Systemic vasculitis: rare diseases with complex diagnosis looking at Car-T

Systemic vasculitides are a heterogeneous group of rare autoimmune diseases characterised by persistent inflammation of blood vessels, potentially affecting organs as diverse as the heart, kidneys, lungs and brain. If not recognised and treated in a timely manner, these conditions can lead to severe complications even in young individuals without known risk factors.

The clinical manifestations of vasculitis vary depending on the type and size of the vessels involved and can range from non-specific symptoms such as fever and weight loss to very typical manifestations.

Among the main forms of systemic vasculitis are those affecting small blood vessels, including eosinophilic granulomatosis with polyangiitis, characterised by elevated levels of certain white blood cells (eosinophils) in the blood and tissues, often associated with asthma and rhinosinusitis, but which can also involve the heart and nervous system, or microscopic polyangiitis and granulomatosis with polyangiitis, which mainly affect the kidneys, skin and lungs. Other important forms of vasculitis affecting larger blood vessels are gigantocellular arteritis (also known as Horton's arteritis), the most frequent form of vasculitis to date, and which occurs mainly in people over the age of 60, and Behçet's syndrome, a condition involving inflammation of vessels of varying size, characterised among other things by recurrent inflammatory thrombotic episodes.
More recently, genetically determined forms of vasculitis have been described, also characterised by various manifestations such as recurrent thrombotic episodes, including stroke, heart attack and pulmonary embolism.

Given the variability of the clinical presentation of these rare conditions, the approach to these conditions is multidisciplinary and the diagnosis is often complex, with a diagnostic delay still common despite the great strides made in recent years by the international scientific community and in particular by the European Vasculitis Society Euvas.

The guidelines of the European Alliance of Associations for Rheumatology (Eular) recommend different therapeutic approaches for the management of systemic vasculitis, which still include the use of systemic cortisone, which is flanked by both traditional immunosuppressive drugs such as cyclophosphamide, but increasingly by new molecules capable of reducing inflammation in a targeted and selective manner. Recently, Aifa approved the reimbursability of avacopan, an oral inhibitor of the complement receptor C5a, indicated for the treatment of granulomatosis with polyangiitis and microscopic polyangiitis. The monoclonal antibodies mepolizumab and benralizumab, capable of blocking the survival of eosinophils, are radically changing the treatment and quality of life of patients with eosinophilic granulomatosis with polyangiitis. Finally, drugs such as JAK-inhibitors, already in use for the treatment of rheumatoid arthritis, are demonstrating efficacy and safety in the treatment of systemic vasculitis such as gigantocellular arteritis.