What is the treatment plan for the FLAMES (Facial weakness, Lethargy, Anterior uveitis, Mouth ulcers, Encephalitis, and Splenomegaly) subtype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)?

Treatment of FLAMES Subtype of MOGAD

The treatment of FLAMES (Facial weakness, Lethargy, Anterior uveitis, Mouth ulcers, Encephalitis, and Splenomegaly) subtype of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) should follow a stepwise approach with high-dose corticosteroids as first-line therapy, followed by plasma exchange or IVIG for severe or steroid-resistant cases, and consideration of long-term immunosuppression for relapsing disease.

Acute Treatment

• High-dose intravenous methylprednisolone (1000 mg daily for 3-5 days) should be initiated immediately upon diagnosis of FLAMES MOGAD 1, 2
• A slow oral prednisone taper (starting at 1 mg/kg/day) over 2-3 months is recommended to prevent early relapses, as MOGAD frequently shows steroid-dependency with flare-ups after steroid withdrawal 1, 2
• For severe attacks or inadequate response to steroids, plasma exchange (5-7 exchanges) or immunoadsorption should be implemented early 1
• Intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days is an alternative for patients who cannot undergo plasma exchange, particularly effective in pediatric patients 1, 2

Treatment Considerations for FLAMES-Specific Manifestations

• Anti-epileptic drugs should be administered for seizure control in the encephalitis component of FLAMES 3, 4
• Facial weakness may require supportive care and physical therapy alongside immunotherapy 3
• Anterior uveitis should be co-managed with ophthalmology, potentially requiring topical steroids in addition to systemic treatment 3
• Mouth ulcers may need symptomatic treatment and oral hygiene measures 3

Maintenance/Preventative Therapy

• Long-term immunosuppression should be considered for patients with relapsing disease course 2, 5
• Rituximab (375 mg/m² weekly for 4 weeks or 1000 mg given twice, two weeks apart) is frequently used for relapsing MOGAD 6, 2
• Alternative options include:
  • Mycophenolate mofetil (1-3 g/day in divided doses) 6, 5
  • Azathioprine (2-3 mg/kg/day) 2, 5
  • Monthly IVIG (0.4-1 g/kg) may be particularly effective in pediatric patients or as add-on therapy 6, 2

Monitoring and Follow-up

• Regular clinical assessments every 3-6 months to evaluate treatment response and detect early signs of relapse 1
• MOG-IgG serum concentrations vary with disease activity (higher during attacks) and treatment status (lower during immunosuppression), so timing of testing is important 1
• If MOG-IgG testing is negative but MOGAD is still suspected, re-testing during acute attacks, treatment-free intervals, or 1-3 months after plasma exchange/IVIG is recommended 1
• MRI monitoring for new or enlarging cortical lesions characteristic of FLAMES 3, 4

Special Considerations

• In cases of co-existing NMDAR encephalitis with MOGAD (which has been reported), screening for teratoma is necessary 1, 6
• Progressive disease course is very atypical for MOGAD and should prompt consideration of alternative diagnoses 7
• CSF analysis typically shows neutrophilic pleocytosis or white cell count >50/μl, which can mimic CNS infection 1, 7
• Avoid medications with known risk of worsening neurological symptoms (similar to myasthenia gravis precautions): beta-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics 1

Treatment Pitfalls to Avoid

• Misinterpreting transient increases in serum IgM levels after rituximab as treatment failure 1
• Stopping steroids too quickly, as MOGAD has a high risk of flare-ups after steroid cessation 1, 2
• Failing to recognize that FLAMES can be mistaken for viral encephalitis, leading to delayed immunotherapy 3, 4
• Treating as multiple sclerosis, as some MS disease-modifying therapies might be ineffective or potentially harmful in MOGAD 1