Should Histoplasmosis be Screened for Before Initiation of Tumour Necrosis Factor Alpha Inhibitors?

Histoplasmosis is a soil-based dimorphic fungus endemic to the Midwest and Southeastern United States and is responsible for infection through inhalation of conidia. Infection is usually asymptomatic, as the fungal growth is contained by formation of granulomas. However, dissemination can occur in immunocompromised hosts due to the lack of optimal activity of interferon gamma, tumour necrosis factor alpha (TNF-alpha) and interleukin-17. There is a significant overlap between the symptomatology of histoplasmosis and granulomatosis with polyangiitis (GPA). We report a case of a 48-year-old female who presented with high-grade fever, worsening generalised weakness and tachycardia. She had a previous history of bilateral cavitary lung lesions for which she was evaluated at an outside facility. As her entire infectious investigation was negative and found to be positive for antineutrophil cytoplasmic antibody (ANCA), a diagnosis of GPA was made, and she was initiated on rituximab infusions 7 weeks prior to her presentation to our facility. Repeat infectious investigations at our facility were positive for (1-3)-β-D-glucan test and urine histoplasma antigen. Prompt discontinuation of rituximab and initiation of systemic antifungal therapy led to clinical improvement. Based on this experience, we highlight the association of histoplasma with ANCA positivity along with the importance of closely monitoring these patients for possible clinical worsening after the initiation of TNF-alpha inhibitors, despite the negative infectious work-up. Also routine screening or pre-emptive therapy for histoplasmosis before the initiation of TNF-inhibitors is not recommended.

Histoplasmosis is associated with ANCA positivity.Despite the negative investigations for histoplasmosis and criteria for GPA being met, patients should be closely monitored for possible clinical worsening after the initiation of immunosuppressive therapy, especially TNF-alpha inhibitors.Current guidelines are not recommending routine screening or pre-emptive therapy for histoplasmosis before initiation of TNF-alpha inhibitors.