Cristiana Alonzi

Diagnosing Hypersensitivity Reactions to Cephalosporins in Children

OBJECTIVES. The goals were to evaluate the usefulness of skin tests, patch tests, serum specific IgE assays, and challenges in diagnosing hypersensitivity reactions to cephalosporins and to clarify the pathogenic mechanism of such reactions. METHODS. Children with immediate manifestations (within 1 hour) underwent immediate-reading skin tests with penicillin reagents and any suspect cephalosporins, serum specific IgE assays, and challenges; some children underwent reevaluations. Children with nonimmediate manifestations (after >1 hour) were assessed with patch tests, delayed-reading skin tests, and challenges. RESULTS. We evaluated 148 children with hypersensitivity reactions to cephalosporins, mainly cefaclor and ceftriaxone; 105 had experienced nonimmediate manifestations (mostly urticarial eruptions and maculopapular rashes) and 43 immediate manifestations (anaphylactic shock, urticaria and/or angioedema, and erythema). None of the nonimmediate reactors demonstrated positive results in patch tests and/or delayed skin tests; only 1 subject displayed immediate positive responses to penicillin skin-test reagents. Among the 104 patients with negative results, 96 underwent challenges; 95 tolerated the challenges, and 1 reacted to the cefaclor pediatric suspension and tolerated the challenge with a cefaclor capsule. In the first allergologic evaluation, 33 of the 43 children with immediate reactions displayed skin-test positivity. Of the 10 patients with negative results, 7 underwent challenges, followed by therapeutic courses and reevaluations for 4. All challenges and therapeutic courses were tolerated; in the reevaluation, 1 girl demonstrated positive skin-test results for both the responsible cephalosporin and penicillin reagents. Overall, IgE-mediated hypersensitivity was diagnosed for 34 (79%) of 43 subjects. CONCLUSIONS. Extremely few nonimmediate manifestations associated with cephalosporin therapy are actually hypersensitivity reactions, whereas most immediate reactions to cephalosporins are IgE-mediated. Cephalosporin skin testing is a useful tool for evaluating such reactions.

Lipid transfer proteins: the most frequent sensitizer in Italian subjects with food-dependent exercise-induced anaphylaxis

Specific food‐dependent exercise‐induced anaphylaxis (S‐FDEIAn) is a distinct form of food allergy in which symptoms are elicited by exercise performed after ingesting food to which the patient has become sensitised. Non‐specific FDEIAn (NS‐FDEIAn) is a syndrome provoked by exercise performed after ingesting any food.

Oral Rush Desensitization in Peanut Allergy: A Case Report

Allergy to peanuts represents one of the most severe food allergies, rarely remitting compared with milk and egg allergy and frequently associated with life-threatening allergic reactions (1, 2). Its prevalence in the United States is 1.1% (3). Clinical manifestations range from vomiting, diarrhea, and local or generalized urticaria–angioedema to dyspnea, hypotension, collapse, and anaphylactic shock (4). Ara h1, Ara h2, and Ara h3 have been identified as the major peanut allergens (5). Currently prolonged strict avoidance represents the only effective means to prevent allergic symptoms, but this is hardly feasible. Peanut-allergic patients are particularly vulnerable to accidental exposure because small traces (doses as low as 100 μg of protein) may provoke severe symptoms (6, 7). Results of peanut allergen monitoring showed a remarkable quantity of products (such as snacks, cereal bars, and potato snacks) with hidden allergen (8). Another study has shown how simple tasks such as shopping and eating in restaurants can be extremely frightening, even perceived as life-threatening (9). We report the case of a woman with peanut allergy who successfully underwent specific rush desensitization by the oral route (10–14).

A Clinical Trial of Oral Hyposensitization in Systemic Allergy to Nickel

Nickel allergy is the most common contact allergy. Some nickel-sensitive patients present systemic (cutaneous and/or digestive) symptoms related to the ingestion of high nickel-content foods, which significantly improve after a specific low nickel-content diet. The etiopathogenetic role of nickel in the genesis of systemic disorders is, furthermore, demonstrated by the relapse of previous contact lesions, appearance of widespread eczema and generalized urticaria-like lesions after oral nickel challenge test. The aim of this study is to investigate the safety and efficacy of a specific oral hyposensitization to nickel in patients with both local contact disorders and systemic symptoms after the ingestion of nickel-containing foods. Inclusion criteria for the recruitment of these patients were (other than a positive patch test) a benefit higher than 80% from a low nickel-content diet and a positive oral challenge with nickel. Based on the previous experiences, our group adopted a therapeutic protocol by using increasing oral doses of nickel sulfate associated to an elimination diet. Results have been excellent: this treatment has been effective in inducing clinical tolerance to nickel-containing foods, with a low incidence of side effects (gastric pyrosis, itching erythema).

Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins

BACKGROUND Studies performed on samples larger than 100 subjects with a documented IgE-mediated hypersensitivity to penicillins have demonstrated a cross-reactivity rate of approximately 1% between penicillins and both imipenem and meropenem, whereas a single study found a cross-reactivity rate of 6.2% with aztreonam in 16 such subjects. OBJECTIVE To assess the cross-reactivity and tolerability of aztreonam and 3 carbapenems (imipenem-cilastatin, meropenem, and ertapenem) in patients with documented IgE-mediated hypersensitivity to penicillins. METHODS A total of 212 consecutive subjects with immediate reactions to penicillins and positive results on skin tests to at least 1 penicillin reagent underwent skin tests with aztreonam and carbapenems; subjects with negative results were challenged with escalating doses of aztreonam and carbapenems. RESULTS All subjects displayed negative skin test results to both aztreonam and carbapenems; 211 accepted challenges and tolerated them. Challenges were not followed by full therapeutic courses. CONCLUSIONS These data indicate the tolerability of both aztreonam and carbapenems in penicillin-allergic subjects. In those who especially require these alternative β-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability.

Absence of cross-reactivity to carbapenems in patients with delayed hypersensitivity to penicillins

Studies performed on subjects with IgE‐mediated hypersensitivity to penicillins have demonstrated a 1% rate of cross‐reactivity between penicillins and both imipenem and meropenem, while a single study found a 5.5% rate of cross‐reactivity with imipenem/cilastatin in subjects with T‐cell‐mediated hypersensitivity to β‐lactams, mostly penicillins. We studied 204 consecutive subjects with a well‐demonstrated T‐cell‐mediated hypersensitivity to assess the cross‐reactivity with carbapenems and the tolerability of such alternative β‐lactams. All 204 subjects underwent skin tests with imipenem/cilastatin and meropenem; 130 of them were skin‐tested also with ertapenem. Subjects with negative test results were challenged with these carbapenems. All subjects displayed negative skin tests to carbapenems and tolerated challenges. These data demonstrate the absence of clinically significant T‐cell‐mediated cross‐reactivity between penicillins and carbapenems. Negative delayed‐reading skin testing with carbapenems in individuals with documented T‐cell‐mediated hypersensitivity to penicillins correlates well with subsequent clinical tolerance of therapeutic doses of carbapenems.

Diagnosing IgE-mediated hypersensitivity to sesame by an immediate-reading “contact test” with sesame oil

of between 5.25 and less than 10, 68%were refractory; and for patients with CU Index values of greater than or equal to 10, 88% were refractory (Fig 3). This suggests that almost 9 of 10 patients with a CU Index greater than or equal to 10 required more than antihistamine and LTRA therapy. Thus the CU Index could help guide whether a more aggressive level of medication will be required to achieve symptom control. One limitation of this study is that it was retrospective and the patients were not assessed and managed according to a common protocol; patients were at most treated with twice the manufacturer’s dose of nonsedating H1-antihistamines and not 4 times the dose, as has been recently identified as effective. Another limitation is that the determination of response to medications was based on a subjective evaluation of the medical record (by M. J. B. and R. K. V.) rather than a validated instrument, such as the Urticaria Activity Score. Despite these limitations, our results suggest that the CU Index has implications for predicting disease severity and responsiveness tomedications. A prospective study of patients with CIU is warranted to validate these findings and to further evaluate the clinical utility of the CU Index. Mark J. Biagtan, MD Ravi K. Viswanathan, MD Michael D. Evans, MS Sameer K. Mathur, MD, PhD

Hypersensitivity to Lamotrigine and Nonaromatic Anticonvulsant Drugs: A Review

Lamotrigine and nonaromatic antiepileptic drugs (valproate, gabapentin, and topiramate) are associated with hypersensitivity reactions, mainly cutaneous eruptions. The underlying mechanisms of these manifestations are not yet completely understood. A cell-mediated pathogenic mechanism has been demonstrated in some cases on the basis of positive patch tests and/or lymphocyte transformation tests. Moreover, an in vitro lymphocyte toxicity assay, which exposes the patients lymphocytes to arene oxides, has detected lymphocyte susceptibility to toxic metabolites in patients with hypersensitivity reactions to lamotrigine. Subjects with a history of mild hypersensitivity reactions and negative allergologic tests can be challenged with the suspected drugs. Challenge tests can also be useful to identify safe alternatives. Our study reports hypersensitivity reactions to lamotrigine and to nonaromatic antiepileptic drugs, especially those assessed by allergologic tests.

Same‐patient allergy to ampicillin and human insulin

clinically justified threshold . This study describes the effect of sublingual immunotherapy (SLIT) on well days in a randomized, double-blind, placebo-controlled, multicentre trial with the high-dose sublingual 6-grass pollen preparation AllerSlit forte. For details of study design, patient characteristics, primary results of SMS and safety, see (3). Well days are defined as days without intake of rescue medication and a symptom score £ 4. The definition is based on an inclusion criterion of the study. Recruited patients had to have a minimum symptom score of 4 on each day during the week after the grass pollen peak. Therefore, well days were correlated with a real improvement in patients symptoms and no need of rescue medication. The number of well days were analysed in 89 patients [active 41; placebo 48; Per Protocol Set (PP)]. After baseline observation during the 2003 grass pollen season, patients received SLIT for 1.5 years until the end of the 2005 pollen season. During the grass pollen season, patients rated 10 different symptoms (four nasal, three ocular, three bronchial) on a scale from 0 to 3 and documented intake of medication in a diary. Data for a 42-day period in the grass pollen season (highest grass pollen count) were evaluated. Differences between treatment groups were checked by using Wilcoxon–Mann–Whitney U-test. The median number of well days in the active and placebo groups did not differ in the baseline year 2003 (P = 0.9538), i.e. patients randomized to active treatment had 4/42 well days (9.5%), and placebo patients 7.5/42 well days (17.9%). After 1.5 years of SLIT in 2005, actively treated patients had a significantly higher median number of well days (22/42; 52.4%) than placebo patients (4.5/42; 10.7%) (P = 0.0007) (Fig. 1). The SMS also significantly improved after 1.5 years of SLIT in comparisonwith placebo [median area under the curve of SMSat baseline: active group 501, placebo group 430; after 1.5 years of SLIT: active 197, placebo 453 (PP; P = 0.0005)] (3). Therefore, the increase in number of well days corresponds well to the results in SMS. Hence, the above-defined well days are an additional variable to measure the efficacy of SIT. Well days confirm the excellent efficacy of the high-dose sublingual grass pollen preparation AllerSlit forte.