Iron deficiency without anaemia in patients with inflammatory bowel disease

Abstract

The significance of iron deficiency without anaemia (IDWA) in patients with inflammatory bowel disease (IBD) is uncertain. In healthy populations IDWA is associated with fatigue. Screening for IDWA in IBD in clinical practice may be reduced given this lack of certainty, so IDWA may be undiagnosed. This thesis aims to understand the current testing and treatment of iron deficiency in IBD, in addition to the number of patients affected. To determine the importance of detecting and treating iron deficiency, the association of iron deficiency and fatigue in patients with IBD was investigated. This thesis comprised of three studies. In the first study, pathology results for iron status and prescription records from patients with IBD under the care of University Hospitals Southampton (UHS) were analysed for the monitoring, detection and treatment of iron deficiency in IBD. A systematic review was undertaken regarding the association of iron deficiency with fatigue in patients with IBD. The third study assessed multiple biochemical measurements of iron status in comparison to patient-reported outcome measures (PROMs) for fatigue, along with grip strength in patients with Crohn’s disease in remission. These were analysed with other variables for determinants of iron status and fatigue as part of the INTICO2 study. Blood tests from patients with IBD at UHS showed that many patients are not screened for iron deficiency, including those who are anaemic. The detected prevalence of iron deficiency was approximately one third, including 22.5% with IDWA. Many patients did not receive iron replacement, leading to a missed opportunity to improve quality of life. In cases where IDWA was not treated, repeat blood tests showed progression to iron deficiency anaemia in multiple cases, especially when inflammation was present. The systematic review found heterogeneity of evidence limited definitive conclusions, though a small worsening of fatigue levels was demonstrated in iron-deficient patients. Results from the INTICO2 study showed iron deficiency occurred in 15.8% of patients with Crohn’s disease in remission. Iron deficiency was not associated with worse self-reported fatigue in patients with Crohn’s disease in remission. Fatigue was associated with other factors, including poor sleep and worse mental health in this cohort. Iron deficiency showed a weak relationship with z-scores for grip strength and there was tendency to worse scores for physical function, though this was not significant. Research on iron deficiency in this thesis highlighted the variation in biochemical cut-offs used to define iron deficiency and how this may affect diagnosis. The UHS laboratory cut-offs which were employed in the studies here were highly specific and may exclude states of iron deficiency that are associated with symptoms. The detected prevalence of iron deficiency varied according to which cut-off values where employed. Consideration should be given to standardising the approach to diagnosis of iron deficiency to ensure equal treatment of patients. A scheme for the proposed management of IDWA and future research is included in this thesis.

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