Myocarditis in a congenital STAT1 gain-of-function patient

Autosomal dominant Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations result in an inborn error of immunity characterized by chronic mucocutaneous candidiasis, recurrent viral and bacterial infections, and diverse autoimmune manifestations. Current treatment consists of chronic antifungal therapy, antibiotics for concomitant infections, and immunosuppressive therapy in case of autoimmune diseases. More recently, treatment with Janus kinases 1 and 2 (JAK1/2) inhibitors have shown promising yet variable results. We describe a STAT1 GOF patient with an incidental finding of elevated cardiac troponins, leading to a diagnosis of a longstanding, slowly progressive idiopathic myocarditis, attributed to STAT1 GOF. Treatment with a JAKinhibitor (baricitinib) mitigated cardiac inflammation on MRI but was unable to alter fibrosis, possibly due to the diagnostic delay, which finally led to fatal arrhythmia. Our case illustrates that myocarditis can be part of the heterogeneous disease spectrum of STAT1 GOF. Given the insidious presentation in our case, we recommend a low treshold for cardiac evaluation in all STAT1 GOF patients.Figure 1. (abstract: 70)Clinical, genetic and laboratory findings in a patient with STAT1 GOF. (A) Patient pedigree. c.963A>T was Sanger sequencing confirmed (data not shown), (B) Clinical pictures of onychomycosis (left) and impact of CMC on the tongue (right), (C) p-STAT1 MFI of patient and age-matched controls (n = 13) on CD14+ monocytes unstimulated and after IFNα (2000 IU/ml) and IFNγ (2000 IU/ml) stimulation for 15 minutes (left); representative histogram of p-STAT1 on CD14+ monocytes in patient and healthy control (right). MFI: mean fluorescence index.Figure 2. (abstract: 70)Radiological findings in a patient with STAT-1 GOF and myocarditis. Cardiac native T1 map, T2 map and late gadolinium enhancement (LGE) MR images. Blue arrows showing regression of subepicardial and myocardial enhancement during treatment.