Comprehensive insights into tuberculosis-associated hemophagocytic lymphohistiocytosis: a systematic review

Abstract

Abstract Background Tuberculosis-associated hemophagocytic lymphohistiocytosis (TB-HLH) presents significant challenges in diagnosis and treatment due to its complex interplay between TB and HLH. This systematic review aims to provide comprehensive insights into the epidemiology, clinical characteristics, and treatment outcomes of TB-HLH patients. Methods We performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Scopus, Web of Science, and Embase up to May 16, 2023, without language restrictions. We included case reports and cases series on patients with both TB and HLH with documented treatment outcomes. Data were analyzed using descriptive statistics, chi-square or Fisher’s exact tests, t-tests, and mortality rates. Significant variables (p < 0.05) from univariate analysis and clinically relevant factors were used in binary logistic regression to determine odds ratios, 95% confidence intervals, and p-values. Results A total of 185 articles involving 213 patients were included. The overall mortality rate was 39%. Age ≥ 44 years and comorbidities were identified as independent risk factors for increased mortality (p = 0.005). Anti-tuberculosis treatment (ATT) combined with HLH-specific therapies, was associated with reduced mortality compared to ATT alone (p < 0.05), especially IVIG (p = 0.04). Conclusion Integrating ATT with HLH-specific therapies significantly enhances survival in TB-HLH patients. Additionally, IVIG plays a key role in improving outcomes. Age ≥ 44 years and comorbidities are critical risk factors for increased mortality. Early and high suspicion of TB-HLH is essential, especially in high TB burden regions or recent travel contexts. Future research should focus on prospective multicenter studies to validate our findings and develop standardized treatment strategies on TB-HLH. PROSPERO CRD42022364180.

Keywords

• Hemophagocytic lymphohistiocytosis
• HLH
• Tuberculosis
• TB-HLH
• Intravenous immunoglobulin