RESUMO
A previously fit and well 38-year-old man presented during the COVID-19 pandemic with dyspnoea, cough and palpitations. C-reactive protein was elevated and chest X-ray demonstrated bilateral lower zone consolidation. SARS CoV-2 swab was negative. He was diagnosed with community-acquired pneumonia and treated with oral antibiotics. He developed severe type 1 respiratory failure and was admitted to the high-dependency unit for non-invasive ventilation. CTPA was negative for pulmonary embolism, instead demonstrating bilateral organising pneumonia. Empirical treatment for swab-negative COVID-19 pneumonitis was started; however, further deterioration ensued and prompted intubation and ventilation. Microbiological testing did not yield any positive results, thereby raising suspicion for the presence of an autoimmune disease. Pulsed intravenous methylprednisolone was administered with good effect. ENA screen was positive for anti-Jo1 and myositis-specific autoantibodies were positive for Ro-52, Ku and PL-12. The patient was extubated and did not exhibit any muscle weakness on clinical examination. Creatine kinase was only mildly elevated. He was diagnosed with amyopathic antisynthetase syndrome - frequently considered as a form of idiopathic inflammatory myopathy (IIM) - and treated with further intravenous methylprednisolone and cyclophosphamide. Oxygen therapy was gradually weaned and the patient discharged on mycophenolate mofetil and a weaning course of oral steroids.
Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Miosite , Pneumonia , Masculino , Humanos , Adulto , Pandemias , Miosite/complicações , Miosite/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Autoanticorpos , Metilprednisolona/uso terapêuticoRESUMO
OBJECTIVES: To assess the best choice of second-line therapy between tumour necrosis factor-inhibitor (TNFi) and biologics of different-mode-of-action (BDMA-rituximab/tocilizumab/abatacept) in rheumatoid arthritis (RA) by evaluating drug-survival following discontinuation of the first-line TNFi. METHODS: This retrospective drug-survival study was performed across two different hospitals by conventional-statistics and machine-learning approach. RESULTS: From a total of 435 patients, 213 (48.9%; TNFi = 122, BDMA = 91) discontinued their second-line biologic {median drug-survival: TNFi, 27 months [95% confidence interval (95%CI) 22-32] vs BDMA, 37 months (95%CI 32-52)}. As a second-line biologic, BDMA was likely to reduce the risk of treatment-discontinuation [hazard-ratio (HR) 0.63, 95%CI 0.48-0.83] compared to TNFi, but only in seropositive-patients (HR 0.52, 95%CI 0.38-0.73), not in seronegative-RA. Drug-survival benefit of BDMA over TNFi was not observed if the seropositive-patients were previously exposed to monoclonal-TNFi (HR 0.77, 95%CI 0.49-1.22) versus soluble-TNFi (etanercept/biosimilars) or if the first-line TNFi was terminated within 23.9 months of initiation (HR 0.97, 95%CI 0.56-1.68). CONCLUSIONS: BDMA, as a second-line biologic, is more likely to be sustained in seropositive-patients, particularly without prior exposure to monoclonal-TNFi. The drug-survival benefit of BDMA was not observed in seronegative-patients or if the first-line TNFi was stopped within 2 years.
Assuntos
Antirreumáticos , Artrite Reumatoide , Inibidores do Fator de Necrose Tumoral , Artrite Reumatoide/tratamento farmacológico , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Terapia Biológica , Antirreumáticos/uso terapêutico , Resultado do Tratamento , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVES: To determine whether concomitant HCQ modulates the increase in erythrocyte mean corpuscular volume (MCV) caused by MTX therapy, and whether this is associated with improved clinical response in RA. METHODS: A retrospective observational analysis was conducted on two independent hospital datasets of biologic-naïve, early-RA patients who started oral MTX. Baseline characteristics, DAS28-ESR and monthly MCV after starting MTX were obtained. Conventional and machine-learning statistical approaches were applied to the discovery cohort (Cohort 1, 655 patients) and results validated using Cohort 2 (225 patients). RESULTS: HCQ therapy with MTX was associated with a 2-fold increase in the likelihood of response defined in this study as clinical remission or low disease activity at 6 months (P <0.001). The improved clinical outcome of combination HCQ and MTX therapy was associated with an accelerated rise in MCV from 2 months after commencing therapy. The increase in MCV at 3 months was equivalent to the contemporaneous reduction in the DAS (DAS28-ESR) in predicting clinical response at 6 months. Using latent class mixed modelling, five trajectories of MCV change over 6 months from baseline were identified. The odds ratio of response to treatment was 16.2 (95% CI 5.7, 46.4, P <0.001) in those receiving combination therapy classified within the MCV elevation >5 fl class, which contained the most patients, compared with MTX alone. CONCLUSION: Our data provide mechanistic insight into the synergistic clinical benefit of concomitant HCQ with MTX, boosting the rise in MCV, which could serve as a companion biomarker of treatment response.
Assuntos
Antirreumáticos/uso terapêutico , Índices de Eritrócitos/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/farmacologia , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/farmacologia , Masculino , Metotrexato/farmacologia , Pessoa de Meia-Idade , Indução de Remissão , Estudos RetrospectivosAssuntos
Tratamento Farmacológico da COVID-19 , Médicos , Doenças Reumáticas , Reumatologia , Anticorpos Monoclonais Humanizados , Ensaios de Uso Compassivo , Hospitalização , Hospitais Gerais , Humanos , Sistema de Registros , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológicoAssuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/uso terapêutico , Anticorpos Antiproteína Citrulinada/sangue , Etanercepte/uso terapêutico , Humanos , Estudos Retrospectivos , Fator Reumatoide/sangue , Resultado do TratamentoRESUMO
Immunoglobulin G4 (IgG4)-related disease is a relatively rare and only recently recognized immune-mediated fibro-inflammatory condition that is commonly associated with autoimmune pancreatitis. Reports have further been characterized in almost all other organ systems, with several lung-related IgG4 disease reports emerging over the past decade. IgG4-related disease affects more than one organ in 60-90% of patients. To this date, there have been few published cases of pathologically proven isolated IgG4-related lung disease (IgG4-RLD), where no other organ is affected. We report an isolated pulmonary case of IgG4-RLD in a 65-year-old female with clinical and radiological manifestations suggestive of primary lung malignancy. CT revealed multiple sub-solid ground glass opacities, several of which were part-solid, others were pure ground glass. Histological analysis revealed IgG4 disease with no evidence of neoplasia. Serum IgG4 levels were elevated (206 mg dl-1). Malignancy was ruled out and the patient was treated with corticosteroids, though there was no change in CT appearance over 16 months. The CT imaging pattern in our case is atypical from previous literature characterisation.
RESUMO
It is well-recognized that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are raised in conditions with ventricular volume and pressure overload. In addition to this established role in left ventricular congestive cardiac failure, there is good evidence that BNP has a diagnostic role in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH). For example, BNP levels can be used to differentiate between dyspneic patients with pure respiratory defects and those with RV dysfunction. Studies in patients with PAH have demonstrated significant correlations between BNP levels and mean pulmonary arterial pressure as well as pulmonary vascular resistance. Additionally, BNP has a prognostic role in patients with RV pressure overload and pulmonary hypertension, and it offers a noninvasive test that can be used to guide therapy in patients with PAH. However, although measured plasma proBNP levels are raised in conditions with RV overload, its biological significance is still not well-understood. In this article, we review the general physiologic and potential therapeutic role of natriuretic peptides in respiratory disease, RV dysfunction, and PAH. Furthermore, we assess the various clues toward natriuretic peptide action coming from laboratory studies. ANP and BNP knockout mice develop cardiac fibrosis and hypertrophy. Potentiation of the natriuretic pathway has been shown to reduce cardiac hypertrophy and PAH. This is likely to take place as a result of increased intracellular cyclic guanosine monophosphate levels and subsequent pulmonary vasorelaxant activity. In view of this evidence, there may be a rationale for the therapeutic use of recombinant BNP or neutral endopeptidase inhibitors under conditions of RV dysfunction and PAH.
Assuntos
Fator Natriurético Atrial/fisiologia , Hipertensão Pulmonar/fisiopatologia , Peptídeo Natriurético Encefálico/fisiologia , Disfunção Ventricular Direita/fisiopatologia , Animais , Biomarcadores/sangue , Cardiomegalia/diagnóstico , Fibrose , Ventrículos do Coração/patologia , Humanos , Hipertensão Pulmonar/diagnóstico , Disfunção Ventricular Direita/diagnóstico , Pressão VentricularRESUMO
Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are increased in conditions with cardiac ventricular volume and pressure overload. The general physiological and potential therapeutic roles of natriuretic peptides in respiratory disease, right ventricular (RV) dysfunction, and pulmonary arterial hypertension (PAH) are reviewed. BNP levels can be used to differentiate between dyspneic patients with a pure respiratory defect and those with RV dysfunction. BNP levels also correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PAH (atrial septal defect, chronic thromboembolic disease, and scleroderma). BNP is a predictor of mortality in patients with primary pulmonary hypertension (PPH). These are important clinical implications in that a noninvasive blood test may be used to identify high-risk patients for more invasive procedures such as cardiac catheterization. BNP or NT-proBNP measurements may also be used to guide therapy (e.g., pulmonary vasorelaxants) in PAH since upregulation of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH. Additionally, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.