Positive Oral Challenge Research Articles

Urticaire chronique par allergie alimentaire au nickel

Allergic contact dermatitis due to nickel is a common and well-known disorder, mediated by T-lymphocytes. The existence of systemic manifestations, especially urticaria due to the nickel contained in food remains a matter of strong debate. The aim of the present study was to demonstrate by a positive placebo-controlled oral challenge test (PCOCT) followed by the disappearance of symptoms after a low nickel diet the existence of true urticaria triggered by nickel contained in food, resulting in chronic urticaria. We studied 21 patients suffering from chronic idiopathic urticaria; all of them had a positive nickel sulfate patch test. A PCOCT with oral nickel pidolate (cumulative dose, 6.9 mg nickel) was performed in each subject. Fifteen of the 21 patients had a positive PCOCT. We observed three different types of response: one immediate response, nine intermediate responses and five delayed responses. A low nickel diet was effective in 11 patients, and drug treatment was stopped completely in nine of them. In addition, removal of a metallic dental prosthesis plus a nickel-avoidance diet in four cases led to a successful result in two of them. The PCOCT was negative in the six other patients; cutaneous itching or laryngeal discomfort without urticaria occurred after the first dose of placebo in two of them. Given these results, we recommend that a diagnosis of nickel-induced food allergy be considered in patients with chronic urticaria if the etiology remains unknown.

Influence of Age on the Outcome of the Atopy Patch Test with Food in Children with Atopic Dermatitis

Influence of Age on the Outcome of the Atopy Patch Test with Food in Children with Atopic Dermatitis

La persistance de l’allergie au lait de vache à propos de 20 cas

Objective. – Cow’s milk allergy is known to disappear in most cases by the age of 2 years, but can sometimes persist longer. The aim of this study is to analyse the natural history of this allergy in children with persistence of that allergy at the age of 2 years. Patients and methods. – This retrospective study has selected among 68 children with cow’s milk allergy and who had undergone a challenge test, those who had persistent allergy after 2 years of age. We included 20 children: 16 boys and four girls from 2 to 14 year old. The diagnosis of persistent milk allergy was proved by challenge test or by accidental ingestion of milk. Results. – Out of the 20 with persistent allergy by the age of 2, seven acquired tolerance between the age of 3 years and 6 months and 9 years and 7 months. We found a predominance of boys (sex ratio 4:1), a high frequency of family atopy (75%) and of other food sensitisation (60%). Gastro-intestinal symptoms were rare (20%). We observed respiratory symptoms secondarily in 75% cases but rarely due to milk. Severe reactions were observed in two cases. A severe reaction was induced by the ingestion of goat’s milk in one case. Specific IgE level of cow’s milk and of casein >2.5 kU/l was always correlated to a positive oral challenge. However, a lower level of specific IgE does not allow to predict a tolerance. Conclusion. – Cow’s milk allergy is not always transient. In case of persistent cow’s milk allergy, a follow-up of specific IgE levels of cow’s milk and of casein is sufficient and oral challenge should be suggested only when these levels are inferior to 2.5 kU/l.

Results of Double-Blind Placebo-Controlled Challenge with Nickel Salts in Patients Affected by Recurrent Aphthous Stomatitis

Background: The aetiology of recurrent aphthous stomatitis (RAS) has so far not been completely clarified. Recently, several studies reported that patients affected by cutaneous diseases (i.e. dermatitis, eczema and urticaria) with positive patch test to nickel have a positive oral nickel challenge. Objective: A retrospective data analysis of patch test and oral nickel challenge in 380 patients (204 women and 176 men) affected by RAS was performed. Patients and Methods: We examined 380 consecutive patients affected by RAS during the period 1990–1999. In 28/380 patients the appearance of their oral symptoms coincided with the fitting of orthodontic appliance, while 352/380 reported that their oral symptoms worsened after the fitting of orthodontic appliance. All patients were studied with the series (European standard series and series for dental materials) for patch tests. Results: Seventy out of 380 patients (18.4%) presented a contact sensitization to nickel sulphate (positive patch test). In all of these, the orthodontic appliance was replaced with one made of nickel-free materials. All patients were re-examined by the dentist 6 months after the removal of the orthodontic appliance. The symptoms had completely remitted in 28/70 patients, partially had improved in 31/70 patients and had remained unchanged in 11/70 patients. In all patients (n = 70) with a positive patch test to nickel we performed an oral double-blind placebo-controlled challenge (DBPC) test with nickel sulphate. The DBPC was positive in 32/70 patients, 21 of whom had partially improved and 11 had not, even after the replacement of the orthodontic appliance with material not containing nickel. None of the 28 patients in complete remission showed an adverse reaction to oral nickel challenge. Conclusion: The results of this study demonstrate that, in some patients with a positive patch test to nickel sulphate, the perpetuation of RAS can be related to a hypersensitivity to ingested nickel salts, independently of local contact to nickel.

Ciprofloxacin skin testing: A retrospective study

RATIONALE: Limited information is available regarding the validity of procedures to diagnose allergic adverse drug reactions (ADRs) associated with fluoroquinolones (FQ). A retrospective study was undertaken to examine the clinical utility of ciprofloxacin (CP) skin testing. MATERIALS AND METHODS: A review of 135 charts from patients seen with suspected FQ associated ADRs between 1996-2001 was con- ducted at the Sunnybrook Drug Safety Clinic. Skin testing (prick and intradermal) was performed to CP (0.0001 mg/ml to 0.1 mg/ml) and levofloxacin (0.0001 mg/ml to 0.1 mg/ml) and oral challenge with CP (250 rag) and/or another FQ was administered following the negative skin tests. RESULTS: False positive reactions were associated with concentrations >0.05 mg/ml. 5/135 (4%) tested positive on the skin testing; 2 to levofloxacin and 3 to CP. 20/135 (15%) were positive on the oral challenge; however, only 9 (7%) subjects had reactions consisting of a rash and/or breathing difficulties within the time frame for an immediate or accelerated reaction (between 0 and 72 hours). The other 11 (8%) false negative reactions were potentially non-allergic (eg, pruritus, lightheadedness). There was a significant relationship between the original reaction history (indicative or non-indicative of immediate hypersensitivity) and positive oral challenge outcomes (true false negative or non-specific reactions) (P=0.0014, 95% CI). The negative predictive value for this test was deter- mined to be 93.1%, which is comparable to the negative predictive value for penicillin, the gold standard for skin testing. CONCLUSIONS: Skin testing should be pursued as a diagnostic tool for suspected allergic ADRs associated with FQ antibiotics.

The atopic dog as a model of peanut and tree nut food allergy.

Animal models are needed that mimic human IgE-mediated peanut and tree nut allergy. Atopic dogs have been previously used in a model of food allergy to cow's milk, beef, wheat, and soy, with the demonstration of specific IgE production and positive oral challenges similar to those seen in human subjects. We sought to sensitize dogs to peanut, walnut, and Brazil nut and to assess whether sensitization is accompanied by clinical reactions and whether there is cross-reactivity among the different preparations. Eleven dogs were sensitized subcutaneously by using an established protocol with 1 microg each of peanut, English walnut, or Brazil nut protein extracts in alum first at birth and then after modified live virus vaccinations at 3, 7, and 11 weeks of age. The dogs were sensitized to other allergens, including soy and either wheat or barley. Intradermal skin tests, IgE immunoblotting to nut proteins, and oral challenges were performed with ground nut preparations. At 6 months of age, the dogs' intradermal skin test responses were positive to the nut extracts. IgE immunoblotting to peanut, walnut, and Brazil nut showed strong recognition of proteins in the aqueous preparations. Each of the 4 peanut- and the 3 Brazil nut-sensitized dogs and 3 of the 4 walnut-sensitized dogs reacted on oral challenge with the corresponding primary immunogen at age 2 years. None of the peanut-sensitized dogs reacted clinically with walnut or Brazil nut challenges. One of the walnut-sensitized dogs had delayed (overnight) vomiting to Brazil nut. On the basis of measurements of the mean amount of allergen eliciting a skin test response in dogs, the hierarchy of reactivity by skin testing is similar to the clinical experience in human subjects (peanut > tree nuts > wheat > soy > barley). Cross-reactivity, which was not apparent between soy and peanut or tree nuts or between peanut and tree nuts, was slight between walnut and Brazil nut. The results give further support to the dog as a model of human food allergy.

Rising prevalence of allergy to peanut in children: Data from 2 sequential cohorts

Background: Allergy to peanut is common. However, it is not known whether the prevalence of sensitization and clinical allergy to peanut is increasing. Objective: We sought to determine any change in the prevalence of peanut sensitization and reactivity in early childhood in 2 sequential cohorts in the same geographic area 6 years apart. Methods: Of 2878 children born between September 1, 1994, and August 31, 1996, living on the Isle of Wight, 1273 completed questionnaires, and 1246 had skin prick tests at the age of 3 to 4 years. Those with positive skin prick test responses to peanut were subjected to oral peanut challenges, unless there was a history of immediate systemic reaction. These data were compared with information on sensitization and clinical allergy to peanut available from a previous cohort born in 1989 in the same geographic area. Results: There was a 2-fold increase in reported peanut allergy (0.5 % [6/1218] to 1.0 % [13/1273]), but the difference was nonsignificant (P = .2). Peanut sensitization increased 3-fold, with 41 (3.3 %) of 1246 children sensitized in 1994 to 1996 compared with 11 (1.1 %) of 981 sensitized 6 years ago (P = .001). Of 41 sensitized children in the current study, 10 reported a convincing clinical reaction to peanut, and 8 had positive oral challenge results, giving an overall estimate of peanut allergy of 1.5% (18/1246). Conclusions: Sensitization to peanut had increased between 1989 and 1994 to 1996. There was a strong but statistically nonsignificant trend for increase in reported peanut allergy. (J Allergy Clin Immunol 2002;110:784-9.)

Lack of Allergic Cross-Reactivity to Cephalosporins Among Patients Allergic to Penicillins

Purpose of the Study. To assess the safety of administering cephalosporins to penicillin-allergic patients.Study Population. Forty-one patients (age 19–72, 14 male/27 female) with confirmed penicillin allergy by history, skin testing and in some cases by penicillin or amoxicillin challenge.Methods. All subjects underwent skin testing for penicilloyl-polylysine (PPL), minor determinant mixture (MDM), benzylpenicillin (PG), and amoxicillin (AX). A wheal 3 mm greater than the saline control was considered positive. If the prick skin tests were negative, than intradermal (ID) tests were performed, where a wheal 5 mm greater than the negative control was considered positive. If the ID tests were negative, PG was administered intramuscularly beginning with 1000 U and increasing incrementally to as high as 1.2 million U. After completing this challenge, the subjects returned in 20 days and was skin tested again and challenged to PG in a similar fashion. In the case of amoxicillin allergy, oral AX was administered in progressively increasing doses from 25 mg up to 500 mg every 45 mins, unless a reaction occurred. Once the diagnosis of penicillin (PCN) allergy was confirmed, cephalosporin testing was performed for cefazoline, cefuroxime, and ceftriaxone at 25 mg/mL and 250 mg/mL by puncture test and at 2.5 mg/mL and 25 mg/mL for ID testing. If the cephalosporin skin testing was negative, doses of each was injected intramuscularly beginning with 25 mg increasing progressively to as much as 500 mg. The challenges occurred over as long as 2 days. All challenges were performed in a single-blinded manner.Results. Thirty-four patients had AX or amoxicillin/clavulanic acid allergy, 1 had AX and cloxacillin allergy, 3 had PG allergy and in 3 cases the drug was unknown. Thirty-eight had a positive skin test to some PCN or AX reagent. Fifteen (36.5%) had positive skin test to AX only with negative skin test to remaining PCN determinants. Ten (24.3%) had 1 or more positive skin tests to PCN determinants and negative to AX. Thirteen (31.7%) had positive skin test to PCN determinants and AX. In 3 subjects, the skin testing for PCN and AX was negative, but they had a positive oral challenge to AX. Two of them who were rechallenged with PCN had good tolerance to it. Four (9.7%) had the diagnosis of PCN allergy made during the rechallenge study 20 days after the initial study. One of these subjects had a systemic reaction during the intradermal test. Skin tests to cephalosporins were negative in 39 patients, equivocal by ID technique in 2 and all 41 tolerated 3 cephalosporins by the intramuscular route.Conclusion. This study indicates that penicillin-allergic patients may receive cephalosporins with a low risk of having an allergic reaction, as long as the cephalosporin has a different side chain from the PCN causing the allergic reaction and the drug is given under careful supervision.Reviewer’s Comments. More than a third of patients with positive skin testing to only AX had negative skin testing to major and minor determinants, which supports testing for AX in addition to standard PCN testing. About 10% of subjects with PCN allergy were diagnosed at rechallenge, which supports the need to include rechallenge in the evaluation of PCN allergy. Previous studies of cross-reactivity between PCNs and cephalosporins have noted as much as a four-fold risk for reactions in PCN-sensitive subjects versus controls. These studies were performed with cephalosporins with similar side chains to PG. Others report between 12% to 38% of PCN-allergic subjects reacted to cephalosporins with similar sidechains, but reactions to cephalosporins without similar side chains have not been described. Therefore, when it comes to cross-reactivity between PCNs and cephalosporins, they are not all alike in the level of risk and those with dissimilar side chains offer the lowest risk of cross-reactivity.

The diagnostic value of crude or boiled extracts to identify tolerant versus nontolerant lentil-sensitive children

The aim of this study was to compare two types of lentil extracts for use in skin prick tests for the diagnosis of lentil clinical allergy. Thirty-six patients with a history of allergic reactions after the ingestion of lentils were skin tested with two types of lentil extracts at 0.05, 0.5, 5, and 10 mg/mL. Both extracts were extracted at 40 degrees C and afterward, one of them was boiled for 15 minutes. Thirty-three of these patients underwent oral challenges with lentils and three had a convincing recent history of lentil anaphylaxis. Twenty patients had a positive oral challenge; 13 were negative. Skin prick tests performed with the boiled extract at 0.5 and 5 mg/mL were positive in 96% and 100% of patients with positive food challenge, and in 31% and 85% of those with negative food challenge, respectively; positive skin test results were similar in both groups using the crude extract. Mean wheal sizes using the boiled extract at 0.5, 5, and 10 mg/mL were significantly greater in patients with a positive oral challenge than in those with a negative one (4.9, 6.8, and 7.4 mm versus 1.9, 3.5, and 5.1 mm, respectively; P < 0.05) These mean values were not statistically different using the crude extract. These data suggest that lentil extracts for the diagnosis of lentil hypersensitivity should be heated, since boiled extracts, used at a concentration of 0.5 or 5 mg/mL, best identify clinically sensitive individuals.

Aspirin induced adverse skin reactions: new pathophysiological aspects

Clinically, aspirin induced adverse skin reactions resemble true immunologically mediated allergic reactions. However, it is well accepted that aspirin intolerance is not mediated by specific IgE antibodies. The exact mechanisms...

The atopy patch test (APT) – a useful tool for the diagnosis of food allergy in children with atopic dermatitis

While immediate-type clinical reactions to food can quite easily be identified by history or measurement of specific IgE in combination with positive oral food challenges, the evaluation of food allergy in the absence of immediate clinical reactions still presents diagnostic difficulties--particularly in children with atopic dermatitis. The objective of this study was to evaluate the diagnostic value of the atopy patch test (APT) with regard to late-phase reactions observed in double-blind, placebo-controlled food challenges with cow's milk, hen's egg, wheat, and soybean. We investigated 75 children (median age 2.1 years) with suspected food allergy by double-blind, placebo-controlled food challenges, specific IgE in serum, skin prick test, and APT. Of the subjects, 69/75 suffered from atopic dermatitis. Of 209 oral challenges, 133 were performed with allergen and 76 with placebo. We assessed 77/133 allergen and 2/76 placebo challenges as positive. In 66 of 77 (86%) positive oral challenges, specific IgE in serum to the corresponding allergen was positive; in 64/77 (83%) the skin prick test, and in 42/77 (55%) the APT was positive. While immediate-type reactions were associated with positive skin prick test and proof of specific IgE in serum, late-phase clinical reactions were associated with a positive APT (sensitivity 76%, specificity 95%). The APT seems to be a valuable additional tool in the diagnostic work-up of food allergy in children with atopic dermatitis - especially with regard to late-phase clinical reactions. The APT may help to prevent unnecessary restrictive diets which may be the consequence of misjudging late reactions by clinical assessment alone.

Specific IgE Levels to Cicer arietinum (Chick Pea) in Tolerant and Nontolerant Children: Evaluation of Boiled and Raw Extracts

The chick pea, Cicer arietinum, is a legume commonly consumed in Spain and other Mediterranean countries. The sera of 29 children (mean age: 8.4 years) with a current or past history of allergic reactions after ingestion of chick pea, and positive skin tests to this legume, were used to study the allergenic composition of raw and boiled chick pea extracts. The patient population was divided into 2 groups: group 1 consisted of 19 patients with clinical sensitivity confirmed by either positive oral challenges or a convincing recent history of anaphylaxis after eating chick peas, and group 2 consisted of 10 patients with clinical sensitivity in the past, but tolerant at the time of blood extraction. Six atopic children, not allergic to legumes, were included as controls. Specific IgE to the raw and boiled extracts was measured by ELISA. The allergenic composition of both extracts was analyzed by SDS-PAGE and immunoblots. There were no significant differences between specific IgE levels to the raw and boiled extracts (p = 0.23). The mean levels in group 1 were significantly higher than in group 2 and controls (p = 0.0001). Multiple IgE binding proteins/peptides were detected in both extracts in the molecular weight range of 10–106 kD. Only nontolerant patients recognized a similar number of bands in both extracts. Chick pea extracts contain a majority of heat-stable allergens, which could be responsible for the clinical sensitivity to chick pea. Patients with a current clinical allergy to chick pea have statistically higher specific IgE levels than tolerant patients and controls.

Evidence for a lipid transfer protein as the major allergen of apricot

Background: Apricots are widely grown in Europe, and allergic reactions are becoming more common, especially oral allergy syndrome. Apricot belongs to the botanical subfamily of Prunoideae, which includes peach, the major allergen of which was identified as a 9-kd protein, a lipid transfer protein (LTP). Objective: The aim of the study was to evaluate the IgE reactivity pattern to an apricot extract in subjects with allergic reactions to apricot, as demonstrated by a positive oral challenge response. Methods: Thirty patients were investigated. All the patients displayed oral allergy syndrome (2 with systemic reactions) to apricot, with positive open food challenge responses, skin prick test responses, and serum-specific IgE antibodies to apricot. The IgE reactivity pattern to apricot extract was identified by using SDS-PAGE and immunoblotting. The major allergen, a 9-kd protein, was then purified by HPLC and characterized by periodic acid–Schiff stain, isoelectric point determination, and N-terminal amino acid sequencing. Results: The sera from all patients allergic to apricot recognized the 9-kd protein, whereas none of the other allergens, with molecular weights from 15 to 80 kd, acted as a major allergen. The 9-kd allergen has an isoelectric point of 8.7 and is not glycosylated. Determination of the N-terminal 34 amino acid sequence showed that it belongs to the LTP family, with a 94% homology with the LTP from peach. IgE blotting of the apricot extract was completely inhibited by the 9-kd purified LTP from peach. Conclusions: The major allergen of apricot is an LTP, which is highly cross-reactive with the LTP from peach. (J Allergy Clin Immunol 2000;105:371-7.)

Clinical Significance of IgE–Binding Activity to Enzymatic Digests of Ovomucoid in the Diagnosis and the Prediction of the Outgrowing of Egg White Hypersensitivity

Background: We frequently encounter subjects without overt symptoms despite high IgE antibodies to egg white and its components. The measurements of these antibodies are not necessarily efficient for the diagnosis or the prediction of the outcome of egg allergy in children. Methods: Specific IgE antibodies to egg white and its components, including ovomucoid, ovalbumin, ovotransferrin and lysozyme, were measured by direct RAST assays. IgE–binding activity to ovomucoid degraded by pepsin, trypsin and chymotrypsin was examined by RAST inhibition. Thirty subjects were divided into two groups with positive (n=18; mean age ± SD = 42 ±25 months) and negative (n=12; mean age ± SD = 48 ±31 months) oral challenge tests with egg white antigens. The individuals with positive results to the first challenge tests were given the second provocation tests at mean intervals of 32 months. IgE–binding activity of the sera collected on the first challenge to these ovomucoid fragments was compared between subjects with positive and negative reactions to the follow–up challenge tests. Results: There were no significant differences in IgE antibody titers to egg white and its components between the positive and negative groups at the first and the second challenge tests. IgE–binding activity to ovomucoid digests after treatments with pepsin (p = 0.000008) and trypsin (p=0.037), except chymotrypsin (p=0.062), were significantly higher in subjects with positive challenge tests than in those with negative results. The difference was most remarkable in the IgE–binding to pepsin digests; the average concentrations (mean – SD and mean + SD) needed for 50% RAST inhibition in the positive group and in the negative group were 2.6 μg/ml (0.3 and 25) and 94.2 μg/ml (24.7 and 358.7), respectively. A significant difference was still observed in the inhibition tests using filtrates of pepsin digests with a membrane with MW 10,000 (p=0.014) and 3,000 (p=0.042) of cutoff. The concentration (mean= 0.8, mean – SD=0.2, mean + SD=3.4; μg/ml) of pepsin–treated ovomucoid required for 50% RAST inhibition in the subjects with positive second challenge results was significantly (p=0.033) lower than that (mean=6.8, mean–SD=0.6, mean + SD=73.9) of the negative group. Conclusion: IgE–binding activity to pepsin–digested ovomucoid was of diagnostic value to distinguish the challenge–positive subjects from the negative subjects. Subjects with high IgE–binding activity to pepsin–treated ovomucoid are unlikely to outgrow egg white allergy.

Specific IgE determinations to crude and boiled lentil (Lens culinaris) extracts in lentil-sensitive children and controls.

The aims of this study were to evaluate the allergenicity of boiled and crude lentil extracts and to compare specific IgE binding in tolerant and nontolerant lentil-allergic children. Thirty-eight children were studied and divided into three groups. Group I comprised 24 children with a positive open oral challenge, or a convincing history of anaphylaxis after the ingestion of lentils; group II comprised nine children with a history of allergic reactions in the past, but currently tolerant of lentils; and group III comprised five children allergic to other legumes, but always tolerant of the ingestion of lentils. Specific IgE determinations and ELISA inhibitions were performed with the crude and boiled lentil extracts. The allergenic profile of both extracts was evaluated by SDS-PAGE and immunoblot. Mean specific IgE levels in group I were significantly higher than in groups II and III. The heating process caused a significant decrease in specific IgE binding. However, IgE-inhibition studies showed that the boiled lentil extract had a greater inhibitory capacity than the crude extract. Immunoblots revealed no important differences in IgE-binding patterns between the two extracts. Multiple allergens were detected in a wide range of molecular masses. Boiled lentil extracts maintain strong allergenicity. Patients who have developed tolerance of lentil ingestion have lower specific IgE levels than symptomatic patients.

Allergy to beta-lactam antibiotics in children.

Skin tests with soluble beta-lactams can be used to diagnose immediate and delayed hypersensitivity (HS) reactions to beta-lactam antibiotics. Very few studies have been performed with children with suspected beta-lactam allergy. In these studies, immediate HS to beta-lactams was diagnosed by skin tests in 4.9% to 40% of children. The diagnostic and predictive values of immediate responses in skin tests are good, because very few children with negative skin test results have positive oral challenge (OC) test results. Delayed responses in skin tests (intradermal and patch tests) have been reported in adult patients and children suffering with urticaria, angioedema, and maculopapular rashes during treatments with beta-lactam antibiotics. However, the diagnostic and predictive values of late responses are unknown. Semi-late responses in skin tests with beta-lactams have never been studied in adults or children. The aims of this study were to confirm or rule out the diagnosis of allergy to beta-lactams in children with histories of adverse reactions to these antibiotics, to determine whether allergic children were sensitized to one or several classes of beta-lactams, and to evaluate the frequency and diagnostic value of immediate, accelerated, and delayed responses in skin tests with beta-lactam antibiotics in children. We studied 325 children with suspected beta-lactam allergy. Skin tests (prick and intradermal) were performed with soluble forms of the suspected (or very similar) beta-lactams and with one or several beta-lactams from other classes. The reaction was assessed after 20 minutes (immediate), 8 hours (accelerated), and 48 to 72 hours (delayed). OCs with the suspected beta-lactams were performed in patients with negative skin test results, except those with severe serum sickness-like reactions and potentially harmful toxidermias. Skin tests and OCs led to the diagnosis of beta-lactam allergy in 24 (7.4%) and 15 (4.6%) of the children, respectively. Thus, only 12% of the children were diagnosed as allergic to beta-lactams by means of skin tests and OC. HS to beta-lactams was suspected from clinical history in 30 (9.2%) children reporting serum sickness-like reactions and potentially harmful toxidermias. In a few children, we diagnosed food allergy and intolerance to excipients or nonsteroidal antiinflammatory drugs. No cause was found in the other children. Based on skin tests and OC, the prevalences of immunoglobulin E-dependent and of semi-late or delayed sensitizations to beta-lactam assessed were similar (6.8% vs 5.2%, respectively). Most immunoglobulin E-dependent sensitizations were diagnosed by means of skin tests (86.4%). In contrast, most semi-late and delayed sensitizations were diagnosed by OC (70.6%). The likelihood of beta-lactam allergy was significantly higher for anaphylaxis (42.9% vs 8.3% in other reactions) and immediate reactions (25% vs 10% in accelerated and delayed reactions). Of the children diagnosed as allergic to beta-lactam by means of skin tests, OC, and clinical history, 11.7% were sensitized to several classes of beta-lactams. The risk was significantly higher in children with anaphylaxis (26. 7% vs 7.5% of the children with other reactions) and in children reporting immediate reactions (33.3% vs 8.5% of the children with accelerated and delayed reactions). Finally, age, sex, personal history of atopy, number of reactions to beta-lactams, and number of reactions to other drugs were not significant risk factors for beta-lactam allergy. The skin tests were safe, and the immediate reaction to skin tests successfully diagnosed allergy to beta-lactam antibiotics in children reporting reactions suggestive of immediate HS. In contrast, most accelerated and delayed reactions were diagnosed by OC. Thus, our results suggest that the diagnostic and predictive values of skin tests for nonimmediate HS to beta-lactams in children are low. (ABSTRACT TRU

Cat sex differences in major allergen production (Fel d 1)

ies by condurango bark indicates cross-reactivity between condurango bark and NRL. Up to now, definite proof of clinically relevant cross-reactivity between NRL and food by both positive oral challenge tests and inhibition tests has been reported only for banana4, 5 and chestnut.6 We here add condurango bark to the list of orally administered substances with proven cross-reactivity to NRL. In view of the high prevalence of NRL allergy and the not uncommon use of condurango bark, allergic reactions to the latter may be more frequent than this single case report suggests. REFERENCES

Predictive value of oral sulfonamide challenge for adverse reactions.

Predictive value of oral sulfonamide challenge for adverse reactions.

Risk factors for fetal macrosomia: the importance of a positive oral glucose challenge test.

The aim of this study was to investigate whether minor abnormalities of glucose metabolism without gestational diabetes are a risk factor for fetal overgrowth. A sample of 1883 unselected white mother-infant pairs were screened for gestational diabetes using a 50 g 1-h oral glucose challenge test (GCT) in two periods of pregnancy: early (16-20 weeks) and late (26-30 weeks). The effects of risk factors (glucose metabolism, previous history of mothers, obesity, multiparity and age of mothers) were estimated using a multinomial logit model. The level of risk was related to gestational age at the appearance of an abnormal GCT. Patients with an abnormal GCT in the early and late periods of pregnancy (Group 1) had a risk of delivering a large for gestational age (LGA) infant seven times higher than the control group (normal GCT in both periods), and patients with a normal GCT in the early period and an abnormal GCT in the late period (Group 2) showed a risk three times higher than the control group. Among the historical risk factors for LGA infants, such as maternal obesity, multiparity, previous gestational diabetes and previous delivery of an infant weighing 4000 g or more, only the latter was associated with fetal overgrowth with a risk level 4.7 higher than the control group. Group 1 patients had a significantly higher incidence of pregnancy-induced hypertension and preterm birth. There were no differences in the frequency of 5-min Apgar score < 7 and metabolic complications among the infants of all groups. We found a significantly higher rate of shoulder dystocia in Group 1 infants than in infants in the other groups. Our results suggest that a positive GCT at 26-30 weeks is the most important risk factor for fetal overgrowth. This result was strongly enforced in patients who had also shown a positive early GCT at 16-20 weeks.

Selecting Skin Testing Reagents to Predict Amoxicillin and Cephalosporin Allergy

Objectives This study assessed the accuracy of a panel of skin testing reagents to detect immunoglobulin E sensitivity to amoxicillin and oral cephalosporins. Methods One hundred and eighty-seven children and adolescents experiencing adverse reactions to amoxicillin (or amoxicillin/clavulanate), and/or an oral cephalosporin, that were considered sufficient to preclude further use were studied. Skin testing with penicillin G, commercial benzylpenicilloyl phosphate, penicillin minor determinant mixture (MDM), ampicillin, cefazolin, cefuroxime, and ceftriaxone was performed according to the suspected drug allergy, followed by an oral challenge, repeat skin testing, and prospective follow-up if no reactions were observed. Results Fifty-four (33.5%) of 161 patients with suspected amoxicillin reactions and 13 (50%) of 26 suspected cephalosporin reactions had positive skin tests or oral challenges. Positive reactions to only the MDM reagent occurred in 9 amoxicillin- or cephalosporin-allergic patients, to only the ampicillin reagent in 4 amoxicillin-allergic patients, and to only a cephalosporin reagent in 3 cephalosporin-allergic patients. No reactions to oral challenge were severe after negative skin testing. During prospective follow-up, one (0.9%) of 107 patients suspected of amoxicillin allergy who completed our skin testing—oral challenge repeat skin test protocol without a reaction and two (1.8%) patients with borderline reactions subsequently developed urticaria 8-16 months later while taking a course of amoxicillin. Reactions were mild. No test negative patients suspected of cephalosporin allergy developed a reaction with a subsequent course of a cephalosporin. Amoxicillin reactors with positive skin tests or oral challenges (N = 54) received 83 treatment courses of cephalosporins uneventfully in prospective follow-up. Conclusions Elective amoxicillin and cephalosporin skin testing and oral challenge protocols are helpful in identifying patients at very low risk for developing subsequent hypersensitivity reactions.