Awareness towards the main ILD among primary care physicians.

Background: Interstitial lung diseases (ILDs) comprise a group of multiple entities sharing some clinical, functional, and radiological similarities. In many countries primary care setting has been devoid of pre- and post-graduate educational interventions focused on basic knowledge on ILD. This, along with usual nonspecificity of symptoms at presentation, may contribute to diagnostic delay in this disease setting. Methods: We designed a study questionnaire to assess the level of awareness on basic diagnostic and management aspects of core ILDs - idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, sarcoidosis, connective tissue disease related-ILD, and drug-induced ILD - among primary care physicians (GPs) from five "ACeS Baixo Vouga" health centres and to perceive possible weaknesses. Differences in awareness between GPs under 45 and over 45 yearsold were also assessed. Results: Globally, 69% of questions were correctly answered but only 21.9% of GPs considered to have a satisfactory self-perceived level of knowledge on ILD. Except sarcoidosis (p=0.017) and some isolated questions on other diseases, no significant differences were found between physicians below 45 years and above. Though, there was a trend to higher awareness in the younger group. The best awareness was seen in sarcoidosis. IPF questions had the worst performance and only 48.5% of GPs recognized the importance of velcro-type crackles in suggesting a possible diagnosis. Conclusion: Specific attention should be devoted to educational interventions directed to GPs on basic notions on the main ILDs. This could improve the usual diagnostic delay in many ILDs, as a timely diagnosis is essential for an early treatment and prolonged patient survival.

Myopathy associated with anti-signal recognition particle antibodies with pulmonary involvement and response to rituximab.

The authors present the case of a 76-year-old female patient with progressive decrease in proximal muscle strength, fatigue, dyspnea, diffuse hand edema and painful triphasic Raynaud's phenomenon. Anti-SRP and anti-SSA antibodies were detected, muscle biopsy revealed changes consistent with necrotizing myopathy and capillaroscopy had findings compatible with systemic sclerosis. High-resolution chest computed tomography revealed interstitial lung disease with a non-specific interstitial pneumonia pattern. Lung function tests demonstrated a forced vital capacity 93% and a diffusing capacity for carbon monoxide of 65% predicted. After multidisciplinary discussion, she was diagnosed with immune-mediated necrotizing myopathy/systemic sclerosis overlap syndrome with pulmonary involvement. Initially, dual immunomodulation therapy with high-dose steroids and intravenous immunoglobulin was started, but after 4 weeks, the patient had clinical and analytical deterioration. At this time, she was started on rituximab, with an excellent and sustained response at both muscle and lung, sustained after 12 months.

Pleuroparenchymal Fibroelastosis Associated with Crohn's Disease: A New Aetiology?

Pleuroparenchymal fibroelastosis (PPFE) is a relatively rare interstitial lung disease (ILD) consisting of elastofibrosis involving the subpleural parenchyma and visceral pleura with an upper lobe predominance. It can be idiopathic or associated with some forms of autoimmune disease. The authors describe the case of a 78-year-old woman with a previous diagnosis of Crohn's disease (CD). She presented with a protracted respiratory infection (with no significant history of previous infections), and underwent high-resolution chest computerized tomography that eventually showed alterations compatible with PPFE. After exclusion of other possible underlying causes, a possible link to CD was considered. Follow-up investigation at 12 months showed clinical and radiological stability and also stable lung function under treatment with hydroxychloroquine and prednisolone. This is the first report of PPFE in the context of CD. Future studies will be important to further investigate this pathological association and its prognostic implications. LEARNING POINTS: Pleuroparenchymal fibroelastosis (PPFE) is an uncommon interstitial lung disease consisting of elastofibrosis involving the subpleural parenchyma and visceral pleura with an upper lobe predominance.PPFE can be idiopathic or associated with several conditions including autoimmune diseases and may be a direct extra-intestinal manifestation of Crohn's disease (CD).The main disease patterns of PPFE in the context of CD are organizing pneumonia, non-specific interstitial pneumonia, granulomatous interstitial lung disease, pulmonary eosinophilia and sterile necrobiotic nodules.

Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities) and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF) of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case.

Simultaneous interstitial pneumonitis and cardiomyopathy induced by venlafaxine / Pneumonite intersticial e miocardiopatia simultâneas induzidas por venlafaxina

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used as an antidepressant. Interindividual variability and herb-drug interactions can lead to drug-induced toxicity. We report the case of a 35-year-old female patient diagnosed with synchronous pneumonitis and acute cardiomyopathy attributed to venlafaxine. The patient sought medical attention due to dyspnea and dry cough that started three months after initiating treatment with venlafaxine for depression. The patient was concomitantly taking Centella asiatica and Fucus vesiculosus as phytotherapeutic agents. Chest CT angiography and chest X-ray revealed parenchymal lung disease (diffuse micronodules and focal ground-glass opacities) and simultaneous dilated cardiomyopathy. Ecocardiography revealed a left ventricular ejection fraction (LVEF) of 21%. A thorough investigation was carried out, including BAL, imaging studies, autoimmune testing, right heart catheterization, and myocardial biopsy. After excluding other etiologies and applying the Naranjo Adverse Drug Reaction Probability Scale, a diagnosis of synchronous pneumonitis/cardiomyopathy associated with venlafaxine was assumed. The herbal supplements taken by the patient have a known potential to inhibit cytochrome P450 enzyme complex, which is responsible for the metabolization of venlafaxine. After venlafaxine discontinuation, there was rapid improvement, with regression of the radiological abnormalities and normalization of the LVEF. This was an important case of drug-induced cardiopulmonary toxicity. The circumstantial intake of inhibitors of the CYP2D6 isoenzyme and the presence of a CYP2D6 slow metabolism phenotype might have resulted in the toxic accumulation of venlafaxine and the subsequent clinical manifestations. Here, we also discuss why macrophage-dominant phospholipidosis was the most likely mechanism of toxicity in this case.

A venlafaxina é um inibidor de recaptação de serotonina e noradrenalina utilizado como antidepressivo. A variabilidade individual ou interações entre fitoterápicos e fármacos podem causar toxicidade induzida por drogas. Relatamos o caso de uma paciente de 35 anos diagnosticada com pneumonite intersticial e miocardiopatia dilatada atribuídas à venlafaxina. A paciente procurou atendimento médico devido a dispneia e tosse seca, que começaram três meses após iniciar tratamento com venlafaxina para depressão. Concomitantemente tomava suplementos fitoterápicos contendo Centella asiatica e Fucus vesiculosus. A radiografia e a CT de tórax revelaram doença pulmonar parenquimatosa (micronódulos difusos e opacidades em vidro fosco) e, simultaneamente, foi diagnosticada uma miocardiopatia por ecocardiograma, que revelou uma fração de ejeção ventricular esquerda (FEVE) de 21%. Uma investigação ampla foi realizada, incluindo LBA, estudos de imagem, detecção de doenças autoimunes, cateterismo cardíaco direito e biópsia miocárdica. Após a exclusão de outras etiologias e a aplicação da Escala de Probabilidade de Reações Adversas a Medicamentos de Naranjo, foi assumido o diagnóstico de pneumonite/miocardiopatia síncronas associadas à venlafaxina. Já foi demonstrado que os suplementos fitoterápicos utilizados pela paciente podem inibir a isoenzima do complexo enzimático citocromo P450, responsável pelo metabolismo da venlafaxina. Após a descontinuação da venlafaxina, verificou-se uma rápida melhora clínica com regressão das alterações radiológicas e normalização da FEVE. Este é um importante caso de toxicidade cardiopulmonar induzida por droga. A administração circunstancial de inibidores da isoenzima CYP2D6 e a presença de um fenótipo de metabolização lenta de CYP2D6 podem ter resultado na acumulação tóxica da venlafaxina e na manifestação clínica subsequente. Aqui, é discutida a hipótese de a fosfolipidose macrofágica ser o mecanismo de toxicidade.

[Acute onset pulmonary toxicity associated to amiodarone]. / Toxicidade pulmonar aguda precoce associada à amiodarona.

Amiodarone is a potent anti-arrhythmic drug with a well-known potential chronic pulmonary toxicity. We describe a case of acute pulmonary toxicity (APT) induced by amiodarone in a 57 year old patient submitted to a perfusion of 900 mg in just 6 hours, to control an auricular flutter with rapid ventricular response. During the administration, the patient developed hemodynamic instability and oxygen dessaturation that led to an electrical cardioversion with return of sinus rhythm. Still, the patient continued in progressive respiratory deterioration with acute bilateral infiltrates on chest x-ray and apparent normal cardiac filling pressures confirmed by echocardiography. Anon-cardiogenic pulmonar edema progressing to clinico-physiological ARDS criteria was diagnosed. Expeditive therapeutic measures were undertaken, namely by initiation of non-invasive positive airway pressure support, that attained a good result.Albeit rare, amiodarone-induced APT might have severe consequences, namely progression to ALI/ARDS with a high mortality index.As it is a frequently prescribed drug, there should be a high clinical suspicion towards this phenomenon, allowing precocious therapeutic measures to be taken in a timely fashion to prevent the associated unfavorable outcome.