Can Histoplasma cause soft tissue masses, especially in immunocompromised individuals?

Can Histoplasma Cause Soft Tissue Masses?

Yes, Histoplasma capsulatum can definitively cause soft tissue masses, particularly in immunocompromised patients through hematogenous dissemination, affecting skin, subcutaneous tissues, and lymph nodes. 1, 2

Mechanism of Soft Tissue Involvement

Hematogenous dissemination from the lungs occurs in virtually all infected individuals during the first 2 weeks of infection before specific immunity develops, allowing the organism to seed soft tissues throughout the body. 2

• Progressive dissemination with soft tissue involvement occurs primarily in patients with CD4+ counts <150 cells/µL, organ transplant recipients, and those at extremes of age. 2
• In immunocompromised hosts, even a tiny inoculum can lead to widespread disseminated infection with soft tissue manifestations. 3

Clinical Presentations in Soft Tissues

Cutaneous Manifestations

• Histoplasma presents with a wide variety of cutaneous manifestations, particularly in disseminated infection or in the immunocompromised. 1
• Skin lesions can occur as nodules, ulcerations, or papular eruptions. 4, 3
• Primary cutaneous histoplasmosis can occur through direct inoculation (e.g., after trauma or procedures), presenting as nodule-like lesions that may progress to ulceration with purulent discharge. 4

Lymph Node Masses

• Lymphadenopathy is common in disseminated disease, with six out of seven patients in one series presenting with peripheral and/or abdominal lymphadenopathy. 3
• CT imaging shows enlarged lymph nodes with homogeneous soft-tissue density (44%), diffuse or central low density (13%), or both (19%). 5

Subcutaneous Nodules

• Patients can develop subcutaneous nodules as part of disseminated infection. 3
• These masses may be mistaken for other infectious or neoplastic processes, particularly in patients with underlying connective tissue diseases. 6

Diagnostic Approach for Soft Tissue Masses

High-Yield Testing Strategy

• For suspected soft tissue histoplasmosis in immunocompromised patients, order Histoplasma antigen in both urine (95% sensitivity) and serum (85% sensitivity) simultaneously. 2
• Fine needle aspiration cytology (FNAC) of soft tissue masses is a reliable tool, showing 2-4 micrometer budding yeasts intracellularly within histiocytes and extracellularly. 3
• Do not rely on antibody testing alone in immunocompromised patients—sensitivity drops to only 18% in organ transplant recipients and 45% in HIV/AIDS patients. 7

Tissue Diagnosis

• Biopsy of soft tissue lesions with histopathologic examination has 75% sensitivity and can demonstrate intracytoplasmic inclusions of Histoplasma. 4, 8
• Culture from tissue specimens is positive in 84% of systemic cases. 8

Treatment Considerations

All patients with disseminated histoplasmosis causing soft tissue masses require antifungal treatment regardless of symptom severity. 1, 2

Severe Disease

• Amphotericin B (0.7 mg/kg/day) is indicated for severe manifestations, followed by itraconazole for maintenance therapy. 1, 2

Mild-to-Moderate Disease

• Itraconazole 200 mg once or twice daily for 12-24 months is the treatment of choice for less severe disseminated disease. 1

Alternative Therapy

• In resource-limited settings where first-line agents are unavailable, trimethoprim-sulfamethoxazole has shown efficacy in case reports of primary cutaneous histoplasmosis. 4

Critical Clinical Pitfalls

• Histoplasmosis can be misdiagnosed as a flare of connective tissue disease or other infections because they share clinical findings. 6
• Mortality in histoplasmosis is 5% in children and 8% in adults, making rapid diagnosis essential. 2, 7
• In-hospital mortality for disseminated disease is 6%, with relapse rates of 9%. 8
• Always consider histoplasmosis in patients from endemic areas (Ohio and Mississippi River valleys) presenting with soft tissue masses, fever, and immunosuppression. 9, 8