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. Author manuscript; available in PMC: 2020 Jul 4.
Published in final edited form as: Paediatr Drugs. 2020 Feb;22(1):29–44. doi: 10.1007/s40272-019-00367-1

Table 2.

Comparison of diagnostic/classification tools for HLH and MAS

HLH 2004a 2016 MAS classification criteriab MS scorec Ferritin:ESR ratiod HScoree MH scoref
(1) Molecular diagnosis (1) Fever in sJIA pt
AND		 (1) Calculation ≥ − 2.1
B-coefficient		 (1) Ferritin/
ESR ≥ 21.5		 (1) Points add to ≥ 169 (1) Points add to ≥ 60
OR
(2) 5/8 Criteria: (2) Ferritin > 684 ng/
mL
AND		 CNS 2.44
Hemorrhagic 1.54
Arthritis − 1.30		 Immunosuppression
0 (no), 18 (yes)
Temp (°C)
 Age at onset (y)
0 (> 1.6), 37 (≤ 1.6)
Neutrophils (× 109/L)
Fever ≥ 38.5 °C
Splenomegaly
Cytopenias in 2/3
lines
Hgb < 9 g/dL
Plts < 100 × 103/mL
Neutrophils < 1 × 103/
mL
TG ≥ 265 mg/dL
and/or fibrinogen
≤ 150 mg/dL
Hemophagocytosis
Low NK cell fxn
Ferritin ≥ 500 ng/mL
Elevated sIL-2 receptor		 (3) 2/4 Criteria:
Plts ≤ 181×103/mL
AST > 48 u/L
TG > 156 mg/dL
Fibrinogen ≤ 360 mg/dL		 Plts (× 109/L) − 0.003
LDH (U/L) 0.001
Fibrinogen (mg/dL)
− 0.004
Ferritin (ng/mL)
0.0001		 0 (< 38.4), 33 (38.4–
39.4), 49 (> 39.4)
Organomegaly
0 (no), 23 (H or SM),
38 (HSM)
Cytopenias
0 (1 line), 24 (2 lines),
34 (3 lines)
Ferritin (ng/mL)
0 (< 2000), 35
(2–6000), 50
(> 6000)
TG (mmoles/L)
0 (< 1.5), 44 (1.5–4),
64 (> 4)
Fibrinogen (gm/L)
0 (> 2.5) or 30 (≤ 2.5)
AST (u/L)
0 (< 30) or 19 (≥ 30)
Hemophagocytosis
0 (no) or 35 (yes)		 0 (> 1.4), 37 (≤ 1.4)
Fibrinogen (mg/dL)
0 (> 131), 15 (≤ 131)
Splenomegaly
0 (no), 12 (yes)
Plts (× 109/L)
0 (> 78), 11 (≤ 78)
Hgb (g/dL)
0 (> 8.3), 11 (≤ 8.3)
Sens: N/A Sens: 73% Sens: 85% Sens: 82% Sens: 93% Sens: 91%
Spec: N/A Spec: 99% Spec: 95% Spec: 78% Spec: 86% Spec: 93%

Sensitivities and specificities in the table refer to the values obtained from the original derivation population in the cited references

AST aspartate aminotransferase, CNS central nervous system involvement, ESR erythrocyte sedimentation rate, fxn function, H hepatomegaly, hemorrhagic hemorrhagic manifestations, Hgb hemoglobin, HLH hemophagocytic lymphohistiocytosis, HSM hepatosplenomegaly, LDH lactic dehydrogenase, MAS macrophage activation syndrome, MH MAS/HLH, MS MAS/sJIA, NK natural killer, Plts platelets, pt patient, s soluble, SM splenomegaly, sens sensitivity, sJIA systemic juvenile idiopathic arthritis, spec specificity, TG triglycerides

a

Adapted from [84] for the diagnosis of HLH in the HLH-2004 clinical trial

b

Adapted from [96, 97] for the classification criteria of MAS in sJIA

c

Adapted from [106] to discriminate between sJIA with MAS from active sJIA

MS score = CNS involvement × 2.44 + hemorrhagic manifestations × 1.54 + arthritis × (− 1.3) + Plts × (− 0.003) + LDH × 0.0001 + fibrinogen × (− 0.004) + ferritin × 0.0001

d

Adapted from [108] to discriminate between sJIA with MAS and active sJIA

e

Adapted from [109] to assess the risk of acquired HLH in adults

f

Adapted from [87] to discriminate between primary HLH and MAS