ORIGINAL ARTICLE Erythropoietin Levels in Children and Adolescents With Inflammatory Bowel Disease Artemis Tsitsika, MD,* Alexandra Stamoulakatou, MD,† Yota Kafritsa, MD,* George Paleologos, MD,‡ Ioanna Panayotou, MD,* Evangelos Premetis, PhD,† Eleftheria Roma, MD,* and Ioannis Papassotiriou, PhD‡ Summary: Iron deficiency anemia (IDA) and anemia of chronic disease (CDA) are often encountered in patients with inflammatory bowel disease (IBD). Inadequate intake or loss of iron is a clear cause of IDA, but mechanisms of CDA induction are multifactorial and involve erythropoiesis disturbance due to circulating inflammation mediators. The authors investigated erythropoietin (Epo) levels in children and adolescents with IBD and correlated them to disease activity, with the aim of gaining an improved understanding of the role of Epo in CDA. Thirty-three patients with IBD were examined (18 boys, 15 girls) ages 4 to 15 years (median 11 years). Two study groups related to the disease activity were formed: group A, those with active disease (n = 21), and group B, those in remission (n = 12). Epo levels were measured using a two-site chemiluminescence immuno- assay. Predictive Epo values in response to the degree of anemia were calculated by the equation: logEpo = (3.48 2 0.20) 3 Hb. According to the results, CDA anemia was present only in patients with active disease. These patients also had a significantly higher possibility of altered Epo levels than expected compared with patients with inactive disease (16/21 vs. 4/12, P , 0.05). It was also interesting that most of the patients with anomalous Epo concentrations presented with an elevated Epo value compared with that expected from the calculation (14/20). It seems that disturbed Epo concentrations are correlated with disease activity in children and adolescents with IBD. It is pos- sible that failure of the bone marrow to respond to increased Epo levels leads to further incremental response. These in turn lead to the high Epo concentrations detected in most of the authors’ patients. Impaired Epo production is another mechanism of CDA development and is the one mainly expressed in patients with low Epo values. Key Words: inflammatory bowel disease, anemia of chronic disease, iron deficiency anemia, erythropoietin (J Pediatr Hematol Oncol 2005;27:93–96) I nflammatory bowel disease (IBD) involves cellular immu- nity activation expressed by both local and systemic disturbances. Local intestinal inflammation is the result of an aberrant immune response to luminal antigen uptake lead- ing to secondary malabsorption and chronic blood loss. 1 In- adequate intake or loss of iron through the above-described situation is the mechanism of iron deficiency anemia (IDA), most often complicating IBD. 2 On the other hand, products of activated inflammatory cells (cytokines) enter the systemic circulation and affect erythropoiesis directly or via the ex- cessive production of free radicals, finally leading to chronic disease anemia (CDA). 3 This type of anemia typically de- velops in patients with chronic inflammatory conditions, and it is described as a defensive mechanism of the host against invading factors. 4 CDA can be diagnosed by concentrations of iron and plasma erythropoietin (Epo). Epo levels are reported to be relatively low (taking into account the degree of anemia) in patients with IBD. 5,6 Administration of recombinant human Epo (rHu-Epo) has therefore been attempted following the renal anemia therapeutic model. 7,8 Conversely, other inves- tigators have found no differences in Epo levels of CDA patients compared with healthy subjects. 9 The therapeutic effectiveness of rHu-Epo has also been questioned because of the variety of mechanisms contributing to the pathophysiology of CDA. The best solution, it has been suggested, is the cure of the underlying disease. 2,10 Data concerning Epo anemia mechanisms in children and adolescents with IBD are limited, although this age group accounts for 25% of all new cases of IBD. Furthermore, CDA is often recognized in childhood, and treatment options have been proposed. 7 Based on the above, more detail on Epo patterns in children and adolescents with IBD seems worth considering. In this study we examined Epo levels in children and ado- lescents with IBD and correlated our findings to the disease activity. The aim of this study was to clarify the Epo-related mechanism of CDA in childhood IBD, leading to an improved assessment of the situation. MATERIALS AND METHODS We collected samples from 40 consecutive patients at the IBD clinic of our hospital. Patients with evidence of vitamin B12 or folate deficiency, as well as those with hemoglobin- opathies or those who had received iron supplementation during the previous year, were excluded from this study. We finally included 33 patients (18 boys, 15 girls) aged 4 to 15 Received for publication May 18, 2004; accepted December 7, 2004. From the *First Department of Pediatrics, Athens University Medical School, Athens, Greece; †Hematology Laboratory, ‘‘Aghia Sophia’’ Children’s Hospital, Athens, Greece; and ‡Department of Clinical Biochemistry, ‘‘Aghia Sophia’’ Children’s Hospital, Athens, Greece. Reprints: Ioannis Papassotiriou, Department of Clinical Biochemistry, ‘‘Aghia Sophia’’ Children’s Hospital, 115 27 Athens, Greece (e-mail: biochem@ paidon-agiasofia.gr or jpapasotiriou@ath.forthnet.gr). Copyright Ó 2005 by Lippincott Williams & Wilkins J Pediatr Hematol Oncol  Volume 27, Number 2, February 2005 93