Donato Quaratino

Lipid transfer protein (Ara h 9) as a new peanut allergen relevant for a Mediterranean allergic population

BACKGROUND Nonspecific lipid transfer proteins (LTPs) represent potent pollen and food allergens. However, the allergenic properties of peanut LTP have not been studied. OBJECTIVE To identify LTP in peanut extract using sera from subjects with peanut allergy and Pru p 3-sensitized subjects from Southern Europe, clone and express this protein, and obtain information on the importance as allergen for these selected patients. METHODS Peanut LTP (Ara h 9) was cloned and sequenced by using a combination of bioinformatic and molecular biology tools (PCR, immunoblotting, Basic Local Alignment Search Tool [BLAST] searches). The immunologic properties of Ara h 9, Ara h 1, Ara h 2, and Ara h 3 were studied by using sera from subjects with peanut and peach allergy from Italy by immunoblotting and allergen microarray technology. RESULTS Two Ara h 9 isoforms-Ara h 9.01 and Ara h 9.02-were cloned and expressed. Ara h 9 represented a minor allergen for subjects with peanut allergy. However, including Ara h 9 as single component for serologic detection of sensitization to peanut by component-resolved diagnosis seems crucial, because the frequency of sensitization to the classic major peanut allergens Ara h 1, Ara h 2, and Ara h 3 was low in these patients from Southern Europe. CONCLUSION Ara h 9 is a new member of the LTP allergen family that seems to play an important role in peanut allergy for patients from the Mediterranean area.

A diagnostic protocol for evaluating nonimmediate reactions to aminopenicillins

BACKGROUND Maculopapular and urticarial rashes are nonimmediate manifestations common during aminopenicillin (AP) treatment, and the former often represent cell-mediated hypersensitivity. OBJECTIVES We sought to determine the significance and incidence of skin test reactions to APs in adults reporting adverse reactions during therapy with these beta-lactams and, particularly, to evaluate the potential of patch tests, delayed-reading skin tests, and challenges in the diagnosis of nonimmediate reactions. METHODS We used skin tests with penicilloylpolylysine, minor determinant mixture, benzylpenicillin, ampicillin, and amoxicillin, as well as patch tests with the last 3 drugs. We also performed in vitro assays for specific IgE and challenges with the suspect penicillin in subjects with nonimmediate reactions. RESULTS Among the 144 patients reporting nonimmediate manifestations (mostly maculopapular rashes), delayed hypersensitivity was diagnosed in 62 on the basis of positive patch test and/or delayed intradermal test results and responses to challenges; negative reactions to challenges allowed us to reasonably exclude the possibility of allergy in 66 subjects, and the challenge confirmed that 1 patient had linear IgA bullous dermatosis. Definitive diagnoses could not be provided for the remaining 15 subjects, who had negative allergologic test results, because they did not consent to challenges. In 40 of 49 immediate reactors, a diagnosis of IgE-mediated hypersensitivity was made. CONCLUSIONS Both patch and intradermal tests are useful in evaluating nonimmediate reactions to APs. Positive patch test and delayed intradermal responses together indicate delayed hypersensitivity. Intradermal testing appears to be more sensitive than patch testing, but the pattern of positive delayed intradermal test responses and negative patch test responses needs further investigation because of false-positive cases.

A case of IgE-mediated hypersensitivity to ceftriaxone

Anaphylactic shock (urticaria, dyspnea, tachycardia, and severe hypotension) developed in a 15-year-old boy with acute bronchitis within 5 minutes of receiving his first intramuscular injection of 1 g of ceftriaxone, which he had tolerated 3 months before. The hypotension and dyspnea resolved 2 hours after emergency treatment with subcutaneous adrenaline, 6-methyl-prednisolone, and chlorphenamine, and the urticaria disappeared after 12 hours. The patient’s personal and family histories were negative for allergic diseases; in particular, the patient had not experienced adverse reactions to other drugs.

IgE‐binding and cross‐reactivity of a new 41 kDa allergen of codfish

Background:  A 41‐kDa IgE‐reactive protein (p41) was purified from raw cod extract. This protein is homologous to an aldehyde phosphate dehydrogenase (APDH). The present study aims to evaluate the IgE‐binding and the cross‐reactivity of this protein in 13 patients allergic to codfish.

Long-Term Tolerability of Nimesulide and Acetaminophen in Nonsteroidal Antiinflammatory Drug-Intolerant Patients

BACKGROUND Oral challenges are used to identify alternative nonsteroidal antiinflammatory drugs (NSAIDs) for patients who react adversely to drugs of this class, but challenge conditions often differ from those in which the drug will actually be used. OBJECTIVE To determine whether the results of oral challenges with nimesulide or acetaminophen, using cumulative administration of a single therapeutic dose while the patient is in good health, can predict the response to multiple doses of the drug during future illness. METHODS Follow-up interviews were conducted with 248 NSAID-intolerant subjects who had tolerated oral challenges with nimesulide and/or acetaminophen 1 to 3 years earlier. We analyzed the adverse reaction rate in light of the febrile/non-febrile nature of the condition treated and the number of doses consumed. RESULTS Nimesulide was tolerated by 115/122 (94.2%) of the patients who had tried it; acetaminophen by 71/75 (94.6%). A total of 8/159 (5%) patients had experienced reactions (seven urticarial and one asthmatic) to one or both drugs. Intolerance was unrelated to the nature of the condition treated or the number of doses administered, but all four patients who failed to tolerate acetaminophen and 3/7 of those who reacted to nimesulide had histories of chronic urticaria. CONCLUSIONS Oral challenges can reliably predict long-term NSAID tolerability in patients with previous adverse reactions to other drugs of this class, except for patients with chronic urticaria.

Tolerability of meloxicam in patients with histories of adverse reactions to nonsteroidal anti-inflammatory drugs

BACKGROUND Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequent, particularly among patients with chronic urticaria or asthma. The need to identify an alternative drug that is safe and reliable is a common problem in clinical practice. OBJECTIVE To assess the tolerability of meloxicam, a new NSAID that selectively inhibits the inducible isoform of cyclooxygenase, in a group of NSAID-sensitive patients. PATIENTS AND METHODS We studied 177 patients who had suffered adverse reactions to one or more NSAIDs. Cutaneous reactions were reported by 83.1% of the subjects (urticaria in 55, angioedema in 52, urticaria/angioedema in 39, and maculopapular rash in 1), respiratory symptoms by 3.9%, both cutaneous and respiratory symptoms by 9%, Stevens-Johnsons syndrome by 2.3%, and anaphylactoid reactions by 1.7%. All subjects underwent a single-blind, placebo-controlled oral challenge with divided therapeutic doses of meloxicam (1.9 mg + 5.6 mg 1 hour later = cumulative dose 7.5 mg). RESULTS Positive reactions were observed in only two cases (1.1%), both manifested exclusively by cutaneous symptoms (urticaria/angioedema in one case and maculopapular rash/facial edema in the second). CONCLUSION Meloxicam seems to be well tolerated by NSAID-sensitive subjects whose reactions are manifested by urticaria/angioedema. Additional study is needed for a more complete assessment of its tolerability in patients with aspirin-induced asthma and other severe manifestations of NSAID sensitivity.

Prevalence of sensitization to Cupressus sempervirens : a 4-year retrospective study

In the last few years Cupressus sempervirens has been identified as the cause of an increasing number of cases of late winter-early spring pollinosis in Mediterranean countries. We conducted a 4-year retrospective study of a large group of subjects with documented allergic respiratory disease in order to determine the prevalence, clinical significance and annual rate of sensitization to C. sempervirens pollen. Anamnestic data and skin prick tests (SPT) with common aeroallergens and C. sempervirens extract were collected from 1397 subjects (712 male and 685 female) resident in Latium, a region in central Italy, with complaints related to upper- or lower-respiratory-tract disorders or conjunctival disease. Two hundred and forty-three subjects (17.4%) showed positive results to C. sempervirens extract: 47 (19.3%) of them were monosensitized. The annual sensitization rate of SPT positivity to C. sempervirens varied from 7.2% in 1995 to 22% in 1998. All the subjects monosensitized to cypress pollen had symptoms from January through April. Our study suggests that sensitivity to C. sempervirens is responsible for respiratory symptoms in an increasing percentage of subjects. Further studies are needed to determine its frequency at the national level.

Tolerability of Rofecoxib in Patients with Adverse Reactions to Nonsteroidal Anti-Inflammatory Drugs: A Study of 216 Patients and Literature Review

Background: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequent, particularly among patients with chronic urticaria or asthma. The identification of an alternative safe and reliable drug is a common problem in clinical practice. Objective: To assess the tolerability of rofecoxib, a new NSAID that selectively inhibits the inducible isoform of cyclooxygenase, in a large group of NSAID-sensitive patients. Methods: We studied 216 patients (164 females and 52 males) who had suffered adverse reactions to one or more NSAIDs; 98 subjects (45.4%) had experienced reactions to only one NSAID (single hypersensitivity) and 118 subjects (54.6%) had reacted to multiple NSAIDs (multiple hypersensitivity). Cutaneous reactions were reported by 79.6% of the subjects, respiratory symptoms by 10.7%, cutaneous and respiratory symptoms by 8.3%, anaphylaxis by 1.4%. All the subjects underwent a single-blind, placebo-controlled oral challenge with divided therapeutic doses of rofecoxib (6.25 mg +18.75 mg 1 h later = cumulative dose of 25 mg). Results: No reactions to the placebo were observed; only 1 subject (0.46%) experienced an urticarial reaction, after the second dose of rofecoxib. Conclusions: Considering previous studies and our own data, rofecoxib was well tolerated by all of the 174 patients with exclusively NSAID-related respiratory symptoms. Rofecoxib also had a very low rate (1.6%) of cross-reactivity in the 600 patients with exclusively cutaneous reactions to NSAIDs.

Selective type-1 hypersensitivity to cefuroxime

at concentrations that started at 0.1 mg/ml and increased in 10-fold steps until a positive reaction occurred, but the concentration did not exceed 100 mg/ml. Only 41% of the children who had positive reactions to WME also reacted to Der p 2. When the children who had positive reactions to these tests were divided according to whether they had a recent history of allergic disease, we found that 48% of the persons who had positive reactions to WME did not report clinically relevant respiratory symptoms. In contrast, this occurred in only 18% of those with positive reactions to Der p 2 (p , 0.001) (Fig. 1). We have previously shown that over 80% of Venezuelan patients attending an allergy clinic are sensitive to house dust mites, and the positive skin test reactions to WME and Der p 2 are very similar.6 Therefore the present results suggest that in the situation of endemic helminthic infection that exists in this country, positive skin test reactions to WME in an unselected group of children does not necessarily indicate an allergic condition. However, testing with purified Der p 2 allergen better discriminates between a nonsymptomatic atopic state and clinically relevant allergy. This might indicate that although many components of house dust mites can stimulate IgE antibody synthesis, the responses against some of these allergens, such as Der p 2, are more closely associated with the manifestation of clinical symptoms than others.

Etoricoxib Tolerability in Patients with Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs

Background: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly observed, particularly among patients with chronic urticaria or asthma. The identification of a safe and reliable alternative is a frequent problem in clinical practice. Our aim was to investigate the clinical tolerability of etoricoxib, a new selective cyclooxygenase-2 inhibitor, in a group of patients with well-established NSAID hypersensitivity. Methods: We assessed 31 adults (21 women and 10 men) who reported one or more adverse reactions to NSAIDs, manifested as cutaneous, respiratory or anaphylactic symptoms. Sixteen of them reported reactions to a single NSAID (single reactors) and 15 to more than one NSAID (multiple reactors); the most frequently involved drug was acetylsalicylic acid. First, each patient underwent allergologic tests (skin and/or oral challenge tests) with culprit NSAIDs and then tolerability tests with increasing doses of etoricoxib up to 120 mg. All challenges were performed under single-blind, placebo-controlled conditions. Results: NSAID hypersensitivity was diagnosed in all 31 patients: 3 displayed positive results to pyrazolone skin tests and the other 28 to challenges with culprit NSAIDs. None reacted to either placebos or etoricoxib. Conclusions: Etoricoxib seems to be a safe alternative for patients with well-demonstrated NSAID hypersensitivity.