Print version ISSN 1413-8670
Braz J Infect Dis vol.14 no.1 Salvador Jan./Feb. 2010
Rodrigo da Costa CarneiroI; Bianca Grassi de MirandaI; Carlos Camilo NetoII; Marina K TsukumoIII; Cibele LC FonsecaIII; João Silva de MendonçaIV
IResidents of Infectious Diseases Department, Hospital do Servidor Público Estadual
IIResident of Pathology Department, Hospital do Servidor Público Estadual
IIIPreceptors of Infectious Diseases Department, Hospital do Servidor Público Estadual
IVDirector of Infectious Diseases Department, Hospital do Servidor Público Estadual
We present two cases of juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis frequently found in rural areas, whose prognosis is poor in children and young adults. They are a 14-year-old boy and a 25-year-old woman, both residents in an urban area in São Paulo - Brazil, without any history of travelling to an endemic area. They have been admitted to the hospital due to fever, weight loss and lymphadenopathy. The diagnosis was confirmed by serologic and histopathologic study. Patients have recovered after therapy with oral itraconazole and were discharged from hospital, maintaining outpatient visits. In this article, the authors discuss the unusual presentation of PCM in an urban area.
Keywords: juvenile paracoccidioidomycosis, lymphadenopathy, Paracoccidioides brasiliensis, urban area.
PCM is a systemic, chronic granulomatous and progressive disease, caused by the dimorphic fungus Paracoccidioides brasiliensis which is restricted to Latin America.1,2 In adults the main presentation is a chronic disease, but in children and adolescents, it is usually an acute or sub-acute disease, and may be severe.3 The acute juvenile form is characterized by a rapid course and a marked involvement of the reticuloendothelial system.4 In the absence of specific therapy, mortality rates are high.5 Follow-up is required after hospital discharge, in regard the possibility of relapses.3
Male, 14-year-old, student, from São Paulo was admitted to hospital in July 2006 with asthenia, weight loss (4 kg), fever (39ºC), low jaundice, coluria and pain in left leg. The signs and symptoms have started one month earlier. He has not travelled to any endemic areas of PCM. Physical examination revealed mild jaundice, disseminated lymphadenopathies varying from 2 to 4 centimeters in diameter, hepatosplenomegaly and a painful mass in left leg proximal extremity (Figure 1). Abdominal and cervical CT confirmed the enlargement of liver, spleen and lymph nodes (Figure 2), and X-rays of the leg showed osteoclastic lesions (Figure 3). Diagnostic is confirmed after cervical lymph node biopsy showed Paracoccidioides brasiliensis (Figure 4) and serologic test for paracoccidioidomycosis (double immunodiffusion). The patient was treated with itraconazole 200 mg per day, with clinical improvement. Hospital discharge occurred after seven days, with subsequent outpatient visits. Itraconazole was given for six months, without any complication in the period.
Female, pre-school teacher, natural from São Paulo, presented to the hospital in June 2006 with fever (38º C), malaise, weight loss (3 kg), generalized arthralgia and lymphadenopathies ranging from 1 to 2 centimeters in diameter. Symptoms have started twenty days before hospital admission. She had never been to endemic areas. Physical examination revealed moderate mucocutaneous pallor, hepatosplenomegaly and generalized lymphadenopathy. Abdominal CT scan confirmed enlargement of the liver and the spleen. Diagnosis is confirmed after cervical lymph node biopsy showed the same findings of case 1 and serologic test for paracoccidioidomycosis (double immunodiffusion). The treatment was initiated with oral itraconazole 200 mg per day and persisted for 6 months. The patient presented a rapid improvement and was discharged from hospital 8 days after admission, with outpatient followup. After 3 months of treatment, the serology marks became negative.
Both patients reported in this article presented with the acute form of PCM, consistent with others reports of the disease in children and adolescents.6-8 Most of clinical manifestations were related to the reticuloendothelial system, such as lymph node enlargement, hepatomegaly and splenomegaly.9 Lymphadenopaty is the most frequent manifestation followed by fever.10 Both were present in our patients.
Hepatic disorders are one of the most reported abnormalities3,11 and were presented in our patients, both with increase in alkaline phosphatase and gamma-glutamyl transferase. In case 1 jaundice was observed, this manifestation is associated with poor prognosis. 12,13 All hepatic changes improved with treatment and the patients didn't show late complications, such as portal hypertension or cholecystitis, in the follow-up period.
Pereira et al. showed bone involvement in 20% of 38 patients with juvenile form of PCM.9 In our case one, osteoclastic lesions were present and had clinical and radiological resolution after therapy.
The identification of fungal elements suggestive of P. brasiliensis in lymph nodes and suspected organs biopsy, or by direct examination of sputum and other clinical specimens, is considerate the gold standard for diagnosis of PCM. Serological test are important in diagnosis and during the follow up in regard to define treatment success. Therapy is successful when serologic titers become negative or remain stable in 1:2 after appropriated therapy. Double immunodiffusion reaction has 80% of sensibility and more than 90% of specificity, otherwise it is an easy laboratorial method.3,9
In the reported cases, histopathologic study of cervical lymph nodes resulted compatible with P. brasiliensis, and the double immunodiffusion reaction was positive initially, with further rise in serology titers, that became negative during treatment with itraconazole. In both patients, serologic tests for histoplamosis resulted negative.
In the cases here presented itraconazole was the therapy of choice according to the Brazilian Paracoccidiodomycosis Consensus recommendations for therapy of mild to moderate cases.3 Itraconazole is well tolerated and effective. Both patients had clinical and serologic improvement, with hospitalization for short period and outpatient visits for six months after ending therapy.
In the last few years, changes in the demographic and geographic patterns of the population with PCM have been observed. The urbanization progress that causes increase in rural population may justify the occurrence of PCM in urban areas. Although, risk factors cannot be identified.14-17 The cases here presented did not have any recognized risk factor that could explain the acquisition of PCM, for both patients have lived in strictly urban areas, denied any rural contact.
Paracoccidioidomycosis is the major systemic mycosis in Latin America. It is usually related to rural areas but in last decades the epidemiology has been changing to urban areas, beforehand not characterized like to be endemic. The juvenile form is associated with worse prognosis and high mortality hates. Clinicians must be aware about this condition in endemic regions.
We thank Luiz Celso Mattosinho França for the histopathological background.
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Resident of Infectious Diseases Department, Hospital do Servidor Público Estadual
Rua Pedro de Toledo, n. 1800
CEP 04039-004, São Paulo, SP, Brazil
Telephone/Fax number: 55 11 55491565
Submitted on: 04/15/2009
Approved on: 05/19/2009
We declare no conflict of interest.