# Rhupus Syndrome With Multiple Drug Intolerances Managed by Reduced-dose Rituximab and Adjunctive Molecular Hydrogen Therapy: A Case Report.
> 多剤不耐性を伴うRhupus症候群に対する低用量リツキシマブと分子状水素の併用：症例報告


## Abstract

A 47-year-old male with a 27-year history of rheumatoid arthritis who subsequently developed systemic lupus erythematosus, meeting criteria for Rhupus syndrome, is described. The patient exhibited intolerance to multiple agents including methotrexate, sulfasalazine, hydroxychloroquine, azathioprine, leflunomide, and standard-dose rituximab. Despite reduced-dose rituximab plus mycophenolic acid, disease activity remained uncontrolled and lupus nephritis was confirmed. Oral molecular hydrogen capsules were introduced as an adjunct in October 2023. Subsequently, anti-dsDNA antibody levels normalized, erythrocyte sedimentation rate and complement values improved, characteristic shifts in T- and B-cell subsets were observed, and prednisone was successfully discontinued. Clinical control was maintained with mycophenolic acid and continued hydrogen supplementation. No significant adverse effects were attributed to hydrogen. Avascular necrosis from prior corticosteroid exposure required hip arthroplasty in January 2025, after which recovery was satisfactory.

### Mechanism

Molecular hydrogen is proposed to exert antioxidant and immunomodulatory effects, leading to shifts in T- and B-cell subset distribution, suppression of anti-dsDNA antibody production, and reduction of systemic inflammatory markers including ESR and complement dysregulation.

## Bibliographic

- **Authors**: Tsai HL, Lu J, Ho YJ, Lui SW, Hsieh TY, Wang K, et al.
- **Journal**: In Vivo
- **Year**: 2026
- **PMID**: [41482402](https://pubmed.ncbi.nlm.nih.gov/41482402/)
- **DOI**: [10.21873/invivo.14221](https://doi.org/10.21873/invivo.14221)
- **PMC**: [PMC12764188](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12764188/)
- **Study type**: human case report
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41482402. https://h2-papers.org/en/papers/41482402
> **Source**: PubMed PMID [41482402](https://pubmed.ncbi.nlm.nih.gov/41482402/)