Insufficient Awareness of Celiac Disease in China: Population-Based Screening is Needed
Celiac disease (CD), once considered a gastrointestinal condition, is now recognized as a systemic autoimmune disease triggered by exposure to dietary gluten in individuals carrying specific human leukocyte antigen (HLA) genotypes, primarily HLA-DQ2 or HLA-DQ8. The classic symptoms of CD include intestinal manifestations such as chronic diarrhea, bloating, abdominal pain, constipation, weight loss, or poor growth in children. Additionally, systemic complications like iron-deficiency anemia, osteoporosis, and neuropathy due to vitamin B12 deficiency are frequently observed in celiac patients. The immune response can also extend beyond the intestines, leading to dermatologic conditions such as dermatitis herpetiformis and an increased risk of miscarriage in women.
First described in 1887 by Samuel Gee, CD was historically considered a rare enteropathy affecting individuals of European ancestry. However, recent studies have revealed that CD is a global health issue, with an estimated prevalence of approximately 0.7% worldwide. Despite this, data on CD in China remain scarce, with most cases documented in isolated case reports or small case series. This suggests that the observed cases may represent only the “tip of the iceberg” of CD in China.
The Emerging Prevalence of Celiac Disease in China
The prevalence of CD in China has been underestimated due to limited research and awareness. A study involving 19,778 Chinese adolescents and young adults revealed a prevalence of CD autoimmunity of 2.19%, with higher seropositivity rates in regions where wheat is a staple food. Other studies have explored CD prevalence in specific clinical populations. For instance, Wang et al. found a seroprevalence of 1.77% among patients with diarrhea-predominant irritable bowel syndrome (IBS), with four out of seven seropositive cases confirmed as CD through duodenal histology. Another study reported a seroprevalence of 22% among patients with type 1 diabetes mellitus and autoimmune thyroid diseases. However, in most studies, seropositive individuals did not undergo biopsy for definitive CD diagnosis.
The development of CD is strongly associated with specific HLA haplotypes, particularly HLA-DQ2 and HLA-DQ8. While these haplotypes are present in approximately 25-30% of the Caucasian population, their prevalence in the Chinese population has been considered lower. However, a meta-analysis by Yuan et al. revealed that 3.4% and 2.1% of the Chinese population carry the HLA-DQ2.5 and HLA-DQ8 haplotypes, respectively. The overall prevalence of HLA-DQ antigens in China was found to be 18.4% for HLA-DQ2 and 8% for HLA-DQ8. Despite the slightly lower prevalence of these haplotypes in China, the rarity of CD in the country cannot be fully explained by genetic factors alone.
Dietary habits, particularly wheat consumption, play a significant role in CD prevalence. While it has been suggested that low wheat exposure may contribute to the low prevalence of CD in China, wheat has been a staple food in the country for over 4,000 years, especially in northern regions. Additionally, the consumption of gluten-rich products like “mianjin” is common. As diets in China become increasingly westernized, the incidence of CD is expected to rise in the future.
The Need for Increased Clinical Awareness
Undiagnosed and untreated CD can lead to severe complications, including malabsorption, lymphoma, and a nearly four-fold increased risk of death. Therefore, raising awareness among clinicians is crucial for promoting active case-finding. Patients presenting with symptoms suggestive of malabsorption, such as chronic diarrhea, bloating, and post-prandial abdominal pain, should be tested for CD. Additionally, clinicians should consider CD in patients with unexplained iron-deficiency anemia, elevated liver enzymes, or type 1 diabetes mellitus, as these conditions are often associated with CD. Studies have shown that symptoms and abnormal lab results often improve after initiating a gluten-free diet.
There is a significant overlap in symptoms between CD and IBS, with 20-50% of celiac patients meeting the Rome criteria for IBS. This overlap can lead to misdiagnosis and delayed CD identification. A meta-analysis found that the pooled prevalence of biopsy-proven CD in IBS patients was 3.3%, with an odds ratio of 4.5, indicating a significantly higher prevalence of CD in individuals with IBS-type symptoms. A study in Shandong Province confirmed this trend in the Chinese population, with 2.85% of IBS patients diagnosed with CD. Therefore, pursuing CD diagnosis more aggressively in patients with suspected IBS could facilitate the identification of celiac patients in China.
Establishing a Standardized Diagnosis for Celiac Disease
The diagnosis of CD requires a combination of medical history, physical examination, positive serology, and characteristic duodenal biopsy findings. Immunoglobulin A anti-tissue transglutaminase (tTG) is the preferred serological test, with a sensitivity of approximately 95% and specificity of 95% or greater. However, a single serological test is insufficient for diagnosis, as positive results depend on gluten ingestion, and gluten-free diets can lead to false-negative results. Duodenal biopsy remains the gold standard for CD diagnosis, with findings of increased intraepithelial lymphocytes, crypt hyperplasia, and villous atrophy. Histological improvement after a gluten-free diet can further confirm the diagnosis.
In China, anti-gliadin antibodies (AGAs) have been commonly used in CD studies. However, AGAs are only accurate when the pre-test prevalence of CD is high or in children under two years of age. Endomysium antibodies and antibodies against human tTGs are considered more specific for CD. Therefore, the adoption of highly sensitive and specific screening tests in China is essential.
Standardized tissue acquisition and histological evaluation are critical for accurate CD diagnosis. Villous atrophy in celiac patients can be patchy, so it is recommended to obtain one to two biopsies from the duodenal bulb and at least four biopsies from the distal duodenum. The modified Marsh classification is commonly used for histological evaluation, although some clinicians prefer a more detailed description, such as the villous height-to-crypt depth ratio (normal ratio: 3:1). It is also important to recognize that other conditions, such as common variable immunodeficiency syndrome, AIDS, enteropathy-associated T-cell lymphoma, and autoimmune diseases, can cause villous atrophy in duodenal biopsies.
The Urgent Need for Population-Based Screening in China
The epidemiological burden of CD in China remains unclear, likely due to low awareness among clinicians and limited access to diagnostic procedures. Population-based screening studies are urgently needed to determine the true prevalence of CD in the country. However, it is important to note that seroprevalence does not equate to biopsy-confirmed CD prevalence. Therefore, conducting duodenal biopsies in seropositive individuals is necessary to rule out false-positive cases. If screening studies confirm a significant underdiagnosis of CD, increasing the availability of gluten-free food products in China will be a major challenge. Conversely, if studies reveal a low prevalence of CD, it would be valuable to explore the potential mechanisms or genetic factors that confer gluten tolerance in the Chinese population.
Through active investigation, the hidden portion of the “celiac iceberg” in China is expected to emerge in the coming years. Addressing the lack of awareness and improving diagnostic capabilities will be essential for managing this potentially widespread but underrecognized condition.
doi.org/10.1097/CM9.0000000000000305
Was this helpful?
0 / 0