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Sickle Cough: A Case of Nonresolving Pneumonia

Computed tomography of the chest. (A) Before treatment, with right pulmonary infiltrates. (B) After 1 year of itraconazole, with marked improvement.

A 26-year-old female graduate student with sickle-cell disease presented with fever, dyspnea, and right shoulder pain. Computed tomography of the chest demonstrated right middle and lower lobe infiltrates (Figure, A). She was diagnosed with pneumonia, acute chest syndrome, and vaso-occlusive crisis and prescribed 5 days of amoxicillin-clavulanic acid.

 

She was readmitted 1 month later with progressive dyspnea, fevers, chest and shoulder discomfort, and persistent infiltrates. She had ongoing fevers despite 5 further days of moxifloxacin. Blood cultures, Legionellaurinary antigen, respiratory virus polymerase chain reaction panel, and bronchoscopy lavage cultures for bacteria, fungi, mycobacteria, and pneumocystis were performed, but no pathogen was identified. After seven days of intravenous piperacillin-tazobactam, her respiratory symptoms gradually improved.

Over the subsequent months her dyspnea and fevers recrudesced. Interval computed tomography of the chest demonstrated worsening subpleural parenchymal opacities, attributed to pulmonary infarction. Concurrently she underwent investigation for multinodular thyroid goiter; thyroid biopsy demonstrated granulomas. Additionally, she had nonresolving shoulder pain. Magnetic resonance imaging revealed osteomyelitis of the right humeral metaphysis with confluent deltoid abscess; purulent drainage was sent for culture. Intravenous ceftriaxone was started empirically. After 1 week of therapy she continued to have fevers and shoulder drainage. Culture of the fluid revealed no growth. Further samples were sent for fungal and mycobacterial culture.

Four days after repeat sampling and after 8 months of diagnostic uncertainty, Blastomyces dermatiditis was identified from the drainage. Antifungal therapy with oral itraconazole was initiated for disseminated blastomycosis. Within 1 month the patient began to improve, with defervescence, removal of abscess drains, and resolution of her goiter. After 12 months of antifungal therapy her pulmonary infiltrates and symptoms resolved entirely, and treatment was discontinued (Figure, B).

Blastomyces is a dimorphic fungus endemic to the American states bordering the Ohio and Mississippi Rivers, as well as the states and Canadian provinces bordering the Great Lakes and St. Lawrence Seaway.1 Predominantly acquired via inhalation, most symptomatic patients present with respiratory symptoms.1 If untreated, there is a propensity for extrapulmonary dissemination, including osteoarticular, genitourinary, intracranial, and very rarely thyroid involvement.1, 2 Although diagnostic delay is common, blastomycosis is usually diagnosed with culture of respiratory secretions, with staining characteristic for broad-based budding yeast.1 The pyogranulomatous infection may reveal inflammatory granulomas on pathology.

All patients with blastomycosis should be treated to prevent extrapulmonary dissemination. Therapeutic options include amphotericin induction therapy for severe disease and itraconazole for maintenance therapy.1 Guidelines recommend treatment beyond clinical and radiographic resolution, with a minimum of 6 months for disseminated disease and at least 12 months for osteoarticular disease, given the higher risk of relapse.1

Patients with sickle-cell disease are immunocompromised by their functional asplenia and defect in phagocytosis of encapsulated organisms, believed to be secondary to defects in alternative pathway complement activation. Does this immunocompromise extend to blastomycosis? Blastomyces has a thick cell wall and requires complement-mediated opsonization and phagocytosis for pathogen killing. One immunologic study demonstrated that 80% of Blastomyces opsonization is driven by the alternative pathway.3 Although this would indicate a potential immunologic predilection for Blastomyces among patients with sickle-cell disease and suggest a theoretical rationale for itraconazole suppressive therapy, there is no clinical evidence to guide this therapeutic decision.

We present the first reported case of disseminated blastomycosis in a patient with sickle-cell disease, identifying a new etiology for acute chest syndrome, demonstrating the diagnostic challenge of nonresolving pneumonia and the natural history of Blastomyces‘ extrapulmonary dissemination.

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-Eric A. Coomes, MD, Paul E. Bunce, MA, MD, FRCPC

This article originally appeared in the September issue of The American Journal of Medicine.

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