| Evidence type (review/cohort/etc) | Population | Key statistics (with numbers) | Triggers/notes | Source (include DOI URL + year) | Context citation id |
|---|---|---|---|---|---|
| Narrative review | General HLH; prevalence estimates from multiple countries | Prevalence estimates reported as Japan **1:800,000**, China **1.04:1,000,000**, England **1–2:1,000,000**; overall mortality **~40%** | Secondary HLH commonly triggered by infections, autoimmune/rheumatologic disease, malignancy, or immunosuppression; **EBV** most frequently implicated in adults | Papazachariou & Ioannou, 2024, DOI: https://doi.org/10.3390/hematolrep16030047 | (pqac-00000000) |
| Review | Adults with secondary HLH, especially malignancy-associated HLH | In North America/Europe, **~50%** of adult HLH is associated with underlying malignancy; malignancy-associated HLH has **<20% 1-year survival** and median survival **~2 months** | Adult HLH triggers include malignancy, rheumatologic disease/MAS, chronic viral infections (**EBV, CMV, VZV, HSV, HIV**), and treatment-related causes such as HCT or CAR-T | Lee & Logan, 2023, DOI: https://doi.org/10.3390/cancers15061839 | (pqac-00000002) |
| ICU/case-based review | Adult HLH, especially ICU presentations | Acute mortality across all combined groups **~40%**; malignancy-associated HLH acute mortality **>80%**; 5-year survival **<15%**; ICU hospital mortality **52–68%**; ferritin **>4,000 µg/L** increases likelihood and **>10,000 µg/L** is highly concerning | In adults, underlying malignancy in **nearly 50%** of cases; lymphomas/leukemia involved in **20%** and **10%** of cases; bacterial infections contribute to **~10%** | de Sousa et al., 2024, DOI: https://doi.org/10.12890/2024_005040 | (pqac-00000003) |
| Scoping review | HLH associated with tick-borne illness, **98 cases** | Mean age **43.7 y**; **64%** male; immunosuppression **21.4%**; thrombocytopenia **81.6%**; mean HScore **209**; mortality **16.3%** | Most common pathogens: **Ehrlichia spp. 45.9%**, **Rickettsia spp. 14.3%**, **Anaplasma phagocytophilum 12.2%**; many recovered with antimicrobials alone | Jevtic et al., 2024, DOI: https://doi.org/10.3390/idr16020012 | (pqac-00000004) |
| Molecular/etiologic stratification study | **92** clinically confirmed secondary HLH patients | Adult infectious-trigger proportions cited: herpesviruses account for **62%** of viral HLH; **43%** due to **EBV** and **9%** due to **CMV**; bacterial infections in **9%** of adult HLH, with **38%** of those bacterial cases due to tuberculosis | Secondary HLH subtyped into infection-, tumor-, and autoimmunity-related causes using Onco-mNGS | Wu et al., 2024, DOI: https://doi.org/10.3389/fimmu.2024.1390298 | (pqac-00000005) |
| Retrospective adult cohort/dissertation | Adults with HLH | Overall adult mortality still **>40%**; monoallelic mutations in familial HLH-related genes found in **43/240 (18%)** secondary HLH cases in cited Italian study; sCD25 was significant prognostic factor (**p = 0.005**) | Secondary HLH in older children/adults triggered by infections, malignancies, autoimmune disease, and immunosuppressive treatment; highlights overlap of genetic susceptibility with “secondary” HLH | Wimmer, 2024, DOI: https://doi.org/10.5282/edoc.33899 | (pqac-00000001, pqac-00000006) |
| ASH Education review | Inpatient HLH across ages | No incidence figure given; diagnostic framework commonly uses **5 of 8 HLH-2004 criteria** | Triggers include infections (**EBV, CMV, HIV, COVID-19, tuberculosis, Leishmania, bacterial sepsis, Rickettsia, Leptospira, Bartonella, Brucella, Ehrlichia**), hematologic malignancies, rheumatologic disease (**sJIA/Still’s, SLE**), and iatrogenic causes (**CAR-T, ICB**) | Zoref-Lorenz et al., 2023, DOI: https://doi.org/10.1182/hematology.2023000509 | (pqac-00000007) |
| Review of ICI-associated HLH cases | **27** patients with immune checkpoint inhibitor-associated HLH | **18 males / 9 females**; mean age **58 y** (range **26–86**); mean time to onset **10.3 weeks**; **22/27** improved after treatment; **4/27** died | Drug/iatrogenic trigger category; common features included fever, cytopenia, splenomegaly, hypofibrinogenemia, marrow hemophagocytosis | Xu et al., 2024, DOI: https://doi.org/10.1080/16078454.2024.2340144 | (pqac-00000002) |
| Systematic review | Tuberculosis-associated HLH, **213 patients** | Overall mortality **39%**; age **≥44 years** and comorbidities were independent risk factors for mortality; ATT + HLH-specific therapy improved survival vs ATT alone | Important infectious trigger in high-TB-burden settings; integrating anti-tuberculosis therapy with HLH-directed therapy improved outcomes | Eslami et al., 2024, DOI: https://doi.org/10.1186/s12879-024-10220-7 | (pqac-00000002) |
| Narrative review | HSV-1/2-triggered HLH, **34 patients** | **50%** adults and **50%** neonates; **64.7%** HSV-1; median in-hospital treatment **21 days**; mortality **41.2%** | Viral-triggered HLH; fever and splenomegaly common; acyclovir and steroids were main therapies | Papazachariou & Ioannou, 2024, DOI: https://doi.org/10.3390/hematolrep16030047 | (pqac-00000000) |
| Cooperative pediatric treatment study | HLH-2004, **369 children <18 y** | At median follow-up **5.2 years**, **230/369 (62%)** alive; **5-year survival 61% (56–67%)**; pre-HSCT mortality **19%** vs **27%** in HLH-94; post-HSCT 5-year survival **66%**, and **70%** in verified familial HLH | Confirms efficacy of etoposide+dexamethasone backbone; HSCT indicated for familial/genetic, relapsing, or severe/persistent disease | Bergsten et al., 2017, DOI: https://doi.org/10.1182/blood-2017-06-788349 | (pqac-00000018) |


*Table: This table compiles key quantitative epidemiology and outcome data for HLH from recent reviews and cohorts, alongside major trigger categories. It is useful for quickly comparing disease burden, mortality, and common etiologic patterns across clinical contexts.*