TY - JOUR
T1 - Iron-deficiency anemia in Castleman disease
T2 - Implication of the interleukin 6/hepcidin pathway
AU - Arlet, Jean Benoît
AU - Hermine, Olivier
AU - Darnige, Luc
AU - Ostland, Vaughn
AU - Westerman, Mark
AU - Badoual, Cécile
AU - Pouchot, Jacques
AU - Capron, Loïc
PY - 2010/12/1
Y1 - 2010/12/1
N2 - In addition to occasional autoimmune hemolytic anemia, unexplained iron-deficiency anemia has been reported in childhood Castleman disease (CD). The recent discovery of hepcidin has regenerated the research on iron metabolism. This hormone is a key regulator of iron homeostasis, mainly by inhibiting intestinal iron absorption. Liver expression of hepcidin increases in response to interleukin 6 (IL-6). With chronic overproduction of IL-6 as a hallmark, CD could be an interesting human model for studying the contribution of the IL-6/hepcidin pathway in the pathogenesis of anemia of chronic disease. We report here the case of a 16-year-old boy with chronic iron-deficiency anemia (plasma ferritin: 19 μg/L; plasma iron: 2.2 μmol/L; negative bone marrow Perls' Prussian blue stain), inflammatory syndrome (C-reactive protein: 108 mg/L), and growth retardation for the previous 2 years. Diagnostic workup revealed a large mesenteric mass corresponding to localized CD of mixed histologic type. Resection of the tumor resulted in complete resolution of iron-deficiency anemia and inflammatory syndrome. Parallel variations of plasma IL-6, C-reactive protein, and hepcidin concentrations, together with tumor immunohistochemistry, strongly suggested that IL-6 synthesized by the tumor caused both the inflammation and iron deficiency through enhancement of hepcidin production by the liver. The results of this unique case study (1) explain the mechanism of iron deficiency observed in some children with CD, (2) confirm in vivo the regulatory effect of IL-6 in human hepcidin production, and (3) suggest that iron deficiency is a causal link between IL-6 and anemia of chronic disease.
AB - In addition to occasional autoimmune hemolytic anemia, unexplained iron-deficiency anemia has been reported in childhood Castleman disease (CD). The recent discovery of hepcidin has regenerated the research on iron metabolism. This hormone is a key regulator of iron homeostasis, mainly by inhibiting intestinal iron absorption. Liver expression of hepcidin increases in response to interleukin 6 (IL-6). With chronic overproduction of IL-6 as a hallmark, CD could be an interesting human model for studying the contribution of the IL-6/hepcidin pathway in the pathogenesis of anemia of chronic disease. We report here the case of a 16-year-old boy with chronic iron-deficiency anemia (plasma ferritin: 19 μg/L; plasma iron: 2.2 μmol/L; negative bone marrow Perls' Prussian blue stain), inflammatory syndrome (C-reactive protein: 108 mg/L), and growth retardation for the previous 2 years. Diagnostic workup revealed a large mesenteric mass corresponding to localized CD of mixed histologic type. Resection of the tumor resulted in complete resolution of iron-deficiency anemia and inflammatory syndrome. Parallel variations of plasma IL-6, C-reactive protein, and hepcidin concentrations, together with tumor immunohistochemistry, strongly suggested that IL-6 synthesized by the tumor caused both the inflammation and iron deficiency through enhancement of hepcidin production by the liver. The results of this unique case study (1) explain the mechanism of iron deficiency observed in some children with CD, (2) confirm in vivo the regulatory effect of IL-6 in human hepcidin production, and (3) suggest that iron deficiency is a causal link between IL-6 and anemia of chronic disease.
KW - Anemia of chronic disease
KW - Castleman disease
KW - Hepcidin
KW - Inflammatory anemia
KW - Interleukin 6
KW - Iron deficiency
UR - http://www.scopus.com/inward/record.url?scp=78649655459&partnerID=8YFLogxK
U2 - 10.1542/peds.2010-1123
DO - 10.1542/peds.2010-1123
M3 - Article
C2 - 21041280
AN - SCOPUS:78649655459
SN - 0031-4005
VL - 126
SP - e1608-e1612
JO - Pediatrics
JF - Pediatrics
IS - 6
ER -