Case Report: Triple autoimmune overlap: rheumatoid arthritis, systemic lupus erythematosus, and hypereosinophilic asthma with systemic manifestations

TL;DR

A rare case of a woman with three overlapping autoimmune conditions—rheumatoid arthritis, lupus, and eosinophilic asthma—was initially misdiagnosed but later reclassified, highlighting the need for careful evaluation of such complex cases.

Contribution

This case expands the concept of 'rhupus' to include an EGPA-spectrum eosinophilic asthma syndrome and emphasizes the importance of timely immunosuppressive treatment.

Findings

The patient's condition was reclassified as hypereosinophilic asthma with systemic manifestations (HASM) rather than EGPA due to absence of ANCA and vasculitis.

Treatment with EGPA-type immunosuppression led to rapid normalization of eosinophils and remission of asthma and sinus disease.

The case illustrates the evolving boundary between EGPA and hypereosinophilic syndromes in clinical practice.

Abstract

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.

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.

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.

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.

Figures