Case report: Myocarditis in congenital STAT1 gain-of function

Area of Science:

• Immunology
• Cardiology
• Genetics

Background:

• Autosomal dominant Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations cause a primary immunodeficiency with mucocutaneous candidiasis, recurrent infections, and autoimmunity.
• Current treatments include antifungals, antibiotics, and immunosuppressants, with Janus kinase (JAK) inhibitors showing variable efficacy.

Observation:

• A patient with STAT1 GOF presented with elevated cardiac troponins, revealing a diagnosis of idiopathic myocarditis.
• This myocarditis was attributed to the underlying STAT1 GOF, highlighting a potential new facet of the disease spectrum.

Findings:

• Treatment with baricitinib, a JAK inhibitor, reduced cardiac inflammation on MRI.
• However, baricitinib did not reverse established cardiac fibrosis, suggesting limitations in later stages of the disease.
• The patient ultimately experienced a fatal arrhythmia, likely due to diagnostic and therapeutic delays.

Implications:

• Myocarditis should be considered within the broad clinical spectrum of STAT1 GOF.
• A proactive approach involving cardiac screening is recommended for individuals with STAT1 GOF due to the potential for insidious cardiac involvement.
• Timely diagnosis and intervention may be critical for improving outcomes in STAT1 GOF-associated cardiac disease.