Arianna Aruanno

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.

Food allergy and food intolerance: diagnosis and treatment

Food allergy is a matter of concern because it affects about 0.5–3.8% of the paediatric population and 0.1–1% of adults, and as well may cause life-threatening reactions. Skin prick testing with food extracts and with fresh foods, the measurement of food-specific IgE, elimination diets and a double-blind, placebo-controlled food challenge are the main diagnostic procedures; many non-validated procedures are available, creating confusion among patients and physicians. The treatment of food allergy is still a matter of debate. Antihistamines, corticosteroids and, if necessary (in case of anaphylaxis), epinephrine, are the drugs of choice for the treatment of symptoms of food allergy. Sodium cromolyn may be used prophylactically even though there are no controlled studies certifying its efficacy. The only etiologic treatment of food allergy is specific desensitization. Sublingual-oral-specific desensitization has been used by our group for the treatment of food-allergic patients with a high percentage of success.

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.

Apple desensitization in two patients with PR‐10 proteins allergy

month later, the patient achieved a complete remission followed by ANCA disappearance within 3 months. He remained healthy after an 18-month follow-up but still steroid dependent for asthma (12 mg/day). In this observation, masitinib allowed asthma control and a rapid discontinuation of steroids. Three hypotheses for the occurrence of the vasculitis can be put forward. Firstly, masitinib-associated CSS as an adverse side-effect of this new drug cannot be excluded because in two recent clinical trials, skin rashes, edema, and petechies were observed in 30%, 20%, and 5%, respectively (1, 2) but were not related to vasculitis or hypereosinophilia. Furthermore, selective inhibition of c-kit, PDGFR, and ABL has been suggested as an alternative therapy for ANCA-associated vasculitis, via the inhibition of T-cell activation and proliferation demonstrated in vitro (4). Therefore, this hypothesis seems unlikely. Secondly, montelukast-associated CSS could be evoked because leukotriene receptor antagonists have been debated for the onset of CSS. Indeed, an increase in circulating leukotrienes, as the consequence of blockade of leukotriene receptors, may initiate vasculitis through strong chemoattraction for neutrophils and eosinophils (5). However, a direct drug effect is unlikely because the onset of CSS usually occurred up to 10 months after starting treatment with leukotriene antagonists (6), whereas our patient had taken montelukast for many years and the vasculitis has not relapsed despite the continuation of this drug. Lastly, and more likely in the authors’ opinion, a flare of CSS may have been promoted by the rapid steroid withdrawal during masitinib treatment, as a steroid-sparing agent. Indeed, in this observation, the lateonset asthma and its severity suggested an underlying and undiagnosed CSS, as asthma often precedes the diagnosis of this vasculitis with a mean time lapse of 9 years (3). Thus, physicians should pay attention to vasculitis symptoms in the course of steroids tapering for asthma, because they can unmask a systemic vasculitis. *Service de Médecine Interne Hôpital Nord Assistance Publique-Hôpitaux de Marseille (AP-HM) Université de la Méditerranée 13915 Marseille France Tel.: +33 4 91 96 87 11 Fax: +33 4 91 96 80 80 E-mail: bgranel@ap-hm.fr

Sublingual immunotherapy for latex allergy: tolerability and safety profile of rush build-up phase

ABSTRACT Objective: Sublingual immunotherapy represents an efficient therapeutic tool for the management of latex allergic patients. Local and systemic adverse reactions are reported, and risk factors for those reactions are poorly understood. The aim of this study is to compare two different rush induction protocols (2-day and 3-day) in terms of safety and tolerability and effectiveness in reaching the maintenance dose. Methods: Twenty-three outpatients (F/M = 18:5; 5–64 years of age), with latex allergy were randomly assigned to: Group 1 (2-day) and Group 2 (3-day). Adverse reactions were classified by their type and severity. Results: Twenty-one subjects, 10 from Group 1 and 11 from Group 2, reached the maintenance dose, 70% of them without side effects. Seven adverse events were reported in Group 1: three were local (oral itching) and spontaneously remitted; four were systemic (Grade-2: two reactions; Grade-3: two reactions) and were effectively controlled with drugs. The protocol was interrupted in two cases because of recurrent reactions. No reactions were reported in Group 2. Age, gender, atopy, specific IgE, skin prick tests and sublingual challenge did not seem to influence the risk of side effects significantly. No significant modification of skin tests and specific IgE levels were reported in both groups. The cutaneous test turned negative in 16 patients, eight from Group 1 (80%) and eight from Group 2 (73%). The remaining patients (two from Group 1 and three from Group 2) showed a reduction of latex reactivity, in terms of symptom score (MIS: 2 vs. 0.5 in Group 1, 3 vs. 1 in Group 2). Conclusions: This study confirms the safety of rush induction. The 3-day protocol was better tolerated than the 2-day. Significant risk factors for the occurrence of adverse reactions were not identified. Only the type of protocol but not patient-related parameters seemed predictive of side-effects.

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.

Challenge tests in the diagnosis of latex allergy

The aim of this study is to evaluate the sensitivity, specificity and safety of challenge tests and their usefulness in the diagnosis of latex allergy. Forty adult subjects (F/M = 34/6, aged 18–66 yrs) with a history of adverse reactions after latex exposure and positive prick test and/or specific IgE to latex were enrolled. They were compared with 20 control subjects. They underwent provocative (cutaneous, mucous-oral, sublingual, conjunctival, nasal, bronchial, vaginal) tests. Symptoms and drug scores were recorded for each patient during challenges. All patients reacted to at least one of the following: cutaneous, nasal and conjunctival tests. No systemic reactions requiring epinephrine occurred. Of the challenges, the vaginal test resulted as the safest, but it had low sensitivity and many limits related to the procedure. According to our data, bronchial and nasal tests had the highest sensitivity (76% and 82% respectively), and were more precise than other tests in determining latex exposure and symptoms, but the bronchial test also presented the highest rate of risk. Mucous and cutaneous tests resulted as the most reliable. For all the tests, specificity and positive predictive value were 100%. All control subjects resulted negative to all challenges. There were no statistically significant changes in skin and serologic tests between the first and second visits. Correlations between MIS and skin tests and between MIS and serum tests were not found. Challenges can be considered safe diagnostic procedures. Tests that most faithfully reproduce natural exposure, on the basis of a patients history, are preferable.