What is the most common cause of reactivation of ocular histoplasmosis?

Most Common Cause of Reactivation of Ocular Histoplasmosis Syndrome

The most common cause of reactivation of ocular histoplasmosis is immune system compromise, particularly when CD4+ T-lymphocyte counts fall below 150 cells/µL. This immune dysfunction allows for reactivation of latent Histoplasma capsulatum infection, which can lead to choroidal neovascularization and subsequent vision loss.

Pathophysiology of Ocular Histoplasmosis Reactivation

Ocular histoplasmosis syndrome (OHS) is characterized by:

• Peripapillary atrophy
• Peripheral chorioretinal scars
• Macular chorioretinal lesions
• Absence of vitreous inflammation

Mechanisms of Reactivation

1. Immunosuppression:

   • HIV infection with CD4+ counts <150 cells/µL 1
   • Immunosuppressive medications, particularly TNF-α inhibitors 2
   • Corticosteroid therapy

2. Fungal Antigen Exposure:

   • Reinfection with Histoplasma capsulatum
   • Chronic fungal infections elsewhere in the body 3

3. Iatrogenic Triggers:

   • LASIK surgery 3
   • Ocular procedures that may disrupt chorioretinal scars

Risk Factors for Reactivation

• Immunocompromised status: Most significant risk factor, especially with CD4+ counts <150 cells/µL 1
• Residence in endemic areas: Ohio and Mississippi River Valleys, Puerto Rico, Latin America
• Presence of perimacular chorioretinal scars: These represent sites of previous infection that may reactivate
• Concurrent fungal infections: Dermatomycoses, onychomycosis, vaginal candidiasis 3
• Male sex and older age: Associated with increased risk of histoplasmosis reactivation 1

Clinical Presentation of Reactivation

When ocular histoplasmosis reactivates, patients may present with:

• Sudden vision loss
• Metamorphopsia (distorted vision)
• Central scotoma
• Abnormal Amsler grid findings
• Choroidal neovascularization (CNV) on examination

Diagnostic Approach

1. Fundoscopic examination: Look for the classic triad of peripapillary atrophy, peripheral chorioretinal scars, and macular lesions
2. Optical coherence tomography (OCT): To detect CNV and monitor disease activity 4
3. Fluorescein angiography: To identify active CNV
4. Histoplasma antigen detection: In urine (95% sensitivity) and serum (85% sensitivity) 5
5. CD4+ count measurement: To assess immune status

Prevention of Reactivation

To prevent reactivation of ocular histoplasmosis:

1. Maintain immune function:

   • Effective antiretroviral therapy in HIV patients to keep CD4+ counts >200 cells/µL 1
   • Careful monitoring when immunosuppressive therapy is necessary

2. Treat concurrent fungal infections:

   • Aggressive treatment of dermatomycoses, onychomycosis, and vaginal candidiasis 3

3. Environmental precautions:

   • Avoid activities that create dust in endemic areas
   • Avoid disturbing areas contaminated with bird or bat droppings 5

4. Regular monitoring:

   • Self-monitoring with Amsler grid
   • Regular ophthalmologic examinations for patients with known OHS

Management of Reactivation

When reactivation occurs with CNV:

1. Anti-VEGF therapy: First-line treatment for subfoveal and juxtafoveal CNV 4
2. Photodynamic therapy: Effective for subfoveal CNV 4, 6
3. Laser photocoagulation: For extrafoveal CNV 4
4. Antifungal therapy: For disseminated disease
   • Liposomal amphotericin B (3-5 mg/kg IV daily) for 1-2 weeks
   • Followed by itraconazole 200 mg twice daily for at least 12 weeks 5

Important Considerations

• Patients with OHS should be informed about their risk for vision loss and taught to self-monitor with an Amsler grid 3
• Unlike toxoplasmosis in immunocompromised hosts, histoplasmosis reactivation typically occurs at the borders of existing scars 7
• Patients on TNF-α inhibitors are at particularly high risk for disseminated histoplasmosis 2
• Regular ophthalmologic follow-up is essential for patients with known OHS, especially those who are immunocompromised

Remember that prompt diagnosis and treatment of reactivation are crucial to preserving vision in patients with ocular histoplasmosis syndrome.