Interleukin-17A-Correlated Myocarditis in Patients with Psoriasis: Cardiac Recovery following Secukinumab Administration

Abstract

(1) Background: Psoriasis (PS) is a common immune-mediated disease of the skin with possible extension to joints, aorta and eye. Myocardial inflammation has rarely been suggested. (2) Aims: Report of PS-related myocarditis. (3) Methods and Results: One hundred consecutive patients with PS were screened for cardiac involvement. Among them, five male patients (aged 56 ± 9.5 years) with a moderate–severe form of PS showed dilated cardiomyopathy (LVEF < 35%) with normal coronary arteries and valves. They underwent a left-ventricular endomyocardial biopsy for evaluation of myocardial substrate. Endomyocardial samples were processed for histology and immunohistochemistry, including myocardial expression of Toll-Like Receptor 4 (TLR4) and interleukin-17A (IL-17A), which play a major role in PS pathogenesis. Real-time PCRs were carried out for cardiotropic viruses, and Western blot analysis was conducted for myocardial expression of IL-17A. Patients’ sera were tested for anti-heart autoantibodies. Active lymphocytic myocarditis was revealed in all five patients, characterized by an absence of viral genomes with PCR, positive anti-heart autoantibodies, overexpression of TLR-4 and enhancement of IL-17-A during western blot analysis, showing a 2.48-fold increase in psoriatic myocarditis compared with no psoriatic myocarditis and a six-fold increase compared to myocardial controls. Treatment included combination of prednisone (1 mg/kg daily for 4 weeks, tapered to 0.33 mg/kg) and azathioprine (2 mg/kg, daily) in 3 pts or secukinumab (SK, 150 mg/weekly for 4 weeks followed by 150 mg/monthly) in 2 pts for 6 months. LVEDD and LVEF improved in the first 3 pts (−14% and + 118%, respectively), while they completely recovered (LVEF > 50%) in the last 2 pts on SK. (4) Conclusions: IL-17A-related myocarditis can occur in up to 5% of patients with PS. It manifests as progressive dilated cardiomyopathy. It may completely recover following SK administration.

Advancing Precision Medicine in Myocarditis: Current Status and Future Perspectives in Endomyocardial Biopsy-Based Diagnostics and Therapeutic Approaches

“…A case report of a patient diagnosed with autoimmune myocarditis associated with psoriasis demonstrated successful use of the IL-17 inhibitor secukinumab in the treatment of autoimmune myocarditis [260]. Furthermore, a recent study of 100 consecutive myocarditis patients revealed that psoriasis involvement occurred in 5% of patients, and complete cure occurred with secukinumab therapy over a six-month period [261]. However, the potential and safety of anti-IL-17 therapy remains to be investigated in larger trials.…”

Myocarditis and Chronic Inflammatory Cardiomyopathy, from Acute Inflammation to Chronic Inflammatory Damage: An Update on Pathophysiology and Diagnosis

“…All patients showed lymphocytic myocarditis and presented anti-heart antibodies cross-reactive to the skeletal muscle. Furthermore, a 2.48-fold overexpression of IL-17A was associated with myocarditis in these patients [ 90 ]. These cited studies and case reports showed an acute onset with severely depressed systolic function as the typical form of myocardial involvement in PS.…”

“…Conduction disorders are reported sporadically, while ventricular and supraventricular arrhythmias are common. CMR showed high native T1 and T2 values associated with the hyperintensity of STIR T2 weighted images, demonstrating edema [ 90 ].…”

“…In the TIMIC trial, patients with HF and chronic infl-CMP with no evidence of myocardial viral genomes were randomized to prednisone plus azathioprine for six months versus placebo; the treatment group experienced a significant decrease in LV volumes and LVEF improvement [ 130 ]. Finally, a promising approach may be the use of specific monoclonal antibodies directed against molecules involved in autoimmunity: in a case series reported by Frustaci et al, the addition of secukinumab, an interleukin-17A inhibitor, to standard immunosuppressive therapy was associated with complete ventricular function recovery in patients with psoriasis-relate myocarditis [ 90 ]. Further studies are needed to confirm this preliminary data and extend it to other autoimmune diseases.…”

Advancements in therapeutic paradigm: Harnessing IL‐17A inhibitor secukinumab to ameliorate psoriasis vulgaris in the presence of resistant pericardial effusion

“…Nevertheless, considering the patient's prolonged history of psoriasis and the established correlation between psoriasis and cardiovascular inflammatory reactions, it is hypothesized that the systemic inflammation associated with psoriasis may have played a role in the development or worsening of the pericardial condition. 3 This potential association, particularly when considering the positive therapeutic response to secukinumab, a medication primarily utilized for psoriasis, emphasizes the significance of considering psoriasis as a potential contributing factor in cases of idiopathic pericarditis. Sustained treatment involved oral methylprednisolone, hydroxychloroquine, and methotrexate with concurrent antituberculosis therapy.…”