJE OBOLELIH...
Topics:

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters