B-Cell-Depleting Therapy Improves Myocarditis in Seronegative Eosinophilic Granulomatosis with Polyangiitis

Abstract

Cardiac involvement is a major mortality cause in eosinophilic granulomatosis with polyangiitis (EGPA), requiring novel therapeutics to spare the use of cyclophosphamide with known cardiotoxicity. Despite the observed efficacy of B-cell-depleting therapy in myocarditis of seropositive microscopic polyangiitis, it remains to be elucidated in seronegative EGPA. A retrospective study was performed in 21 hospitalized active patients aged 20 to 70 years with five-factor score 1 or 2, eosinophil counts 10,034 ± 6641/μL and vasculitis scores 27 ± 6. Overt myocarditis was identified in 10 cases, at disease onset in 6 and relapse in 4, with endomyocarditis in 4 and myopericarditis in 4. Five seronegative and one seropositive patient received rituximab with an induction regimen 375 mg/m2 weekly × 4 for refractory or relapse disease, and the same regimen for annual maintenance therapy. All cases had lower eosinophil counts, improved cardiac dysfunction and clinical remission with a relapse-free follow-up, 48 ± 15 months after the induction treatment. One seronegative endomyocarditis patient had eosinophilia and disease relapse with asthma attack and worsening cardiac insufficiency 24 months after induction, achieving clinical remission under anti-IL-5 therapy. Our findings suggest the suppression of IL-5-mediated eosinophilia as an action mechanism of B-cell-depleting therapy in seronegative EGPA myocarditis.

Current treatment and immunomodulation strategies in Acute Myocarditis

“…108 Overall, case reports show high-dose corticosteroids were used to successfully treat all forms of EM. [109][110][111][112][113][114][115] In cases associated with EGPA, cyclophosphamide, AZA, rituximab, and mepolizumab were also used. [113][114][115] A case of EM with Churg-Strauss syndrome was treated with combined high-dose corticosteroids and cyclophosphamide, whereas in EM associated with HES, only prednisone or methylprednisolone were used.…”

“…[109][110][111][112][113][114][115] In cases associated with EGPA, cyclophosphamide, AZA, rituximab, and mepolizumab were also used. [113][114][115] A case of EM with Churg-Strauss syndrome was treated with combined high-dose corticosteroids and cyclophosphamide, whereas in EM associated with HES, only prednisone or methylprednisolone were used. [109][110][111][112] Owing to the uncommon nature of the condition, there are no trials for the management of EM; therefore, evidence is limited to case reports, metaanalyses, and retrospective case studies.…”

Autoimmune liver diseases in systemic rheumatic diseases

“…Testing for ANCA can support the diagnosis of ANCA-associated vasculitis including eosinophilic granulomatosis with polyangiitis (also referred to as EGPA), granulomatosis with polyangiitis and microscopic polyangiitis (also referred to as MPA) in spite of seropositivity in only one-third of EGPA cases[ 159 ]. Notably, ANCA has a diagnostic relevance beyond SV, justifying its occurrence in suspected type I AIH which is lacking conventional autoantibodies[ 160 ].…”