2. Hyperferritinemic Syndromes
The hyperferritinemic syndromes pathogenesis is extremely complex and
variable. Genetic mutations, infections, underlying diseases, and
immunosuppression can play a distinct role in these conditions, leading
to the unique epilogue that is
hyperferritinemia (>
500 µg/L) and hyperinflammation (28, 29). According to Schulter et al.
(29), despite the numerous protagonists that can play a role in the
development of hyperferritinemic syndrome, they might converge in at
least two mechanisms that provoke hyperferritinemia: over activation of
T lymphocytes and over-activity of IFN-γ (29). Nevertheless, recent
evidences described the direct role of the H-chain of ferritin in
activating macrophages to increase the secretion of inflammatory
cytokines (30).
Several diseases that may present both hyperinflammation and
hyperferritinemia have been grouped under this common umbrella named
hyperferritinemic syndrome (Table 1).
These include MAS, a secondary
form of HLH (also called hemophagocytic syndrome), AOSD, cAPS and septic
shock (31, 32). Although these conditions are characterized by different
pathogenesis and clinical presentation, it is likely that
pathogenically elevated levels of
ferritin sustain the inflammatory process (31).
Nonetheless, hyperferritinemia is not specific of the abovementioned
hyperferritinemic syndromes. Indeed, levels up to 2000 µg/L of ferritin
can be found in other conditions such as liver damage and infections,
even if the first is one of the possible clinical manifestations of HLH
while the second is the most common trigger of secondary HLH (33).