The Hyperferritinemic Syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome

Table 2 Common clinical manifestations and laboratory abnormalities: MAS, AOSD, cAPS and septic shock

	Septic shock	cAPS	AOSD	MAS
Hyperferritinemia	+ [15, 39]	[71%] [8]	[70 to 89%] [40, 41]	[87 to 100%] [42]
Range of ferritin levels (ng/mL)*	21 to 2,210 [15]	250 to 2,875 [8]	223,6 to 54924 [43]	994 to 189,721 [44]
Hypercytokinemia	+ [45]	+ [46], [47]	+ [48]	+ [49–53]
Infection as a trigger	[100%] [54]	+ [46]	+ [41]	+ [55]
Fever	+ [54]	+ [56]	[82 to 100%] [41]	[78 to 94%] [42]
Multiorgan involvement	[100%] [54]	[100%] [46]	+ [41]	+ [14, 55, 57]
Hepatomegaly	Rare [14]	NR	[42%] [41]	[61 to 88%] [42]
Splenomegaly	Rare [14]	NR	[22 to 65%] [41]	[45 to 59%] [42]
Hemophagocytosis	+ [14]	NR	+ [3, 40]	[81%] [42]
Thrombocytopenia	+ [14], [54]	[46%] [58]	-	[89%] [42]
Anemia	+ [54]	Hemolytic anemia [35%] [58]	[68%] [41]	[67 to 82%] [42]
Leukopenia	+ [14], [54]	NR	-	[39 to 56%] [42]
Neutropenia	+ [54]	NR	-	+ [14, 55, 57]
Neutrophilia	+ [54]	+ [56]	[81%] [41]	-
Macrophage activation	+ [14]	NR	+ [59]	+ [14, 55, 57]
Low/absent NK activity	+ [14]	NR	+ [60]	+ [14, 55, 57]
Sol. IL-2R >2,400 U/ml	+ [14]	NR	+ [48]	+ [14, 55, 57]
Abnormal liver function tests	+ [54]	+ [56]	[73%] [41]	[94%] [42]
HyperTG	+ [14]	NR	NR	[77 to 100%] [42]
Coagulopathy	+ [54]	DIC [15%] [58]	Rare [41]	+ [55]
Hypofibrinogenemia	+ [14], [54]	[15%] [58]	Rare [41]	[78 to 89%] [42]
ESR/CRP (↑ or ↓)	↑ [54]	↑ [46]	↑ [99%] [41]	ESR ↓ [79 to 92%] [42] CRP ↑ [61]

[%], percentage of association reported in the literature; +, positive association but not precise percentage reported; -, not associated; NR, no reported association.
CRP C reactive protein, DIC disseminated intravascular coagulation, ESR elevated sedimentation rate, hyperTG hypertriglyceridemia, sol. IL-2R, soluble IL-2 receptor.
* There is only our study on cAPS and it is a small cohort, and there are only a few studies on ferritin levels in sepsis, so the values of ferritin in these two conditions may be underestimated.
Table 2. All four conditions are life-threatening events in which an uncontrolled and immune response, triggered in most cases by infectious agents, leads to a severe hyperinflammation. There is evidence of hypercytokinemia and hyperferritinemia during the symptomatic period of the diseases. With the exception of the cAPS, for which there is no information in the literature, there is an impaired or absent function in natural killer (NK) and cytotoxic T cells.

ISSN: 1741-7015