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4.  Food dependant exercise induced anaphylaxis a retrospective study from 2 allergy clinics in Colombo, Sri Lanka 
The aetiology of anaphylaxis ranges from food, insect venom, drugs and various chemicals. Some individuals do not develop anaphylaxis with the offending agent unless ingestion is related temporally to physical exertion, namely food dependent exercise induced anaphylaxis (FDEIA). The foods implicated are wheat, soya, peanut, milk and sea food. A retrospective study on patients with FDEIA from two Allergy clinics in Sri Lanka from 2011 to 2015 is reported. Patients were selected who fulfilled the following criteria: clinical diagnosis of anaphylaxis according to the World Allergy Organization (WAO) criteria, where the onset of symptoms was during exertion, within 4 h of ingesting a food, the ability to eat the implicated food independent of exercise, or exercise safely, if the food was not ingested in the preceding 4 h and an in vitro (ImmunoCap serum IgE to the food) or in vivo (skin prick test) test indicating evidence of sensitivity to the food. There were 19 patients (12 males: 7 females). The ages ranged from 9 to 45 (mean 22.9, median 19 years). Eight patients (42.1%) were in the 9–16 age group. Those below 16 years had a male:female ratio of 3:5, while for those above 16 years it was 9:2. Wheat was the only food implicated in FDEIA in all patients and was confirmed by skin prick testing, or by ImmunoCap specific IgE to wheat or ω − 5 gliadin. All patients had urticaria, while 5/19 (26.3%) had angioedema of the lips. Fifteen patients (78.9%) had shortness of breath or wheezing, while 8 (42.1%) had lost consciousness. Nine patients (47. 3%) had hypotension. Fourteen (73.6%) of our patients had severe reactions, with loss of consciousness or hypotension, while 5 (26.3%) had symptoms related to the gastrointestinal tract. One patient developed anaphylaxis on two occasions following inhalation of ganja, a local cannabis derivative along with the ingestion of wheat and exertion. Wheat is the main food implicated in FDEIA in Sri Lanka. A local cannabis derivative, ganja has been implicated as a cofactor for the first time.
PMCID: PMC4513746  PMID: 26213534
Anaphylaxis; FDEIA; Wheat; Food allergy; Exercise
5.  Retrospective case note review of chronic spontaneous urticaria outcomes and adverse effects in patients treated with omalizumab or ciclosporin in UK secondary care 
Omalizumab is approved in the UK as add-on treatment for chronic spontaneous urticaria (CSU) in patients with inadequate response to H1-antihistamines. Ciclosporin is an established but unlicensed 3rd line option for CSU. Two parallel retrospective observational studies were conducted to describe outcomes of treatment and adverse events with omalizumab or ciclosporin for CSU treatment.
Data from UK specialist centres prescribing omalizumab (five centres) or ciclosporin (three centres) in CSU patients were collected from hospital records by clinical staff and pooled for analysis.
Forty-six patients prescribed omalizumab and 72 patients prescribed ciclosporin were included. Twenty-two (48%) omalizumab-treated patients had paired Urticaria Activity Scores (UAS7), showing a 25.4 point improvement during treatment (P < 0.0001). Paired Dermatology Life Quality Index (DLQI) was available in 28 (61%) omalizumab-treated and 17 (24%) ciclosporin-treated patients. At least a 75% improvement in DLQI score was observed in 79% of omalizumab-treated and 41% of ciclosporin-treated patients, and 65% of omalizumab-treated patients had complete resolution of their quality-of-life impairment (DLQI 0–1) versus 21% of ciclosporin-treated patients. Clinician comments reported symptom clearance in 15/36 (42%) omalizumab-treated and 10/60 (17%) ciclosporin-treated patients. Proportions of patients with adverse events were similar but those for omalizumab resembled CSU symptoms, making causality assignment difficult, whereas those for ciclosporin were consistent with its known adverse effect profile.
Validated patient-reported measures of disease severity and quality of life should be used routinely in CSU management. Based on clinician comments and DLQI scores, symptoms and quality of life showed a greater improvement in the omalizumab-treated cohort than in the ciclosporin-treated cohort.
PMCID: PMC4507325  PMID: 26195984
Chronic spontaneous urticaria; Ciclosporin; Observational; Omalizumab; Retrospective
6.  CSACI position statement: epinephrine auto-injectors and children < 15 kg 
Epinephrine (adrenaline) is the treatment of choice for anaphylaxis. While other medications, including H1-antihistamines, H2-antihistamines, corticosteroids, and inhaled beta-2 agonists are often used to treat anaphylaxis in the emergency setting, none of these medications has been shown to reverse anaphylaxis. Fatal anaphylaxis is related to the delayed use of epinephrine. In community settings, epinephrine is available as an auto-injector in two doses, 0.15 mg and 0.3 mg. The recommended dose for children is 0.01 mg per kilogram. For infants at risk of anaphylaxis in the community, there are few options with regard to providing an optimal epinephrine dose for first-aid treatment. The Canadian Society of Allergy and Immunology (CSACI) therefore recommends, for the child weighing less than 15 kg, given the lack of a suitable alternative, prescribing the 0.15 mg epinephrine autoinjector. Adverse effects of an epinephrine dose of 0.15 mg given intramuscularly in infants or children weighing less than 15 kg are expected to be mild and transient at the plasma epinephrine concentrations achieved; therefore, these effects need to be measured against the consequences of not receiving epinephrine at all, which can include fatality.
PMCID: PMC4485331  PMID: 26131015
Epinephrine; Anaphylaxis; Infant; CSACI position statement; Allergy
7.  Allergy immunotherapy prescribing trends for grass pollen-induced allergic rhinitis in Germany: a retrospective cohort analysis 
Allergy immunotherapy is an effective treatment for patients with allergic rhinitis whose symptoms are unresolved with pharmacotherapy. Allergy immunotherapy for grass pollen-induced allergic rhinitis is available in three modalities: subcutaneous immunotherapy and sublingual immunotherapy as a tablet or drop. This study aimed to understand trends in allergy immunotherapy prescribing and practice patterns for grass allergies in adult and paediatric patients in Germany.
A retrospective cohort study was conducted using IMS Disease Analyzer in Germany. Patients with an allergy immunotherapy prescription for grass pollen (Anatomical Therapeutic Chemical [ATC] classification code V01AA02) from September 2005 to December 2012 were included in the study. General Practitioners (GPs), dermatologists, Ear, Nose and Throat (ENT)-specialists, paediatricians and pneumologists were included as the allergy immunotherapy prescribing physicians in the study. Descriptive analyses were conducted on patient characteristics at index and prescribing physician specialty; a test for trend was conducted for timing of initiation of first allergy immunotherapy prescription in each annual prescribing season.
Eighteen thousand eight hundred fifty eligible patients were identified during the study period. The majority of patients received subcutaneous immunotherapy; however, the proportion of patients receiving sublingual immunotherapy tablets increased from 8 % in 2006/2007 to 29 % in 2011/2012 (p < 0.001). Initiation of subcutaneous immunotherapy and Oralair® generally peaked during each prescribing year in two seasons (September-October and January) while GRAZAX® prescriptions peaked in autumn (September-October). ENT-specialists and dermatologists were the largest allergy immunotherapy prescribers in adults, while paediatricians and ENT-specialists were the largest prescribers of allergy immunotherapy in paediatric patients.
Subcutaneous immunotherapy remained the dominant allergy immunotherapy modality for grass pollen-induced allergic rhinitis in Germany for adult and paediatric patients; however, there was a marked increase in proportion of patients receiving sublingual immunotherapy tablets from 2006/2007 to 2011/2012, after their introduction to the market in 2006. ENT-specialists, dermatologists and paediatricians were responsible for the majority of prescribing. The predominance of particular modalities within certain physician specialties likely reflects different treatment goals or needs.
PMCID: PMC4470112  PMID: 26085832
Allergens; Clinical immunology; Paediatrics; Grass pollen allergy; Rhinitis
8.  Successful desensitization in a boy with severe cow’s milk allergy by a combination therapy using omalizumab and rush oral immunotherapy 
Rush oral immunotherapy (OIT) combined with omalizumab (OMB) has been reported to be an effective and safe treatment for severe milk allergies. However, no report has described long-term follow-up observations after OMB discontinuation. The purpose of this case report was to evaluate the safety and efficacy of rush OIT in combination with OMB during a long period of treatment.
Case presentation
A 5-year-old boy presented with a past history of two severe episodes of anaphylaxis (at the age of 2 and 3 years) after consuming small amounts of cow’s milk (CM). Before the OIT, the total immunoglobulin E (IgE) level was 654 IU/mL, and specific-IgE (sIgE) levels for CM, casein, and β-lactoglobulin were 77.0 kUA/L, 86.2 kUA/L and 12.0 kUA/L, respectively. The skin prick test (SPT) for CM showed a wheal (diameter, 20 mm) and erythema (diameter, 50 mm). In the open food challenge, he reacted to a 0.2 mL ingestion of CM and presented with dyspnea and laryngospasms, and he was then administrated 150 mg OMB every 2 weeks for 8 weeks. In the 9th week, he was admitted to hospital for the rush phase of the OIT. Once he was able ingest a dose of 200 mL CM without having an adverse reaction, he was discharged and allowed to continue a daily dose of 200 mL CM at home. During this phase, the sIgE levels were elevated, but the end-point titration values from the SPT gradually decreased, and the SPT was negative after 1 year of OMB treatment.
Five months after discontinuation of OMB, the daily CM ingestion was ceased for a 2-week period, followed by an oral food challenge (OFC) that was negative. The patient experienced only five mild adverse events during the course of rush OIT, even after the discontinuation of OMB and his quality of life improved dramatically afterwards.
The combination therapy of rush OIT and OMB successfully maintained desensitization to CM in a boy with severe allergies. We propose that a negative SPT may be useful to guide discontinuation of OMB in such patients.
PMCID: PMC4461908  PMID: 26064142
Rush oral immunotherapy; Omalizumab; Food allergy; Cow’s milk
9.  The effect of a new communication template on anticipated willingness to initiate or resume allergen immunotherapy: an internet-based patient survey 
A patient’s knowledge of his/her allergic condition and treatment is a key factor in adherence and effectiveness.
To assess patients’ understanding of allergy and acceptance of allergen immunotherapy on the basis of (i) information given by their physician at the time of prescription and (ii) a new communication template viewed some months later, we performed an Internet-based survey of patient panels in France, Germany, Spain, the USA and Russia. The survey participants were either recent “early abandoners” (having discontinued allergen immunotherapy before the end of the prescribed course) or “non-starters” (having decided not to initiate a course of allergen immunotherapy recommended by their physician). All participants completed an on-line questionnaire immediately before and immediately after viewing the new communication template. The study’s main objectives were to validate the new communication template and to assess its impact on anticipated willingness to initiate or resume allergen immunotherapy.
We surveyed a total of 261 patients (France: 57; Germany: 51; Spain: 52; USA: 51; Russia: 50), comprising 127 “early abandoners” and 134 “non-starters”. The mean time since symptom onset and selection for the study was 14.5 years. Subcutaneous allergen immunotherapy had been prescribed in 60 % of cases. Twenty-eight percent of the participants did not know for which allergy they were being treated. Early abandoners reported a perception of low effectiveness (39 %) and complained about expense (39 %) and practical constraints (32 %). Twenty-two percent of the non-starters feared side effects. The communication template was considered to be clear (by 92 % of the patients), convincing (by 75 %) and reassuring (by 89 %); 80 % of the participants felt better informed afterwards, and 67 % stated that viewing the communication template would have made them more likely to continue or initiate allergen immunotherapy (overall willingness score: 5.65 out of 10 before viewing and 7.1 out of 10 afterwards).
After viewing a new communication template on allergy and allergen immunotherapy, patients participating in the survey felt better informed and more likely to initiate or complete this therapy. It now remains to investigate the communication template’s effect on actual acceptance of and adherence to allergen immunotherapy.
Electronic supplementary material
The online version of this article (doi:10.1186/s13223-015-0083-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4443522  PMID: 26015786
Allergen immunotherapy; Allergy; Adherence; Information; Patient-physician communication
10.  The Allergic Rhinitis – Clinical Investigator Collaborative (AR-CIC): nasal allergen challenge protocol optimization for studying AR pathophysiology and evaluating novel therapies 
The Nasal Allergen Challenge (NAC) model allows the study of Allergic Rhinitis (AR) pathophysiology and the proof of concept of novel therapies. The Allergic Rhinitis – Clinical Investigator Collaborative (AR-CIC) aims to optimize the protocol, ensuring reliability and repeatability of symptoms to better evaluate the therapies under investigation.
20 AR participants were challenged, with 4-fold increments of their respective allergens every 15 minutes, to determine the qualifying allergen concentration (QAC) at which the Total Nasal Symptom Score (TNSS) of ≥10/12 OR a Peak Nasal Inspiratory Flow (PNIF) reduction of ≥50% from baseline was achieved. At the NAC visit, the QAC was used in a single challenge and TNSS and PNIF were recorded at baseline, 15 minutes, 30 minutes, 1 hour, and hourly up to 12 hours. 10 additional ragweed allergic participants were qualified at TNSS of ≥8/12 AND ≥50% PNIF reduction; the Cumulative Allergen Challenge (CAC) of all incremental doses was used during the NAC visit. 4 non-allergic participants were challenged with the highest allergen concentration.
In the QAC study, a group qualified by only meeting PNIF criteria achieved lower TNSS than those achieving either TNSS criteria or PNIIF+TNSS (p<0.01). During the NAC visit, participants in both studies reached their peak symptoms at 15minutes followed by a gradual decline, significantly different from non-allergic participants. The “PNIF only” group experienced significantly lower TNSS than the other groups during NAC visit. QAC and CAC participants did not reach the same peak TNSS during NAC that was achieved at screening. QAC participants qualifying based on TNSS or TNSS+PNIF managed to maintain PNIF scores.
Participants experienced reliable symptoms of AR in both studies, using both TNSS and PNIF reduction as part of the qualifying criteria proved better for qualifying participants at screening. Phenotyping based on pattern of symptoms experienced is possible and allows the study of AR pathophysiology and can be applied in evaluation of efficacy of a novel medication. The AR-CIC aims to continue to improve the model and employ it in phase 2 and 3 clinical trials.
PMCID: PMC4419495  PMID: 25945101
Allergic rhinitis; Nasal allergen challenge; Allergic rhinitis; Clinical investigator collaborative
11.  Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma 
Determining the cellular and molecular phenotypes of inflammation in asthma can identify patient populations that may best benefit from targeted therapies. Although elevated IL-6 and polymorphisms in IL-6 signalling are associated with lung dysfunction in asthma, it remains unknown if elevated IL-6 levels are associated with a specific cellular inflammatory phenotype, and how IL-6 blockade might impact such inflammatory responses.
Patients undergoing exacerbations of asthma were phenotyped according to their airway inflammatory characteristics (normal cell count, eosinophilic, neutrophilic, mixed granulocytic), sputum cytokine profiles, and lung function. Mice were exposed to the common allergen, house dust-mite (HDM), in the presence or absence of endogenous IL-6. The intensity and nature of lung inflammation, and levels of pro-granulocytic cytokines and chemokines under these conditions were analyzed.
Elevated IL-6 was associated with a lower FEV1 in patients with mixed eosinophilic-neutrophilic bronchitis. In mice, allergen exposure increased lung IL-6 and IL-6 was produced by dendritic cells and alveolar macrophages. Loss-of-function of IL-6 signalling (knockout or antibody-mediated neutralization) abrogated elevations of eosinophil and neutrophil recruiting cytokines/chemokines and allergen-induced airway inflammation in mice.
We demonstrate the association of pleiotropic cellular airway inflammation with IL-6 using human and animal data. These data suggest that exacerbations of asthma, particularly those with a combined eosinophilic and neutrophilic bronchitis, may respond to therapies targeting the IL-6 pathway and therefore, provide a rational basis for initiation of clinical trials to evaluate this.
PMCID: PMC4397814  PMID: 25878673
Airway inflammation; Asthma; Allergy; Bronchitis; Eosinophil; Neutrophil; Granulocyte; IL-6; IL-6R; House dust-mite (HDM)
12.  Sensitization to workplace respiratory allergens among bakery workers in Douala, Cameroon: a cross-sectional study 
Sensitization to flour or fungal alpha-amylase is a prerequisite for the development of respiratory allergy in bakers. The knowledge of occupational allergen sensitization among bakery workers will facilitate the implementation of preventive measures for respiratory allergies in bakeries. The objective of this study was to determine the prevalence and factors associated with sensitization to wheat flour and α-amylase in bakers in Douala.
A cross-sectional study was conducted in 42 of the 151 bakeries that are present in the city of Douala. Demographics, clinical data, as well as results of skin prick tests to wheat flour, α-amylase and common aeroallergens were collected from all participants. A logistic regression model of the SPSS.20 software was used to identify factors associated with sensitization to wheat flour and α-amylase.
Of the 229 participants included in the study, 222 (96.9%) were male. The mean age was 36.3 ± 8.9 years. The prevalence of sensitization to flour and α-amylase were 16.6% and 8.3% respectively. After multivariate analysis, factors associated with sensitization to flour were work seniority and sensitization to storage mites while an age of 30 years and above was the only factor associated with sensitization to α-amylase.
Bakers in Douala are at risk of sensitization to occupational allergens. The environmental hygiene in bakeries, health surveillance and the use of personal protective equipment could reduce the risk of respiratory allergies among bakers.
PMCID: PMC4396722  PMID: 25873977
Asthma; Wheat allergen; α-amylase; Allergen sensitization; Bakeries
13.  Central obesity and other factors associated with uncontrolled asthma in women 
Asthma remains an uncontrolled disease. The Comorbidities, particularly obesity, and several other factors have been identified as being individually associated with asthma control, and these factors vary among different countries and between sexes. Studies have suggested that the harmful effects of these factors are greatest among women. The aim of the present study was to identify associated factors with uncontrolled asthma in women at the outpatient clinic of a Federal University Hospital in Rio de Janeiro, Brazil.
Cross-sectional study with asthmatic women, older than 18 years old. All subjects were included according to stringent criteria. The study used a structured questionnaire with data about demographic variables, education level, comorbid conditions, and disease history. Anthropometric and spirometric measurements were obtained. Asthma control was assessed by three different tools: the Asthma Control Test (ACT), the Asthma Control Questionnaire (ACQ) and the Global Initiative for Asthma (GINA) criteria.
A total of 124 women were included, and 57%, 38% and 21% were totally controlled according to ACT, ACQ and GINA criteria, respectively. A total of 31.5% were obese. According to the CI (Conicity Index) and WC (waist circumference) respectively, 84% and 68% were centrally obese. There was no association between asthma control and age, education, duration of the disease or BMI (Body Mass Index) in the three models, but there was a significant association between central obesity and asthma control with the ACQ and GINA assessment tools, controlling for explanatory variables such as GERD (gastroesophageal reflux disease). Pre-bronchodilator percent predicted forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were significantly associated with age and FVC was also associated with central obesity.
Asthma remains uncontrolled in women despite treatment, and central obesity seems to have a negative influence on the control of the disease. We believe that women should be studied as a separate group and suggest prospective studies with assessment of fat distribution and biomarkers, controlling for possible comorbidities associated with asthma control.
PMCID: PMC4391683  PMID: 25859274
Asthma control; Women; Central obesity; Comorbidities
14.  The role of flavor and fragrance chemicals in TRPA1 (transient receptor potential cation channel, member A1) activity associated with allergies 
TRPA1 has been proposed to be associated with diverse sensory allergic reactions, including thermal (cold) nociception, hearing and allergic inflammatory conditions. Some naturally occurring compounds are known to activate TRPA1 by forming a Michael addition product with a cysteine residue of TRPA1 through covalent protein modification and, in consequence, to cause allergic reactions. The anti-allergic property of TRPA1 agonists may be due to the activation and subsequent desensitization of TRPA1 expressed in sensory neurons. In this review, naturally occurring TRPA1 antagonists, such as camphor, 1,8-cineole, menthol, borneol, fenchyl alcohol and 2-methylisoborneol, and TRPA1 agonists, including thymol, carvacrol, 1’S-1’- acetoxychavicol acetate, cinnamaldehyde, α-n-hexyl cinnamic aldehyde and thymoquinone as well as isothiocyanates and sulfides are discussed.
PMCID: PMC4404258  PMID: 25897313
Flavor and fragrance chemicals; Allergy; TRPA1; Isothiocyanates; Bradykinin receptors
15.  Allergy to cooked, but not raw, peas: a case series and review 
Allergic reactions to legumes are common.Food allergy to cooked, but not raw, pea has been rarely reported in the literature. This case series describes five children who had various IgE-mediated symptoms upon consumption of cooked pea, but tolerated raw pea. Skin testing then confirmed positive responses to cooked, but not raw, peas. It is important to consider allergy to cooked legumes, even in the context of raw legume tolerance.
PMCID: PMC4372996  PMID: 25810727
Food allergy; Pea; Legume
16.  CSACI position statement: systemic effect of inhaled corticosteroids on adrenal suppression in the management of pediatric asthma 
Asthma is a chronic inflammatory disease of the airways that affects a growing number of children and adolescents. Inhaled corticosteroids (ICS) are the mainstay of treatment in persistent asthma, with a stepwise approach to increasing doses of ICS depending on asthma severity and control. ICS have known local and systemic side effects, of which adrenal suppression is still under-recognized. The latter is associated with chronic exposure and higher doses, although it has rarely been reported in children receiving low doses for a short period of time. The Canadian Society of Allergy and Clinical Immunology (CSACI) therefore recommends that physicians screen for adrenal suppression in children receiving high doses for more than 6 months and to consider screening those on medium dose if the risk is deemed higher by factors that increase an individual’s systemic corticosteroid exposure. Morning serum cortisol level can be used as a screening tool and abnormal results or normal results with a high index of suspicion should be confirmed with low-dose ACTH stimulation tests.
PMCID: PMC4369840  PMID: 25802532
Asthma; Inhaled corticosteroids; Fluticasone; Adrenal suppression
17.  Evaluation of patients’ expectations and benefits in the treatment of allergic rhinitis with a new tool: the patient benefit index – the benefica study 
Symptoms of allergic rhinitis (AR) have a detrimental effect on quality of life. The AR-Patient Benefit Index (AR-PBI), a specific self-assessment tool has been developed to assess treatment-related benefit in two separate sections: the Patient Needs Questionnaire (PNQ) which explores the patient’s expectations before treatment and the Patient Benefit Questionnaire (PBQ) which evaluates treatment benefit. For the PNQ, three dimensions summarize patients’ expectations: symptoms, social life and emotional state, thus covering a larger field than symptomatic relief. The aim of the study was to validate the French language version of the AR-PBI and to assess the treatment-related expectations and benefits provided in patients with allergic rhinitis treated with H1-antihistamines in a real-life study.
BENEFICA was a prospective, observational study involving patients with allergic rhinitis who were starting treatment with H1-antihistamines. The Patient Needs Questionnaire (PNQ) was administered before treatment (D0) and the Patient Benefit Questionnaire (PBQ) was collected after a 14-day course of H1-antihistamines (D15). Discomfort (visual analog scale), and quality of life (miniRQLQ) were measured on D0 and D15.
Three thousands and eighty-nine patients were enrolled in the study: mean age 39 ± 14 years, women 52%, 81% of patients with moderate to severe persistent rhinitis (Allergic Rhinitis and its Impact on Asthma, ARIA); 19% had (a) concomitant condition(s), 18% were asthmatic, and 12% had atopic dermatitis. Discomfort and quality of life improved between D0 and D15. AR-PBI was 2.7 ± 0.8, superior to 1 (threshold for clinically relevant benefit) for 97% of patients and greater in patients willing to continue the treatment. PBI was moderately correlated to change in miniRQLQ (r = −0.45, p < 0.0001) and change in discomfort (r = −0.38, p < 0.0001), suggesting a richer conceptual content than symptoms relief.
The French version of the Allergic Rhinitis-Patient Benefit Index (AR-PBI) has been validated. It complements the discomfort and quality of life tools and assesses the needs and benefits in patients suffering from allergic rhinitis. This new tool may help physicians to better understand patients’ expectations and to discuss treatment issues with their patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s13223-015-0073-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4349226  PMID: 25741366
Allergic rhinitis; Satisfaction; Patients’ needs; Treatment-related benefit; Antihistamine; AR-PBI; Patient benefit index; Real-life study
18.  Insights and advances in chronic urticaria: a Canadian perspective 
In the past few years there have been significant advances which have changed the face of chronic urticaria. In this review, we aim to update physicians about clinically relevant advances in the classification, diagnosis and management of chronic urticaria that have occurred in recent years. These include clarification of the terminology used to describe and classify urticaria. We also detail the development and validation of instruments to assess urticaria and understand the impairment on quality-of-life and the morbidity caused by this disease. Additionally, the approach to management of chronic urticaria now focuses on evidence-based use of non-impairing, non-sedating H1-antihistamines given initially in standard doses and if this is not effective, in up to 4-fold doses. For urticaria refractory to H1-antihistamines, omalizumab treatment has emerged as an effective, safe option.
PMCID: PMC4336710  PMID: 25705232
Chronic urticaria; Diagnosis; Classification; Management; Immunology; Antihistamines; Up-dosing; Omalizumab
19.  Reviewer acknowledgement 2014 
Contributing reviewers
The editors of Allergy, Asthma & Clinical Immunology would like to thank all of our reviewers who have contributed to the journal in Volume 10 (2014).
PMCID: PMC4320480  PMID: 25663841
20.  Clinical validation of controlled grass pollen challenge in the Environmental Exposure Unit (EEU) 
The Environmental Exposure Unit (EEU), a controlled allergen exposure model of allergic rhinitis (AR), has traditionally utilized ragweed pollen. We sought to clinically validate the use of grass pollen in the EEU.
Healthy volunteers with a history of AR symptoms during grass pollen season and supportive skin test responses attended the EEU for 3 hrs of rye grass pollen exposure (Lolium Perenne). Non-atopic controls were also recruited. Participants assessed individual rhinoconjunctivitis symptoms to generate Total Nasal Symptom Score (TNSS; max 12) and Total Symptom Score (TSS; max 24) and recorded Peak Nasal Inspiratory Flow (PNIF) q30min while in the EEU. Participants returned the following day for an additional 3 hrs of pollen exposure. Two separate groups allowed for the exploration of lower vs. higher pollen concentrations and subsequent effects on symptoms.
78 participants were screened, of whom 39 were eligible and attended the 2x3h EEU visits, plus 8 non-atopic controls. Mean TSS, TNSS and PNIF values amongst participants in the higher pollen concentration group (target 3500 grains/m3) after the first 3 hr exposure were 18.9, 9.7 and 68 L/min, respectively. In comparison, mean TSS, TNSS and PNIF values in the lower pollen concentration (2500 grains/m3) group were only 13.3, 7.6, and 82 L/min, respectively. The subsequent day of pollen exposure did not appreciably alter the maximal TSS/TNSSs, but rather resulted in a more rapid onset of symptomatology, with higher mean scores at the 30 min, 60 min and 90 min timepoints. The non-atopic controls remained asymptomatic.
This study provides clinical validation of the ability to generate allergic rhinoconjunctivitis symptoms amongst grass-allergic individuals in the EEU.
PMCID: PMC4316395  PMID: 25653682
Allergic rhinitis; Environmental exposure unit; Grass pollen; Controlled allergen challenge
21.  Asian sand dust aggregate causes atopic dermatitis-like symptoms in Nc/Nga mice 
Asian sand dust (ASD) originates from the arid and semiarid areas of China, and epidemiologic studies have shown that ASD exposure is associated with various allergic and respiratory symptoms. However, few studies have been performed to assess the relationship between skin inflammation and ASD exposure.
Twelve-week-old NC/Nga mice were divided into 6 groups (n = 8 for each group): hydrophilic petrolatum only (control); hydrophilic petrolatum plus ASD (ASD); hydrophilic petrolatum and heat inactivated-ASD (H-ASD); Dermatophagoides farinae extract (Df); Df and ASD (Df + ASD), and; Df and H-ASD (Df + H-ASD). The NC/Nga mice in each group were subjected to treatment twice a week for 4 weeks. We evaluated skin lesions by symptoms, pathologic changes, and serum IgE levels.
ASD alone did not induce atopic dermatitis (AD)-like skin symptoms. However, Df alone, Df + H-ASD and Df + ASD all induced AD-like symptoms, and dermatitis scores in the group of Df + ASD group were significantly greater than that of the Df group (P = 0.0011 at day 21; and P = 0.017 at day 28). Mean serum IgE was markedly increased in the Df and Df + ASD groups, compared to the ASD and control groups (P < 0.0001), and serum IgE levels in the Df + ASD group were significantly higher compared to the Df group (P = 0.003).
ASD alone did not cause AD-like symptoms in NC/Nga mice. However, AD-like symptoms induced by Df, a major allergen, were enhanced by adding ASD. Although no epidemiological studies have been conducted for the association between ASD and symptoms of dermatitis, our data suggest that it is likely that ASD may contribute to the exacerbation of not only respiratory symptoms, but also skin diseases, in susceptible individuals.
PMCID: PMC4311458  PMID: 25642251
Dermatitis; Atopic; Dermatophagoides farina; Mice
22.  Removal of peanut allergen Ara h 1 from common hospital surfaces, toys and books using standard cleaning methods 
In children, a diagnosis of peanut allergy causes concern about accidental exposure because even small amounts of peanut protein could trigger an allergic reaction. Contamination of toys, books or other items by peanut butter in areas where individuals have eaten may occur in hospital waiting rooms and cafeterias. It is not known if hospital cleaning wipes are effective in removing peanut allergen.
The purpose of this study was to determine whether cleaning peanut contaminated items with common household and hospital cleaning wipes would remove peanut allergen.
5 mL of peanut butter was evenly smeared on a 12 inch by 12 inch (30.5 by 30.5 cm) square on a nonporous (laminated plastic) table surface, a plastic doll, and a textured plastic ball, and 2.5 mL was applied to smooth and textured book covers. Samples for measurement of Ara h 1 were collected prior to the application of the peanut butter (baseline), and after cleaning with a common household wipe and two commercial hospital wipes. A monoclonal-based ELISA for arachis hypogaea allergen 1 (Ara h 1), range of detection 1.95-2000 ng/mL, was used to assess peanut allergen on each item. The samples were diluted 1:50 for testing.
At baseline, there was no detectable Ara h 1 allergen on any item at baseline. Detectable Ara h 1 was detected on all products after applying peanut butter (range 1.2-19.0 micrograms/mL).
After cleaning with any product, no Ara h 1 was detected on any item.
Table surfaces, book covers and plastic toys can be cleaned to remove peanut allergen Ara h 1 using common household and hospital cleaning wipes. Regular cleaning of these products or cleaning prior to their use should be promoted to reduce the risk of accidental peanut exposure, especially in areas where they have been used by many children.
PMCID: PMC4312450  PMID: 25642252
Food allergy; Peanut allergen; Cleaning; Hospital; Contamination; Ara h 1
23.  Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization 
It hasn’t been clearly understood yet whether sensitization to antibiotics, the virus itself or transient loss of drug tolerance due to the virus, is responsible for the development of maculopapular exanthems following amoxicillin intake in patients with infectious mononucleosis. We aimed to examine whether sensitization to penicillin developed among patients with skin rash following amoxicillin treatment within infectious mononucleosis.
Ten patients were investigated for drug sensitization by lymphocyte transformation test and six patients were further tested by prick-, intradermal and patch tests employing the penicillin’s main antigens.
Lymphocyte transformation test showed negative results with amoxicillin, while one patient had positive reaction to cefixime. Six patients with suspected sensitization to amoxicillin were then investigated by in vivo tests. Prick tests were negative in all six patients, but the intradermal tests showed positive reactions in four patients.
Our data demonstrate that in vitro testing is not sensitive enough in determining drug sensitization to penicillin. In vivo tests should be performed to detect sensitization and indeed with skin tests our results confirmed that sensitization to aminopenicillin may develop within infectious mononucleosis.
PMCID: PMC4362637  PMID: 25784943
Amoxicillin; Sensitization to antibiotics; Infectious mononucleosis; Drug tests
24.  Allergy to sunflower seed and sunflower butter as proposed vehicle for sensitization 
It is hypothesized that household exposure to allergenic proteins via an impaired skin barrier, such as atopic dermatitis, may contribute to the development of IgE sensitization. Household presence of peanut is a risk factor for the development of peanut allergy in children. Sunflower seed butter is a peanut-free alternative to peanut butter, and sunflower seed allergy is an uncommon but reported entity.
Case presentation
A 3 year old boy presented with oral discomfort that developed almost immediately after he ate sunflower seeds for the first time. He was given a dose of diphenhydramine. Subsequently he vomited, and his symptoms gradually resolved. A similar episode occurred to a commercial snack made with sunflower seed butter. Skin prick testing demonstrated a large positive (10 mm wheal) wheal-and-flare response to a slurry of fresh sunflower seed within 3–4 minutes associated with severe pruritus.
This child has an older sibling with confirmed peanut allergy (PNA). After the PNA diagnosis was made, the family home became peanut-free. In lieu of peanut butter, sunflower butter was purchased and eaten frequently by family members, but not by the child reported herein.
Subsequent to the episodes above, the child ate a bread roll with visible poppy seeds and developed itchy throat, dyspnea, and urticaria. Epicutaneous skin testing elicited a >10 mm wheal size within 3–4 minutes in response to a slurry of whole poppy seeds and 8 mm to fresh pumpkin seed, which had never been consumed.
A case of sunflower allergy in the context of household consumption of sunflower butter has not yet been reported. We suggest that homes which are intentionally peanut-safe may provide an environment whereby infants with impaired skin barrier are at increased risk of allergy to alternative “butter” products being used, via cutaneous exposure to these products preceding oral introduction to the child.
PMCID: PMC4311509  PMID: 25642250
Sunflower seed; Allergy; Risk factors
25.  The relationship between allergy and asthma control, quality of life, and emotional status in patients with asthma: a cross-sectional study 
Psychiatric comorbidities are prevalent in patients with chronic somatic disorders such as asthma. But, there is no clear evidence regarding the effect of atopic status and the type of sensitized allergen on emotional status. The aim of the present study was to investigate the effects of house dust mites and pollen allergies on emotional status, asthma control and the quality of life in patients with atopic asthma.
The study included 174 consecutive patients who were diagnosed with asthma accoring to the GINA criteria and who did not receive therapy for their allergy. All patients underwent a skin prick test. The asthma control, quality of life, and emotional status were evaluated using the ACT (asthma control test), AQLQ (asthma-specific quality of life questionnaire), and HAD (hospital anxiety depression questionnaire).
Atopy was detected in 134 (78.7%) patients. Of those patients: 58 (33.3%) had anxiety and 83 (47.7%) had depression. There was no relationship between emotional status, atopic status, and the type of indoor/outdoor allergen. Furthermore, there was no relationship between atopy and asthma severity, asthma control, and the quality of life. The anxiety and depression scores were significantly higher and the quality of life scores lower in the uncontrolled asthma group. The ACT and AQLQ scores were also lower in the anxiety and depression groups.
It was concluded that anxiety and depression are prevalent in patients with uncontrolled asthma, and atopic status did not affect the scores in ACT, AQLQ, and emotional status tests.
PMCID: PMC4311476  PMID: 25642249
Atopy; Asthma control; Quality of life; Emotional status; Depression; Anxiety

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