Fatal Pulmonary Failure—A Rare Case of Blastomycosis Induced Acute Respiratory Distress Syndrome: A Case Report and Literature Review

Abstract

Blastomycosis is a systemic fungal infection caused by Blastomyces dermatitidis, primarily found in the Ohio and Mississippi River valleys. It often presents nonspecific symptoms, and while pulmonary involvement is common, progression to acute respiratory distress syndrome (ARDS) is rare but severe. This report examines a 55-year-old female patient with multiple comorbidities who developed ARDS due to blastomycosis. Imaging revealed multilobar infiltrates and pleural effusion, with cultures confirming blastomycosis. Despite broad-spectrum antibiotics and antifungal therapy, a delayed diagnosis led to respiratory failure and death. The case emphasizes the diagnostic challenges of blastomycosis, which can mimic conditions like bacterial pneumonia and malignancy. Treatment with amphotericin B is crucial for severe cases, but delays in diagnosis can worsen outcomes. This highlights the necessity for prompt diagnosis and comprehensive management, including early recognition of fungal infections in critically ill patients.

Introduction

Blastomycosis is a systemic fungal infection caused by Blastomyces dermatitidis, an organism primarily found in regions of the Ohio and Mississippi River valleys, the Great Lakes, and parts of Canada. It typically occurs through inhalation of airborne spores, leading to pulmonary infection. ¹ The estimated incidence of blastomycosis varies by region, but 1 study reported an annual incidence of 0.3 per 100 000 persons. ² While 50% of infected individuals remain asymptomatic, those who develop symptoms often present with nonspecific respiratory complaints such as cough, fever, and malaise. ³ While pulmonary involvement is common, it rarely progresses to acute respiratory distress syndrome (ARDS). This is more likely to occur in patients with preexisting comorbidities. ⁴ We present a case of a 55-year-old female who developed an exceptionally rare and fatal occurrence of ARDS secondary to blastomycosis. Despite the initiation of broad-spectrum antibiotics and antifungal therapy, a delayed diagnosis contributed to the patient’s progressive respiratory failure and eventual death. This case highlights the need for early diagnosis of fungal infections in patients from endemic areas with severe pneumonia. It emphasizes the importance of quick identification, particularly in those experiencing progressive respiratory failure. Given the rarity of ARDS from blastomycosis and its diagnostic challenges, this case aims to raise awareness and stress the value of timely intervention to improve patient outcomes.

Case Presentation

A 55-year-old female with a significant medical history of type 2 diabetes mellitus, hypertension, end-stage renal disease on hemodialysis, hypothyroidism, active half pack per day for 30 years smoker, and chronic obstructive pulmonary disease (COPD). She was a resident of a nursing home and unemployed with no known occupational exposures. She presented after experiencing hypotension during dialysis along with fever, shortness of breath, and confusion. Initial vital signs were significant for mean arterial pressure of 67 mm Hg and oxygen saturation (SpO₂) of 96% on the 4L nasal cannula. The patient was afebrile on arrival, with a temperature of 98.6°F. Initial laboratory tests revealed a white cell count (WBC) of 18.3 × 10⁹/L (normal 4.5-10 × 10⁹/L), hemoglobin of 8.0 g/dL (normal 12.0-16.0 g/dL), C-reactive protein (CRP) of 18.3 mg/dL (normal ≤ 0.5 mg/dL), procalcitonin of 3.6 ng/mL (normal ≤ 0.5 ng/mL), and serum creatinine of 3.2 mg/dL (normal 0.60-1.2 mg/dL), prompting hospitalization for suspected sepsis. Hemoglobin A1C was 7.6%. Chest X-ray (CXR) revealed multilobar left-sided infiltrates and a left pleural effusion (Figure 1). Blood pressure (BP) improved with intravenous fluids. Due to the severity of the condition, empiric antimicrobial therapy with vancomycin and piperacillin-tazobactam was initiated. Azithromycin was added for atypical pneumonia coverage, and methylprednisolone was added due to the severity of pneumonia, which was later switched to oral prednisolone. A thoracentesis was performed to drain 600 mL of complicated parapneumonic pleural effusion. Pleural fluid analysis showed protein of <3 gm/dL and LDH of 54 U/L, indicating transudative fluid. Cell counts of pleural fluid showed 85% neutrophils, 4% lymphocytes, 4% macrophages, and 7% mesothelial cells. Cultures taken from the pleural fluid were negative. She initially showed improvement; however, her respiratory condition worsened on hospital day 8. She required an increasing oxygen supply of up to 15 L, and her blood pressure dropped again, necessitating a norepinephrine infusion. A chest computed tomography (CT) scan revealed extensive left-sided consolidation and effusion (Figure 2). Her respiratory condition continued to worsen, requiring escalation to continuous positive airway pressure (CPAP). Despite the administration of Vancomycin, meropenem, and a chest tube to drain pleural effusion, her condition deteriorated with worsening consolidation in the right basilar region. Bronchoscopy was postponed as the patient was hesitant about intubation. However, blood cultures and tests for serum histoplasmosis and blastomycosis antigens were obtained as the patient resides around the Ohio River. As the patient was anuric, no urine antigens for these organisms were collected.

Figure 1.

Chest X-ray anteroposterior showing diffuse hazy airspace disease and opacification through the left lung with small left pleural effusion. A left-sided vascular catheter is also seen.

Figure 2.

(A-D): Chest CT showing extensive consolidation of the left upper lobe, lingula, and left upper lung lobes, accompanied by moderate left (*) and small right pleural effusions. There is also mediastinal lymphadenopathy (Arrow). The right lung shows multiple right lung nodules (circle).

The patient’s clinical course was complicated by worsening hypotension, requiring the addition of vasopressin and stress doses of steroids for septic shock. She subsequently had worsening lung infiltrates (Figure 3), developed ARDS, and was ultimately intubated on hospital day 10; the same day, a bronchoscopy was performed, and BAL was collected. A concern of fungal infection was communicated to microbiology, which in return communicated back by the presence of large numbers of broad-based budding yeasts on BAL that immediately prompted the initiation of Liposomal amphotericin B therapy 5 mg/kg on hospital day 13, as the patient was on continuous replacement therapy (CRRT). On the same day, the results of serum blastomycosis return positive. Unfortunately, the patient’s clinical condition continued to decline, with refractory hypotension, worsening thrombocytopenia, and persistent multiorgan failure. Despite maximal ventilatory and hemodynamic support, the patient passed away on hospital day 14. BAL and fungal blood cultures also confirmed Blastomyces 14 days after the patient passed away.

Figure 3.

Chest X-ray anteroposterior showing bilateral pulmonary infiltration with more severe infiltration of the left lung. There is also small right upper lobe infiltration, which may represent cavitation (circle). An endotracheal tube, nasogastric tube, and left-sided vascular catheter are also seen.

Discussion

Blastomycosis dermatitidis is typically transmitted through inhalation. While some individuals remain asymptomatic, others develop pneumonia, and in some instances, the disease can disseminate, affecting skin, bone, and the central nervous system. ⁵ Nevertheless, Patients mainly present with nonspecific symptoms like malaise, fever, and weight loss. Pulmonary involvement may be coupled with a mass-like lesion on the X-ray that is sometimes misdiagnosed as cancer. ⁶ It is reported that 10% of patients with pulmonary blastomycosis may end up having ARDS, which has high mortality rates of 50-90%, unlike other ARDS etiologies. ⁷ The mechanism of blastomycosis-induced ARDS is believed to be an overwhelming immune reaction to the organism leading to ARDS. ⁸

Schwartz et al. conducted a thorough historical case series involving 43 patients diagnosed with ARDS due to blastomycosis. These patients were treated in intensive care units (ICU) between 1992 and 2014. Among the patients, 63% were male, and 44% had diabetes. The median duration from initial presentation to the development of respiratory failure requiring mechanical ventilation (MV) was 3 days. In addition, 84% of the patients experienced shock, and 30% had acute kidney impairment that necessitated replacement therapy. Extrapulmonary manifestations of blastomycosis were observed in 37% of the cases. Imaging results showed that 63% had involvement of more than 4 quadrants on CXR, with 77% displaying infiltrates and the remaining instances showing a miliary pattern. The severity of ARDS was categorized as mild in 2 patients (5%), moderate in 12 patients (28%), and severe in 29 patients (67%). ⁹ A study reported that diabetes was more common among hospitalized patients with pulmonary blastomycosis who required ICU care compared to those who did not (36% vs 16%; P = .02). ¹⁰

The incidence of blastomycosis in nonendemic regions is rising, driven by factors such as an increasing population of immunosuppressed individuals and potential climate-related changes. However, clinician unfamiliarity with the disease in these areas often leads to misdiagnosis, delaying appropriate treatment and increasing the risk of severe systemic infections.^11,12 Another major in diagnosing blastomycosis is its non-specific presentation and the delay in obtaining results, particularly in remote areas, which can worsen patient prognosis. The diagnostic tests available include histopathology and cytopathology, antibody testing (which has low sensitivity and specificity), antigen detection in the urine of infected individuals, and culture tests. While cultures are confirmatory, they can take 4 to 6 weeks to yield results. ¹³ In our case, a positive Blastomyces serum antigen test confirmed the diagnosis of blastomycosis; however, it took almost 5 days for the results to come back. BAL and fungal blood cultures also corroborated the diagnosis, although the results came out late, as fungal growth in culture may not be helpful for critically ill patients who require immediate intervention. Thus, clinicians should maintain a high index of suspicion for blastomycosis in patients presenting with severe pneumonia or rapidly progressing respiratory failure in endemic areas to avoid treatment delay, which plays a crucial role in the patient’s outcome.

The CXR of 63 patients with proven pulmonary blastomycosis was evaluated to identify common imaging findings. Key features include airspace consolidation (76%), upper lobe involvement, and cavitation (37%). Associated findings such as pleural effusions or lymphadenopathy occur in about 20% of patients, with 37% showing cavitation in consolidated areas. These patterns emphasize the need for careful clinical evaluation in endemic regions, integrating imaging, patient history, and lab results for accurate diagnosis. ¹⁴

Management strategies, per Schwartz et al., included the use of amphotericin B (n = 42, 98%), vasopressors (n = 36, 84%), corticosteroids (n = 22, 51%), renal replacement therapy (n = 13, 30%), and extracorporeal membrane oxygenation (ECMO; n = 4, 11%). Despite these interventions, the overall mortality rate was 40% (n = 17), highlighting the significant risk associated with ARDS caused by blastomycosis. ⁹

The primary treatment for severe or life-threatening blastomycosis is intravenous liposomal amphotericin B. Patients can be transitioned to oral azole therapy, such as itraconazole, for long-term management.^15,16 Amphotericin B at a daily dose of 0.7 to 1.0 mg/kg is required, with total doses ranging from 2000 to 3000 mg. Critical cases necessitate rapid dose escalation to this maintenance level within 24 to 48 hours. For instance, a critically ill patient weighing 110 kg received an initial dose of 100 mg, maintained over 30 days. ¹⁷ In our case, liposomal amphotericin B at a dosage of 5 mg/kg was initiated with the first dose, as the patient was undergoing CRRT, which began on day 12 of hospitalization. Unfortunately, due to a delay in diagnosis, the patient’s condition continued to decline, resulting in refractory hypotension and multiorgan failure.

A study examined the outcomes and risk factors associated with severe pulmonary blastomycosis that required MV in the United States. Using data from the Nationwide Inpatient Sample from 2006 to 2014, the analysis included 1848 patients, of which 11.9% required MV. The mortality rate for this group was 39.7%, in contrast to just 2.5% for those who did not need MV. Patients on MV experienced a median time to death of 12 days, while survivors had a median hospital stay of 22 days. Key factors linked to higher mortality included female gender (odds ratio [OR], 1.84) and older age (OR of 1.64 for every 10-year increase). ¹⁶

Regarding prognosis, a case series describing the survivors involving 5 of the 10 patients who survived blastomycosis-induced ARDS discussed the benefits of an aggressive treatment approach. Survivors of overwhelming pulmonary blastomycosis with ARDS were predominantly treated with intravenous amphotericin B at quickly escalating doses as described above. All surviving patients required prolonged MV, with a mean duration of 40 days. Despite severe initial presentations, including diffuse bilateral infiltrates and profound oxygenation impairment, 5 of the 10 patients survived, and all were asymptomatic at follow-up (1-10 years). Long-term pulmonary function tests revealed variable recovery: some survivors demonstrated normal lung volumes and diffusion capacities, while others had persistent restrictive changes and reduced diffusion capacity associated with fibrosis. Radiographic infiltrates resolved over time, though focal interstitial fibrosis persisted in some cases. No relapses were observed, highlighting the effectiveness of timely antifungal therapy and meticulous supportive care in improving outcomes for this severe condition. ¹⁷

The debate over using corticosteroids highlights their potential to suppress excessive immune responses to the organism. However, their immunosuppressive effects could also increase the fungal burden, which raises concerns. ⁸ A report by Furlan et. Al supports the use of steroids in the treatment of blastomycosis-induced ARDS as the patient they described significantly improved after initiating methyl prednisone and ultimately recovered. ¹⁸

In the study by Schwartz et al, corticosteroid use did not show a survival benefit in either univariate (P = .43) or multivariate analyses (OR = 0.52, 95% confidence interval = 0.11-2.34). Bootstrap analyses indicated that around 500 patients would be needed to demonstrate a significant reduction in mortality, emphasizing the study’s limited sample size. ⁹ However, there are no current clear recommendations for steroid use, but it is hypothesized that individuals with exaggerated inflammatory responses might benefit from steroid use. ¹⁶ Another potentially useful modality is ECMO, which might prolong the time available to diagnose and initiate treatments in patients with severe blastomycosis. ¹⁷

Conclusion

This case highlights the need to consider blastomycosis in patients with severe pneumonia who do not respond to treatment, especially in endemic areas. Blastomycosis, a potentially life-threatening fungal infection, can rapidly progress to ARDS, particularly in individuals with diabetes. Early diagnosis is essential, but this case demonstrates the challenges in identifying blastomycosis, as its symptoms can mimic those of other conditions, leading to treatment delays. Despite appropriate antifungal therapy, the delayed diagnosis contributed to the patient’s deterioration and eventual death. This emphasizes the importance of clinicians maintaining a high suspicion for fungal infections in endemic regions to avoid delays that can impact survival.