Alberto Venuti

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.

Evaluation of adverse cutaneous reactions to aminopenicillins with emphasis on those manifested by maculopapular rashes

We assessed 195 subjects with histories of adverse reactions to aminopenicillins, using 1) skin tests with penicilloyl polylysine (PPL), minor determinant mixture (MDM), benzylpenicillin (PG), amoxicillin, and ampicillin (read after 20 min and 48 h); 2) patch tests with PG, amoxicillin, and ampicillin; and 3) RAST for penicilloyls G and V. Oral challenges with ampicillin, amoxicillin, and penicillin V were administered to 34/60 patients reporting maculopapular reactions. Immediate hypersensitivity (IH), in most cases for both penicillin and aminopenicillins, was diagnosed (based on skin tests, RAST, or both) in 35 subjects who had suffered anaphylactic shock, or urticaria, angioedema, or both urticaria and angioedema. Thirty‐three of the 60 subjects reporting maculopapular reactions presented delayed intradermal and patch‐test positivity, indicating delayed hypersensitivity (DH), for ampicillin and amoxicillin, and three were also positive for PG. Diagnoses were confirmed with oral challenges in 18/33. The remaining 27/60 were negative in all allergologic tests, with oral‐challenge confirmation in 16. Our findings highlight the importance of the amino group in DH to aminopenicillins. Moreover, the mean time interval between the last reaction and our tests was significantly (P < 0.01) longer in DH subjects (54.96 months) than in those with IH (18.62 months), suggesting that the time of testing is less important in cases of DH.

Diagnostic work-up for food-dependent, exercise-induced anaphylaxis.

Fourteen patients with suspected food‐dependent, exercise‐induced anaphylaxis (EIAn) were subjected to prick tests with commercial food extracts and common airborne allergens, prick + prick tests with fresh foods, determination of total IgE levels, and specific IgE for 31 foods (CAP System FEIA RAST). All were positive for two or more foods; 10 presented hypersensitivity to 11 or more foods. On the basis of these findings, history data, and responses to food‐exercise challenges (treadmill stress tests 90 min after meals containing none of the suspected foods and none associated with skin‐test and/or RAST positivity) and suspected food‐exercise challenges (SFECs — administered after meals containing the suspected food), three patients were diagnosed as having specific food‐dependent EIAn (for wheat in two cases, tomato in one). In nine others, the presence of specific IgE for numerous foods (including those suspected on the basis of histories and utilized in the SFECs) suggests involvement of specific food hypersensitivity, although SFEC confirmation could not be obtained. Avoidance of all foods associated with test positivity 4 h before exercise has prevented all further EIAn episodes in these 12 patients. In two others, the reactions did not appear to be related to IgE directed against specific food allergens, and these subjects have eliminated further reactions by avoiding all meals for the 4 h preceding exercise. These findings emphasize the importance of allergologic testing with a wide panel of food allergens (including foods used for seasoning, such as garlic or parsley) in all patients with suspected food‐dependent EIAn. Prick + prick tests with fresh foods and the CAP System RAST disclosed numerous hypersensitivities.

Diagnosing Nonimmediate Reactions to Penicillins by in vivo Tests

Background: Maculopapular and urticarial rashes are nonimmediate manifestations common during penicillin treatment; the former often represent cell-mediated hypersensitivity. Our objectives were to assess the incidence of allergy in adults reporting nonimmediate manifestations during penicillin therapy and to evaluate the diagnostic potential of patch tests, delayed-reading skin tests and challenges in such cases. Methods: We used prick and intradermal tests as well as patch tests with penicillin determinants, ampicillin, amoxicillin and any other suspect penicillins. We also performed challenges with the suspect antibiotics. Results: Such antibiotics were aminopenicillins in 93.1% of 259 patients, most of whom had suffered from maculopapular rashes followed by piperacillin (4.2%). Three subjects displayed immediate skin test positivity. Ninety-four subjects showed patch test and delayed intradermal test positivity to the culprit penicillin (90 to aminopenicillins and 4 to piperacillin) and were considered as having had delayed hypersensitivity reactions. Five of the 8 subjects who displayed delayed intradermal test positivity and patch test negativity to the suspect penicillin underwent challenges, 2 reacted positively to the responsible aminopenicillin. Among the remaining 154 with negative results in allergologic tests, 125 agreed to undergo challenges; only 3 reacted. In all, 98 patients – 93 of whom had experienced maculopapular rashes – displayed delayed hypersensitivity (94 to aminopenicillins and 4 to piperacillin). Conclusions: Both patch and intradermal tests are useful in evaluating nonimmediate reactions to penicillins, particularly maculopapular rashes. Patch test and delayed intradermal positivity together indicate delayed hypersensitivity. Intradermal testing appears to be slightly more sensitive than patch testing.

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.

Prevalence of Sensitization to Alternaria in Allergic Patients in Italy

BACKGROUND The actual prevalence of sensitization to Alternaria is not known, partly due to the unreliability of diagnostic extracts. OBJECTIVE To assess skin positivity to extracts of Alternaria in a wide population of Italian patients suffering from respiratory symptoms using a biologically standardized extract. METHODS A total of 2942 patients were skin prick tested with Alternaria, and a panel of common inhalant allergens. Blood samples for specific IgE quantitation were taken both from patients positive and from patients negative (control group) to Alternaria extract. RESULTS Three hundred six patients (10.4%, ranging from 1.8% in Turin to 29.3% in Cagliari) were positive to Alternaria; 37 were sensitized to only this mold, while the remaining 269 were sensitized to at least one other allergen. Of the Alternaria-positive patients, 79.7% suffered from rhinitis and 53.3% from asthma, either alone or associated with other symptoms. CONCLUSIONS We suggest that, at least in Italy and in countries with similar climatic and environmental situations, standardized Alternaria extract should be included in the panel commonly used in investigating the allergen responsible in patients suffering from respiratory allergy.

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.

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.

ASA disease: the clinical relationship of nasal polyposis to ASA intolerance.

SummaryWe studied the complex relationship between nasal polyposis and ASA (acetylsalicylic acid) intolerance in 154 patients with nasal polyps. The clinical histories of all patients were reviewed, and diagnostic tests for immune or allergic causes and the responsiveness of patients to challenges with ASA-substitutive drugs were analyzed. A third of our patients tested were found to have positive personal histories of atopy and 35% showed ASA intolerance. Although 40% had bronchial asthma, only 16.8% of all patients had positive tests for allergy. We were unable to find a specific mechanism to explain the relationship between nasal polyposis and ASA intolerance and further investigations are still required.

Intolerance to aspirin: clinical and immunological studies.

Skin-tests, patch-tests, Prausnitz-Küstner reactions, passive cutaneous anaphylaxis in guinea pigs according to Ovary and lymphocyte proliferation tests in vitro using thymidine 2-C14 have been carried out in 31 patients with aspirin intolerance. Acetylsalicyclic acid, aspiryl-polylysine, lysine acetylsalicylate, and sodium salicylate were used in these investigations. Collagen-induced platelet aggregation according to BORN in the presence of aspirin was also studied. An immunological mechanism was revealed in only a small percentage of the patients studied, indicating in the remaining cases the possible role of nonimmunological processes or the inadequacy of the test technique employed.