Hipersensibilidade a Anti-inflamatórios Não Esteróides em Doentes Asmáticos com Idade Pediátrica

Introdução: Os dados publicados sobre a frequência de hipersensibilidade (HS) a anti-inflamatórios não esteróides (AINEs) em doentes asmáticos são discrepantes, sendo escassos na população pediátrica. O objectivo deste estudo foi avaliar a frequência de HS a AINEs, reportada por inquérito telefónico em doentes asmáticos com idade pediátrica. Métodos: Incluíram -se os doentes com idades entre 6 e 17 anos com clínica de asma confirmada por prova de broncodilatação positiva, realizada no período entre 1 de Agosto de 2008 e 30 de Novembro de 2010. Aplicou-se um inquérito telefónico para questionar sobre alguma reacção adversa a fármacos, nomeadamente a AINEs. Perante o reportar de reacção adversa a AINEs, detalhava-se fármaco envolvido, idade na primeira reacção, manifestações clínicas, intervalo entre a toma e o início da reacção, reprodutibilidade, evicção do fármaco implicado e tolerância de fármacos alternativos. Resultados: Foram selecionados, por prova de broncodilatação positiva, 184 doentes. Foi possível aplicar o inquérito a 111/184 (60,3%). A maioria (59,4%) era do género masculino, com 11 ± 3,1 anos. Nove doentes (8,1%) reportaram reacção de HS a AINEs, reprodutível em três. A primeira reacção ocorreu com uma idade mediana de 2 anos (P25:1,8; P75:5,75), abaixo dos 10 anos em todos os doentes. O ibuprofeno foi o fármaco implicado em todos os casos, sendo o paracetamol usado em alternativa. Todos descreveram reacções imediatas, com as seguintes manifestações: respiratória (7), cutânea (3), gastrintestinal (1). A frequência reportada de sintomas respiratórios como manifestação de reacção de HS a AINEs nesta amostra de doentes asmáticos foi de 6,3% (7/111). Quatro doentes (3,6%) estavam sob evicção de AINEs apesar de negarem qualquer reacção de HS prévia. Conclusões: A frequência reportada de HS a AINEs contraria os dados que descrevem estas reacções como infrequentes abaixo dos 10 anos de idade. O paracetamol parece ser uma alternativa segura.

Investigation and Control of a Large Outbreak of Multi-Drug Resistant Tuberculosis at a Central Lisbon Hospital

An increase in the number of new cases of tuberculosis (TB) combined with poor clinical outcome was identified among HIV-infected injecting drug users attending a large HIV unit in central Lisbon. A retrospective epidemiological and laboratory study was conducted to review all newly diagnosed cases of TB from 1995 to 1996 in the HIV unit. Results showed that from 1995 to 1996, 63% (109/173) of the Mycobacterium tuberculosis isolates from HIV-infected patients were resistant to one or more anti-tuberculosis drugs; 89% (95) of these were multidrug-resistant, i.e., resistant to at least isoniazid and rifampicin. Eighty percent of the multidrug-resistant strains (MDR) available for restriction fragment length polymorphism (RFLP) DNA fingerprinting clustered into one of two large clusters. Epidemiological data support the conclusion that the transmission of MDR-TB occurred among HIV-infected injecting drug users exposed to infectious TB cases on open wards in the HIV unit. Improved infection control measures on the HIV unit and the use of empirical therapy with six drugs once patients were suspected to have TB, reduced the incidence of MDR-TB from 42% of TB cases in 1996 to 11% in 1999.

Hyper-IgD and Periodic Fever Syndrome: a New MVK Mutation (p.R277G) Associated with a Severe Phenotype

Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM#260920) is a rare recessively-inherited autoinflammatory condition caused bymutations in the MVK gene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes of fever and inflammation. Herewe report on the case of a 2 year-old Portuguese boy with recurrent episodes of fever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. Mutational MVK analysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G) mutation, while the healthy non consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, where as anakinra showed positive responses only at high doses. The p.R277Gmutation here described is a novel missense MVK mutation, and it has been detected in this casewith a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies.

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.