Giant Cell Myocarditis: Is It Time to Redeploy Cytokine Inhibitors?

Giant cell myocarditis (GCM) is a rare, aggressive T-lymphocyte-mediated inflammatory cardiac disorder associated with high mortality. Diagnosis relies on endomyocardial biopsy, revealing lymphocytic infiltrates, granulomas, and myocyte necrosis, with cardiac MRI serving as a valuable non-invasive adjunct. Due to its rarity and coding limitations, GCM remains poorly captured in epidemiological data, hindering robust clinical trials. Current treatment strategies are largely based on case reports and off-label immunosuppressive use, with limited success using conventional DMARDs. Emerging evidence supports targeting T-cell-mediated and cytokine-driven pathways, including TNF inhibitors, JAK inhibitors (e.g., tofacitinib, ruxolitinib), and IL-2-targeted therapies (e.g., basiliximab). Tofacitinib, in particular, offers rapid, broad-spectrum immunomodulation and favourable pharmacokinetics. Although high-quality evidence is lacking, real-world data and coordinated international efforts (e.g., multicentre case series, registries) may help define optimal therapeutic strategies. With increasing availability of biosimilars and off-patent biologics, early cytokine inhibition could represent a paradigm shift in the management of this life-threatening condition.