SIRM-SIAAIC consensus, an Italian document on management of patients at risk of hypersensitivity reactions to contrast media.

Hypersensitivity reactions (HRs) to contrast media (CM) can be distinguished in immune-mediated (including allergic reactions) and non-immune-mediated reactions, even if clinical manifestations could be similar. Such manifestations range from mild skin eruptions to severe anaphylaxis, making it important for radiologists to know how to identify and manage them. A panel of experts from the Società Italiana di Radiologia Medica e Interventistica (SIRM) and the Società Italiana di Allergologia, Asma e Immunologia Clinica (SIAAIC) provided a consensus document on the management of patients who must undergo radiological investigations with CM. Consensus topics included: the risk stratification of patients, the identification of the culprit CM and of a safe alternative by an allergy workup, as well as the use of premedication and the correct procedure to safely perform an elective (i.e., scheduled) or urgent examination. The most important recommendations are: (1) in all patients, a thorough medical history must be taken by the prescribing physician and/or the radiologist to identify at-risk patients; (2) in patients with hypersensitivity reactions to CM, the radiologist must consider an alternative, non-contrast imaging study with a comparable diagnostic value, or prescribe a different investigation with another class of CM; (3) if such options are not feasible, the radiologist must address at-risk patients to a reference centre for an allergy evaluation; (4) if timely referral to an allergist is not viable, it is recommended to use a CM other than the responsible one, taking into account cross-reactivity patterns; in the case of patients with histories of severe reactions, the presence of an anesthesiologist is also recommended and a premedication is suggested.

Intradermal Tests With Drugs: An Approach to Standardization.

Background: Intradermal tests (IDTs) are performed and interpreted differently in drug allergy centers making valid comparison of results difficult. Objective: To reduce method-related and intercenter variability of IDTs by the introduction of a standardized method. Materials and methods: In 11 centers of the European Network for Drug Allergy, IDTs were prospectively performed with saline and with amoxicillin (20 mg/ml) using (1) the local method and (2) the standardized European Network in Drug Allergy (ENDA) method (0.02 ml). The diameters of the initial injection wheal (Wi) for the different volumes and sites injected obtained from each center were analyzed. Results: The most reproducible method was to fill a syringe with test solution, then expel the excess fluid to obtain exactly 0.02 ml. The median Wi diameter with 0.02 ml injection using the standardized method was 5 mm [range 2-10 mm; interquartile range (IQR) 5-5 mm; n = 1,096] for saline and 5 mm (range 2-9 mm; IQR = 4.5-5 mm; n = 240) for amoxicillin. IDT injection sites did not affect the Wi diameter. Training improved precision and reduced the variability of Wi diameters. Conclusion: Using the standardized IDT method described in this multicenter study helped to reduce variability, enabling more reliable comparison of results between individuals and centers.

The utility of the basophil activation test in the diagnosis of immediate amoxicillin or amoxicillin-clavulanate hypersensitivity in children and adults.

BACKGROUND: The basophil activation test (BAT), has been proposed as a possible assay for the diagnosis of immediate-type allergy to beta-lactams (BLs). The aim of this study was to assess the utility of BAT in the diagnosis of amoxicillin (AMX) or AMX-clavulanate (AMX-C) IgE-mediated hypersensitivity in children and adults. MATERIAL AND METHODS: Eighteen children and 21 adults, with clinical history of immediate reactions to AMX or AMX-C, were referred to Anna Meyer Children's Hospital and San Giovanni di Dio Hospital, respectively. They underwent in vivo tests (skin prick test and intradermal test). Moreover, BAT with AMX or AMX-C was performed within 6 months from the reaction. RESULTS: In the pediatric group, the concordance between the skin tests (ST) and BAT results was 83.3%. Upon comparing the symptom grades and ST results to the BAT results, we found that the reaction severity and ST positivity did not correlate with BAT results in children. In the adult group, the concordance between the ST and BAT results was 61.9%. Upon comparing patients with severe reactions and patients with mild reactions in terms of BAT results, we found a BAT sensitivity of 38.5% and a specificity of 100%. When comparing the symptom grades to the BAT results, we found that no patients with mild symptoms had a positive BAT result, whereas 38.5% of patients with severe symptoms had a positive BAT result. CONCLUSIONS: BAT does not seem to be a useful tool to increase the sensitivity of an allergy work-up to diagnose immediate hypersensitivity to AMX or AMX-C.

Antidrug antibodies against TNF-blocking agents: correlations between disease activity, hypersensitivity reactions, and different classes of immunoglobulins.

Although anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA), survival rates and resistance-to-therapy data confirm that about 30% of RA patients fail to respond. The aim of this study was to evaluate the correlations between the development of antidrug antibodies, specific IgG4 antibodies against TNF inhibitors, and resistance to therapy in RA patients. This retrospective study involved 129 patients with established RA naïve to biological agents (98 females and 32 males, mean age 56.7±12.3 years, disease duration 6.3±1.2 years, baseline Disease Activity Score [DAS]-28 3.2-5.6) who received treatment with anti-TNF agents after the failure of conventional disease-modifying antirheumatic drugs (32 received infliximab [IFX], 58 etanercept [ETN], and 39 adalimumab [ADA]). After 6 months of treatment, the patients were classified as being in remission (DAS28 <2.6), having low disease activity (LDA; DAS28 2.6-3.2), or not responding (NR: DAS28 >3.2). The patients were also tested for serum antidrug antibodies and IgG4 antibodies against TNF inhibitors. After 24 weeks of treatment, 38% of the ETN-treated patients and 28% of those treated with ADA had injection-site reactions; the rate of systemic reactions in the IFX group was 25%. The differences among the three groups were not statistically significant (P=0.382; ETN versus ADA P=0.319). The percentages of patients with adverse events stratified by drug response were: LDA 8% and NR 18% in the ADA group; in remission 3%, LDA 22%, and NR 10% in the ETN group; and LDA 6% and NR 16% in the IFX group (P=0.051). The percentages of patients with antidrug antibodies were: ADA 33.3%, ETN 11.5%, and IFX 10.3% (P=0.025; ADA versus ETN P=0.015). The percentages of patients with IgG4 antibodies were: ADA 6%, ETN 13%, and IFX 26% (P=0.017; ADA versus ETN P=0.437). Associations between antidrug antibodies, specific IgG4 antibodies, and adverse reactions were not significant for any of the three drugs. IgG4 levels were higher in the ADA group than in the other two groups, and higher in the patients with worse DAS28 (NR) and in those experiencing adverse events. These data suggest a possible association between IgG4 levels and worse DAS28 (r (2)=5.8%, P=0.011). The presence of specific IgG4 antibodies against TNF blockers in patients with RA might affect the drugs' activity. Patients with injection-site reactions and IgG4 against ETN may show a decreased response.

Spondylarthritis presenting with an allergic immediate systemic reaction to adalimumab in a woman: a case report.

INTRODUCTION: The efficacy of adalimumab, a fully human anti-tumor necrosis factor α recombinant antibody, has dramatically improved the quality of life of patients with rheumatoid and psoriatic arthritis and Crohn's disease. Because it is fully human, one should not expect immune reactions to this molecule. Adverse reactions to adalimumab are limited mainly to injection site reactions and are very common. Immediate systemic reactions are rarely reported. CASE PRESENTATION: We report the case of a 61-year-old Caucasian woman who was treated with adalimumab for spondylarthritis and developed injection site reactions after the sixth dose. After a two-month suspension, she recommenced therapy and experienced two systemic reactions. The first occurred after one hour with itching of the palms and soles and angioedema of the tongue and lips. Thirty minutes after the next dose the patient had itching of the palms and soles with diffusion to her whole body, angioedema of the lips, dizziness and visual disturbances. A skin-prick test and intra-dermal tests with adalimumab gave strong positive results at the immediate reading. However, serum-specific immunoglobulin E (IgE) to adalimumab were not detectable by using Phadia solid phase, especially harvested for this case, in collaboration with our Immunology and Allergy Laboratory Unit. Her total IgE concentration was 6.4 kU/L. CONCLUSION: We describe what is, to the best of our knowledge, the first reported case of immediate systemic reaction to adalimumab studied with a skin test giving positive results and a serum-specific IgE assay giving negative results. The mechanism of the reaction must be immunologic but not IgE-mediated.

Acute ST-segment elevation myocardial infarction complicating amoxycillin-induced anaphylaxis: a case report.

A 70-year-old man experienced an amoxycillin-induced anaphylactic reaction complicated by acute inferior myocardial infarction with transient ST-segment elevation. There was a spontaneous resolution of ST-segment elevation and the patient was treated for anaphylaxis. Coronary angiography showed severe obstructive coronary atherosclerosis, but not involving the infarct-related artery. Percutaneous coronary intervention of the affected artery was then performed and the patient was discharged three days later. Acute ST-elevation myocardial infarction has been described as one of the severe, still rare cardiovascular complications of anaphylaxis. In the present case, according to the previous reports, the main pathogenetic mechanism involved appears to have been coronary vasospasm probably caused by the release of potent vasoactive mast cell derived mediators in the setting of anaphylaxis.

Detection of specific IgE to quinolones.

BACKGROUND: In the last years, immediate reactions to quinolone antibiotics have been observed with increasing frequency, mainly urticaria, angioedema, and shock. No test was available because of the high incidence of false-positive results on skin tests. Thus the pathogenesis, value of diagnostic procedures, and cross-reactivity have not been evaluated in a systematic way. OBJECTIVE: We sought to assess whether these reactions are IgE mediated and whether an in vitro test for quinolone-specific IgE is useful in the diagnosis and understanding of cross-reactivity. METHODS: We assayed specific serum IgE to quinolones using epoxy-activated sepharose 6B as the solid phase in 55 patients with immediate adverse reactions; specificity of IgE binding was demonstrated by inhibition tests. RESULTS: The test yielded positive results in 30 (54.5%) patients who were tested 1 to 48 months after the reaction had occurred. The quinolone-specific IgE seems to disappear more slowly in atopic patients. The cross-reactivity between various quinolones allowed us to identify a common structural motif within quinolones that might be responsible for clinical and serologic cross-reactivity. CONCLUSION: A substantial portion of immediate reactions to quinolones appear to be IgE mediated. Cross-reactivity of IgE among different quinolones is frequent and suggests that a common avoidance of quinolones should be attempted in all patients with respective symptoms.