The Impact of Corticosteroids on the Outcome of Fungal Disease: a Systematic Review and Meta-analysis

Abstract

Abstract Purpose of Review Corticosteroids have a complex relationship with fungal disease — risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids on mortality and visual outcome in different fungal diseases. Recent Findings Corticosteroids are a risk factor of aspergillosis for patients who have COVID-19, and they also led to a worse outcome. Similarity, corticosteroids are a risk factor for candidemia and mucormycosis. Some researchers reported that using topical corticosteroid in keratitis was associated with worse visual outcome if fungal keratitis. Some studies showed that corticosteroids are linked to a negative outcome for non-HIV patients with Pneumocystis jirovecii pneumonia (PCP), in contrast to those with HIV and PCP. Summary In 59 references, we found that corticosteroid therapy showed a worse clinical outcome in invasive aspergillosis (IA) (HR: 2.50, 95%CI: 1.89–3.31, p < 0.001) and chronic pulmonary aspergillosis (CPA) (HR: 2.74, 95%CI: 1.48–5.06, p = 0.001), PCP without HIV infection (OR: 1.29, 95%CI: 1.09–1.53, p = 0.003), invasive candidiasis and candidaemia (OR: 2.13, 95%CI: 1.85–2.46, p < 0.001), mucormycosis (OR: 4.19, 95%CI: 1.74–10.05, p = 0.001) and early in the course of fungal keratitis (OR: 2.99, 95%CI: 1.14–7.84, p = 0.026). There was equivocal outcome in cryptococcal meningoencephalitis in AIDS and primary coccidioidomycosis, while corticosteroid therapy showed a better outcome in PCP in HIV-infected patients (RR: 0.62, 95%CI: 0.46–0.83, p=0.001) and fungal keratitis patients after keratoplasty surgery (OR: 0.01, 95%CI: 0.00–0.41, p = 0.041) and probably in cryptococcal meningoencephalitis in non-immunocompromised patients. A sub-analysis in invasive aspergillosis and CPA showed that use of more than 2 mg/kg/day of prednisolone equivalents per day is a significant factor in increasing mortality (HR: 2.94, 95%CI: 2.13–4.05, p < 0.001). Corticosteroid therapy during invasive fungal disease was usually associated with a slightly or greatly increased mortality or worse visual outcome (in fungal keratitis), with two disease exceptions. Avoiding the addition of corticosteroids, or minimising dose and duration in those who require them, is likely to improve the outcome of most life- and vision-threatening fungal diseases. This review provides a cornerstone for further research in exploring the accuracy of suitable dose and duration of corticosteroids treatment in fungal diseases.