Crohn’s disease is a recurrent disorder of the gastrointestinal tract, often accompanied by complicated extraintestinal manifestations. Iron deficiency (ID) and iron deficiency anemia (IDA) are frequently encountered in up to 90% of IBD patients due to chronic active illness[2,19]. Oral iron therapy has been shown to be less effective in patients with higher CRP, which supports that serum iron homeostasis is affected by inflammation. In this study, we evaluated the association between serum indicators related to iron stores and disease severity and found that the detection of decreased serum iron and total iron binding capacity was effective in screening patients with serious disease.
In this study, serum iron concentration and TIBC were decreased significantly in patients with moderate clinical disease. This is consistent with the progression in Crohn’s disease. CD can affect any region within the gastrointestinal tract. Chronic bleeding caused by segmental ulceration or mucosal inflammation predisposes patients to lose massive amounts of iron[3,4]. The involvement of the duodenum-jejunum and reduced daily food intake due to fear of gastrointestinal symptoms can aggravate iron malnutrition. Furthermore, the complex interplay of cytokines produced by the inflamed intestine and the surrounding mesentery and hepcidin can also contribute to iron deficiency[1,21]. Two major relevant sources of hepcidin are hepatocytes and dendritic cells in the intestinal tract[10,20]. Functionally active hepcidin from the liver is upregulated by cytokines and binds to ferroportin on enterocytes via the blood circulation, inducing degradation of this iron transporter. In the absence of DC-derived hepcidin during inflammation, ferroportin in macrophages and neutrophils is retained, and iron is released extracellularly. These changes limit iron absorption and transport to the plasma. Systemic inflammation had a significant impact on serum iron homeostasis. This was in line with our results showing that serum iron and TIBC correlated negatively with CDAI scores, and the specificity of decreased serum iron was very high in distinguishing moderate CD patients. Combined detection of these two indicators would be useful in screening serious CD patients.
Ferritin is a measure of stored iron content and is decreased in the condition of iron deficiency. Previous studies reported that ferritin was positively correlated with hepcidin and negatively correlated with the efficacy of oral iron treatment[5,23]. These results suggested that ferritin may be increased due to active intestinal inflammation. For CD patients, severe inflammation is often accompanied by iron deficiency, and false normal ferritin may be found. This may explain why the difference in ferritin was not significant between patients and controls in our study. Both serum ferritin and transferrin are active-phase reactants. Transferrin is responsible for transferring iron from the sites of absorption to all tissues. The level is high in patients with iron deficiency, but it will decrease during inflammation. Therefore, false normal values were commonly found in the condition of anemia of inflammation. In our study, although transferrin and transferrin saturation seemed lower in patients with moderate CD, neither of them was useful in screening patients with serious disease.
We found that disease localization and behavior were not associated with severity. This was consistent with the study of Aksan A et al. It seemed that serum iron concentration and transferrin saturation tended to decrease in patients with higher SES-CD, but the differences were not significant. This result was reasonable because SES-CD is based on colonoscopy findings and cannot reflect lesions beyond the stricture or in the upper gastrointestinal tract. Although ulcers are an important indicator of SES-CD, iron deficiency is not only associated with ulceration or bleeding[4,18,26,27].
Dietary Fe intake is reduced in CD patients as a result of avoidance of certain fiber-rich and Fe-fortified cereals due to the fear of exacerbating gastrointestinal symptoms.Active disease can decrease absorption and increase energy expenditure[28,29]. Combined, these factors contribute to the weight loss observed. Undernutrition has a negative impact on the disease process and increases the rate of postoperative complications and mortality[29,30,31,32]. BMI<18.5kg/m2 is one of the criteria for undernutrition. It was not surprising to find that this metric was an indicator for serious Crohn’s disease.
There are some limitations in this study. First, age was not comparable between CD patients and controls. This may have a negative impact on the reliability of our conclusion. Therefore, logistic regression analysis was used to exclude the influence of confounding factors, and we found that decreased serum iron and total iron binding capacity were correlated with clinical disease severity. Second, no patients with severe clinical activity were included in this study. This may be due to the improvement of patients’ health consciousness; they will seek medical advice in time as gastrointestinal symptoms appear. We will include more patients in a future study and try to obtain data from patients with severe disease. Third, this was a single-center prospective study, and the sizes of the patient groups were small after classification based on the CDAI scores or SES-CD. We described the observed results but lacked data on patients after immunotherapy and iron supplementation. Further study on the correlation between the changes in these indicators and that of CDAI scores after treatment would be useful in supporting our conclusion.