Unusual osseous presentation of blastomycosis in an immigrant child: a challenge for European pediatricians
© Codifava et al.; licensee BioMed Central Ltd. 2012
Received: 9 August 2012
Accepted: 3 December 2012
Published: 10 December 2012
Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitidis is a systemic pyogranulomatous infection, endemic in United States and Canada, with few reported cases in Africa and Asia. It is uncommon among children and adolescents, ranging from 3% to 10%. Clinical features vary from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass. Blastomycosis can originate a "metastatic disease" in the skin, bones, genitourinary tract and central nervous system. Bone is the third most common site of blastomycotic lesions, after lung and skin. Bones may be involved in 14-60% of cases of blastomycosis. Direct visualization of single broadbased budding yeast with specific stains in sputum or tissue samples at microscopy is the primary method for diagnosis, while culture is timeconsuming and other methods are unreliable.
We report a case of severe osteoarticular Blastomycosis occurring in a 3-years-old presented to our Emergency Department with pain and swelling of the left knee, successfully treated with surgical curettage and antifungal therapy. To our knowledge this is the first case reported in Europe.
Blastomycosis represents a challenge for European physicians, and it should be included in the differential diagnosis of unexplained infections in patients coming from endemic areas.
KeywordsBlastomyces dermatitidis Blastomycosis Osteomyelitis Itraconazole
Blastomycosis is a systemic pyogranulomatous disease caused by the thermally dimorphic fungus Blastomyces dermatitidis (Bd). It is endemic in Southern, Southeastern and Midwestern states of the United States and Canada, with few reported cases in Africa and Asia and no cases are reported in Europe. The organism’s ecological niche is wet soil that has been enriched with animal droppings, rotting wood and other decaying vegetable matter. Outdoor activities are associated with blastomycosis infection. Less commonly, direct cutaneous inoculation via a penetrating outdoor injury, a laboratory accident or an animal bite can occur. Disruption of wet soil or organic matter containing Bd mycelia releases infectious conidia, which are consequently inhaled by a susceptible host. In the lungs alveolar macrophages, neutrophils and monocytes provide natural resistance to infection with conidia. The clinical features of blastomycosis range from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass. If host responses in the lung fail to contain the infection, a lymphohematogenous spread follows, disseminating to almost any organ: skin, bones, genitourinary tract and central nervous system. Fulminant manifestation occurs in both immunocompetent and immunocompromised patients. Blastomycosis, unlike Aspergillosis or Candidiasis, is not considered an opportunistic infection, but AIDS or transplanted patients are more likely to have disseminated disease[1, 2]. The ability to mimic other diseases often leads to erroneous diagnosis delaying the appropriate treatment. We describe a case of blastomycosis that occurred as a sporadic localized osteolytic lesion of the distal femur and caused a muscle abscess in a young African child. To our knowledge this is the first case described in Europe.
At histochemical stains, fungal structures were positive for Periodic-acid-Schiff (PAS) and methenamine silver (Grocott) (Image 2b), but negative with mucicarmine, then resulting more consistent with Blastomycosis.
The drained material newly cultured resulted again negative for bacteria and fungi and serum antibodies for Bd, C. neoformans, B. Burgdorferi; B. henselae; antigens of Aspergillus, Weil-Felix and Widal-Wright reactions, Quantiferon-TB gold resulted negative. Unfortunately in our molecular biology lab the specific primers for Blastomyces were not available at this time. Subsequently, the paucity of specimen remained did not consent to perform a valuable test with PCR. After surgical curettage, i.v. lipid amphotericin B (ampB) (0.7 mg/kg/day) was administered for 2 weeks, with evident clinical improvement. The patient was discharged with step-down therapy with oral itraconazole (10 mg/kg/day) for 6 months. Liver function, checked for possible epatotoxicity, was found normal. At 3, 9, 12 and 18-moths follow-up no limitation of movements nor pain were noted and X-Ray and MR (Figure1b) showed total resolution of the lesion with bone reapposition.
Blastomycosis is an uncommon mycotic infection, endemic in North America, but substantially unknown in Europe. This mycotic disease is rare among children and adolescents, representing only 3-10% of the cases. In children, the lungs are most frequently involved. Extrapulmonary or disseminated blastomycosis occurs in approximately 10% of children and is usually heralded by prior pulmonary symptoms. A review of known cases diagnosed in Africa between 1951 and 1987 revealed that, among the 81 African patients, bone involvement, with or without extension to the overlying subcutaneous tissues and skin, was the most common presentation of disease.
Bone is the third most common site of blastomycotic lesions, after lung and skin. Bones may be involved in 14-60% of cases of blastomycosis, and any bone can be implicated[5, 6]. Synovial joint involvement has also been reported. Patients with blastomycotic osteomyelitis have pain and swelling at the site, often associated with overlying skin abscess or ulcer. Areas of bone involvement usually appear as lucent (X-ray) or low-attenuation (CT) lesions with indistinct margins but have no radiologic specific features to help distinguish them from other forms of osteomyelitis or neoplasm. Specifically, the lack of periosteal reaction radiographically diverts the differential diagnosis away from osteomyelitis. Most bone lesions will resolve with antifungal treatment, but in many instances surgical treatment may be necessary, including debridement and curettage[6, 8, 9]. Children are allegedly unusual host for blastomycosis. As it can mimic other diseases, such as bacterial infection or malignancy, diagnosis can be mistaken or delayed even in endemic Countries. A case occurring in a non-endemic area can represent a Bd transferred from an endemic area, or a reactivation after the patient has moved from an endemic area, as it probably was in our case. Bd grows in a mycelia form at room temperature and it converts to a yeast form within tissues and in culture at 37°C. The rarity of this infection at our latitude justifies the unavailability of specific tests. Culturing the fungus in specific Sabouraud dextrose agar is highly reliable but it requires 2–6 weeks.
Antibodies to Bd detection tests are considered inadequate for diagnosis.
Antigen detection in urine, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) fluid, serum and other sterile body fluids has low specificity, being also positive in patients with histoplasmosis and paracoccidoidiomycosis. Methods based on PCR have shown promise but they are not widely available yet[1, 10]. Direct visualization of single broad-based budding yeast, stained with haematoxylin-eosin, PAS and Gomori methenamine silver (GMS) stain in sputum or tissue samples at microscopy is the primary method with which a diagnosis is made. Bd is not colored by mucicarmine stain, unlike Cryptococcus. As serologic search for antibodies is inadequate for diagnosis and a negative culture does not exclude the possibility of infection, the role of cytology and histopathology was determinant in our case, as already elsewhere described[9, 10]. Obviously in the absence of PCR and/or DNA-RNA sequences the diagnosis of blastomycosis is only presumptive. A retrospective study of 2007, reviewing 45 cases of skeletal blastomycosis, reported a median delay in diagnosis of more than 2 months. The delay in diagnosis of the present case was 30 days. In a country “destination of immigration”, Blastomycosis represents a challenge for European paediatricians, and it should be included in the differential diagnosis of unexplained infections in patients coming from endemic areas.
Written informed consent was obtained from the patient’s parents for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Series Editor of this journal.
Hematoxylin and eosin
Gomori methenamine silver
All the authors wish to thank G. Zavarise
(Department of Pediatrics, Sacro Cuore di Negrar Hospital , Verona, Italy) for the scientific support.
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