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Risk factors for invasive fungal infections in patients with connective tissue disease: Systematic review and
Anji Xiong1, Wenxuan Luo2, Xiaoyu Tang2
1Department of Rheumatology and Immunology, Nanchong Central Hospital, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, Nanchong, Sichuan, China; Inflammation and Immunology Key Laboratory of Nanchong, Nanchong, China.
Objective:
Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and mortality. We attempted to determine the potential risk factors associated with IFIs in CTD.
Methods:
We systematically searched PubMed, Embase, and the Cochrane Library databases for relevant articles published from the database inception to February 1, 2023.
Results:
Twenty-six studies were included in this systematic review and meta-analysis. Risk factors identified for IFIs were diabetes (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.00 to 2.64), pulmonary diseases (OR 3.43; 95% CI 2.49 to 4.73), interstitial lung disease (ILD; OR, 4.06; 95% CI, 2.22 to 7.41), renal disease (OR, 4.41; 95% CI, 1.84 to 10.59), glucocorticoid (GC) use (OR, 4.15; 95% CI, 2.74 to 6.28), especially moderate to high-dose GC, azathioprine (AZA) use (OR, 1.50; 95% CI, 1.12 to 2.01), calcineurin inhibitor (CNI) use (OR, 2.49; 95% CI, 1.59 to 3.91), mycophenolate mofetil (MMF) use (OR, 2.83; 95% CI, 1.59 to 5.03), cyclophosphamide (CYC) use (OR, 3.35; 95% CI, 2.47 to 4.54), biologics use (OR, 3.43; 95% CI, 2.36 to 4.98), and lymphopenia (OR, 4.26; 95% CI, 2.08 to 8.73). Hydroxychloroquine (HCQ) use reduced risk of IFIs (OR, 0.67; 95% CI, 0.54 to 0.84). Furthermore, 17 of the 26 studies only reported risk factors for Pneumocystis jiroveci pneumonia (PJP) in patients with CTD. Pulmonary disease; ILD; and the use of GC, CNIs, CYC, methotrexate (MTX), MMF and biologics, and lymphopenia increased the risk of PJP, whereas the use of HCQ reduced its risk.
Conclusion:
Diabetes, pulmonary disease, ILD, renal disease, use of GC (especially at moderate to high dose) and immunosuppressive drugs, and lymphopenia were found to be associated with significant risk for IFIs (especially PJP) in patients with CTD. Furthermore, the use of HCQ may reduce the risk of IFIs in patients with CTD.
Insights
Invasive fungal infections (IFIs) are a significant risk for patients with connective tissue disease (CTD). Risk factors include diabetes, pulmonary disease, immunosuppressive drugs, and lymphopenia, while hydroxychloroquine may reduce IFI risk.
Area of Science:
- Rheumatology and Infectious Diseases
- Immunology and Pharmacology
Background:
- Invasive fungal infections (IFIs) pose a serious threat to patients with connective tissue diseases (CTD), contributing to substantial morbidity and mortality.
- Identifying specific risk factors for IFIs in this vulnerable population is crucial for effective prevention and management strategies.
Approach:
- A systematic review and meta-analysis was conducted, searching major databases (PubMed, Embase, Cochrane Library) up to February 1, 2023.
- Twenty-six studies were included to identify and quantify risk factors associated with IFIs in patients with CTD.
Key Points:
- Significant risk factors for IFIs in CTD patients include diabetes, pulmonary diseases (especially interstitial lung disease), renal disease, and lymphopenia.
- The use of immunosuppressive medications, including glucocorticoids (particularly moderate to high doses), azathioprine, calcineurin inhibitors, mycophenolate mofetil, cyclophosphamide, and biologics, significantly increases IFI risk.
- Conversely, hydroxychloroquine use was associated with a reduced risk of IFIs in this patient group.
Conclusions:
- Diabetes, pulmonary and renal diseases, lymphopenia, and the use of various immunosuppressive agents are key risk factors for IFIs, particularly Pneumocystis jiroveci pneumonia (PJP), in patients with CTD.
- Hydroxychloroquine may offer a protective effect against IFIs in patients with CTD, warranting further investigation.
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