What is the next step in treatment for a patient with pemphigus vulgaris and a positive Interferon-Gamma Release Assay (IGRA) test, but no evidence of active or past tuberculosis infection on High-Resolution Computed Tomography (HRCT) chest?

Treatment of Latent Tuberculosis in Pemphigus Vulgaris with Positive IGRA and Normal HRCT

Initiate latent tuberculosis infection (LTBI) treatment before starting or continuing immunosuppressive therapy for pemphigus vulgaris, as the positive IGRA with normal chest imaging confirms LTBI requiring treatment to prevent reactivation. 1

Diagnostic Confirmation

Your patient's clinical picture is straightforward:

• Positive IGRA test indicates latent tuberculosis infection in the absence of active disease 1
• Normal HRCT chest effectively rules out active pulmonary TB and confirms this is latent rather than active infection 2, 3
• Absence of respiratory symptoms further supports LTBI rather than active disease 1
• The immunosuppression from both pemphigus vulgaris and planned immunosuppressive therapy significantly increases reactivation risk 1

Treatment Algorithm for LTBI

Recommended LTBI treatment regimens (in order of preference):

• Rifampin for 4 months is the preferred short-course regimen 2, 1
• Isoniazid for 9 months is an alternative option 2, 1

Critical Drug Interaction Considerations

If planning rituximab or other immunosuppressive therapy:

• Rifampin should be AVOIDED as it is a strong CYP3A inducer that significantly reduces levels of many immunosuppressive agents including rituximab 2
• Isoniazid is preferred but requires dose adjustments - it inhibits CYP450 3A4 and may increase drug levels of certain immunosuppressants 2
• Consultation with a TB specialist is mandatory to select the optimal regimen given planned immunosuppressive therapy 2

Timing of Immunosuppressive Therapy

For pemphigus vulgaris treatment:

• Begin LTBI treatment BEFORE initiating or resuming biologic/immunosuppressive therapy 1
• Immunosuppressive therapy can be started after 1 month of LTBI treatment according to American College of Rheumatology guidelines 1
• Monitor for hepatotoxicity throughout LTBI treatment, particularly with isoniazid 1

Pemphigus Vulgaris Management During LTBI Treatment

First-line therapy for pemphigus vulgaris should proceed as follows:

• Start with oral prednisolone 0.5-1 mg/kg/day for milder cases or 1 mg/kg/day for more severe disease 2
• High-potency topical corticosteroids can be used as adjunctive therapy, particularly if systemic corticosteroid doses need to be minimized 4
• Plan to add corticosteroid-sparing immunosuppressant (azathioprine 2-3 mg/kg/day or mycophenolate mofetil 2-3 g/day) once LTBI treatment is established 2
• Rituximab (2 x 1000 mg infusions, 2 weeks apart) is FDA-approved for pemphigus vulgaris and can be considered after 1 month of LTBI treatment 2, 5

Monitoring Strategy

During LTBI treatment:

• Monitor for clinical symptoms of TB reactivation rather than repeat IGRA testing 1
• Monitor liver function tests regularly due to hepatotoxicity risk with LTBI medications 1
• Assess for drug interactions if immunosuppressive therapy is initiated 2

After completing LTBI treatment:

• No routine repeat chest imaging is needed if patient remains asymptomatic 2, 3
• Consider annual TB screening only if ongoing risk factors for TB exposure exist 1

Key Pitfalls to Avoid

• Do NOT delay LTBI treatment - the risk of TB reactivation with immunosuppression is substantial 1
• Do NOT use rifampin-based regimens without carefully reviewing drug interactions with planned immunosuppressive therapy 2
• Do NOT start high-dose immunosuppression before initiating LTBI treatment 1
• Do NOT assume normal chest imaging means no TB risk - LTBI requires treatment in immunocompromised patients regardless of imaging 1, 3

Prophylaxis Considerations

When rituximab is used for pemphigus vulgaris:

• PCP prophylaxis should be considered during and following rituximab treatment 5
• Methylprednisolone 100 mg IV (or equivalent) is recommended 30 minutes prior to each rituximab infusion 5