Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset.

BACKGROUND: Amoxicillin-clavulanic acid (AX-CL) is the most consumed betalactam antibiotic worldwide. We aimed to establish the different phenotypes of betalactam allergy in those referring a reaction with AX-CL and to investigate the differences between immediate and non-immediate onset. METHODS: Cross-sectional retrospective study performed at Hospital Clínico San Carlos (HCSC) and Hospital Regional Universitario de Málaga (HRUM) in Spain. Patients reporting reactions with AX-CL who completed the allergy workup between 2017 and 2019 were included. Data of reported reaction and allergy workup were collected. Reactions were classified as immediate and non-immediate with 1hour cut-off point. RESULTS: We included 372 patients (HCSC 208, HRUM 164). There were 90 (24.2%) immediate, 252 (67.7%) non-immediate reactions, and 30 (8.1%) with unknown latency. Allergy to betalactams was ruled-out in 266 (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population were allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%) and to betalactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and non-immediate reactions respectively, with a relative risk of 5.06 (95%CI 3.64-7.02) of an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with late-positive intradermal test (IDT) to CL were diagnosed of CL allergy. CONCLUSION: Allergy diagnosis was confirmed in a minority of the whole study population, but 5 times more frequently in those reporting immediate reactions, making this classification useful in risk stratification. Late-positive IDT for CL has no diagnostic value and its late reading could be retrieved from the diagnosis work-up.

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization.

Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure.

Component-resolved diagnosis in hymenoptera allergy.

Component-resolved diagnosis based on the use of well-defined, properly characterised and purified natural and recombinant allergens constitutes a new approach in the diagnosis of venom allergy. Prospective readers may benefit from an up-to-date review on the allergens. The best characterised venom is that of Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of Vespula vulgaris have been identified and include phospholipase A1 (Ves v1), hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an increasing cause of allergy in Europe, although only few allergens have been identified in this venom. In this review, we evaluate the current knowledge about molecular diagnosis in hymenoptera venom allergy.

Key Issues in Hymenoptera Venom Allergy: An Update.

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

Clinical Practice Guidelines for Diagnosis and Management of Hypersensitivity Reactions to Contrast Media.

The objective of these guidelines is to ensure efficient and effective clinical practice. The panel of experts who produced this consensus document developed a research protocol based on a review of the literature. The prevalence of allergic reactions to iodinated contrast media (ICM) is estimated to be 1:170 000, that is, 0.05%-0.1% of patients undergoing radiologic studies with ICM (more than 75 million examinations per year worldwide). Hypersensitivity reactions can appear within the first hour after administration (immediate reactions) or from more than 1 hour to several days after administration (nonimmediate or delayed reactions). The risk factors for immediate reactions include poorly controlled bronchial asthma, concomitant medication (eg, angiotensin-converting enzyme inhibitors, ß-blockers, and proton-pump inhibitors), rapid administration of the ICM, mastocytosis, autoimmune diseases, and viral infections. The most common symptoms of immediate reactions are erythema and urticaria with or without angioedema, which appear in more than 70% of patients. Maculopapular rash is the most common skin feature of nonimmediate reactions (30%-90%). Skin and in vitro tests should be performed for diagnosis of both immediate and nonimmediate reactions. The ICM to be administered will therefore be chosen depending on the results of these tests, the ICM that induced the reaction (when known), the severity of the reaction, the availability of alternative ICM, and the information available on potential ICM cross-reactivity. Another type of contrast media, gadolinium derivatives, is used used for magnetic resonance imaging. Although rare, IgE-mediated reactions to gadolinium derivatives have been reported.

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

INTRODUCTION: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. MATERIALS AND METHODS: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. RESULTS: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. CONCLUSIONS: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

Longitudinal Validation of the Spanish Version of the Health-Related Quality of Life Questionnaire for Hymenoptera Venom Allergy (HRQLHA).

BACKGROUND AND OBJECTIVE: The Spanish version of the health-related quality of life questionnaire for allergy to hymenoptera venom (HRQLHA) has been shown to be reliable, internally consistent, and externally valid. The aim of this study was to complete the validation of the HRQLHA by analyzing its sensitivity to changes (longitudinal validity) using the sting challenge test (SCT) as the variable of change. PATIENTS AND METHODS: Patients over the age of 17 years with a systemic allergic reaction to Apis, Vespula, or Polistes venom were included during their first year of venom-specific immunotherapy. Patients were assigned to either a group that underwent the SCT or a control group that did not. All patients completed the HRQLHA at baseline and after a period of 2 to 4 months, during which time the SCT was performed in the active group, with no intervention in the control group. RESULTS: Fifty patients were included in the study: 25 in the SCT group and 25 in the control group. The patients in the SCT group showed a significant improvement in mean HRQLHA score (+0.35, P=.03) after the SCT, while those in the control group showed no significant changes in questionnaire scores. CONCLUSIONS: Our results demonstrate the sensitivity of the HRQLHA to changes and thus complete the longitudinal validation of the questionnaire. A well-tolerated SCT improves the quality of life of venom-allergic patients as it reduces anxiety associated with the fear of being stung.

Component-resolved diagnosis of vespid venom-allergic individuals: phospholipases and antigen 5s are necessary to identify Vespula or Polistes sensitization.

BACKGROUND: Cross-reactivity between hymenoptera species varies according to the different allergenic components of the venom. The true source of sensitization must therefore be established to ensure the efficacy of venom immunotherapy. OBJECTIVE: In the Mediterranean region, Polistes dominulus and Vespula spp. are clinically relevant cohabitating wasps. A panel of major vespid venom allergens was used to investigate whether serum-specific IgE (sIgE) could be used to distinguish sensitization to either vespid. METHODS: Fifty-nine individuals with allergic reactions to vespid stings and positive ImmunoCAP and/or intradermal tests to vespid venoms were studied. sIgE against recombinant and natural venom components from each wasp species was determined using the ADVIA Centaur(®) system. RESULTS: sIgE against recombinant antigen 5s sensitization to be detected in 52% of the patients tested (13/25). The sensitivity increased to 80% (20/25), when using natural antigen 5s, and to 100% with the complete panel of purified natural components, because the sIgE was positive to either the antigen 5s (Pol d 5/Ves v 5) or to the phospholipases (Pol d 1/Ves v 1) of the two vespids, or to both components at the same time. In 69% of cases, it was possible to define the most probable sensitizing insect, and in the rest, possible double sensitization could not be excluded. Vespula hyaluronidase was shown to have no additional value as regards the specificity of the assay. CONCLUSIONS: The major allergens of P. dominulus' and Vespula vulgaris' venom, namely phoshpholipases and antigen 5s, are required to discriminate the probable sensitizing species in vespid-allergic patients.

Urticaria due to antihistamines.

H1-antihistamines are probably the most frequently used drugs in allergic diseases, with widely established efficacy, tolerance, and safety. We report a patient with urticaria due to ingestion of ebastine and fexofenadine. Skin prick tests, patch tests, and basophil activation tests with the implicated drugs and antihistamines from other families were negative. The oral challenges with the implicated antihistamines and other antihistamines tested were positive, but the patient tolerated an oral challenge with cetirizine. We present a patient with urticaria induced by different antihistamines in whom the diagnosis was established by oral challenge. The mechanism of sensitization remains unclear.

Systemic dermatitis due to tetrazepam.

Cutaneous adverse reactions to benzodiazepines seem to be rare. We report a 61-year-old man with adverse reactions after ingestion of metamizole, diclofenac, and tetrazepam. Skin prick tests with metamizole, diclofenac, and tetrazepam were negative. Patch tests with metamizole, diclofenac, and tetrazepam (all at 5% in aqueous solution) were performed, and were positive for tetrazepam. Oral challenge was performed with metamizole, acetylsalicylic acid, diclofenac, and tetrazepam with a positive result for diclofenac and tetrazepam. The patient tolerated other benzodiazepines. We present a patient who can tolerate diazepam but who had a type IV hypersensitivity reaction to tetrazepam confirmed by patch testing and oral challenge. The patient also presented an immediate hypersensitivity reaction after taking diclofenac.