Severe myopathy complicating multisystem inflammatory syndrome in adults (MIS-A) in a young man.

We report the case of a man in his early 30s who presented with high fever, cervical lymphadenopathy, maculopapular rash and considerably elevated inflammatory markers. Further evaluations revealed cardiomyopathy and renal failure. During hospitalisation he developed profound generalised muscle weakness caused by diffuse myopathy without elevated creatine kinase. He was eventually diagnosed with multisystem inflammatory syndrome in adults (MIS-A) after it was established that he had been suffering from COVID-19 5 weeks prior to presentation. He was started on intravenous immunoglobulins and high-dose corticosteroids, after which symptoms resolved rapidly. MIS-A is a rare but severe complication of COVID-19, whose pathogenesis is insufficiently understood. This case provides further insight into this new disease entity by describing a previously unreported disease progression with severe inflammatory myopathy without elevated creatine kinase.

CFTR-function and ventilation inhomogeneity in individuals with cystic fibrosis.

BACKGROUND: Increased (abnormal) ventilation inhomogeneity in individuals with mild Cystic Fibrosis (CF) lung disease may become a treatable trait for small-molecule therapeutics improving Cystic Fibrosis Transmembrane Regulator (CFTR) function. The relationship between CFTR function and ventilation inhomogeneity is unknown. We aimed to identify and quantify increased ventilation inhomogeneity in relation to CFTR function. METHODS: This was an international, multi-center, cross-sectional study. We collated data from individuals aged 3-25 years with minimal (CFTR-MF) or residual (CFTR-RF) function of a variety of CFTR genotypes and FEV1 ≥ 70% predicted. We measured lung function using nitrogen multiple-breath washout and spirometry. We compared lung clearance index (LCI) and FEV1 between individuals with CFTR-MF vs CFTR-RF using a mixed effects multi-variable linear regression model to account for study differences and a logistic model based on propensity-score matching to adjust for possible confounding. RESULTS: We included 141 with CFTR-MF and 35 with CFTR-RF. LCI (> 1.96 z-score) was elevated in 71.6% individuals with CFTR-MF and in 40.0% with CFTR-RF. FEV1 (< -1.96 z-score) was reduced in 11.3% individuals with CFTR-MF and in 5.7% with CFTR-RF. The mean difference (95% CI) of LCI and FEV1 between CFTR-MF and CFTR-RF was 3.71 (1.63 to 5.79) and -0.40 (-0.83 to 0.02) z-score. The LCI differences were similar after adjustment for confounders and in individuals with normal FEV1. CONCLUSION: Increased ventilation inhomogeneity is associated with less CFTR function. In individuals with mild CF lung disease, LCI can identify and quantify increased ventilation inhomogeneity, a candidate treatable trait.