Neuromuscular blocking agent drug challenge: a literature review and protocol proposal with biological evaluation.

BACKGROUND: Drug challenge is the gold standard for identifying causative agents of drug allergies. Although clinical guidelines have recently been published, they do not recommend neuromuscular blocking agent (NMBA) drug challenges. NMBA challenges are rendered difficult by the lack of homogeneity of routine allergy work-ups and the necessity of a specialised setting. Several scenarios support NMBA challenges, such as an ambiguous allergy work-up, a high suspicion of a false-positive skin test or identification of a well tolerated alternative NMBA strategy. Furthermore, routine allergy work-ups may not recognise non-IgE mechanisms, such as IgG or MRGPRX2, whereas drug challenges may reveal them. Finally, if the culprit NMBA is not identified, subsequent anaesthesia regimens will be challenging to implement, resulting in increased risk. OBJECTIVES: This literature review discusses the indications, strategies, doses, monitoring methods, limitations, and unresolved issues related to drug challenges for NMBAs. DESIGN: The literature review included randomised controlled trials, observational studies, reviews, case reports, series, and comments on humans. DATA SOURCES: Studies were retrieved from databases (PubMed) and electronic libraries (OVID, EMBASE, Scopus, etc.). ELIGIBILITY CRITERIA: All studies that referred to the NMBA challenge were included without publication date limitations. RESULTS: NMBA challenge may be considered in NMBA anaphylaxis patients with inconclusive or ambivalent IgE diagnostic work-up under controlled conditions (presence of anaesthetists and allergists with continuous monitoring in a secured environment). To illustrate its utility, a case report of a double NMBA challenge in a patient with NMBA cross-reactivity is presented, along with biological explorations to detect subclinical cellular activation, a novel aspect of this procedure. CONCLUSION: Drug challenges could be implemented during the NMBA allergy work-up under strict safety conditions at specialised centres with close collaboration between anaesthetists and allergists. This could decrease uncertainty and contribute to defining a safer strategy for subsequent anaesthetic drug regimens.

[Retrospective analysis of perioperative anaphylactic shock induced by cefuroxime].

This study investigated the characteristics and frequency of perioperative anaphylactic shock induced by cefuroxime, so as to provide a reference for the safe and rational use of cefuroxime in the perioperative period. Cases of perioperative anaphylactic shock caused by cefuroxime in our hospital from 2011 to 2021 were extracted from the Adverse Drug Reaction Monitoring System. Literature reporting adverse drug reactions (ADR) including cefuroxime-induced anaphylactic shock in perioperative settings was collected from the CNKI, VIP, Wanfang, PubMed, and Web of Science databases from their respective inception to May 2022. Statistical analysis was performed for all cases of cefuroxime-induced perioperative anaphylactic shock. A total of 31 patients were included [13 men (48.1%) and 14 women (51.9%)], most of whom were over 60 years old (n=16, 59.3%); 9 (29.0%) patients had a history of drug allergy; 5 (16.1%) patients had received skin tests, but with negative results; 28 (90.3%) patients received treatment intravenously; 22 (71.0%) patients were treated after anesthesia. For 20 (64.5%) patients the ADR occurred within 10 minutes after anesthesia. The main manifestations were hypotension, dyspnea, rash, and tachycardia. For all patients, symptoms resolved after withdrawal of the drug and active rescue, and there were no deaths. A history of allergy and skin test findings may have limitations in predicting perioperative anaphylactic shock caused by cefuroxime; greater vigilance should be exercised when using cefuroxime in the perioperative period. Close monitoring is recommended for patients undergoing treatment with cefuroxime. Rescue therapy should be administered for allergic shock, and suitable response measures must be taken in a timely manner to ensure the safety of patients.

Clinical and Immunological Characterization of Perilla Seed Allergy in Children.

BACKGROUND AND OBJECTIVES: Perilla seeds are known to cause immediate allergic reactions. However, reports on perilla seed allergy are limited to a few case reports worldwide, and there is currently no diagnostic test for this allergy. Our objective was to analyze the clinical and immunological characteristics of perilla seed allergy and to identify allergens for the development of diagnostic methods. METHODS: Twenty-one children with clinical perilla seed allergy were enrolled from 2 tertiary hospitals between September 2016 and June 2019. Using perilla seed extract, we developed a skin prick test (SPT) and an IgE enzyme-linked immunosorbent assay (ELISA) for diagnosis of perilla seed allergy. IgE immunoblotting was performed to identify putative allergenic components, and amino acid composition analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The median age of children with perilla seed allergy was 3 years; the proportion of children with anaphylaxis was 28.6%. SPT was performed with perilla seed in 15 of 21 children, all of whom tested positive. On ELISA, 85.7% of children tested positive for perilla seed-specific IgE. Proteins with molecular weights of 50, 31-35, and 14-16 kDa bound to the sera of >50% of children with perilla seed allergy. LC-MS/MS analysis of these 3 protein fractions showed 8 putative proteins, including perilla oleosin (Accession No. 9963891), to be allergens. CONCLUSIONS: This study documented the clinical characteristics and immunological profiles of 21 children with perilla seed allergy. Our results suggest that oleosin is one of the major allergens in perilla seeds.

Neuromuscular blocking agent induced hypersensitivity reaction exploration: an update.

Acute hypersensitivity reactions (AHRs) occurring in present-day anaesthesia can have severe, sometimes fatal, consequences and their incidence is increasing. The most frequent allergens responsible for AHR during anaesthesia are neuromuscular blocking agents (NMBAs) (70% of the cases) followed by antibiotics (18%), patent blue dye and methylene blue dye (5%), and latex (5%). Following an AHR, strategies for subsequent anaesthetic procedures (especially the choice of an NMBA) may be difficult to formulate due to inconclusive diagnostic analysis in up to 30% of AHRs. Current diagnosis of AHR relies on the detection of mast cell degranulation products and drug-specific type E immunoglobulins (IgE) in order to document an IgE-mediated anaphylaxis (IgE endotype). Nonetheless, other IgE-independent pathways can be involved in AHR, but their detection is not currently available in standard situations. The different mechanisms (endotypes) involved in peri-operative AHR may contribute to the inconclusive diagnostic work-up and this generates uncertainty concerning the culpable drug and strategy for subsequent anaesthetic procedures. This review provides details on the IgE endotype; an update on non-IgE related endotypes and the novel diagnostic tools that could characterise them. This detailed update is intended to provide explicit clinical reasoning tools to the anaesthesiologist faced with an incomplete AHR diagnostic work-up and to facilitate the decision-making process regarding anaesthetic procedures following an AHR to NMBAs.

Hypersensitivity reactions to chemotherapy: an EAACI Position Paper.

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

Upper and lower respiratory airway complaints among female veterinary staff.

OBJECTIVE: Working with animals is characterized by exposure to particulate, biological or chemical matter, and respiratory complaints are common. The aim of our cross-sectional study was to assess the prevalence of respiratory symptoms and diagnoses among veterinary staff. METHODS: Participants working in veterinary practices were examined and a detailed questionnaire was used to collect data. IgE tests to common and animal allergens were performed to specify sensitization. Associations with respiratory outcomes were analysed using logistic regression models while controlling for potential confounders. RESULTS: Atopy was seen in 31% of the 109 female participants. Symptoms of rhinoconjunctivitis were the most frequent complaints (n = 92; 84%). In 18% the diagnosis was confirmed by physicians. Symptoms of upper and lower airways were highly correlated and an asthma diagnosis was confirmed in 11% of participants. Modelling revealed that sensitization against cats/dogs was a significant risk factor for respiratory symptoms of upper [odds ratio (OR) 4.61; 95% confidence interval (CI) 1.13-18.81] and lower airways (OR 5.14; 95% CI 1.25-21.13), physician-confirmed rhinoconjunctivitis (OR 13.43; 95% CI 1.69-106.5) and asthma (OR 9.02; 95% CI 1.16-70.39) in assistant staff of small-animal practices. CONCLUSIONS: In several cases, rhinoconjunctivitis worsened after entering the profession. Atopy and specific sensitization to cats/dogs were risk factors for health impairments. Thus, to implement preventive measures, veterinary practice staff should be educated that upper respiratory tract symptoms are not harmless and should be diagnosed and treated early.

Refractory cytokine release reaction to Nivolumab: Following desensitization algorithms to optimize the management of drug hypersensitivity.

INTRODUCTION: Nivolumab is a fully human IgG4 monoclonal antibody (moAb) against programmed cell death protein 1, approved for the treatment of over ten types of cancer. The use of this and other moAbs has augmented considerably in recent years and this in turn has caused an increase of hypersensitivity reactions (HSR). CASE REPORT: We present the case of a patient with metastatic renal cell cancer (RCC) who developed a grade 3 cytokine release reaction (CRR) to nivolumab. The maintenance of the symptoms despite of the administration of symptomatic treatment and slowing down the infusion rate of nivolumab during the 1st and 2nd reaction required an allergy evaluation of our patient. MANAGEMENT AND OUTCOME: Skin testing to Nivolumab with negative results and baseline tryptase within the normal range were observed during the allergy workout. A desensitization protocol with specific premedication was applied to reintroduce the moAb, with no further issues. Moreover, a follow up of the patient in the oncology setting was done showing disease stabilization. DISCUSSION: The CRR should be treated by desensitization, in contrast to infusion reactions. The diagnosis of CRR phenotype is based on the clinical presentation and recently, and elevation of IL-6 levels has been shown to be a useful biomarker along with negative skin testing. We can conclude that after a HSR and an appropriate allergy diagnosis of CRR, nivolumab can be safely reintroduced by desensitization without reducing the target dose or the appropriate dilution concentration.

Clinical characteristics of cat sensitized adults, cat ownership and cat owners' attitudes.

Background: Cat allergen sensitization is a significant risk factor for allergic rhinitis and asthma. There are insufficient data on the preferences and attitudes of cat owners who have a cat allergy. Objective: To investigate the clinical characteristics of adults sensitized to cats and their association with cat ownership, and to assess owners' attitudes and behaviors. Methods: The study evaluated adult patients, ages between 19 and 74 years, who were sensitized to cat allergen as confirmed by skin-prick tests. The demographic and clinical data of the patients were obtained retrospectively from the hospital medical records system. A telephone interview with patients was conducted to evaluate whether they owned a cat and their attitudes toward cat allergy. A total of 143 patients who could not be reached by telephone or who refused to participate in the study were excluded. Patients were categorized into never owned a cat, early cat ownership (having a cat or cats in the first 2 years of the patient's life), and past and current cat ownership according to the status of patients at the time of their skin-prick test. Current cat owners were questioned whether they relinquished their cats and the presence and the degree of symptoms of both patients who relinquished their cats and patients who continued to live with their cats. Results: A total of 245 patients (women/men, 151/94) with a mean age of 31.56 ± 11.33 were included in the study. Eighty-three patients (33.9%) were current cat owners. After the skin-prick test, 54 cat owners (66.1%) continued living with their cats. Two-thirds of these owners were symptomatic, with 95% experiencing nasal symptoms. Only five of the patients with symptoms (14.3%) reported worsening symptoms. Any significant impact on symptoms was not determined with regard to number of cats, cat breeds, and precautionary measures. Conclusion: Cat allergen is a potential risk for public health. The clinician must engage in shared decision-making as to what type of environmental changes that the patient is willing to make and what treatment options, if any, they are ready to accept, recognizing that most patients will prefer to keep their cats.

Prognosis of food-induced anaphylaxis in children: A single-center real-life study.

Background: Food allergies are known to resolve over time, but there is little information on the natural history of food-induced anaphylaxis (FIA). Objective: This study aimed to evaluate the natural history of FIA in children and determine the factors that affect prognosis. Methods: Children with FIA who were followed up for at least 3 years, between 2010 and 2020, were included. Patients' families were contacted by telephone to question their child's tolerance status and invite them for reevaluation if uncertain. The patients were grouped as tolerant or persistent according to parent reports or reevaluation results. Logistic regression analysis was performed to determine the factors that affected persistence. Results: The study included 185 patients (62.2% boys) with 243 anaphylactic reactions to various foods. Fifty-eight patients (31%) gained tolerance within a 3-year follow-up period. Tolerance rates were higher in patients with FIA to milk (40%) and egg (43.9%) compared with to tree nuts (18.8%), legumes (5.6%), and/or seafood (11.1%) (p < 0.001). In a multivariate analysis, risk factors for persistent FIA were multiple food anaphylaxis (odds ratio [OR] 3.755 [95% confidence interval {CI}, 1.134-12.431]; p = 0.030), total IgE > 100 kU/L (OR 5.786 [95% CI, 2.065-16.207]; p = 0.001), and skin-prick test wheal size > 10 mm (OR 4.569 [95% CI, 1.395-14.964]; p = 0 .012) at presentation. Conclusion: Approximately a third of the patients with FIA developed tolerance within 3 years. Clinicians should remember that children with food allergies, even anaphylaxis, may develop tolerance over time. Regular follow up and reevaluation of tolerance status are necessary to avoid unnecessary elimination.

Female sex as a risk factor for penicillin drug allergy in the inpatient setting.

Background: Penicillin is the most common reported drug allergy. Previous literature suggests that there is increased prevalence of penicillin drug allergy in female patients in the outpatient setting. However, this is poorly described in the inpatient setting. Objective: This study was performed to determine whether female sex is an independent risk factor for penicillin allergy in the inpatient setting. Methods: A retrospective review of electronic medical records (January 1, 2001-December 31, 2017) was performed for patients with a history of penicillin allergy who underwent penicillin skin testing (PST). Each chart review included the age at initial skin testing, sex, medications, and medical co-morbidities. The study was approved by the institutional review board. Results: 30,883 patients underwent PST with 29,354 and 1,529 occurring in the outpatient and inpatient setting respectively. 170 patients tested positive with a ≥ 5x5 wheal. Of the 170 positive patients, 122 were female (72%) and 48 were male (28%). 15 patients tested positive in the inpatient setting. Of the 1506 adult patients tested in the inpatient setting, 809 were female and 697 were male. 12 females (92.3%) and 1 one male (7.7%) tested positive with a ≥ 5x5 wheal (OR-10.5; 95% CI-1.4-80.8; p-value=0.02). 23 pediatric patients were tested in the inpatient setting. Two pediatric male patients were positive and no female pediatric patients tested positive (OR-1.7; 95% CI-0.5-5.9; p-value=0.5). Conclusion: In the inpatient setting, adult females are 10 times more likely to have a positive PST compared to males. Female sex may be a potential risk factor for objective penicillin drug allergy in the inpatient setting.

[Allergy Diagnostics 2021]. / Allergologische Diagnostik 2021.

Allergic diseases are among the most common diseases worldwide. For appropriate management knowledge of the allergy trigger is crucial. The clinical picture of allergic diseases is diverse and correct diagnosis is often a challenge. The allergist needs to distinguish intolerances from allergies and infectious diseases from non-infectious triggers. Test results have to be interpreted accordingly to differentiate sensitizations from allergies. In this review current state of the art diagnostic measures to diagnose type I and type IV allergies are described and discussed.Immediate type allergies such as allergic rhinoconjunctivitis, asthma and anaphylaxis are mediated by allergen-specific IgE antibodies detectable both in serum and tissue. Typical triggers are pollen, mites, animal epithelia, food, insect toxins and pharmaceuticals. In everyday practice, diagnostics are based on three complementary pillars: the allergy-specific anamnesis as a prerequisite of correct interpretation of subsequent diagnostic tests like skin testing and serological immunoglobulin detection. These can be supplemented as required and available by provocation tests to prove clinical reactivity and cellular assays to demonstrate the cellular immune response.Type IV allergic reactions are mediated by T cells causing contact allergy with a local eczematous reaction with a latency of several hours to days. Some 3,500 triggers, often from occupational environment, are known; e. g., nickel, chromium, cobalt, fragrances, rubber, plastics, preservatives, dyes, neomycin, benzocaine, sulfonamides, quinidine, wool wax, perubalsam, eye therapeutics, light filter substances, disinfectants, pesticides, technical oils or plants. Diagnosis of contact allergy combines the history of cutaneous exposure with associated symptoms and patch testing, with detection of a late phase clinical reaction after 6 to 48, up to a maximum of 96 hours after antigen contact.

Comprehensive Review on Banana Fruit Allergy: Pathogenesis, Diagnosis, Management, and Potential Modification of Allergens through Food Processing.

The pulp of the banana fruit is rich in bioactive compounds like dietary fibers, low glycemic carbohydrates, natural sugars, vitamins, minerals and antioxidants. These beneficial compounds are responsible for the proper functioning of immune system and enhance prevention against various deadly diseases like cancer, diabetes and heart diseases. Despite having, positive effects, the fruit are recognized as an important source for causing allergy to 0.6% of people in general population and up to 67 and 46% for people with asthma or atopic dermatitis. Fruit allergy is one of the most common food allergies witnessed worldwide. Banana fruit allergy results from the abnormal immune response to the banana proteins soon after its consumption. Symptoms range from oral allergy syndrome (OAS) to the life-threatening anaphylaxis. IgE reactivity of banana is associated with different proteins of which six proteins have been identified as major allergens, viz., Mus a1 (Profilin-actin binding protein), Mus a 2 (Class 1 chitinase), Mus a 3 (Nonspecific lipid transfer protein), Mus a 4 (Thaumatin like protein), Mus a 5 (Beta 1,3 glucanase) and Mus a 6 (Ascorbate peroxidase). This review focuses on pathogenesis, clinical features, diagnosis, and different food processing methods to mitigate the allergenicity of banana fruit.

[LITTLE FIRE ANT (WASMANNIA AUROPUNCTATA) IN ISRAEL - FROM NUISANCE TO LIFE-THREATENING].

INTRODUCTION: The little fire ant (LFA) is an invasive ant species, increasingly found in wide distribution in Israel. Although it's sting is painful and itchy, for the most part, no serious adverse effects have been reported so far. We describe the case of a young boy with recurrent, life threatening anaphylactic reactions after stings, all occurring during the summer months, in areas where LFA infestations have been identified. An ad hoc skin test, developed with the cooperation of the allergy and entomology team, identified an immediate IgE-mediated reaction to LFA whole body extract, present in our patients and absent in healthy controls. This report may be the first identifying the LFA as a potential cause of severe anaphylactic reactions, but unfortunately, given the wide spread of these pests, it may be that such unrecognized reactions have already been treated by medical teams and misclassified as idiopathic anaphylaxis.

[Аllergic sensitization in children with atopic dermatitis in the first 2 years of life according to the results of skin tests].

Atopic dermatitis (AD) is associated with food allergies (FA), which frequency and structure varies from region. The objective of the research was to determine the structure of FA in children (<2 years) with AD and to analyze age-specific sensitization. Methods. 79 children with AD aged 2-24 months were examined (Russia, Moscow). Skin prick tests (SPT) with food allergens were used to determine sensitization, if necessary additional SPT with aeroallergens were performed. Results. 51.9% of patients had hypersensitivity to at least 1 allergen. Positive SPT for egg were detected in 38.0%, cow's milk - in 27.8%, fish - in 10.1%. Allergy to fish occurred predominantly in the 2nd year of life (35.0% vs 4.8, p=0.02). Soy, peanuts, and nuts were detected in less than 5% of patients. At 2-6 months of age, sensitization was found in 36.4%, and after 6 months in 57.9% (p=0.08). In the group with FA before 6 months of age (n=8), 7 patients were sensitized to egg and 6 to milk. The prevalence of milk and egg allergy did not differ between exclusively breastfed and formula-fed children. Hypersensitivity to allergens was found in 4 of 10 breastfeeding patients, for compared to 3 of 11 exclusive formula-feeding patients (p=0.66). Acute allergic reactions were reported in 6.3% of patients with AD, which was 12.2% of children with FA. Triggers were egg (n=5) and fish (n=4). Anaphylaxis did not occur until 6 months of age. The frequency of severe reactions was about the same in children 1st and 2nd years of age (p=0.64). SPT urticaria size, defined in points (max=4), did not differ between children 2-24 months of age. Egg and nut allergens showed the maximum skin reaction: medians were 3 [2; 4] and 1.5 [0.75; 2.5] points. Milk allergens caused significantly less reaction compared with egg (p<0.01). These differences were absent when comparing reactions to individual milk serum fraction proteins and reactions to egg. Hypersensitivity to non-food allergens was found in 41.5% of children with FA (21.5% of children with AD), mainly sensitization to cat epithelium, birch, house dust and dog epithelium was detected. Conclusion. Sensitization to milk proteins and eggs is the leading since 2 months of age, without differences in relation to the age of the infant and the type of feeding. In all cases of moderate AD, SCT is applicable in children 0-2 years of age, with practically no age restrictions.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

A combined risk modeling strategy for clinical prediction of beta-lactam allergies in children.

Background: Drug provocation test (DPT) without skin tests is increasingly recommended in the evaluation of children with low-risk beta-lactam (BL) allergies. However, risk definitions are unclear. Objective: The aim of this study was to compose a clinical predictive model that could identify the children at low risk who could safely undergo direct DPT. Methods: The clinical data of 204 children who underwent a full diagnostic algorithm for suspected BL allergy were analyzed. Clinical data were used to construct mathematical predictive model for confirmed BL allergies. A prospective new sample was used for external validation of the final model. Results: The presentations during the index reaction were anaphylaxis in 5.9% and cutaneous reactions in the majority. BL allergy was confirmed in 15.7% of suspected cases. A backward multiple logistic regression model showed that a family history of drug allergy (adjusted odds ratio [aOR], 5.52), anaphylaxis (aOR, 5.14), any atopic disease other than asthma (aOR, 4.38), and a reaction interval of 0-6 hours during the index reaction (aOR, 5.32) were significantly associated with a confirmed BL allergy. A mathematical combined model based on these factors showed a sensitivity of 77.8% and a negative predictive value (NPV) of 94.3%. The validation study replicated sensitivity and NPV values of the main cohort. Conclusion: The risk definition in BL allergies should depend on population-specific predictive models, including a combination of significant risk factors rather than empiric risk approaches. This may help to accurately determinate children at low risk who may safely proceed to direct DPT.

The impact of skin prick testing on pain perception and anxiety in children and parents.

BACKGROUND: Skin prick testing (SPT) is a major diagnostic tool in patients with allergic symptoms. The testing process may involve pain, anxiety, and stress on children and parents. OBJECTIVE: We aimed to measure the level of pain and anxiety before and after SPT in children and parents, and tried to identify predictive factors. METHODS: The children underwent SPT and parents completed the State Trait Anxiety Inventory (STAI) S-Anxiety before and after SPT, T-Anxiety before SPT. The study nurse completed Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores (<5 years) or Wong-Baker FACES Pain Rating Scale (VAS), (≥5 years) after the SPT, in order to quantify pain. RESULTS: A total of 523 children (5.3 [2.8-9.1] [median, interquartile range] years old, 59.5% male) were evaluated. Parent gender was a predominant factor for anxiety, as mothers had a higher pre-test STAI (S-Anxiety) score, STAI (T-Anxiety), and post-test STAI (S-Anxiety) score than fathers (p < 0.001). Pre-test STAI (S-Anxiety) scores of parents decreased with increasing age (for 0-<5 years, 5-<12 years, and ≥12 years; [p for trend = 0.016]). The children tested on the back had higher VAS scores compared with the ones tested on the forearm [2[0-4] vs 2[0-2], [p = 0.005]). Risk factors determining higher general anxiety STAI (T-Anxiety) scores above the median were female sex for the parent (OR = 1.68; 95% CI [1.10-2.57]; p = 0.017), and parent's education level being greater than or equal to high school level (OR = 1.83; 95% CI [1.27-2.64]; p = 0.001). CONCLUSION: SPT may cause anxiety and pain in a subgroup of children particularly in younger age, and if performed on the back. Anxiety levels were higher in mothers, and in parents with high education levels.

Polymethylmethacrylate Collagen Gel-Injectable Dermal Filler for Full Face Atrophic Acne Scar Correction.

BACKGROUND/OBJECTIVES: This trial evaluated the effectiveness and safety of Bellafill for full-face acne scar treatment. PATIENTS AND METHODS: In this open-label, nonrandomized, multicenter pilot study investigating the use of polymethylmethacrylate for full-face atrophic acne scar correction, 42 adult subjects with a mean age of 43 years were treated and assessed for safety and effectiveness at Months 4 and 7. There were no hypersensitivity reactions to pretreatment skin testing or during scar treatments. RESULTS: At 4 and 7 months after initial treatment, 92% and 95% of subjects, respectively, were responders with ≥1-point improvement on the 5-point Acne Scar Assessment Scale. Subjects reported very high levels of improvement on the Global Aesthetic Improvement Scale (GAIS), with 95% of subjects reporting "improved or better" at 4 months and 90% at 7 months. The outcome of the physician GAIS was also high with 92% of patients classified as "improved or better" at 4 months and 97% at 7 months. There were only 2 device-related adverse events, both mild events related to Bellafill skin test (bruising, ecchymosis). There were no serious adverse events in response to the treatment product in this short-term follow-up study. CONCLUSION: Polymethylmethacrylate is effective for treating full-face acne scarring. Clinicaltrials.gov #NCT02642627.

Purified Protein Derivative Skin test prior to bacillus Calmette-Guérin Therapy May have Therapeutic Impact in Patients with Nonmuscle Invasive Bladder Cancer.

PURPOSE: We investigated the clinical impact of the purified protein derivative skin test prior to bacillus Calmette-Guérin therapy in patients with nonmuscle invasive bladder cancer treated with adjuvant bacillus Calmette-Guérin therapy. MATERIALS AND METHODS: A total of 498 patients with nonmuscle invasive bladder cancer treated with adjuvant bacillus Calmette-Guérin were included in study, of whom 320 underwent the purified protein derivative skin test 1 to 2 weeks prior to therapy. Oncologic outcomes and the rate of bacillus Calmette-Guérin related side effects were statistically evaluated. RESULTS: The mean ± SD 5-year recurrence-free survival rate in patients who did vs did not undergo the purified protein derivative skin test was 66.6% ± 2.8% and 59.1% ± 4.1%, respectively, which was significantly different (p = 0.048). No significant difference was observed in the progression-free survival rate between patients who did vs did not undergo the test. Multivariate Cox regression analysis revealed that a history of recurrence (HR 1.59, p = 0.02), multiple tumors (HR 1.95, p <0.01), the bacillus Calmette-Guérin Connaught strain (HR 0.71, p = 0.04), 7 or more bacillus Calmette-Guérin instillations (HR 0.70, p = 0.04) and undergoing the purified protein derivative skin test (HR 0.72, p = 0.04) were independently associated with tumor recurrence. Major bacillus Calmette-Guérin related side effects were noted in 77 of the 320 patients (24.1%) who did vs 27 of the 178 (15.2%) who did not undergo the test, which was significantly different (p = 0.02). CONCLUSIONS: The purified protein derivative skin test prior to bacillus Calmette-Guérin treatment enhances the therapeutic effects of this treatment and potentially results in a higher incidence of major bacillus Calmette-Guérin related side effects. Combination therapy with bacillus Calmette-Guérin using the purified protein derivative skin test may improve the oncologic outcomes of that therapy.

Conjunctival allergen provocation test : guidelines for daily practice.

Conjunctival allergen provocation test (CAPT) reproduces the events occurring by instilling an allergen on the ocular surface. This paper is the compilation of a task force focussed on practical aspects of this technique based on the analysis of 131 papers. Main mechanisms involved are reviewed. Indications are diagnosing the allergen(s)-triggering symptoms in IgE-mediated ocular allergy in seasonal, acute or perennial forms of allergic conjunctivitis, especially when the relevance of the allergen is not obvious or in polysensitized patients. Contraindications are limited to ongoing systemic severe pathology, asthma and eye diseases. CAPT should be delayed if receiving systemic steroids or antihistamines. Local treatment should be interrupted according to the half-life of each drug. Prerequisites are as follows: obtaining informed consent; evidencing of an allergen by skin prick tests and/or serum-specific IgE dosages; being able to deal with an unlikely event such as acute asthma exacerbation, urticaria or anaphylaxis, or an exacerbation of allergic conjunctivitis. Allergen extracts should be diluted locally prior to administration. Positive criteria are based on itching or quoted according to a composite score. An alternative scoring is based on itching. CAPT remains underused in daily practice, although it is a safe and simple procedure which can provide valuable clinical information.