What is Paracoccidioidomycosis?

From the Guidelines

Paracoccidioidomycosis should be treated with itraconazole (200 mg daily for 9–12 months) as the therapy of choice for patients with mild-to-moderate forms of the disease. This recommendation is based on the most recent and highest quality study available, which was published in 2021 in The Lancet Infectious Diseases 1. The study emphasizes the importance of microscopy in the diagnosis of paracoccidioidomycosis, particularly using optical brighteners, and highlights the role of serological testing in reference laboratories with known and published performance characteristics.

Some key points to consider in the management of paracoccidioidomycosis include:

• The use of co-trimoxazole (for 18–24 months) as a therapeutic alternative to itraconazole 1
• The reservation of short (2–4 weeks) induction therapy with AmB for severe cases or immunocompromised patients, followed by 200–400 mg of itraconazole 1
• The importance of regular monitoring of liver function during treatment, as antifungal medications can cause hepatotoxicity
• The need for nutritional support, as many patients present with weight loss and malnutrition

In terms of diagnosis, it is essential to note that:

• Microscopy has an important role in the diagnosis of paracoccidioidomycosis, particularly using optical brighteners 1
• Serological testing should only be done by reference laboratories, using reagents with known and published performance characteristics 1

Overall, the management of paracoccidioidomycosis requires a comprehensive approach, including accurate diagnosis, appropriate antifungal therapy, and supportive care to prevent relapse and improve patient outcomes.

From the Research

Definition and Causes of Paracoccidiomycosis

• Paracoccidiomycosis is a systemic fungal infection caused by Paracoccidioides brasiliensis 2.
• The infection is endemic in subtropical areas of Latin America and has a high prevalence in Brazil 2.
• The disease is acquired by airborne inhalation of conidia and is frequently observed in adult male rural workers 2.

Clinical Manifestations

• The juvenile type of this mycosis is less prevalent (5-10% of clinical cases) and attacks both sexes 2.
• The clinical presentation resembles severe tuberculosis, leukaemia or lymphoma 2.
• Radiologic abnormalities in the lung fields may be seen, and mucous membrane lesions occasionally occur 2.
• The disease has different clinical manifestations that require differentiation with tuberculosis, Hodgkin disease, several systemic and subcutaneous mycoses, and squamous cell carcinoma 3.

Diagnosis

• The diagnosis is confirmed by finding yeast-like elements of P. brasiliensis in microscopic examinations of wet preparations of specimens submitted for mycologic studies 2.
• Histologic and serologic studies may also assist in the diagnosis of this mycosis 2.
• Diagnosis can be made by finding the organism in a biopsy specimen and isolating it in fungal culture 3.

Treatment

• Sulfonamides, ketoconazole, itraconazole, fluconazole and amphotericin B have been successfully used in the treatment of paracoccidioidomycosis 2.
• Itraconazole is the treatment of choice, being effective in more than 95% of cases 2.
• Co-trimoxazole is still frequently used especially in chronic progressive disease and as maintenance after a course of amphotericin B in severe cases of this mycosis 2.
• Sulfamethoxazole-trimethoprim can be used for mild forms, and itraconazole for moderate cases 3.
• Fluconazole and voriconazole can be used for meningeal involvement, and amphotericin B is indicated for severe disease 3.
• The combination of sulfamethoxazole and trimethoprim (SMX-TMP) is most commonly used in clinical practice due to its higher availability in public health services 4.
• SMX-TMP has shown good efficacy, with 73.6% of patients exhibiting an adequate therapeutic response 4.

Treatment Response and Factors Associated with Therapeutic Failure

• Treatment nonadherence and PCM-HIV coinfection are factors associated with therapeutic failure 4.
• The frequency of adequate therapeutic response gradually decreases as the duration of treatment decreases 4.
• The search for new alternatives for treating the most severe forms of paracoccidioidomycosis is an ongoing challenge, and novel treatments may be found among new classes of drugs, drug combinations, or agents capable of modulating the immune response 5.