tive predictive value of provocation tests with beta-lactams. Allergy 2010; 65: 327-332.Provocation tests with beta-lactams play an important role in the diagnosis of hypersensitivity reactions to these antibiotics (1-3). In particular, drug provocation tests are included in both of the diagnostic algorithms of the European Network for Drug Allergy (ENDA) for evaluating immediate and nonimmediate hypersensitivity reactions to beta-lactams (2, 3). Immediate reactions are those occurring within the first hour after the last drug administration and are manifested clinically by urticaria, angioedema, rhinitis, bronchospasm and anaphylactic shock. Non-immediate reactions occur more than one hour after the last drug administration. The main non-immediate reactions are maculopapular eruptions and delayed-appearing urticaria/angioedema.Indications of provocation tests with beta-lactams are extensive for the European Academy of Allergology and Clinical Immunology -ENDA group (2-4) and more restricted for the American Academy of Allergy Asthma and Immunology (5). Recently, ENDA simplified the protocol of provocation tests in patients with immediate reactions to beta-lactams by reducing the number of doses (6). In addition, the ENDA questionnaire (7) allows patients with a potential beta-lactam allergy to be identified, and recommendations on drug provocation tests are available (4).Though not well established, the negative predictive value is important for both the patient and the physician. The patient has to know whether a reaction can occur after taking a drug, which was tested negatively. It is now well known that adverse drug reaction and especially drug allergy/ hypersensitivity are sources of anxiety and led to an avoidance of the drug. On the other hand, the physician has to Keywords allergy; beta-lactams; drug provocation tests; hypersensitivity; negative predictive value. Only 118 (25.8%) were re-exposed to the negatively tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h after drug administration) reaction: five urticaria, three exanthema and one undefined cutaneous reaction. None were severe. Only four accepted a re-challenge, negative in two cases and positive in the two others. The negative predictive value was 94.1% (89.8-98.3) (111 out of 118 patients). Conclusion: Although the negative predictive value of drug provocation tests may not be 100%, none of the false negative patients experienced a life-threatening reaction. This should reassure doctors who might hesitate to prescribe beta-lactams, even in patients with negative allergic work-ups.

Carboplatin, a second-generation platinum compound, is a chemotherapeutic drug effective in many types of cancers. Its use is limited by the development of systemic allergic reactions in up to 30% of the cancer patients. Therefore, it is very important to make a correct diagnosis of true carboplatin allergy, for the crucial clinical implications. In this regard, no biological test is actually available to detect specific immunoglobulin E in the sera of patients allergic to carboplatin. We evaluated a new experimental biological test in patients with suspected immunoglobulin E-mediated reactions to carboplatin. Three patients with suspected hypersensitivity reactions to carboplatin underwent skin tests with an undiluted aliquot (10 mg/ml) of carboplatin preparation planned for infusion. Total serum immunoglobulin E and specific immunoglobulin E to the two platinum salts carboplatin and cisplatin were determined with the ImmunoCAP system (Phadia AB, Uppsala, Sweden). We detected specific immunoglobulin E to carboplatin in all three patients, whereas specific immunoglobulin E to cisplatin was observed in one patient. The positivity of specific immunoglobulin E against carboplatin in these three patients is a new and encouraging observation for the development of a new important instrument that can help clinicians in their therapeutic decisions, after a hypersensitivity reaction to a platinum salt.

Of the 67 studied cases with history of beta-lactam hypersensitivity reactions, 18 (27%) were confirmed after testing. A combination of skin testing, specific IgE determination and drug challenge is necessary since none has sufficient sensitivity to be used alone.

A link between amoxicillin-induced rash in infectious mononucleosis and allergy has been previously reported. However, the pathophysiological cause and aspects are unclear. Additionally, the complex immunological interaction between the host and Epstein-Barr virus needs to be studied. This article reports a case of amoxicillin-induced rash in infectious mononucleosis resulting in an exuberant rash, facial edema, and marked eosinophilia, which prompted additional workup. Both the eosinophilia and the rash brought to light a possible association with a persistent delayed-type hypersensitivity. Further scientific discussion and investigation can identify predictive indicators that can portend clinical outcome.

Objective:Characterization of the adverse drug reactions (ADR) reported by the immunoallergology department (IAD), Centro Hospitalar de São João (Porto), to the Northern Pharmacovigilance Centre (NPC).Methods:An observational, descriptive and retrospective study was conducted, based in a spontaneous report system. Participants were all the patients from the IAD, with suspected ADR, reported to NPC by specialists after the study was completed.Results:Studied population had a median age of 41 years, with the predominance of the female gender (73.2%). Allergic rhinitis and asthma were the most frequent comorbidities. All studied ADR were type B, 89.6% were serious, 86.4% unexpected and 2.6% associated with drugs that presented less than 2 years in the market. The most represented drug classes were the non-steroidal anti-inflammatory drugs (NSAIDs) (52.6%) and antibiotics (25.2%). Skin symptoms represented 61.2% of the reported complaints. About 52.9% of these ADR occurred in less than one hour after intake. The most frequent ADR treatment at the time of the reaction was drug interruption (86.2%), followed by the prescription of anti-histamines (42.2%).Conclusions:Reported ADR to NPC by the Drug Alert Unit were mainly serious, unexpected, associated with NSAIDs and antibiotics and related with marketing authorization medicines older than two years. These results could be very useful to develop strategies to prevent the clinical and economic consequences of ADR.

Methylphenidate is the treatment of choice in attention-deficit/hyperactivity disorder (ADHD). The authors report the case of a 7 year old boy with ADHD and psoriasis who developed generalised erythema, pruritus and fever 5 hours after the first oral administration of methylphenidate. After 2 days of treatment the drug was discontinued with complete resolution of symptoms. Later on, the drug was re-introduced with recurrence of the same clinical symptoms. Patch tests were performed with negative results. Desensitization was proposed and performed because there is no alternative treatment for ADHD. After the therapeutic dose was achieved, the mother interrupted drug intake because of a misunderstanding of instructions, and a mild rash subsided when another pill was administered. After this event the same desensitization procedure was carefully repeated. Interruption of drug intake during desensitization and consequent recurrence of clinical symptoms highlights the importance of continued exposure to the culprit drug in this kind of procedure. This modified protocol may enable patients with cutaneous reactions to this drug, to maintain therapy without recurrent reactions.

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