Toxicidade pulmonar induzida pela rapamicina

Lung toxicity induced by rapamycin

 

C Damas ¹

A Oliveira ²

A Morais ³

 

Resumo

As doenças pulmonares induzidas por fármacos constituem uma causa crescente de morbilidade, tendo sido descritas diferentes formas de toxicidade associadas a inúmeras substâncias. O sirolimus (rapamicina) é um fármaco imunossupressor usado de forma crescente no contexto do transplante de órgãos sólidos, nomeadamente no transplante renal. A toxicidade pulmonar tem sido descrita como um dos potenciais efeitos laterais, nomeadamente causando formas de pneumonite intersticial ou, mais raramente, hemorragia alveolar. Os autores descrevem os casos de quatro doentes (3 do sexo masculino, 1 do sexo feminino) com idades compreendidas entre os 46-71 anos, recipientes de transplante renal (rim cadáver) há 3 anos (1 doente) e 7 anos (3 doentes). A imunosupressão consistia em micofenolato mofetil, prednisolona e rapamicina. Os quatro doentes foram admitidos por febre, tosse produtiva (2) e dispneia (3). Apresentavam imagem radiológica de infiltrados pulmonares bilaterais de predomínio basal. O LBA mostrou alveolite linfocítica em 3 doentes, tendo-se observado no entanto diferentes relações CD4/CD8., para além de neutrofilia em 2 deles. No restante doente, observou-se hemorragia alveolar grave. Não houve em nenhum dos casos qualquer isolamento de micro organismos patogénicos no LBA. As queixas apresentadas, bem como as alterações radiológicas regrediram com a suspensão do fármaco. Estes quatro casos revelaram alguma variedade, quer na apresentação clínica, quer nos achados dos exames subsidiários efectuados, nomeadamente no LBA. Este facto pode ter como causa diferentes mecanismos fisiopatológicos a nível do pulmão induzidos pelo sirolimus.

Palavras-chave: Sirolimus, toxicidade pulmonar, lavado broncoalveolar.

 

Abstract

Drug induced lung diseases (DILD) are an increasingly cause of morbidity. Many drugs have been described, causing several patterns of injury. Sirolimus is an immunosuppressive agent increasingly used in renal and other solid organ transplantation. Pulmonary toxicity has been recognised as a potential complication associated to this medication. Interstitial pneumonitis and more rarely alveolar haemorrhage have been described. The authors describe 4 cases (3 men and 1 woman) between 46-71 years, transplanted three years ago (1 patient) and 7 years ago (3 patients). All of them were medicated with micofenolato mofetil, prednisone and sirolimus. All patients had fever at admission, 3 patients had dyspnoea and 2 productive cough. Diffuse pulmonary infiltrates with basal predominance in HRCT scan were present in the four patients. BAL showed lymphocytic alveolitis in 3 cases, however with a different CD4/CD8 ratio. In additio to lymphocytosis, neutrophilia was observed in 2 patients. One patient showed serious alveolar haemorrhage in BAL. Pulmonary infections were ruled out by specific BAL staining and cultures. After drug suspension, all patients showed a clear improvement. These case studies show some diversity in clinical presentation and in the features of some exams, namely in BAL. This may suggest different underlying pathophysiology entities induced by sirolimus.

Key-words: Sirolimus, lung toxicity, bronchoalveolar lavage.

 

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Bibliografia

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¹ Interna complementar de Pneumologia

² Interna complementar de Nefrologia

³ Assistente hospitalar de Pneumologia

 

Hospital de São João, Serviço de Pneumologia, Porto (EPE)

Director: Prof. Doutor J. Agostinho Marques

Faculdade de Medicina da Universidade do Porto

 

Hospital de São João (EPE), Serviço de Pneumologia

Alameda Hernâni Monteiro

4200 – Porto

 

Recebido para publicação/received for publication: 06.06.02

Aceite para publicação/accepted for publication: 06.07.11