AIM: To evaluate the effectiveness of a rapid and easy fingertip whole blood point-of-care test for celiac disease (CD) case finding and diet monitoring.

METHODS: Three hundred individuals, 206 females (68.7%) and 94 males (31.3%), were submitted to a rapid and easy immunoglobulin-A-class fingertip whole blood point-of-care test in the doctor’s office in order to make immediate clinical decisions: 13 healthy controls, 6 with CD suspicion, 46 treated celiacs, 84 relatives of the celiac patients, 69 patients with dyspepsia, 64 with irritable bowel syndrome (IBS), 8 with Crohn’s disease and 9 with other causes of diarrhea.

RESULTS: Upper gastrointestinal endoscopy with duodenal biopsies was performed in patients with CD suspicion and in individuals with positive test outcome: in 83.3% (5/6) of the patients with CD suspicion, in 100% of the patients that admitted gluten-free diet transgressions (6/6), in 3.8% of first-degree relatives (3/79) and in 2.9% of patients with dyspepsia (2/69). In all these individuals duodenal biopsies confirmed CD (Marsh’s histological classification). The studied test showed good correlation with serologic antibodies, endoscopic and histological findings.

CONCLUSION: The point-of-care test was as reliable as conventional serological tests in detecting CD cases and in CD diet monitoring.

Celiac disease (CD) is a multifactorial disorder that occurs in genetically susceptible individuals. CD is considered an immune-mediated enteropathy caused by a permanent intolerance of the small bowel mucosa to gluten, and affects approximately 1% of the world population[1]. In our geographic area the estimated prevalence is 1/475[2]. Individuals with CD can be asymptomatic or can present a variety of gastrointestinal symptoms or extra-intestinal manifestations and often the diagnoses of dyspepsia or irritable bowel syndrome (IBS) are suggested[3]. The diagnosis of CD is based on serologic and histopathologic findings. Antiendomysial (EMA) and anti-tissue transglutaminase antibodies, class IgA, are considered highly specific serological markers for CD. Biopsies of the proximal small bowel in positive individuals for these antibodies confirm the diagnosis of CD[1].

As CD is a disorder that can be ruled out in the differential diagnosis of several gastrointestinal diseases, non-invasive tests are recommended as a first-step to screening patients before small intestinal biopsy to confirm CD[1,4]. Also, gluten-triggered tissue autoantibodies can be determined to aid in monitoring the diet and for case findings of CD in at-risk groups such as relatives[5] and in patients with other autoimmune diseases[6-8].

The conventional tests, EMA determined by indirect immunofluorescence and anti-tTG performed by ELISA, require sera samples, are laborious and time-consuming, need special laboratorial centers, are expensive and the results are available only after a time lag. So, a rapid test, with a result which can be available immediately, will help the physicians to make decisions at their own offices[9].

The aim of this study was to evaluate the effectiveness of a rapid and easy immunoglobulin-A-class whole blood point-of-care test for celiac autoantibody detection in patients routinely seen in the clinic, to enable immediate clinical decisions.

Table 1 shows the positivity of the Biocard Celiac-Test™ with the corresponding percentages.

The test was negative in the controls, in CD patients with strict adherence to a GFD, in the second-degree relatives, in IBS, in Crohn’s disease and diarrhea of different etiologies. Positive tests were detected in 83.3% of patients with suspicion of CD, in 100% of the patients that admitted diet transgressions, in 3.8% of the first-degree relatives and in 2.9% of patients with dyspepsia.

Considering only the female gender, the positivity of the studied test was 75.0% (3/4) for patients with CD suspicion, 66.7% (4/6) for patients with GFD transgressions, 5.3% (3/56) for first-degree relatives, and 4.3% (2/46) for patients with dyspepsia.

One female (HK) was negative for the rapid test, but positive for IgA EmA. Biopsy confirmed CD. IgA anti-tTG was determined in the sera of the patient (HB) with Biocard test positive and IgA EmA negative, with a resulting antibody level of 193 U, and CD confirmed by duodenal biopsy. IgA EmA was also determined in all the individuals with Biocard test positive (n = 16); 2 were negative (12.5%) for these antibodies (Table 2).

Duodenal biopsy was performed in 15 of the 16 individuals with positive Biocard test and recommended for one first-degree relative. Lesions characterized as Marsh III-C were seen in 11 cases or 73.3% (5 CD suspicion, 4 with GFD transgressions, 1 first-degree relative and 1 with and 1 without dyspepsia); Marsh III-A were detected in 2 patients with GFD transgressions and in 1 patient with dyspepsia (20.0%); Marsh type I was seen in one young first-degree relative (6.7%) (mother and aunt with CD). The number of IEL was increased in all the positive individuals (100%). Table 2 shows the demographic data of these individuals in relation to the positivity of IgA EmA and the endoscopic and histological evaluations.

CD has become more common than in the past, and can be diagnosed at any age[1]. However, it frequently remains undetected for long periods of time, because of failure by health care professionals to recognize the disorder, probably due to the variable clinical presentation or failure to perform appropriate diagnostic tests[21].

In the present study, there was a young adult preponderance in all groups, indicating that it is important to exclude CD in the differential diagnosis of gastrointestinal complaints in this age group. However, we must remember that this affliction occurs also in patients of more than 60 years (as is shown here in the case of a male, 62 years, with recent-onset diarrhea)[22].

The female preponderance, also reported by several authors in different countries, alerted us to investigate carefully women with digestive or systemic symptoms[8,23]. When we considered only female gender, we observed that the percentage of CD case findings was higher than the total number of positive individuals in first-degree relatives and in patients with dyspepsia.

In this investigation, in the CD-suspicion group, the point-of-care test was positive in 83.3% (5/6) patients, similar to the report of Korponay-Szabó et al[24]. It is possible that a patient can have only one CD-specific test positive, as was the case of the female patient with Biocard test negative and IgA EmA positive, or the male 62-year-old with this test positive, anti-tTG increased (193 U) and IgA EmA negative (Table 2). These cases demonstrate that more than one test is recommended if CD is suspected[4].

Patients with CD should be evaluated at regular intervals by a health care team, including a physician and a dietician, but there are no clear guidelines as to the optimal means to monitor adherence to a GFD. Dietary compliance as assessed by interview is the best marker of CD due to low cost, non-invasiveness and strong correlation with serological tests and intestinal damage[17]. Repeat serologic testing after 6 mo or more on a GFD can be helpful. The disappearance or decline of CD-specific serum antibodies during a diet is a further indication of dietary adherence and antibody testing is therefore recommended in dietary monitoring of CD (sensitivity varies from 29% to 100%)[24]. However, antibody tests might not reveal slight dietary transgressions[25]. In the present experience, the Biocard test recognized the disappearance of anti-tTG antibodies in all the patients with a GFD compliance and was positive in 14% (6/43) of the patients who admitted transgressions: they were young patients (median age 24 years), confirming the reports that adolescents had difficulties adhering strictly to the diet[26-28]. The positivity of the test presumes major dietary transgressions[25]. Notably, repeat biopsies are no longer required, but in the patients with positive tests the biopsy was performed for correlation (Table 2).

Dietary compliance varies a great deal in CD around the world. The compliance is related to the physician’s recommendations but also to the collaboration of the families. It is important to know about the adherence to a GFD due to the probability of nutritional imbalances in children and adolescents[28]. So, an easy test at the office or at home can be very useful to detect transgressions because positivity rate correlates with dietary lapses[24].

The prevalence of CD in first-degree relatives of patients with CD undergoing intestinal biopsy varies from 5.5%[29] to 22.5%[30]. In a previous study with 115 Brazilian relatives, we reported 15.6% CD prevalence[5], with female preponderance, and in the present study there was 3.8% of test positivity (Table 2)[31]. All were female: 1 sister and 1 daughter of the same family; 1 mother. This mother currently presents severe dyspeptic complaints. Her positivity for the point-of-care test occurred 7 years after the first IgA EmA negative determination, showing that the relatives need to be re-evaluated periodically[32]. In some individuals, only more subtle changes of crypt lengthening with an increase in IEL, or simply an increase in IEL, are present. So, it is important that the slides be viewed by an experienced pathologist familiar with the spectrum of mucosal changes in CD. The example is the patient LGS (Table 2) with positive serologic tests, normal endoscopy and duodenal mucosa with preserved architecture, but with an increased number of IEL[15,16].

In this investigation, there was no positivity in second-degree relatives. However, this was a small group. In a previous study with more Brazilian relatives we reported 5.9% of positivity[32].

Although dyspepsia may be part of the clinical spectrum in CD patients, there are scarce data about its prevalence in silent CD[33]. Duodenal biopsy undertaken during routine upper GI endoscopy in adults has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of CD in high-risk groups such as those with anemia and/or chronic diarrhea.

In this study there was 2.9% of test positivity in dyspepsia patients, both young female patients without diarrhea (Table 1). The correlations with IgA EmA and intestinal biopsy were 100% (Table 2). This result is similar to the findings of Riestra et al[33] in Spain (2.2% also in women); Ozaslan et al[21] in Turkey (1.5% in women). In another Brazilian region, Lima et al[34] reported 1.4% positivity in women. In summary, CD should be kept in mind as a cause of dyspepsia during clinical assessments[35]. Serological screening can be recommended for patients with refractory dyspepsia, especially females[35]. A GFD may still bring symptomatic relief for dyspeptic symptoms in CD[36].

Diarrhea is part of the clinical spectrum of IBS; the habitual tests are normal and the nutritional state is not compromised. There is a female prevalence probably related to hormones[37-39]. In the present study 46 of 64 diarrhea patients were female (71.8%), median age 46.8 years, similar to previous reports[40]. Even when CD was suspected in IBS, none of our patients were positive for anti-tTG point-of-care test (Table 1).

Patients with Crohn’s disease can present chronic diarrhea as the only manifestation. At the beginning of the evaluation, differential diagnosis with CD can be pertinent, mainly in children and adolescents. In this study 62.5% (5/8) were female, mean age 35.6 years, almost the same characteristics of the women with CD[20,40]. None of the patients with Crohn’s disease were positive for the point-of-care test (Table 1).

In the differential diagnosis of chronic diarrhea, a serological test to suggest or rule out CD is pertinent, especially in the doctor’s office, to guide subsequent investigations. In 9 patients of this investigation, who were point-of-care test negative, the final diagnosis confirmed that the patients were not celiac patients[3,41,42].

In a cost-effectiveness analysis in our geographic area, south of Brazil, the cost of IgA EmA or anti-tTG is 8 times the cost of the studied test, another reason to use this screening. The same conclusions were reported by Crovella et al[42] in another Brazilian area (Recife, Northeast).

To conclude, in this study the results of the point-of-care test showed good correlation with positivity of IgA EmA antibodies, endoscopic and histological findings (Table 2). As the test is quick, economical, easy to perform and as reliable as the conventional serological tests in CD case finding and in diet monitoring, it can be performed on site in the physician’s office and in primary care[24,43].