Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment?
BACKGROUND
Hyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH.


METHODS
We conducted a multi-center cohort study of children in Turkish Pediatric Intensive Care units with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS treated with less immunosuppression (plasma exchange and intravenous immunoglobulin or methyl prednisolone) or with the primary HLH protocol (plasma exchange and dexamethasone or cyclosporine A and/or etoposide). The primary outcome assessed was hospital survival.


RESULTS
Twenty-three children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS were enrolled (median ferritin = 6341 μg/dL, median number of organ failures = 5). Univariate and multivariate analyses demonstrated that use of plasma exchange and methyl prednisolone or intravenous immunoglobulin (n = 17, survival 100%) was associated with improved survival compared to plasma exchange and dexamethasone and/or cyclosporine and/or etoposide (n = 6, survival 50%) (P = 0.002).


CONCLUSIONS
Children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS can be successfully treated with plasma exchange, intravenous immunoglobulin, and methylprednisone. Randomized trials are required to evaluate if the HLH-94 protocol is helpful or harmful compared to this less immune suppressive and cytotoxic approach in this specific population.
Department of Pediatric Intensive Care, Bezmialem Vakif University, Faculty of Medicine, Vatan Caddesi, Istanbul, 34093, Turkey. d-demirkol@hotmail.com
Demet
D
Demirkol
Dincer
D
Yildizdas
Benan
B
Bayrakci
Bulent
B
Karapinar
Tanil
T
Kendirli
Tolga F
TF
Koroglu
Oguz
O
Dursun
Nilgün
N
Erkek
Hakan
H
Gedik
Agop
A
Citak
Selman
S
Kesici
Metin
M
Karabocuoglu
Joseph A
JA
Carcillo
D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016638:Critical Illness; D016572:Cyclosporine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005293:Ferritins / Q000097:blood*; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000150:complications* / Q000628:therapy*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000209:etiology* / Q000628:therapy*; D055501:Macrophage Activation Syndrome / Q000209:etiology* / Q000628:therapy*; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology* / Q000628:therapy*; D010951:Plasma Exchange; D011239:Prednisolone / Q000627:therapeutic use; D012044:Regression Analysis; D018805:Sepsis / Q000209:etiology* / Q000628:therapy*; D015996:Survival Rate; D016896:Treatment Outcome; D014421:Turkey
D000972:Antineoplastic Agents, Phytogenic; D005938:Glucocorticoids; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D005047:Etoposide; D003907:Dexamethasone; D016572:Cyclosporine; D005293:Ferritins; D011239:Prednisolone