Global trends in incidence and prevalence of achalasia, 1925–2021: A systematic review and meta‐analysis

Abstract

Background

Achalasia poses a significant socioeconomic burden, yet global trends remain undocumented. This study aims to describe the worldwide trends in the incidence and prevalence of achalasia from 1925 to 2021 and explore their correlation with various factors through a comprehensive systematic review.

Methods

We searched the PubMed/MEDLINE, Embase, and Cochrane databases from inception to 30 June 2023, to identify studies reporting the incidence or prevalence of achalasia in the general population. This study utilized pooled estimates with 95% confidence intervals (CI) to estimate the incidence and prevalence of achalasia, and conducted various subgroup analyses.

Results

A total of 26 eligible studies covering approximately 269 million participants and 20,873 patients from 14 countries across five continents were included. Global pooled incidence and prevalence of achalasia were estimated to be 0.78 cases per 100,000 person‐years (95% CI, 0.64–0.93; number of studies, 26; sample population, 269,315,171) and 10.82 cases per 100,000 person‐years (95% CI, 8.15–13.48; number of studies, 14; sample population, 192,176,076), respectively. The incidence of achalasia was higher in Oceania (than Asia and Africa) and in adults (than children) after the introduction of the Chicago classification. Prevalence followed a similar pattern. The pooled incidence of achalasia showed an overall upward trend from 1925 to 2021 (1925–1999; 0.40 [0.32–0.49] vs. 2018–2021; 1.64 [1.33–1.95] cases per 100,000 person‐years).

Conclusions

The incidence and prevalence of achalasia have notably increased, particularly with advancements in diagnosis, and show significant variation worldwide, despite the large heterogeneity within the sample population. Further studies are necessary to accurately assess the global incidence and prevalence of achalasia.

Key summary.

Summarise the established knowledge of this study

• Achalasia is a rare motility disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter, and has a high economic burden due to serious symptoms and risk factors for malignancy.

What are the significant and/or new findings of this study?

• Global pooled incidence and prevalence of achalasia were estimated to be 0.78 cases per 100,000 person‐years and 10.82 cases per 100,000 person‐years.

• The incidence of achalasia was higher in Oceania (compared to Asia and Africa) and in adults (compared to children) after the introduction of the Chicago classification.

• The incidence and prevalence of achalasia tended to gradually increase over time, and this became noticeable with the development of novel diagnostic tools and the introduction of systematic diagnostic criteria.

INTRODUCTION

Achalasia is a rare motility disorder of the esophagus characterized by impaired relaxation of the lower esophageal sphincter. ¹ Not only does this condition impose high economic burdens, but it also poses a significant risk factor for esophageal cancer. ¹ , ²

Considering the studies organized thus far or the pathophysiological mechanism, the incidence and prevalence of achalasia increase with age and are known to be common in patients in their 50s or older. ¹ , ² However, no studies have systematically analyzed differences between races or countries or specified changes in worldwide incidence and prevalence based on variations in years and diagnostic criteria/tools.

Understanding the global incidence and prevalence of achalasia and its temporal trends is crucial for informing medical policies and guiding future research directions. Therefore, this study aims to comprehensively analyze the global, regional, and national trends in the incidence and prevalence of achalasia from 1925 to 2021, including various subgroup analyses.

METHODS

This systematic literature review and meta‐analysis were undertaken to examine global trends in the incidence and prevalence of achalasia. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, ³ and the protocol was registered in PROSPERO (CRD42023457597).

Search strategy and study selection

We conducted a comprehensive search of PubMed/MEDLINE, Embase, and Cochrane databases from their inception to 30 June 2023, to identify studies reporting the incidence or prevalence of achalasia. These studies utilized appropriate diagnostic methods relevant to the time of the study and encompassed all age groups. Eligibility criteria included studies with participants from the general population or community‐based datasets.

To ensure the validity of our results, several exclusion criteria were applied. Studies lacking essential measures such as the number of cases, population, year of occurrence, or collection period were excluded. We utilized the calculation results from the included studies, entering only the incidence (or prevalence) and the corresponding population with an exact date and period match. Additionally, biased samples, including individuals attending health checkups at screening clinics, employees at institutions, or university students, were excluded. Studies with the same target population or fewer than 50 participants were also omitted. Given the absence of interventional studies, our inclusion criteria were limited to general population‐based observational studies with larger sample sizes. Language restrictions were not imposed, and when necessary, content was verified through translation.

The databases were searched using the terms “achalasia,” which were combined using the set operator “AND” with studies identified using the terms “incidence” or “prevalence” as free text terms. Initially, 1221 studies were screened; subsequently, the titles and abstracts of all selected studies were rescreened to identify potential suitability. Non‐eligible studies were excluded after the initial screening. A recursive search was performed using the bibliographies of all eligible papers. Two investigators (KL and WC) independently assessed the eligibility for the study, and disagreements were resolved through discussion with a third investigator (DKY).

Data extraction and statistical analysis

Data were independently extracted by two investigators (KL and WC) using Microsoft Excel 2013 (Microsoft, Redmond, WA, USA). The following data were collected from each study: the first author, year, country, region, number of cases, study period, study design, population, data source, and diagnosis. The incidence and prevalence rates of achalasia in the total population and subgroups were extracted from each study. As representative incidence and prevalence for each study, we used the mean annual values. If the included studies provided data for individual years, we used the data for each year. Otherwise, we used the mean annual incidence based on the middle year of the study period. All studies were assessed for risk of bias (RoB) using the criteria developed by Hoy et al. ⁴ Based on an evaluation of nine items, a study was deemed to have low RoB if three or fewer items were relevant, and high RoB if seven or more were applicable.

Subgroup analyses were conducted based on sex, age group (adults and children), year group (before 2000, 2000–2009, 2010–2013, 2014–2017, and 2018–2021), national development level, continent (Africa [Algeria, Zimbabwe], Asia [Israel, Japan, Singapore, South Korea], Europe [Iceland, Italy, Netherlands, United Kingdom], North America [Canada, United States], Oceania [Australia, New Zealand]), data source (research validated and code‐based), and diagnostic criteria (before and after 2009). ⁵ We classified countries into two groups based on the human development index (HDI). ⁶ The first group consisted of countries with an HDI greater than 0.92, which included Canada, Japan, the Netherlands, New Zealand, Singapore, South Korea, the United Kingdom, and the United States. The second group comprises countries with an HDI lower than 0.92, such as Algeria, Israel, Italy, and Zimbabwe. We assumed that the cases were randomly sampled from the population and that the incidence and prevalence rates were approximately normally distributed.

A Der Simonian and Laird random‐effects model was used to estimate the pooled estimate for global incidence and prevalence, along with 95% confidence intervals (CIs). Heterogeneity was quantified using the I² statistic via Q‐statistics. ⁷ Egger's regression test was employed in this meta‐analysis to assess publication bias. ⁸ Furthermore, a 95% prediction interval was calculated to make predictions about the effect size of a new study that would be expected to arise from the same population as the included studies. ³ This interval provides a range within which the true effect size of the new study is likely to fall with a certain level of confidence. Microsoft Excel and R software (version 3.1.1; R Foundation, Vienna, Austria) were used to calculate the main results and generate all tables. Statistical significance was set at two‐sided p < 0.05.

RESULTS

Initially, the search strategy identified 2306 studies. Of these, 26 studies met the eligibility criteria, ² , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² , ³³ involving 269,315,171 participants and 20,873 patients with achalasia from 14 countries across five continents. Figure 1 shows a global incidence and prevalence map, and figure S1 summarizes the results of the search strategy. Data of patients with achalasia from 1922 to 2021 were extracted, and all studies were conducted in a single country. Table 1 shows the details of all the included studies. The studies included in the analysis encompass both code‐based and researcher‐validated studies, not exclusively reliant on the diagnosis with high‐resolution manometry (HRM). Thus, for a comprehensive analysis, we examined all studies that initially defined participants as achalasia during the study period. Additionally, we selected and analyzed studies that align with the current standard for achalasia, specifically researcher‐validated studies utilizing HRM for diagnosis. The incidence and prevalence data are presented in Table S1, while the incidence trend is illustrated in Figure S2.

FIGURE 1.

Global incidence (a) and prevalence (b) of achalasia, 1925–2021. Pooled estimates: cases per 100,000 population.

TABLE 1.

Summary of the included studies.

First author, year	Country	Region	Mean annual incidence		Study period	Study design	Population	Data source	Diagnosis
			Cases, n	Total (male/female)
Arber et al., 1993	Israel	Tel aviv	162	0.97 (0.95/0.99)	1973–1983	Retrospective	All	Hospital	EM, endoscopy, esophagography
Birgisson et al., 2007	Iceland	‐	62	0.55 (0.58/0.52)	1952–2002	Retrospective	All	Database, manual searching	ICD code, EM, esophagography
Duffield et al., 2017	Australia	South	288	2.30 (2.55/2.05)	2004–2013	Prospective	Adults	Australian Bureau of statistics	EM
Earlam et al., 1969	United States	Rochester	7	0.58 (1.04/0.17)	1925–1964	Retrospective	All	Mayo clinic, medical institutions	Esophagography
Farrukh et al., 2008	United Kingdom	Leicester	14	0.89 (1.17/0.62)	1986–2005	Retrospective	Adults	National census	EM, endoscopy, esophagography
Galen et al., 1982	United States	Virginia	31	0.61	1975–1978	Retrospective	All	Medical college of Virginia	EM, endoscopy, esophagography
Gennaro et al., 2011	Italy	Veneto	365	1.59 (1.59/1.58)	2001–2005	Retrospective	All	Hospital discharge database	ICD‐9, case notes
Harvey et al., 2019	United Kingdom	England	10,509	1.99 (2.02/1.97)	2006–2015	Retrospective	All	Hospital episode statistics	ICD‐9, EM, endoscopy
			711	1.53 (1.47/1.60)				The health improvement network
Ho et al., 1999	Singapore	‐	48	0.29 (0.30/0.28)	1989–1996	Prospective	All	National University hospital	EM, endoscopy, esophagography
Howard et al., 1992	United Kingdom	Edinburgh	38	0.81 (0.80/0.83)	1986–1991	Retrospective	All	City hospital	EM
Inoue et al., 2023	Australia	West	296	1.50 (1.50/1.51)	2012–2021	Retrospective	All	Royal Perth hospital	HRM
Kim et al., 2014	South Korea	‐	191	0.39 (0.33/0.44)	2007–2011	Retrospective	All	National health insurance	ICD‐10
Kim et al., 2023	South Korea	‐	3065	0.67 (0.63/0.71)	2009–2017	Retrospective	All	National health insurance	ICD‐10
Marlais et al., 2011	United Kingdom	Total	228	0.18	1998–2008	Retrospective	Children (<16 years)	British association of Pediatric Surgeons database	ICD‐10
		England	193	0.18
		Northern Ireland	25	0.24
		Scotland	7	0.11
		Wales	3	0.07
Mayberry et al., 1980	United Kingdom	Cardiff	48	0.40 (0.24/0.41)	1926–1977	Retrospective	All	Hospital	EM, endoscopy, esophagography
Mayberry et al., 1985	United Kingdom	Nottingham	53	0.51	1966–1983	Retrospective	All	Hospital	EM, endoscopy, esophagography
Mayberry et al., 1987	United Kingdom	England	216	0.9 (0.9/0.9)	1972–1983	Retrospective	All	Hospital	Case notes
		Scotland	699	1.15 (1.10/1.20)
Mayberry et al., 1988	United Kingdom	Eire	15	0.31	1976–1985	Retrospective	Children (<15 years)	British association of Pediatric Surgeons	Case notes
		England and Wales	106	0.10
		Northern Ireland	7	0.06
		Scotland	1	0.02
Mayberry et al., 1988	New Zealand	North and South Island	152	0.95 (0.94/0.97)	1980–1984	Retrospective	All	National health statistics center	Case notes
Sadowski et al., 2010	Canada	Alberta	463	1.63 (1.85/1.43)	1996–2007	Retrospective	All	Alberta health ministry database	ICD‐9, 10, procedure code
Samo et al., 2017	United States	Chicago	246	1.07 (1.05/1.10)	2004–2014	Retrospective	Adults	Northwestern medicine enterprise data Warehouse database	HRM
Sato et al., 2019	Japan	‐	289	0.40 (0.44/0.37)	2005–2017	Retrospective	All	Japan medical data center database	ICD‐10
Smits et al., 2016	Netherlands	‐	87	0.10 (0.12/0.08)	1990–2013	Retrospective	Children (<18 years)	Dutch governmental database	EM, endoscopy, esophagography, HRM
Stein et al., 1985	Zimbabwe	Bulawayo, Harare	25	0.03 (0.05/0.02)	1974–1983	Retrospective	All	Hospital	Endoscopy, esophagography, case notes
Tebaibia et al., 2016	Algeria	Wilayas	1256	0.16 (0.15/0.16)	1990–2014	Prospective	All	Continuing medical education	EM, endoscopy, esophagography
van Hoeij et al., 2018	Netherlands	‐	907	2.2 (2.2/2.2)	2006–2014	Retrospective	Adults	Dutch healthcare insurance company	ICD‐10

Abbreviations: EM, Esophageal manometry (conventional); HRM, High resolution manometry; ICD‐9,10, International Classification of Diseases ninth, 10th Revision.

Global pooled incidence of achalasia

A total of 26 studies had incidence data, ² , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ , ²² , ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² , ³³ and the global pooled incidence of achalasia was 0.78 cases per 100,000 person‐years (95% CI, 0.64–0.93; I ² = 99.230%), with a 95% prediction interval of −0.03–1.60 (Table 2).

TABLE 2.

Global incidence of Achalasia from 1925 to 2021.

	Included studies (subgroup a )	Number of participants	Pooled estimates (95% CI), cases per 100,000 population	Heterogeneity I 2, %	Egger's p‐value	95% prediction interval
Overall	26 (32)	269,315,171	0.78 (0.64–0.93)	99.230	0.014	−0.03–1.60
Sex
Male	22 (24)	119,473,703	0.90 (0.69–1.10)	97.346	0.001	−0.07–1.86
Female	22 (24)	120,375,948	0.85 (0.65–1.05)	97.999	<0.001	−0.10–1.80
Age group
Adults	4 (4)	8,001,692	1.64 (0.90–2.38)	94.168	0.628	−1.88–5.16
Children	3 (6)	28,285,163	0.10 (0.03–0.18)	94.335	0.627	−0.15–0.36
Year group b
1925–1999	14 (29)	73,849,982	0.40 (0.32–0.49)	88.700	<0.001	0.06–0.74
2000–2009	12 (35)	433,169,613	1.45 (1.19–1.72)	99.032	<0.001	−0.10–3.01
2010–2013	8 (28)	510,769,779	1.51 (1.25–1.77)	98.899	0.005	0.12–2.90
2014–2017	5 (14)	337,301,126	1.37 (1.03–1.71)	98.774	0.155	−0.02–2.76
2018–2021	1 (4)	8,303,716	1.64 (1.33–1.95)	19.938	0.001	0.73–2.55
Development
HDI >0.92	22 (28)	224,329,780	0.80 (0.64–0.97)	99.230	0.030	−0.07–1.68
HDI <0.92	4 (4)	45,485,331	0.65 (0.28–1.02)	99.173	0.231	−1.09–2.39
Continent
Africa	2 (2)	39,361,585	0.09 (−0.03–0.21)	94.657	NA	NA
Asia	5 (5)	109,213,195	0.50 (0.27–0.74)	95.645	0.351	−0.36–1.45
Europe	12 (17)	104,787,037	0.76 (0.56–0.97)	99.254	0.017	−0.14–1.67
North America	4 (4)	9,549,125	0.94 (0.54–1.34)	87.026	0.115	−0.91–2.79
Oceania	3 (4)	6,404,229	1.41 (0.74–2.08)	96.679	0.762	−1.82–4.63
Data source
Researcher validated	20 (26)	145,540,201	0.77 (0.59–0.95)	99.067	<0.001	−0.15–1.69
Code‐base	6 (6)	124,274,910	0.82 (0.52–1.13)	99.439	0.622	−0.26–1.91
Diagnostic criteria b
Before 2009	24 (64)	507,019,595	1.02 (0.88–1.16)	98.716	<0.001	−0.04–2.07
After 2009	8 (46)	856,374,620	1.48 (1.28–1.69)	98.759	<0.001	0.19–2.77

^a Subgroups represent regions or districts in the included studies.

^b If the included studies provided individual year data, we used those data; otherwise, we used the mean annual incidence based on the middle year of the study period.

Auxiliary to Table 2 results, Table S3 compares subgroup differences in the incidence of achalasia in this study. A total of 22 studies had information on sex; the incidence was 0.90 cases per 100,000 person‐years (95% CI, 0.69–1.10) in males and 0.85 cases per 100,000 person‐years (95% CI, 0.65–1.05) in females. The incidence in adults was 1.64 cases per 100,000 person‐years (95% CI, 0.90–2.38), whereas the incidence in children was 0.10 cases per 100,000 person‐years (95% CI, 0.03–0.18). This difference was statistically significant (p < 0.001). Based on the study year, the global incidence of achalasia tended to increase overall, and the difference has been remarkable since 2000, when HRM was introduced (Figure 2 and Table 2). In addition, when comparing the two groups based on whether CC 2009 was enacted or not, 1.02 cases per 100,000 person‐years (95% CI, 0.88–1.16) before CC and 1.48 cases per 100,000 person‐years (95% CI, 0.90–2.38) after CC were found, which were also statistically significant (p < 0.001). The incidence was also compared between country groups divided by an HDI of 0.92. The incidence of countries with HDI >0.92 was 0.80 cases per 100,000 person‐years (95% CI, 0.64–0.97), and the incidence of countries with HDI <0.92 was 0.65 cases per 100,000 person‐years (95% CI, 0.28–1.02), but the difference was not statistically significant (p = 0.468). When examined by continent, the incidence in Africa was the lowest (0.09 cases per 100,000 person‐years [95% CI, −0.03–0.21]), followed by Asia, Europe, and North America, and the highest in Oceania, with 1.41 cases per 100,000 person‐years (95% CI, 0.74–2.08). For further details, please refer to Table S3. According to the data source, in the subgroup analysis, one group used researcher‐validated sources, such as test results or surgical records, and the other used diagnostic codes or surgery/procedure codes for achalasia treatment. When comparing the two groups, the difference in incidence was insignificant (0.77 vs. 0.82 cases per 100,000 person‐years, p = 0.782). Nevertheless, comparisons between subgroups may lack validity due to significant heterogeneity. The pooled incidence of achalasia showed an overall upward trend from 1925 to 2021 (1925–1999; 0.40 [0.32–0.49] vs. 2018–2021; 1.64 [1.33–1.95] cases per 100,000 person‐years) (Figure 2).

FIGURE 2.

Temporal trends in incidence (a) and prevalence (b) of achalasia, 1925–2021. Pooled estimates: cases per 100,000 population.

Global pooled prevalence of achalasia

In our systematic review, 14 studies ² , ¹² , ¹⁴ , ¹⁸ , ¹⁹ , ²¹ , ²⁴ , ²⁶ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² , ³³ with prevalence data were used to estimate the global pooled prevalence of achalasia (Table 3). It was estimated to be 10.82 cases per 100,000 person‐years (95% CI, 8.15–13.48; I ² = 99.619%) with a 95% prediction interval of −0.56–22.20. In prevalence, subgroup analysis (Table S4) was performed, and the items compared were the same as in incidence. There was no significant difference in prevalence according to sex (8.97 cases per 100,000 person‐years [95% CI, 2.02–15.93] vs. 7.64 cases per 100,000 person‐years [95% CI, 2.31–12.98]. As in the incidence, adults had a significantly higher prevalence compared with children (15.41 cases per 100,000 person‐years [95% CI, 13.67–17.14] vs. 0.90 cases per 100,000 person‐years [95% CI, 0.66–1.14]. In the continental comparison, there were no African prevalence data; therefore, only the remaining four continents were compared. Asia had the lowest prevalence (6.83 cases per 100,000 person‐years [95% CI, 3.96–9.67]), Oceania had the highest prevalence (16.90 cases per 100,000 person‐years [95% CI, 15.13–18.67]), and there was little difference between Europe and North America (12.63 vs. 12.57 cases per 100,000 person‐years, respectively). In the intercontinental bilateral comparison, some values were significant, whereas others were not (Table S4). Conversely, there was a slight difference in the prevalence by country classification based on the HDI (10.68 cases per 100,000 person‐years [95% CI, 7.97–13.38] in HDI >0.92 vs. 12.60 cases per 100,000 person‐years [95% CI, 11.72–13.46] in HDI <0.92) and the prevalence according to the data source (11.67 cases per 100,000 person‐years [95% CI, 7.04–16.30] in researcher validated vs. 9.33 cases per 100,000 person‐years [95% CI, 6.40–12.27] in code‐based). Both were statistically insignificant (p = 0.185 in HDI and p = 0.403 in the data source). It's important to note that, similar to the incidence findings, differences between subgroups could be inaccurate due to heterogeneity.

TABLE 3.

Global prevalence of Achalasia from 1952 to 2021.

	Included studies (subgroup a )	Number of participants a	Pooled estimates (95% CI), cases per 100,000 population	Heterogeneity I 2, %	Egger's p‐value	95% prediction interval
Overall	14	192,176,076	10.82 (8.15–13.48)	99.619	0.443	−0.56–22.20
Sex
Male	4	28,289,376	8.97 (2.02–15.93)	98.775	0.109	−24.94–42.89
Female	4	28,155,847	7.64 (2.31–12.98)	98.345	0.051	−19.59–34.88
Age group
Adults	2	6,734,464	15.41 (13.67–17.14)	67.093	NA	NA
Children	1	6,214,286	0.90 (0.66–1.14)	NA	NA	NA
Year group b
1952–1999	5 (9)	65,743,363	7.54 (4.74–10.35)	98.852	0.058	−3.05–18.14
2000–2009	5 (10)	36,906,370	16.24 (12.32–20.16)	99.054	<0.001	1.00–31.48
2010–2013	5 (11)	94,677,659	16.58 (9.66–23.51)	99.813	<0.001	−11.06–44.23
2014–2017	5 (6)	72,534,124	14.85 (9.43–20.27)	99.630	0.052	−5.39–35.09
2018–2021	1 (1)	2,065,774	16.90 (15.13–18.67)	NA	NA	NA
Development
HDI >0.92	13	190,523,903	10.68 (7.97–13.38)	99.614	0.360	−5.45–26.99
HDI <0.92	1	1,652,173	12.60 (11.72–13.46)	NA	NA	NA
Continent
Asia	5	109,984,175	6.83 (3.96–9.67)	99.226	0.464	−4.46–18.08
Europe	6	75,102,159	12.63 (3.94–21.32)	99.733	0.022	−19.87–45.13
North America	2	5,023,968	12.57 (9.04–16.10)	92.140	NA	NA
Oceania	1	2,065,774	16.90 (15.13–18.67)	NA	NA	NA
Data source
Researcher validated	9	78,943,578	11.67 (7.04–16.30)	99.652	0.002	−25.75–25.79
Code‐base	5	113,232,498	9.33 (6.40–12.27)	98.720	0.203	−2.21–20.88
Diagnostic criteria b
Before 2009	9 (19)	89,073,442	12.13 (9.06–15.19)	99.419	<0.001	−2.55–26.81
After 2009	8 (18)	169,277,557	16.02 (12.58–19.45)	99.761	<0.001	2.44–29.55

^a Subgroups represent regions or districts in the included studies.

^b If the included studies provided individual year data, we used those data; otherwise, we used the prevalence rate at the end of the study year.

Publication bias assessment

Funnel plots were used to evaluate asymmetry in the included studies. This result was found to have a low risk of publication bias (Egger test: p = 0.014 for the overall incidence of achalasia and p = 0.443 for the overall prevalence of achalasia). However, in several subgroup analyses, the funnel plots showed asymmetry, suggesting a publication bias. A detailed description of the funnel plots used in our study is shown in Figures S3–S43.

Risk of bias was evaluated for 27 studies, and one study was excluded from the analysis due to high RoB. ³⁴ Seven studies were found to have a moderate RoB ⁹ , ¹¹ , ¹⁴ , ¹⁵ , ²⁰ , ²⁵ , ³³ and the remaining 19 studies were evaluated to have a low RoB. ² , ¹⁰ , ¹² , ¹³ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²¹ , ²² , ²³ , ²⁴ , ²⁶ , ²⁷ , ²⁸ , ²⁹ , ³⁰ , ³¹ , ³² The details of the RoB in the studies included in the analysis are listed in Table S5.

DISCUSSION

Key findings

Our systematic review and meta‐analysis complied incidence and prevalence data from 1925 to 2021 from 14 countries across five continents (Table S2). The global pooled incidence and prevalence of achalasia were estimated to be 0.78 cases per 100,000 person‐years and 10.82 cases per 100,000 person‐years, respectively. The incidence of achalasia was greater in Oceania, in adults, and after the introduction of the CC 2009. The incidence and prevalence of achalasia have increased significantly and show considerable variation across regions worldwide.

Comparison with previous studies

Some earlier reviews and incidence/prevalence studies of achalasia briefly touched upon epidemiology. ¹ , ²⁴ , ²⁷ , ²⁸ , ³¹ However, these studies did not delve into differences by continent and race, rates by age, or global trends in incidence and prevalence. To the best of our knowledge, our study represents the first comprehensive analysis of global incidence and prevalence trends. Moreover, it stands as the inaugural synthesis of analyses that consider regional, demographic, and social factors, data sources, and diagnostic criteria.

Possible explanation of our results

In comparison to the period before 2000, our study revealed a substantial 4.1‐fold increase in the incidence and a 2.2‐fold increase in the prevalence of achalasia. Several factors may contribute to this rise. Firstly, the introduction of innovative diagnostic tools, such as HRM, along with the establishment of systematic diagnostic standards, has likely played a significant role. Secondly, in this study, the incidence increased with increasing age is confirmed (Figure S44). The life span of the world population is increasing. ³⁵ Thirdly, improved worldwide access to healthcare services may be a contributing factor, supported by the higher incidence observed in countries with HDI >0.92 in our study. Additionally, the prevailing view that achalasia shares a pathophysiology with autoimmune diseases is supported by the frequent co‐occurrence of Sjögren's syndrome, type 1 diabetes mellitus, and hypothyroidism in achalasia patients. ¹ , ³⁶ With various autoimmune diseases on the rise globally, achalasia appears to follow a similar trend. ³⁷

The observed differences in incidence and prevalence across countries and continents can be attributed not only to variations in the developmental level of countries but also to other potential factors. These may include differences in dietary patterns, ³⁸ , ³⁹ genetic factors, ¹ and the extent of healthcare coverage for various examinations and treatments. ³⁵ , ⁴⁰

Strengths and limitations

This study had several limitations. First, our data are lacking in South America, the Middle East (except Israel) and Africa. Second, some of the included studies did not include sex or age data. This suggests that the analyses of sex and age may differ from reality. Third, the diagnosis of achalasia requires not only HRM, but also esophagography and esophagogastroduodenoscopy. ¹ , ²⁵ , ⁴¹ Therefore, it is difficult to diagnose achalasia in an environment with poor medical access; in our study, the data for countries with HDI <0.92 are relatively scarce. Therefore, underdiagnosed populations in these environments may be significantly higher. Fourth, the data analysis included both code‐based studies and studies that did not exclusively use HRM for diagnosis. Six code‐based studies ² , ²¹ , ²³ , ²⁴ , ³¹ , ³³ were incorporated into this meta‐analysis, each employing one or more cross‐validation methods to define cases. Among the researcher‐validated studies, excluding three studies, diagnoses were made using methods other than HRM, primarily conventional manometry. In some studies, there was a mix of periods where HRM was used and others where it was not. Consequently, the three studies that adhered to the current criteria for achalasia were separated and subjected to further analysis. Due to the limited number of included studies, the analysis results were presented in an incidence and prevalence table and underwent trend analysis with regression (Table S1 and Figure S2). Fifth, the timing of study inclusion varies in each country. As the incidence and prevalence differ by country or continent, the studies included in the analysis were conducted in different years, leading to some inconsistencies in the incidence and prevalence graph (Figure 2). Sixth, some pooled estimates or 95% prediction intervals estimated as negative values in Tables 2 and 3 were considered to have limited data bias. ⁴² Seventh, our analysis revealed significant heterogeneity. This aligns with previous meta‐analyses reporting increased incidence and prevalence of the disease, which also showed a higher tendency for heterogeneity. ³⁸ , ⁴³ , ⁴⁴ , ⁴⁵ Consequently, we refrained from conducting a meta‐regression analysis due to the substantial degree of heterogeneity between studies in our analysis. Therefore, the results of our study must be interpreted with great care, considering this aspect.

Despite these limitations, our study has several strengths. We comprehensively searched multiple databases to identify relevant studies on achalasia. In addition, our study visualized the changes in incidence and prevalence over time and analyzed the trends following the introduction of HRM and the establishment of CC. The incidence and prevalence were also compared according to sex, age, region, national development level, and data source. Accordingly, through this systematic review and meta‐analysis, we found out that there was no significant difference in incidence and prevalence according to sex, data source (Researcher validated vs. code based), and national development level (HDI >0.92 vs. Human development index <0.92) worldwide. Conversely, we showed that the incidence and prevalence were significantly higher in adults than in children, lower in Asia and Africa, and highest in Oceania. In addition, the incidence and prevalence by country were visualized on a world map to make it easy to see at a glance.

Further considerations and policy implication

Based on the findings of our study, both the incidence and prevalence of achalasia have exhibited an overall increase. Several factors suggest that the prevalence of this disease is likely to continue rising in the future, including the increasing life expectancy and incidence of autoimmune diseases. However, diagnosis of achalasia requires significant medical accessibility. ¹⁷ , ²⁷ , ²⁸ , ³⁰ , ³² , ⁴⁶ Consequently, there are concerns that many cases may go unrevealed in underdeveloped countries. Moreover, in the subgroup analysis based on national development levels, the incidence and prevalence exhibited opposing tendencies, hinting at differences in accessibility to curative treatment. This underscores the importance of not only improving the diagnosis but also enhancing treatment access in underdeveloped countries. Furthermore, an analysis of the incidence and prevalence by subtype of achalasia and the change in incidence and prevalence according to the updated version of the CC needs to be performed.

CONCLUSION

Despite several limitations such as heterogeneity, this study presents information on global trends in the incidence and prevalence of achalasia over time, exploring variations by sex, age, geographical region, and diagnostic criteria. The rising incidence of achalasia is evident, especially with the development of HRM and the implementation of diagnostic systems, suggesting a potential increase in the global health burden in the future. To achieve more accurate incidence and prevalence estimates, additional data from the South American and African continents, as well as underdeveloped countries with limited medical access, are essential. The substantial variation in achalasia incidence and prevalence observed worldwide in this study supports the influence of genetic, cultural, and environmental factors. Consequently, beyond the findings of this study, further exploration of these factors is crucial for enhancing global health outcomes in the future.

AUTHOR CONTRIBUTIONS

The author contributions were as follows. Conceptualization: Kwanjoo Lee, Wonyoung Cho, and Dong Keon Yon; Acquisition, analysis, or interpretation of data: In Kyung Yoo, Abdullah Özgür Yeniova, Jong Woo Hahn, Min Seo Kim, Soo‐Young Yoon, Masoud Rahmati, Jun Hyuk Lee, Myeongcheol Lee, Wonyoung Cho, and Dong Keon Yon; Drafting of the manuscript: Kwanjoo Lee, Sung Pyo Hong, Wonyoung Cho, and Dong Keon Yon; Critical revision of the manuscript for important intellectual content: In Kyung Yoo, Abdullah Özgür Yeniova, Jong Woo Hahn, Min Seo Kim, Soo‐Young Yoon, Masoud Rahmati, Jun Hyuk Lee, Myeongcheol Lee, Wonyoung Cho, and Dong Keon Yon; Statistical analysis: Kwanjoo Lee, Wonyoung Cho, and Dong Keon Yon; Supervision: Dong Keon Yon.

CONFLICT OF INTEREST STATEMENT

The authors declare that they have no conflicts of interest.

ETHICS APPROVAL

Not applicable.

INFORMED CONSENT

Not applicable.

Supporting information

Supplementary Information S1

Supplementary Information S2

Lee K, Hong SP, Yoo IK, Yeniova AÖ, Hahn JW, Kim MS, et al. Global trends in incidence and prevalence of achalasia, 1925–2021: a systematic review and meta‐analysis. United European Gastroenterol J. 2024;12(4):504–15. 10.1002/ueg2.12555

DATA AVAILABILITY STATEMENT

All data are provided in the Article and in the appendix. The study protocol, statistical code, and data set are available from DKY (email: yonkkang@gmail.com).