History Of Adverse Reactions Research Articles

Hypersensitivity Reactions to Paracetamol in Children: A Study of 25 Cases

Purpose of the Study. Reports of paracetamol (acetaminophen) allergic and nonallergic hypersensitivity reactions are rare. However, urticaria, angioedema, dyspnea, and allergic and nonallergic anaphylactic reactions have been reported in both children and adults in association with paracetamol administration. Most reactions to paracetamol occur in patients with a nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs (NSAIDs). Alternatively, reactions may result from an allergic hypersensitivity to paracetamol, with tolerance of NSAIDs. This study reports an investigation of 25 children with suspected paracetamol hypersensitivity. Study Population. Twenty-five children, aged 8 months to 15 years, with a history of adverse reactions associated with paracetamol administration. In 12 of the 25 children studied, paracetamol adverse reactions were associated with concurrent administration of other medications or biological agents. Methods. Diagnosis of paracetamol hypersensitivity was based on either clinical history or the results of an oral challenge test. Reported reactions included urticaria, angioedema, conjunctivitis, dyspnea, and a maculopapular rash. Oral challenge tests with paracetamol were performed in the hospital setting. Paracetamol dosing was initiated at 1 mg and gradually increased until the appropriate cumulative dose for age and weight was achieved. An oral challenge with acetylsalicylic acid was performed in 1 child with a history highly suggestive of paracetamol hypersensitivity. Results. Paracetamol hypersensitivity was diagnosed in 1 patient (4%) on the basis of clinical history. The child reported accelerated reactions on 2 occasions, including facial angioedema, conjunctivitis, and dyspnea with wheezing, after isolated intake of paracetamol. Oral challenge to acetylsalicylic acid in this patient induced urticaria and angioedema. Oral challenges to paracetamol in the 24 other children studied were tolerated. Conclusions. Results of this study of 25 children with suspected paracetamol hypersensitivity concur with those of previous reports: paracetamol hypersensitivity is rare and is associated with hypersensitivity reactions to antiinflammatory medications. Reviewer Comments. Adverse reactions temporally associated with paracetamol may result from reactions to other medications or the underlying conditions for which these medications have been prescribed. Diagnostic evaluation of suspected paracetamol hypersensitivity is complicated further by the lack of validated, available skin or in vitro testing. Adverse reactions to paracetamol can be both allergic and nonallergic in nature. The results of this study underscore the need for careful evaluation for both paracetamol and NSAID hypersensitivity in children with a history suggestive of adverse reactions to paracetamol.

Prevalence of sensitization to food allergens, reported adverse reaction to foods, food avoidance, and food hypersensitivity among teenagers

There is a paucity of information on food hypersensitivity (FHS) among teenagers. We sought to investigate the sensitization rates, perception of FHS, food avoidance, and FHS assessed by means of food challenges among teenagers. This cohort study recruited 757 eleven-year-olds and 775 fifteen-year-olds in the United Kingdom. Sensitization rates, reported rates of FHS, and rates of food avoidance were measured. The prevalence of FHS was established by using food challenges. The prevalence of reported FHS among the 11- and 15-year-old cohorts was 11.6% (90/775) and 12.4% (94/757), respectively. One hundred twenty-two (15.7%) and 142 (18.7%) of the 11- and 15-year-olds reported they were avoiding some food. The rates of sensitization to the food allergens were 5.1% (36/699) and 4.9% (32/649) for the 11- and 15-year-olds, respectively. FHS was confirmed in 8 (1.0%) 11-year-old children and 8 (1.0%) 15-year-old children by means of open food challenge and in 1 (0.1%) 11-year-old and 4 (0.5%) 15-year-olds by means of double-blind, placebo-controlled food challenge. The prevalence of FHS, as confirmed by using open food challenges and positive skin prick test responses plus a history of adverse reactions, was 18 (2.3%) of 775 in the 11-year-old cohort and 17 (2.3%) of 757 in the 15-year-old cohort. The rate of reported FHS was significantly more than sensitization to the predetermined allergens (odds ratio, 2.17; 95% CI, 1.47-3.18; P < .001 in the 11-year-olds; odds ratio, 2.73; 95% CI, 1.81-4.13; P < .001 in the 15-year-olds). By means of objective assessment, 2.3% of both 11- and 15-year-old children had FHS, with the majority showing immediate reactions.

Improvements in an oral aspirin challenge protocol for the diagnosis of aspirin hypersensitivity

Oral aspirin challenge (OAC) is used to confirm aspirin hypersensitivity (AHs) but there is no consensus on a standardized protocol. As a prior clinical history of adverse reactions to aspirin is poorly predictive of a positive result from formal aspirin challenge, many patients have an OAC performed. We retrospectively identified and prospectively validated how a 1-day OAC protocol could be modified, and patient selection improved, to deliver a safe and more efficient service. In a retrospective audit of 45 OACs using a 2 h dose interval, all reactions occurred within 90 min of the threshold dose. Forty OACs were then performed using a 90-min dose interval. This reduced the mean duration of a positive and negative OAC from 6 to 5 h and from 8 to 6 h, respectively. Histories of multiple manifestations of AHs were found in 91.6% (11) of those with asthma, 87.5% (7) with angiooedema, 70.6% (12) with rhinosinusitis, 63.6% (7) with chronic non-vasculitic urticaria and all with anaphylaxis, who developed a positive OAC. None of those with anaphylaxis, 8.3% (1) with asthma and 12.5% (1) with angiooedema, with a positive OAC, had a history of a single manifestation of AHs. The efficiency of an OAC service can safely be improved by reduction of the dose interval from 2 to 1 (1/2) h, and more targeted patient selection, as the likelihood of a positive OAC increases among patients with a history of asthma, angiooedoema or anaphylaxis with multiple manifestations of AHs.

2 Diseases: Management of patients presenting the first signs or a history of adverse reactions of anti-TNFα?

2 Diseases: Management of patients presenting the first signs or a history of adverse reactions of anti-TNFα?

Patch testing with a new fragrance mix detects additional patients sensitive to perfumes and missed by the current fragrance mix

The currently used 8% fragrance mix (FM I) does not identify all patients with a positive history of adverse reactions to fragrances. A new FM II with 6 frequently used chemicals was evaluated in 1701 consecutive patients patch tested in 6 dermatological centres in Europe. FM II was tested in 3 concentrations - 28% FM II contained 5% hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral), 2% citral, 5% farnesol, 5% coumarin, 1% citronellol and 10%alpha-hexyl-cinnamic aldehyde; in 14% FM II, the single constituents' concentration was lowered to 50% and in 2.8% FM II to 10%. Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable, none. Positive reactions to FM I occurred in 6.5% of the patients. Positive reactions to FM II were dose-dependent and increased from 1.3% (2.8% FM II), through 2.9% (14% FM II) to 4.1% (28% FM II). Reactions classified as doubtful or irritant varied considerably between the 6 centres, with a mean value of 7.2% for FM I and means ranging from 1.8% to 10.6% for FM II. 8.7% of the tested patients had a certain fragrance history. Of these, 25.2% were positive to FM I; reactivity to FM II was again dose-dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2 groups of history - certain and none - values for sensitivity and specificity were calculated: sensitivity: FM I, 25.2%; 2.8% FM II, 8.1%; 14% FM II, 13.5%; 28% FM II, 17.6%; specificity: FM I, 96.5%; 2.8% FM II, 99.5%; 14% FM II, 98.8%; 28% FM II, 98.1%. 31/70 patients (44.3%) positive to 28% FM II were negative to FM I, with 14% FM II this proportion being 16/50 (32%). In the group of patients with a certain history, a total of 7 patients were found reacting to FM II only. Conversely, in the group of patients without any fragrance history, there were significantly more positive reactions to FM I than to any concentration of FM II. In conclusion, the new FM II detects additional patients sensitive to fragrances missed by FM I; the number of false-positive reactions is lower with FM II than with FM I. Considering sensitivity, specificity and the frequency of doubtful reactions, the medium concentration, 14% FM II, seems to be the most appropriate diagnostic screening tool.

Refusal to take ivermectin: the associated 'risk' factors in Hoima district, Uganda

Community-directed treatment with ivermectin (CDTI), for the control of onchocerciasis, was launched in Uganda in 1997. In East Africa, as in other endemic areas, the refusal to take the drug reduces treatment coverage and therefore poses a serious threat to attempts to eliminate onchocerciasis as a disease of public-health importance. In early 2003, an attempt was therefore made to determine the factors associated with refusal to take ivermectin during mass treatment in 2002, by interviewing the individuals, from three Ugandan villages with CDTI, who had been eligible to receive ivermectin. The subject's socio-demographic characteristics, history of adverse reactions and participation in CDTI-related activities were explored, as potential 'risk' factors for refusing ivermectin in the treatment round in 2002. When odds ratios (OR) for refusal and their associated 95% confidence intervals (CI) were calculated, the villagers aged 18-35 years were found more likely to have received ivermectin in 2002 than their older counterparts (OR = 0.55; CI = 0.33-0.93). Individuals with an inter-current medical condition were also more likely to have received ivermectin in 2002 than the other villagers (OR = 0.56; CI = 0.32-0.99). Worryingly, the ingestion of ivermectin at any time before the 2002 treatment round was strongly associated with refusal to take ivermectin in that round (OR = 7.72; CI = 2.00-29.81), although there was no evidence that the adverse effects of treatment were significantly reducing coverage.

Assessment of oral bisphosphonate use in elderly patients with varying degrees of kidney function

Background: Oral bisphosphonates are prescribed for millions of men and women in the United States who have osteopenia or osteoporosis. However, there are limited data on the use of oral bisphosphonates in patients with kidney impairment. Objective: The purpose of this study was to evaluate changes in calculated creatinine clearance (CrCl) and reported adverse events in elderly patients with varying degrees of kidney function who were taking oral bisphosphonate therapy. Methods: The present study was a retrospective review of the medical records of elderly patients (age range, 65–89 years) who were prescribed oral bisphosphonates for a diagnosis of osteoporosis or osteopenia at the University of Colorado Hospital Seniors Clinic during the period January 1999 through March 2003. Data on age, sex, body weight, height, blood urea nitrogen and serum creatinine concentrations, and adverse-reaction history were collected. Clinic notes were reviewed to determine whether patients had taken an oral bisphosphonate previously or whether bisphosphonate therapy was initiated during the study period. The Cockcroft-Gault equation was used to calculate CrCl. Rates of drug-related adverse events were compared in patients with and without severe kidney impairment. For the purposes of this study, severe kidney impairment was defined as a CrCl <35 mL/min. Results: Data from 181 patients (88.4% female, 11.6% male; mean age, 79.2 years) who received oral bisphosphonates were included in the analysis. One hundred fourteen (63.0%) patients began bisphosphonate therapy during the study period. The mean duration of bisphosphonate therapy was 22.3 months. Thirty-one (17.1%) patients taking bisphosphonates had severe kidney impairment. There was no change in calculated CrCl after the initiation of oral bisphosphonate therapy in patients who started therapy during the study period. Adverse drug events, 19 of them related to the gastrointestinal system, occurred in 24 (13.3%) patients. Overall, 19.4% (6/31) of patients with severe kidney impairment and 12.0% (18/150) of those without severe kidney impairment experienced adverse events; the difference between groups was not statistically significant. No reported adverse drug event required hospitalization or emergency treatment. Conclusions: When prescribed for elderly patients with varying degrees of kidney function, oral bisphosphonate therapy was well tolerated and was not associated with a decline in calculated CrCl.

Bet v 1 homologues in strawberry identified as IgE‐binding proteins and presumptive allergens

No strawberry allergen has so far been identified and characterized. Serum samples were collected from patients with a suggestive case history of adverse reactions to strawberry and other fruits. Extracts from fresh and frozen strawberries were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blotting and mass spectrometry. Patient blood samples were analysed for inhibition of IgE binding and basophil degranulation. Several IgE-binding proteins could be detected. In more than half of the patient sera, a 20/18-kDa doublet band was observed in Western blotting. These two bands were excised and analysed by mass spectrometry showing the presence of proteins belonging to the Bet v 1 family of allergens. Inhibition of the IgE binding to the 20/18-kDa doublet was obtained by addition of two recombinantly expressed allergens belonging to the Bet v 1 family (Bet v 1 and Mal d 1) and strawberry protein extract. In a cell-based assay of patient blood samples, basophil degranulation could be induced by strawberry protein extract and by Bet v 1 and Mal d 1. We conclude that strawberry homologues to Bet v 1 may be allergens of importance for adverse reactions to strawberry.

Approach to "aspirin allergy" in cardiovascular patients.

Aspirin (ASA), by irreversibly inhibiting platelet cyclooxygenase-1 enzyme (COX-1), prevents platelet aggregation and is the mainstay of pharmacotherapy of patients with coronary artery disease (CAD). Long-term ASA therapy reduces mortality in CAD patients after an initial coronary event. Periprocedural ASA therapy significantly reduces major adverse cardiovascular events (MACE) after percutaneous coronary interventions.1,2 Despite a plethora of clinical data showing marked efficacy of ASA therapy in cardiovascular patients, ASA use continues to be less than optimal in real-world registries.3,4 A history of adverse reactions to ASA may prevent long-term use in a cardiovascular patient, thereby reducing optimal event protection. Most adverse reactions to ASA, such as gastrointestinal intolerance, are predictable and are dose and host related.5 However, ASA can also cause a hypersensitivity reaction, of which there are 3 types: respiratory sensitivity (asthma and/or rhinitis), cutaneous sensitivity (urticaria and/or angioedema), and systemic sensitivity (anaphylactoid reaction).6 Various terms have been used to describe the hypersensitivity reactions to ASA, including ASA intolerance, ASA idiosyncrasy, pseudoallergic reactions, and ASA sensitivity.7 The prevalence of ASA sensitivity in cardiovascular patients is not well known. Besides substitution with an alternative class of antiplatelet agents such as thienopyridines, ASA desensitization is an option for ASA-allergic patients who require long-term therapy for cardiovascular diseases.7 In this article, we review various hypersensitivity reactions to ASA and discuss desensitization protocols to allow ASA therapy in ASA-sensitive cardiovascular patients. ### ASA-Exacerbated Respiratory Disease ASA-exacerbated respiratory disease (AERD) is a triad of asthma, ASA sensitivity, and rhinitis/nasal polyps. Patients with AERD have aggressive mucosal inflammation and suffer from precipitation of asthma and rhinitis after ingestion of ASA and nonsteroidal antiinflammatory drugs (NSAIDs).8 AERD is also commonly referred to as ASA-sensitive, ASA-induced, or ASA-intolerant asthma. AERD is the cause of 10% to 15% of all cases of asthma,8 is usually …

Intra-abdominal, crystal-storing histiocytosis due to clofazimine in a patient with lepromatous leprosy and concurrent carcinoma of the colon

We report a case with abdominal complications of clofazimine treatment which included blackish discolouration of the lymph nodes, omentum and peritoneum. A 44-year-old female with lepromatous leprosy and a history of adverse reaction to clofazimine 2 years previously, presented with rectosigmoid junction adenocarcinoma. Laparotomy revealed an inoperable tumour with pigmentation of the bowel, serosa and peritoneum. A second operation had o be performed for transverse loop colostomy and a mesenteric lymph node biopsy sent for frozen section showed typical clofazimine crystals. Despite widespread use for many years in the treatment of leprosy, this drug is not known to be carcinogenic and this case provides no evidence for an association or link between its use and the patient's cancer. Apart from its use in leprosy, clofazimine may be used in the treatment of disseminated Mycobacterium avium-intracellulare infection, Buruli ulcer due to M. ulcerans and occasionally in other mycobacterial infections. An awareness of the rare side-effect described above may help in the clinical assessment and management of such cases, including the avoidance of unnecessary laparotomy.

FS06.7 The new fragrance mix II – test results of a multicentre European Study

A new fragrance mix (FM II) with 6 frequently used chemicals was evaluated in consecutive patients patch tested in 6 dermatological centres in Europe. 28% FM II contained 5% Lyral, 1% citral, 5% farnesol, 5% coumarin, 1% citronellol and 10% alpha‐hexyl cinnamic aldehyde (AHCA); in 14% FM II the single constituents’ concentrations was lowered to 50% and in 2.8% FM II to 10%. Each patient was classified regarding a history of adverse reactions to fragrances: certain, probable, questionable and none. The frequency of positive reactions to the currently used 8% fragrance mix (FM I) and the new mix in 1703 patients was as follows: FM I, 6.6%; 2.8% FM II, 1.3%; 14% FM II, 2.9%; 28% FM II, 4.1%. The number of doubtful/irritant reactions was 7.2% for FM I and ranged from 1.8% to 10.6% for FM II.8.7% of tested patients had a certain fragrance history. Of these 25.2% were positive to FM I, reactivity to FM II was dose‐dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2 groups of history – certain and none – values for sensitivity (sens) and specificity (spec) were calculated. Sens: FM I, 27.2%; 2.8% FM II, 8.7%; 14% FM II, 15.9%; 28% FM II, 21.5%. Spec: FM I, 96.3%; 2.8% FM II, 99.5%; 14% FM II, 98.7%; 28% FM II, 97.9%. 31/70 (44.3%) patients positive to 28% FM II were negative to FM I. In the group of patients with a certain history a total of 6 patients was found reacting only to FM II. Simultaneous break‐down testing with the single constituents produced positive reactions in 54.3% for 28% FM II and 48% for 14% FM II. Lyral was the dominating single constituent with positive reactions (37.1% for 28% FM II, 36% for 14% FM II), followed by citral, farnesol, citronellol, AHCA and coumarin. Chemical analysis for the 6 constituents of FM II was performed on 25 products used by 12 patients being patch test positive to FM II. Lyral was detected in 76% of these products, citral in 16% and AHCA in 8%. In conclusion, the new FM II detects additional patients with contact allergy to fragrances missed by the currently used FM I. The medium concentration, 14% FM II, is probably the most useful one for diagnostic screening.

IgE Binding to Raw and Boiled Shrimp Proteins in Atopic and Nonatopic Patients with Adverse Reactions to Shrimp

Background: Characterization of seafood allergens is important to understand the immune response to these allergens. Moreover, a detailed comparison between atopic and nonatopic patients with adverse reactions to shrimp has never been reported. Methods: Raw and boiled shrimp extracts were analyzed by immunoblotting using sera from 9 atopic and 7 nonatopic patients with a history of adverse reactions to shrimp, and 13 control subjects. Total IgE, specific IgE and skin prick tests (SPT) to shrimp were also investigated. Results: The level of specific IgE to shrimp was higher in atopic patients than nonatopic patients (p < 0.05). Symptoms, SPT results and major allergens involved were similar in atopic and nonatopic patients. The 16.5-kD protein had the highest frequency of IgE binding followed by the 40-kD protein in these patients. Other minor IgE-binding proteins were observed at the 20-, 22-, 54-, 72-, 129- and 140-kD regions. Patients who had binding to the 16.5-kD protein had either positive (25% raw/31% cooked) or negative (13% raw/cooked) CAP-FEIA-RAST, while patients who recognized the 40-kD protein all had positive (31% raw/19% cooked) CAP-FEIA-RAST. All control subjects had negative immunoblots for these two proteins. Conclusion: The 16.5-kD protein was the most frequent protein identified regardless of CAP-FEIA-RAST results, while the 40-kD protein was only present in patients with positive CAP-FEIA-RAST. Therefore, 16.5-kD protein may be an important allergen that is clinically relevant in both atopic and nonatopic patients with adverse reactions to shrimp even if it is not detected by the CAP-FEIA-RAST system.

Safety of Selective COX‐2 Inhibitors in Aspirin/Nonsteroidal Anti‐inflammatory Drug‐Intolerant Patients: Comparison of Nimesulide, Meloxicam, and Rofecoxib

Background. Intolerance to acetylsalicylic acid (ASA) and other nonsteroidal anti‐inflammatory drugs (NSAIDs) is a crucial problem in clinical practice. There is, therefore, a need for safer NSAIDs in patients with analgesic intolerance. Objective. To assess the safety of nimesulide, meloxicam, and rofecoxib, selective COX‐2 inhibitors, in a group of ASA/NSAIDs‐intolerant patients. Method. Tolerances to nimesulide, meloxicam, and rofecoxib were assessed by single‐blind placebo‐controlled oral challenges. One hundred twenty‐seven subjects with history of adverse reaction to ASA/NSAIDs received oral challenges with nimesulide, 61 subjects were challenged with meloxicam, 51 subjects were challenged with rofecoxib, and 37 subjects were challenged with all three drugs. Placebos were given to all patients on the first day of the study. On the second day, one‐fourth and three‐fourths of the therapeutic doses of the active drugs (nimesulide 100 mg, meloxicam 7.5 mg, or rofecoxib 25 mg) were given at 60‐minute intervals. There was at least a 3‐day interval between challenge tests. Erythema, pruritus accompanied by erythema, urticaria/angioedema, rhinorrhea, nasal obstruction, sneezing, dyspnea, or cough associated with a decrease of at least 20% in the forced expiratory volume (FEV1) and hypotension were considered as positive reactions. Results. Positive reactions to the nimesulide, meloxicam, and rofecoxib challenges were observed in 18/127 (14.3%), 5/61 (8.1%), and 1/51 (2.0%) patients, respectively. In each group of nine patients, there were two patients with asthma and four who developed skin type reactions and asthmatic reactions, respectively, to the nimesulide challenge. Among five patients who reacted to the meloxicam challenge, asthmatic type reactions were detected in two asthmatics. Only one urticarial type reaction was observed with rofecoxib challenge in one patient who presented with anaphylaxis to ASA/NSAIDs. All patients with asthma tolerated rofecoxib without any adverse effects. None of the patients reacted to the placebo. Among 37 patients challenged with all three drugs, 11 reacted to nimesulide, and one patient reacted only to meloxicam. Three patients reacted to more than one of the drugs tested, and one of them reacted to all drugs. Conclusion. This is the first placebo‐controlled report comparing these three drugs. The results indicate that among these alternative drugs for ASA/NSAIDs‐intolerant patients, rofecoxib seems to have the most favorable tolerability.

Orange-induced skin lesions in patients with atopic eczema: evidence for a non-IgE-mediated mechanism.

Oranges are suspected of inducing adverse skin reactions in patients with atopic eczema. We studied 21 adult patients with atopic eczema and a history of adverse reactions to oranges and 10 patients without. A dietary history, skin tests, serum IgE and oral provocation tests with oranges were obtained. Severity of eczema was monitored by SCORAD, and serum tryptase, eosinophil cationic protein and urinary methylhistamine were measured. No allergic reactions were found to orange in skin prick or patch tests. However, 23 patients (74%) had specific serum IgE to orange. Oral provocation testing resulted in pruritic eczematous or maculopapular skin lesions predominantly at the predilection sites in 16 patients (52%). The SCORAD increased significantly in patients positive to the oral provocation test (p <0.05). Specific IgE to orange did not correlate with the clinical outcome of the oral provocation test. No significant changes were found in serum mast cell tryptase, eosinophil cationic protein or in urinary methylhistamine excretion. The negative results in the skin tests and a lack of correlation between specific IgE and oral provocation tests indicate that non-IgE-mediated mechanisms are involved in cutaneous adverse reactions to oranges in patients with atopic eczema.

On-line internet facilities for contact allergy software: CDESK/PRO.

In order to find sensitizers additional to the current fragrance mix (FM) a series of fragrance materials (series II) was evaluated in 6 dermatological centres in Europe. 11 of the test materials were essential oils, the remaining 7 being either mixtures of isomers or simple chemicals of frequent usage in the perfume industry. 1606 patients were consecutively tested with series II and 8% FM. Each patient was classified regarding a history of adverse reactions to scented products: certain, probable, questionable, none. Reactions to FM occurred most frequently in 11.4% of the subjects. The 6 materials with the highest reactivity after the FM were ylang‐ylang oil (YY) I (2.6%), YY II (2.5%), lemongrass oil (1.6%), narcissus absolute (1.3%), jasmine absolute (1.2%) and sandalwood oil (0.9%). 48 (3.0%) of the patients reacted only to materials of series II and not to FM. 6.0% of 1606 patients gave a history of adverse reactions to fragrances which was classified as certain. This group reacted to FM only in 22.9%, to series II and FM in 15.6% and to series II only in 5.2%. 63.5% of the patients reacting to both FM and 1 of the materials of series II had some type of positive fragrance history, which was higher in comparison to those with isolated reactions to FM (46.2% of 121) or to series II, respectively, (45.8% of 48). However, this difference was not statistically significant. In conclusion, the materials of series II identified a further subset of patients with a fragrance problem, which would have been missed by the current FM as the single screening tool for patch testing.

Ethanol as a cause of hypersensitivity reactions to alcoholic beverages.

Adverse reactions after ingestion of alcoholic beverages are common. Metabolic differences in individuals and also the histamine content in alcoholic beverages have been implicated. By contrast pure ethanol has rarely been reported as a cause of hypersensitivity reactions and its mechanism has not been clarified yet. To determine whether ethanol itself accounts for alcohol hypersensitivity in patients with anaphylactic reactions after alcohol intake. In search of possible pathomechanisms all patients were analysed by skin prick testing and sulfidoleukotriene production of peripheral leucocytes using ethanol and its metabolites. Double-blind, placebo-controlled food challenges with a cumulated amount of 30 mL ethanol were performed in 12 adult patients with a positive history of adverse reactions after consumption of different alcoholic beverages. Skin prick tests and measurement of sulfidoleukotriene production were performed using different concentrations of ethanol and acetaldehyde from 50 to 1000 mm. Oral challenges with pure ethanol were positive in six out of eleven patients. All challenge-positive patients, but also four out of five challenge-negative patients, showed an increased sulfidoleukotriene production in-vitro compared with healthy controls. Skin prick tests using alcoholic beverages, ethanol, acetaldehyde and acetic acid were negative in all patients (12/12). Our study shows that ethanol itself is a common causative factor in hypersensitivity reactions to alcoholic beverages. These reactions occur dose-dependent and a non-IgE-mediated pathomechanism is likely, because skin prick tests were negative in all cases. Increased sulfidoleukotriene production was determined in some patients, but is no reliable predictor. Therefore oral provocation tests remain indispensable in making the diagnosis of ethanol hypersensitivity.

Marginal seal of sealant and compomer materials with and without enameloplasty

Although true allergic reactions to local anaesthetics are rare in the general population, the importance of the problem among asthmatic children has yet to be documented.Skin prick, intradermal and incremental challenge tests with lidocain were performed in 157 asthmatic children aged 8-15 years and compared with 72 nonasthmatic children of a similar age. All of the asthmatic subjects were allergic to at least one allergen, most frequently pollens and house dust mites. Prick testing began with an undiluted solution in patients without a history of allergy and with 1:100 dilution in those with a reaction history. Following negative prick testing, intradermal or incremental challenge tests were performed.A total of 125 patients (80%) had been given local anaesthetics in the past, only three children gave history of an adverse local reaction. At the end of the tests, none of the subjects including controls, were found to have immediate or delayed-type allergy to lidocain.Local anaesthetic allergy does not seem to be a serious problem among asthmatic children and testing in all asthmatic children is not warranted. Those with an adverse reaction history to local anaesthetics should be tested with these drugs.

Sensitivity to local anaesthetics among asthmatic children

Summary.Objectives.Although true allergic reactions to local anaesthetics are rare in the general population, the importance of the problem among asthmatic children has yet to be documented.Sample and methods.Skin prick, intradermal and incremental challenge tests with lidocain were performed in 157 asthmatic children aged 8–15 years and compared with 72 nonasthmatic children of a similar age. All of the asthmatic subjects were allergic to at least one allergen, most frequently pollens and house dust mites. Prick testing began with an undiluted solution in patients without a history of allergy and with 1:100 dilution in those with a reaction history. Following negative prick testing, intradermal or incremental challenge tests were performed.Results.A total of 125 patients (80%) had been given local anaesthetics in the past, only three children gave history of an adverse local reaction. At the end of the tests, none of the subjects including controls, were found to have immediate or delayed‐type allergy to lidocain.Conclusions.Local anaesthetic allergy does not seem to be a serious problem among asthmatic children and testing in all asthmatic children is not warranted. Those with an adverse reaction history to local anaesthetics should be tested with these drugs.

Tomato (Lycopersicon esculentum) allergens in pollen-allergic patients

This study was undertaken to investigate the relevance of tomato allergy in pollen-allergic patients, and to identify and characterize tomato allergens. Therefore, sera of a group of 32 pollen-allergic patients with a history of adverse reactions to tomato were investigated by means of immunoblotting and specific IgE measurements (CAP, EAST, EAST inhibition and CCD [cross-reactive carbohydrate determinants] – ELISA). IgE-reactive spots on 2D blots were analyzed by amino acid microsequencing. Tomato allergy was found to occur with a prevalence of about 9% in our group of birch pollen-allergic patients. Of the patients with adverse reactions to tomato, 44% presented IgE to tomato profilin and 35.5% specific IgE to CCD. Two patients were sensitized to a lipid transfer protein in tomato. Microsequencing of other IgE-reactive proteins, separated by 2D-gel electrophoresis and transferred to PVDF membranes, revealed β-fructofuranosidase, polygalacturonase 2A, and pectinesterase as further tomato allergens. Our data show that tomato is a relevant allergenic food in pollen-allergic patients. It seems that the majority of pollen-associated allergies to tomato is caused by known ubiquitous allergenic structures such as profilin and cross-reactive IgE-binding N-glycans. Furthermore, lipid transfer protein, as well as polygalacturonase 2A, pectinesterase and β-fructofuranosidase may represent birch pollen-independent tomato allergens for certain patients.

Dapsone-Induced Methemoglobinemia in Pediatric Oncology Patients: Case Examples

Over the last 25 years, significant advances have been made in supportive care of the immunocompromised patient. One significant advance is the use of trimethoprim-sulfamethoxazole (TMP-SMZ) in the prevention of Pneumocystic carinii pneumonia (PCP). Although TMP-SMZ remains the drug of choice for PCP prophylaxis, children who develop or have a history of adverse reactions must be prescribed an alternative treatment. In these instances, medications such as dapsone, aerosolized pentamidine, or atovaquone are prescribed. This report discusses four children with sulfa allergy who were prescribed dapsone and later developed methemoglobinemia. Although methemoglobinemia is associated with dapsone, there was no reference found regarding this link in the pediatric oncology literature. The purpose of these clinical examples is to alert the pediatric nurse and advanced practitioner to the association of dapsone and methemoglobinemia.