Case Presentation: A 55-year-old previously incarcerated male with a history of tuberculosis and a 27-year-old incarcerated male both with a history of cough and hemoptysis, and a 56-year-old female with pulmonary nodules, right ankle pain, and swelling, all presented to the ED at a tertiary center in Wisconsin. All three patients shared a constellation of symptoms including cutaneous lesions on the face and extremities in the setting of tuberculosis-like symptoms. None of the patients had recently traveled or were immunocompromised. Because of these concerns, the patients were placed in isolation while imaging and an infectious workup were completed. Additionally, these patients were initiated on empiric antibiotic therapy with vancomycin and a 3rd or 4th generation cephalosporin with only mild improvement. Chest x-ray and CT were notable in all cases of TB-like lesions including interstitial opacities, multifocal consolidations, cavitary lesions, and granulomatous lesions. Despite these findings, AFB cultures and interferon-gamma testing were repeatedly negative prompting further investigation. The diagnosis was made after cutaneous cultures or tissue biopsies were obtained showing broad-based budding yeast and urine antigen samples testing positive for Blastomyces. These cases displayed evidence of disseminated blastomycosis; having cutaneous lesions, meningitis, and RLE abscess associated with ankle involvement and osteomyelitis respectively. The antimicrobial therapy was modified to itraconazole or voriconazole depending on affected organ systems in addition to amphotericin given the disseminated nature of the disease. All three cases showed signs of improvement following initiation of amphotericin and supportive medical management. The first two cases were discharged following improvement in their condition and the final case required surgical management given the extensive nature of her osteoarticular disease.

Discussion: Blastomycosis is a fungal infection caused the Blastomyces ssp. The organism is endemic to Ohio, the Mississippi River Valleys, Great Lake regions, and the Southeastern United States where its annual incidence is < 1 per 100,000 people. While typically presenting in males, risk factors more commonly include compromised immune status and occupational exposures. Immunocompetent patients with blastomycosis often present with flu-like symptoms which resolve within days. Severe presentations such as pneumonia and respiratory failure are seen in elderly and immunocompromised patients. In severe disease, the fungus can disseminate to other organs; most commonly skin papules and plaques resembling cellulitis followed by lytic bone lesions as seen in the cases above. Disseminated blastomycosis can be difficult to diagnose as the disease mimics tuberculosis clinically and on imaging. It can involve nearly any organ system further complicating diagnosis. The treatment of choice is based on the presenting symptoms. In moderate disease, itraconazole is the preferred treatment whereas amphotericin is favored more in severe infections such as those with CNS involvement.

Conclusions: We present these cases to raise awareness about the different signs and symptoms of blastomycosis, allowing for early diagnosis and initiation of appropriate treatment to prevent systemic dissemination. Although uncommon, it is important to maintain a high degree of suspicion for Blastomyces dissemination regardless of the immunological status of a patient.