Paracoccidioidomycosis (South American blastomycosis)



Paracoccidioidomycosis (South American blastomycosis)


Wanda Sonia Robles and Mahreen Ameen


Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports


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Paracoccidioidomycosis (PCM) is a chronic, progressive, granulomatous mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis. It primarily affects the lungs and is believed to be acquired from inhalation of the fungus that resides in soil and plants of endemic regions. PCM is restricted to Latin America, where it is the most prevalent systemic endemic mycosis. It has been reported in nearly all countries from Mexico to Argentina, with the exception of the Caribbean islands and Chile. Eighty percent of cases occur in Brazil, with the highest incidence in the state of Sao Paulo. This is followed by Venezuela, Colombia, Ecuador, and Argentina. PCM characteristically affects those working in agriculture and in rural areas. Because of the long latency period, the disease may appear many years after a person has left an endemic region. Untreated PCM has one of the highest rates of mortality of all the systemic mycoses.


There are two main clinical forms: an acute or subacute form, and a unifocal or multifocal chronic form. The acute form affects young people of both sexes and involves mainly the reticuloendothelial system. This form of infection is often severe and carries a worse prognosis. The chronic form most commonly affects adult males, and causes pulmonary and/or mucocutaneous disease. Most cases of pulmonary infection have an indolent course. Only 2% of those infected develop the disseminated form of disease. Dissemination occurs most commonly to the mucosae of the upper airways and upper gastrointestinal tract. Cutaneous and lymph node involvement is common, and other organ systems may be involved such as the adrenal glands (causing Addison’s syndrome), bones, and central nervous system. Oral lesions affect the gingiva, the hard palate, lips, and tongue. Nasal and pharyngeal ulcers can give rise to dysphagia and dysphonia. Ulcerative lesions can be painful, and are characterized by a punctate vascular pattern over a granulomatous base. Cutaneous lesions are highly polymorphic, consisting of verrucous and ulcerative papules, plaques, and nodules. Centrofacial localization is typical and usually a result of dissemination of oral lesions. PCM is also characterised by massive and visible cervical and submandibular lymphadenopathy, which may progress to form abscesses with draining sinuses. Other lymph glands may also become enlarged. Primary mucocutaneous infection is rare, but can occur following direct inoculation of the skin or mucous membranes. It can arise from using twigs to clean the teeth, which is practiced in rural Brazil.


Disseminated infection is severe in the immunocompromised, including those co-infected with HIV. The mortality rate with HIV infection is high, ranging from 30% to 45%. However, the incidence of PCM in patients with AIDS in Latin America is low, and this has been attributed to the widespread use of trimethoprim–sulfamethoxazole as prophylaxis for Pneumocystis carinii pneumonia.



Management strategy


P. brasiliensis is highly sensitive to antifungal drugs, and therefore a large therapeutic armamentarium exists to treat PCM. Itraconazole is the drug of choice for the treatment of mild to moderate acute and chronic clinical forms of PCM. It is given at a dose of 100–200 mg daily for a mean period of 6 months (range 3–12 months) depending on clinical response. It gives a cure rate of 90%, and recurrence rates of 0-15% have been reported after a median of 12 months, depending on comorbidities such as alcoholism, malnutrition, and AIDS. Ketoconazole (200–400 mg daily) is also highly effective, 90% of patients responding after 6–12 months of treatment with only a 10% relapse rate. However, adverse effects are common especially with long-term treatment. With the availability of newer antifungals, its use has decreased. Sulfonamides (sulfadiazine, sulfamethoxypyridazine, sulfadimethoxine, trimethoprim–sulfamethoxazole) are an attractive option as they are inexpensive and well-tolerated. However, therapy duration is characteristically long, usually 2 to 3 years. Compliance can therefore be a problem, which might explain their lower cure rate of only 70%. In addition, they have a significant relapse rate of 35%. They are still commonly used as first agents in endemic regions because of their ready availability and low cost. Parenteral amphotericin B (cumulative dose of 1–2 g based on clinical response) is the drug of choice for severe or refractory infection. The cure rate is only 60%, but consideration must be given to the fact that it is usually given to the most severely ill patients. The relapse rate with amphotericin B is generally higher than with itraconazole, occurring in 20–30% of cases. Long-term maintenance therapy with an azole or sulfonamide is therefore required. In cases of central nervous system (CNS) PCM, sulfadiazine appears to be equally effective as amphotericin B. More recently, voriconazole, an extended-spectrum triazole, has demonstrated comparable efficacy and tolerability to itraconazole in the treatment of PCM. However, its high costs make it prohibitive for use in most endemic settings. There are few studies demonstrating the efficacy of fluconazole for PCM. It has been suggested that it may be useful in the management of CNS PCM given its excellent CNS penetration. Long-term follow-up after treatment of PCM is required as relapse rates are unknown.



Specific investigations






Rapid diagnosis may be achieved by direct microscopic examination of sputum or other exudates in potassium hydroxide. P. brasiliensis appears as large, round yeast cells with multiple budding. Culture of sputum, skin, lymph node, or bone marrow specimens on Sabouraud dextrose agar can recover the organism, but may require 20–30 days for growth. Biopsy specimens reveal granuloma formation, and Gomori methenamine silver stain reveals yeast cells. There are several serological tests which detect antibodies against the fungus, and they can provide results earlier than culture or histopathology. The most common test is immunodiffusion, which has high specificity but sensitivity varies depending on the type of antigen used. Therefore, a negative serologic response does not exclude PCM, particularly in the immunocompromised.







Paracoccidioidomycosis in patients with human immunodeficiency virus: review of 12 cases observed in an endemic region in Brazil.

Paniago AM, de Freitas AC, Aguiar ES, Aguiar JI, da Cunha RV, Castro AR, et al. J Infect 2005; 51: 248–52.


This study demonstrated that the lymph nodes were the organ most commonly involved (n=10, 83.3%), followed by the lung (n=7, 58.3%). Papulonodular ulcerative skin lesions affected 50% (n=6), and oral mucosal ulcerative lesions were present in 42% (n=5). A single patient had pleural involvement with a secondary pathological rib fracture. Seven patients had multi-organ involvement. All patients were treated with trimethoprim–sulfamethoxazole, and seven patients in addition received amphotericin B. However, eight patients (67%) died as a result of disease progression.

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Aug 7, 2016 | Posted by in Dermatology | Comments Off on Paracoccidioidomycosis (South American blastomycosis)

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