|Year : 2019 | Volume
| Issue : 1 | Page : 23-28
Celiac disease in children
Anjum Saeed1, Asaad Mohamed Assiri2, Huma Arshad Cheema3
1 Department of Pediatrics, Division of Pediatric Gastroenterology, The Children's Hospital, Lahore, Pakistan; Prince Abdullah Bin Khalid Celiac Disease Research Chair, King Saud University Medical City, Riyadh, Saudi Arabia
2 Prince Abdullah Bin Khalid Celiac Disease Research Chair, King Saud University Medical City; Department of Pediatric, College of Medicine, King Saud University Medical City, Riyadh, Saudi Arabia
3 Department of Pediatrics, Division of Pediatric Gastroenterology, The Children's Hospital, Lahore, Pakistan
|Date of Web Publication||7-Jan-2019|
Division of Pediatric, Gastroenterology, Department of Pediatrics, The Children's Hospital, Lahore
Source of Support: None, Conflict of Interest: None
Celiac disease (CD) is a chronic enteropathy due to ingestion of gluten and related products leading to villous injury and its various manifestations. It has a strong genetic tendency with the presence of human leukocyte antigen (HLA-DQ 2, DQ 8) in more than 98% of these patients with CD. Western studies documented 0.5%–1% prevalence of CD but it is not an uncommon condition in the Arabic peninsula. Classical gastrointestinal (GI) manifestations are common in the toddler's age group while non-GI manifestations predominate in the adolescents and older children. High-risk groups and associated conditions need special considerations for screening CD. European and Americans guidelines are available for diagnosing these children and recommend to screen with anti-tissue transglutaminase antibodies which have got very high sensitivity and specificity. North American guidelines recommend to do small bowel biopsies and interpreted by Marsh grading. Gluten-free diet for the rest of life is still a recognized therapy for these children under the supervision of an expert dietician dealing with CD. National awareness programs and seminars may help in identifying this underdiagnosed condition to avoid morbidity and mortality related to this lifelong disorder.
Keywords: Celiac disease, children, gluten-free diet
|How to cite this article:|
Saeed A, Assiri AM, Cheema HA. Celiac disease in children. J Nat Sci Med 2019;2:23-8
| Introduction|| |
Celiac disease (CD) also called gluten-sensitive enteropathy has been known since long time and thefirst scientific contribution was made by Samuel Gee in 1888. A lot of work has been done to know about epidemiology, exact genetic link, environmental factors and clinical presentation in the last two decades. CD is not an uncommon disease having a prevalence of about 0.5%–1% in the general population in the west. Exact prevalence is not known in Saudi Arabia due to lack of national epidemiological studies but recent reports showed a high prevalence of CD in Saudi Arabia.
CD with underlying autoimmune pathogenesis triggers an immune response in genetically susceptible individuals when gluten is ingested. With persistent exposure to specific protein present in different products such as wheat, barley and rye damages the villous part of small intestine leading to various manifestations of the disease. There is a strong genetic association of CD with human leukocyte antigen (HLA) class II haplotypes DQ2 and DQ8 which is present in more than 98% individuals with CD.,
The clinical presentation of CD is variable being nonclassical presentation predominant in the current literature. Classical CD presents with chronic malabsorptive diarrhea, abdominal distension, failure to thrive while nonclassical CD presents with short stature, resistant anemia, constipation, rickets, and seizure disorder. One of the rare presentation is celiac crises which is difficult to manage if not picked and treated well in time.,,,
The diagnosis of CD is based on clinical suspicion, serological markers, and small bowel biopsies. With the newer serological screening tools such as anti-tissue transglutaminase antibodies (tTG), antiendomysial antibodies, and deamidated antigliadin antibodies, a lot of new CD cases are being picked up. Endoscopy with small bowel biopsies is still considered the gold standard for CD patients., Marsh-Oberhuber scoring is being used to grade or classify the disease which range from preinfiltrative to flat destructive (0°C–3°C, respectively).
The management of CD should be multidisciplinary involving primary physician, expert dietician, pediatric gastroenterologist, and input from the national celiac organization for available resources of natural and prepared gluten-free diet (GFD). The most important treatment aspect of confirmed CD is lifelong adherence to GFD and regular follow-up with the treating physician and dietician. With proper compliance to GFD, children usually catch up their growth potential, and other complications associated with the disease can be prevented., In this review, we discuss epidemiology, pathogenesis, current classification, diagnostic modalities, and treatment of this important and frequently encountered condition according to the current available literature.
| Epidemiology|| |
CD was primarily considered a disease of Europeans, but with the technological advances and availability of very powerful serological tests, a good number of cases are being reported from the developing countries. The prevalence of CD has been increasingly recognized in the last two decades from worldwide. Western data showed a prevalence of 3–13/1000 individuals with higher frequency in 1st degree relatives of CD.,
Due to lack of national epidemiological studies, exact prevalence is not known in Saudi children, but recent workup showed a high rate of CD in this part of the world. Data from other Arab countries such as Egypt and Tunisia also indicate a common disease in Arab population. Other countries having high incidence of CD include South Asia, Africa, Mediterranean countries whereas it appears to be rare disease in China. The children of Sweden populations are at the greatest risk among all other countries.,,,
| Pathogenesis|| |
The precise mechanism of immunological events leading to mucosal damage in CD is still to be developed, but the main event of the sequence seems an interaction of tTG modified gliadin peptide to the HLA-DQ molecule as an antigen presentation to the T cells., The gliadin modified by the tTG has a great affinity for the DQ-2 peptide-binding groove and also proposed stimulus for anti-tTG antibodies leading to T-cell activation with the formation of cytokines. This process is thought to occur in discrete regions just under the intestinal mucosal epithelium in patients with CD, but the precise sequence of events culminating in mucosal remodeling remains unclear. As of the T-cell role in the pathogenesis, humoral response in the intestinal mucosal changes may also be involved. This is evident by tTG antibodies which are known to inhibit transforming growth factor affecting the integrity of the villous structure. Understanding the probable immune mechanisms leading to mucosal damage in CD is essential if alternative non-dietary therapies are to be developed in the future.
The genetic basis of the disease is shown by frequent intrafamilial clustering and significant association with HLA. Human leukocyte antigen DQ2 and DQ8 are present in more than 99% patients with CD against 40% presence in the general population. The presence of HLA-DQ2 and DQ8 is necessary for the development of CD but it is not sufficient, and another gene or genes at some non-HLA locus must be involved. Non-HLA genes presumably are stronger determinant for disease association than HLA genes. Moreover, HLA typing may be helpful in those setting where small bowel biopsies are not conclusive with high index of suspicion of CD as the absence of HLA-DQ2 and DQ8 certainly rules out the possibility of CD.,,
High risk and associated autoimmune conditions
In general, it is observed that autoimmune disorders have a genetic factor with an environmental stimulus to initiate clinical disease. As an autoimmune basis, certain autoimmune disorders and syndromes have significant association with the CD including type 1 diabetes, autoimmune hypothyroidism, autoimmune hepatitis, connective tissue disorder, Down syndrome, Turner and William syndromes. In addition to above-mentioned high-risk group, 1st and 2nd degree relatives and IgA deficient patients are also at high risk for CD.,,,,,,, A summary of associated conditions and autoimmune disorders is given in [Table 1].
|Table 1: Gastrointestinal and nongastrointestinal presentation, high risk conditions, and different associations of CD patients|
Click here to view
Infections and feeding practices
Infections are still considered as one of the predisposing factors for the development of CD in children, but other factors such as antibiotics use, breastfeeding, and gluten introduction at an earlier age do not confer validity in multiple studies. Two large randomized trials from Europe showed no difference between CD and breastfeeding and gluten introduction and ESPGHAN recommends to start gluten between 4 and 12 months of life safely. In addition, no evidence was found between milk protein introduction and development of CD.
Role of microbiome
The current research is mainly focused on the role of microbiota in the development of CD in children. Few recent studies showed the altered microbiota in these patients and explained the association of microbiota and development of immune system in CD.
| Oslo Classification of Celiac Disease|| |
CD is subtyped into four different categories based on presentation as per Oslo classification which include classical (typical), nonclassical (atypical), subclinical (asymptomatic), and potential CD. Classical CD presents with chronic malabsorptive diarrhea, abdominal distension, failure to thrive, and wasting between 1 and 2 years of life, but the current literature reports high or equal frequency in older children with nonclassical CD. Nonclassical (atypical) CD has minimal or absent malabsorptive symptoms, and usual pattern of presentation includes short stature, pallor, isolated vomiting or constipation, recurrent abdominal pain, ataxia, seizure disorder, and unexplained rickets. This is becoming a predominant mode of presentation, especially in older children and adolescents. Some symptoms may overlap between these 2 types. In both classical and nonclassical CD, the serologic test results are abnormal and varying degrees of villous atrophy is present. In subclinical CD, previously referred to as asymptomatic CD, the disease is below the threshold of clinical detection without symptoms or signs sufficient to trigger CD testing in routine clinical practice. Some of these individuals might be screened as they have a high risk of developing CD. These patients will have abnormal serologic test results, as well as villous atrophy. In potential CD, previously called latent CD, the patient has an abnormal antibody test, but normal small intestinal histology. Several of these individuals will develop the intestinal lesion over time, thus requiring careful monitoring and follow-up.
| Clinical Manifestations|| |
Trend of clinical manifestations has been changing with more atypical features and increasing age at the development of symptoms of CD-like adolescents and young adults and reported in literature over the last two decades., The CD is more prevalent in females due to unknown reasons. Gastrointestinal (GI) manifestations are still observed in early childhood, but non-GI features are now equally common. Supposedly, environmental triggers are considered one of the factors in this change in clinical presentation or alternatively, due to greater appreciation of the protean nature of the condition.,
The clinical presentation of CD in pediatrics differs from that of adult patients. The most common GI clinical presentation includes loose motions that remain persistent, recurrent abdominal pain or discomfort, bloating, anorexia, and vomiting. Chronic malabsorptive diarrhea leads to growth failure and other micronutrient deficiencies. Constipation may be one of the presenting symptoms in children.,,, Celiac crises is another rare but well-recognized presentation and the trigger of crises is usually uncontrolled diarrhea leading to electrolyte imbalance, shock, metabolic acidosis, and death if not managed well in time. A summary of associated conditions and autoimmune disorders is given in [Table 1].
Apart from intestinal symptoms, some of CD patients also observe extraintestinal symptoms which needs high index of suspicion. These symptoms include short stature, resistant iron deficiency anemia, hypothyroidism, unexplained rickets, pubertal delay, menstrual irregularities, recurrent abortions, dental enamel deformities, dermatitis herpetiformis, epilepsy, cardiomyopathy, pancreatitis, weakness, and lethargy.,,,,,,,,, A summary of associated conditions and autoimmune disorders is given in [Table 1].
| Diagnosis of Celiac Disease|| |
Diagnosis of CD is based on high index of clinical suspicion, serological markers, and small bowel biopsies. North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) suggests small bowel biopsies in all the suspected cases whereas European (ESPGHAN) put forward the criteria for the diagnosis excluding biopsies.
One of the most common screening tests performed for the diagnosis of CD is the detection of IgA tTG and is being done on those consuming normal diet. The sensitivity and specificity (95% and 96%, respectively) of tTG is excellent in picking up CD cases and currently recommended screening test by both NASPGHAN and ESPGHAN. In younger children <2 years of age, tTG is not very sensitive, deamidated antigliadin, and antiendomysial antibodies are preferred. In cases of IgA deficiency, IgG-based tTG, and deamidated antigliadin antibodies are recommended though the sensitivity is not very high. Antigliadin antibodies and anti-reticulin antibodies are not recommended anymore and obsolete because of very low sensitivity.,,,,
A summary is given in [Table 2] describing sensitivities and specificities for different commonly used serological tests in children for CD.
|Table 2: Different tests with sensitivities and specificities used in children|
Click here to view
Endoscopic small bowel biopsies are considered gold standard for the diagnosis of CD. Because of patchy nature of disease, multiple biopsies are suggested from the second part of duodenum and duodenal cap to increase the yield of diagnosis. Scalloping and flat mucosa may suggest endoscopic diagnosis but not confirmatory. Marsh-Oberhuber scoring is being used to grade or classify the disease which range from preinfiltrative to flat destructive (0°C–3°C respectively) as shown in [Table 3]. Marsh type 3 is confirmed celiac and type 2 with positive tTG is also considered positive CD.,,,
| Treatment|| |
Gluten free diet (GFD) which include wheat, barley, and rye for the rest of life is still the most effective and recognized therapy for the CD patients., An experienced dietician supervision for these patients is required in reference to compliance and monitoring for growth percentile. Once compliance is reassured there is remarkable clinical improvement with disappearance of antibodies and normal intestinal mucosa in 6 months to 1-year duration.,, Oats are considered safe and tolerated well if taken care not contaminated with wheat during production and cultivation. Dietary measures in addition to GFD are sometimes required in the initial management which include avoidance of lactose, provision of vitamins (fat soluble and water soluble), and iron supplements. Rarely corticosteroids are required for the treatment of life-threatening situations during a celiac crisis. Alternative therapies in addition to GFD involving immunomodulation and other mechanistic hit may become reality in future.,,
| Conclusion|| |
CD is one of the common GI disorders with a broad spectrum of clinical presentation and affects all age groups with familial clustering. High-risk conditions need to be vigilantly screened as well as autoimmune disorders if any suspicion arises. Very powerful and strong serological markers are available for screening these suspected children. Small bowel biopsies with Marsh interpretation are still considered mandatory for confirmation of CD. GFD for rest of life under the supervision of an experienced dietician is still recognized as a sole therapy for these affected children. Societal and national awareness workshops and seminars need to be held more often for early screening and detection of this rising entity to prevent the morbidity and mortality with appropriate and timely taken measures.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]