Lucilla Pascolini

Tolerability of Aztreonam in Patients with Cell-Mediated Allergy to β-Lactams

Background: Cross-reactivity between aztreonam and β-lactams is poor, but tolerability of aztreonam has been assessed in a few groups of patients suffering from IgE-mediated allergy to β-lactams. The aim of this study was to assess the cross-reactivity of aztreonam with other β-lactams and its tolerability in patients with cell-mediated allergy to these drugs. Methods: We studied 78 patients with cell-mediated allergy to β-lactams who underwent skin prick, immediate and delayed-reading intradermal tests as well as patch tests with penicilloyl-polylysine, minor determinant mixture, semi-synthetic penicillins, cephalosporins, aztreonam and imipenem. Patients with negative allergy testing with aztreonam underwent an intramuscular test dosing and were observed for 3 h. Results: Our patients experienced 94 non-immediate reactions; delayed-onset urticaria (34 cases), maculopapular exanthema (13 cases), urticaria/angioedema (15 cases) and itching erythema (13 cases) were the most reported symptoms. Amoxicillin (35 cases), ampicillin (28 cases) and bacampicillin (18 cases) were the most involved drugs. All patients had a positive patch test and/or a positive delayed-reading intradermal test to at least 1 β-lactam antibiotic and none had a positive patch or delayed-reading intradermal test to aztreonam. Then, 65 patients underwent intramuscular test dosing with aztroenam, and none of them had a clinical reaction. Conclusions: Our data confirm the lack of cross-reactivity between β-lactams and aztreonam in patients with cell-mediated allergy to these drugs. Delayed-reading intradermal tests and patch tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in β-lactam-allergic patients.

Sublingual desensitization in patients with wasp venom allergy: preliminary results.

The aim of this paper is to assess in an open prospective pilot case-control study the tolerability, safety and efficacy of an ultra-rush sublingual immunotherapy (SLIT) protocol with Vespula venom in wasp allergic patients compared to subcutaneous immunotherapy (SCIT). Forty-one wasp allergic patients were treated with sublingual (SLIT group) or subcutaneous (SCIT group) ultrarush immunotherapy with Vespula venom extract. All patients underwent skin tests and serum specific IgE and IgG4 detection before enrolment and after 6, 12 and 24 months of immunotherapy. The SLIT group consisted of 21 (6 females and 15 males) patients who received increasing doses of Vespula venom (Aquagen, ALK-Abelló) until the final dose of 30 drops of extract in 3 hours, containing 100,000 SQ-U/ml. The maintenance dose was of 10 drops of pure venom extract 3 times a week, for a total dose of 100,000 SQ-U weekly (corresponding to 100 μg of venom extract). The SCIT group consisted of 20 patients (16 males and 4 females) who were treated with subcutaneous ultrarush immunotherapy with Vespula venom extract (Pharmalgen, Alk-Abelló). Patients received 101.1 μg of Vespula venom in 3 hours and were treated with 100 μg of wasp venom monthly. During the ultrarush sublingual treatment 2 patients (9.5%) experienced mild side-effects. Specific IgE and specific IgG to wasp venom did not show any significant modification. Four patients were field-stung by a wasp during the treatment (for a total of 6 stings). Two patients (3 stings), with a previous clinical history of a grade III and IV reaction, did not experience any reaction. One patient, with a previous grade II reaction, showed a large local reaction. The fourth patient, with a previous grade III reaction, was re-stung twice (after 12 and 24 months) with two systemic reactions (SR) (mild throat constriction). During the ultrarush SCIT phase, 3 (15%) patients experienced side-effects: 2 of them showed a large local reaction and 1 had headache and stomach ache. Specific IgE showed a significant (P=0.001) increase after 6 months of treatment and then returned to baseline levels while specific IgG showed a significant (P=0.001) increase after 6, 12 and 24 months in comparison with baseline. Nine patients were field-stung during the treatment: 8 of them experienced large local reactions; one patient (11%) experienced an SR (dizziness). Our results, even if in a small number of patients, suggest that in patients with Hymenoptera sting allergy SLIT could be efficacious with a good tolerability profile when compared to SCIT. Larger studies are needed to assess efficacy, safety and tolerability profile of wasp venom SLIT.

Cross‐reactivity and tolerability of imipenem in patients with delayed‐type, cell‐mediated hypersensitivity to β‐lactams

Background:  Administration of imipenem‐cilastatin to patients with IgE‐mediated hypersensitivity to β‐lactams has always been considered potentially harmful. Recent studies have demonstrated the tolerability of carbapenems (imipenem‐cilastatin and meropenem) in patients with IgE‐mediated hypersensitivity to β‐lactams; there are no studies on this topic regarding patients with cell‐mediated allergy to β‐lactams. The aim of this study is to assess cross‐reactivity and tolerability of imipenem in patients with cell‐mediated allergy to β‐lactams.

Profilin Desensitization in Two Patients with Plant-Derived Food Allergy

Profiling are “panallergens”, responsible for many cross-reactivities between inhalant, latex and plant-derived food allergens. We evaluated the effectiveness and the safety of sublingual desensitization treatment (SLIT) in two patients with allergic respiratory and food diseases. Skin prick tests, IgE and IgG4 assays to pollens, some plant-derived foods, profilin, non-lipid specific transfer protein and PR 10 proteins were performed. The patients also underwent double-blind placebo-controlled challenge (DBPCFC) with the culprit foods and profilin and then a SLIT with it. Both the patients had positive SPT, specific IgE and DBPCFCs with profilin and some vegetables referred in anamnesis. They therefore underwent SLIT with profilin extract. At the end of treatment, the patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Profilin desensitization allowed our patients to manage their diet without restriction, eating several foods previously not tolerated.

Allergic and non-allergic drug hypersensitivity reactions in children.

Adverse drug reactions (ADR) are an important medical problem. The aim of this study is to investigate the clinical characteristics of children with ADR and to assess the tolerability of alternative drugs in children (under 16 yrs of age) with a history of ADR. We studied 278 children (132 males and 146 females). Patients were studied by recording personal history and performing in vivo skin testing, in vitro laboratory tests and challenge tests. Patients who had experienced mild adverse reactions underwent challenge tests without any premedication; patients with a clinical history of moderate reactions, received a premedication with sodium cromolyn 30 min before the oral challenge; patients with a clinical history of severe reactions or undergoing parenteral challenges, were given an antihistamine 30 minutes before. A total of 660 adverse events were reported with 126 different drugs involved. Antimicrobial agents were the most involved drugs (51.7%). Non-steroidal anti-inflammatory drugs were involved in 22.7% of episodes. The most reported symptoms were cutaneous. Allergy testing was negative in 272 patients. A diagnosis of drug allergy was reported for 6 patients. A total of 669 challenge tests were performed. 639 were negative at first attempt while 22 were positive. Eight were repeated using a different premedication and resulted negative. Hypersensitivity drug reactions in children are mainly non-allergic. A premedication with sodium cromolyn or with oral H1-antihistamines may be useful in preventing ADR.

Utility of Basophil Activation Test for monitoring the acquisition of clinical tolerance after oral desensitization to cow’s milk: Pilot study

Objective The quantification of basophil activation by flow cytometry is a useful tool for the assessment of immediate-type responses to food allergens and the prediction of clinical tolerance in food allergy patients. The aim of this study is to investigate how the analysis of allergen-induced CD63 up-regulation by flow cytometry can be effective in monitoring the acquisition of clinical tolerance by specific oral desensitization in food allergy. To our knowledge, this is the first study to examine this topic. Materials and methods Three male patients affected by cow’s milk allergy underwent successful oral desensitization to cow’s milk. In order to monitor the acquired clinical tolerance that occurred after treatment, we performed laboratory tests for total and specific IgE, specific IgG4 and the Basophil Activation Test (BAT) both at baseline and at the end of the desensitization protocol. Results Using a fluorescent enzyme immunoassay, the comparison of specific cow’s milk antibodies before and after treatment showed a decrease of specific IgE levels, without reaching normal values, and an increase of specific IgG4 levels. A complete suppression of cow’s milk proteins (α-lactoalbumin, β-lactoglobulin and casein) induced CD63 regulation was observed in all three reported cases. Conclusions Using flow cytometry, food allergen-specific basophil responses could be monitored in order to identify an acquired tolerance induced by desensitization treatment. Although further studies are needed to develop this important new topic, it was interesting to note that the BAT seemed to be more sensitive and characterized by a close correlation with clinical tolerance.

Sublingual immunotherapy with natural rubber latex: a case report with 8‐year follow‐up

We report a patient who successfully underwent sublingual latex immunotherapy and who has been followed-up for 8 years. Since the 1970s, type I allergy to natural rubber latex (NRL) has been a public health problem (1). Symptoms of NRL allergy range from contact urticaria and asthma to anaphylaxis. They are elicited by direct contact with NRL items (e.g. medical devices) or by inhalation of airborne latex proteins. Proper diagnosis of latex allergy is important for appropriate preventive measures and treatment.

The clinical meaning of positive latex sIgE in patients with food/pollen adverse reactions.

Natural rubber latex allergy (NRL-A) is an international problem of public health. About 50–60% of NRL-A patients may present adverse reactions after ingestion of cross-reacting vegetable foods. This condition, called “Latex-fruit Syndrome”, is a matter of research. The aim of our study is to distinguish between clinical/subclinical latex-fruit syndrome and cross-sensitization to latex and food/pollen allergens on the basis of latex recombinant allergens. We studied 51 patients with food hypersensitivity and serological evidence of NRL sensitization. The subjects underwent an accurate allergological evaluation (skin prick test with latex, food and pollen extracts, specific IgE to latex and recombinant allergens, challenge provocation tests). The patients were divided in two groups: group A) 34 patients with clinical and serological latex and fruit/vegetable allergies; group B) 17 patients allergic to fruits/vegetables and/or pollens, with serological, but not clinical NRL-A. All the latex challenge tests resulted positive in group A patients and only two patients of group B presented positive cutaneous challenge tests. Moreover, specific IgE-antibodies were detected to rHev b 5, to rHev b 6.01, to rHev b 6.02 and to rHev b 8 (and other profilins) of group A patients, while in group B we observed a monosensitization to Hev b8, probably linked to a cross-sensitization to pollens and foods. At the present state of knowledge, we need a multi-parametric approach based on a combination of clinical history, diagnostic tests (CRD) and latex challenge tests to make diagnosis of latex-fruit syndrome.

Delayed hypersensitivity to heparin in a patient with cancer: fondaparinux may be safe but needs to be tested

Venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism, is the second leading cause of death in patients with cancer (1). Anticoagulant therapy, such as heparin, is used for prophylaxis and treatment for thrombosis in patients with cancer. Heparin may cause all types of allergic reactions, particularly cell-mediated type IV and antibody-mediated type II reactions (2). Risk factors for cell-mediated hypersensitivity to heparins include female sex, obesity, and long treatment duration.

Profilin desensitisation in patients with adverse reaction after plant-derived: our experience

Profilins constitute a family of highly conserved proteins, which are present in all eukaryotic cells and are involved in processes related to cell motility. The first allergenic profilin was described in birch pollen and was designated Bet v 2. Allergenic profilin were identified in tree and grass pollens, in weeds, in plant-derived foods, as well as in latex. Due to conserved structure of the profilins, specific IgE may cross-react with homologues from virtually every plant source. Therefore, profilin sensitization is a risk factor for allergic reactions to multiple pollen and food allergen sources. Profilins are randomly distributed in pulp and peel and they are labile to heat denaturation and pepsin digestion. In fact the ingestion of vegetables in profilin sensitized patients usually determines reactions restricted to the oral cavity (oral allergy syndrome, OAS), despite in literature systemic reactions to zucchini and litches are reported. We describe the history of six patients with adverse reactions after eating plant-derived food and positive allergological evaluation (skin tests, specific IgE, basophil activation test and double-blind placebo-control challenges (DBPCFC) for profilin, that have been undergone to desensitization treatment. The protocol of desensitization started with a drop of profilin solution (50 µg/ml) diluted 1:1018 in water until the highest dose of 10 drops of undiluted solution three times a week. They underwent this desensitization treatment at home and were followed in Day Hospital regimen monthly. According to the protocol they were trained in medical treatment of allergic reactions and equipped with an emergency kit: autoinjectable epinephrine, betamethasone and clorphenamine. At the end of the treatment all patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Moreover, the desensitization with profilin has proved to be safe as no serious adverse events were observed in our patients. Profilin desensitization allowed that our patients could manage their diet without restriction, eating several foods previously not tolerated.