Allergy to beta-lactam antibiotics in children: Risk factors for a positive diagnostic work-up.

BACKGROUND: Allergy to beta-lactam (ßL) antibiotics is highly reported in children, but rarely confirmed. Risk factors for a positive diagnostic work-up are scarce. The primary aim was to characterize the cases of children with confirmed ßL allergy, investigating potential risk factors. Secondary aims were to assess the prevalence of allergy to ßL in this population and to confirm the safety of less extensive diagnostic protocols for milder reactions. METHODS: We reviewed the clinical data from all children evaluated in our Department for suspected ßL allergy, over a six-year period. RESULTS: Two hundred and twenty children (53% females) with a mean age of 6.5±4.2 years were evaluated. Cutaneous manifestations were the most frequently reported (96.9%), mainly maculopapular exanthema (MPE). The reactions were non-immediate in 59.5% of the cases. Only 23 children (10.5%) were diagnosed with allergy to ßL. The likelihood of ßL allergy was significantly higher in children with a family history of drug allergy (p<0.001) and in those with a smaller time period between the reaction and the study (p=0.046). The probability of not confirming ßL allergy is greater in children reporting less severe reactions (p<0.001) and MPE (p<0.001). We found the less extensive diagnostic protocol in milder reactions safe, since only 4.2% of the children presented a positive provocation test (similar reaction as the index reaction). CONCLUSION: This study highlights family history of drug allergy as a risk factor for a positive diagnostic work-up. Larger series are required, particularly genetic studies to accurately determine future risk for ßL allergy in children.

Clinical approach on challenge and desensitization procedures with aspirin in patients with ischemic heart disease and nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Hypersensitivity to acetylsalicylic acid (ASA) constitutes a serious problem for subjects with coronary artery disease. In such subjects, physicians have to choose the more appropriate procedure between challenge and desensitization. As the literature on this issue is sparse, this study aimed to establish in these subjects clinical criteria for eligibility for an ASA challenge and/or desensitization. METHODS: Collection and analysis of data on ASA challenges and desensitizations from 10 allergy centers, as well as consensus among the related physicians and an expert panel. RESULTS: Altogether, 310 subjects were assessed; 217 had histories of urticaria/angioedema, 50 of anaphylaxis, 26 of nonimmediate cutaneous eruptions, and 17 of bronchospasm related to ASA/nonsteroidal anti-inflammatory drugs (NSAID) intake. Specifically, 119 subjects had index reactions to ASA doses lower than 300 mg. Of the 310 subjects, 138 had an acute coronary syndrome (ACS), 101 of whom underwent desensitizations, whereas 172 suffered from a chronic ischemic heart disease (CIHD), 126 of whom underwent challenges. Overall, 163 subjects underwent challenges and 147 subjects underwent desensitizations; 86 of the latter had index reactions to ASA doses of 300 mg or less. Ten subjects reacted to challenges, seven at doses up to 500 mg, three at a cumulative dose of 110 mg. The desensitization failure rate was 1.4%. CONCLUSIONS: In patients with stable CIHD and histories of nonsevere hypersensitivity reactions to ASA/NSAIDs, an ASA challenge is advisable. Patients with an ACS and histories of hypersensitivity reactions to ASA, especially following doses lower than 100 mg, should directly undergo desensitization.

An unusual case of delayed-type hypersensitivity to ceftriaxone and meropenem.

Recent studies have demonstrated a low cross-reactivity between ß-lactam antibiotics and carbapenems in IgE-mediated reactions. There are no studies on cross-reactivity of meropenem in patients with non-immediate hypersensitivity to cephalosporins. We describe a case of a 13-year-old male, admitted in Neurosurgery with a severe extradural empyema complicating frontal sinusitis, submitted to an emergent bifrontal craniotomy. A generalized maculopapular exanthema, fever and malaise, appeared by the 7th day of meningeal doses of ceftriaxone, clindamycin and vancomycin. Those were replaced by meropenem, with posterior worsening of the reaction and mucosal involvement. A new scheme with amikacin, metronidazole and linezolid was done with improvement. Skin prick, intradermal and patch tests to penicillins, ceftriaxone and meropenem were negative. Lymphocyte transformation test was positive to ceftriaxone and negative to meropenem.Non-immediate T cell mechanism seems to be involved. Diagnosis work-up couldn't exclude cross-reactivity between ceftriaxone and meropenem.

Desensitisation to aspirin in antiphospholipid antibody syndrome

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Assessment of asthma control: clinical, functional and inflammatory aspects.

BACKGROUND: Asthma is a complex disease with numerous markers of severity/activity. Clinical assessment,functional parameters and inflammation biomarkers are the most used A correlation between them is difficult, as each one evaluates a particular aspect of the disease. OBJECTIVE AND METHODS: To explore the possible association between asthma control, pulmonary function and inflammation in patients with asthma, consecutive asthmatics underwent simultaneous spirometry (measurement of FEV1), exhaled nitric oxide (eNO) evaluation and Asthma Control Test (ACTTM) questionnaire. RESULTS: The study included 232 asthmatics (mean age: 37.48 years; 78.4%female): 43% had uncontrolled asthma (ACTTM < or = 19) with FEV1 mean values of 83.3% +/- 21.8; 48% partially controlled (ACTTM: 20-24) with FEV1 of 87.6% +/- 17; 9% complete control (ACTTM = 25) with FEV1 of 93.1 +/- 20.6. The relation ACTTM/FEV1 and ACTTM/FEF 25-75% was statistically significant (p = 0.001 and p = 0.034, respectively). Among patients with eNO < 35 ppb, 66% had FEV1 > 80% and 52% had ACTTM > 19. No association was found combining ACTTM/eNO or FEV1/eNO. A subgroup of 66 patients was evaluated twice. CONCLUSION: An association was found between ACTTM and spirometry, with higher ACTTM scores reflecting less bronchial obstruction. The authors advise a combined approach in asthma follow-up, involving clinical aspects, functional parameters and inflammation biomarkers, although in some circumstances ACT could be a valid instrument to be used alone to assess control.

Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper.

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

Possible DRESS syndrome in a child with borreliosis

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General considerations on rapid desensitization for drug hypersensitivity - a consensus statement.

Drug hypersensitivity reactions can occur with most drugs, are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance of a compound responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated. It is a high-risk procedure used only in patients in whom alternatives are less effective or not available after a positive risk/benefit analysis. Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs. Desensitization is mainly performed in IgE-mediated reactions, but also in reactions where drug-specific IgE have not been demonstrated. Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication. Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course. In this paper, some background information on rapid desensitization procedures is provided. We define the drugs and drug reactions indicated for such procedures, describe the possible mechanism of action, and discuss the indications and contraindications. The data should serve as background information for a database (accessible via the EAACI-homepage) with standardized protocols for rapid desensitization for antibiotics, chemotherapeutic agents, monoclonal antibodies/fusion proteins, and other drugs.