Celiac Disease Patients Presenting With Anemia Have More Severe Disease Than Those Presenting With Diarrhea

doi:10.1016/j.cgh.2013.05.030

Clinical Gastroenterology and Hepatology

Volume 11, Issue 11, November 2013, Pages 1472-1477

https://doi.org/10.1016/j.cgh.2013.05.030 Get rights and content

Background & Aims

Anemia is considered to be an atypical or silent presentation of celiac disease, compared with the classic presentation with diarrhea. However, little information is available about how these groups compare in terms of disease severity. We compared the severity of celiac disease between patients who present with anemia vs those who present with diarrhea.

Methods

The study cohort was selected from a database of patients with celiac disease who were evaluated at a tertiary referral center between 1990 and 2011. Severity of celiac disease was assessed by the degree of villous atrophy and clinical and serologic parameters. Patients were compared according to mode of presentation and sex. Multivariable analyses, adjusting for age and sex, were conducted to assess the association between the mode of celiac disease presentation and cholesterol level, bone density, severity of villous atrophy, erythrocyte sedimentation rate, and level of anti–tissue transglutaminase.

Results

Of 727 patients, 77% presented with diarrhea and 23% with anemia (92% iron deficient). On multiple regression analysis, presentation with anemia was associated with lower levels of total cholesterol (P = .02) and high-density lipoprotein (P = .002) and a higher erythrocyte sedimentation rate (P = .001) and level of anti–tissue transglutaminase (P = .01). Presentation with anemia was associated with lower level of cholesterol only in women. Anemic patients were more than 2-fold more likely to have severe villous atrophy and a low bone mass density at the time they were diagnosed with celiac disease than patients who presented with diarrhea.

Conclusions

Celiac disease patients who present with anemia have more severe disease than those who present with diarrhea. There also appear to be sex-specific differences with regard to the association between anemia and the different features of celiac disease.

Section snippets

Study Design and Subjects

Patients were selected for analysis from a database of 1451 CD patients who were evaluated at a tertiary referral center. We classify patients into their major mode of presentation, ie, the reason they were tested and diagnosed with CD.²¹ The presentations are (1) a classic presentation of diarrhea/malabsorption; (2) anemia; (3) reduced bone mineral density (BMD); (4) the recognition of findings at endoscopy performed for reasons other than assessment of malabsorption/diarrhea or anemia; (5)

Results

Of 1451 patients in the database, 727 patients (50%) met the inclusion criterion of having a presentation with anemia or diarrhea; 562 (77%) presented with diarrhea and 165 (23%) with anemia (Figure 1). Iron deficiency anemia was predominant among anemic patients (92%). Patients presenting initially with anemia were older than those who presented with diarrhea (45 ± 15 vs 42 ± 18 years, P = .07), whereas both groups had female preponderance (∼70%) and similar body mass index (BMI) (∼23 kg/m²) (

Discussion

Although indices of symptoms²⁶ and quality of life²⁷ have been developed in CD, there is no current standard method of global disease assessment of severity in CD as there is for patients with inflammatory bowel disease. Intuitively, patients presenting with diarrhea may be considered to be more severely affected, but there is little evidence to support this.17, 19 Our study showed a significant association between presentation with anemia and more severe clinical, serologic, and histologic

Acknowledgments

Part of this research was submitted to the American Gastroenterological Association meeting (Digestive Diseases Week) in Orlando, Florida in 2013.

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Currently, the atypical CD form is the most common with non-digestive symptoms. The increase in severity in these symptoms not related to CD has been associated with an heterogeneous immune response which is able to interfere with the diagnosis [11]. Therefore, early detection of CD is necessary in order to reduce the risk due to continuous gluten exposure, especially in patients with extraintestinal manifestations which can lead to a late diagnosis of the disease, unlike patients with classical CD whose typical gastrointestinal symptoms allow an early diagnosis [12].
In clinical practice, celiac disease (CD) is monitored through anti-transglutaminase (TGA-IgA) antibody levels. The normalization of serum levels in successive periodic measurements indicates good response and adherence to dietary treatment.
To evaluate the factors associated with the evolution of TGA-IgA antibodies and their association with dietary non-compliance and diseases related to CD.
This prospective observational study was carried out in 254 participants, who were recruited from patients from a hospital in southern Spain. Information about sex, age, serological test results, HLA DQ2/DQ8 haplotypes, mucosal atrophy, gastrointestinal and extra-intestinal symptoms, as well as diagnosis of diseases related to CD, was collected.
Clinical manifestations, such as diarrhoea, abdominal pain and weight loss, showed differences according to sex and age. Children under 18 years of age presented a degree of total or severe atrophy of the intestinal villi. TGA-IgA antibodies concentrations were directly associated with the number of digestive disorders manifested by the patient and the record of dietary non-compliance and inversely related to the number of extra-digestive disorders.
Adolescents between 12 and 18 years old were the least monitored as well as the group with more extra-intestinal symptoms reported. Therefore, it is necessary to develop strategies in clinical practice aimed at this population group and continuous monitoring should be implemented to improve life quality and reduce complications that may arise in the long term.
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Furthermore, healing often is delayed and incomplete in adults compared with the pediatric population.24,25 Although complications of malnutrition, such as anemia,4,26,27 muscle wasting, bone loss, and delayed wound healing, remain the main concern in CeD patients noncompliant with a GFD, they also are at high risk for refractory CeD and malignancy.16 It is suggested that women with CeD have a higher miscarriage risk.28,29
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. In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients.
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Diagnostic findings and long-term prognosis in children with anemia undergoing GI endoscopies
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In these circumstances, the presence of anemia rarely influences the decision to perform endoscopy. Nevertheless, anemia predicts more severe histopathology in celiac disease37-39 and could thus support EGD in cases with borderline positive serology. In case of IBD suspicion, the hemoglobin level may affect the urgency of endoscopies.
Intestinal diseases are regarded as a common cause of anemia, but the diagnostic outcomes of children with anemia undergoing endoscopic investigations are unclear. We investigated this issue in a large cohort of children.
Indications for and findings of consecutive gastrointestinal (GI) endoscopies were collected. Clinical presentation and diagnostic outcomes were compared between anemic and nonanemic patients and between anemic patients with and without a diagnosis. Diagnoses received during follow-up were collected.
Of 2395 consecutive endoscopies, 251 children with and 613 children without anemia had undergone either diagnostic esophagogastroduodenoscopy (EGD) (51.4% and 51.4%, respectively), colonoscopy (4.0% and 11.4%), or both (45.8% and 37.8%). Children with anemia more often received diagnoses (72.9% vs 39.3%; odds ratio [OR], 4.18; 95% confidence interval [CI], 3.03-5.77), particularly of celiac disease (26.3% vs 15.5%, P < .001) and of inflammatory bowel disease (31.1% vs 9.1%, P < .001), than did nonanemic children. The diagnosis in anemic patients was predicted by age 5 to 12 years (OR, 3.52; 95% CI, 1.27-9.75), presence of diarrhea (OR, 2.04; 95% CI, 1.07-3.90), melena/hematochezia (OR, 2.40; 95% CI, 1.17-4.92), poor growth (OR, 3.94; 95% CI, 1.70-9.15), positive celiac serology (OR, 11.81; 95% CI, 3.47-40.12), high calprotectin (OR, 12.86; 95% CI, 4.00-41.32), hypersedimentation (OR, 2.65; 95% CI, 1.29-5.44), and hypoalbuminemia (OR, 5.05; 95% CI, 1.56-16.34). Thirty children with anemia (12.0%) had no GI symptoms, and 22 of them (73.3%) were given diagnoses at the time of the endoscopies. All 22 had additional laboratory abnormalities, whereas these were present in only 2 of 8 undiagnosed children. None of them was diagnosed later in the follow-up of up to 11 years, in contrast to 4 (6.7%) of all anemic and 33 (8.9%) of all nonanemic patients.
Anemia increased the probability of being given a diagnosis, emphasizing its importance as an alarm symptom. However, endoscopies in anemic patients without additional symptoms or laboratory abnormalities seldom improved the diagnostic yield.
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: Conflicts of interest The authors disclose no conflicts.

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Original articleAlimentary tractCeliac Disease Patients Presenting With Anemia Have More Severe Disease Than Those Presenting With Diarrhea

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Design and Subjects

Results

Discussion

Acknowledgments

Lancet

Am J Gastroenterol

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Clin Gastroenterol Hepatol

Gastroenterology

Digestive and Liver Disease

Clin Gastroenterol Hepatol

Am J Gastroenterol

Am J Gastroenterol

Am J Med

Gastroenterology

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study

Arch Intern Med

Seroprevalence, correlates, and characteristics of undetected coeliac disease in England

Gut

Effect of gender on the manifestations of celiac disease: evidence for greater malabsorption in men

Scand J Gastroenterol

Trends in the presentation of celiac disease

Am J Med

Anemia in celiac disease is multifactorial in etiology

Am J Hematol

Symptoms and haematologic features in consecutive adult coeliac patients

Scand J Gastroenterol

Celiac disease

N Engl J Med

Prediction of clinical and mucosal severity of coeliac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase

J Pediatr Gastroenterol Nutr

Original article
Alimentary tract
Celiac Disease Patients Presenting With Anemia Have More Severe Disease Than Those Presenting With Diarrhea