In a patient with myeloperoxidase (MPO) deficiency and a positive Candida glabrata vaginal culture, does an axial yeast skin rash indicate a systemic infection?

MPO Deficiency with C. glabrata and Axial Skin Rash: Systemic Infection Assessment

An axial yeast skin rash in an MPO-deficient patient with C. glabrata vaginal colonization should raise significant concern for disseminated candidiasis and warrants aggressive diagnostic evaluation including skin biopsy with culture, blood cultures, and consideration of systemic antifungal therapy.

Critical Context: MPO Deficiency and Candida Risk

MPO deficiency creates a specific vulnerability to invasive Candida infections through impaired neutrophil extracellular trap (NET) formation, which is essential for fungal containment 1. Complete MPO deficiency prevents NET formation entirely, while partial deficiency only delays it 1. This defect particularly compromises NET-dependent inhibition of Candida albicans growth 1. Importantly, a fatal case of disseminated candidiasis has been documented in an MPO-deficient patient, demonstrating that this combination can be lethal 2.

Distinguishing Local from Systemic Disease

Features Suggesting Systemic Candidiasis:

• Skin lesion characteristics: Disseminated candidiasis presents with discrete pink to red papules (0.5-1.0 cm) or nodular lesions, typically on the trunk and extremities 3, 4
• Lesion evolution: Lesions may develop central pallor or become hemorrhagic if thrombocytopenia is present 3
• Distribution pattern: Multiple lesions appearing as asymptomatic or slightly pruritic macules, papules, or nodules on trunk and extremities suggest hematogenous spread 4
• Systemic symptoms: High fever and poor general condition at onset are characteristic 4

C. glabrata-Specific Concerns:

C. glabrata has intrinsic reduced azole susceptibility and can cause refractory mucosal candidiasis, particularly in immunosuppressed patients 3. While vulvovaginal candidiasis alone is common in healthy women and typically unrelated to systemic disease 3, the combination of MPO deficiency, C. glabrata colonization, and new skin lesions creates a higher-risk scenario.

Diagnostic Algorithm

Immediate steps required:

• Skin biopsy with culture: Recovery of fungi from skin or soft tissue aspiration/biopsy almost always warrants aggressive systemic therapy 3
• Blood cultures: Obtain immediately, though disseminated candidiasis develops cutaneous lesions in only 13% of cases, and blood cultures may be negative in 50-75% of systemic candidiasis cases 3, 4
• Histopathology: Look for yeasts, pseudohyphae, or true hyphae in tissue specimens 4

Clinical assessment priorities:

• Evaluate for fever, myalgias, and signs of deep tissue involvement 3
• Assess for painful myositis (most common with C. tropicalis but can occur with other species) 3
• Examine for muscle or soft tissue abscess formation 3

Treatment Considerations

If Systemic Infection Confirmed or Highly Suspected:

For C. glabrata specifically, azole therapy is frequently unsuccessful 3. Treatment options include:

• Echinocandins (caspofungin, micafungin, anidulafungin) are preferred for invasive C. glabrata given azole resistance 3
• Amphotericin B formulations remain effective alternatives 3
• Voriconazole or posaconazole may be considered but have variable efficacy against C. glabrata 3

If Limited to Vaginal Disease:

For C. glabrata vulvovaginal candidiasis without systemic involvement:

• Topical boric acid 600 mg intravaginally daily for 14 days is preferred 3, 5, 6
• Alternative: 17% flucytosine cream alone or combined with 3% amphotericin B cream for 14 days 3, 5, 6
• Nystatin intravaginal suppositories are another option 5

Critical Pitfalls to Avoid

• Underestimating risk: The combination of complete MPO deficiency and Candida exposure has resulted in fatal disseminated candidiasis 2. Do not dismiss new skin lesions as simple dermatitis.

• Relying on blood cultures alone: Blood cultures are negative in 50-75% of systemic candidiasis cases 4. Negative blood cultures do not exclude disseminated disease.

• Assuming vaginal candidiasis is benign: While vulvovaginal candidiasis is typically localized in immunocompetent hosts 3, 5, MPO deficiency fundamentally alters this risk profile 1, 2.

• Delayed tissue diagnosis: Skin biopsy should be performed urgently rather than waiting for clinical deterioration 3.

• Inadequate antifungal coverage: If systemic infection is suspected, empiric therapy should cover azole-resistant organisms including C. glabrata 3.