Summary:Background. Evidence regarding drug provocation test (DPT) with chemo-therapeutic agents is scarce. The aim of our study is to describe the experience of DPT in patients with a history of hypersensitivity reactions (HSRs) to antineoplastic and biological agents. Methods. Eight-year retrospective, observational, descriptive study of patients with a history of HSRs to chemo-therapy who were submitted to DPT. Anamnesis, skin tests (ST) and DPT were analyzed. Patients with a negative DPT were submitted to at least one regular supervised administration (RSA). Patients with positive DPT or HSR during RSA were offered rapid drug desensitization (RDD). Results. A total of 54 patients were submitted to DPT. The most common suspected drugs were platins (n = 36), followed by taxanes (n = 11). Most of the initial reactions were classified as grade II (n = 39) according to Brown's grading system. ST with platinum (n = 35), taxanes (n = 10) and biological agents (n = 4) were negative, except for one intradermal test with paclitaxel, which was positive. A total of 64 DPTs were performed. Eleven percent of all DPTs were positive [platins (n = 6), doxorubicin (n = 1)]. Of the 57 RSA with the culprit drugs, 2 were positive (platins). The diagnosis of hypersensitivity was confirmed by DPT/RSA in 9 patients. All patients with positive DPT/RSA presented HSRs of equal or less severity than the initial one. Conclusions. DPT followed by RSA allowed to exclude HSRs in 45 patients (55 culprit drugs). DPT before desensitization prevents non-hypersensitivity patients from undergoing RDD. In our study DPT was safe, all reactions were managed by an allergist.

BACKGROUND AND OBJECTIVE:Drug-induced anaphylaxis is an unpredictable and potentially fatal adverse drug reaction. The aim of this study was to identify the causes of drug-induced anaphylaxis in Portugal.METHODS:During a 4-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 313 patients with drug anaphylaxis were received and reviewed. Statistical analysis included distribution tests and multiple logistic regression analysis to investigate significance, regression coefficients, and marginal effects.RESULTS:The mean (SD) age of the patients was 43.8 (17.4) years, and 8.3% were younger than 18 years. The female to male ratio was 2:1.The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (47.9% of cases), antibiotics (35.5%), and anesthetic agents (6.1%). There was a predominance of mucocutaneous symptoms (92.2%), followed by respiratory symptoms (80.4%) and cardiovascular symptoms (49.0%). Patients with NSAID-induced anaphylaxis showed a tendency towards respiratory and mucocutaneous manifestations. We found no significant associations between age, sex, or atopy and type of drug. Anaphylaxis recurrence was observed in 25.6% of cases, and the risk was higher when NSAIDs were involved.CONCLUSIONS:NSAIDs were the most common cause of anaphylaxis in this study and were also associated with a higher rate of recurrence. We stress the need for better therapeutic management and prevention of recurring episodes of drug-induced anaphylaxis.

Clopidogrel is an antiplatelet drug widely used for treatment and prevention of a variety of cardiovascular diseases. We report a successful desensitization to clopidogrel in a 70-year-old Caucasian man with delayed hypersensitivity (HS) reaction. He developed lip, hand and foot swelling, erythematous papular non-pruritic lesions and arthralgias 2 weeks after starting treatment with clopidogrel 75 mg/d. A 3-hour desensitization protocol was started, achieving a cumulative dose of 154 mg without any reaction, and a daily dose of 75 mg was recommended. On the 4th day, the patient developed skin lesions similar to the previously described. He was treated with topical steroids and oral antihistamines, and the daily dose of clopidogrel was reduced to 20 mg. A new desensitization protocol was established, with a slow dose increment, according to the patient's response. It was only possible to achieve the dose of 75 mg/d after 2 months. Although well tolerated by most patients, HS reactions with clopidogrel may occur and desensitization is rising as a safe alternative in those patients. In delayed reactions with cutaneous lesions, a slower desensitization protocol may be necessary, as in this case.

Introduction and Aims: To evaluate the efficacy and safety of telmisartan combined with clopidogrelin and/or leflunomide for patients with lgA nephropathy and whether the combination therapy surpass telmisartan in decreasing proteinuria and protecting renal function. Methods:We enrolled 400 patients aged 18-55 years from 13 centers in Beijing who had proteinuria 0.5 ̃3.5g per day, baseline serum creatinine (SCr) <265.2μmol/L (3mg/ dl). All patients were eluted by taking telmisartan 80mg per day for 4 weeks and then randomly assigned to receive at least 24 weeks of treatment with telmisartan 80mg per day + clopidogrelin placebo + leflunomide placebo (group A), telmisartan 80mg per day + clopidogrelin 50mg per day + leflunomide placebo (group B), telmisartan 80mg per day + clopidogrelin placebo + leflunomide 20mg per day (group C), telmisartan 80mg per day + clopidogrelin 50mg per day + leflunomide 20mg per day (group D). Comparison of 24-hr urinary protein excretion, the serum creatinine, eGFR, albumin, cholesterol and uric acid, before and after the therapy were assessed. Results: No statistically significant differences were observed for any baseline clinical data including age, gender, BMI, blood pressure, proteinuria, serum creatinine, eGFR, serum uric acid in the four groups (P>0.05). After treatment for 24 weeks, a significant decline of proteinuria was observed in the four groups (P <0.05), while those in group C (1.20±0.76 vs 0.77±0.42 g/24h) and group D (1.16±0.63 vs 0.74±0.49 g/24h) were decreased more significantly than in group A (1.15±0.87 vs 0.92±0.58 g/24h) and group B (1.11±0.83 vs 0.89±0.42 g/24h) (P<0.05). Mixed effects were showed that telmisartan, leflunomide, and telmisartan combined with leflunomide were effective in lowering proteinuria (P<0.01) by model analysis. The extent of serum creatinine decline in group C and group D displayed more significantly than that in group A and group B (P<0.05). The levels of eGFR in group C and group D were increased more than those in group A and group B. The decline of serum uric acid in group C and group D displayed more significantly than group A and group B (P<0.05). There were no significant differences in the results of albumin and cholesterol among the four groups (P > 0.05). No obvious adverse reactions were found in the four groups. Conclusions: In the selected patients with IgA nephropathy, telmisartan combined with leflunomide was safe and effective in decreasing proteinura and protecting short-term renal function. Larger randomized studies would be needed to confirm these results in the long run.

Nasal obstruction is one of the most common symptoms, and septoplasty one of the most frequently performed surgeries in otorhinolaryngology. In order to evaluate the subjective response to septoplasty the AAO-HNS implemented the NOSE scale, developed and validated for North-Americans. The authors carried out the adaptation and validation of the NOSE scale for Portuguese language and population, allowing its further use in Portuguese studies. Subsequently, the validated Portuguese NOSE scale was employed in the evaluation of subjective results in a cohort of 100 patients that underwent septoplasty. A pre-operatory NOSE value of 74,6 was found, in contrast to 19,3 found in the post-operatory period. The results statistically confirmed the success of septoplasty in the improvement of nasal obstruction in patients with deviated nasal septum. The Portuguese NOSE scale confirmed to be a simple, rapid and reliable method for the evaluation of subjective nasal obstruction.