Skin Test Sensitivity Research Articles

Scientific platform, development and implementation of effective immunodiagnosis of tuberculosis infection in the Russian Federation

The review presents scientific information about modern approaches to immunodiagnosis of tuberculosis infection in the Russian Federation, which allows to control the spread of infection and prevent the development of the disease in individuals infected with Mycobacterium tuberculosis (MTB). The results of Russian and foreign studies have shown a low total sensitivity of the Mantoux tuberculin skin test, which indicates a low predictive value of the test for the diagnosis of tuberculosis infection. The article presents the results of preclinical and clinical studies of a new diagnostic test for the detection of tuberculosis infection using Diaskintest. The results substantiate the purpose of Diaskintest for the diagnosis of tuberculosis infection, assessment of the process activity; differential diagnosis of tuberculosis; differential diagnosis of post-vaccination and infectious immune response (delayed-type hypersensitivity); monitoring the effectiveness of treatment. The article presents the results information on the screening of tuberculosis infection in the Russian Federation using Diaskintest, its significance, efficacy, and safety. The results of scientific studies carried out in recent years to assess the effectiveness of immunodiagnostics in the Russian Federation give reason to believe that the introduction of a modern screening method for diagnosing tuberculosis infection using Diaskintest can significantly improve the quality of doctors work on the early detection of various manifestations of tuberculosis infection and significantly reduce the states material costs for combating with tuberculosis.

High conversion of tuberculin skin tests during the first year of antiretroviral treatment among South African adults in primary care.

Anergy reduces the sensitivity of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis infection in people living with HIV. Antiretroviral treatment (ART) can reverse TST anergy, but data is scarce. To estimate TST conversion rates and factors associated with TST conversion, TST was placed at ART initiation, and 6 and 12 months thereafter (if TST negative at prior assessment). Of 328 ART-eligible participants, 70% (231/328) had a valid TST result of whom 78% (180/231) were TST negative. At 6-month follow-up, 22% (24/109, 95% confidence interval [CI] 15%, 31%) of participants on ART, without incident tuberculosis (TB), and with a valid TST result converted to a positive TST. Of these 109 individuals, those with baseline CD4+ cell count >250 cells/μl were more likely to TST convert compared to those with baseline CD4+ cell count ≤250 cells/μl (odds ratio [OR] 3.54, 95% CI 1.29, 11.47). At 12 months post-ART initiation, an additional 12% (9/78, 95% CI 6, 20) of participants on ART, without incident TB and with a valid TST result experienced TST conversion. After 1 year on ART, TST conversion rate was 38 per 100 person-years (95% CI 26, 52), and lower in individuals with baseline CD4+ cell count ≤250 cells/μl (23/100 person-years, 95% CI 11, 41) compared to those with baseline CD4+ cell count >250 cells/μl (50/100 person-years, 95% CI 32, 73). TST conversion rate in the first year of ART is high, especially among people with CD4+ cell count >250 cells/μl. A TST-based eligibility strategy at ART initiation may underestimate eligibility for preventive therapy for tuberculosis.

The IL-1promoter-driven luciferase reporter cell line THP-G1b can efficiently predict skin-sensitising chemicals.

IL-1functions as an essential pro-inflammatory mediator for the sensitisation of allergic contact dermatitis (ACD). However, studies conducted to date have typically used a limited number of haptens and examined their effects only on murine ACD or murine dendritic cells (DCs). It therefore remains unclear whether IL-1α and/or IL-1β is produced in ACD induced by haptens other than those commonly used in mouse ACD models, and whether they are essential for sensitisation leading to ACD in humans. In addition, it is unclear whether human DCs also produce IL-1α or IL-1β after stimulation by haptens in general. Here, we first demonstrated that 10 haptens (3 extreme, 1 strong, 3 moderate and 3 weak) increased both IL-1α mRNA and IL-1β mRNA expression by the human monocyte cell line THP-1, a commonly used surrogate of DCs in in vitro skin sensitisation tests. Next, we constructed an in vitro skin sensitisation test using a stable IL-1β reporter cell line, THP-G1b, and evaluated whether 88 haptens and 34 non-haptens increase IL-1β reporter activity. We found that 94% of 77 haptens evaluated after considering their applicability domain and solubility in the chosen media stimulated reporter activity. These studies demonstrated that most haptens, irrespective of their potency, increased IL-1β mRNA expression by THP-1 cells, confirming that human DCs also produce IL-1β after stimulation by most haptens. The luciferase assay using THP-G1b cells is thus another skin sensitisation test based on the adverse outcome pathway with reasonable performance.

Properties of a bovine collagen type I membrane for guided bone regeneration applications

Abstract Dental implant treatment requires an available bone volume in the implantation site to ensure the implant’s mechanical stability. When the bone volume is insufficient, one must resort to surgical means such as guided bone regeneration (GBR). In GBR surgery, bone grafts and membranes are used. The objective of this work is to manufacture and characterize the in vitro and in vivo properties of resorbable collagen type I membranes (Green Membrane®) for GBR. Membrane surface morphology was characterized by SEM and roughness was measured using an interferometric noncontact 3D system. In vivo skin sensitization and toxicity tests have been performed on Wistar rats. Bone defects were prepared in 24 adult male rats, filled with biomaterials (Blue Bone® and Bio Oss®) and covered with collagen membranes to maintain the mechanical stability of the site for bone regeneration. The incisions were closed with simple stitches; and 60 days after the surgery, the animals were euthanized. Results showed that the analyzed membrane was homogeneous, with collagen fiber webs and open pores. It had no sign of cytotoxicity and the cells at the insertion site showed no bone morphological changes. There was no tissue reaction and no statistical difference between Blue Bone® and Bio Oss® groups. The proposed membrane has no cytotoxicity and displays a biocompatibility profile that makes it suitable for GBR.

Amino acid derivative reactivity assay-organic solvent reaction system: A novel alternative test for skin sensitization capable of assessing highly hydrophobic substances.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative to animal testing that focuses on protein binding. The ADRA is a skin sensitization test that solves problems associated with the direct peptide reactivity assay. However, when utilizing the ADRA to evaluate highly hydrophobic substances with octanol/water partition coefficients (logKow) of >6, the test substances may not dissolve in the reaction solution, which can prevent the accurate assessment of skin sensitization. Therefore, we developed the ADRA-organic solvent (ADRA-OS) reaction system, which is a novel skin sensitization test that enables the assessment of highly hydrophobic substances with a logKow of >6. We discovered that the organic solvent ratio, the triethylamine concentration, and the ethylenediaminetetraacetic acid disodium salt dihydrate concentration participate in reactions with the nucleophile N-(2-(1-naphthyl)acetyl)-l-cysteine (NAC) and sensitizers that are used in ADRA and in stabilizing NAC. Thus, we determined the optimal reaction composition of the ADRA-OS according to L9 (33 ) orthogonal array experiments. Using this test, we assessed 14 types of highly hydrophobic substances. When we compared the results with ADRA, we found that ADRA-OS reaction system has high solubility for highly hydrophobic substances and that it has a high predictive capacity (sensitivity: 63%, specificity: 100%, accuracy: 79%). The implication of the results is that the novel ADRA-OS reaction system should provide a useful method for assessing the skin sensitization of highly hydrophobic substances with a logKow of >6.

A Pilot Clinical Study of Ocular Prosthesis Fabricated by Three-dimensional Printing and Sublimation Technique.

PurposeWe sought to evaluate the safety and effectiveness of patient-specific ocular prostheses produced by three-dimensional (3D) printing and the sublimation technique. A comparison with prostheses produced using manual manufacturing methods was then performed.MethodsTo confirm the biological and physiochemical safety, cytotoxicity, systemic acute toxicity, intradermal reaction, and skin sensitization tests were conducted according to the International Organization for Standardization guidelines. The compressive strength of the prostheses was also tested. Further, a case series of three patients who wore the 3D printed prostheses for more than eight hours daily for 4 weeks was executed. Self-assessments by these individuals using a questionnaire and safety evaluations focusing on the occurrence of conjunctival inflammation or allergic reactions according to the Cornea and Contact Lens Research Unit criteria by slit-lamp examination and similarity assessment were completed.ResultsThe 3D printed ocular prostheses met the necessary qualifications per the biological and physiochemical safety tests, showing the absence of cytotoxicity, acute systemic toxicity, intradermal reactivity, and skin-sensitizing potency. Also, there was no difference in strength test results between previous ocular prostheses and the 3D printed ones. Self-assessment by the patients yielded satisfactory results, with no significant difference in the level of satisfaction reported for the 3D printed and previous handmade ocular prostheses. The 3D printed prosthesis did not trigger any side effects in the conjunctival sac and showed similar objective findings with respect to the color of the iris, sclera, and vessel patterns.ConclusionsOur study confirms the biologic and physiochemical safety of 3D-printed ocular prostheses created using computer-aided design technology and a sublimation technique. The patients’ questionnaires and the judgment of the ophthalmologists/ocularists showed that the 3D printed ocular prosthesis was acceptable in function and appearance through a case series report.

Enhancing between-facility reproducibility of the SH test as an in vitro skin sensitization test by the improved test method.

There has been an increased demand to eliminate animal experiments and to replace the experiments with alternative tests for assessing the safety of cosmetics. The SH test is an in vitro skin sensitization test that evaluates the protein binding abilities of a test substance. Skin sensitization must be evaluated by multiple test methods. The SH test uses the same cell line and measuring instruments as the human Cell-Line Activation Test (h-CLAT), which is one of the test methods used to evaluate different key events and is listed in the OECD test guidelines. There are cost advantages to usher the SH test into facilities that are already running the h-CLAT. The SH test is conducted only at a facility that has developed the SH test because studies on the between-facility reproducibility and validity have not been performed. Therefore, to verify the transferability of the SH test and the between-facilities reproducibility, we evaluated the reproducibility of the SH test results at three facilities, including the development facility. After an initial round of testing, the protocol was refined as follows to improve reproducibility among the three facilities: i) determine the optimum pH range, ii) change the maximum applicable concentration of water-soluble substances, and iii) define the appropriate dispersion conditions for evaluating hydrophobic substances. These refinements markedly enhanced the between-facility reproducibility (from 76.0% to 96.0%) for the 25 substances evaluated in this study. This study confirmed that the SH test is an effective skin sensitization test method with high technical transferability and between-facility reproducibility.

Comparison of Sensitivities of Skin Prick and Intradermal Tests with Oral Rechallenge Test: A Prospective Interventional Hospital-Based Study.

Background:Identification of culprit drug causing adverse cutaneous drug reactions may not be possible clinically due to the intake of more than one drug.Aim:To compare the sensitivity of skin tests with gold standard oral rechallenge test to detect adverse cutaneous drug reactions.Materials and Methods:This is a prospective interventional hospital-based study of patients with adverse cutaneous drug reactions attending the outpatient department of dermatology and venereology at a tertiary care center over a 12-month period. Skin prick tests, intradermal tests, and oral rechallenge tests were performed in these patients and their sensitivities were compared. The data of quantitative nature is presented in mean and standard deviation, and categorical variables are presented in number and percentage. The sensitivity of skin tests is compared with the gold standard oral rechallenge test.Results:A total of 49 patients with adverse cutaneous drug reactions were evaluated. Clinical spectrum of adverse cutaneous drug reactions ranged from mild to severe, with fixed drug eruption being the commonest (55.1%) followed by maculopapular exanthem (32.7%). The highest incidence was with fluoroquinolones (43.8%) followed by nonsteroidal anti-inflammatory drugs. Fluoroquinolones were the major cause of fixed drug eruption followed by nonsteroidal anti-inflammatory drugs. The sensitivity of skin prick test and intradermal tests were 49% and 73%, respectively and the difference was highly significant (P < 0.001). The difference in sensitivity in skin prick test versus oral rechallenge test and intradermal test versus oral rechallenge test was also highly significant (P < 0.001).Limitations:Small sample size was a major limitation. Histopathological examinations and human leukocyte antigen associations could not be done.Conclusion:Predominant causative drugs were fluoroquinolones followed by nonsteroidal anti-inflammatory drugs. Sensitivities of skin prick test and intradermal test were quite good and these skin tests should be performed before oral rechallenge test in cases of adverse cutaneous drug reactions.

Efficacy of erector spinae plane block with opioid-sparing analgesic technique in breast-conserving surgery.

PurposeBreast-conserving surgery (BCS) is a surgical method designed to minimize intraoperative tissue injury. Although this technique is minimally invasive, it can cause significant postoperative pain and may be a risk factor for persistent pain. Erector spinae plane block (ESPB) is an easy interfascial plane block for analgesia in patients undergoing breast surgery. The primary outcome was the numeric rating scale scores measured separately on the breast and axilla. Secondary outcomes included correlation between pain score and skin sensitivity test.MethodsForty patients were divided into 2 groups (ESPB group and control group). Patients in the ESPB group received an ESPB 30 minutes before the induction of general anesthesia, whereas patients in the control group did not receive any regional analgesia during the perioperative period.ResultsMedian pain scores of the breast were significantly lower in the ESPB group than that in the control group at 12, 24, and 48 hours after surgery. However, the median pain scores of the axilla were not significantly different between the groups, and the pain score was unrelated to skin sensitivity.ConclusionESPB can effectively alleviate acute postoperative pain with an opioid-sparing analgesic technique in patients undergoing BCS, and a strong correlation is lacking between pain scores and skin sensitivity test.

Skin Sensitization Tests: The LLNA and the RhE IL-18 Potency Assay.

Contact allergy is of considerable importance to the toxicologist, and regulatory authorities worldwide require testing for skin sensitization potential and appropriate hazard labeling to enable management of the risk to human health. Although traditionally the identification of skin-sensitizing chemicals has been carried out using animal models, in Europe legislative changes have promoted, and now require, the use of non-animal methods (i.e., Cosmetic Directive, REACH). Several in vitro alternatives for hazard identification have now been validated, but do not provide information on the potency of a skin sensitizer. Here, we describe an animal model, the local lymph node assay (LLNA), and an in vitro model, the RhE IL-18 potency assay, in the context of the identification and potency classification of skin sensitizers. These two assays have been chosen among the different available tests as representative of an alternative in vivo model (the LLNA) and a promising in vitro method with the potential of both hazard identification and potency classification.

Interpretation of tuberculin skin test in bacillus calmette–guerin-vaccinated children

Objective: The objective was to determine the sensitivity and specificity of tuberculin skin test (TST) in Bacillus Calmette–Guerin (BCG)-vaccinated children for diagnosis of tuberculosis (TB). Materials and Methods: This observational study was conducted at a single tertiary care center over a period of 32 months from March 2012 to November 2014. All children up to 15 years of age who had received BCG at birth, suspected of TB, and referred to pediatric TB clinic were enrolled in the study. All patients were given TST by 5 Tuberculin Unit Purified Protein Derivative-Standard. The diagnosis of TB was based on either clinical, histopathological, or bacteriological grounds. Results: Out of 371 patients, 341 (91.91%) had TB. TST was positive in 227 (61.2%) and negative in 144 (38.8%) patients. The sensitivity of TST to detect active TB was 62.8% and specificity was 56.7%. TST cutoff as ≥15 mm increased specificity of TST to 73.3%, but sensitivity decreased to 25.8%. Age, gender, and contact with TB patients did not affect TST results. Conclusion: The accuracy of TST for the diagnosis of TB is low with low sensitivity and specificity. By increasing the cutoff for positive TST to >15 mm, the number of false-positive TST can be reduced.

Safety evaluation of 2-aza-8-oxohypoxanthine by &lt;i&gt;in vitro&lt;/i&gt; skin sensitization and human tests

Safety evaluation of 2-aza-8-oxohypoxanthine by &lt;i&gt;in vitro&lt;/i&gt; skin sensitization and human tests

3R Kuramına Göre Güncel Deri Duyarlılığı Testleri

Deri duyarlılığı, çeşitli hücreler ve moleküller arasında yüksek koordineli etkileşim gerektiren son derece karmaşık ve sıkı düzenlenmiş biyolojik bir süreçtir. Alerjik kontakt dermatit ile sonuçlanan deri duyarlılığı, önemli bir mesleki ve çevresel sağlık sorunudur. Duyarlılaştırma potansiyelinin ölçümü, kozmetik ve kişisel bakım ürünlerinde kullanılan bileşenlerin geliştirilmesi ve risk değerlendirmesi için temel bir adımdır ve test sonucu, bir kimyasalın alerjik kontakt dermatite neden olma potansiyelini gösterir. Son yıllarda, ürün güvenliğini sağlamak için laboratuvar hayvanlarının kullanılmadığı alternatif yöntemlere öncelik verilir. Bu yolda, 3R kuramı ile bilimsel çalışmanın kalitesinden ödün vermeden rasyonel bir strateji izlenir. Alternatif yöntemler; toksikolojik bir son noktayı belirlerken, test başına hayvan sayısını, acısını ve sıkıntısını azaltan yöntemlerin kullanımı veya yer değiştirme ile sonuçlanan yeni teknikleri içerir. Konu, amaç ve teknik açıdan uygunsa in vivo yöntemlere tercih edilebilir veya entegre biçimde kullanılabilir. Alternatif yöntemlerin entegrasyonu ile in vivo yöntemlere olan gereksinim azalır. Test edilecek kimyasal madde sayısının her geçen gün arttığı düşünülürse, alternatif yöntemlerin kullanılması duyarlılık ölçümünün optimizasyonuna katkı sağlar. Avrupa Birliği ve Güney Kore, kozmetik ve kişisel bakım ürünleri için sadece alternatif hayvan dışı testleri kabul eder. Yasal sınırlamaların ve dünya çapında artan değere sahip olmalarının bir sonucu olarak alternatif yöntemler için çeşitli ülkelerde validasyon merkezleri kurulmuştur. Bu derlemede, deri duyarlılığı testlerinde gelinen son nokta ve entegre yaklaşımlar hakkında bilgi verilmiştir.

Latest Trends of Skin Sensitization Test Methods

Latest Trends of Skin Sensitization Test Methods

Skin sensitization test of potassium hydroxide in guinea pigs

This study was to evaluate the skin sensitization of potassium hydroxide (KOH) by the guinea pig maximization test. In the preliminary test, the induction and challenge dose of KOH were determined as 1.0 and 0.2%, respectively. Guinea pigs were sensitized with intradermal injection of 0.1ml KOH for 24 h. After 1 week, 1.0% of KOH was treated on the site of injection and 0.2% of KOH was challenged 2 weeks later. The average skin reaction evaluated by erythema and edema on the challenge sites and sensitization rate in the KOH-treatment group at 24 h were 0.0 and 0%, respectively, which are substantially low compared with in the 2,4-dinitrochlorobenzene-treatment group (positive control group) (average skin reaction: 3.0, sensitization rate: 100%) and identical with in the distilled water-treatment group (negative control group), representing a weak sensitizing potential. The average skin reaction and sensitization rate observed at 48 h were 0.0 and 0% in the KOH-treatment group, respectively, and 2.0 and 100% in the positive control group, respectively. It was concluded that 1.0% of KOH classified to Grade I, induced no sensitization when tested in guinea pigs.

Cephalosporin Hypersensitivity: Descriptive Analysis, Cross-Reactivity, and Risk Factors

Cephalosporins, which belong to the beta-lactam therapeutic class, are increasingly used throughout the world. Few large studies on this issue have been conducted, and most of them have been performed as part of penicillin hypersensitivity studies. We described our 26-year experience exploring cephalosporin drug hypersensitivity, from which we identified epidemiological and cross-reactivity data. We included 476 patients who reported drug hypersensitivity reaction (DHR) to cephalosporin and underwent an allergy workup between January 1992 and July 2018 in the Allergy Unit of the University Hospital of Montpellier (France). According to their structural side chain R1 homology, we worked with 4 classes of cephalosporins. Logistic regression analysis was used to search for risk factors for hypersensitivity to cephalosporin (positive skin test [ST] or drug provocation test [DPT] results). Cephalosporin hypersensitivity was proven in 22.3% of the patients referred in our Unit, according to positive ST (51.9%) or DPT to the culprit drug (48.1%). One in 5 patients were children, and cephalosporin hypersensitivity was confirmed in 15% (47.6% of them by means of ST). In the cephalosporin hypersensitive population, initial reactions were mostly immediate (68.9%) and anaphylactic (72.7%). Cross-reactivity with aminopenicillins was the most frequent pattern of cross-reactivity. In multivariate analysis, immediate reactions (odds ratio [OR]= 3, 95% confidence interval [CI] [1.6-5.5], P < .001), anaphylactic shock (OR= 6.5, 95% CI [3.3-13.1], P < .001) and anaphylaxis (OR= 3.1, 95% CI [1.6-6.1], P < .001), and multiple reactions to the same or several cephalosporins (OR= 2.0, 95% CI [1-3.5], P= .04) were statistically associated with confirmed DHR. DPT was generally safe, but elicited anaphylaxis in 20% of patients. Systemic reactions during skin testing occurred in 9.1% of positive patients, almost always related to anaphylactic index reactions. Nonimmediate confirmed DHR to cephalosporins were rare and occurred in less than 10% of the positive patients. Almost a quarter of the tested patients were confirmed as hypersensitive to cephalosporins; sensitivity of skin testing was 51.9%, and thus, half of the positive patients needed a DPT to prove the diagnosis.

Accounting for Precision Uncertainty of Toxicity Testing: Methods to Define Borderline Ranges and Implications for Hazard Assessment of Chemicals

For hazard classifications of chemicals, continuous data from animal‐ or nonanimal testing methods are often dichotomized into binary positive/negative outcomes by defining classification thresholds (CT). Experimental data are, however, subject to biological and technical variability. Each test method's precision is limited resulting in uncertainty of the positive/negative outcome if the experimental result is close to the CT. Borderline ranges (BR) around the CT were suggested, which represent ranges in which the study result is ambiguous, that is, positive or negative results are equally likely. The BR reflects a method's precision uncertainty. This article explores and compares different approaches to quantify the BR. Besides using the pooled standard deviation, we determine the BR by means of the median absolute deviation (MAD), with a sequential combination of both methods, and by using nonparametric bootstrapping. Furthermore, we quantify the BR for different hazardous effects, including nonanimal tests for skin corrosion, eye irritation, skin irritation, and skin sensitization as well as for an animal test on skin sensitization (the local lymph node assay, LLNA). Additionally, for one method (direct peptide reactivity assay) the BR was determined experimentally and compared to calculated BRs. Our results demonstrate that (i) the precision of the methods is determining the size of their BRs, (ii) there is no “perfect” method to derive a BR, alas, (iii) a consensus on BR is needed to account for the limited precision of testing methods.

The modified IL-8 Luc assay, an in vitro skin sensitisation test, can significantly improve the false-negative judgment of lipophilic sensitizers with logKow values > 3.5.

False-negative judgment due to poor chemical solubility is a problem with in vitro skin sensitisation tests. Water-insoluble chemicals are typically dissolved in DMSO in most sensitisation tests but precipitate when diluted with medium beyond their solubility in water. Such tests lack procedures to rule out false-negative judgments due to poor solubility. The IL-8 Luc assay (OECD442E) is unique in that if chemicals do not dissolve at 20mg/mL in medium and have no effect on IL-8 luciferase activity (IL8LA), they are classified as indeterminate. The purpose of the present study was to reduce the number of indeterminate chemicals and improve assay performance. The IL-8 Luc assay can simultaneously examine glyceraldehyde 3-phosphate dehydrogenase luciferase activity (GAPLA) and IL8LA, and thus we examined the correlation between the reduction of GAPLA (defined as Inh-GAPLA) and the reduction of propidium iodide (PI)-excluding cells for three sensitizers and three non-sensitizers. We observed a significant correlation between luciferase activity driven by the GAPDH promoter of THP-G8 cells and the number of viable cells. Furthermore, chemicals providing an Inh-GAPLA value below 0.8 always reduced the ratio of PI-excluding cells to less than 0.6. Using the modified criteria, indeterminate chemicals are judged as negative if they provide Inh-GAPLA values below 0.8. This modification reduced the number of indeterminate chemicals and increased specificity, highlighting the unique advantage of the IL-8 Luc assay.

Hypersensitivity Reactions to Multiple Iodinated Contrast Media.

The incidence of hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) has risen over last years, representing an important health problem. HSRs to ICMs are classified into immediate reactions (IRs) and non-immediate reactions (NIRs) according to if they occur within 1 h or longer after ICM administration. The diagnosis of HSRs to ICM is complex as skin test (ST) sensitivity ranges widely, and drug provocation test (DPT) protocols are heterogeneous. In this manuscript, we describe the clinical characteristics of a series of patients confirmed as HSR to ICM and the diagnosis procedure carried out, looking into those cases confirmed as HSRs to multiple ICMs. For this purpose, we prospectively evaluated patients suggestive of HSRs to ICMs and classified them as IRs or NIRs. STs were carried out using a wide panel of ICMs, and in those with a negative ST, a single-blind placebo controlled DPT was performed with the culprit. If ST or DPT were positive, then tolerance was assessed with an alternative negative ST ICM. We included 101 cases (12 IRs and 89 NIRs) confirmed as allergic. Among them, 36 (35.64%) cases were allergic to more than one ICM (8 IRs and 28 NIRs). The most common ICM involved were iomeprol and iodixanol. Although not statistically significant, the percentage of patients reporting anaphylaxis was higher in patients allergic to multiple ICMs compared with patients allergic to a single ICM (50 vs. 25%). Likewise, the percentage of positive results in STs was higher in patients allergic to multiple ICMs compared with those allergic to a single ICM (for IR 62.5 vs. 25%, p > 0.05; and for NIR, 85.71 vs. 24.59%, p < 0.000). In cases allergic to more than one ICM, DPT with negative-ST ICM was positive in more than 60% (24/36) of cases. Therefore, allergy to multiple ICMs is common, associated to severe reactions in IRs, and confirmed frequently by positive STs. The allergological work-up should include DPT not only to establish the diagnosis but also to identify safe alternative ICM, even if ICM is structurally unrelated and ST is negative. More studies are needed to clarify mechanisms underlying cross-reactivity among ICMs.

Induration or erythema diameter not less than 5\u2009mm as results of recombinant fusion protein ESAT6-CFP10 skin test for detecting M. tuberculosis infection

BackgroundRecombinant fusion protein ESAT6-CFP10 (EC) is a newly developed skin test reagent for detecting Mycobacterium tuberculosis (M. tuberculosis) infection. In this study, we evaluated whether induration and erythema could be used as diagnostic indicators for EC skin test to detect M. tuberculosis infection.MethodsA total of 743 tuberculosis patients and 1514 healthy volunteers underwent an EC skin test. The diameters of induration and erythema were measured with Vernier caliper, 24 h, 48 h, and 72 h after skin testing. Related indicators of EC reagent diagnostic test were tested, and the diagnostic effects of the four diagnostic indicators for EC skin test were compared.ResultsThe sensitivity of induration / erythema measurement was lower at 24 h after EC skin test than at 48 h or 72 h (P<0.01). There was no difference in consistency (P = 0.16) between induration with clinical diagnosis, and erythema with clinical diagnosis at 48 h (88.88 and 90.16%, Kappa value was 0.75 and 0.78, respectively). In patients, the sensitivity of erythema measurement was higher than induration measurement (P<0.01). In healthy volunteers, the specificity of erythema measurement was lower than induration at 24 h after skin test, but there was no difference at 48 h after skin test (P = 0.22). In BCG vaccination volunteers, the specificity of induration and erythema were higher than 90%. In addition, there was a high consistency of induration and erythema. When induration or erythema was used as a positive diagnostic indicator, the sensitivity of the EC skin test was improved, and was no different from the other three indicators in terms of specificity and consistency with clinical diagnosis.ConclusionsInduration or erythema diameter not less than 5 mm could be used as a diagnostic indicator for detecting M. tuberculosis infection.Trial registrationPhase III clinical trial of recombinant Mycobacterium tuberculosis ESAT6-CFP10 allergen; CTR20150695; registered in December 16, 2015.