General and context-specific diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH)9,12,19,39
| Familial HLH . | Reactive HLH . | Context-specific . | ||
|---|---|---|---|---|
| HLH-20049 If criterion 1 or 2 is fulfilled. 1) A molecular diagnosis consistent with HLH 2) 5 of the 8 criteria: • Fever • Splenomegaly • Cytopenias: 2 out of 3 lineages ○ Hemoglobin <9 g/dL ○ Platelets <100 × 109/L ○ Neutrophils <1.0 × 109/L • Triglycerides ≥265 mg/dL OR Fibrinogen ≤150 mg/dL • Hemophagocytosis in bone marrow or spleen or lymph nodes. No evidence of malignancy • Low or no NK cell activity • Ferritin ≥500 µg/L • sCD25 ≥ 2400 U/mL | H-Score12 >169 points is the optimal diagnostic threshold for HLH. Addition of the points according to: | Malignancy-associated optimized HLH inflammatory (OHI) index19 sCD25 > 3,900 U/mL AND Ferritin >1,000 ng/mL Systemic juvenile arthritis associated with EULAR/ACR/PRINTO for MAS39 Serum ferritin level >684 ng/mL AND Any 2 of the following: • Platelet count ≤181 × 109/L • AST >48 units/L • Triglyceride >156 mg/dL OR Fibrinogen ≤360 mg/dL | ||
| Variable | Categories | Points | ||
| Known underlying immunosuppression* | No | 0 | ||
| Yes | 18 | |||
| Temperature, °F (°C) | <101.1 (<38.4) | 0 | ||
| 101.1–102.9 (38.4-39.4) | 33 | |||
| >102.9 (>39.4) | 49 | |||
| Organomegaly | No | 0 | ||
| Hepatomegaly or splenomegaly | 23 | |||
| Hepatomegaly and splenomegaly | 38 | |||
| Number of cytopenias** | 1 lineage | 0 | ||
| 2 lineages | 24 | |||
| 3 lineages | 34 | |||
| Ferritin, ng/mL (µg/L) | <2000 | 0 | ||
| 2000–6000 | 35 | |||
| >6000 | 50 | |||
| Triglyceride, mg/dL (mmol/L) | <132.7 (<1.5) | 0 | ||
| 132.7-354 (1.5–4) | 44 | |||
| >354 (>4) | 64 | |||
| Fibrinogen, mg/dL (g/L) | >250 (>2.5) | 0 | ||
| ≤250 (≤2.5) | 30 | |||
| AST, U/L | <30 | 0 | ||
| ≥30 | 19 | |||
| Hemophagocytosis features on bone marrow aspirate | No | 0 | ||
| Yes | 35 | |||
| *HIV positive or receiving long-term immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine). | ||||
| **Defined as hemoglobin ≤9.2 g/dL and/or WBC ≤5×109/L and/or platelets ≤110×109/L. | ||||
| Familial HLH . | Reactive HLH . | Context-specific . | ||
|---|---|---|---|---|
| HLH-20049 If criterion 1 or 2 is fulfilled. 1) A molecular diagnosis consistent with HLH 2) 5 of the 8 criteria: • Fever • Splenomegaly • Cytopenias: 2 out of 3 lineages ○ Hemoglobin <9 g/dL ○ Platelets <100 × 109/L ○ Neutrophils <1.0 × 109/L • Triglycerides ≥265 mg/dL OR Fibrinogen ≤150 mg/dL • Hemophagocytosis in bone marrow or spleen or lymph nodes. No evidence of malignancy • Low or no NK cell activity • Ferritin ≥500 µg/L • sCD25 ≥ 2400 U/mL | H-Score12 >169 points is the optimal diagnostic threshold for HLH. Addition of the points according to: | Malignancy-associated optimized HLH inflammatory (OHI) index19 sCD25 > 3,900 U/mL AND Ferritin >1,000 ng/mL Systemic juvenile arthritis associated with EULAR/ACR/PRINTO for MAS39 Serum ferritin level >684 ng/mL AND Any 2 of the following: • Platelet count ≤181 × 109/L • AST >48 units/L • Triglyceride >156 mg/dL OR Fibrinogen ≤360 mg/dL | ||
| Variable | Categories | Points | ||
| Known underlying immunosuppression* | No | 0 | ||
| Yes | 18 | |||
| Temperature, °F (°C) | <101.1 (<38.4) | 0 | ||
| 101.1–102.9 (38.4-39.4) | 33 | |||
| >102.9 (>39.4) | 49 | |||
| Organomegaly | No | 0 | ||
| Hepatomegaly or splenomegaly | 23 | |||
| Hepatomegaly and splenomegaly | 38 | |||
| Number of cytopenias** | 1 lineage | 0 | ||
| 2 lineages | 24 | |||
| 3 lineages | 34 | |||
| Ferritin, ng/mL (µg/L) | <2000 | 0 | ||
| 2000–6000 | 35 | |||
| >6000 | 50 | |||
| Triglyceride, mg/dL (mmol/L) | <132.7 (<1.5) | 0 | ||
| 132.7-354 (1.5–4) | 44 | |||
| >354 (>4) | 64 | |||
| Fibrinogen, mg/dL (g/L) | >250 (>2.5) | 0 | ||
| ≤250 (≤2.5) | 30 | |||
| AST, U/L | <30 | 0 | ||
| ≥30 | 19 | |||
| Hemophagocytosis features on bone marrow aspirate | No | 0 | ||
| Yes | 35 | |||
| *HIV positive or receiving long-term immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine). | ||||
| **Defined as hemoglobin ≤9.2 g/dL and/or WBC ≤5×109/L and/or platelets ≤110×109/L. | ||||
AST, aspartate aminotransferase; EULAR/ACR/PRINTO, European League Against Rheumatism/American College of Rheumatology/Pediatric Rheumatology International Trials Organization; NK, natural killer; sCD25, soluble CD25/soluble interleukin-2 receptor alpha; WBC, white blood cell.