Paracoccidioidomycosis
Paracoccidioidomycosis (PCM), historically known as Lutz-Splendore-Almeida disease or South American blastomycosis, is a chronic systemic fungal infection caused by the dimorphic fungi Paracoccidioides brasiliensis and Paracoccidioides lutzii. It is endemic to tropical and subtropical Latin America, particularly Brazil, Colombia and Venezuela.
Infection usually begins in the lungs after spores are inhaled from cultivated soil. From there the fungus spreads through the blood and lymphatics, producing characteristic lesions in the mouth and nose (mulberry-like lesions), skin, lymph nodes and adrenal glands. At Haute-Derma, we confirm PCM by its unmistakable microscopic signature: yeast cells budding in every direction to form the "mariner's wheel" (ship's wheel) appearance.
Microbiology and Pathogenesis
Dimorphism and the Protective Role of Estrogen
- Environmental form (25°C): In moist, decaying soil on coffee and tobacco farms, the fungus grows as white to gray mold and produces small spores (microconidia).
- Tissue (parasitic) form (37°C): Inside the human body it converts into large, round, thick double-walled yeast cells measuring 10–30 µm (up to 60 µm).
- The estrogen effect (a striking sex difference): Adult men develop the disease 10 to 15 times more often than women, even though rates of silent infection (positive antibodies) are similar in both sexes. In women, 17β-estradiol binds to a receptor in the fungus and directly blocks the switch from mold to yeast, a step the fungus must complete to cause disease.
The "Mariner's Wheel" (Ship's Wheel) Appearance
The hallmark of Paracoccidioides is multiple budding:
- A large central mother cell gives rise to many tiny daughter cells (2–5 µm) attached by narrow necks around its entire circumference.
- The result looks like a ship's steering wheel (mariner's wheel) or "Mickey Mouse ears", a finding of very high diagnostic value for this disease.
Clinical Forms
Adult (Chronic) Form — more than 80% of cases: typically men aged 30–60 who work in agriculture.
- Mulberry-like (moriform) stomatitis: Shallow, ill-defined ulcers appear on the gums, palate, lips, tongue and nasal lining. Their base is speckled with fine red hemorrhagic dots that resemble a mulberry. The ulcers are very painful, make swallowing difficult and can loosen the teeth until many fall out.
- Periorificial skin lesions: The infection spreads from the mouth and nose to the skin of the lips and chin, forming warty plaques and ulcerated nodules covered with dry crust.
Juvenile (Acute/Subacute) Form — 5%–10% of cases: affects children and young adults under 30 of both sexes.
- This form progresses quickly and mainly targets the reticuloendothelial system: matted clusters of enlarged neck and mesenteric lymph nodes (which may drain pus, much like tuberculous lymphadenitis), an enlarged liver and spleen, bone marrow involvement and nodules under the skin. Mouth lesions are uncommon.
Adrenal Involvement: The fungus can infiltrate and destroy both adrenal glands in up to 50% of patients with the chronic form, leading to chronic adrenal insufficiency (Addison disease) with low blood pressure, generalized skin darkening, fatigue and low sodium.
Differential Diagnosis of Widespread Mucocutaneous Disease
| Paracoccidioidomycosis | Oral Mucosal Tuberculosis | Oral Squamous Cell Carcinoma (SCC) |
|---|---|---|
| Mulberry-like ulcers speckled with hemorrhagic dots | Necrotic, crumbly ulcers with ragged edges; very painful | Firm-edged, necrotic, fungating tumor that bleeds easily |
| Loose, falling teeth; large neck nodes that may drain pus | Matted neck nodes with accompanying lung disease | Hard, fixed regional nodes from metastasis |
| Multiple-budding yeast (mariner's wheel) | Acid-fast bacilli (AFB / Ziehl-Neelsen positive) | Atypical keratinocytes with abnormal mitoses |
| Strong male predominance (13:1) | Similar in men and women | Depends on smoking and alcohol history |
| Itraconazole / co-trimoxazole | Antituberculous therapy: RIF + INH + PZA + EMB | Surgical excision / radiotherapy / chemotherapy |
Our Diagnostic Workup at Haute-Derma
Mucosal Smear Cytology / Direct Microscopy
- Technique: Material is scraped from the base of a mulberry-like mouth ulcer or the edge of a skin lesion and treated with 10%–20% KOH.
- Findings: Very large round yeast cells (10–30 µm) with refractile double walls, ringed by multiple small buds that form a clear "mariner's wheel".
Skin or Mucosal Biopsy:
- Epidermis/mucosa: Pseudoepitheliomatous hyperplasia with neutrophilic microabscesses.
- Dermis: Suppurative, necrotizing granulomas rich in multinucleated Langhans giant cells.
- PAS and GMS stains: The fungal walls stain black or deep red, clearly outlining mother cells with multiple buds.
Systemic and Adrenal Assessment:
- Chest X-ray or CT to look for "butterfly-wing" lung infiltrates.
- Morning blood cortisol to detect coexisting adrenal insufficiency early.
Treatment at Haute-Derma
Mild to Moderate Disease
- Itraconazole (first-line, gold standard):
- Dose: 200 mg/day taken once daily after the main meal.
- Duration: 9 to 12 months, until the mucosal lesions have fully healed and serology has turned negative.
- Trimethoprim-sulfamethoxazole (co-trimoxazole, TMP-SMX) — alternative:
- Dose: 800/160 mg twice daily.
- Duration: 18 to 24 months. Treatment takes longer than with itraconazole, but the drug is inexpensive and penetrates well into the nervous system and adrenal glands.
Severe or Disseminated Disease
- Induction: Intravenous liposomal amphotericin B (3–5 mg/kg/day) for 2 to 4 weeks until the patient is clinically stable.
- Consolidation: Switch to oral itraconazole 200 mg/day for at least 12 to 24 months.
