A prospective study evaluating the correlation between local weather conditions, pollen counts and pruritus of dogs with atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (cAD) is a hereditary, generally pruritic and predominantly T-cell-driven inflammatory skin disease, involving an interplay between skin barrier abnormalities, allergen sensitisation and microbial dysbiosis. The individual immunological response is predominantly against environmental allergens, including mite antigens; mould spores; and pollen from grasses, trees and weeds. Airborne pollens show fluctuating patterns during the year. OBJECTIVE: The aim of this prospective study was to evaluate the influence of local pollen concentrations and weather conditions on the clinical signs of atopic dogs, and to investigate any possible correlations with the results of intradermal testing (IDT). MATERIALS AND METHODS: Thirty-seven privately owned atopic dogs in Bavaria were surveyed from 1 April to 30 November 2021. Owners were asked to record pruritus using a validated Visual Analog Scale (PVAS) score and the weekly medication of their dog. Furthermore, weather data, including pollen count, rainfall, relative humidity, hours of sunshine and temperature from the dog's location were collected daily. RESULTS: Of the evaluated parameters, only humidity and medication scores correlated positively with the PVAS scores of the atopic dogs. There was no correlation between specific pollen counts and PVAS scores of dogs with positive IDT reactions to that pollen. CONCLUSION AND CLINICAL RELEVANCE: The outcome of this study highlights the importance of a careful interpretation of positive IDT results in dogs with cAD and questions the validity of airborne pollen trap methodology in representing pollen exposure for dogs at ground level.

Local anesthetics allergy in children: Evaluation of diagnostic tests with Real-Life data.

BACKGROUND: Local anesthetic (LA) drugs are commonly used in clinical practice to provide effective analgesia, including in dentistry and minor surgical procedures. The perception of a high risk of allergy in daily applications leads to the referral of atopic patients and those with other drug allergies to allergy clinics for the evaluation of allergic reactions to LA. The aim of this study was to determine who should be referred to the allergy clinic for LA allergy testing, assess the frequency of LA allergy in pediatric patients, and identify the negative predictive value of skin tests in diagnosis. METHODS: January 2017-July 2023, the clinical and laboratory data, as well as the results of drug allergy tests, of patients referred to our pediatric allergy clinic by dentists and physicians performing minor surgical procedures with suspected LA allergy were retrospectively evaluated. RESULTS: Our study included a total of 153 patients, comprising 84 girls (54.9%) and 69 boys (45.1%), with a mean age of 8.9 (±3.3) years. The most common reason for referral was a history of non-LA drug allergies (n = 66, 43.2%), followed by asthma (n = 25, 16.3%). Hypersensitivity reactions (HRs) with LA were most commonly associated with articaine (n = 7, 4.8%), followed by lidocaine (n = 6, 4.1%). When intradermal tests were evaluated, 17 patients (11.1%) had a positive test result. The positivity for lidocaine was 70.6% (n = 12), and prilocaine was 29.4% (n = 5). Subcutaneous provocation was administered to 109 patients (71.2%), and one patient exhibited local erythema and swelling with prilocaine. CONCLUSION: Although LA allergy is a rare occurrence, consultations of this nature are frequently requested from allergy clinics in real life. Considering the negative predictive value of skin tests performed with LA drugs, the reaction rate appears to be low in patients with atopy or other drug allergies. It is crucial for all relevant healthcare professionals to be knowledgeable about the appropriate approach to suspected LA allergies to avoid unnecessary tests. To the best of our knowledge, our study is the most comprehensive work in the literature that evaluates the results of diagnostic tests in children referred with a suspicion of LA allergy.

Cutaneous anaphylactoid reaction to polyoxyethylene hydrogenated castor oil in dogs.

BACKGROUND: Polyoxyethylene hydrogenated castor oil (HCO ethoxylates) is a nonionic surfactant used as an excipient for ointments and injections in human and veterinary drugs. Several polyethylene glycol (PEG) derivatives can be obtained depending on the number of moles of ethylene oxide (EO). HCO ethoxylates have the potential to cause anaphylactoid reactions. There is little published information about these types of reactions in dogs. OBJECTIVE: To determine the potential for HCO-ethoxylate-containing drugs to cause anaphylactoid reactions in dogs, employing intradermal testing (IDT) with various concentrations of HCO ethoxylates (HCO-25, -40, -60 and -80). ANIMALS: Four healthy male laboratory dogs. MATERIALS AND METHODS: We performed IDT with drugs containing HCO ethoxylates and HCO ethoxylates alone to determine threshold concentrations. The IDT scores and threshold concentrations were compared. Analysis of skin biopsies from IDT sites was used to measure the percentage of degranulated mast cells. The effect of histamine at IDT sites was investigated by pre-treatment with an antihistamine. RESULTS: All HCO-ethoxylate-containing drugs caused a wheal-and-flare reaction. The threshold concentrations (0.001% and 0.00001%) of each HCO-ethoxylate depended on the number of moles of EO (p < 0.05). Mast cell degranulation was enhanced by all HCO ethoxylates. The HCO-60-induced reaction was suppressed by an oral antihistamine. CONCLUSIONS AND CLINICAL RELEVANCE: The threshold concentration can serve as a consideration for developing safe new drug formulations and for clinical decision-making around using drugs containing PEG derivatives. IDT is useful to predict the risk of adverse effects. Antihistamines could demonstrate a prophylactic effect.

Reactions to environmental allergens in cats with feline lower airway disease.

Objectives: Aeroallergens have been discussed as potential triggers for feline asthma (FA), which can be induced experimentally by allergen sensitization. To date, only few studies have investigated reactions to environmental allergens in cats with naturally occurring feline lower airway disease (FLAD). The aim of the study was to compare results of intradermal testing (IDT) and serum allergen-specific immunoglobulin E-(IgE) testing (SAT) in cats with FLAD, and to investigate possible associations with allergen exposure. Material and methods: Eight cats with eosinophilic airway inflammation (EI), ten cats with mixed inflammation (MI), six with neutrophilic inflammation (NI), and 24 healthy cats (HC) were included. Cats diagnosed with FLAD were assigned to the different inflammatory groups based on bronchoalveolar lavage fluid (BLAF) cytology. SAT was performed in all cats; IDT was only carried out in cats with FLAD. Information about the cats' environment and potential allergen exposure was obtained using an owner questionnaire. Results: In comparison to 83% of HC with positive reactions on SAT only 52% of cats with FLAD had positive responses (p = 0.051). Significantly more positive reactions per cat were detected on IDT than on SAT (p = 0.001). No significant difference was found for positive reactions per cat on SAT when compared between HC, NI, EI, and MI (p = 0.377). Only "slight" agreement was found for most allergens when reactions obtained in both tests in cats with FLAD were compared, except for "moderate" agreement for English plantain (k = 0.504) and Alternaria alternata (k = 0.488). Overall, no clear association between the cats' environment and allergen reactions were detected. Conclusions and clinical importance: Interpretation of allergy test results in cats with FLAD should be done in the context of clinical signs and individual factors.

Remimazolam Anaphylaxis during Induction of General Anesthesia Confirmed by Provocation Test-A Case Report and Literature Review.

Background: Remimazolam besylate, a newly developed drug, is linked to various anaphylaxis cases. We present a case of remimazolam anaphylaxis confirmed using a provocation test. Case: A 51-year-old female patient was scheduled for humeral pinning. General anesthesia was induced using remimazolam, rocuronium, and remifentanil. After tracheal intubation, the patient experienced decreased blood pressure, increased heart rate, and a systemic rash. Epinephrine was administered repeatedly, and the patient's vital signs stabilized. Acute phase tryptase levels were within normal limits. After four weeks, intradermal test results were negative. When remimazolam was administered intravenously for the provocation test, facial swelling, flushing, and coughing occurred, which improved with epinephrine. The culprit drug was identified as remimazolam using a provocation test. Conclusions: When anaphylaxis occurs during anesthesia induction, remimazolam should not be ruled out as the causative drug. If the skin test result for remimazolam is negative, a provocation test should be considered. The provocation test should be initiated cautiously at a low dose under careful patient monitoring.

Exudative pleural effusion caused by lung fluke infection: A practical diagnostic approach.

OBJECTIVES: Pleural effusion caused by lung fluke is a rare etiology of exudative pleural effusion (EPE), which is often misdiagnosed or delayed. We aim to summarize the diagnosis and treatment course of EPE caused by lung fluke infection and put forward a practical diagnosis approach. METHODS: We retrospectively analyzed the diagnosis and treatment of 14 cases of EPE caused by lung fluke infection diagnosed by enzyme-linked immunosorbent assay of serum antibodies or egg detection. RESULTS: All patients (100%) with an absolute count of eosinophils in peripheral blood exceeded 0.5 × 109/l, and 10 patients (71.4%) had a history of special ingestion. Eosinophilic PE occurred in 11 patients (78.6%), pleural biopsy of medical thoracoscopic demonstrated eosinophils infiltration in nine patients (64.3%), and parasite eggs in one patient. All patients showed positive intradermal tests for Paragonimus-specific antigens and enzyme-linked immunosorbent assay of serum antibodies to Paragonimus. CONCLUSION: For patients with unexplained PE, lung fluke infection should be highly suspected when pleural fluid or pleural biopsy shows eosinophilic PE or eosinophils infiltration, especially for patients with certain diet history.

Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

Skin prick tests are not useful for the qualification for venom immunotherapy in children.

Background: The basis for qualification for venom immunotherapy (VIT) is the fulfilment of both the clinical and immunological criteria. Diagnostic tests that confirm the immunological criterion of an IgE-mediated sensitization include skin prick tests (SPT), intradermal tests (IDT), and serum specific IgE (sIgE) for the culprit venom. Objective: This study aimed to assess the usefulness of SPT as the immunological marker in the diagnosis of insect venom sensitization in children with history of systemic reaction (SR) to insect sting evaluated by means of I-IV-grades Mueller's scale. There are no such studies in children. Methods: This cross-sectional study sample consisted of 416 children aged 3-18 years (mean age 10.6 ± 3.8), 76% males, all with the history of a systemic reaction (SR) after a Hymenoptera sting (48% of grade III/IV according to Mueller scale), diagnosed between 1999 and 2019 in the tertiary referral centre. The standard diagnostic tests were used. Specificity, sensitivity, and positive and negative predictive values were computed to assess the diagnostic properties of the clinical tests to distinguish between mild and severe SR. To assess the relative value of an individual test in predicting the qualification to VIT we incorporated the Shapley value (SV). Results: Positive SPT results were found in up to no more than 3% of children; among them less than 1% had only positive SPT and were negative for sIgE and IDT. Approximately 85% of the children had detectable venom sIgE, followed by positive IDT (75%). Almost 70% of children had positive both sIgE and IDT results. In children with grade III/IV reaction, about 80% of children had positive results of both of these tests. sIgE and IDT had sensitivity >0.80, whereas SPT had high specificity (>0.97) in differentiating between mild and severe SR. Relative value of diagnostic tests in predicting qualification to VIT varied between venoms. Bee venom IDT had higher SV (0.052) than sIgE (0.041). In contrast, wasp venom sIgE had higher SV (0.075) than IDT (0.035). Conclusion: SPTs are not an useful immunological marker of venom sensitization in children, and eliminating SPT does not result in a loss of diagnostic accuracy. Limiting diagnostics to venom sIgE and IDT would shorten the procedure and reduce costs. Future studies are needed to determine if venom sIgE as the first line diagnostic test, with IDT added only if the venom sIgE is undetectable, is an optimal diagnostic process.

Post-orgasmic illness syndrome with positive intradermal test for autologous semen.

Post-orgasmic illness syndrome (POIS) is a rare disease characterized by flu-like symptoms persisting for 2-7 days after ejaculation. POIS has been chiefly attributed to allergic reactions to autologous seminal plasma. However, the exact pathophysiology remains unclear, and there is no effective treatment. We present the case of a 38-year-old man with a 10-year history of recurrent episodes of flu-like symptoms of 1-week duration after ejaculation. The patient was diagnosed with irritating bowel syndrome because of fatigue, myalgia, and lateral abdominal pain. After starting infertility treatment and increasing the frequency of intercourse with his wife, the patient noticed these symptoms after ejaculation. Based on these episodes and symptoms, POIS was suspected. To diagnose POIS, a skin prick test and an intradermal test were performed using his seminal fluid, with the latter yielding a positive result. The patient was diagnosed with POIS, and treatment with antihistamines was continued. Due to its rarity, POIS is often underdiagnosed and underreported; however, the skin test can be a valid diagnostic tool. In this case, the intradermal test result was positive according to the broadly accepted criteria for POIS. Although quality of life is often severely affected in patients with POIS, a lack of a clear understanding of the pathogenesis of POIS prevents early diagnosis. To make diagnoses earlier, it is undoubtedly important to take a detailed medical history and perform skin allergy tests, although the latter requires further validation.

Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset.

BACKGROUND: Amoxicillin-clavulanic acid (AX-CL) is the most consumed betalactam antibiotic worldwide. We aimed to establish the different phenotypes of betalactam allergy in those referring a reaction with AX-CL and to investigate the differences between immediate and non-immediate onset. METHODS: Cross-sectional retrospective study performed at Hospital Clínico San Carlos (HCSC) and Hospital Regional Universitario de Málaga (HRUM) in Spain. Patients reporting reactions with AX-CL who completed the allergy workup between 2017 and 2019 were included. Data of reported reaction and allergy workup were collected. Reactions were classified as immediate and non-immediate with 1hour cut-off point. RESULTS: We included 372 patients (HCSC 208, HRUM 164). There were 90 (24.2%) immediate, 252 (67.7%) non-immediate reactions, and 30 (8.1%) with unknown latency. Allergy to betalactams was ruled-out in 266 (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population were allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%) and to betalactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and non-immediate reactions respectively, with a relative risk of 5.06 (95%CI 3.64-7.02) of an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with late-positive intradermal test (IDT) to CL were diagnosed of CL allergy. CONCLUSION: Allergy diagnosis was confirmed in a minority of the whole study population, but 5 times more frequently in those reporting immediate reactions, making this classification useful in risk stratification. Late-positive IDT for CL has no diagnostic value and its late reading could be retrieved from the diagnosis work-up.

COVID-19 vaccine provocation test outcome in high-risk allergic patients: A retrospective study from a tertiary hospital in Indonesia.

Background: High COVID-19 vaccine coverage is essential. Patients who are considered high risk for hypersensitivity reactions and have had an allergic reaction to the COVID-19 vaccine are usually referred to an allergist for assessment of vaccination. Administration of a vaccine graded challenge (also known as a provocation test) is an option that can be considered in this population. This primary objective of this study is to describe the outcome of the COVID-19 vaccine provocation test and to understand the predicting factors associated with hypersensitivity reaction after the provocation test as the secondary objective. Methods: Adult patients with a history of hypersensitivity reaction to the first COVID-19 vaccine and high-allergic patients who underwent COVID-19 vaccine provocation test up until May 2022 were included. A protocol using skin prick test (SPT), intradermal test (IDT), followed by graded challenge was developed for the determined vaccine used. Results: A total of 232 patients were included in the analysis. Twenty-eight had hypersensitivity to their first COVID-19 vaccine dose and 204 were high risk for allergic reaction. Hypersensitivity reactions occurred in 20 patients (8.6%, 95% CI: 5-12.2%), consisting of 4 reactions after SPT, 9 after IDT, 7 during or after titrated challenge. Half of the reactions were mild; however, 3 patients developed severe reactions. Patients with history of anaphylaxis were more likely to experience hypersensitivity reaction after provocation test (aRR = 2.79, 95% CI: 1.05-7.42). Conclusion: Provocation test in COVID-19 vaccination has a high success rate in patients with a history of hypersensitivity to the first COVID-19 vaccine and in high allergic patients. History of anaphylaxis is associated with hypersensitivity reaction after a COVID-19 vaccine provocation test.

Utility and Safety of Skin Tests in Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): A Systematic Review.

BACKGROUND: Determination of culprit drug in drug reaction with eosinophilia and systemic symptoms (DRESS) is crucial. Skin tests have been used, although it remains unclear how sensitive these are. OBJECTIVE: To determine the value of skin tests in the assessment of drug causality in DRESS. METHODS: A systematic literature search was conducted for publications from 1996 onward of skin tests (skin prick test = SPT, patch test = PT, intradermal test = IDT) performed in clearly defined DRESS cases. Outcomes of testing, drug culpability assessments, and challenge test data were extracted. RESULTS: A total of 17 articles met inclusion criteria. In 290 patients with DRESS, patch testing was most frequent (PT = 97.2% [n = 282], IDT = 12.4% [n = 36], SPT = 3.1% [n = 9]). Positive results were noted in 58.4% (n = 160 of 282) of PTs, 66.5% of IDTs, and 25% of SPTs. When confidence of drug causality was high (n = 73 of 194), testing did not correlate well with clinical suspicion: PTs, 37.6%; IDTs, 36.5%. Direct comparison of skin testing with provocation testing (n = 12) showed 83.3% correlation. Positive IDT results were reported in 8 negative PT cases. CONCLUSIONS: Skin tests, particularly PTs and IDTs, have been reported as tools for diagnosis of causal drugs in DRESS. Heterogeneity in methodology, results analysis, and reporting of cohorts make meta-analysis to determine sensitivity and specificity of published literature impossible and highlight weaknesses in the field. We propose that international collaboration is essential to harmonize the methodology and reporting measures from hypersensitivity testing studies in larger cohorts.

Study of Excipients in Delayed Skin Reactions to mRNA Vaccines: Positive Delayed Intradermal Reactions to Polyethylene Glycol Provide New Insights for COVID-19 Arm.

BACKGROUND: Skin local reactions to mRNA COVID-19 vaccines have been linked to the use of vaccine excipients. The aim of the study is to evaluate the role of skin testing excipients in delayed skin reactions due to mRNA COVID-19 vaccines. METHODS: Skin testing among a group of healthcare workers with skin reactions due to mRNA vaccines was performed. Patch testing and intradermal testing (IDT) with polyethylene glycol (PEG)-400, PEG-2000, trometamol, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine were performed. Healthcare workers without skin reactions to vaccines were used for skin testing as controls. RESULTS: Thirty-one healthcare workers (from a total of 4315 vaccinated healthcare workers) experienced cutaneous adverse vaccine reactions. Skin testing was performed in sixteen of the healthcare workers (11 delayed large local reactions (DLLR) and 5 widespread reactions). Positive IDT for PEG-2000 1% in DLLR was seen in 10 (90.9%) patients, in comparison with one (16.6%) individual with a delayed widespread reaction. Delayed positive IDT reactions for PEG-2000 1% on day 2 were observed in three (27.3%) patients with DLLR. Patch testing of the excipients was negative. Among 10 controls, only one exhibited a transient positive IDT reaction to PEG-2000 1%. CONCLUSIONS: Immediate and delayed reactions to IDT are frequently detected in patients with DLLR. The observation of positive delayed intradermal reactions to PEG disclosed only in patients with DLLR reinforces a possible role of PEG in the development of these reactions. Skin testing of other excipients is of little importance in clinical practice.

COVID vaccination can be performed in patients with a history of allergic reactions to the vaccines or their components: experience from a specialist clinic in South Australia.

BACKGROUND: The development of vaccines against SARS-CoV2 has been a key public health response to the COVID-19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines. AIM: A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia. METHODS: Patients referred to a state-wide COVID-19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin-prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1-S), excipients (polyethylene glycol and polysorbate 80), excipient-containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions. RESULTS: Fifty-three patients underwent testing for possible excipient allergy (n = 19), previous non-COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID-19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18-83 (median 54) years. Forty-four patients tested negative and 42 of these received at least their first dose of a COVID-19 vaccine. Nine patients tested positive to excipients or excipient-containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1-S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1-S was successfully vaccinated with ChAdOx1-S. CONCLUSION: Even in a high-risk population, most patients can be vaccinated with available COVID-19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.

Radiocontrast Media Hypersensitivity Reactions in Children.

Hypersensitivity reactions to radiocontrast media seem to be rare in children. Furthermore, the use of radiocontrast media in children remains quite safe in terms of the severity of reactions. Since pediatric guidelines are lacking, the diagnostic workup employed in adults could be adapted to children, taking into account that results have not yet been validated in this age group. Specific protocols for risk stratification and management of severe reactions have been proposed so far.

Diagnosis of non-immediate hypersensitivity to amoxicillin in children by skin test and drug provocation tests: A retrospective case-series study.

BACKGROUND: Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. METHODS: We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60-90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. RESULTS: This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. CONCLUSIONS: Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.