Description of allergic phenotype in patients with eosinophilic oesophagitis: management protocol proposal.

There is a profile of patient with eosinophilic oesophagitis and atopic background, marked by the existence of IgE-mediated sensitizations. Our aim is to report the observed sensitivities to environmental and food allergens and panallergens in patients with eosinophilic oesophagitis with atopic background as well as characterizing other markers or analytical parameters. We suspect that the prevalence of sensitization to panallergens will be high and this will probably be relevant in terms of the onset and clinical course of the disease. We collated clinical and analytical data from 160 adult patients with a reported diagnosis of eosinophilic oesophagitis. These patients were studied between 1 January 2012 and 31 December 2020. During an initial visit skin tests were performed with full batteries of routine aero-allergens and foodstuffs. Patients were subsequently referred for blood test and determination of specific IgE, blood count and total IgE (in all cases), as well as eosinophilic cation protein and IMMUNOISAC in the centres in which this was available. We were able to detect a broad spectrum of sensitizations to environmental, foodstuffs and panallergens. The most common allergic disease was rhinoconjuntivitis. The sensitizations observed to foodstuffs were atypical for the adult population and were not responsible for manifestations compatible with immediate allergy. An important percentage of patients presented seasonal worsening of choking symptoms. We should be able to identify patients with eosinophilic oesophagitis and atopic background. Identifying this phenomenon would enable giving dietary and environmental recommendations as well as more specific and effective treatments to our patients.

Eosinophilic Esophagitis: Review and Update.

Background: Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia. Probably, in a few years, EoE may no longer be considered a rare disease. Methods: This article discusses new aspects of the pathogenesis, symptoms, diagnosis, and treatment of EoE according to the last published guidelines. Results: The epidemiological studies indicate a multifactorial origin for EoE, where environmental and genetic factors take part. EoE affects both children and adults and it is frequently associated with atopic disease and IgE-mediated food allergies. In patients undergoing oral immunotherapy for desensitization from IgE-mediated food allergy the risk of developing EoE is 2.72%. Barrier dysfunction and T-helper 2 inflammation is considered to be pathogenetically important factors. There are different patterns of clinical presentation varying with age and can be masked by adaptation habits. Besides, symptoms do not usually correlate with histologic disease activity. The diagnostic criteria for EoE has evolved but mainly requires symptoms of esophageal dysfunction with histologic evidence of a peak value of at least 15 eosinophils per high-power field. Endoscopies have to be repeated in order to diagnose, monitor, and treat EoE. Treatment of EoE can be started either by drugs (PPIs and topical corticosteroids) or elimination diets. The multistage step-up elimination diet management approach of EoE is promising. Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment. Conclusions: Research in recent years has contributed to a better understanding of EoE's pathogenesis, genetic background, natural history, allergy workup, standardization in assessment of disease activity, evaluation of minimally invasive diagnostic tools, and new therapeutic approaches. However, several unmet needs are to be solved urgently, as finding a non-invasive disease-monitoring methods and biomarkers for routine practice, the development or new therapies, novel food allergy testing to detect triggering foods, drug, and doses required for initial therapy and safety issues with long-term maintenance therapy, amongst others. Besides, multidisciplinary management units of EoE, involving gastroenterologists, pediatricians, allergists, pathologists, dietitians, and ENT specialists are needed.

The Basophil Activation Test Can Be of Value for Diagnosing Immediate Allergic Reactions to Omeprazole.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly used to treat gastrointestinal diseases. Incidence of hypersensitivity reactions to PPIs has risen, likely because of increased consumption. Their diagnosis is difficult, with skin tests (STs) presenting low sensitivity, making it necessary to perform drug provocation tests (DPTs). The value of in vitro tests for the diagnosis of immediate reaction to PPI is unclear. OBJECTIVE: To analyze the diagnostic value of the basophil activation test (BAT) in a group of patients diagnosed with immediate allergy to omeprazole. METHODS: The study included 42 patients with confirmed immediate allergic reactions to omeprazole confirmed by positive ST results or DPT results and 22 age- and sex-matched subjects tolerant to PPIs. BAT was performed with omeprazole, pantoprazole, and lansoprazole using CD63 and CD203c as activation markers. RESULTS: ST sensitivity was 66.7% with a specificity of 100%. BAT using CD63 with a stimulation index of more than 2 as positive revealed a sensitivity of 73.8%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 66.7%. BAT was positive in 57.1% of patients with negative ST result, and thus by combining ST and BAT we can correctly diagnose 85.7% of patients with immediate allergy to omeprazole. CONCLUSION: BAT represents a complementary tool for inclusion in the allergological workup for patients allergic to omeprazole. When combined with ST, it can be of value to guide the clinician as to whether to perform a DPT.

Role of Histamine Release Test for the Evaluation of Patients with Immediate Hypersensitivity Reactions to Clavulanic Acid.

BACKGROUND: Immediate hypersensitivity reactions to clavulanic acid (CLV) seem to be on the increase. Diagnosis is mainly based on skin testing and the drug provocation test (DPT), procedures that are not risk free. The aim of this study was to evaluate whether the histamine release test (HRT) could help evaluate patients with selective hypersensitivity to CLV. METHODS: Eighteen patients with immediate selective hypersensitivity reactions to CLV (positive skin tests to CLV but negative to the major and minor determinants of benzylpenicillin and amoxicillin; negative DPT to benzylpenicillin and amoxicillin) and 21 controls with tolerance to CLV were included. Direct and passive HRT, using patient whole blood or 'IgE-stripped' donor blood sensitized by patient serum, respectively, were performed by stimulating the blood with CLV, and basophil histamine release was detected by fluorometric determination. RESULTS: The clinical symptoms were anaphylaxis (n = 6), urticaria (n = 9) and urticaria-angioedema (n = 3). The median time interval between the reaction and the study was 225 days (interquartile range, IQR: 120-387.5) and between drug intake and the development of symptoms 30 min (IQR: 6.25-30). We obtained similar data for both the direct and passive HRT, with a sensitivity and specificity of 55 and 85%, respectively, a positive predictive value of 76% and a negative predictive value of 69%. CONCLUSIONS: The sensitivity of both the direct and passive HRT for diagnosing patients with immediate allergy to CLV is less than 60%. However, the passive HRT has the advantage that it is based on the testing of serum samples that can be handled more easily than fresh blood samples.

Selective sensitization to Penicillin V with tolerance to other betalactams.

BACKGROUND: Penicillin G and V have the same betalactam ring. Penicillin V (phenoxymethylpenicillin) results from the substitution of the phenyl acetic acid of benzylpenicillin by the phenoxy methyl side chain. METHODS: Our patient was a 34-year-old man who experienced generalized urticaria after ingestion of Penicillin V. We performed skin prick tests and intradermal tests with a battery of betalactams including Penicillin V. We also determined specific IgE against penicillin V, penicillin G, amoxicillin, and ampicillin and performed a single-blind oral challenge with Penicillin V, amoxicillin, cefuroxime, and ceftazidime. RESULTS: The results of skin prick and intradermal tests with the betalactams included were negative. Specific IgE with betalactams was < 0.10 IU/L. The result of a single-blind oral challenge with Penicillin V was positive: 40 minutes after receiving 125 mg of Penicillin V, the patient presented generalized pruritus with hives on his back and chest. He tolerated oral administration of amoxicillin, cefuroxime, and ceftazidime. CONCLUSION: We report an exceptional case of sensitization to Penicillin V with negative results in the allergy workup. Diagnosis was based on a positive single-blind oral challenge result. The patient tolerated other betalactams. We provide a brief summary of the most relevant recent patents.

Paracetamol-induced fixed drug eruption at an unusual site.

BACKGROUND: Paracetamol (acetaminophen) is a widely used analgesic/antipyretic drug for which hypersensitivity reactions appear to be increasingly frequent. OBJECTIVE: We report the case of a woman who experienced several delayed selective reactions induced by paracetamol: fixed drug eruptions (FDEs) with typical features but an unusual distribution (hard palate and a maculopapular rash. METHODS: Skin tests: prick, intradermal and patch tests as well as a single-blind oral challenge test (OCT) were performed. RESULTS: Skin tests were negative. The OCT was necessary to confirm the diagnosis. Interestingly, the challenge test elicited an FDE-type lesion instead of a maculopapular rash. CONCLUSIONS: Our findings could reflect 2 different clinical patterns of delayed allergic reactions, or, more probably, the initial phase of a unique clinical entity that was stopped by the corticosteroids prescribed during the challenge. However, we were unable to confirm these hypotheses. The uncommon anatomical site of the lesions (hard palate) is noteworthy. Some relevant patents are also summarized in this paper.