Cutaneous Cryptococcosis Diagnosis
For suspected cutaneous cryptococcosis, obtain a skin biopsy for both histopathology and fungal culture, which remain the gold standard for diagnosis, and then perform mandatory lumbar puncture plus serum cryptococcal antigen testing to exclude disseminated disease, even in neurologically asymptomatic patients. 1, 2, 3
Diagnostic Workflow
Initial Skin-Based Diagnosis
- Obtain skin biopsy from the lesion for histopathological examination and fungal culture, as these are the definitive diagnostic methods 1, 4, 3
- Look for characteristic thick-walled encapsulated yeast cells (3-6 μm diameter) with narrow-based budding on histopathology 1, 3
- India ink staining of skin scrapings or biopsy material can provide rapid presumptive diagnosis by revealing the polysaccharide capsule 1
- Culture specimens on fungal media and observe for up to 14 days to allow adequate growth 1
- Use phenoloxidase and canavanine-glycine-bromothymol blue tests to identify the specific Cryptococcus species (C. neoformans vs C. gattii) 5
Critical Distinction: Primary vs Secondary Cutaneous Disease
This distinction fundamentally changes treatment intensity and duration. Primary cutaneous cryptococcosis (PCC) is localized skin infection from direct inoculation, while secondary cutaneous disease indicates disseminated infection with hematogenous spread. 1, 4
Mandatory Evaluation to Exclude Dissemination
Even if skin lesions appear isolated, all patients must undergo systematic investigation to rule out disseminated disease: 2, 4, 5
- Lumbar puncture with CSF analysis (opening pressure, cell count, protein, glucose, India ink stain, cryptococcal antigen, and culture) to exclude CNS involvement 1, 2
- Serum cryptococcal antigen testing using lateral flow assay (>95% sensitivity and specificity for disseminated disease) 2
- Blood cultures using lysis-centrifugation method for optimal recovery 1
- Chest imaging (chest X-ray or CT) to evaluate for pulmonary involvement 6
Clinical Features Suggesting Cutaneous Cryptococcosis
Cutaneous lesions are highly variable and may present as: 1, 5
- Papules, nodules, or pustules (often resembling molluscum contagiosum)
- Infiltrative or tumoral masses (up to 40 cm diameter reported)
- Chronic draining necrotic ulcers
- Cellulitis-like presentations
- Most commonly affect face, scalp, and upper extremities
Risk Stratification
Identify immunosuppression status, as this determines treatment approach: 1, 4, 5
- Long-term corticosteroid therapy (most common risk factor in PCC)
- Solid organ transplantation
- HIV/AIDS with CD4 <200 cells/μL
- Hematologic malignancies
- Sarcoidosis
- Diabetes mellitus
Important caveat: PCC can occur in truly immunocompetent hosts, typically following traumatic inoculation through skin injury 7, 4, 5
Ancillary Testing
- Serum cryptococcal antigen titer: If positive (≥1:512), this indicates high fungal burden and disseminated disease 6, 2
- Mass spectrometry can identify specific serotypes (e.g., C. neoformans serotype A) 3
- Antifungal susceptibility testing should be considered for treatment failures or relapse 6
Common Diagnostic Pitfalls
- Failing to perform lumbar puncture: Cryptococcus has strong CNS tropism, and 5-10% of patients with cutaneous lesions may have asymptomatic meningitis that precedes neurological symptoms by weeks 1, 2
- Misdiagnosing as other skin conditions: The protean manifestations mimic bacterial cellulitis, pyoderma gangrenosum, or other fungal infections 4, 3
- Inadequate culture observation time: Cryptococcus may require up to 14 days for growth 1
- Assuming immunocompetence excludes diagnosis: While rare, PCC does occur in immunocompetent patients 7, 4
- Treating empirically without culture: Species identification and susceptibility testing guide optimal therapy and predict outcomes 5