biostudies-literatureUnknown16Li J<h4>Background</h4>Overlap between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) ("rhupus") is recognized, but coexistence with a severe eosinophilic asthma syndrome is exceptionally rare. We describe a triple autoimmune overlap of RA, SLE, and hypereosinophilic asthma with systemic manifestations (HASM), initially managed as ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) and subsequently re-classified in light of evolving concepts.<h4>Case presentation</h4>A 44-year-old woman with a 10-year history of seropositive RA developed alopecia, Coombs-positive hemolytic anemia, hypocomplementemia, and ANA and anti-Sm positivity, fulfilling SLE criteria. While receiving prednisone, hydroxychloroquine and conventional DMARDs, she subsequently developed adult-onset asthma, chronic rhinosinusitis with nasal polyps, and marked hypereosinophilia (>3.5×10⁹/L). Secondary causes were excluded; bone marrow showed reactive eosinophilia and ANCA (indirect immunofluorescence and ELISA for MPO/PR3) remained negative. She was diagnosed and treated as ANCA-negative EGPA with high-dose glucocorticoids plus methotrexate and hydroxychloroquine, leading to rapid normalization of eosinophils and durable remission of asthma and sinus disease.<h4>Discussion</h4>In retrospect, and according to the ERS/GERM'O'P proposal, this eosinophilic disorder is best classified as HASM within the EGPA-hypereosinophilic spectrum because ANCA and biopsy-proven vasculitis were absent. The case illustrates the evolving boundary between EGPA and hypereosinophilic syndromes and extends the concept of rhupus to include an EGPA-spectrum eosinophilic asthma syndrome.<h4>Conclusion</h4>New-onset eosinophilic asthma in patients with established rheumatic disease should prompt evaluation for EGPA-spectrum or hypereosinophilic disorders. Even when the final label is HASM rather than definite EGPA, timely institution of EGPA-type immunosuppression may avert organ damage.Frontiers in immunology1659370https://www.ebi.ac.uk/biostudies/studies/S-EPMC12852425biostudies-literatureCase Report: Triple autoimmune overlap: rheumatoid arthritis, systemic lupus erythematosus, and hypereosinophilic asthma with systemic manifestations.PMC12852425Long TZou YLi JYu RZhang JZhang YLi SGZhang LfalseCase Report: Triple autoimmune overlap: rheumatoid arthritis, systemic lupus erythematosus, and hypereosinophilic asthma with systemic manifestations.<h4>Background</h4>Overlap between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) ("rhupus") is recognized, but coexistence with a severe eosinophilic asthma syndrome is exceptionally rare. We describe a triple autoimmune overlap of RA, SLE, and hypereosinophilic asthma with systemic manifestations (HASM), initially managed as ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) and subsequently re-classified in light of evolving concepts.<h4>Case presentation</h4>A 44-year-old woman with a 10-year history of seropositive RA developed alopecia, Coombs-positive hemolytic anemia, hypocomplementemia, and ANA and anti-Sm positivity, fulfilling SLE criteria. While receiving prednisone, hydroxychloroquine and conventional DMARDs, she subsequently developed adult-onset asthma, chronic rhinosinusitis with nasal polyps, and marked hypereosinophilia (>3.5×10⁹/L). Secondary causes were excluded; bone marrow showed reactive eosinophilia and ANCA (indirect immunofluorescence and ELISA for MPO/PR3) remained negative. She was diagnosed and treated as ANCA-negative EGPA with high-dose glucocorticoids plus methotrexate and hydroxychloroquine, leading to rapid normalization of eosinophils and durable remission of asthma and sinus disease.<h4>Discussion</h4>In retrospect, and according to the ERS/GERM'O'P proposal, this eosinophilic disorder is best classified as HASM within the EGPA-hypereosinophilic spectrum because ANCA and biopsy-proven vasculitis were absent. The case illustrates the evolving boundary between EGPA and hypereosinophilic syndromes and extends the concept of rhupus to include an EGPA-spectrum eosinophilic asthma syndrome.<h4>Conclusion</h4>New-onset eosinophilic asthma in patients with established rheumatic disease should prompt evaluation for EGPA-spectrum or hypereosinophilic disorders. Even when the final label is HASM rather than definite EGPA, timely institution of EGPA-type immunosuppression may avert organ damage.2025-01-01T00:00:00Z20252026-06-19T03:14:16.024Z2026-06-19T03:07:32.331ZS-EPMC128524254162484310.3389/fimmu.2025.1659370