Intracutaneous Tests Research Articles

Two cases of anaphylaxis to macrogol 6000 after ingestion of drug tablets

AllergyVolume 61, Issue 8 p. 1021-1021 Two cases of anaphylaxis to macrogol 6000 after ingestion of drug tablets H. Hyry, H. Hyry Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this authorA. Vuorio, A. Vuorio Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this authorE. Varjonen, E. Varjonen Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this authorJ. Skyttä, J. Skyttä Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this authorS. Mäkinen-Kiljunen, S. Mäkinen-Kiljunen Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this author H. Hyry, H. Hyry Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this authorA. Vuorio, A. Vuorio Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this authorE. Varjonen, E. Varjonen Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this authorJ. Skyttä, J. Skyttä Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this authorS. Mäkinen-Kiljunen, S. Mäkinen-Kiljunen Skin and Allergy HospitalPO Box 160FIN-00029 HUSFinlandTel: +358 9 4711Fax: + 358 9 471 86474E-mail: heli.hyry@hus.fiSearch for more papers by this author First published: 06 July 2006 https://doi.org/10.1111/j.1398-9995.2006.01083.xCitations: 27 Macrogol (polyethyleneglycol) 6000 frequently used as a vehicle in tablet form medication causes anaphylactic reactions. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume61, Issue8August 2006Pages 1021-1021 RelatedInformation

Pitfalls in drug allergy skin testing: false–positive reactions due to (hidden) additives

Skin testing for drug hypersensitivity is a valuable diagnostic tool and a well established procedure for betalactams and corticosteroids. Although appropriate patch, prick or intracutaneous testing usually permits unequivocal interpretation, the possibility of false-positive reactions must be kept in mind. We report two patients, one with a suspected penicillin allergy and one with a suspected steroid allergy, in whom positive skin tests initially yielded a false diagnosis. In both cases, other findings were inconsistent with the positive skin tests. Therefore, further investigations were performed. After the test preparations had been analysed, the skin test was extended to include the additives, which then yielded the diagnosis of sensitization to the surfactant polysorbate 80 (PS 80, contained in the penicillin test solution) and the emulsion stabilizer carboxymethylcellulose (CMC, contained in the steroid preparation), respectively. It should be noted that positive reactions to test solution additives, as in the first case, may lead to a lifelong false diagnosis of (penicillin) allergy, whereas an undiagnosed allergy to additives in parenteral applications, as in the second case, might prove fatal.

Anaphylaxis to isosulfan blue and cross-reactivity to patent blue V: case report and review of the nomenclature of vital blue dyes

Blue dyes used for lymphatic mapping in sentinel lymph node biopsy cause intraoperative anaphylactic reactions in up to 2.7% of patients. With increasing implementation of this technique, the incidence of anaphylaxis to these dyes can be expected to increase. In the literature, the chemically often unrelated and inconsistently designated dyes have been confused, adding to other inconsistencies in the nomenclature. To demonstrate the nomenclature, chemical and physiologic differences, and allergenicity of the various blue dyes used in a medical context. We describe a patient with an intraoperative grade IV anaphylactic reaction to isosulfan blue. Immediate-type hypersensitivity was proved by positive skin test reactions and CD63 expression to isosulfan blue and cross-reactivity to patent blue V. A review of the literature clarified the exact nomenclature of the blue dyes and the possible pitfalls of confusing nomenclature in the context of structurally closely related dyes with different allergenic properties. For the detection of type I hypersensitivity, intracutaneous tests are valuable tools. An IgE-mediated mechanism has been shown recently. In most cases, sensitization exists without known previous exposure in a medical context. This may be due to the widespread use of such dyes in objects of everyday life. Preoperative antiallergic medication use does not prevent anaphylactic reactions but apparently reduces their severity. For better comparison and precision, the Chemical Abstracts Service number of the respective dye should always be given.

Discontinuation of intracutaneous reaction test A questionnaire survey of surgery departments

Discontinuation of intracutaneous reaction test A questionnaire survey of surgery departments

Anaphylaxie auf Protonenpumpenhemmer

Introduction: During the last years, increasing numbers of proton pump inhibitors have been introduced into the market and the range of indications for which they are used has expanded. In this context, also the reports on allergic reactions, particularly immediate type reactions, to representatives of this group have increased. Next to some single case reports on vasculitis, erythematous, bullous or exfoliative dermatitis and others, there are escalating numbers of reports on anaphylactoid reactions to omeprazole, pantoprazole and lansoprazole. So far, the diagnostic procedures have not been evaluated. Patients: We report on six patients with immediate-type hypersensitivity to pantoprazole, who underwent skin prick tests, intracutaneous tests and CAST as well as LTT. Results; All these test procedures were not useful as there were false positive as well as false negative results, therefore, skin tests and laboratory investigations were not sensitive enough. So far, provocation tests are still the gold standard. Conclusion; Currently, accidental reexposures or controlled provocation tests are the most reliable tools in the clinical diagnosis of these reactions. This may be due to the fact that proton pump inhibitors are rapidly metabolized by the gastric parietal cells to a sulfonamide derivative. As one explanation, the hypersensitivity reaction may occur to the metabolite and not to the parent drug. However, experienced physicians should only do provocation tests under intensive surveillance conditions.

Tuberculosis in children

Epidemiology of tuberculosis (TB) in childhood is closely related to TB in adults. Serious manifestations are often observed in children with TB. Immunological immaturity and social dependence facilitate the spread of infection. Paediatricians account in practise both primary TB, with hilar lymphadenopathy, and subacute or chronic pulmonary complications, in TB disease. Children appear to have a higher risk of having extrapulmonary TB involving any organ. The diagnosis of tuberculosis reactivation/re-infection, is based in the isolation of the agent in the sputum [7]. Primary TB is difficult to diagnose, usually established by indirect signs of low epidemiological specificity, symptoms, chest radiography and the intracutaneous tuberculin test. In this context, one can understand the importance of correct interpretation of the chest radiograph. Chest CT is recommended if the chest radiograph is equivocal. In addition, an overview of extrapulmonary cases of TB – of the spine, bone and lymph nodes – including the role of other imaging modalities (Us and MR) will be presented [1,3].

Allergy and “toxic mold syndrome”

"Toxic mold syndrome" is a controversial diagnosis associated with exposure to mold-contaminated environments. Molds are known to induce asthma and allergic rhinitis through IgE-mediated mechanisms, to cause hypersensitivity pneumonitis through other immune mechanisms, and to cause life-threatening primary and secondary infections in immunocompromised patients. Mold metabolites may be irritants and may be involved in "sick building syndrome." Patients with environmental mold exposure have presented with atypical constitutional and systemic symptoms, associating those symptoms with the contaminated environment. To characterize the clinical features and possible etiology of symptoms in patients with chief complaints related to mold exposure. Review of patients presenting to an allergy and asthma center with the chief complaint of toxic mold exposure. Symptoms were recorded, and physical examinations, skin prick/puncture tests, and intracutaneous tests were performed. A total of 65 individuals aged 1 1/2 to 52 years were studied. Symptoms included rhinitis (62%), cough (52%), headache (34%), respiratory symptoms (34%), central nervous system symptoms (25%), and fatigue (23%). Physical examination revealed pale nasal mucosa, pharyngeal "cobblestoning," and rhinorrhea. Fifty-three percent (33/62) of the patients had skin reactions to molds. Mold-exposed patients can present with a variety of IgE- and non-IgE-mediated symptoms. Mycotoxins, irritation by spores, or metabolites may be culprits in non-IgE presentations; environmental assays have not been perfected. Symptoms attributable to the toxic effects of molds and not attributable to IgE or other immune mechanisms need further evaluation as to pathogenesis. Allergic, rather than toxic, responses seemed to be the major cause of symptoms in the studied group.

Allergy testing on the IMMULITE 2000 Random-Access immunoanalyzer – a clinical evaluation study

We aimed to evaluate the diagnostic performance of the IMMULITE 2000 Allergy System from Diagnostic Products Corporation (DPC) for the detection of inhalant and food allergies, focusing on inhalant and food screens, mixes and single allergens. Serum samples were collected from new, unselected patients who were referred to the allergist for a suspected allergy. Patients were classified as study diagnosis-positive for inhalant (food) allergy if they had both a positive clinical examination/history and a positive skin test for inhalant (food) allergy; otherwise - failing one or both of these criteria - they were classified as study diagnosis-negative. Classification and testing of the serum samples was carried out in a blinded fashion. Values greater than 0.35 kU/L were considered positive. Of the 118 patients included, 63 were considered study diagnosis-positive for inhalation and/or food allergy. DPC inhalation screening showed 82% total agreement (TA) and 91% sensitivity relative to the study diagnoses. The DPC food panel showed 96% TA and 98% specificity relative to the study diagnoses. Relative to specific intracutaneous testing (ICT), the DPC D1, E1 and E5 assays had sensitivity of 82-90%; tree and grass panels had sensitivity of 74% and 95%. The DPC weed panel and initial lots of DPC E5 had poor sensitivity (<40%); mold panel sensitivity was equally low for both DPC and the routinely used Pharmacia assay (36%). Relative to skin prick testing (SPT), specific food allergens had TA of 94-98% and specificity of 95-100%. In patients classified by the combination of clinical examination/history and skin test results, the DPC IMMULITE 2000 Allergy System generally demonstrated acceptable sensitivity, specificity and TA compared to the study diagnoses, both at the screening level and at the level of panels and single allergens.

Characterization of a population presenting with suspected mold-related health effects

Numerous epidemiologic studies have reported a relationship between dampness and increased respiratory symptoms in adults and children, which has led to increasing concerns among the general population about potential mold-related health effects. To identify characteristics of patients with possible mold-related health effects that might help allergists better understand how to evaluate such patients in their practices. The parameters that were evaluated for the total population included age, sex, upper and lower respiratory tract symptoms, systemic symptoms, atopic status, pet ownership, smoking history, mold sensitization, mold exposure, and exposure location. Subgroups stratified by atopic status, mold sensitization, and indoor mold exposure confirmed by an environmental mold report prepared by certified industrial hygienists were also analyzed. Significant associations were determined by correlation coefficients and logistic regression analysis. A total of 135 patients with possible mold-related health effects secondary to prolonged indoor mold exposure were evaluated. For the overall population, a strong correlation was found among atopy, mold sensitization, and sensitization to specific molds identified in the patient's environmental report. Mold intracutaneous testing was not useful for discriminating between atopic and nonatopic individuals. There were no associations among the patients' presenting symptoms, atopic status, and magnitude of mold exposure. Similar findings were identified when subgroup analysis was performed. Patients who present with mold-related health effects manifest heterogeneous characteristics. Medical history, skin testing, and current indoor mold sampling practices have significant limitations in establishing a causal link among mold exposure health effects.

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Berufsbedingte allergische Rhino-konjunktivitis, Proteinkontaktdermatitis, Asthma bronchiale und Kontakturtikaria auf Rinderallergene bei einer Landwirtin

A 40-year-old female farmer is described, with a rare coexistence of 4 different occupational diseases sharing one common cause: allergy to cow epithelium (Bos domesticus). First symptoms started after 6 years of working on the farm. The allergic diseases appeared in the following sequence: rhinitis, protein contact dermatitis, asthma, conjunctivitis, and finally contact urticaria. The time span between the first and the last allergic manifestation to develop was 9 years. By the time of examination, 4 shock organs (the upper and lower airway, conjunctivae and the skin) were involved. Skin prick tests with common aeroallergens, farm animals, pets, and agricultural dusts were all negative, total IgE was within normal range (90 kU/l). Intracutaneous test and bronchial provocation with cow epithelium allergens were both positive. Specific IgE was detected to cow dander (CAP class 3) but not to bovine serum albumin (CAP 0). A positive reaction to goat dander (i.c. positive, CAP 2) was interpreted as a cross reactivity, because the patient never had contact with goats. The article also reviews known sources of cow allergens and occupations at risk. Besides farmers and veterinary surgeons, also butchers, cheese makers, bakers, cooks, laboratory workers and even beauticians may be at risk for developing occupational allergy to cow allergens.

Fondaparinux: a suitable alternative in cases of delayed‐type allergy to heparins and semisynthetic heparinoids? A study of 7 cases

Hypersensitivity to unfractionated and low-molecular-weight heparins and semisynthetic heparinoids is increasingly common. 7 female patients between 30 and 74 years with delayed-type allergy to heparins and semisynthetic heparinoids were investigated for (cross)-reactivity to fondaparinux, a new pentasaccharide with selective factor Xa inhibition. All patients showed delayed-type reactions to heparins and some additional cross-reaction to a heparinoid on intracutaneous testing. 6/7 tolerated fondaparinux on intradermal testing as well as on subcutaneous challenge testing. However, the 7th patient developed a characteristic delayed-type reaction to both skin tests with fondaparinux. Fondaparinux is a new synthetic pentasaccharide with a molecular weight of 1.728 Da. In some patients with cross-reactivity between various heparins and semisynthetic heparinoids, lepirudin, a recombinant hirudin, may be a safe and effective alternative. However, combined allergy to hirudin and heparins has been reported. Sometimes, intravenous administration of heparins or heparinoids may be tolerated. However, these patients are at risk of developing a systemic reaction. The pathogenesis of heparin hypersensitivity is not fully understood. Heparins may act as haptens by binding to dermal and/or subcutaneous structural proteins. The chemical structures of heparins and fondaparinux are different concerning their alpha- and beta-configuration and the molecular weight. However, some of their functional groups are nearly identical and therefore similar chemical and pharmacological reactivity is to be expected. Fondaparinux seems to be a valuable alternative in most cases of heparin and hirudin hypersensitivity. The clearly rare cross-reaction between fondaparinux and heparins, now confirmed by us, may be due to differences in the response to haptens.

Relevance of Ara h1, Ara h2 and Ara h3 in peanut-allergic patients, as determined by immunoglobulin E Western blotting, basophil-histamine release and intracutaneous testing: Ara h2 is the most important peanut allergen.

A number of allergenic proteins in peanut has been described and the relative importance of these allergens is yet to be determined. We have investigated the relevance of previously identified peanut allergens in well-characterized peanut-allergic patients by in vitro, ex vivo and in vivo assays. Thirty-two adult peanut-allergic patients were included based on careful and standardized patient history and the presence of peanut-specific IgE. The diagnosis peanut allergy was confirmed using double-blind placebo-controlled food challenges in 23 patients. Major peanut allergens Ara h1, Ara h2 and Ara h3 were purified from peanuts using ion-exchange chromatography. IgE immunoblotting was performed and IgE-cross-linking capacity was examined by measuring histamine release (HR) after incubating patient basophils as well as passively sensitized basophils with several dilutions of the allergens. Intracutaneous tests (ICTs) using 10-fold dilution steps of the purified allergens and crude peanut extract were performed. Ara h2 was recognized most frequently (26 out of 32) in all tests and induced both positive skin tests and basophil degranulation at low concentrations, whereas Ara h1 and Ara h3 were recognized less frequently and reacted only at 100-fold higher concentrations as analysed with HR and intracutaneous testing (ICT). Next to the three tested allergens, proteins with molecular weights of somewhat smaller than 15 kDa were identified as a IgE-binding proteins on immunoblot in the majority of the patients (20 out of 32). We conclude that Ara h2 is, for our patient group, the most important peanut allergen, and that previously unidentified peanut proteins with molecular weights of somewhat smaller than 15 kDa may be important allergens as well. ICT in combination with basophil-HR and IgE immunoblotting provides insight in the patient specificity towards the individual peanut allergens.

FS09.1 Diacetylmorphine (heroin) allergy

Since heroin is delivered to a selected group of drug addicts under supervision of nurses in the Netherlands, we reported about several nurses who presented with work‐related eczema and positive patch tests to heroin. To investigate the prevalence of heroin contact allergy among all workers in this heroin delivery project, a study was started using questionnaires. Altogether 31 nurses reported work‐related complaints out of 100 who returned questionnaires. Besides reports of eczema, mainly of eyelids (probably airborne) and hands, there were mucosal and respiratory complaints. Patch tests were performed in 25 nurses with complaints; in 9 of them a heroin contact allergy could be confirmed. In 6 out of these 9 nurses this was combined with mucosal or respiratory complaints. There were also 6 nurses with mucosal or respiratory complaints without a contact allergy. Contact dermatitis from opioids, such as morphine and codeine, has been documented among opioid industry workers, nurses, doctors, pharmacists, and in patients. In conclusion heroin appears to be a potent contact allergen, causing contact dermatitis. Mucosal and respiratory complaints however, cannot be explained by this contact allergy; they might be caused by a type‐1‐allergy to heroin, or by a direct histamine liberating effect. Opioids are known histamine liberators causing urticaria, rhinitis and anaphylactoid reactions; therefore intracutaneous tests with heroin are unreliable. In an ongoing research project it will be attempted to detect specific IgE to heroin in the 12 workers with mucosal or respiratory complaints; within the next few months results will be available.

Analysis of T cell activation pathways in patients with liver cirrhosis, impaired delayed hypersensitivity and other T cell-dependent functions.

Patients with cirrhosis of the liver frequently demonstrate anergy in intracutaneous tests and fail to respond to vaccination, suggesting impaired delayed hypersensitivity and other T cell-dependent functions in vivo. T cell activation through the coordinated interaction of different cells of the immune system (B cell, antigen-presenting cells (APC)) is an important step in the induction of cellular and humoral immune responses. Impaired T cell-dependent functions in patients with liver cirrhosis may thus be explained by defective T cell activation. We prospectively investigated T cell activation pathways in 12 patients (nine males, three females) with alcoholic liver cirrhosis (seven Child Pugh stage A and B (CP A + B), five Child Pugh stage C (CP C)) and five healthy controls and compared the in vitro results of T cell activation with data obtained in vivo, e.g. intracutaneous tests and vaccination against hepatitis B surface antigen (HBs-Ag). Five out of eight patients who completed vaccination against hepatitis B virus infection were non-responders; one of the three responders had a non-protective anti-HBs titre. Moreover, three of five patients with alcoholic liver cirrhosis CP A + B, and two out of three with CP C were anergic in intracutaneous tests to a set of diverse antigens. All parameters of T cell activation were normal, including proliferation mediated by CD2, CD3-T cell receptor (TCR) complex, and CD28; acquisition of responsiveness to exogenous IL-2 and IL-4; activation of proteinkinase C (PKC) by phorbol ester and calcium influx by addition of ionomycin. The ability of monocytes to deliver costimulatory signals was preserved in patients with alcoholic cirrhosis. In addition, serum of patients with alcoholic liver disease did not inhibit T cell proliferation. We conclude that, although in patients with alcoholic liver cirrhosis T cell-dependent functions are impaired in vivo, T cell activation pathways are not responsible for the observed immune defect.

Improvement of quality of life and daytime sleepiness in Perennial Allergic Rhinitis patients treated with immunotherapy

Purpose: The purpose of this study was to investigate the effectiveness of Immunotherapy (SIT) in improving the quality of life (QoL), reducing nasal symptoms (NS) and lessening the daytime sleepiness (DTS) in Perennial Allergic Rhinitis patients. Method: Cohort (QoL and NS) and cross-sectional studies (DTS) were done to determine the improvement of QoL, reduction of NS and lessening of DTS of PAR who received SIT 1997–2000. The data obtained from 34 medical records of a Private Allergy Clinic in Bandung, Indonesia, were clinical profiles of PAR patients, QoL (by Juniper's, with permission), NS and DTS (by Multiple Sleep Latency Test). The SIT is based on Skin End-Point Titration test (SET) and intracutaneous provocative food test (IPFT) as suggested by AAOAF, using standardized Allergen extract. Results: The longer the period of SIT treatment the lesser the level of DTS (p≤0.005) the lower the NS (p≤0.001). The SIT can also improve the overall QoL of PAR patients (p<0.001) since it proves a significant correlation between Qol and DTS (r=−0.637, p<0.001), NS and DTS (r=−0.734, p<0.001) and NS and QoL (r=0.9, p<0.001). Conclusion: The study concludes that SIT and IPFT are effective in reducing NS and lessening the DTS. This study also demonstrates that the better the QoL, the lesser DTS. We will later conduct a prospective cohort study to obtain a better perception concerning the correlation between SIT, NS, DTS and Qol. Purpose: A cross-sectional study that investigates the effectiveness of immunotherapy (IMT) in improving the quality of life (QoL), reducing nasal symptoms (NS) and the daytime sleepiness (DTS) of Perennial Allergic Rhinitis (PAR) patients. Method: In 1997–2000, 34 PAR patients between 11–56 years old participated in the study. Two subjects were in the preparation stage of IMT treatment, while the rest had been treated by IMT for 6–36 months using standardized allergen extract. The IMT treatment is based on Skin Endpoint Titration (SET) suggested by AAOAF. The assessment includes the NS, the QoL (Juniper's Quality of Life Questionnaires, with permission) and the DTS (by Multiple Sleep Latency Test). Results: The longer the period of IMT treatment the lesser the level of DTS (Kruskal–Wallis test, p=0.029) and the lower the NS (p=0.075). Although the study does not show that IMT can improve the overall QoL of PAR patients (p=0.20), it proves a significant correlation between QoL and DTS.

IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone

Background: Propyphenazone (1,2–dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenyl-3H-pyrazol-3-one; PP) is a nonsteroidal anti-inflammatory drug frequently used as mild analgesic medicament. It belongs to the chemical group of pyrazolones. Severe adverse reactions to PP are frequent and have generally been regarded as pseudoallergic or intolerance reactions. Presently, there are no useful in vitro test systems available for the detection of antibodies directed against analgesic drugs. Objective: The purpose of this study was to unequivocally demonstrate that IgE-mediated Type I allergy is the main mechanism leading to immediate-type adverse reactions to the analgesic drug PP. Methods: We investigated 53 young adult patients with adverse reactions to PP. All patients developed symptoms suggestive of IgE-mediated anaphylaxis within 30 minutes after intake of a painkiller containing PP. Patients were subjected to skin tests (prick test and intracutaneous test). In addition, a novel ELISA system was developed to prove the existence of specific IgE antibodies in patients' sera. Results: In 44 of 53 (83%) patients, skin tests showed typical wheal and flare reactions. Significant amounts of PP-specific serum IgE was detected in 31 of 53 (58%) of the serum samples. Moreover, in 7 of 9 patients with skin test negative results, PP-specific IgE could be detected. The assay was PP-specific because only PP, but no other pyrazolone derivative (antipyrine, aminophenazone, or metamizol), was able to inhibit IgE-binding in the system. Conclusion: Propyphenazone is a sensitizing agent in susceptible individuals and can elicit IgE-mediated anaphylaxis. By using skin tests and our ELISA system we were able to confirm Type I allergy in 51 of 53 (96%) patients in this study.

Comparison of Allergen-Induced Late Inflammatory Reactions in the Nose and in the Skin in House Dust Mite-Allergic Patients with or without Asthma

Background: It remains to be established which factors contribute to the occurrence of asthma in allergic individuals. We hypothesized that differences in the late allergic inflammatory reaction to allergen between asthmatic and non-asthmatic house dust mite-allergic individuals might contribute to the difference in the clinical presentation of allergy. Aim: To compare allergen-induced changes in parameters for cellular inflammation during the phase of the late allergic reaction in the skin and nose, in house dust mite-allergic individuals with or without asthma. Material and Methods: Nasal and dermal allergen challenges with house dust mite (Dermatophagoides pteronyssinus) extract were performed in 52 house dust mite-allergic individuals, of whom 26 had mild to moderate persistent asthma and 26 had perennial rhinitis without current or past asthmatic symptoms. Serial nasal lavage samples were analyzed for the presence of inflammatory cells (eosinophils and neutrophils) and soluble markers associated with cellular inflammation [interleukin-5 (IL-5), interleukin-8 (IL-8), eosinophil cationic protein (ECP) and myeloperoxidase (MPO)]. Macroscopic late phase skin reactions were studied after intracutaneous skin tests with house dust mite extract. Results: Fixed dose nasal allergen provocation elicited a similar degree of immediate allergic reaction as judged by plasma protein exudation and histamine concentrations in asthma and non-asthmatic rhinitis. Subsequently, no differences between groups were found during the phase of the late allergic reaction (4–24 h) in inflammatory cell influx, plasma protein leakage, ECP or MPO. Likewise, there were no differences in levels of chemotactic cytokines IL-5 and IL-8. In agreement with the results of nasal challenge, the late skin reaction after dermal challenge with a fixed allergen dose and after an allergen dose 10,000 times above the skin threshold for an early skin reaction did not differ between the groups. Conclusion: House dust mite-allergic patients with or without asthma have very similar late allergic inflammatory reactions in the skin and in the nose after allergen challenge. Hence, it is unlikely that the occurrence of pulmonary symptoms in asthma is explained by a general tendency of asthmatics to have an enhanced late allergic cellular inflammatory response. Nasal and dermal allergen provocations are adequate models to study allergen-induced inflammation but probably lack the pivotal link which is essential for the development of asthma.

An analysis of ISO intracutaneous reactivity test results to justify a reduction in animal requirements.

The ISO intracutaneous reactivity test is the standard protocol for determining a medical device's potential for causing irritation. The authors present data indicating that the number of animals required per test can be reduced from three rabbits to two.

Hipersensibilidad a los antígenos del Trichophyton rubrum en podólogos atópicos y no atópicos

Podiatrists as well as manicurists are exposed to inhale nail dust contaminated with mycotic particles when filing and burring the onychomycotic nails of their patients. As some of them with atopic background suffered worsening of their symptoms we decided to study the immune response to the fungus Trichophyton rubrum (Tr) that was isolated from the nail dust obtained from the podiatrists office. A detailed clinical record, intracutaneous skin tests with a extract of Tr and the serum levels of total and specific IgE were performed in rhinitis-asthma as well as control patients. As the asthmatic group refused to perform the challenge bronchial test with Tr we developed a guinea pig experimental model with daily aerosolization of Tr during 12 weeks studying the levels of specific IgE and IgG as well as the lung's histopathology. Atopic patients showed positive immediate skin tests with Tr and both groups revealed delayed hypersensitivity to the antigen.RAST-IgE-anti-Tr and RAST-inhibition confirmed the specificity of the antibodies. Guinea pigs also synthetized IgG and IgE anti-Tr and suffered different degrees of lung lesions similar to those of hypersensitivity pneumonitis. Atopic podiatrists are exposed to fungal allergens that may participate or aggravate their previous respiratory conditions.