Cryptococcosis
Cryptococcosis is a dangerous invasive systemic fungal infection caused by two species complexes of encapsulated yeasts: Cryptococcus neoformans (seen mainly in immunocompromised people, particularly those with HIV/AIDS or on immunosuppressive drugs) and Cryptococcus gattii (which can also cause disease in people with normal immunity).
Infection begins in the lungs after inhaling desiccated yeast cells or basidiospores found in decaying pigeon droppings or eucalyptus canopies. From the lungs, the fungus enters the bloodstream and has a particular predilection for the central nervous system, causing acute or chronic meningitis. The skin is the second most common site outside the lungs, involved in 10%–15% of disseminated cases. At Haute-Derma, we treat skin lesions caused by Cryptococcus as a clinical "alarm bell" that allows a life-threatening systemic fungal infection to be diagnosed in time.
Microbiology and Pathogenesis
Biology and Capsule Structure
- Cryptococcus spp. are round to oval yeasts, 4–10 µm in size, that reproduce by narrow-based budding.
- Large polysaccharide capsule: Unlike most fungi, Cryptococcus is surrounded by a thick mucopolysaccharide capsule made mainly of glucuronoxylomannan (GXM) and galactoxylomannan (GalXM). The capsule can swell until the whole cell reaches up to 30 µm.
- How the capsule drives virulence:
- It blocks phagocytosis by macrophages and neutrophils.
- It reduces complement recognition and suppresses T-cell responses.
- It sheds soluble GXM antigen into the blood, which neutralizes the host's antibodies.
Melanin and Spread to the Nervous System and Skin
- Cryptococcus produces the enzyme laccase, which builds melanin in the cell wall from diphenolic compounds. Melanin shields the fungus from reactive oxygen species (ROS) released by immune cells and from high body temperature.
- After crossing the alveoli, the fungus travels freely in plasma or hides inside macrophages (the Trojan horse mechanism) to reach the meninges and the dermis.
Clinical Forms in the Skin
Disseminated (Secondary) Cutaneous Cryptococcosis — more than 90% of skin cases: the result of bloodstream spread from the lungs.
- Umbilicated papules (molluscum contagiosum-like lesions): The most common form. Firm pink-red or skin-colored papules, 2–10 mm across, with a necrotic, umbilicated center, clustered on the face, neck and chest.
- Cellulitis and subcutaneous abscesses: Raised, swollen red plaques that soften into cold abscesses under the skin, which rupture and drain pus chronically.
- Ulcers and vegetative plaques: Well-defined shallow ulcers with a gray-red necrotic granulation base and a firm, irregular, heaped-up edge.
Primary Cutaneous Cryptococcosis (PCC) — rare:
- Follows a penetrating injury that inoculates the fungus directly into the skin (often in gardeners or farmers).
- Presents as a single ulcer or an indurated plaque or pustule on a limb. There is no lung or nervous system involvement, and serum CrAg is usually negative or positive only at a low titer.
Differential Diagnosis
| Cryptococcosis (C. neoformans) | Talaromycosis (T. marneffei) | Histoplasmosis (H. capsulatum) |
|---|---|---|
| Round yeast (4–10 µm) with a thick polysaccharide capsule | Oval yeast (2–6 µm) that divides by a transverse septum | Small yeast (2–4 µm) with narrow-based budding inside macrophages |
| Mucicarmine (+), Alcian blue (+), India ink (+) | Giemsa (+), GMS (+) showing the septum | Wright-Giemsa (+), GMS (+) small budding forms |
| Narrow-based budding | Fission (transverse septum) | Narrow-based budding |
| Produces melanin (Fontana-Masson +) | Releases a soluble red pigment into SDA medium | No melanin |
| Amphotericin B + flucytosine > fluconazole | Liposomal amphotericin B > itraconazole | Liposomal amphotericin B > itraconazole |
Our Diagnostic Workup at Haute-Derma
India Ink Wet Mount and Rapid Antigen Test (CrAg LFA):
- India ink wet mount: Fluid aspirated from a skin abscess or scraped from an ulcer base is mixed with a drop of India ink. Under the microscope, the polysaccharide capsule excludes the ink and stands out as a clear halo against the black background.
- Cryptococcal antigen test (CrAg lateral flow assay): A rapid LFA that detects GXM antigen in blood or lesional fluid, with very high sensitivity and specificity (> 98%).
Skin Biopsy and Special Stains:
- H&E stain: Yeast cells appear surrounded by a clear, halo-like space where the capsule has shrunk.
- Mayer's mucicarmine stain — the gold standard: Specifically stains the capsule's mucopolysaccharide a bright pink to carmine red.
- Fontana-Masson stain: Stains melanin in the fungal cell wall black, which is especially useful for capsule-deficient variants.
MANDATORY MENINGITIS ASSESSMENT: Every patient diagnosed with disseminated cutaneous cryptococcosis must undergo a lumbar puncture to measure opening pressure and to perform India ink microscopy, CSF CrAg testing and culture, even if there is no headache or neck stiffness yet.
Treatment Protocol at Haute-Derma
Standard Regimen for Disseminated Disease or Concurrent Meningitis
- Induction therapy (at least 2 weeks):
- Liposomal amphotericin B: 3–4 mg/kg/day by IV infusion.
- Flucytosine (5-FC): 100 mg/kg/day orally in 4 divided doses. The combination kills the fungus quickly and lowers the risk of relapse.
- Consolidation therapy (8 weeks):
- Fluconazole: 400–800 mg/day orally.
- Maintenance therapy (secondary prophylaxis):
- Fluconazole: 200 mg/day continuously for at least 12 months (and, in patients with HIV, until the CD4 count has stayed above 100 cells/µL for more than 6 months).
