Correlation of anti-Pru p 3 IgE levels with severity of peach allergy reactions in children

BackgroundPeach allergy is regarded as one of the most important fresh fruit allergies. Data are available on the state-of-the-art diagnosis, including food challenges, and a component-resolved diagnosis. However, the roles played by different peach allergens with respect to symptom severity are not completely understood.ObjectiveTo evaluate the role of serum specific IgE to peach and recombinant allergens in the diagnosis of peach allergies in Italian children.MethodsForty-four children with peach allergy confirmed by a placebo-controlled food challenge were divided into 2 groups based on their symptom severity: patients with mild oral allergy syndrome (OAS) and patients with systemic symptoms (SS). The presence of specific IgE to peach and rPru p 1, rPru p 3, and rPru p 4 was determined.ResultsThe presence of specific IgE to Pru p 4 and Pru p 1 was found significantly more frequently in patients with OAS, whereas specific IgE to Pru p 3 was not found significantly more frequently in patients with SS. Only anti-rPru p 4 IgE levels were significantly higher in patients with OAS, whereas no significant differences were found in anti-rPru p 1 and anti-rPru p 3 IgE levels between patients with OAS compared with patients with SS.ConclusionIn Italian children with peach allergies, the presence of specific IgE to Pru p 3 is not associated with SS, and the levels of specific IgE to Pru p 3 do not correlate with the severity of the reactions.     

Induction of accelerated reactions to amoxicillin by T-cell effector mechanisms

BackgroundAlthough allergic drug reactions have been considered to be immediate (IgE mediated) or delayed (T-cell effector mechanisms), accelerated reactions have also been defined; however, they have not been sufficiently studied.ObjectiveTo study the mechanisms involved in accelerated reactions to amoxicillin.MethodsWe monitored the response in 3 patients who had an accelerated reaction to amoxicillin. A T-cell effector response was searched after a Drug Provocation Test. Symptoms were recorded after initiation of the reaction, and sequential samples were taken at different intervals after challenge. Skin biopsy specimens were also taken, and a lymphocyte transformation test (LTT) was performed.ResultsAfter the drug provocation test, all 3 patients had a positive response within 2 to 6 hours of drug administration, with full expression at 6 hours, requiring corticoids and antihistamine treatment. They had generalized erythema with facial angioedema but no cardiovascular or respiratory symptoms. Monitoring of the response revealed the presence in the skin of CD4 and CD8 lymphocytes with increased expression of homing and cell activation markers. Immunohistochemistry revealed a perivascular mononuclear cell infiltrate with activated CD4 and CD8 cells expressing perforin and granzyme B. No tryptase release was detected in either the affected tissue or the peripheral blood. The LTT result was positive in all 3 patients.ConclusionWe found that accelerated reactions to β-lactams are mediated by effector T cells. The increase in different T-cell markers and a positive LTT result to amoxicillin, in parallel with the occurrence of symptoms after challenge, support this mechanism.     

Facial thermography is a sensitive and specific method for assessing food challenge outcome

BACKGROUND: Oral challenge is widely used for diagnosing food allergy but variable interpretation of subjective symptoms may cause error. Facial thermography was evaluated as a novel, objective and sensitive indicator of challenge outcome. METHODS: A total of 24 children with a history of egg allergy underwent oral challenge, which were scored positive when objective symptoms occurred or negative after all doses were consumed without reaction. Facial temperatures were recorded at baseline and 10-min intervals. The difference between mean and baseline temperature (DeltaT), maximum DeltaT during challenge (DeltaT(max)) and area under curve of DeltaT against time (DeltaTAUC) were calculated for predefined nasal, oral and forehead areas, and related to objective challenge outcome. RESULTS: There were 13 positive and 11 negative challenges. Median nasal DeltaTAUC and DeltaT(max) were greater in positive compared with negative challenges (231- and 5-fold, respectively; P < 0.05). In positive challenges, nasal temperatures showed an early transient rise at 20 min, preceding objective symptoms at median 67 min. There was a sustained temperature increase from 60 min, which was reduced by antihistamines. A cut-off for nasal DeltaT(max) of 0.8 degrees C occurring within 20 min of the start of the challenge predicted outcome with 91% sensitivity (positive predictive value [PPV] 100%) and 100% specificity (negative predictive value [NPV] 93%). Subjective symptoms occurred in four of 13 positive and three of 11 negative challenges. CONCLUSIONS: Facial thermography consistently detects a significant early rise in nasal temperature during positive compared with negative food challenges, which is evident before objective symptoms occur. Thermography may therefore provide a sensitive method to determine outcome of food challenges and investigate the pathophysiology of food allergic reactions.     

Skin testing and drug challenge outcomes in antibiotic-allergic patients with immediate-type hypersensitivity

Background

The evaluation of antibiotic immediate-type hypersensitivity is intricate because of nonstandardized skin testing and challenge method variability.

Recent developments in drug hypersensitivity in children

ABSTRACT

Introduction: Drug allergy is an important public health problem that causes 0.4–10.3% of hospital admissions in children. The epidemiology, clinical spectrum, diagnosis, and management of drug hypersensitivity reactions (DHRs) differ in pediatric and adult patients. However, the same algorithms used in adults have often been applied in the pediatric population due to a lack of evidence in the literature.

Areas covered: In this review, we aimed to discuss recent developments in the area of pediatric DHRs based on the growing body of literature advancing our understanding of the epidemiology, clinical aspects, and diagnostic approaches to DHRs in children.

Expert opinion: Misdiagnosis, under-diagnosis, and self-diagnosis are common problems related to drug allergies in children. Viral infections are particularly frequent in children and make diagnosis difficult. Identifying true DHR is a key step in the management of drug allergy in children. Therefore, a complete allergy work-up with standardized drug allergy tests is necessary. In order to eliminate non-standardized tests, future studies including larger numbers of children should be conducted to determine more accurate standardized tests for diagnosing DHRs in the pediatric population.     

Clinical thresholds to egg, hazelnut, milk and peanut: results from a single-center study using standardized challenges

BackgroundLarge studies of individual thresholds and risk profiles for foods are sparse. Previous reports indicate that thresholds adjusted for the protein content in foods would be comparable.ObjectiveTo establish and compare clinical threshold values for egg, hazelnut, milk and peanut, and correlating them to severity of symptoms.MethodsSeven hundred eighty-one challenges were performed in 487 patients (age range, 0.5–73.5 years). Using interval censoring survival analysis, the dose distribution of thresholds was fitted to a log-normal function. Symptom score was correlated to thresholds.ResultsBased on the 405 challenges resulting in objective signs, similar distribution of thresholds for hazelnut, milk, and peanut challenges were found, whereas individuals with egg allergy were bimodally distributed with a high or a low threshold. Eliciting dose in 10% (95% confidence interval) was 42.9 (24-76.8) mg whole eggs, 133.8 (95.9–186.6) mg whole hazelnut, 106.5 (59.7–190.6) mg roasted peanut, and 2.9 (1.5–5.4) mL milk. Adults showed more severe symptoms and signs than children, and peanut caused more severe reactions than the 3 other foods.ConclusionThresholds for the different foods were not comparable, and eliciting dose for the 4 foods differed, even if adjusted for protein content. Increasing age but not a low threshold dose is associated with severe symptoms on challenge. Peanuts elicit more severe reactions than the other foods.     

Symptom Provocation During Aerobic and Dynamic Supervised Exercise Challenges in Adolescents With Sport-Related Concussion

ContextSupervised exercise challenges (SECs) have been shown to be safe and beneficial in the early symptomatic period after concussion. Thus far, most in-clinic SECs studied have included a form of basic aerobic exercise only. An SEC that also includes dynamic forms of exercise mimics all steps of a standard return-to-play progression and may enhance the detection of concussion symptoms to guide in-clinic management decisions.ObjectiveTo determine whether an SEC that includes a dynamic SEC (DSEC) uncovered symptoms that would not have been identified by an SEC involving an aerobic SEC (ASEC) alone in adolescent patients with sport-related concussion.DesignRetrospective case series.SettingMultidisciplinary sport concussion clinic at a tertiary care center.Patients or Other ParticipantsA total of 65 adolescent athletes (mean age = 14.9 ± 2.0 years, 72.3% males) who underwent an in-clinic SEC within 30 days of concussion.Main Outcome Measure(s)Presence of pre-exercise symptoms and symptom provocation during the SEC were recorded, with exercise-provoked symptoms categorized as occurring during ASEC or DSEC.ResultsOf the total patient sample, 69.2% (n = 45/65) experienced symptom provocation at some point during the SEC. Symptoms were provoked in 20 patients during the ASEC, whereas 25 completed the ASEC without symptom provocation before becoming symptomatic during the subsequent DSEC and 20 completed the SEC without any symptom provocation. Of the 65 patients in the total sample, 46 were asymptomatic immediately before the SEC. Of these previously asymptomatic patients, 23.9% (n = 11/46) experienced symptom provocation during the ASEC, and an additional 37.0% (n = 17/46) remained asymptomatic during the ASEC but then developed symptoms during the DSEC.ConclusionsThe ASEC alone may not detect symptom provocation in a significant proportion of concussion patients who otherwise would develop symptoms during a DSEC.     

When is an oral food challenge positive?

Oral food challenges still remain the gold standard in the diagnosis of food related symptoms and are performed to obtain a clear 'yes or no' response. However, this is often difficult to achieve, and so proposals may be appropriate for criteria on when to stop oral food challenges. In daily practice it makes sense to challenge until clear objective symptoms occur without harming the patient. Clinical symptoms should be objective and/or: (a) severe or (b) reproducible or (c) persisting. A sensitive parameter for a beginning clinical reaction is a general change of mood. The sooner symptoms appear, the more likely they are to represent a 'true' positive reaction and the more organ systems are involved the easier it is to assess an oral food challenge as positive. In the case of subjective symptoms, the number of placebo doses should be increased. In unclear situations, the observation time until the next dose should be prolonged or the same dose repeated. Transient objective clinical symptoms usually end up in a positive challenge result. There are a number of causes for false positive and false negative challenge results, which should be considered. The aim of all oral challenge testing should be to hold the balance between two conflicting aspects: on the one hand the need to achieve clear and justified results from oral food challenges in order to avoid unnecessary diets, and on the other hand to protect patients from any harm caused by high doses of a potentially dangerous food.     

Allergic diseases in the elderly population: a single-center experience

Background/aim Although allergic diseases are generally considered to be diseases of childhood and youth, the first symptoms of allergic diseases can be seen in old age sometimes. The aim of this study was to determine the prevalence and characteristics of allergic diseases in the elderly population admitted to the allergy unit on an outpatient basis.Materials and methods The files of the patients who applied to our clinic’s allergy unit during the 8-year period were retrospectively analyzed. The data of patients aged ≥ 65 years were obtained from the files of our allergy unit archive.ResultsA total of 1272 patients aged ≥ 65 years old were included in the study. The mean age was 70 years (range: 65–97 years). Most of the patients were female (n = 704, 55.3%). Of the patients, 887 (69.8%) presented with cutaneous symptoms, and urticaria was identified in 500 of them (56.3%). Drug hypersensitivity reactions were detected in 175 (13.7%) patients. A total of 71 (5.6%) patients had asthma, 65 (5.1%) had anaphylaxis, 48 (3.8%) had allergic rhinitis, 24 (1.9%) had hymenoptera venom allergy, and 18 (1.4%) had food allergies.Atopy history (OR = 2.323, 95% CI = 1.590–3.393, p < 0.001) and comorbidity (OR = 1.631, 95% CI = 1.050–2.533, p = 0.029) were found to be risk factors for drug hypersensitivity reactions. Male sex (OR = 3.462, 95% CI = 1.097–10.933, p = 0.034) and atopy history (OR = 14.877, 95% CI = 6.081–36.393, p < 0.001) were found to be risk factors for hymenoptera venom allergy.ConclusionDiagnosis becomes difficult due to the perception that allergic diseases mainly affect young people. Clinical symptoms are not evident in the elderly and age-related difficulties are encountered in diagnostic tests. There is a need to develop specific guidelines for the diagnosis of allergic diseases in the elderly.     

Hypersensitivity to tetracyclines: Skin testing,graded challenge,and desensitization regimens

BackgroundHypersensitivity reactions (HSRs) to tetracyclines and the related compound, tigecycline, can limit the use of these medications and compromise optimal patient care. Despite this, there is little discussion in the literature describing the presentation of these reactions or guiding clinicians on the management of these reactions in adult and pediatric patients.ObjectiveTo describe the clinical features, optimal diagnostic approach, and management of HSRs to tetracyclines.MethodsPatients with reactions to tetracyclines at our institution from 2011 to 2019 were identified by retrospective chart review. Skin testing protocols were designed for each antibiotic. Graded challenge and desensitization procedures were devised based on medical history, skin testing results when available, and need for readministration.ResultsThe HSRs to tetracyclines, their workup, and management are described for 10 patients, aged 7 to 68 years. Our skin testing protocols for doxycycline, minocycline, and tigecycline described herein had good negative predictive value. When skin testing was negative and the initial reaction was not severe, graded challenge to the culprit drug was performed. Using the included procedures, 3 patients were desensitized to oral doxycycline, 3 to oral minocycline, and 2 to intravenous tigecycline. All the desensitizations were successful.ConclusionOnce identified, HSRs to tetracyclines can be further evaluated with skin testing and graded challenge and managed in appropriate cases with desensitization. These procedures can facilitate first-line therapy for patients who require tetracyclines but developed hypersensitivity reactions.     

The negative predictive value of 5-day drug provocation test in nonimmediate beta-lactam allergy in children

BackgroundExtending the drug provocation test (DPT) period is recommended for patients with suspected nonimmediate beta-lactam antibiotic (BLA) allergy and negative DPT. No consensus has been reached regarding the duration of prolonged provocation.ObjectiveWe aimed to determine the negative predictive value (NPV) of the 5-day extended DPT.MethodsParents of patients with suspected nonimmediate mild cutaneous reactions with BLAs who had been subjected to 5-day DPT with culprit drugs were questioned by telephone interview about reexposure to the tested drug. Patients with reported reaction during reexposure were reevaluated. Skin tests and serum-specific immunoglobulin E (IgE) analysis were not performed before first DPT.ResultsA total of 355 patients had negative results in 5-day DPT. The median age at DPT was 4.2 years, and 52.9% were male. The families of 255 patients (72%) could be contacted. Of these 255 patients, 179 (70%) had used the same drug, and reactions were reported for 6 (3.4%) of those patients, who were subsequently reevaluated. Five of the 6 patients had DPT with amoxicillin-clavulanate and 1 with cefixime. When detailed history was taken, 2 of the 5 patients with amoxicillin-clavulanate reaction were found to have used the drug unintentionally after their reaction to reexposure and did not have any symptoms. One of the patients underwent allergy workup and tested negative, and the other 2 refused the test. The patient with reported cefixime reaction underwent repeated allergy workup and tested negative. Therefore, the NPV of 5-day prolonged DPT was 98.9%.ConclusionThe 5-day prolonged DPT has high NPV and seems appropriate in duration for children with suspected nonimmediate-BLA allergy.     

Wheat allergy: a double-blind, placebo-controlled study in adults

BACKGROUND: Wheat is believed to be an uncommon cause of food allergy in adults; the number of studies that address IgE mediated wheat allergy in adults is all too few. OBJECTIVE: Determine how many subjects with a history of wheat allergy have real allergy by double-blind, placebo-controlled food challenge; identify the symptoms manifested during the challenge; determine the lowest provocation dose; determine the performance characteristics of wheat skin prick test and specific IgE; identify subjects with real wheat allergy for potential immunoblotting studies. METHODS: Patients underwent skin test with commercial wheat extract; specific wheat IgE was determined. Subjects were challenged with 25 g wheat. Subjects who were positive to raw wheat challenge underwent cooked wheat challenge. RESULTS: Thirty-seven double-blind placebo-controlled wheat challenges were performed on 27 patients. A total of 13 of 27 (48%) patients had a positive result. Eleven subjects with positive raw wheat challenge underwent cooked wheat challenge: 10 were positive. The provocation dose range was 0.1 to 25 g. Twenty-seven percent of the subjects allergic to wheat had a provocation dose that was < or =1.6 g. CONCLUSION: Wheat causes real food allergy in adults. More than a quarter of the patients allergic to wheat reacted to less than 1.6 g wheat. Specific IgE was more sensitive than skin test for wheat; however, specificity and predictive values were low for both tests. Thus, these tests should not be used to validate diagnosis of wheat allergy.     

Mast cell hyperplasia induced by multiple challenge with cedar pollen in sensitised guinea pigs

Objective and design: Because immediate aller gic symptoms are aggravated by repetitive antigen challenges in a guinea pig model of Japanese cedar pollen-induced conjunctivitis, we determined whether conjunctival mast cells are different in number between the acute and chronic stages. Methods: Sensitised guinea pigs were challenged by dropping a pollen suspension into their eyes once a week. Conjunctival tissue sections were stained with toluidine blue. Ophthalmic lavage was performed to assay for mast cell mediators. Results: At the 20th and 40th challenges, the number of mast cells increased by 4- to 5-fold compared with the 1st challenge. Although mast cell degranulation was insignificant 10 min after the 1st challenge, the 20th and 40th challenges produced significant degranulation. After multiple challenges, the amount of histamine and tryptase-like activity in the lavage fluid was dramatically increased. Conclusion: Increased mast cells are associated with aggravated symptoms. Mast cell mediators may be involved in pathogenesis at the chronic stage. Received 26 April 2005; returned for revision 6 June 2005; returned for fnal revision 16 June 2005; accepted by A. Falus 23 June 2005     

Prevention of nonsteroidal inflammatory drug-induced urticaria and/or angioedema

BackgroundUrticaria and/or angioedema (U/AE) are the most frequent and less severe forms of nonallergic hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Management of NSAID-induced U/AE includes (1) the avoidance of the culprit drug and of cyclooxygenase (COX) 1 inhibitors, (2) the use of weak COX-2 inhibitors, and/or (3) desensitization to aspirin. Because these possibilities may have drawbacks, we tested the possibility of preventing NSAID-induced U/AE by the administration of antihistamines and/or a combination of antihistamines and leukotriene antagonists.ObjectiveTo test the preventive effect of antihistamines and/or leukotriene antagonists on the development of U/AE in patients with a history of NSAID hypersensitivity confirmed by a positive challenge result.MethodsA single, placebo-controlled, oral challenge using the culprit NSAID was applied to 65 patients with a history of NSAID-induced U/AE. In the case of recurrence of the symptoms, another oral challenge was performed under premedication with antihistamines alone or combined antihistamines and leukotriene antagonists.ResultsA total of 59 of 65 patients (90%) tolerated a normal dose of NSAID, confirming previous data on the poor reproducibility of nonallergic hypersensitivity reactions to NSAIDs on challenge. Of the 6 patients who experienced recurrence of the U/AE on NSAID challenge, antihistamines and combined antihistamines and leukotriene antagonists prevented the hypersensitivity reactions in 2 and 3 of them, respectively. Only 1 patient still developed a moderate NSAID-induced urticaria despite the double premedication.ConclusionTreatment with NSAIDs at normal doses is possible and well tolerated in patients who have experienced NSAID-induced U/AE, which could be prevented by the concomitant use of antihistamines and leukotriene antagonists.     

Immune Tolerance to Drugs. I. Long-Term Tolerability of Rokitamycin in Patients with Antibiotics Hypersensitivity

Macrolides are considered one of the safest anti-infective groups in clinical use and are well-tolerated as alternative antibiotics in patients with a previous adverse reaction to other classes of antibiotics. However there is scarce information in the literature about their long-term tolerability. The present study was performed to determine whether the results of a challenge test with rokitamycin could predict the response to ingestion of rokitamycin during illness. The study was carried out on 335 patients, who experienced adverse reactions to one or more antibiotics. All patients received peroral challenges with rokitamycin (granules or capsules). On the first day patients received a number of placebo doses equivalent to the rokitamycin doses. One week later, the test was administered by increasing doses of rokitamycin at 60 min intervals until the common daily therapeutic dose of 406.25 mg was reached (31.25-93.75-125-156.25 mg). A questionnaire was distributed to all subjects. In particular, subjects were asked to clarify any reactive symptom they had developed after ingestion of the drug. It was found that only 3.1% (4/129) of subjects, who used this drug, reported adverse reactions: three experienced urticaria/angioedema and one patient experienced erythema multiforme during treatment. This study, points out a low percentage of adverse reactions to rokitamycin after a negative challenge test, thus, emphasizing both safety and good predictive value as a challenge test.     

Challenges faced by families of critically ill patients during the first wave of the COVID-19 pandemic

ObjectiveTo understand how surrogates of critically ill patients adjusted to challenges that resulted from the COVID-19 pandemic.MethodsParticipants (N = 62) were surrogates of critically ill adults with COVID-19 in the ICU at an urban, academic medical center from March to June 2020. Participants were recruited using convenience sampling and took part in one-time qualitative individual interviews via telephone. Qualitative data were analyzed using thematic content analysis.ResultsQualitative analyses yielded four types of challenges: Communication with the medical team, communication among family members, understanding and tracking medical information, and distress related to visitor restrictions. To adjust to challenges related to communication, participants developed routines for receiving updates from the medical team and providing updates to other family members. To adjust to the challenge related to comprehension, participants sought information from external sources such as family members in healthcare fields. To adjust to the challenge related to visitation, participants found some comfort in video calls with the patient.ConclusionsSurrogates of critically ill patients with COVID-19 faced multiple types of challenges yet adjusted to those challenges.Practical ImplicationsFuture research should focus on ways to support the wellbeing of surrogates during times of restricted hospital visitation.Clinical trial registered at ClinicalTrials.gov (NCT03969810).