In adult patients with systemic lupus erythematosus and refractory vasculitic skin ulcers, acute macular neuroretinopathy, or lupus nephritis unresponsive to standard immunosuppressive therapy, should hyperbaric oxygen therapy be used, and what are the recommended protocol, contraindications, and monitoring?

Hyperbaric Oxygen Therapy for Systemic Lupus Erythematosus

Hyperbaric oxygen therapy (HBOT) is not recommended as standard treatment for lupus and is not mentioned in any major international lupus treatment guidelines; however, it may be considered as adjunctive therapy in highly specific refractory scenarios—specifically vasculitic skin ulcers unresponsive to immunosuppression and acute macular neuroretinopathy—when combined with appropriate immunosuppressive therapy. 1, 2

Standard Treatment Framework

The established treatment approach for SLE prioritizes:

• Hydroxychloroquine as universal background therapy for all patients unless contraindicated, which reduces flares and limits organ damage 1, 2
• Glucocorticoids at the lowest effective dose (prednisone ≤7.5 mg/day for maintenance) 1
• Immunosuppressive agents (mycophenolate mofetil, cyclophosphamide, azathioprine, or rituximab) for organ-threatening disease 1, 2

HBOT: Limited Evidence for Specific Scenarios

Refractory Vasculitic Skin Ulcers

HBOT may be considered as adjunctive therapy alongside rituximab and immunosuppression for large refractory vasculitic ulcers that have failed high-dose steroids and conventional immunosuppressants. 3

• One case report demonstrated sustained clinical improvement when HBOT was combined with rituximab and methotrexate after failure of high-dose steroids and other immunosuppressants 3
• The mechanism addresses tissue hypoxia and promotes wound healing in ischemic ulcers 3
• Critical caveat: HBOT was never used as monotherapy; it was always combined with immunosuppression targeting the underlying autoimmune vasculitis 3

Acute Macular Neuroretinopathy

HBOT combined with immunosuppression may aid functional and anatomical recovery in AMN associated with SLE when standard high-dose steroid therapy alone is insufficient. 4

• Two cases showed functional and anatomical improvements with 12 cycles of HBOT added to immunosuppression when high-dose steroids alone were inadequate 4
• Visual field scotomas completely resolved, and retinal thinning was prevented 4
• The rationale is addressing vaso-occlusive ischemic injury to the outer retina 4

Lupus Nephritis: No Role for HBOT

For lupus nephritis (Class III/IV), the evidence-based approach is mycophenolate mofetil (3 g/day for 6 months) or low-dose intravenous cyclophosphamide (total 3 g over 3 months) combined with glucocorticoids, not HBOT. 1, 2

• For refractory lupus nephritis, switching from MPA to cyclophosphamide, cyclophosphamide to MPA, or adding rituximab is recommended 1
• ACE inhibitors or ARBs are indicated for proteinuria >50 mg/mmol 1, 2
• HBOT has no established role in lupus nephritis treatment 1, 2

Recommended HBOT Protocol (When Used)

Based on the limited case reports:

• 12 cycles of HBOT at standard hyperbaric protocols 4
• Always combined with immunosuppression (rituximab, methotrexate, or high-dose steroids) 3, 4
• Initiated when standard immunosuppressive therapy shows inadequate response 3, 4

Contraindications to HBOT

Standard hyperbaric medicine contraindications apply:

• Untreated pneumothorax (absolute contraindication)
• Severe chronic obstructive pulmonary disease with CO2 retention
• Uncontrolled seizure disorders
• Concurrent doxorubicin or bleomycin therapy
• Claustrophobia (relative contraindication)

Monitoring Considerations

When HBOT is used adjunctively:

• Continue monitoring lupus disease activity with anti-dsDNA, complement levels (C3/C4), complete blood count, and organ-specific parameters 1
• Monitor for HBOT-specific complications: barotrauma, oxygen toxicity seizures, myopia progression
• Assess wound healing progress for vasculitic ulcers with serial measurements and photography 3
• Visual field testing and optical coherence tomography for AMN cases 4

Critical Clinical Pitfalls

• Never use HBOT as monotherapy for lupus manifestations; the underlying autoimmune process requires immunosuppression 3, 4
• Do not delay standard immunosuppressive therapy to pursue HBOT; it is adjunctive only 1, 2
• HBOT is not a substitute for guideline-directed therapy in lupus nephritis, neuropsychiatric lupus, or other major organ involvement 1, 2
• The evidence base consists of case reports only; no randomized controlled trials exist 3, 4

Practical Algorithm for HBOT Consideration

1. Confirm SLE diagnosis and specific manifestation (vasculitic ulcers or AMN) 3, 4
2. Initiate or optimize standard immunosuppressive therapy per guidelines 1, 2
3. Document inadequate response to standard therapy (persistent ulcers >4-6 weeks or worsening AMN despite steroids) 3, 4
4. Exclude HBOT contraindications (pneumothorax, severe COPD, seizures)
5. Refer to hyperbaric medicine for evaluation if standard therapy fails 3, 4
6. Continue immunosuppression throughout HBOT course 3, 4
7. Monitor for both lupus activity and HBOT complications 3, 4