Anaemia in pediatric celiac disease: association with clinical and histological features and response to a gluten-free diet
Rajalahti T, Reop M, Kivelä L et al
Journal of Paediatric Gastroenterology and Nutrition, e-pub ahead of print, March 2016
Coeliac disease (CD) is one of the most common, lifelong gastrointestinal disorders in children. One of the most common manifestations of CD in children in iron-deficiency anaemia. Even mild or subclinical anaemia can be detrimental to health since it predisposes to poor cognitive and psychomotor development and to impaired immune defence. This retrospective study compared a variety of clinical, histological, serological and laboratory findings and dietary response between children presenting with and those without anaemia at CD diagnosis.
Journal of Paediatric Gastroenterology and Nutrition, e-pub ahead of print, March 2016
Coeliac disease (CD) is one of the most common, lifelong gastrointestinal disorders in children. One of the most common manifestations of CD in children in iron-deficiency anaemia. Even mild or subclinical anaemia can be detrimental to health since it predisposes to poor cognitive and psychomotor development and to impaired immune defence. This retrospective study compared a variety of clinical, histological, serological and laboratory findings and dietary response between children presenting with and those without anaemia at CD diagnosis.
Serological findings were collected from the medical records of 455 children with biopsy-proven CD diagnosed at the Department of Paediatric Gastroenterology, Tampere University Hospital, Finland from the year 2000 onwards. Children were divided into those with and those without anaemia at the time of CD diagnosis, and all study variables were compared between groups, including:
Serum IgA and tTG and EmA antibodies, and total IgA were measured using validated laboratory techniques. Iron-related laboratory parameters were also measured and recorded as available. A minimum of four distal duodenal biopsies were taken in all cases and the severity of small bowel damage was graded by pathologists into partial villous atrophy, subtotal and total villous atrophy. Adherence to the gluten free diet (GFD) was evaluated after 6-12 months. Haemoglobin, tTG and EmA antibodies were measured after a median of 12 months on a GFD.
Of the 455 children studies, 82 (18%) were found to have anaemia at diagnosis. Children with anaemia were significantly older and had fewer family members with CD compared to non-anaemic patients. The main clinical presentation at diagnosis was more often extraintestinal. Of specific gastrointestinal symptoms, the anaemic patients suffered less from vomiting, and there was also a non-significant trend towards more constipation and less diarrhoea. The median values for both tTG and EmA antibodies were higher in the anaemia group at diagnosis. Anaemic children also had more severe small bowel mucosal damage, with a higher proportion of total villous atrophy.
Children in the anaemia group showed significantly poorer adherence to the GFD at follow-up, however, in all cases there were only occasional lapses and none reported unrestricted gluten consumption. After a median of 12 months on a GFD, coeliac autoantibody and haemoglobin levels were significantly improved in both groups, but the anaemia group still yielded significantly lower median haemoglobin levels than the non-anaemic group. Four subjects suffered from persistent anaemia despite being on a strict GFD and demonstrating good clinical and serological response. Twenty five anaemic children initiated oral iron supplementation after diagnosis (including 3 of the 4 with persistent anaemia). Overall, clinical response to the GFD (as measured by disappearance of symptoms, marked decrease of CD autoantibodies and improvement of growth abnormalities and abnormal laboratory values) was seen in 94.3% of anaemic children and 96.6% of non-anaemic children.
The main finding in this study was that children with anaemia at the time of CD diagnosis had more severe disease in terms of serology and small bowel histology, compared to those without anaemia at diagnosis. In addition, the anaemic children showed incomplete recovery of haemoglobin values, even after a median of 1 year on a GFD. This finding correlates with similar work published within adult coeliac populations1. It seems logical that severe enteropathy should predispose to iron deficiency due to the reduced absorptive surface of the intestine, although this was not supported by a correlating higher incidence of diarrhoea or poorer growth within the anaemic group, as might be expected. It seems possible that anaemia might not simply be an outcome of CD but perhaps also an active player in CD pathogenesis. In a previous study, Matysiak-Budnik et al2 reported that gluten may enter the body via enterocyte transferrin receptors, whose expression is increased during iron deficiency. As a result, anaemia could further promote gluten exposure, leading to a self-perpetuating pathogenic loop.
The authors of this study concluded that the presence of anaemia at CD diagnosis is associated with more advanced clinical and histological presentation. Therefore, early detection of anaemia in this patient group is important to prevent possible permanent complications related to advanced CD. Clinicians should also be aware that the recovery of anaemic patients may take longer than expected, despite a strict GFD and thus special emphasis should be placed on the follow-up of this patient group.
References
- Demographics
- Anthropometrics
- Co-morbidities
- Family history of CD
- Type of clinical presentation (gastrointestinal/ extraintestinal/ screen detected)
- Severity of presentation
Serum IgA and tTG and EmA antibodies, and total IgA were measured using validated laboratory techniques. Iron-related laboratory parameters were also measured and recorded as available. A minimum of four distal duodenal biopsies were taken in all cases and the severity of small bowel damage was graded by pathologists into partial villous atrophy, subtotal and total villous atrophy. Adherence to the gluten free diet (GFD) was evaluated after 6-12 months. Haemoglobin, tTG and EmA antibodies were measured after a median of 12 months on a GFD.
Of the 455 children studies, 82 (18%) were found to have anaemia at diagnosis. Children with anaemia were significantly older and had fewer family members with CD compared to non-anaemic patients. The main clinical presentation at diagnosis was more often extraintestinal. Of specific gastrointestinal symptoms, the anaemic patients suffered less from vomiting, and there was also a non-significant trend towards more constipation and less diarrhoea. The median values for both tTG and EmA antibodies were higher in the anaemia group at diagnosis. Anaemic children also had more severe small bowel mucosal damage, with a higher proportion of total villous atrophy.
Children in the anaemia group showed significantly poorer adherence to the GFD at follow-up, however, in all cases there were only occasional lapses and none reported unrestricted gluten consumption. After a median of 12 months on a GFD, coeliac autoantibody and haemoglobin levels were significantly improved in both groups, but the anaemia group still yielded significantly lower median haemoglobin levels than the non-anaemic group. Four subjects suffered from persistent anaemia despite being on a strict GFD and demonstrating good clinical and serological response. Twenty five anaemic children initiated oral iron supplementation after diagnosis (including 3 of the 4 with persistent anaemia). Overall, clinical response to the GFD (as measured by disappearance of symptoms, marked decrease of CD autoantibodies and improvement of growth abnormalities and abnormal laboratory values) was seen in 94.3% of anaemic children and 96.6% of non-anaemic children.
The main finding in this study was that children with anaemia at the time of CD diagnosis had more severe disease in terms of serology and small bowel histology, compared to those without anaemia at diagnosis. In addition, the anaemic children showed incomplete recovery of haemoglobin values, even after a median of 1 year on a GFD. This finding correlates with similar work published within adult coeliac populations1. It seems logical that severe enteropathy should predispose to iron deficiency due to the reduced absorptive surface of the intestine, although this was not supported by a correlating higher incidence of diarrhoea or poorer growth within the anaemic group, as might be expected. It seems possible that anaemia might not simply be an outcome of CD but perhaps also an active player in CD pathogenesis. In a previous study, Matysiak-Budnik et al2 reported that gluten may enter the body via enterocyte transferrin receptors, whose expression is increased during iron deficiency. As a result, anaemia could further promote gluten exposure, leading to a self-perpetuating pathogenic loop.
The authors of this study concluded that the presence of anaemia at CD diagnosis is associated with more advanced clinical and histological presentation. Therefore, early detection of anaemia in this patient group is important to prevent possible permanent complications related to advanced CD. Clinicians should also be aware that the recovery of anaemic patients may take longer than expected, despite a strict GFD and thus special emphasis should be placed on the follow-up of this patient group.
References
- Abu Daya H, Lebwohl B, Lewis SK et al. Celiac disease patients presenting with anaemia have more severe disease than those presenting with diarrhea. Clinical Gastroenterol Hepatol 2013; 11:1472-7.
- Matysiak-Budnik T, Moura IC, Arcos-Fajardo M et al. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J Exp Med 2008; 205:143-54
www.drschaer-institute.com