Table 5 MAS presentations in different diseases and differentiation between MAS and disease activities
Standard | Statement | LE | SoR | Mean rate ± SD | % of agreement | Level of agreement |
|---|---|---|---|---|---|---|
MAS presentations with different diseases | ||||||
SLE | - Diagnostic criteria for macrophage activation syndrome complicating systemic lupus erythematosus(preliminary diagnostic guidelines for MAS as a complication of juvenile SLE according to Parodi et al.) [19] The diagnosis of MAS requires the simultaneous presence of at least 1 clinical criterion and at least 2 laboratory criteria. Bone marrow aspiration for evidence of macrophage hemophagocytosis may be required only in doubtful cases. Clinical criteria 1. Fever (>38°C) 2. Hepatomegaly (>3 cm below the costal arch) 3. Splenomegaly (>3 cm below the costal arch) 4. Hemorrhagic manifestations (purpura, easy bruising, or mucosal bleeding) 5. Central nervous system dysfunction (irritability, disorientation, lethargy, headache, seizures, or coma) Laboratory criteria 1. Cytopenia affecting 2 or more cell lineages (white blood cell count ≤ 4.0 × 109/L, hemoglobin ≤ 90 gm/L, or platelet count ≤ 150 × 109/L 2. Increased aspartate aminotransferase >40 units/L) 3. Increased lactate dehydrogenase (>567 units/L) 4. Hypofibrinogenemia (fibrinogen ≤1.5 gm/L) 5. Hypertriglyceridemia (triglycerides >178 mg/dL) 6. Hyperferritinemia (ferritin >500 μg/L) Histopathologic criterion Evidence of macrophage hemophagocytosis in the bone marrow aspirate | 3 | B | 8.3 ± 1.4 | 91.3 | H |
Systemic auto-inflammation | - Clinically: persistent fever, fatigue, hepatosplenomegaly, hepatic impairment, serositis, lymphadenopathy, case response to corticosteroid treatment - Lab: dropping of platelets (disproportionate with other inflammatory markers), pancytopenia, low fibrinogen level, clotting abnormalities, hyponatremia, perforin gene mutation, evidence of macrophage hemophagocytosis in the bone marrow aspirate | 3 | B | 8.04 ± 1.8 | 91.3 | H |
Kawasaki disease | - MAS may occur in any stage of KD (acute stage, subacute stage, or recovery stage) and may also occur prior to a KD diagnosis, but in most cases, it appears simultaneously with KD - Hepatosplenomegaly, neurological manifestations - Cytopenia, drop in ESR, or a disproportion between ESR and CRP levels, hyperferritinemia - Though bone marrow evidence of hemophagocytosis can be pathognomonic, failure to reveal hemophagocytosis does not exclude the diagnosis of MAS as histopathologic features of hemophagocytosis may not be present in the initial stages | 3 | B | 7.86 ± 1.9 | 95.65 | H |
Differentiation between MAS and disease activities | ||||||
sJIA | - Usually, MAS occurred in clinically active and resistive cases - MAS develops in the earlier phases or may be the presenting manifestation of sJIA; however, onset has been reported as long as 14 years after the initial diagnosis - The child complains of fatigue, tiredness, persistent high fever, more prominent hepatosplenomegaly, and lymphadenopathy, and rashes become petechial not evanescent salmon-pink rashes - MAS-associated SJIA tends to have more hepatosplenomegaly and lymphadenopathy than does MAS-associated SLE - Platelet count drop is the first most common early manifestations of MAS in sJIA patients, pancytopenia, dropped ESR due to hypofibrinogenemia, disproportion between ESR and CRP levels - Serum ferritin levels are the highest in the MAS-associated SJIA condition - So, persistent fever, neurological manifestations, and dropping of ESR are the most differentiating features between sJIA and MAS | 1 | A | 8.34 ± 1.8 | 95.65 | H |
Systemic auto-inflammatory diseases (SAIDS) | - When MAS complicating SAIDS: - Fever becomes persistent, unremitting, high-grade, apparently unexplained - Rashes become petechial not polymorphic - Serositis becomes more severe, with prominent hepatosplenomegally - Neurological symptoms may occur - Pancytopenia, elevated serum transaminases, hypofibrinogenemia - In contrast in SAIDS, high ESR, procalcitonin, and CRP are usually reported in SAIDS | 2 | B | 8.26 ± 1.8 | 91.3 | H |
Kawasaki disease | - - MAS-associated Kawasaki (KD) patients always present hepatosplenomegaly, whereas this is an uncommon presentation in patients with active KD | 3 | B | 8.09 ± 2.3 | 88.9 | H |
SLE | - MAS may occur in lupus patients, sometimes as the first presentation, although not as common as sJIA - Lab tests in favor of SLE flare include nephritis, hypocomplementemia, and elevated ESR | 2 | B | 8.3 ± 1.8 | 88.9 | H |
Infection | - Fever becomes more persistent not responding to antipyretics, with poor general status Hepatosplenomegaly, lymphadenopathy, petechial rashes, and neurological insult may occur Pancytopenia, dropped ESR due to hypofibrinogenemia, disproportion between ESR and CRP | 2 | B | 8.17 ± 1.8 | 88.9 | H |