Overview of Drug Allergy: From Immunogenetic Basis to Practice.

Drug therapy is often a balance between the beneficial and harmful effects of drugs. Drug allergic reactions are adverse reactions mediated by immunological mechanisms and usually not related to the pharmacological actions of the drug. They can be classified based either on the clinical presentation or the underlying immunological mechanism. Although uncommon, drug allergic reactions are unpredictable and can be very severe, even life threatening. The aim of this review was to provide clinicians from different medical specialties with a working tool to improve management of their patients with suspected drug allergy. It was conducted as a nonsystematic review, and attempts to describe the complexity of drug allergy. The information included ranges from pathophysiology to the heterogeneous clinical presentation, with a special focus on the drugs most frequently involved, as well as a classification of reactions and risk factors. Despite all advances in this challenging and complex field of allergy and clinical immunology, drug allergy is not yet fully established and understood. An exceptional contribution was brought by pharmacogenomics, even though a specific pharmacogenetic association has only been defined for a very limited number of drugs. Further studies are needed to obtain clearer answers when managing each individual case of drug allergy.

A terapêutica farmacológica consiste, frequentemente, num equilíbrio entre os efeitos benéficos e prejudiciais dos fármacos. As reações alérgicas a fármacos são reações adversas mediadas por mecanismos imunológicos e não relacionadas com as ações farmacológicas do fármaco. Podem ser classificadas quer com base na apresentação clínica, quer no mecanismo imunológico subjacente. Embora pouco comuns, as reações alérgicas a fármacos são imprevisíveis, podendo ser graves e potencialmente fatais. O objetivo da presente revisão da literatura foi disponibilizar aos clínicos de diversas áreas médicas uma ferramenta de trabalho para uma melhor abordagem dos seus doentes com suspeita de alergia a fármacos. Foi conduzida de forma não sistemática e procura descrever a complexidade das reações alérgicas a fármacos, desde a fisiopatologia à heterogeneidade da apresentação clínica. Foi dado especial destaque aos fármacos mais frequentemente envolvidos, à classificação das reações e aos fatores de risco. Apesar de todos os avanços nesta área desafiante e complexa da alergologia e imunologia clínica, a alergia a fármacos não está ainda completamente compreendida e estabelecida. A farmacogenética trouxe um contributo excecional, embora apenas para um número muito limitado de fármacos esteja definida uma associação farmacogenética. São necessários estudos adicionais que permitam obter respostas mais diretas na abordagem de cada caso individual de alergia a fármacos.

Prevalence of abacavir-associated hypersensitivity syndrome and HLA-B*5701 allele in a Portuguese HIV-positive population.

BACKGROUND: Human Immunodeficiency Virus (HIV)-positive patients treated with the antiretroviral drug abacavir (ABC) may develop a potentially fatal ABC-associated hypersensitivity syndrome (ABC-HS), typically characterized by fever, malaise, rash, vomiting/diarrhoea and/or dyspnoea/cough. ABC-HS has been strongly associated with HLA-B*57:01 carriage and screening for this allele is recommended. OBJECTIVE: To determine the prevalence of HLA-B*57:01 and to characterize suspected ABC-HS in the adult HIV population from our hospital during a 7-year period. METHODS: Clinical data on patients under ABC treatment from January 2006 to December 2012 were analyzed to search for symptoms of ABC-HS. Reactions of suspected ABC-HS were characterized. HLA-B*57:01 and patch tests (1% and 10% ABC in petrolatum) with readings at 48 h were performed in those without previous testing. From January 2008 routine HLA-B*57:01 screening was implemented. RESULTS: From January 2006 to December 2007, 186 patients began treatment with ABC (data from 163 were available): 7 (4%) patients stopped ABC for suspected ABC-HS (71% males, median age 45 years) and the median time for onset of the reaction after starting ABC was 7 days. Four of the 7 patients had the HLA-B*57:01 allele and 2 of these 4 had positive patch tests. After HLA-B*57:01 screening implementation (January 2008), 573 patients were evaluated and 35 (6.1%) were HLA-B*57:01 positive; no suspected ABC-HS were observed since then. CONCLUSION: Four patients with suspected ABC-HS (of 6 screened) were HLA-B*57:01 positive. No ABC-HS occurred since January 2008, after HLA-B*57:01 screening was implemented.

Melkersson-Rosenthal syndrome - delay in the diagnosis of an early-onset oligosymptomatic variant.

Melkersson-Rosenthal syndrome is a rare neuro-mucocutaneous disease with a chronic intermittent course, characterized by a classic triad of orofacial swelling, fissured tongue (lingua plicata) and facial paralysis. The authors describe the case of an oligosymptomatic variant (lip and tongue involvement) with childhood onset, whose diagnosis was only established at the age of 19 years. The syndrome's pathophysiology is unclear and the treatment is challenging; corticosteroid therapy is the mainstay of treatment and is associated with clinical and histological improvement.