Saudi Journal of Gastroenterology
Home About us Instructions Submission Subscribe Advertise Contact Login    Print this page  Email this page Small font sizeDefault font sizeIncrease font size 
Users Online: 6322 

ARTICLES Table of Contents   
Year : 2003  |  Volume : 9  |  Issue : 2  |  Page : 75-78
The significance of elevated serologic markers of celiac disease in children with juvenile rheumatoid arthritis

1 Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
2 Department of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Click here for correspondence address and email

Date of Submission15-Oct-2002
Date of Acceptance15-Mar-2003


Aim: The aim of this study is to determine the frequency of celiac disease (CD) in a group of children with juvenile rheumatoid arthritis (JRA) and determine the correlation between the presence of the serologic markers and the histological diagnosis of CD. Patients and Methods : Forty-two children (24 females) with JRA, aged between 5-15 years underwent study of serologic markers for CD (gliadin-IgA, gliadin-IgG, reticulin and endomysium-IgA antibodies). Endoscopic intestinal biopsy was performed in patients who had positive serologic markers for CD. The diagnosis of CD was based on the classic finding of villous atrophy and crypt hypertrophy. Results: Eighteen patients (42.8%) had serologic markers for CD; ten of them with a systemic form, five with a polyarticular form and three with a pauciarticular form of JRA. Levels of AGA ­IgG were high in 14 patients (77.8%), four patients (22.2%) had high levels of AGA-IgA and seven patients (38.9%) had anti-endomysium antibodies (AEA). One patient had anti-reticulin antibodies (ARA) 5.5%. Sixteen patients underwent intestinal biopsy; in only one patient with AEA antibodies (2.38%), biopsy revealed typical finding of CD. The patient with CD showed improvement in both growth parameter as well as articular symptoms after starting gluten-free diet Conclusion: Our study shows that the screening for silent CD among children with JRA may be useful. Those patients with AEA need further follow up since these antibodies are quite sensitive and specific for CD

Keywords: Juvenile rheumatoid arthritis, celiac disease, antigliadin antibodies

How to cite this article:
Al-Mayouf SM, Al-Mehaidib AI, Alkaff MA. The significance of elevated serologic markers of celiac disease in children with juvenile rheumatoid arthritis. Saudi J Gastroenterol 2003;9:75-8

How to cite this URL:
Al-Mayouf SM, Al-Mehaidib AI, Alkaff MA. The significance of elevated serologic markers of celiac disease in children with juvenile rheumatoid arthritis. Saudi J Gastroenterol [serial online] 2003 [cited 2022 Nov 29];9:75-8. Available from:

Children with juvenile rheumatoid arthritis (JRA) may develop gastrointestinal symptoms and growth failure either as part of the disease itself or as a complication of the treatment. However, primary gastrointestinal diseases including CD were described in different rheumatic diseases including chronic idiopathic arthritis [1],[2],[3] . Knowing that CD may exist as a latent or clinically silent in children; [4] we investigated the frequency of CD among a group of children with JRA and tried to explore if there is correlation between the presence of the serologic markers and the histological diagnosis of CD.

   Patients and Methods Top

A cross-sectional study involved 42 children with JRA, (24 females), whose ages ranged from 5-15 years) and all patients were followed at the pediatric rheumatology clinic at King Faisal Specialist Hospital and Research Center, Riyadh. The diagnosis of JRA based on the criteria established by the American College of rheumatology (ACR) [5] . Twenty-seven patients (64.3%)had a systemic form, ten (23.8%) had a polyarticular form and five (11.9%) had a pauciarticular form of JRA. None of the patients was known to have CD. Clinical characteristics of the patients including gastrointestinal symptoms, anthropometric measurement and medication at the time of screening were recorded. All patients underwent screening for CD by determination of the antigliadin (AGA) IgG and IgA, antireticulin (ARA) and antiendomysium (AEA) IgA antibodies. The AGA­IgG and IgA antibodies were determined with modified enzyme-linked immunosorbent assay (ELISA) method known as flouroenzyme immune assay (FEIA) using Pharmacia UniCAP-100 system. The ARA and AEA-IgA antibodies were determined with indirect immunofluorescence methods using rat kidney and monkey esophagus tissue substrate respectively (INOVA CAT# 508170 and 508330). The lower limit of positivity for AGA-IgG was l8mg/L and that for AGA-IgA 3mg/L, while the results of ARA and AEA-1,A were expressed semi­quantitatively as negative, weakly positive or strongly positive. Patients in whom serologic markers for CD (at least one of the four screening markers) were detected, underwent endoscopic intestinal biopsy. The diagnosis of CD was based on the classic finding of villous atrophy and crypt hyperplasia. The procedure was performed after an informed consent from the parents was obtained.

   Results Top

Eighteen out of 42 screened JRA children (42.8%) were positive for at least one of the serologic markers for CD. Twelve had gastrointestinal symptoms in term of anorexia; abdominal pain, vomiting or diarrhea and 24 children had inadequate growth parameters (weight or height below the third percentile or both). There was no significant difference in the clinical characteristics or medication between children with positive and negative serologic markers for CD [Table - 1]. The levels of AGA-IgG were high in 14 children (77.8%) and of these, 6 were suffering from a systemic form, five from a polyarticular form and three from a pauciarticular form. Four children (22.2%) had high levels of AGA-IgA (three systemic form and one polyarticular form) and seven patients (38.9%) had AEA-IgA (six had systemic form and one had polyarticular form) while only one patient (5.5%) had ARA antibodies [Table - 2]. Sixteen patients underwent the intestinal biopsy, while two patients refused the procedure. None of the patients had complication. Only one patient had typical villous atrophy and crypt hyperplasia consistent with CD.

She had a systemic form of JRA with severe polyarticular pattern requiring Prednisone 1­2mg/kg/day, naproxen 15m-/kg/day and methotrexate 15mg/m2/week. She was suffering from gastrointestinal symptoms and her height and weight curves were below the 3 rd percentile. All her serologic markers for CD were detected. She showed improvement in her growth parameters as well as the articular symptoms after starting the gluten-free diet. On the other hand, intestinal biopsy revealed mild focal villous atrophy in two patients with systemic form of JRA, both of them had positive AEA-IgA. The histology findings are not diagnostic of celiac disease in these two patients, however, they may be potential to develop celiac disease in the future. Details of the correlation between the clinical features, the serologic markers for CD and the result of intestinal biopsy are shown in [Table - 2].

   Discussion Top

Children with JRA may present with significant gastrointestinal symptoms and growth failure. Though most of these complications are induced by the medications or the disease itself, other possibilities including primary gastrointestinal diseases should be considered. Several studies have shown an association between CD and different rheumatic diseases [1],[2],[6] Celiac disease has been described in children with chronic idiopathic arthritis [3],[7] . The clinical spectrum of CD is wide, varying from CD with malabsorption and nutritional deficiency to clinically silent disease [4] .

Determination of serologic markers is widely used as a non-invasive method of screening for CD.

These markers are variable in sensitivity and specificity for diagnosis of CD but the most reliable diagnostic marker is AEA with high positive and negative predictive values (97% and 98% respectively [8],[9] . However, it is generally accepted that the appearance of flat small intestinal mucosa with the histological features of hyperplastic crypts while the patient is eating a normal diet containing gluten is essential for a diagnosis of CD [10] Nonetheless latent expressed and silent CD maybe more common than expected [4] . There are few described patients in whom the initial intestinal biopsy was normal but who were later found to have CD [11],[12] . Some authors suggested to identify a CD silent/ latent CD, is to measure specific serologic markers such as AEA [13] . In our study, we screened 42 children with JRA, 36 patients had either gastrointestinal symptoms or growth failure. We found a frequency of CD of 2.38%, which is in agreement with other studies [6],[7] . Two patients had mild focal intestinal villous atrophy in presence of positive AEA, gastrointestinal symptoms and/or growth failure. Rebiopsy after a follow-up period may confirm the typical histological features of CD in those patients; this may increase the frequency of CD in our JRA population up to 7%. All of our symptom-free patients with isolated AGA-IgG had normal biopsy; this may confirm that elevated AGA­ IgG might be one of the non-specific inflammatory markers of JRA [14] . In contrast three patients with gastrointestinal symptoms and/or growth failure and positive AEA had abnormal biopsy. We may conclude from this study that AEA screening for CD among children with JRA may be useful. Those patients with positive AEA antibodies need further follow up since these antibodies are quite sensitive and specific for CD.

   References Top

1.Collin P, Maki M. Associated disorders in celiac disease: clinical aspects. Scand Gastroentrol 1994: 29: 769-75.  Back to cited text no. 1    
2.Buderus S, Wagner N, Lentze M. Concurrence of celiac disease and juvenile dermatomyositis: result of a specific immunogenetic susceptibility? J Pediatr Gastroentrol Nutr 1997; 25: 101-3.  Back to cited text no. 2    
3.Lepore L, Martelossi S. Pennesi M, Falcini F, Frmini M, Ferrari R, Perticarari S, et al. Presence of celiac disease in patients with juvenile chronic arthritis. J Pediatr 1996; 129: 311-3.  Back to cited text no. 3    
4.Ferguson A, Arranz E, O'mahony S. Clinical and pathological spectrum of coeliac disease-active, silent, latent, potential. Gut 1993; 34: 150-1.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Cassidy J, Levinson J, Bass J, et al. A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum 1986; 29: 274­81.  Back to cited text no. 5    
6.Collin P, Korpela M, Hallstrom 0, Viander M, Keyrilainen O, Maki M. Rheumatic complaints as presenting symptom in patients with coeliac disease. Scand J Rheumatol 1992; 21: 20-3.  Back to cited text no. 6    
7.George E, Cate R, Van Suijlekom-Smit L, Van Blomberg B, Stapel S, Van Elburg R, Mearin M. ,Juvenile chronic arthritis and coeliac disease in the Netherlands. Clin Experim Rheumatol 1996; 14: 571­5.  Back to cited text no. 7    
8.Rossi T, Tjota A. Serologic indicators of celiac disease. J Pediatr Gastroentrol Nut 1998; 26: 205-10.  Back to cited text no. 8    
9.Chan K, Phillips A, Mirakan R, Walker-Smith J. Endomysial antibody screening in children. J Pediatr Gastroentrol Nut 1994; 18: 316-20.  Back to cited text no. 9    
10.Walker-Smith J, Guanalini S, Schmitz J, Shmerling D, Visakorpi J. Revised criteria for diagnosis of coeliac disease. Arch Dis Child 1990; 65: 909-11.  Back to cited text no. 10    
11.Maki M, Holm K, Koslamies S, Hallstrom O, Visakorpi J. Normal small bowel biopsy followed by coeliac disease. Arch Dis Child 1990; 65: 1137-41.  Back to cited text no. 11    
12.Collin P, Helin H, Maki M, Hallstrom 0, Karvoven A. Follow-up of patients positive in reticulin and gliadin antibody tests with normal small-bowel biopsy findings. Scand J Gastroentrol 1993; 28:595­8.  Back to cited text no. 12    
13.Korponay I, Koracs J, Lorincz M, Goracz G, Szabados K, Balogh M. Prospective significance of antiendomysium antibody positively in subsequently verified celiac disease. J Pediatr Gastroentrol Nut 1997; 25: 56-63.  Back to cited text no. 13    
14.Lepore L, Pennesi M, Ventura A, Torre G, Folcini F. Lucchesi A, Perticarari S. Anti-alpha-gliadin antibodies are not predictive of celiac disease in juvenile chronic arthritis. Acta Pediatr 1993; 82: 569­73.  Back to cited text no. 14    

Correspondence Address:
Sulaiman Mohammed Al-Mayouf
Consultant and Head, Section of Rheumatology Service, King Faisal Specialist Hospital and Research Centre, P.O Box 3354, Riyadh 11211
Saudi Arabia
Login to access the Email id

Source of Support: None, Conflict of Interest: None

PMID: 19861810

Rights and PermissionsRights and Permissions


  [Table - 1], [Table - 2]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

    Patients and Methods
    Article Tables

 Article Access Statistics
    PDF Downloaded1    
    Comments [Add]    

Recommend this journal