Cutaneous blastomycosis: a clue to a systemic disease

A 55-year-old male presented with back pain and slightly tender annular plaques with central ulceration on his face. A skin biopsy revealed scattered yeast with broad based buds. A CT scan of the abdomen revealed a pathologic T12 fracture. Tissue obtained from the spine confirmed budding yeasts. The patient was diagnosed with disseminated blastomycosis. The patient was treated with amphotericin and itraconazole and completely recovered.     

Paracoccidioidomycosis: epidemiological,clinical, diagnostic and treatment up-dating

Paracoccidioidomycosis is an acute - to chronic systemic mycosis caused by fungi of the genus Paracoccidioides. Due to its frequent tegument clinical expression, paracoccidioidomycosis is an important disease for dermatologists, who must be up-to-date about it. This article focuses on recent epidemiological data and discusses the new insights coming from molecular studies, as well as those related to clinical, diagnostic and therapeutic aspects. In the latter section, we give particular attention to the guideline on paracoccidioidomycosis organized by specialists in this subject.     

DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS

Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 10³, 10⁴ or 10⁵ P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 10⁵ yeast cells can be used as standard in this model.     

DECREASING PREVALENCE OF THE ACUTE/SUBACUTE CLINICAL FORM OF PARACOCCIDIOIDOMYCOSIS IN MATO GROSSO DO SUL STATE,BRAZIL

With the objective to evaluate the behavior of paracoccidioidomycosis in the last three decades, clinical and epidemiological data of 595 patients admitted to clinical services of the Federal University of Mato Grosso do Sul from 1980 to 2009 were investigated. Gender, age distribution, clinical form, comorbidity with tuberculosis or AIDS, and mortality were compared by decades of clinical admission. It was shown that during the three decades there was a decrease in women percentage, and the same manner occurred a reduction in participants in the age group of 20 to 39 years. Moreover, the acute/subacute forms have been diminished in the period. These fluctuations are closely related and can be simultaneously analyzed. Increased AIDS co-infection prevalence from the first to the second decade was also revealed, coinciding with the appearance of the retroviral epidemic and stabilizing during the third decade. No change in the tuberculosis co-infection rate was observed (overall = 6.9%). It reinforces the importance of this co-morbidity. The overall mortality rate remained steady at 6.7%, not varying significantly from one decade to another. The persistent mortality rate calls attention to the importance of this neglected disease.     

Epidemiological survey of histoplasmine and paracoccidioidine skin reactivity in an agricultural area in Bolívar state, Venezuela

Paracoccidiodomycosis and histoplasmosis are endemic diseases in the south of Venezuela, representing a public health problem. Prevalence of Paracoccidiodes brasiliensis and Histoplasma capsulatum infections were estimated in Monte Ralo, a rural community area of Bolivar state using paracoccidiodine and histoplasmine skin tests. Paracoccidiodine was intradermically injected to 173 persons and readings were made at 24 and 48 h afterwards to 167 persons (97.85%). Reaction was positive in 8.5% (n = 14) at 24 h post-injection and 13.2% (n = 20) at 48 h. Farmers showed the higher percentage of positivity at 24 and 48 h. One hundred-seventy five persons were intradermically injected with histoplasmine but 167 and 157 of them attended for reading of the dermal reaction at 24 and 48 h post-injection respectively. Tests were positive in 25.7% (n = 43) at 24 h and 42.7% (n = 67) at 48 h. Further studies are needed in surrounding places to delimit the endemic area of these mycosis in the Bolivar state. However, epidemiological vigilance of PCM and H should be considered by local health authorities.     

Disseminated paracoccidioidomycosis in a liver transplant patient

Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis complex and P. lutzii. It is a rare disease in non-HIV-induced immunosuppressed individuals. In organ transplant recipients, it is more frequently associated with immunosuppression after kidney transplantation. In a liver transplant patient, only one case has been published in the literature to date. The present report comprises the case of a 47-year-old female patient with disseminated skin lesions associated with signs and symptoms of systemic involvement of paracoccidioidomycosis that manifested one year after liver transplantation and under an immunosuppression regimen with tacrolimus and mycophenolate mofetil.     

Visceral paracoccidioidomycosis in a gold miner from Brazil

Zusammenfassung: Es wird über einen 49-jährigen Deutschen berichtet, der nach 15-jährigem Aufenthalt in Südameri-ka an einer Paracoccidioidomykose er-krankte. Er litt an einer Cheilitis, einer erosiven Stomatitis, einer Laryngitis und einer beidseitigen Pilzpneumonie; außer-dem bestand der Verdacht auf ein Pilzgra-nulom des Gehirns. Die Diagnose wurde kulturell und serologisch gesichert. Die Ausbildung typischer Hefeformen mit mul-tiplen Sprossungen (“Steuerradformen”) benötigt oft länger als einen Monat (in die-sem Fall 6 Wochen), was die Diagnostik bei unklaren Krankheitsbildern erschwert. Der Patient wurde zunächst mit Amphotericin B und Sulfamethoxazol/Trimethoprim behandelt. Beide Medikamente muß-ten wegen Nebenwirkungen abgesetzt wer-den, obwohl Amphotericin B gut wirksam war. Ketoconazol war bei unserem Patien-ten weniger gut wirksam, während unter Itraconazol eine weitere deutliche Besse-rung eintrat. Nebenwirkungen wurden unter den beiden letztgenannten Medika-menten nicht beobachtet. Summary: We report on a 49 years old patient who developed paracoccidioidomycosis after working in a gold mine in South America. The patient suffered from cheilitis, stomatitis, laryngitis, and bilateral pneumonia. Additionally, there was evidence for cerebral granuloma. The diagnosis was confirmed by culture and serologic methods. Paracoccidioides brasilien-sis grows slowly and more than a month may elapse (in this case 6 weeks) before typical yeast-like forms with multiple buds (steering-wheel fungus cells) appear in culture, which often complicates the diagnosis if there is no typical clinical picture. The patient was treated with amphotericin B and sulfamethoxazole/trimethoprim, and a clinical response to therapy was observed. However, therapy had to be stopped because of severe side effects. Ketoconazole was less effective, but further clinical improvement was achieved under itraconazole without untoward side effects.     

Paracoccidioidomycosis (South American blastomycosis): A report of an imported case previously diagnosed as tuberculosis

A case of paracoccidioidomycosis, previously treated for tubercolosis for two years, is reported. Combined treatment with oral ketoconazole and sulfamethoxypyridazine was successful. The problem of a. low index of suspicion among physicians for tropical mycoses, which are very rarely observed in Italy, is discussed.Corresponding author     

The role of interleukin-10 in the differential expression of interleukin-12p70 and its beta2 receptor on patients with active or treated paracoccidioidomycosis and healthy infected subjects

Paracoccidioidomycosis patients present an antigen-specific Th1 immunosuppression. To better understand this phenomenon, we evaluated the interleukin (IL)-12 pathway by measuring IL-12p70 production and CD3+ T cell expression of the IL-12 receptor (IL-12R)beta1/beta2 chains, induced with the main fungus antigen (gp43) and a control antigen, from Candida albicans (CMA). We showed that gp43-induced IL-12p70 production and IL-12Rbeta2 expression were significantly decreased in acute and chronic patients as compared to healthy subjects cured from PCM or healthy infected subjects from endemic areas. Interestingly, the healthy infected subjects had higher gp43-induced IL-12p70 production and beta2 expression than the cured subjects. The addition of a neutralizing anti-IL-10 antibody to the cultures increased IL-12p70 levels and beta2 expression in acute and chronic patients to levels observed in cured subjects. Conversely, addition of the cytokine IL-10 strongly inhibited both parameters in the latter group. In conclusion, we have shown that paracoccidioidomycosis-related Th1 immunosuppression is associated with down-modulation of the IL-12 pathway, that IL-10 may participate in this process, and that patients cured from paracoccidioidomycosis may not fully recover their immune responsiveness.     

Serum levels of sTNF-R1, sTNF-R2 and CXCL9 correlate with disease activity in adult type paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is the most common systemic mycosis in Latin America. A major problem in the management of PCM is to determine the best time to discontinue therapy due to the high relapse rate among patients. Soluble TNF receptors (sTNF-R) levels and chemokines are associated with disease activity in several infectious, inflammatory and autoimmune disorders. The aim of the present work was to evaluate levels of sTNF-R1, sTNF-R2 and chemokines in serum of patients with adult type of PCM, before and after antifungal therapy, and to correlate those levels to disease activity. Concentrations of sTNF-R1, sTNF-R2 and CXCL9 were higher in untreated patients and decreased progressively with treatment. The serum marker with the best accuracy to discriminate PCM cases from controls was sTNF-R2. sTNF-R1 did not drop to control levels before 36 months of treatment. CCL2 and CCL3 levels were low at baseline in PCM patients, raised significantly after 12 months of treatment and diminished thereafter. CCL24 levels were higher after 36 months of antifungal therapy in PCM patients. CCL11 levels were not statistically different from control subjects. sTNF-R1, sTNF-R2 and CXCL9 may be useful as laboratory parameters to assess disease activity in PCM patients.