Demographic Profile and Clinical Presentation of Celiac Disease in the Pakistani Population: A Systematic Review and Meta-analysis

Abstract

Background

Celiac disease (CD) is an increasingly recognized autoimmune enteropathy triggered by gluten ingestion. While its global prevalence is well-documented, data from South Asia, particularly Pakistan, remain fragmented. This systematic review and meta-analysis aimed to consolidate available evidence on the demographic characteristics and clinical presentations of CD in the Pakistani population.

Materials and methods

A comprehensive literature search of PubMed, Google Scholar, and Cochrane databases was conducted in accordance with PRISMA guidelines. Studies were selected based on predefined PICOS criteria, including biopsy and serology-confirmed CD cases from Pakistan. Data extraction focused on demographics, symptoms, histology, laboratory parameters, and autoimmune associations. Statistical analysis was performed using a random-effects model.

Results

Fourteen studies encompassing 1,578 patients were included. The pooled female prevalence was 51.5%, with mean ages of 7.6 years in pediatric and 35.5 years in adult patients. Iron deficiency anemia (65.9%) and diarrhea (64.6%) were the most common clinical presentations. Atypical presentations like bloating, oral ulcers, and psychiatric symptoms were also reported. Histologically, villous atrophy (96.9%) and intraepithelial lymphocytosis (84.5%) were predominant. Celiac disease was associated with autoimmune diseases, notably psoriasis (25%), hypothyroidism (12.6%), and autoimmune hepatitis (12.5%). Family history was reported in 10.6% of cases. Laboratory findings revealed low mean hemoglobin (9.57 gm/dL) and albumin (2.88 gm/dL), indicating nutritional compromise.

Conclusion

Celiac disease in Pakistan presents with a diverse clinical spectrum and frequent extraintestinal manifestations. Delayed diagnosis, nutritional deficiencies, and autoimmune overlap are common. Enhanced awareness and diagnostic accessibility are urgently needed to improve early recognition and management.

Introduction

Celiac disease (CD) is an immune-mediated enteropathy that is triggered by the consumption of gluten in susceptible individuals, presenting with a diversity of gastrointestinal and extraintestinal symptoms, serologic findings of anti-tTG antibodies, and small intestine mucosal injury, including villous atrophy.¹ Once perceived as an infrequent condition, CD is currently established as an international health problem, with its prevalence reaching close to 1% in most populations.² Nonetheless, the burden and epidemiological pattern of the disease can be quite dissimilar according to geographical, ethnic, nutritional, and health-access variables.³

The South Asian population, including that of Pakistan, has traditionally been underrepresented in research on CD.⁴ Although large epidemiologic data of Western populations are available, studies from Pakistan are largely based on small numbers of samples or the experience of individual centers.⁵ Delays in diagnosis continue to be prevalent due to inadequate awareness among physicians, the absence of routine screening, and inconsistent availability of endoscopy and histology.⁶ This quite frequently leaves a large number of undiagnosed or misdiagnosed patients, especially within rural and disadvantaged populations.

In Pakistan, presentation of CD is not always as described classically.⁵ Although diarrhea, weight loss, and abdominal pain are still common, most patients also present with atypical or non-gastrointestinal manifestations like iron deficiency anemia, short stature, irregular periods, or neuropsychiatric symptoms. There is also mounting evidence of CD sharing associated autoimmune disorders like type 1 diabetes, autoimmune hepatitis, and hypothyroidism.⁷ Demographic characteristics, such as age at presentation and gender, also seem to be different and need further studies.

In spite of sporadic accounts of CD from different medical institutions throughout the nation, there is no overall synthesis of published data to provide an insight into the overall demographic and clinical picture of CD in Pakistan's population base. Such data are of great importance in informing national diagnosis strategies, influencing doctor awareness, and ultimately determining earlier detection and management outcomes.

This systematic review and meta-analysis aim to consolidate data from published Pakistani studies to define the demographic characteristics and clinical presentations of patients with CD. The study intends to achieve this by identifying prevailing trends and indicating main gaps, hence presenting an integrated national picture that can be used to inform public health policy as well as clinical practice.

Materials and Methods

This study was conducted according to the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines.⁸ Since this is a review of existing literature, there was no need for ethical approval from the Institutional Review Board (IRB).

Literature Search

Comprehensive literature search was performed by two authors independently using PubMed, Google Scholar, and Cochrane. A literature search was performed based on the following search string ‘[(“CD” OR “coeliac disease”) AND (“Pakistan”) AND (“demographics” OR “clinical presentation” OR “symptoms” OR “abdominal pain” OR “diarrhea” OR “anemia”)]’ (Supplementary Table 1). The search included all relevant articles published up to May 18, 2025. Additional references were identified through manual screening of the bibliographies of selected articles.

Table 1.

Baseline characteristics of the patients with celiac disease

Study name	Study type	Sample size (n)	Mean age (years)	Male (%)	Female (%)	Type of population
Arshad et al.7	Cross-sectional	126	35.5 ± 12.3	38.9	61.1	Adult
Ahmed et al.9	Cross-sectional	33	–	42.4	57.6	Adult
Butt et al.5	Cross-sectional	142	–	37.3	62.7	Adult
Imran et al.10	Cross-sectional	90	–	42.7	57.3	Pediatric
Farina et al.12	Observational	12	–	41.6	58.4	Adult
Masood et al.13	Prospective cohort	60	38 ± 10.5	36.6	63.6	Adult
Jabeen et al.14	Cross-sectional	113	7.27 ± 3.68	42.0	58.0	Adult
Ikram et al.15	Cross-sectional	24	–	55.0	45.0	Adult
Aziz et al.11	Retrospective	66	6.25 ± 1.56	59.1	40.9	Adult
Abbas et al.16	Retrospective	77	–	53.2	46.8	Adult
Khan et al.17	Observational	20	24.30 ± 12.4	55.0	45.0	Adult
Panezai et al.18	Cross-sectional	23	–	82.6	17.4	Adult
Jalil et al.19	Cross-sectional	149	10.2 ± 3.1	53.7	46.3	Pediatric
Jamila et. al.21	Cross-sectional	643	–	54.1	45.9	Pediatric

Study Selection

All those studies were selected, which fulfill the selection criteria described as PICOS: (population) (1): Patients of all age-groups in Pakistan with CD confirmed on the basis pf serology and histology; (2) I (intervention) and (3) C (comparison) was not applicable as it was an observational study; (4) O (outcome): demographic data, clinical symptoms, histopathological findings, laboratory parameters, and autoimmune associations; (5) S (studies): studies that were published in the English language and were either cross-sectional or cohort studies. All studies not meeting the above-mentioned criteria were excluded.

Inclusion and Exclusion Criteria

Studies conducted on the Pakistani population with biopsy and serology confirmed CD, and participants reporting demographic or clinical data were enrolled in our meta-analysis.

Exclusion Criteria

Case reports, editorials, review articles, and studies lacking extractable patient-level data and duplicates or overlapping study populations were excluded from the study.

Data Extraction

Two independent reviewers screened titles and abstracts for relevance. Full texts were retrieved for potentially eligible studies. Discrepancies were resolved through mutual discussion. Of the 59 initially identified records, 51 were retained after removing duplicates. Full-text screening was conducted for 36 articles, and finally, 14 studies were included in the meta-analysis. A structured data extraction form was used to collect relevant variables from each study. Extracted data included: author name, publication year, study design, sample size, age and gender distribution, clinical symptoms, laboratory and histopathological findings, family history of CD, and presence of associated autoimmune conditions.

Quality Assessment and Publication Bias

Each included study was assessed for methodological quality using the Newcastle–Ottawa Scale (NOS), which evaluates participant selection, comparability, and outcome assessment. Studies were classified as high (7–9 points), moderate (5–6 points), or low (<5 points) quality.

Statistical Analysis

Statistical analysis was carried out by using the Review Manager (version 5.4; Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2020). Pooled prevalence and mean values were calculated. A random-effects model was applied to account for expected heterogeneity across studies. For continuous variables such as hemoglobin and albumin, pooled mean differences with 95% confidence intervals (CI) were calculated. For categorical variables such as symptom frequency, pooled proportions were computed. Heterogeneity was assessed using the I² statistic, with values above 50% considered substantial.

Results

Initial Literature Search and Basic Study Characteristics

A total of 69 studies were initially identified through the search strategy. After removing 8 duplicates, 61 articles were screened based on title and abstract. Full texts were assessed for 37 studies, and ultimately 14 met the eligibility criteria for inclusion.^5,7,9–20 These studies encompassed a cumulative population of 1,578 patients with biopsy and serology-confirmed CD. Studies varied in design, included both pediatric and adult populations, and were predominantly cross-sectional (Fig. 1; Table 1).

Fig. 1.

PRISMA flow diagram showing the initial literature search and included studies in meta-analysis

Quality and Publication Bias Assessment

All included studies were subjected to quality assessment using the NOS. Of the 14 studies, five were graded as high quality, seven as moderate, and two as low-quality studies. Most studies performed well in participant selection and outcome ascertainment, but comparability between groups was less frequently addressed (Supplementary Table 2).

Demographics of CD in Pakistan

The pooled prevalence of female patients was 51.48% (95% CI: 45.14–57.82), indicating a slight female predominance. Pediatric patients had a pooled mean age of 7.64 years (95% CI: 7.37–7.91), while adult patients had a mean age of 35.46 years (95% CI: 33.86–37.06). These data were derived from both retrospective and prospective studies, along with cross-sectional studies across various provinces in Pakistan (Fig. 2).

Fig. 2.

Forest plot showing prevalence of female gender in the celiac disease population

Clinical Presentations of CD in Pakistan

Iron deficiency anemia was the most common presenting symptom observed in 65.92% (95% CI: 61.98–69.86) followed by diarrhea in 64.6% (95% CI: 60.85–68.35), stunted growth in 58.74% (95% CI: 53.83–63.65) bloating in 58.5% (95% CI: 53.42–63.58), and abdominal pain in 49.7% (95% CI: 46.05–53.35). Among the less frequent manifestations, oral ulcers were observed in 19.36% (95% CI: 15.31–23.41), menstrual irregularities were noticeably observed in 17.53% (95% CI: 10.29–24.77), while psychiatric disturbances were observed in 12.7% (95% CI: 6.90–18.50) (Fig. 3).

Fig. 3.

Forest plot showing clinical presentation of celiac disease in the Pakistani population

Histological Features Associated with CD

Three key histopathological features were consistently reported: villous atrophy in 96.87% (95% CI: 95.67–98.07), increased intraepithelial lymphocytes in 84.46% (95% CI: 81.87–87.05), and crypt hyperplasia in 14.47% (95% CI: 11.45–17.49) (Fig. 4).

Fig. 4.

Forest plot showing histological changes in celiac disease

Association of CD with Other Disorders

In our population, various autoimmune conditions were observed to be associated with CD. Among them, psoriasis was the most commonly observed associated autoimmune condition noticed in 25% (95% CI: 17.346–32.64) followed by hypothyroidism in 12.65% (95% CI: 9.34–15.96), autoimmune hepatitis (AIH) in 12.5% (95% CI: 6.82–18.18), and diabetes mellitus in 10.64% (95% CI: 6.38–14.90). Other less commonly associated conditions were PCOS in 11% (95% CI: 5.9–16.1), osteoporosis in 8.35% (95% CI: 4.34–12.36), and SLE in 8.3% (95% CI: 3.4–13.20). The pooled prevalence of autoimmune conditions was 11.41% (95% CI: 9.69–13.14), indicating a strong link between CD and other autoimmune disorders (Fig. 5).

Fig. 5.

Forest plot showing the association of celiac disease with other disorders

Family History of CD

Four studies reported data on family history. The pooled prevalence of positive family history was 10.55% (95% CI: 5.57–15.52) (Fig. 6).

Fig. 6.

Forest plot showing prevalence of family history of celiac disease

Laboratory Parameters

Laboratory parameters included serum albumin, hemoglobin, and alanine transaminase (ALT). The pooled mean serum albumin was 2.88 gm/dL (95% CI: 2.74–3.02), while the mean hemoglobin was 9.57 gm/dL (95% CI: 9.41–9.74), indicating a widespread burden of anemia and malnutrition. Alanine transaminase levels were reported in four studies, with a pooled mean of 33.54 U/L (95% CI: 33.24–33.84), which may indicate hepatic involvement or comorbid liver disease like AIH in some patients (Fig. 7).

Fig. 7.

Laboratory parameters in patients with celiac disease. (A) Mean albumin; (B) Mean hemoglobin; (C) Mean ALT

Discussion

This meta-analysis consolidates the current knowledge regarding the demographic profiles and the variety of clinical presentations of CD in the Pakistani population. In this study, we extracted data from 14 studies with a combined sample of 1,578 patients.

One of the key observations we derived from this study was the association of female gender with CD in the Pakistani population. This synchronizes with worldwide data proposing a superior incidence rate for CD in females, explained by a generalized female predisposition towards autoimmune diseases.²² All European and North American studies provide a female-to-male CD cohort ratio ranging from 2:1 to 3:1.^23,24 However, in the Pakistani population, this ratio is less than 2:1, which can be attributed to discrepancies in culture and poor access to healthcare and late presentation to the gastroenterology outpatient clinics.

Age-wise, pediatric and adult individuals had different presentations, with a mean age of 7.64 years and 35.46 years, respectively. This broad age range indicates both early and late diagnoses, in each case probably related to different extents of clinical awareness and infrastructural provision. Western nations, where screening within at-risk populations is more prevalent, have earlier median ages of diagnosis.²⁵ In Pakistan, most are diagnosed only when severe or unusual symptoms develop, a consequence of both limited physician exposure to CD and restricted means for diagnosis in peripheral health facilities.

Clinically, iron deficiency anemia (65.9%) and chronic diarrhea (64.6%) were the most frequently observed findings in our population. These are consistent with global literature, where iron deficiency anemia was found to be the most frequent extraintestinal symptom of CD.²⁶ The prevalence of anemia in our cohort may also be aggravated by endemic nutritional deficiencies.²⁷ Likewise, diarrhea (58.7%) and stunted stature in children are consistent with reports from children in other low- and middle-income countries where they have a high prevalence rate of chronic malnourishment.²⁸

In our population, atypical presentations like bloating (58.5%), abdominal pain (49.7%), oral ulcers (19.3%), and psychiatric symptoms (12.7%) were relatively common. This consolidates with prior knowledge that CD, especially in adults, often presents with atypical symptoms. Unlike prior studies, in which atypical presentations were largely overshadowed by gastrointestinal symptoms, current studies from Western populations more commonly highlight atypical and silent presentations.^29,30 The current findings affirm Pakistani clinicians’ need to remain suspicious when faced with such heterogeneous symptomatology.

Histologically, the most common finding was villous atrophy (96.8%) and intraepithelial lymphocytosis (84.5%). These findings are consistent with the Marsh classification criteria commonly utilized in CD diagnosis by clinicians throughout the world.³⁰ In relation to European data where Marsh III lesions prevail, our data manifest with a comparable trend, validating our spectrum of pathology.

In our population, we noticed that CD was associated with many other conditions, especially autoimmune conditions like psoriasis (25%), hypothyroidism (12.6%), autoimmune hepatitis (12.5%), and type 1 diabetes mellitus (10.6%). International literature, as by Li Voon Chong et al.,^31,32 has recurrently described a strong correlation between CD and autoimmune thyroiditis and type 1 diabetes. Our findings confirm this trend, with regional variation (e.g., increased psoriasis rates), potentially due to local genetic and environmental influences unique to South Asia.

We observed a family history of CD in only 10.5% of patients, a rate lower than that observed in Western populations, from 15 to 20%.³³ This can be attributed to the lack of knowledge and unawareness, or cultural barriers to tracing familial disease histories in Pakistani settings.

Finally, in our study, we observed the association of biochemical alterations such as low average hemoglobin (9.57 gm/dL) and albumin (2.88 gm/dL) levels with CD; thus, they reflect advanced disease at the time of presentation, frequently following severe nutritional deprivation. By contrast, studies from Scandinavian nations indicate less severe biochemical alterations at diagnosis because of early screening and intervention.³⁴ Overall, this meta-analysis highlights delayed diagnosis and diagnostic complexity of CD in Pakistan, with varied clinical presentations, severe nutritional deficiencies, and underestimated autoimmune overlap. These findings necessitate national awareness programs, including CD in differential diagnoses for non-specific complaints, and strengthening capabilities in diagnostic modalities.

This study has some limitations. First, the included studies were heterogeneous in terms of study design, sample size, population type, diagnostic criteria, and reported outcomes. Second, most studies were observational and cross-sectional in nature, which limits the ability to establish causal associations. Third, data on several important variables, including duration of symptoms, adherence to a gluten-free diet, long-term outcomes, and regional variation within Pakistan, were inconsistently reported. Fourth, some outcomes were derived from a limited number of studies, which may reduce the precision of pooled estimates. Finally, publication bias and underreporting cannot be completely excluded, especially because data on celiac disease from Pakistan remain limited and largely based on single-center experiences.

Conclusion

In summary, this systematic review and meta-analysis highlight the wide range of presentation and large burden of illness of CD in the Pakistani population. Iron-deficiency anemia, diarrhea, stunted growth, and bloating—when combined with atypical presentations of psychiatric illness and menstrual abnormalities—represent delayed diagnosis and low awareness of CD among the Pakistani population. The strong association with autoimmune diseases, including hypothyroidism, autoimmune hepatitis, and psoriasis, indicates the systemic nature of the condition and presses on the evaluation of these conditions at the time of diagnosis of CD. These observations underscore the pressing need for increased physician awareness, the regular inclusion of CD in the evaluation of nonspecific GI and extraintestinal complaints, and improved access to diagnostic services throughout Pakistan to enable earlier diagnosis and reduce disease-related morbidity.

This systematic review and meta-analysis provides a consolidated overview of the demographic profile and clinical presentation of celiac disease in the Pakistani population. The findings highlight that celiac disease frequently presents with iron-deficiency anemia, diarrhea, stunted growth, bloating, and other atypical extraintestinal manifestations. The study also emphasizes the association of celiac disease with autoimmune disorders, including hypothyroidism, autoimmune hepatitis, and psoriasis. These findings are clinically important because they support the need for greater physician awareness, earlier diagnostic evaluation, and improved access to serological and histological testing in Pakistan, particularly among patients with unexplained anemia, chronic gastrointestinal symptoms, growth failure, or autoimmune disease.

Acknowledgment

The corresponding author would like to acknowledge the support of the clinical, administrative, and researches involved in facilitating this study.

Authors’ Contributions

All authors contributed substantially to the conception and design of the study, data collection, data analysis, interpretation of results, manuscript drafting, and critical revision of the manuscript. All authors reviewed and approved the final version of the manuscript and agree to be accountable for the accuracy and integrity of the work.

Supplementary Materials

The supplementary tables 1 and 2 are available on its journal website www.ejohg.com

Orcid

Raja TY Khan https://orcid.org/0000-0002-5504-5084

Data Availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.