INTRODUCTION:Blastomycosis-induced acute respiratory distress symdrome (ARDS) is associated with a mortality rate of 50-89% despite adequate antifungal therapy. While corticosteroids are recommended for the treatment of severe pulmonary infections with pneumocystis jirovecii or histoplasma capsulatum in order to decrease the lung damage from the marked host inflammatory response, their role in the treatment of severe pulmonary infections with blastomycosis has not been established yet.
CASE PRESENTATION:We report the cases of two previously healthy adults presenting with severe ARDS due to infection with blastomycosis dermatitidis. Patient 1 is a 21 year old African-American male with a four week history of diffuse skin lesions and septic arthritis. He developed ARDS requiring mechanical ventilation with 100% FiO2 and PEEP of 15 cm H2O. Chest x-ray (CXR) and chest computer tomography (CT) scan showed bilateral alveolar infiltrates (Fig. 1). The PaO2/FiO2 (P/F) ratio was 66. Bronchoscopy with bronchoalveolar lavage (BAL) was perfomed. The BAL fluid showed 94% neutrophils. Serum and BAL histoplasma antigen assays (which detect both histoplasmosis and blastomycosis antigens) were positive at 13.1 and 1.1 units, respectively. Culture and histology of a lip biopsy revealed blastomyces dermatitidis. The patient’s ARDS worsened despite adequate antifungal coverage with amphotericin B deoxycholate at 1mg/kg intravenously (IV). Dramatic improvement was seen after initiation of methylprednisolone (60 mg IV every six hours). The P/F ratio increased to 208. The patient was extubated after six days. Patient 2 is a 43 year old African-American male with a six week history of fever, back pain and dyspnea resulting in ARDS, which required mechanical ventilation with 100% FiO2 and PEEP of 15 cm H2O. Initial P/F ratio was 62. CXR showed diffuse bilateral nodular airspace disease. Chest CT revealed diffuse bilateral coarse pulmonary interstitial infiltrates (Fig. 2) and a compression fracture of the T9 vertebral body. Histoplasma urine and serum antigens were positive at 25.9, and 7.5 units, respectively. Bronchoscopy with BAL revealed blastomyces dermatitidis. Amphotericin B (1 mg/kg IV) was initiated. However, the patient continued to deteriorate despite antifungal therapy. Methylprednisolone (250 mg IV every six hours) was started in addition to amphotericin B. This resulted in significant clinical improvement (P/F ratio 166). FiO2 was decreased to 40% over the next seven days. Both patients survived their hospital stay and did well on follow up.
DISCUSSIONS:While clinical trials do not support the routine use of steroids in ARDS, a subset of patients with an exaggerated inflammatory response may still benefit from this intervention. This includes patients with severe pneumocystis pneumonia or severe community acquired pneumonia (CAP). Respiratory failure and death in the setting of pneumocystis pneumonia are more closely correlated with the degree of the inflammatory response than with the number of pneumocystis organisms. Similarly, the inflammatory response in the setting of severe pulmonary histoplasmosis or severe CAP is thought to contribute to the respiratory compromise. It is conceivable that a blastomycosis-induced hyperinflammation-syndrome contributes to the clinical deterioration and respiratory failure seen in severe pulmonary blastomycosis. This can occur despite adequate antifungal therapy. The diverse genomic and nongenomic antiinflammatory effects of corticosteroids may attenuate this marked inflammatory response.
CONCLUSION:This is the first report to demonstrate that treatment with corticosteroids may be of benefit in patients with severe blastomycosis-induced ARDS.
DISCLOSURE:Tim Lahm, No Financial Disclosure Information; No Product/Research Disclosure Information