Relevance of the diagnosis of hypersensitivity reactions to antineoplastic and biological agents: experience with drug provocation test.

Summary: Background. Evidence regarding drug provocation test (DPT) with chemotherapeutic 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. This was an eight-year retrospective, observational, descriptive study of patients with a history of HSRs to chemotherapy 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 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.

Portuguese version of Parent-reported Drug Hypersensitivity Quality of Life Questionnaire (P-DrHy-Q): assessment of reliability and validity.

Summary: Background. Drug hypersensitivity in children impacts the quality of life of the patients and their caregivers. The parent-reported drug hypersensitivity quality of life questionnaire (P-DrHy-Q), the first disease-specific quality-of-life questionnaire for caregivers who have children with drug hypersensitivity, was recently developed. The aim of this study was to assess the validity and reliability of the portuguese version of the P-DrHy-Q. Methods. A translation of the Parent-reported Drug Hypersensitivity Quality of Life Questionnaire (P-DrHy-Q) to the Portuguese population was performed, assessing its applicability in 74 caregivers from two allergy departments. The analyses included internal consistency (Cronbach's alpha) and test-retest reliability: 14 caregivers completed the P-DrHy-Q without any intervention one week after answering the first questionnaire. Results. The 12-item scale assessed the mental health and social activity. The internal consistency of the scale was good (Cronbach's alpha = 0.884) and the test-retest associations were excelent (intra-class correlation coefficient = 0.985; p < 0.001). The mean value of the questionnaire was 37.01 (SD 18.57) with Mental Health being more affected than Social Activity. Employed caregivers had a significant higher score (p < 0.001). No other factor was statistically significant. Conclusions. The Portuguese version of the P-DrHy-Q is valid for evaluating quality of life impairment in Portuguese caregivers of children with drug hypersensitivity. Its application might be relevant for future research and provide clinicians and researchers with a tool to define which psychosocial support is required to provide more comprehensive care in drug hypersensitivity.

Hypersensitivity to antiretroviral drugs.

Summary: Background. Antiretroviral therapy (ART) may be responsible for hypersensitivity reactions varying in severity, clinical manifestations and frequency. Case report. We report the case of a 47-year-old woman with HIV infection who developed a delayed mucocutaneous reaction after treatment with ART. Hypersensitivty reaction (HR) to emtricitabine and tenofovir was considered probable based on positive patch tests (PT) and hypersensitivity reaction to nevirapine was confirmed by drug provocation test. Discussion. The diagnosis of HR to ART remains a diagnostic challenge, partly due to unknown mechanism and the absence of validated diagnostic tools. Patch testing may represent a useful method for confirming hypersensitivity. Further investigation in this area is required, so that successful management strategies can be offered, preventing loss of potent and viable antiretroviral agents.

Drug-induced anaphylaxis survey in Portuguese Allergy Departments.

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.

Desensitization to clopidogrel: a tailor-made protocol.

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.

Drug-induced anaphylaxis survey in Portuguese Allergy Departments

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 (AU)

Antecedentes: La anafilaxia inducida por medicamentos es una reacción adversa impredecible y potencialmente fatal. El objetivo de este estudio fue identificar las causas de la misma en Portugal. Método: Durante un periodo de 4 años fue desarrollado un sistema de notificación nacional de anafilaxia enfocado al informe voluntario de los alergólogos. Se recopilaron 313 casos de pacientes con anafilaxia por medicamentos. El análisis estadístico incluyó test de distribución y regresión logística múltiple para analizar la significación y los coeficientes de regresión y efectos marginales. Resultados: La edad media de los pacientes fue de 43.8 ± 17.4 años, 8.3% menores de 18 años. La relación mujer/varón fue de 2:1. El grupo más frecuentemente implicado fue el de los analgésicos antiinflamatorios no esteroideos (AINEs), seguido de los antibióticos y anestésicos en 47.9%, 35.5% y 6.1% de los casos respectivamente. Se observó un predominio de los síntomas mucocutáneos (92.2%), seguidos de los respiratorios (80.4%) y cardiovasculares (49.0%). Los pacientes con anafilaxia por AINEs mostraban más síntomas respiratorios y mucocutáneos. No se encontró asociación entre edad, género y atopia con los diferentes grupos de medicamentos. La recurrencia de anafilaxia se observó en el 25.6% de los casos, con un riesgo incrementado cuando los AINEs eran los responsables. Conclusiones: En este estudio, los AINEs fueron los medicamentos más frecuentemente implicados en las reacciones de anafilaxia y mostraron más frecuencia de reincidencia de las reacciones. Es importante evaluar bien los tratamientos y prevenir la reincidencia de anafilaxia por medicamentos (AU)

Possible DRESS syndrome in a child with borreliosis

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Immediate hypersensitivity to penicillins with negative skin tests--the value of specific IgE.

The determination of specific IgE in patients with history of penicillins hypersensitivity is simple, safe and widely available. The positive and negative predictive values of this determination, however, are not yet established. In order to evaluate them, we performed specific IgE determination and diagnostic drug challenges in a group of 22 patients with a clear history of immediate penicillins hypersensitivity but negative skin tests. In this sample, the positive and negative predictive values were 29% and 87%, respectively. This seems to indicate that a positive specific IgE is not enough to confirm the diagnosis, and further study is necessary.

Work up of patients with history of beta-lactam hypersensitivity.

INTRODUCTION: Beta-lactam antibiotics are the most frequent cause of antibiotic hypersensitivity reactions. The study of all cases of suspected beta-lactam hypersensitivity is highly important, to avoid the use of less efficient or more expensive alternatives, for fear of a reaction. MATERIALS AND METHODS: Sixty-seven consecutive patients with suspected beta-lactam hypersensitivity reactions were studied. Skin prick tests (SPT), intradermal tests (IDT) and specific IgE determination were performed. In non-immediate reactions, epicutaneous testing was also done. If all were negative, a drug challenge was performed. RESULTS: Sixty-seven patients (54 female symbol), with a mean age + or - SD of 36.6 + or -19.3 years (4-78 years) were studied. The self-reported antibiotics were amoxicillin and amoxicillin/clavulanic acid in 30 (45%), penicillin in 24 (36%), cephalosporins in 11 (16%) and flucloxacillin in 2 (3%). SPT and IDT were positive in 6 patients (9%) and specific IgE in 11 (16%). Only one patient had both positive specific IgE and skin tests. Of the remaining 51 cases, 33 underwent a drug challenge with the culprit antibiotic, with a positive reaction in 2 (6%). In all positive cases and when a drug challenge with the suspected antibiotic was not indicated, a challenge with an alternative drug was done, all with negative results. CONCLUSIONS: 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.

Work up of patients with history of beta-lactam hypersensitivity

Introduction: Beta-lactam antibiotics are the most frequent cause of antibiotic hypersensitivity reactions. The study of all cases of suspected beta-lactam hypersensitivity is highly important, to avoid the use of less efficient or more expensive alternatives, for fear of a reaction. Materials and methods: Sixty-seven consecutive patients with suspected beta-lactam hypersensitivity reactions were studied. Skin prick tests (SPT), intradermal tests (IDT) and specific IgE determination were performed. In non-immediate reactions, epicutaneous testing was also done. If all were negative, a drug challenge was performed. Results: Sixty-seven patients (54 women), with a mean age ± SD of 36.6 ± 19.3 years (4–78 years) were studied. The self-reported antibiotics were amoxicillin and amoxicillin/clavulanic acid in 30 (45%), penicillin in 24 (36%), cephalosporins in 11 (16%) and flucloxacillin in 2 (3%). SPT and IDT were positive in 6 patients (9%) and specific IgE in 11 (16%). Only one patient had both positive specific IgE and skin tests. Of the remaining 51 cases, 33 underwent a drug challenge with the culprit antibiotic, with a positive reaction in 2 (6%). In all positive cases and when a drug challenge with the suspected antibiotic was not indicated, a challenge with an alternative drug was done, all with negative results. Conclusions: 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 (AU)

Desensitization to methylphenidate--the relevance of continued drug intake for a successful outcome.

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.

Desensitization to methylphenidate – The relevance of continued drug intake for a successful outcome

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 generalise derythema, 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 wasre-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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Delayed hypersensitivity reactions to corticosteroids.

BACKGROUND: Corticosteroids (CS) are widely used in the treatment of asthma, allergic disorders and other immunological diseases due to their anti-inflammatory and immunosuppressive properties. Physicians seldom suspect them of causing allergic reactions. However, more and more cases of hypersensitivity reactions to CS have been described. Reports of delayed allergic reactions to CS in patients with asthma or allergic rhinitis are scarce. MATERIAL AND METHODS: We report the case of a 44-year-old woman with a history of mild persistent asthma and intermittent allergic rhinitis, treated with inhaled beclomethasone and salbutamol, who developed a delayed mucocutaneous and respiratory reaction after substitution of beclomethasone with budesonide. CONCLUSIONS: The interest of this case lies in the rarity of allergic reactions from inhaled CS in patients with asthma and/or rhinitis. These reactions therefore represent a diagnostic and therapeutic challenge.

Nimesulide-induced fixed drug eruption.

BACKGROUND: Nimesulide is a cyclooxygenase (COX) inhibitor with a high degree of selectivity to COX-2. It is a widely used and well tolerated nonsteroidal antiinflammatory drug that also has analgesic and antipyretic properties. The most frequently reported side effects concern the gastrointestinal tract. Pruritus and skin rash are the most common cutaneous adverse reactions. There are only eight cases of fixed drug eruptions due to nimesulide, described in the literature. CASE REPORT: The authors report a case of a patient with a history of antihistamine hypersensitivity who developed a bullous form of pigmented fixed drug eruption after nimesulide ingestion. Patch tests performed on residual skin lesion were positive to nimesulide, confirming that this was the culprit drug. CONCLUSIONS: Fixed drug eruptions are common cutaneous drug reactions, often misdiagnosed. A detailed anamnesis and physical examination are the key to suspect this condition.

Delayed hypersensitivity reactions to corticosteroids

Background: Corticosteroids (CS) are widely used in the treatment of asthma, allergic disorders and other immunological diseases due to their anti-inflammatory and immunosuppressive properties. Physicians seldom suspect them of causing allergic reactions. However, more and more cases of hypersensitivity reactions to CS have been described. Reports of delayed allergic reactions to CS in patients with asthma or allergic rhinitis are scarce. Material and methods: We report the case of a 44-year-old woman with a history of mild persistent asthma and intermittent allergic rhinitis, treated with inhaled beclomethasone and salbutamol, who developed a delayed mucocutaneous and respiratory reaction after substitution of beclomethasone with budesonide. Conclusions: The interest of this case lies in the rarity of allergic reactions from inhaled CS in patients with asthma and/or rhinitis. These reactions therefore represent a diagnostic and therapeutic challenge

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