What to do next in a patient with pemphigus vulgaris (an autoimmune skin disease) planned for rituximab (rituximab) treatment who has a positive IGRA (Interferon-Gamma Release Assay) test?

Management of IGRA-Positive Patient with Pemphigus Vulgaris Planned for Rituximab

You must initiate treatment for latent tuberculosis infection (LTBI) and delay rituximab for at least 1 month after starting anti-tubercular therapy. 1

Immediate Next Steps

1. Confirm TB Status and Rule Out Active Disease

• Obtain a chest radiograph immediately to evaluate for active tuberculosis or past TB exposure 1
• If the chest X-ray shows abnormalities suggestive of TB, perform sputum examination to exclude active disease 1
• Consider referral to an infectious disease specialist or pulmonologist for TB management 1

2. Initiate LTBI Treatment Before Rituximab

The critical principle: rituximab carries extremely high risk for TB reactivation due to profound B-cell depletion. 1, 2

• Start anti-tubercular prophylaxis immediately upon confirming LTBI (positive IGRA with negative chest X-ray and sputum) 1
• Wait a minimum of 1 month after initiating LTBI treatment before administering the first dose of rituximab 1
• Standard LTBI regimens include:
  • Isoniazid for 9 months (preferred)
  • Rifampin for 4 months (alternative)
  • 3-month isoniazid-rifapentine regimen (alternative)

3. Special Considerations for Rituximab and TB Risk

Rituximab is classified as a high-risk immunosuppressive agent for HBV reactivation with a 16.9% reactivation rate in exposed patients, and TB reactivation follows similar high-risk patterns. 1 The drug causes:

• Profound and durable B-cell depletion lasting 6-12 months 1
• HBV reactivation documented up to 12 months post-treatment, suggesting prolonged immunosuppression 1
• Similar extended risk period applies to TB reactivation 2

The FDA label for rituximab explicitly warns about reactivation of latent infections, including viral infections, which can be fatal. 2

Treatment Algorithm for Your Patient

If Chest X-ray is NEGATIVE (LTBI only):

1. Start LTBI treatment today
2. Continue current pemphigus management (likely corticosteroids ± other immunosuppressants) 1
3. Schedule rituximab for 4-6 weeks from now (minimum 1 month after starting LTBI treatment) 1
4. Continue LTBI prophylaxis throughout rituximab treatment and for several months after completion 1

If Chest X-ray is POSITIVE or Active TB Suspected:

1. Complete full treatment course for active TB before any rituximab 1
2. Delay rituximab until TB treatment is completed 1
3. Optimize pemphigus control with alternative agents during this period (high-dose corticosteroids, azathioprine, mycophenolate mofetil, or IVIg) 1

Monitoring During and After Rituximab

Extended monitoring is essential because rituximab causes prolonged immunosuppression:

• Monitor for TB symptoms monthly during rituximab treatment and for at least 12 months after completion 1, 2
• Clinical signs to monitor: fever, night sweats, weight loss, persistent cough, hemoptysis 1
• IGRA testing will remain positive even after successful LTBI treatment, so rely on clinical monitoring rather than repeat testing 1
• Screen for other infections given rituximab's broad immunosuppressive effects 2

Critical Pitfalls to Avoid

Do not start rituximab without addressing the positive IGRA. The combination of:

• Rituximab's profound B-cell depletion 1
• Likely concurrent corticosteroid use for pemphigus 1, 3
• Possible additional immunosuppressants 1

Creates an extremely high risk for TB reactivation, which can be fatal. 2

Do not assume the patient can wait for pemphigus treatment. While delaying rituximab by 4-6 weeks:

• Optimize corticosteroid dosing 1
• Consider adding or continuing adjuvant immunosuppressants (azathioprine or mycophenolate mofetil) 1
• IVIg can be used as a bridge therapy if disease is severe 4

Pemphigus Management During TB Treatment Period

Your patient still needs effective pemphigus control during the 1-month (minimum) delay:

• Continue or optimize systemic corticosteroids (typically prednisolone 1-2 mg/kg/day for disease control) 1
• Add conventional immunosuppressants if not already on them: mycophenolate mofetil (2-3 g/day) or azathioprine (1-3 mg/kg/day) 1
• These agents have lower TB reactivation risk than rituximab and can maintain disease control 1

Once rituximab is started after appropriate TB prophylaxis, the evidence strongly supports its efficacy: 89% complete remission rates when combined with short-term prednisolone, with clinical responses typically within 6 weeks 3, 1