“Sincerity is the key to success. Once you can fake that, you’ve got it made.”
The above quote is not particularly related to this blog post –but I like it.
A recent study (F Minoia et al. J Pediatr 2017; 189: 72-8) provides data supporting a scoring system which helps distinguish primary hemophagocytic lymphohistiocytosis (HLH) from macrophage activation syndrome (MAS).
Background: “By convention, secondary HLH seen in rheumatic disorders is termed macrophage activation syndrome…occurs most commonly in systemic juvenile idiopathic arthritis (sJIA).” Both HLH and MAS are life-threatening, though HLH tends to be more severe. The treatment for the two disorders is much different.
HLH typically develops in the first year of life, though some remain asymptomatic until later. Identification of pathologic mutations (primary HLH is not a single disease) is considered the gold standard, but this “takes weeks to complete and is not available in many resource-limited areas.”
In this study, the authors reviewed clinical features from 362 patients with MAS and 258 patients with HLH to develop a scoring system that more readily distinguished these conditions.The data from 80% of the patients was used to construct the scoring system and then this was validated with the remaining 20%. MH Score:
- Age of onset, years: 0 points if >1.6 yr, 37 points if ≤1.6 yr
- Neutrophil count, x 10 to the 9th/L: 0 points if >1.4, 37 points if ≤1.4
- Fibrinogen, mg/dL: 0 points if >131, 15 points if ≤131
- Splenomegaly: 0 points if no, 12 points if yes
- Platelet count, x 10 to the 9th/L: 0 points if >78, 11 points if ≤78
- Hemoglobin, g/dL: 0 points if >8.3, 11 points if ≤8.3
The age of onset and severe neutropenia are weighted the most heavily as they most heavily influence the odds ratio of having HLH; with multivariate analysis (Table 3), age of onset ≤1.6 yrs had an OR of 40.3, and neutrophil count ≤1.4 had an OR of 39.3. All of the other parameters had OR between 2.9 and 4.4. Hepatomegaly favored HLH as well but was not independently associated with the diagnosis.
How to use this scoring system:
- In this cohort, the MH score ranged from 0 to 123. The median value was 97 for HLH and 12 for MAS.
- A cutoff of ≥60 yielded a sensitivity of 91% and specificity of 93% for the diagnosis of HLH. Higher values increased the probability of HLH further.
Most laboratory studies were more abnormal with HLH; however, both ferritin elevation and LDH elevation were more pronounced with MAS. Median ferritin was 5353 with MAS and 2910 with HLH. Median LDH was 1230 with MAS compared with 696 with HLH.
This study validated the MH score for distinguishing HLH from MAS associated with sJIA; this can allow early introduction of aggressive treatment and appropriate genetic/immunologic evaluation. The applicability of the MH score for distinguishing HLH from other conditions is unclear. Further prospective evaluation of the MH score is needed.
My take: This is a very helpful study and is likely to influence diagnostic workup and management of these sick patients. Due to the liver and spleen abnormalities, pediatric gastroenterologists need to be able to recognize both HLH and MAS.
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