Diagnosis Of Hypersensitivity Research Articles

Outcomes of office-based, open food challenges in the management of food allergy

This letter reports the largest series of open oral food challenges in the literature to date. It describes the feasibility and utility of oral food challenge, further justifying its use in the everyday practice of allergy.

Hypersensitivity to Hymenoptera Venom: Advances in Diagnosis and Implications for Treatment

Diagnosis and treatment of hypersensitivity to Hymenoptera venom took a landmark step forward in the late 1970s with the introduction of venom as an adequate material instead of whole body extracts. Since then, venom immunotherapy (VIT) has provided allergic subjects with a complete protection from fatal anaphylaxis and prevented about 90% of all reactions to stings. The cross-reactivity among some venom components, particularly important in the case of cross-reacting carbohydrate determinants, has often made it difficult to recognize the true causative venom to be used in VIT. Recently, the introduction of purified and recombinant allergens, such as Api m 1 from honeybee venom, Ves v 5 from yellow jacket venom, and Pol d 5 from wasp venom, have allowed a more precise diagnosis with identification of the causative venom component. This paves the way for a patient-tailored VIT in the near future. Another issue which needs to be addressed is the improvement in the safety of VIT with honeybee venom, which is significantly less favourable in comparison to vespid venom. A number of molecular approaches are under investigation in order to achieve this objective. Alternative routes of administration, such as the sublingual and the intralymphatic, have also been proposed, but there are not yet sufficient data available to demonstrate their feasibility. This review also presents patents on new trends in therapies for the management of hypersensitivity to hymenoptera venom.

Dentin Hypersensitivity: Recent Concepts in Management

Tooth sensitivity is a very common clinical presentation which can cause considerable concern for patients. Dentin hypersensitivity (DH) is characterized by short sharp pain arising from exposed dentin in response to stimuli. The most widely accepted theory of how the pain occurs is Brannstrom’s hydrodynamic theory, fluid movement within the dentinal tubules. The condition generally involves the facial surfaces of teeth near the cervical aspect and is very common in premolars and canines. This condition is frequently encountered by dentists, periodontists, hygienists and dental therapists. Some dental professionals lack confidence in treating DH. The management of this condition requires a good understanding of the complexity of the problem, as well as the variety of treatments available. This review considers the etiopathogenesis, incidence, diagnosis, prevention and management of dentinal hypersensitivity. DH is diagnosed after elimination of other possible causes of the pain. Any treatment plan for DH should include identifying and eliminating predisposing etiologic factors. Professionals should appreciate the role causative factors play in localizing and initiating hypersensitive lesions. It is important to identify these factors so that prevention can be included in the treatment plan. Treatments can be self-administered by the patient at home or be applied by a dental professional in the dental office. At-home methods tend to be simple and inexpensive and can treat simultaneously generalized DH affecting many teeth. Desensitizing treatment should be delivered systematically, beginning with prevention and at-home treatments. The latter may be supplemented with in-office modalities.

Outpatient Aspirin Desensitization for Patients With Aspirin Hypersensitivity and Cardiac Disease

Cardiac disease is common and often treated with aspirin therapy. Patients who develop an immunoglobulin E (IgE) hypersensitivity reaction to aspirin must abort treatment and receive alternative antithrombotic agents. Aspirin desensitization is a therapeutic procedure that may allow patients with a history of hypersensitivity to safely resume aspirin treatment. A variety of inpatient desensitization protocols have been published for IgE-mediated reactions, but outpatient regimens have not been previously reported. We aimed to determine the efficacy and safety of a multiday outpatient aspirin desensitization protocol for patients with an IgE-mediated aspirin hypersensitivity. We retrospectively assessed the efficacy of a multidose aspirin desensitization protocol performed in a university allergy-immunology clinic between July 2006 and December 2009. Patients were referred for a diagnosis of aspirin hypersensitivity and required aspirin for cardiac disease treatment. The protocol involved 10 or 12 aspirin doses depending on the final dose of 81 or 325 mg. Patients were desensitized over 2 to 3 half-days and were able to return home in between desensitization sessions. A total of 9 patients with cardiac disease and aspirin hypersensitivity underwent an outpatient multiday aspirin desensitization. Eight patients (89%) were successfully desensitized and 1 patient declined to continue with further desensitization. No adverse reactions requiring inpatient hospital care occurred during desensitization. This novel outpatient multiday aspirin desensitization protocol was a safe and effective approach for the treatment of aspirin hypersensitivity in patients with cardiac disease who require aspirin therapy. This flexible protocol is convenient for patients by avoiding hospital admission and full-day time commitments.

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA# and GA2LEN/HANNA*

Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs.

Use of Basophil Activation Test in a Case of Oxaliplatin ypersensitivity

Up to now, oxaliplatin hypersensitivity diagnosis relies upon an evocative clinical history and a confirmation by skin tests, especially intradermal tests. We report here a case of anaphylactic reaction to oxaliplatin. Besides the usual in vivo tests, we applied the basophil activation test (BAT) to confirm the diagnosis. Concordance between BAT and skin tests results suggests the usefulness of the in vitro test as diagnostic tool in drugs hypersensitivity. Further studies will be required to standardize BAT in this indication.

Assessing potential determinants of positive provocation tests in subjects with NSAID hypersensitivity

Provocation tests (PTs) with the suspected compounds are considered the 'gold standard' for establishing or excluding a diagnosis of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). However, only a few studies have evaluated the potential determinants of positive responses to PTs. The aims of this study are to assess the reliability of clinical histories as indicators of NSAID hypersensitivity, as well as the risk factors for a positive PT. Two hundred and seventy-five subjects with an unequivocal history of NSAID hypersensitivity reactions underwent PTs with the suspected drugs. To establish the potential determinants of positive PTs, we examined the following variables: gender, age at the time of reaction (<40 or ≥40 years), family and personal histories of atopy, patients who had reacted to one or more NSAIDs, time interval between drug intake and symptom onset (immediate or non-immediate reactions), time interval between the last drug reaction and the allergologic examination (≤12 or >12 months), and inclusion in a category of the Stevenson et al. classification. Two hundred and fourteen (77.8%) subjects tolerated the suspected drugs and 61 (22.2%) reacted. Age <40 years, male gender, immediate reactions, and time interval ≤12 months were significant risk factors for a positive PT. Our study confirms that clinical histories are not reliable tools for diagnosing NSAID hypersensitivity. Therefore, we recommend that suspected cases should undergo drug PTs. However, further studies on large samples of NSAID-sensitive patients are necessary to establish the risk factors that allow the number of candidates for PTs to be reduced.

475 Allergy to Oral Macrolides Antibiotics in Children

Background: Allergic or pseudo-allergic reactions to macrolides antibiotics are relatively uncommon (0.4-3% of treatments). The allergological work-up for the diagnosis of macrolides hypersensitivity is undefined. Methods: In our study we analyzed 95 children with history of macrolides reactions. Skin tests were performed according to EAACI guidelines by prick tests (PT) followed by intradermal test (ID) with the culprit drug. Oral Double Blind Provocation Tests (ODBPT) were performed in order to exclude or confirm a real state of drug hypersensitivity and to check the cross-reactivity. Results: 46 females and 49 males (mean age 6.2 years) described a total of 102 reactions to macrolides (28 immediate and 70 late). The most frequently involved drug was clarithromycin (69.6%). It mainly provoked mucocutaneous eruptions. All the children with suspected clarithromycin allergy underwent the ODBPT, but the diagnosis was confirmed in the 6.25% of cases and they all tolerated an alternative macrolidic drug. Azythromycin resulted less frequently involved (19,6%) but it caused the more severe reactions. The two patients (50% of those with history of immediate reactions) with anaphylaxis to azythromycin had positive skin tests with the culprit drug, however they both tolerated clarithromycin. Conclusion: Clarithromycin even being the most common cause of allergic reactions, it usually provokes mild cutaneous flares and a real state of hypersensitivity is rarely proven. On the contrary, azythromycin rarely resulted as cause of drug reactions but when it occurs these are severe. At last even in case of anaphylaxis allergy to macrolides seems not to be a class allergy.

Treating Dentin Hypersensitivity

Methods used by dental practitioners to diagnose and treat dentin hypersensitivity are not well documented. The authors conducted a survey of dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) to ascertain the treatment methods they used. Methods. Via an Internet survey, the authors collected data regarding methods used for diagnosis and treatment of dentin hypersensitivity from 209 Northwest PRECEDENT dentists. The PRECEDENT dentists indicated that they most often used fluoride varnishes and gels, advice regarding toothbrushing and diet, bonding agents, restorative materials and glutaraldehyde/2-hydroxyethyl methacrylate (HEMA) to treat dentin hypersensitivity. They reported that the most successful treatments were fluorides, glutaraldehyde/HEMA, bonding agents, potassium nitrates and restorative treatments; they considered observation, advice regarding toothbrushing and diet and laser therapy to be the least successful. Dentists listed fluorides, calcium phosphates, glutaraldehyde/HEMA and bonding agents as the treatments most desirable for inclusion in a future randomized clinical trial of dental hypersensitivity treatments. Dentists rely on patients to assess the severity of dentin hypersensitivity. Modalities for the diagnosis and treatment of hypersensitivity are diverse. Methods used to diagnose and treat dentin hypersensitivity in practice are challenging to justify. Practitioners should be aware of the diversity of methods available for diagnosing and treating dentin hypersensitivity as they manage the care of their patients with this condition.

Patch testing in drug allergy

The review intends to clarify understanding of when and how skin patch tests can be used to help drug allergy diagnosis and identify causally relevant drugs. It aims to give an understanding of which clinical patterns of drug reaction are produced by T-lymphocyte-mediated pathomechanisms since these are what are detected by patch tests. It also covers fundamental principles underlying patch test methodology and summarizes clinical patterns and causal drugs for which patch tests have reasonable value to diagnose culprit drugs. A number of recent studies have consolidated evidence that the use of patch tests in drug hypersensitivity diagnosis is not a robust science. The field is bedeviled by the lack of standardized approach to ascertain and define clinical entities in a sufficiently clear way that allows researchers to be confident that patch tests are used appropriately in T-cell-mediated clinical conditions. The literature is confounded by case series including patch tests from conditions which may be the wrong type of test causing the sensitivity of the test system to be measured incorrectly. For certain drug eruptions mediated by T cells (exanthemata, acute generalized exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, erythema multiforme/toxic epidermal necrolysis, fixed drug eruption and symmetrical drug-related intertriginous and flexural exanthem) patch tests can elicit positive responses in a proportion of cases. The test works best with aromatic anticonvulsants and various antibiotics but does not appear to work consistently with a wide range of drugs. A coordinated and systematic research effort is required to resolve inconsistencies to encourage greater utilization of this potentially important diagnostic methodology.

Dentine hypersensitivity – Australian dentists’ perspective

Dentine hypersensitivity is a frequent clinical presentation though inadequately comprehended by dentists. The objective of this study was to describe Australian dentists' perception on the occurrence, predisposing factors, triggers, diagnosis and management of dentine hypersensitivity. Eight hundred dentists were randomly selected using the Australian Dental Association membership list and invited to participate in a questionnaire-based survey. Out of 295 responding dentists, 284 private practitioners were included in the final analysis. Most dentists perceived that the occurrence of dentine hypersensitivity was <20% and commonest among 30-49 year olds. According to them, abrasion and gingival recession were the main predisposing factors whilst cold stimuli were the commonest trigger. A differential diagnosis-based approach was adopted by a majority to diagnose dentine hypersensitivity although routine screening was resorted to by a few. Most dentists were aware of the current mechanisms underlying dentine hypersensitivity whereas the majority perceived that ongoing predisposing factors was the main reason for dentine tubules to remain exposed. The commonest management strategy employed by most dentists was to prescribe desensitizing agents for home use. Australian dentists' perception of dentine hypersensitivity is generally consistent with the current scientific consensus on this subject.

Role of minor determinants of amoxicillin in the diagnosis of immediate allergic reactions to amoxicillin

Skin testing of subjects with immediate hypersensitivity to amoxicillin is performed using major and minor determinants of benzylpenicillin plus amoxicillin. However, sensitivity is not optimal, and other determinants need to be considered. We assessed the sensitivity of stable, well-characterized minor determinants of amoxicillin in subjects with immediate allergic reactions to amoxicillin to improve skin test sensitivity. Amoxicillin, amoxicilloic acid, and diketopiperazine were prepared and characterized by reverse-phase HPLC, tested in vivo by skin testing and in vitro by basophil activation test and RAST inhibition assay. Patients with immediate hypersensitivity to amoxicillin were selected: Group A (n = 32), skin test positive just to amoxicillin; Group B (n = 19), skin test positive to benzylpenicillin determinants; Group C (n = 10), skin test negative and amoxicillin drug provocation test positive. In Group A, 27 subjects (81.8%) were skin test positive to amoxicillin, ten (30.3%) to amoxicilloic acid, two (6.1%) to diketopiperacine, and six (18.2%) negative. In Group B, nine (50%) were positive to amoxicillin, eight (42.1%) to amoxicilloic acid, none to diketopiperacine, and nine (50%) negative. In Group C, skin tests were negative. BAT was positive to amoxicillin in 26 patients (50.9%), to amoxicilloic acid in 15 (29.1%), and diketopiperazine in four (7.8%). RAST inhibition studies showed > 50% inhibition in all sera, with the highest concentration of amoxicillin and amoxicilloic acid. The combination of minor determinants of amoxicillin, amoxicilloic acid, and diketopiperazine seems to be of no greater value than the use of amoxicillin alone. Further efforts are needed to find new structures to improve sensitivity in the diagnosis of immediate hypersensitivity to betalactams.

Article Commentary: A Cytological Assay for Diagnosis of Food Hypersensitivity in Patients With Irritable Bowel Syndrome

Article Commentary: A Cytological Assay for Diagnosis of Food Hypersensitivity in Patients With Irritable Bowel Syndrome

Acoustic Rhinometry in the Evaluation of Nasal Lysine Aspirin Challenge

Nasal lysine aspirin (Lys-ASA) challenge is an alternative to oral and bronchial challenges in the diagnosis of aspirin (ASA) hypersensitivity. The aim of the study was to evaluate the acoustic rhinometry as an objective method of assessment of Lys-ASA nasal challenge. Twenty patients with aspirin induced asthma (ASA-S) and 10 controls (ASA-NS group: 5 patients with allergic rhinitis and 5 healthy subjects) were included. Nasal challenge was performed with placebo (saline) and 14.4 mg of Lys-ASA introduced as aerosol to both nostrils (total dose: 16 mg of acetylsalicylic acid). Measurements of nasal volume bilaterally were performed with the use of acoustic rhinometer before and 1, 2, 4 and 24 hours after the challenge. For further analysis the sum of both nasal cavities volume at the level of 2 to 5 cm from nostrils was used. Mean total bilateral volume in ASA-S group after placebo was: 7.74, 6.21, 7.11, 7.12, 7.24 cm(3) and 7.24, 5.77, 6.31, 6.27, 6.98 cm(3) after Lys-ASA (before and after 1, 2, 4 and 24 hours, respectively; p = 0,048 and p = 0,02, in 2nd and 4th hour, Lys-ASA v. placebo, Wilcoxon's test). With cut off point of nasal volume decrease by 10% in the 1st hour the sensitivity of the test was 70%, specificity 60%, positive predictive value 77.78% and negative predictive value 50%. In conclusion, acoustic rhinometry with measurement of nasal cavities volume changes at 2 to 5 cm from nostrils does not appear to be sufficiently sensitive and specific as a single method for evaluation of studied challenge method.

Clinical laboratory assessment of immediate-type hypersensitivity

Clinical laboratory analyses aid in the diagnosis and management of human allergic (IgE-dependent) diseases. Diagnosis of immediate-type hypersensitivity begins with a thorough clinical history and physical examination. Once symptoms compatible with an allergic disorder have been identified, a skin test, blood test, or both for allergen-specific IgE antibodies provide confirmation of sensitization, which strengthens the diagnosis. Skin testing provides a biologically relevant immediate-type hypersensitivity response with resultant wheal-and-flare reactions within 15 minutes of allergen application. Allergen-specific IgE antibody in serum is quantified by using 3 laboratory-based autoanalyzers (ImmunoCAP, Immulite, and HYTEC-288) and novel microarray and lateral-flow immunoassays. Technologic advances in serologic allergen-specific IgE measurements have involved increased automation, with enhanced reproducibility, greater quantification, lower analytic sensitivity, and component-supplemented extract-based allergen use. In vivo provocation tests involving inhalation, ingestion, or injection of allergens serve to clarify discordant history and skin- or blood-based measures of sensitization. Other diagnostic allergy laboratory analyses include total and free serum IgE measurement, precipitating IgG antibodies specific for organic dusts, mast cell tryptase, and indicator allergen analyses to assess indoor environments to promote patient-targeted allergen avoidance programs. A critique is provided on the predictive utility of serologic measures of specific IgE for food allergy and asthma. Reasons for the lack of clinical utility for food-specific IgG/IgG4 measurements in allergy diagnosis are examined. When the specific IgE measures are inconsistent with the clinical history, they should be confirmed by means of repeat and alternative method analysis. Ultimately, the patient's clinical history remains the principal arbiter that determines the final diagnosis of allergic disease.

Hipersensibilidade alimentar em cães

Realizou-se um estudo retro e prospectivo em 117 cães com prontuários suspeitos de apresentarem hipersensibilidade alimentar. Os animais foram distribuídos em dois grupos: os do grupo I (n=86) foram atendidos em 1993 e 1994 e os do grupo II (n=31) em 1995. Os cães de ambos os grupos foram caracterizados quanto aos aspectos epidemiológicos e clínicos. Os do grupo II foram submetidos a exames complementares para a diferenciação diagnóstica do prurido, incluindo: hemograma, micológico e parasitológico cutâneo, coproparasitológico, histológico de pele e sorológicos - RAST (radioimunoensaio) e ELISA (ensaio imunoenzimático) - ambos para determinação de IgE contra antígenos alimentares -, e ao exame da dieta de eliminação seguida pela exposição provocativa. Este último exame foi o mais confiável para o estabelecimento do diagnóstico, ao determinar que 20 cães, provenientes de ambos os grupos, eram alérgicos a alimentos. Pelos RAST e ELISA, não foi possível demonstrar resultados confiáveis quando comparados aos resultados com a dieta de eliminação. Os animais acometidos foram principalmente machos, com raça definida e na faixa etária de um a seis anos. Os principais alimentos incriminados foram a carne bovina, o arroz e a carne de frango.

Society of Oral Medicine, Chinese Stomatological Association Guideline for the diagnosis and management of dentin hypersensitivity

一、牙本质敏感的定义 通过对文献的全面回顾,参考加拿大专家委员会及Holland等提出的牙本质敏感定义,将牙本质敏感定义为:暴露的牙本质对外界刺激产生短而尖锐的疼痛,并且不能归因于其他特定原因引起的牙体缺损或病变,典型的刺激包括温度刺激、吹气刺激、机械性刺激或化学刺激.

Allergy Diagnostic Testing in Clindamycin-Induced Skin Reactions

Background: In clinical practice, clindamycin is increasingly used because of its good tolerability and high efficacy with excellent tissue penetration. However, with increased application of clindamycin, the frequency of side effects such as skin eruptions rises and the need for diagnostic testing to identify clindamycin allergy increases. The aim of this retrospective analysis was to demonstrate the results of skin and challenge tests in cases of clinically suspected clindamycin allergy. Methods: We evaluated 33 patients with a history of a skin reaction in temporal relation to treatment with clindamycin using standardized patch and prick skin testing. In the case of negative skin tests, oral challenges were performed. Results: Clindamycin hypersensitivity was excluded in 20 patients by negative skin tests and subsequently tolerated oral challenge tests. In 5 patients, positive skin tests strongly suggested delayed-type non-IgE-mediated allergic clindamycin hypersensitivity. In 6 skin test-negative patients (2 patients refused challenge tests), a rash was provoked by controlled challenge tests. Conclusions: The evaluation of patients with clindamycin-associated skin reactions should include appropriate allergologic tests establishing or excluding the diagnosis of clindamycin hypersensitivity. Combined testing, i.e. skin tests and subsequent challenge tests, appears to be necessary to definitely confirm or rule out the presence of allergic clindamycin hypersensitivity.

Benzylpenicillin skin testing is still important in diagnosing immediate hypersensitivity reactions to penicillins

The fact that both Hollister-Stier and Allergopharma ceased the production of penicilloyl-polylysine (PPL) and minor determinant mixture (MDM) in 2004 is severely hampering the diagnosis of beta-lactam hypersensitivity and may produce negative consequences. To assess the contribution of skin testing with benzylpenicillin to the diagnosis of immunoglobulin E-mediated hypersensitivity to penicillins, in order to determine how much such testing could compensate for PPL and MDM unavailability. We selected patients with histories of immediate reactions to penicillins and positive results to skin tests for one or more penicillin reagents (PPL, MDM, or benzylpenicillin), one or more semi-synthetic penicillins (ampicillin, amoxicillin, or piperacillin), or both. A total of 300 patients were selected, 105 in the French center and 195 in the Italian centers. Amoxicillin and ampicillin were the main responsible drugs. The most common clinical manifestation was anaphylaxis. The reagents most frequently positive to skin tests were amoxicillin (188, 62.7%), ampicillin (151, 50.3%), and benzylpenicillin (111, 37.0%). Among the 300 subjects, 113 (37.7%) were positive only to semi-synthetic penicillins, 109 (36.3%) to both semi-synthetic penicillins and the classic penicillin reagents, and 78 (26.0%) only to the latter. In the last group, 64 (21.3% of the 300 subjects) were positive only to PPL and/or MDM and 14 (4.7%) to benzylpenicillin, of whom 8 (2.7%) were positive only to the latter. Skin testing with benzylpenicillin can partially compensate for PPL and MDM unavailability. Moreover, it can slightly increase the allergologic workup's sensitivity and therefore reduce the number of potentially dangerous challenges.

Diagnosis and treatment of dentinal hypersensitivity

This bibliographic review provides a general view of the etiology, characteristics and treatment of dentinal hypersensitivity, so that professionals can use this information in the therapeutic management of this clinical condition. For this purpose, the authors have analyzed whole texts of relevant articles on the subject. This study showed that the predisposing factors associated with the causes of dentinal hypersensitivity must be controlled or eliminated, by educating the patient regarding the excessive intake of acidic food, as well as providing guidance on the proper tooth brushing technique and analysis of occlusion. Effective treatment must be preceded by a proper diagnosis, established after the exclusion of any other possible causes of the pain. These cases must be managed efficiently, quickly and permanently. The availability of a wide variety of treatment could be an indicator that there is still no effective desensitizing agent to completely resolve the patient's discomfort, or that it is difficult to treat, irrespective of the available treatment options. Even with the large number of published studies, it has not been possible to reach a consensus about the product that represents the gold standard in the treatment of dentinal hypersensitivity.