Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy.

BACKGROUND: The bead-based epitope assay has been used to identify epitope-specific (es) antibodies and successfully used to diagnose clinical allergy to milk, egg, and peanut. OBJECTIVE: We sought to identify es-IgE, es-IgG4, and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the bead-based epitope assay. METHODS: Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled. Seventy-nine peptides from α-/ß-gliadin, γ-gliadin, ω-5-gliadin, and high- and low-molecular-weight glutenin were commercially synthesized and coupled to LumAvidin beads (Luminex Corporation, Austin, Tex). Machine learning methods were used to identify diagnostic epitopes, and performance was evaluated using the DeLong test. RESULTS: The analysis included 122 children (83 wheat-allergic and 39 wheat-tolerant; 57.4% male). Machine learning coupled with simulations identified wheat es-IgE, but not es-IgG4 or es-IgG1, to be the most informative for diagnosing wheat allergy. Higher es-IgE binding intensity correlated with the severity of allergy phenotypes, with wheat anaphylaxis exhibiting the highest es-IgE binding intensity. In contrast, wheat-dependent exercise-induced anaphylaxis showed lower es-IgG1 binding intensity than did all the other groups. A set of 4 informative epitopes from ω-5-gliadin and γ-gliadin were the best predictors of wheat allergy, with an area under the curve of 0.908 (sensitivity, 83.4%; specificity, 88.4%), higher than the performance exhibited by wheat-specific IgE (area under the curve = 0.646; P < .001). The predictive ability of our model was confirmed in an external cohort of 71 patients (29 allergic, 42 nonallergic), with an area under the curve of 0.908 (sensitivity, 75.9%; specificity, 90.5%). CONCLUSIONS: The wheat bead-based epitope assay demonstrated greater diagnostic accuracy compared with existing specific IgE tests for wheat allergy.

Treatment Difficulties in Wheat Oral Immunotherapy and the Predictive Value of Wheat-Specific IgE.

BACKGROUND: Factors associated with wheat oral immunotherapy (OIT) difficulties in patients with IgE-mediated wheat allergy have not been well studied. OBJECTIVE: We aimed to assess factors associated with difficulties in wheat OIT. METHODS: We retrospectively collected data from children under 18 years of age with history of IgE-mediated wheat allergy who underwent wheat OIT. The initial specific IgE (sIgE) of wheat and omega-5-gliadin, wheat skin prick test (SPT) sizes, eliciting doses, and adverse reactions during the OIT were evaluated. RESULTS: A total of 81 children were enrolled, with a mean age of 7.0 ± 2.7 years at the initiation of wheat OIT. The median follow-up duration was 2 years (IQR 1.2 -3.0 years). Difficulties in wheat OIT included patients who experienced frequent reactions (at least grade 2 or exercise-induced reactions) or deviated from the up-dosing protocol, which we defined as 'Complicated cases.' Twenty-six patients (32.1%) were complicated cases. Initial wheat-sIgEs were significantly higher in complicated cases than in noncomplicated cases (median of 192.3 kUA/L (IQR 30.4-590.0) vs 6.9 kUA/L (IQR 1.9-100.0) (p = 0.001)). Initial omega-5-gliadin-sIgEs in the complicated group were also significantly higher, with a median of 15.0 kUA/L (IQR 6.3-69.8) vs 1.6 kUA/L (IQR 0.2-11.4) (p < 0.001). The risk factors for complicated cases include higher omega-5-gliadin-sIgEs and anaphylaxis during the oral food challenge test (aOR 1.035 and 5.684, respectively). CONCLUSION: The initial wheat and omega-5-gliadin-sIgEs were significant risk factors for complicated OIT patients and could be used to monitor these patients carefully during the OIT period.

Children with wheat anaphylaxis and with low wheat specific IgE have a different IgE immunoblot pattern than those with high wheat specific IgE.

BACKGROUND: Children with wheat anaphylaxis can present with a wide range of wheat-specific IgE (sIgE). OBJECTIVE: To identify differences in clinical features and predominant wheat allergens sensitized by these patients. METHODS: Children with history of wheat anaphylaxis were recruited. Skin prick test (SPT) to wheat, sIgE to wheat, omega-5 gliadin (ω5G), lipid transfer protein (LTP) were investigated. Profiles of IgE-bound wheat allergens were studied to identify predominant wheat allergens. RESULTS: Twenty-nine children (17 males) aged 1-18 years were enrolled. Sixteen patients (55.2%) had wheat-sIgE > 100 kUA/L (WAhi) and 13 patients (44.8%) had wheat-sIgE < 34 kUA/L (WAlo). The median of peak wheat-sIgE in WAhi and WAlo were 340.5 kUA/L (IQR 184.3, 564.5) and 12.2 kUA/L (IQR 1.4, 41.3), respectively. Oral food challenge test (OFC) was carried out in 12 of 13 patients in the WAlo group, all of which had positive results. Eight of these 12 patients developed anaphylaxis during OFC despite having wheat-sIgE less than 10 kUA/L. There were no differences in clinical characteristics and atopic history between WAhi vs. WAlo. Medium to low molecular weight gliadin (< 40 kDa) and glutenin (< 60 kDa) were commonly recognized by patients with WAhi. IgE immunoblot pattern among the WAlo group was more widely dispersed than those with WAhi. CONCLUSIONS: Wheat anaphylaxis can occur in patients with low wheat-sIgE. Predominant wheat allergens recognized by patients with WAlo were different than those with WAhi. Such difference could be responsible for anaphylaxis at even low levels of wheat-sIgE.

Comprehending the allergen repertoire of shrimp for precision molecular diagnosis of shrimp allergy.

BACKGROUND: Clinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations. METHODS: Sera were collected from 85 subjects with challenge-proven or doctor-diagnosed shrimp allergy in Hong Kong and Thailand. The IgE-binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA. RESULTS: Ten IgE-binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic-calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid-binding protein (Pen m 13, 37.5%). Component-based tests yielded significantly higher area under curve values (0.77-0.96) than shrimp extract-IgE test (0.70-0.75). Yet the best component test differed between populations; Pen m 1-IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients. CONCLUSION: Pen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent.

Characterization of children with IgE-mediated wheat allergy and risk factors that predict wheat anaphylaxis.

BACKGROUND: The number of children presenting with IgE-mediated wheat reactions to academic medical centers in Thailand continues to increase. OBJECTIVE: Improved knowledge about the clinical characteristic of wheat allergy is urgently needed to better understand the risk factors and to improve proper treatment in this patient population. METHODS: A cross-sectional study using questionnaire review of children who presented with IgE-mediated wheat allergy during 2001 to 2015 was performed. Patients were divided into the wheat anaphylaxis (WA) or the only skin symptoms (SO) group. RESULTS: One hundred children were enrolled. Fifty-one and 49 patients were allocated to the WA and SO group, respectively. The median age was 40.5 months (range: 6-200), and the median age of onset was 7 months (range: 3-96). The vast majrity (90%) developed their first reaction after their first ingestion of wheat. Atopic dermatitis (AD) was found to be the only significant difference between groups and found more commonly in SO than in WA (59.2% vs. 35.3%, p = 0.02). Median mean wheal diameter (MWD) of skin prick test (SPT) and median sIgE level to wheat were higher in WA than in SO (8 vs. 3 mm, p < 0.001; and, 33.3 vs. 3.6 kUA/l, p < 0.001). CONCLUSIONS: Children with wheat allergy presented very early in life. AD was found in approximately half of the patients, and more commonly in SO. Median MWD of SPT and sIgE level to wheat were significantly higher in WA. These data will aid in further planning for a larger survey and intervention study in wheat allergy.

Clinical characteristics and outcomes of ocular allergy in Thai children.

BACKGROUND: Allergic conjunctivitis (AC) is the most common ocular condition in allergic children. In tropical countries, the study about the clinical features and outcome of treatment is very limited. OBJECTIVE: To review clinical characteristics and outcomes of treatment in children with ocular allergy. METHODS: Children with history of AC were classified to seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). The clinical history and outcome of treatment were recorded. RESULTS: One hundred and sixty-four children were recruited. PAC was the most common type (61.6%), followed by SAC (21.3%), VKC (12.2%), and AKC (4.9%). Male preponderance was found in all groups. Mean age of onset was 6.8 ± 2.8 years. Allergic rhinitis was the most common co-morbidity (97.6%). The common sensitized allergen is house-dust mites (86.1%). Standard treatments in all groups were natural tear and topical olopatadine. Add-on medications were usually needed in severe types of AC (VKC, AKC). History of topical corticosteroid use was 68.8% and 12.5% in VKC and AKC, respectively. All of them can discontinue topical corticosteroid when topical tacrolimus was applied. The overall remission was found 35% in VKC group and 63% in AKC group. The median duration of treatment was 20.5 months in VKC group and 11 months in AKC group. CONCLUSIONS: most Thai children with AC sensitized to house-dust mites. In severe forms of AC, most patients needed addon medication. The use of topical calcineurin inhibitor as an add-on therapy can decrease the use of topical corticosteroid.

Systemic absorption of epinephrine compared between the intranasal and intramuscular routes of administration in healthy adults.

BACKGROUND: Epinephrine 5 mg administered via the intranasal (IN) route was shown to be bioequivalent to epinephrine 0.3 mg administered via the intramuscular (IM) route in our preliminary study. OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of IN and IM epinephrine absorption in a larger group of healthy adults (n = 12). METHODS: Each subject was administered IN saline, IN epinephrine (5 mg), and IM epinephrine (0.3 mg) on 3 separate days. Plasma epinephrine levels were determined using liquid chromatography-tandem mass spectrometry. RESULTS: IN epinephrine administration showed significant systemic absorption compared to IN saline control with the areas under the curve (AUC0-180 min) of 4.4 (4.9) ± 4.0 and 0.2 (0.5) ± 0.3 ng.min/mL, respectively; the values are mean (median) ± standard deviation. IN epinephrine absorption was about 0.5-fold that of IM epinephrine (AUC0-180 min 10.0 (9.2) ± 8.6 ng.min/mL), but the difference was not statistically significant (p = 0.16). The mean peak epinephrine concentration and the time to reach it were also not significantly different between the IN and IM routes. The corresponding values were 120 pg/mL and 41 min for IN, and 209 pg/mL and 41 min for IM, respectively. CONCLUSIONS: The systemic absorption of IN epinephrine 5 mg was significantly different from the control IN saline and about 0.5-fold that of IM epinephrine 0.3 mg. Although epinephrine administration via the less invasive IN route is safe and feasible, further investigations are necessary to achieve an adequate and consistent systemic absorption comparable to that of the conventional IM injection.

Clinical practice guidelines for the diagnosis and management of atopic dermatitis.

Atopic dermatitis (AD), a chronic, relapsing dermatitis, is characterized by dry and pruritus skin in patients with a personal or family history of atopy. It affects up to 20% of children and 1-3% of adults in most countries worldwide, and leads to significant treatment costs and morbidity. These guidelines are developed in accordance with evidence-based publications and expert opinions. Following simple algorithms, the guidelines aim to assist adult and pediatric physicians in the better care of patients with AD. As with other diseases, there have been several diagnosis criteria proposed over time. Nonetheless, the classical Hanifin and Rajka criterion with no pathognomonic laboratory biomarkers is still the most widely used worldwide for the diagnosis of AD. The management of AD must be considered case by case to provide suitable care for each patient. Basic therapy is focused on avoiding specific/unspecific provoking factors and hydrating skin. Topical anti-inflammatory treatments such as glucocorticoids and calcineurin inhibitors are suggested for disease flare, and proactive therapy is best for long-term control. Other therapies, including antimicrobial agents, systemic antihistamines, systemic anti-inflammatory agents, immunotherapy, phototherapy, and psychotherapy, are reviewed in these guidelines. Crisaborole, a new topical phosphodiesterase 4 inhibitor, can be used twice daily in AD patients over three months old. Dupilumab, a biological drug for patients with moderate-to-severe AD, may be considered in patients with no improvement from other systemic treatments.

Accuracy of in-house alcohol-dissolved wheat extract for diagnosing IgE-mediated wheat allergy.

BACKGROUND: The standard method for diagnosing immediate wheat allergy is oral food challenge test (OFC). However, OFC can provoke anaphylaxis during the challenge process. Skin prick test (SPT) using commercial wheat extract yielded unsatisfactory result for diagnosis of wheat allergy. As a result, an in-house, alcohol-dissolved (Coca-10% EtOH) wheat extract was developed to improve accuracy of the SPT. OBJECTIVE: To determine the accuracy of in-house, alcohol-dissolved wheat extract in children with immediate wheat allergy. METHODS: This prospective cross-sectional study included children with history of immediate reaction after wheat ingestion. SPTs with commercial and in-house Coca-10% EtOH wheat extract were performed and wheat and omega-5 (ω-5) gliadin specific IgE (sIgE) were measured. Patients with no history of recent anaphylaxis after wheat ingestion underwent OFC with 31 grams of wheat flour. RESULTS: Thirty children were recruited. Thirteen of those had history of anaphylaxis after wheat ingestion. Eleven of the remaining 17 children (64.7%) had a positive result for wheat challenge test. Wheal size of 3 mm for both in-house and commercial wheat extract yielded the best accuracy for the test. Using these cutoff parameters, in-house Coca-10% EtOH wheat extract yielded 91.7% sensitivity, 66.7% specificity, and 86.7% accuracy. Comparatively, the commercial extract yielded 70.8% sensitivity, 100% specificity, and 76.6% accuracy. CONCLUSIONS: SPT using in-house Coca-10% EtOH wheat extract yielded better accuracy than commercial extract for diagnosing immediate type wheat allergy in children.

Prevalence and severity of asthma, rhinoconjunctivitis and eczema in children from the Bangkok area: The Global Asthma Network (GAN) Phase I.

BACKGROUND: As noted in the reports of ISAAC phase I and III, allergic diseases are very common in Thailand, especially among younger children. OBJECTIVE: The objectives of this project are to study the prevalence and severity of the most common allergic diseases. i.e. asthma, rhinoconjunctivitis and eczema among children living in Bangkok. METHODS: A cross-sectional multi-centers survey using GAN Core questionnaires on asthma, rhinoconjunctivitis and eczema symptoms were completed by parents of children aged 6-7 years and children aged 13-14 years. RESULTS: The total of 6,291 questionnaires were eligible for the analysis. The cumulative vs. 12-month period prevalence of the three conditions for all children were: 24.4% vs. 13.5% for wheezing, 51.1% vs. 43.6% for rhinitis and 15.8% vs. 14.2% for eczema, respectively. The period prevalence of wheezing for younger children (14.6%) was higher than for older children (12.5%). Prevalences of severe wheeze and exercise wheeze were more common among older children (2.9% and 14.8%). The 12-month prevalences of rhinitis (43.6%) and rhinoconjunctivitis (16.3%) were higher in both age groups. Eczema, as the same to the other conditions, occurred more frequently in both groups (period prevalence of 14.3% and 14.0%) comparing to ISAAC phase III. CONCLUSION: Allergic conditions are very common diseases among children residing in Bangkok. There is an urgent need for an in-depth study to define epidemiological factors responsible for this increase.

Prevalence and risk factors of allergic rhinitis in children in Bangkok area.

BACKGROUND: Allergic rhinitis (AR) is a disease with a high global disease burden and significant morbidity and expense. Risk factors are not well understood. OBJECTIVE: The objective of our project is to study the prevalence and risk factors of AR in children living in the Bangkok area. METHODS: A cross-sectional, multi-center survey using new GAN core questionnaires on current AR and risk factors was completed by 3,074 parents of children aged 6-7 years and by 3,217 children aged 13-14 years, directly. RESULTS: The prevalence of current AR in children aged 6-7 years and 13-14 years was 15.0% (95% confidence interval [CI]:13.8-16.3%) and 17.5% (95% CI: 16.2-18.8%), respectively. The prevalence of severe AR in children aged 6-7 years and 13-14 years was 1.0% (95% CI: 0.6-1.3%) and 1.9% (95% CI: 1.4-2.4%), respectively. Co-morbidity with asthma and eczema was 27.1% and 24.6%, respectively. Significant factors associated with AR include parental history of asthma (p = 0.025), parental history of AR (p < 0.001), parental history of eczema (p < 0.001), lower respiratory tract infection in the first year of life (p < 0.001), breastfeeding (p = 0.019), current use of paracetamol (p < 0.001), exercise (p < 0.001), current cat exposure (p = 0.008), and truck traffic on the street of residence (< 0.001). CONCLUSION: AR is a common disease among children residing in Bangkok. This study confirms that a family history of atopy (asthma, AR, and eczema), antibiotics given in the first year of life, current paracetamol use, exercise, current cat exposure, and truck traffic on the street of residence are important and significant risk factors for AR symptoms.

Early introduction of allergenic foods for the prevention of food allergy from an Asian perspective-An Asia Pacific Association of Pediatric Allergy, Respirology & Immunology (APAPARI) consensus statement.

Emerging evidence for the early introduction of allergenic foods for the prevention of food allergies, such as peanut allergy in Western populations, has led to the recent publication of guidelines in the USA and Europe recommending early peanut introduction for high-risk infants with severe eczema or egg allergy. Peanut allergy is, however, much less prevalent in Asia compared to the West. Varying patterns of food allergy are seen even within Asian countries-such as a predominance of wheat allergy in Japan and Thailand and shellfish allergy in Singapore and the Philippines. Customs and traditions, such as diet and infant feeding practices, also differ between Asian populations. Hence, there are unique challenges in adapting guidelines on early allergenic food introduction to the Asian setting. In this paper, we review the evidence and discuss the possible approaches to guide the timely introduction of allergenic food in high-risk infants in Asia.

Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome.

PURPOSE: Patients with 22q11.2 deletion syndrome have a variable decrease in immunological parameters, especially regarding T cell counts. The aim of this study was to investigate immunological change over time and factors associated with immunological recovery among patients with 22q11.2 deletion syndrome. METHODS: Patients with 22q11.2 deletion syndrome diagnosed by fluorescence in situ hybridization (FISH) were studied. Immunological parameters were evaluated every 6 months until patients returned to normal. Infection and vaccination histories were recorded and analyzed, and Kaplan-Meier survival curves were plotted to describe resolution of immunodeficiency. RESULTS: Forty-nine patients with an age range of 4 to 222 months were included. Twenty-five (51%) patients were female. In hypocalcemia, the odds ratio for CD4 lymphopenia was 17.03 (95%CI 1.82-159.23; p value = 0.01). Thirty patients (61.2%) exhibited decreased CD4+ T cell numbers, which returned to normal level in 18 (60%) patients. Median age of CD4+ T cell resolution was 2.5 years. T cell functions were abnormal in three patients. T cell functions returned to normal in all patients at a median age of 1.1 years. Six patients (13.5%) had abnormal serum immunoglobulin levels, with levels improving in four patients at 1.4 years of age. The most common infection was pneumonia (69.4%). BCG vaccination was administered in 47 of 49 patients at birth. Among 32 patients who had T cell defect, one patient developed BCGitis and one developed disseminated BCG. CONCLUSION: Immunodeficiencies identified among patients with 22q11.2 deletion syndrome were T cell defect (65.3%) and decreased immunoglobulin levels (12.2%). Median age of CD4 resolution was 2.5 years.

Age of resolution from IgE-mediated wheat allergy.

BACKGROUND: The natural history of wheat allergy varies among different countries. OBJECTIVE: To study the age of resolution from IgE-mediated wheat allergy and to define the predictors of wheat tolerance. METHODS: Patients with a history of immediate reactions after wheat ingestion were enrolled. Skin prick test (SPT) and measurement of serum specific IgE (sIgE) to wheat and ω-5 gliadin were performed. Oral challenge to wheat was performed to determine wheat tolerance. RESULTS: Fifty-five patients, aged 6 months to 12 years, were studied. The median age of wheat tolerance was 76 months (range 37-114 months). The percentage of children with wheat tolerance was 14.7% at age 2 years, 27% by age 4, 45.7% by age 5 and 69% by age 9. Predictors for wheat tolerance were SPT for wheat less than 3 mm of wheal diameter (hazard ratio 8.9), sIgE levels of wheat and ?-5 gliadin less than 0.35 (HR 4.3) and 0.35 kAU/L (HR 44), respectively, duration of onset of symptoms to time of physician diagnosis less than 36 months (HR 7.6) and no history of allergic rhinitis (HR 4.8). CONCLUSIONS: Forty percent of children with IgE-mediated wheat allergy develop tolerance by the age of 5 years. Size of SPT, IgE level of wheat and ω-5 gliadin, time from onset of symptoms to physician diagnosis and history of allergic rhinitis are helpful for predicting wheat tolerance.

The proportion of local allergic rhinitis to Dermatophagoides pteronyssinus in children.

BACKGROUND: Local allergic rhinitis (LAR) is diagnosed by the positive response to nasal allergen provocation test (NAPT) to aeroallergen and/or local synthesis of specific IgE (sIgE). This entity is found in half of the adults with non-allergic rhinitis (NAR). In children, very few data of the prevalence and characteristics of LAR were reported. METHODS: Children 8-18 years with NAR were recruited. A NAPT with Dermatophagoides pteronyssinus extract (NAPT-Dp) at 200, 600, and 2000 AU/ml, respectively, at 15-min interval was performed. The immediate response was assessed using the clinical symptom score, peak nasal inspiratory flow (PNIF), and acoustic rhinometry (ARM). The nasal tryptase and sIgE-Dp were measured at baseline and 15 min and 1 h after a positive NAPT-Dp. Two allergic rhinitis (AR) patients were used as positive controls. RESULTS: Fifty-four NAR children (61.1% boys) with the mean ± SD age of 11.1 ± 2.1 years were enrolled. The median duration of disease was 6.3 years. The most frequent comorbidity was asthma (38.9%). Eighty-seven percent of patients had mild persistent severity. NAPT-Dp was positive in 2/54 (3.7%) of NAR children who had increased symptom score and decreased minimal cross-sectional area (MCA) on ARM as well as PNIF. However, there was no change in the nasal tryptase and sIgE-Dp. The control AR patients had positive NAPT-Dp and increased nasal tryptase at 15 min without the change of sIgE-Dp. CONCLUSION: LAR is an uncommon condition in children. Further investigation in a large population of children with NAR is needed.

A preliminary study of intranasal epinephrine administration as a potential route for anaphylaxis treatment.

BACKGROUND: The intranasal (IN) administration of epinephrine could be an alternative route for anaphylaxis treatment. Although IN epinephrine absorption has been demonstrated in animals, such data in humans are still lacking. OBJECTIVE: To study the pharmacokinetics of IN epinephrine absorption in humans. METHODS: Each healthy adult (n = 5) was administered IN saline, IN epinephrine at various doses (i.e., 0.3, 0.6, 1.25, 2.5 and 5 mg), and intramuscular (IM) epinephrine at 0.3 mg. Plasma epinephrine levels at baseline and various time points up to 120 minutes after administration were determined using high-performance liquid chromatography with electrochemical detection. RESULTS: Significant systemic absorption of epinephrine via IN route was observed only at the dose of 5 mg, and the absorption thereof was comparable to that of IM epinephrine; the average area-under-curve (AUC) values at 0-120 minutes for IN saline, IM epinephrine, and 5 mg IN epinephrine were 0.3, 18.3, and 19.4 ng.min/mL, respectively. In addition, the peak epinephrine concentrations and the time to reach them were also not significantly different between IM and 5-mg IN epinephrine; the corresponding values (mean ± SD) were 309 ± 88 pg/mL and 67 ± 43 min for IM epinephrine, and 386 ± 152 pg/mL and 70 ± 17 min for 5 mg IN epinephrine. CONCLUSION: This preliminary study showed that epinephrine can be significantly absorbed via the IN route in humans. However, it requires a higher IN dose (5 mg) than the usual IM dose (0.3 mg) to achieve comparable systemic epinephrine absorption.

Clinical practice guideline for diagnosis and management of urticaria.

Urticaria is a common skin condition that can compromise quality of life and may affect individual performance at work or school. Remission is common in majority of patients with acute spontaneous urticaria (ASU); however, in chronic cases, less than 50% had remission. Angioedema either alone or with urticaria is associated with a much lower remission rate. Proper investigation and treatment is thus required. This guideline, a joint development of the Dermatological Society of Thailand, the Allergy, Asthma, and Immunology Association of Thailand and the Pediatric Dermatological Society of Thailand, is graded and recommended based on published evidence and expert opinion. With simple algorithms, it is aimed to help guiding both adult and pediatric physicians to better managing patients who have urticaria with/without angioedema. Like other recent guideline, urticaria is classified into spontaneous versus inducible types. Patients present with angioedema or angioedema alone, drug association should be excluded, acetyl esterase inhibitors (ACEIs) and non-steroidal anti-inflammatory drugs (NSAIDs) in particular. Routine laboratory investigation is not cost-effective in chronic spontaneous urticaria (CSU), unless patients have clinical suggesting autoimmune diseases. Non-sedating H1-antihistamine is the first-line treatment for 2-4 weeks; if urticaria was not controlled, increasing the dose up to 4 times is recommended. Sedating first-generation antihistamines have not been proven more advantage than non-sedating antihistamines. The only strong evidence-based alternative regimen for CSU is an anti-IgE: omalizumab; due to very high cost it however might not be accessible in low-middle income countries. Non-pharmacotherapeutic means to minimize hyper-responsive skin are also important and recommended, such as prevention skin from drying, avoidance of hot shower, scrubbing, and excessive sun exposure.

Role of atopy patch test for diagnosis of food allergy-related gastrointestinal symptoms in children.

BACKGROUND: Double-blind, placebo-controlled food challenge is the gold standard for diagnosing food allergy. However, it is a time-consuming procedure and requires onsite medical supervision and resuscitating medicines and devices on hand. The objective of this study was to compare the atopy patch test (APT) with the oral food challenge test (OFC) in children with suspected food allergy-related gastrointestinal (GI) symptoms. METHODS: A prospective self-controlled study enrolled children with a history of suspected food allergy-related GI symptoms. Skin prick test (SPT) and APT using lyophilized and commercial allergen extracts for cow's milk, egg, wheat, soy, and shrimp were evaluated, and OFC was performed. RESULTS: Thirty-nine patients (25 boys, median age 2.4 yrs) with 76 events of suspected food allergy-related GI symptoms were enrolled. SPT was positive in 11/76 events (14.5%). Sensitivity, specificity, predictive values, and likelihood ratio were calculated related to the food challenge outcome. Of 41 OFC, 30 (73.2%) were positive. APT using lyophilized allergen extracts yielded high sensitivity (80%) and high positive predictive value (85.7%). APT using commercial allergen extracts yielded low sensitivity (30%) but high specificity (90%). The negative predictive value of APT using lyophilized and commercial allergen extracts was 53.8% and 32.2%, respectively. All cases with positive APT using lyophilized allergen extracts together with positive SPT also had positive OFC. CONCLUSION: In contrast to commercial extracts, APT with lyophilized allergen extracts is reliable, safe, and maybe useful for the diagnosis of suspected food allergy-related GI symptoms in children. OFC is still needed in most of the cases.

Clinical characteristics of recurrent acute rhinosinusitis in children.

OBJECTIVE: Recurrent acute rhinosinusitis (RARS) is defined as multiple episodes of acute rhinosinusitis in which the symptoms and signs of infection resolve completely between episodes. Limited data are available on the characteristics and preventive therapy of RARS. This study evaluated the clinical characteristics and predisposing factors of RARS in children as well as the preventive therapy. METHODS: Medical records of children with RARS diagnosed between January 2010 and December 2012 were obtained. Demographic data, presenting symptoms, predisposing factors and preventive therapy were reviewed. RESULTS: Ninety-four children with RARS were recruited. The mean age was 7.7±2.6 years, with a mean age of onset of 4.0±1.4 years. Sixty-one patients (64.9%) were boys and 56 patients (59.6%) had family history of atopy. The most common presenting symptom of RARS was purulent nasal discharge (100.0%), followed by nasal congestion (68.1%) and postnasal drainage (31.9%). The most common predisposing factor for RARS was immunoglobulin G subclass deficiency (78.7%), followed by non-allergic rhinitis (64.9%) and allergic rhinitis (35.1%). Sixty-five children (69.1%) received preventive therapy for RARS. The responses to preventive measures were: 80.0% (32/40 patients) to oral antibiotic prophylaxis, 50.0% (11/22 patients) to adenotonsillectomy, 91.7% (11/12 patients) to specific allergen immunotherapy, 27.3% (3/11 patients) to gentamicin nasal irrigation, and 66.7% (4/6 patients) to intravenous immunoglobulin. CONCLUSION: The most common presenting symptoms of RARS in children were purulent nasal discharge, nasal congestion and postnasal drainage. Children with RARS should be evaluated for the presence of underlying conditions such as immunodeficiency and allergic disease, which led to the appropriate management for these children.

Vernal keratoconjunctivitis: a severe allergic eye disease with remodeling changes.

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner-Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual-acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness. Understanding of pathogenesis of VKC may lead to better therapy for these unfortunate patients.