Incidence, predictors, and treatment outcomes of biphasic anaphylaxis in the emergency department of a tertiary hospital:A 5-year retrospective study.

BACKGROUND: Biphasic anaphylaxis despite successful treatment has an incidence of 4-5% based on NIAID/FAAN criteria. Our study aimed to investigate the frequency and predictive factors associated with biphasic reactions within the emergency department (ED) at Siriraj Hospital. METHODS: This observational study assessed medical records of anaphylaxis and anaphylactic shock patients at Siriraj Hospital's ED from January 2015 to December 2019. Of these, a random sample was reviewed and validated by allergists. Telephone interviews were performed to collect more data. Uni- or biphasic response were analyzed descriptively. Prediction modeling was performed. RESULTS: Among 1888 ED anaphylaxis cases, 601 were randomly sampled; 239 patients completing interviews were analyzed. The incidence of biphasic reactions was 7.1% (17/239) of cases. Common triggers of biphasic responses were foods (57.7%), drugs (31%), other known allergens (5.9%). Shellfish, edible insects, and wheat were the leading food triggers. Biphasic responses were significantly associated with history of drug allergy, any allergic disease, allergic rhinitis, number of prior anaphylactic reactions, angioedema, less generalized erythema, less reaction to shellfish, reaction to NSAIDs, and no epinephrine giving at ED visit (all p < 0.1). From a 3-predictor prognostic model including drug/idiopathic reaction, duration from onset to first epinephrine > 60 minutes, and any cutaneous edema/angioedema with an area under the curve of 0.72 (95%CI 0.54, 0.90). CONCLUSION: The incidence of biphasic response was 7.1%. Predictors of biphasic response were drug/idiopathic reac- tion, any cutaneous edema/angioedema, and time from onset to first epinephrine > 60 minutes.

Validity and reliability of the Thai version of Food Allergy Quality of Life Questionnaire - Adult Form (FAQLQ-AF) and Food Allergy Independent Measure - Adult Form (FAIM-AF).

BACKGROUND: Food allergy affects the patient's quality of life (QoL) and leads to anxiety and depression. In addition to routine treatment, QoL evaluation should also be performed in patients with food allergies. The validated Food Allergy Quality of Life Questionnaire - Adult Form (FAQLQ-AF) and Food Allergy Independent Measure - Adult Form (FAIM-AF) have been well accepted and available in many languages. OBJECTIVE: Translate FAQLQ-AF and FAIM-AF into Thai and perform reliability and validity tests in Thai adult patients with food allergies. METHODS: The translation process was performed according to the ISPOR Task Force for Translation and Cultural Adaptation. Participants 18 years or older and with physician-diagnosed food allergies were included in the study. Thai versions of FAQLQ-AF and FAIM-AF were administered to participants at baseline and after two weeks. The intraclass correlation coefficient and Cronbach's α coefficient were evaluated to demonstrate both questionnaires' test-retest reliability and internal consistency. RESULTS: The study included 104 participants. The Thai version of FAQLQ-AF and FAIM-AF demonstrated good reliability, with intraclass correlation coefficients of 0.83 (95%CI 0.76, 0.88) and 0.85 (95%CI 0.79, 0.90), respectively. The validity was excellent, with Cronbach's α coefficient of 0.91 and 0.92, respectively. Both questionnaires were moderately correlated (r = 0.69, P < 0.001), but poorly correlated with the 36-Item Short Form Survey, which is usually used to evaluate general health status. CONCLUSIONS: To evaluate the QoL in adult patients with food allergies, the Thai versions of FAQLQ-AF and FAIM-AF are valid, reliable, and more suitable than the general questionnaire.

Prevalence and characteristics of adult patients with adult-onset and childhood-onset food allergy.

BACKGROUND: IgE-mediated food allergy (FA) affects health-related quality of life, and may cause life-threatening reactions. Few studies characterizing adult FA patients have been reported, especially first ever reaction (FER) in adult-onset. OBJECTIVE: We describe the characteristics of adult FA patients, especially FER and compare these characteristics between childhood- and adult-onset FA. METHODS: A cross-sectional study of all adult patients visiting the Allergy Clinic, Siriraj Hospital at the outpatient department between January 2009 to December 2019 was conducted. Demographic, clinical data, and first reaction in life data were collected. Adult-onset was defined as ≥ 18 years old. RESULTS: Of 711 patients visiting the clinic, 174 (24.4%) were FA with a median age of 31.0 years (interquartile range 24.0, 44.0 years); 29.3% were male. FA patients had significantly higher prevalence of sensitization to cockroach compared with non-FA patients (67.4% vs. 56.3%); p = 0.016). The three most common food triggers were shellfish (68.0%), wheat (28.7%), and fruit and vegetables (10.0%). Before diagnosis, 56.7% (97/171) experienced at least 1 food-related anaphylaxis. Of the 166 patients compared on age of onset, 127 (76.5%) were adult-onset. In FER, patients with adult-onset had significantly more reactions to fruit and vegetables, more respiratory system involvement, and more other systems involvement [OR 8.95 (1.13, 1157); p = 0.034; OR 3.15 (95%CI 1.30, 8.25), p = 0.011; OR 10.8 (1.35, 1404), p = 0.019, respectively]. In sensitivity analysis, the cardiovascular system involvement was also significantly more common [OR 2.78 (1.05, 9.15); p = 0.038]. CONCLUSIONS: Shellfish was the most common trigger foods in adult FA patients. In FER, anaphylaxis was common for adult-onset. Adult-onset FA patients also had more respiratory, cardiovascular, and other systems involvements than childhood-onset ones. FA awareness, early diagnosis, and proper management are encouraged. Further studies on the adult-onset food allergic patients are required.

Patient-rated angioedema severity using a novel photo-aid for predicting non-mast cell mediator-induced angioedema diagnosis.

Background: Patients with non-mast cell mediator-induced angioedema (NM-AE) usually experience a diagnostic delay. Therefore, a clinical tool for predicting NM-AE diagnosis is essential. Objective: To identify clinical predictors related to a confirmed diagnosis of NM-AE. Methods: Participants with a history of recurrent AE with unknown causes were enrolled. They were classified into mast cell mediator-induced AE (M-AE) and NM-AE according to the response to anti-mast cell mediator therapy. All participants were asked to rate their worst AE ever experienced (% Photomax) from 0 to 100% using a novel photo aid. Clinical characteristics were recorded and analyzed by univariable and multivariable analysis. Results: Thirty-five participants were included, 25 with NM-AE and 10 with M-AE. AE located at extremities, face, and genitalia and positive family history were significantly associated with NM-AE. The AE severity in the NM-AE group was significantly higher than in the M-AE group, with the mean % Photomax of 82.4 ± 20.3 vs 47.5 ± 25.6 (p < 0.001), respectively. Univariable analysis showed that the % Photomax (every 10% increase), feet AE and hands AE were predictive of being NM-AE with the area under the receiver operating characteristic curve (AuROC) of 0.87 (95% CI 0.75, 0.99), 0.85 (95% CI 0.72, 0.98), and 0.84 (0.69, 0.99), respectively. Multivariable analysis showed that the combination of hands AE and % Photomax enhanced diagnostic accuracy (AuROC 0.94, 95% CI 0.86, 1.0) and constituted the prototype formula for calculating the diagnostic probability. Conclusion: Patient-rated angioedema severity using a novel photo aid combined with hands AE had a high probability of diagnosing NM-AE.

Not Just a Banana: The Extent of Fruit Cross-Reactivity and Reaction Severity in Adults with Banana Allergy.

This cross-sectional study aimed to investigate the prevalence and clinical characteristics of cross-reactivity and co-allergy to other plant foods among adult patients with IgE-mediated banana allergy in Thailand. A structured questionnaire was used to assess clinical reactivity, and cross-reactivity diagnoses were based on reactions occurring within 2 years of banana allergy onset, within 3 h of intake, and confirmed by allergists. Among the 133 participants, the most commonly associated plant foods with clinical reactions were kiwi (83.5%), avocado (71.1%), persimmon (58.8%), grapes (44.0%), and durian (43.6%). Notably, 26.5% of the reported reactions to other plant foods were classified as severe. These findings highlight the common occurrence of cross-reactivity/co-allergy to other plant foods in banana-allergic patients, with a significant proportion experiencing severe reactions. Travelers to tropical regions should be aware of this risk and advised to avoid specific banana cultivars and plant foods with reported high cross-reactivity. The inclusion of self-injectable epinephrine in the management plan for patients with primary banana allergy should be considered due to the substantial proportion of reported severe reactions and the wide range of clinical cross-reactivity and co-allergy observed.

Perioperative immediate hypersensitivity incidence, clinical characteristics, and outcomes after allergological evaluation: A multi-disciplinary protocol from tertiary hospital, Thailand.

BACKGROUND: Perioperative immediate hypersensitivity reaction (POH) is an immediate hypersensitivity reaction during an anesthesiologist monitored procedure. We report data of clinically-suspected POH (csPOH) patients undergoing an allergist-performed unified diagnostic workup algorithm for POH. OBJECTIVE: To describe the characteristics of patients with csPOH, POH events, and the POH outcomes of procedures after the unified diagnostic workup algorithm for POH. METHODS: A prospective cohort was conducted in adult patients with csPOH at Siriraj Hospital, a tertiary hospital, in Thailand from January 2018 to August 2022. Diagnostic workup for POH by the allergist included an initial assessment, followed by comprehensive allergological evaluation. Patients were then follow-up for POH outcomes during subsequent anesthesia procedures. RESULTS: Of 68 patients were csPOH, only 52 patients were diagnosed with POH by allergists. The incidence was 1:4,304 anesthetic procedures for POH, and 1:11,900 anesthetic procedures for at least grade III POH. Most patients had a grade III (51.2%) or II (46.4%) reaction. The leading identified causative agents were antibiotics (36.8%), antiseptics (21%), latex (13.1%), and morphine (13.1%). Cefazolin and chlorhexidine were the most common antibiotic and antiseptic, respectively. During a median follow-up time of 2.1 years, all 14 patients completing comprehensive allergological evaluation underwent subsequent anesthesia without recurrence of POH. CONCLUSIONS: The incidence of POH at our hospital was comparable to the global incidence. Antibiotics were the most common causative agent. Complete records, collaboration among the multidisciplinary team, and comprehensive evaluation of POH allow for safe subsequent procedures.

As-needed versus regular intranasal corticosteroid for allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Daily intranasal corticosteroid (INCS) is recommended for treating allergic rhinitis (AR). Nevertheless, patients are generally not adherent and use it on-demand. The data on the efficacy of as-needed INCS was insufficient. OBJECTIVE: We conducted a systematic review and meta-analysis to assess the efficacy of as-needed INCS compared with regular use for AR. METHODS: We searched PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) until May 2021. A pairwise meta-analysis used a random-effects model to estimate the pooled standardized mean difference (SMD). The primary outcome was the total nasal symptom score (TNSS) changes from baseline at 4 and 6 weeks. Secondary outcomes were the changes of individual nasal symptom score and quality-of-life (QoL) score. RESULTS: We identified five eligible RCTs with a total of 436 patients with AR. Only four studies had adequate data for quantitative synthesis. The TNSS changes of as-needed INCS were not significantly different from the regular use at both 4 (SMD 0.23 [95%CI: -0.14 to 0.60], p = 0.230) and 6 weeks (SMD 0.21 [95%CI: -0.02 to 0.44], p = 0.080). Most of the changes of individual nasal symptom scores and QoL scores were not significantly different between the two regimens. At 50% or more INCS dose of regular use, as-needed and regular INCS provided a similar efficacy. The treatment effect was, however, less sustained with as-needed INCS. CONCLUSIONS: The efficacy of as-needed use of INCS at 50% of corticosteroid exposure was comparable to regular use in improving nasal symptoms and QoL.

Efficacy and Safety of House Dust Mite Sublingual Immunotherapy Tablet in Allergic Asthma: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: House dust mite sublingual immunotherapy (HDM SLIT) effectively treats allergic rhinitis (AR). However, the evidence of HDM SLIT for allergic asthma remained limited. OBJECTIVE: To systematically review the efficacy and safety of HDM SLIT tablets in patients with allergic asthma. METHODS: We performed a systematic search through PubMed, Scopus, EMBASE, Web of Science, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials (RCTs) that addressed the efficacy and safety of HDM SLIT tablets compared with placebo or no intervention in allergic asthma from their inception date until September 2021. The primary outcome was the reduction in inhaled corticosteroids (ICS) dose. Additional outcomes were asthma control, exacerbation, lung function, quality-of-life, and adverse events. RESULTS: There were 7 RCTs, 5 studies in allergic asthma (4 in adults and 1 in children), and 2 in AR with or without asthma. The 6 standardized quality (SQ) HDM effectively reduced ICS dose in well- to partly controlled mild-to-moderate asthma in 1 RCT. Two RCTs evaluated the efficacy of 6 SQ and 12 SQ HDM in reducing asthma exacerbation in partly controlled moderate-to-severe asthma, and their results were inconsistent. One study in children with mild-to-moderate asthma found no benefit of HDM SLIT. Two RCTs in AR with or without mild-to-moderate asthma showed improvement of asthma symptoms. Adverse events were primarily local, and anaphylaxis treated with epinephrine was reported in 3 patients. CONCLUSIONS: The HDM SLIT tablets tend to effectively reduce ICS use in adults and adolescents with well- to partly controlled mild-to-moderate allergic asthma with a favorable safety profile.

Fatal liver mass rupture in a common-variable-immunodeficiency patient with probable nodular regenerating hyperplasia.

BACKGROUND: Nodular regenerating hyperplasia (NRH) is the most common liver involvement in common variable immunodeficiency (CVID). Most patients are asymptomatic with gradually increasing alkaline phosphatase (ALP) and mildly elevated transaminase enzymes over the years. We report the first case of fatal liver mass rupture in a CVID patient with probable NRH. CASE PRESENTATION: A 24-year-old man was diagnosed with CVID at the age of 1.25 years. Genetic testing revealed a transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI) mutation. He had been receiving intravenous immunoglobulin (IVIg) replacement therapy ever since then. The trough level of serum IgG ranged between 750-1200 mg/dL. However, he still had occasional episodes of lower respiratory tract infection until bronchiectasis developed. At 22 years old, computed tomography (CT) chest and abdomen as an investigation for lung infection revealed incidental findings of numerous nodular arterial-enhancing lesions in the liver and mild splenomegaly suggestive of NRH with portal hypertension. Seven months later, he developed sudden hypotension and tense bloody ascites. Emergency CT angiography of the abdomen showed NRH with intrahepatic hemorrhage and hemoperitoneum. Despite successful gel foam embolization, the patient died from prolonged shock and multiple organ failure. CONCLUSIONS: Although CVID patients with NRH are generally asymptomatic, late complications including portal hypertension, hepatic failure, and hepatic rupture could occur. Therefore, an evaluation of liver function should be included in the regular follow-up of CVID patients.

Clinical characteristics and aspirin desensitization in Thai patients with a suggestive history of NSAID-exacerbated respiratory disease.

BACKGROUND: Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is characterized by the triad of chronic rhinosinusitis with nasal polyp, asthma, and aspirin (ASA) or NSAID hypersensitivity. Previous study of NERD has rarely been reported in Asian population. OBJECTIVE: To investigate the clinical characteristics and outcomes of aspirin desensitization (ASAD) in Thai NERD. METHODS: This retrospective chart review included patients with a suggestive history of NERD with or without ASAD from the Adult Allergy Clinic of Siriraj Hospital (Bangkok, Thailand) during January 2008 to December 2018. RESULTS: Ten NERD patients were recruited. The median age of onset was 30 years. Comorbid atopic diseases were found in 4 patients. Asthma control level was step 3 of the Global Initiative for Asthma (GINA) guideline or greater in all patients. Five patients had reactions to more than one NSAIDs. Ibuprofen was the most common culprit agent. Reactions frequently involved the respiratory and cutaneous systems. Four patients underwent ASAD followed by ingestion of ASA 300-600 mg daily. One patient discontinued ASA after taking ASA 600 mg daily for 3 months due to severe gastrointestinal side effect. The remaining three patients successfully continued ASA 300 mg daily as maintenance to control sino-nasal inflammation and to prevent recurrence of nasal polyp. None of the 4 patients required sinus surgery revision. CONCLUSIONS: NERD is a difficult-to-treat disease with unique clinical characteristics. ASAD followed by a maintenance dose of ASA 300 mg daily was found to be effective and well-tolerated in most patients.

Guidelines for the management of asthma in adults: Evidence and recommendations.

The multidisciplinary experts in Thailand developed an asthma management recommendation that was relevant to low-middle income countries (LMICS). Populations level consideration about asthma management is emphasized. The healthcare systems, access to and availability of treatments as well as the asthma populations vary from country to country in LMICS. The feasibility in clinical practice for implementation is also a major issue. For these reasons, the practice guidelines that are relevant to local contexts are essential to improve better asthma control. Furthermore, integrative and collaboration between asthma experts and the public health sector to implement and discriminate such guidelines will help to achieve these challenging goals. The topics covered include the current asthma situation in Thailand and the Asia-Pacific region, the definition of asthma, asthma diagnosis, assessment of asthma patients, asthma treatment - both pharmacological and non-pharmacological, management of asthma exacerbation, management of asthma comorbidities, treatment of asthma in special conditions, severe and uncontrolled asthma, Thai alternative medicine and asthma, and asthma and coronavirus disease-19 (COVID-19).

Concomitant chronic spontaneous urticaria treatment might hinder the diagnosis of occupational latex-induced anaphylaxis: A case report.

BACKGROUND: Cutaneous manifestations of chronic spontaneous urticaria (CSU) are identical to type 1 hypersensitivity reactions. The daily occurrence of rash from occupational allergy could be misinterpreted as CSU exacerbation. OBJECTIVE: We aim to report a nurse with concomitant CSU suffering from latex-induced anaphylaxis. METHODS: Skin tests, specific IgE using ImmunoCAP, and gloves challenge were performed. RESULTS: A 27-year-old nurse with CSU suffered from several episodes of severe urticarial flare. H1-antihistamine up-dosing and oral corticosteroid burst were given. Unfortunately, she developed 3 episodes of anaphylaxis during her routine nursing care work on a medical ward, leading to allergist consultation. She had positive latex-specific IgE (6.86 kUA/L) and positive gloves challenge test. CONCLUSIONS: Concomitant CSU treatment might hinder the recognition of latex allergy by masking or delaying skin manifestations. IgE-mediated allergy should be suspected if there was a change in severity or frequency of previously controlled CSU or the presence of systemic symptoms.

Successful identification of culprit drugs of perioperative anaphylaxis by repeated skin testing after negative first skin tests in a patient with a long distant history of perioperative anaphylaxis.

BACKGROUND: Perioperative anaphylaxis is a severe immediate hypersensitivity reaction to drugs administered in immediate temporal association to surgical procedures. The European Academy of Allergy and Clinical Immunology recommends allergologic tests be performed within the golden period of between 1 and 4 months after the date of the event to avoid false negatives. Nonetheless, many obstacles prevent patients from receiving diagnostic tests within the recommended time frame. CASE PRESENTATION: A 39-year-old male with congenital glaucoma had a history of multiple episodes of perioperative anaphylaxis since the age of 1 year including generalized urticaria, bronchospasm, cyanosis, and hypotension. Because the sequence of events was unclear due to incomplete documentation of operations and the destruction of medical records, the allergists tested different perioperative drugs on the patient. Although the first test results were all negative, repeated tests at 6 weeks were positive for morphine and ketamine. We identified more than one causative drug at the second round of skin tests. Using recommended skin test concentrations, negative skin tests in 5 control subjects could support the validity of the second test. The patient underwent sinus surgery in the next 3 months after the second skin test using propofol, midazolam, sevoflurane, chlorhexidine, and cefazolin without any anaphylactic reactions. CONCLUSIONS: Repeated skin tests after negative results of the first tests may identify the causative drugs, thus providing optimal patient safety, and should be considered under the physician's discretion together with consideration of the severity of the allergic symptoms, time interval from last reactions, and the patient's consent.

CoronaVac COVID-19 Vaccine-Induced Anaphylaxis: Clinical Characteristics and Revaccination Outcomes.

Anaphylaxis to CoronaVac, an inactivated vaccine against COVID-19, is extremely rare. We report 12 cases of anaphylaxis after CoronaVac administration, focusing on clinical characteristics and management outcomes. Skin test and graded vaccine challenge were successfully performed in our cases and might be considered if an inactivated vaccine is the only remaining option.

Omega-5 and Gamma Gliadin are the Major Allergens in Adult-Onset IgE-Mediated Wheat Allergy: Results from Thai Cohort with Oral Food Challenge.

BACKGROUND: Various clinical patterns based on routes of sensitization and sensitized allergens are reported in adult-onset IgE-mediated wheat allergy. There is still a paucity of data on IgE-bound wheat allergen profiles in wheat challenge-proven adult-onset wheat allergic cases. Therefore, we aim to identify the major sensitized allergens in Thai adult-onset wheat allergic patients whose first symptom occurred after the age of 18 years despite previous tolerance. METHODS: This cross-sectional pilot study recruited patients from the Thai Adult-onset IgE-mediated Wheat Allergy Cohort (TAWAC). The sera of patients with mostly challenge-proven cases were selected for allergen study, including ImmunoCAP and IgE-bound gliadins along with glutenins profiles. The IgE-bound proteins were identified by liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). Direct binding of IgE to recombinant gliadin and glutenin was performed to confirm the results of immunoblot and LC-MS/MS. RESULTS: Eleven wheat-dependent exercise-induced anaphylaxis (WDEIA) and 4 typical wheat allergy (WA) patients were enrolled. Serum IgE from >50% of bound proteins had a molecular weight ranging from 35 to 55 kDa in both gliadin and glutenin extracts. Further, ELISA demonstrated that γ-gliadin and ω5-gliadin were the most important major allergens. Other major allergens include α/ß-gliadin, HMW glutenin, and possibly α-amylase inhibitor or LWM glutenin. Gamma-gliadin sensitization was found in all WA patients (4/4), while ω-5 gliadin was found in all WDEIA patients (11/11) from ELISA. CONCLUSION: Wheat γ-gliadin and ω-5 gliadin are major wheat allergens among adult-onset wheat allergy patients in Thailand. Component-resolved diagnosis using γ-gliadin might be helpful in high suspicion of wheat allergy.

As-Needed Versus Regular Use of Fluticasone Furoate Nasal Spray in Patients with Moderate to Severe, Persistent, Perennial Allergic Rhinitis: A Randomized Controlled Trial.

BACKGROUND: Using intranasal corticosteroid (INCS) regularly is recommended for treating perennial allergic rhinitis. However, no studies have evaluated "as-needed" use. OBJECTIVE: To compare the efficacy between as-needed and regular use of INCS in patients with moderate to severe perennial allergic rhinitis. METHODS: In a 6-week randomized controlled trial, participants were assigned to either fluticasone furoate (FF) nasal spray, (27.5 µg) 2 sprays once daily for 1 week, followed by as-needed use (FF-as-needed) for 5 more weeks or 2 sprays once daily for 6 weeks (FF-regular). The primary outcome was a change in the total nasal symptom score (TNSS). The secondary outcomes were the change in nasal peak inspiratory flow, Rhinoconjunctivitis Quality of Life-36 Questionnaire score, and cumulative FF dose. RESULTS: In total of 108 patients, 53 and 55 patients were randomized to the FF-as-needed and FF-regular group, respectively. The difference in mean change in TNSS between the 2 groups was not significant at week 6 (1.21 points; 95% CI, -0.08 to 2.49; P = .066). The FF-regular group tended toward a greater improvement in TNSS. The FF-regular group had a higher mean change in nasal peak inspiratory flow than the FF-as-needed group at week 6 (-19.21 L/min; 95% CI, -33.54 to -4.89; P = .009). Both groups had similar improvement in Rhinoconjunctivitis Quality of Life-36 Questionnaire. The mean cumulative FF dose in the FF-as-needed group was 51% that of the FF-regular group. CONCLUSIONS: Both as-needed and regular use of INCS had similar improvement in TNSS and RCQ-36 score in patients with perennial allergic rhinitis. As-needed use had half of INCS exposure of the regular use.

Clinical value of in vitro tests for the management of severe drug hypersensitivity reactions.

Drug hypersensitivity reactions (DHRs) occasionally present with severe cutaneous adverse reactions (SCARs) which result in a high risk of morbidity and mortality. Although SCARs are rare, the occurrence could lead to a significant increase in healthcare and economic burden, especially when more than one possible culprit drug is implicated. Therefore, the accurate identification of the culprit drug(s) is important for correct labeling and subsequent patient education and avoidance. To date, clinical evaluation using causality assessment has limitations because the assessment may be inaccurate due to the overlapping timelines when multiple drugs are initiated/continued. Moreover, drug provocation tests (DPTs) which is the gold standard in diagnosis, are contraindicated, and in vivo skin tests may also be associated with risks of triggering SCAR. The European Network for Drug Allergy recommended that in vitro tests, if available, should be performed before any in vivo tests. Basophil activation tests and lymphocyte transformation tests, could serve as reliable in vitro tests for both immediate and delayed-type DHR. Many academic medical centers with affiliated laboratory services offer these tests in the diagnostic evaluation of SCARs in clinical practice. This not only complements identification of the culprit drug(s), but may also be used to test for potentially non cross-reactive alternatives, hence avoiding DPTs. In this review, we summarize the roles of in vitro tests in identifying the culprit drug(s) in SCARs, issues with utilization and interpretation of test results, and our experience in clinical practice.

Successful Deferasirox Rechallenge and Treating Through Reaction in a Patient with Challenge-Proven Mild Immediate Reaction: A Case Report.

This is the first report of successful deferasirox administration, using graded challenge and treating through, in a patient with mild immediate hypersensitivity reaction. Beginning with drug graded challenges could indicate the eliciting dose and reaction severity which are important for the management plan in the next step. This approach could be a safe shortcut in a stable patient with a mild reaction and a long avoidance period.

Clinical Characteristics and Proposed Wheat-Cofactor Challenge Protocol with a High Diagnostic Yield in Adult-Onset IgE-Mediated Wheat Allergy.

BACKGROUND: IgE-mediated wheat allergy in adults can be childhood or adulthood onset. Adult-onset wheat allergy has been reported, but data on clinical characteristics and practical food challenge protocols are scarce. OBJECTIVE: We aimed to describe the clinical characteristics of adult-onset wheat allergy, laboratory results, and outcomes of a modified 3-day challenge protocol using a combination of aspirin, wheat, and exercise. PATIENTS AND METHODS: Patients with histories compatible with adult-onset wheat allergy were recruited from Siriraj Hospital, Thailand. Clinical history, skin prick tests (SPTs), and specific IgE (sIgE) levels were ascertained. Patients with no food challenge contraindications were asked to volunteer for wheat challenge. A modified 3-day protocol using 300 mg of acetylsalicylic acid, 60-75 g of wheat flour, and exercise was used for confirmatory diagnosis of conventional wheat allergy (WA) and wheat-dependent exercise-induced anaphylaxis (WDEIA). RESULTS: Thirty-three patients were recruited. The mean age of onset was 29.7 years (SD 10.5). SPTs yielded positivity rates of 9.1%, 84.8%, and 81.8% in commercial wheat, in-house gliadin, and in-house glutenin extracts, respectively. sIgE yielded a positivity rate of 61% and 88% in wheat and ω5-gliadin, respectively. Eighteen patients underwent oral wheat challenges. Of these, 17 patients (94.4%) had positive challenges leading to definite diagnoses of WA (35%), and WDEIA (65%). One WDEIA patient developed hypotensive anaphylaxis in the protocol. CONCLUSION: WDEIA was the most common phenotype. Our modified 3-day protocol could differentiate WA and WDEIA and yielded a high positivity rate (94.4%). It should be used cautiously as severe reactions can occur.