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.

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.

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).

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.

Achalasia is a rare esophageal disease with potentially lethal complications. Knowledge of the outcomes of the different surgical treatment modalities for achalasia by Heller's cardiomyotomy (HCM) helps to choose the safest and most effective option. However, data on the management of achalsia using a Heller myotomy is limited in Africa. Thus, our aim was to determine the perioperative morbidity, mortality and short-term functional outcomes of HCM in Cameroon.

We conducted a cohort study throughout a 10-year chart review of patients who underwent HCM for achalasia and were followed up postoperatively for at least three months at two tertiary health centers in Cameroon. We analyzed demographic data, preoperative clinical and imaging data, treatment details, and outcomes at three to twelve months after HCM using the Eckardt score.

We enrolled 29 patients with achalasia having a mean age of 24 ± 16 years and predominantly females (M/F of 1/3.8). The mean symptom duration was 51 ± 20 months. In 80% of cases, the diagnosis was made through a conventional x-ray contrast imaging or "barium swallow test" (93%) and/or an upper gastrointestinal endoscopy (86%). The gold standard diagnostic method via esophageal manometry was unavailable. Preoperatievly, all patients had symptoms suggestive of an active achalasia. HCM was performed via laparotomy in 75% as opposed to 25% laparoscopic HCM procedures. Dor's anterior partial fundoplication was the main anti-reflux procedure performed (59%). Mucosal perforations were the only intraoperative complications in eight patients (2 during laparoscopy vs. 6 during laparotomy; p > 0.5) and were managed successfully by simple sutures. Postoperative complications were non-severe and occurred in 10% of patients all operated via laparotomy. The mean postoperative length of hospital stay was 7 ± 3 days for laparotomy vs. 5 ± 2 days for laparoscopy; p > 0.5. The perioperative mortality rate was nil. Overall, the short-term postoperative functional outcome was rated excellent; average Eckardt score of 1.5 ± 0.5 (vs. preoperative Eckardt Score of 9 ± 1; p < 0.0001).

Achalasia is diagnosed late in this resource-limited setting. HCM yields satisfactory outcomes, especially via laparoscopic management. An improvement in diagnostic esophageal manometry and mini-invasive surgical infrastructure and the required surgical training/skills are needed for optimal achalasia care.

Esophageal motility disorders (EMDs) are a known risk factor for esophageal candidiasis (EC), but this relation has not been described particularly well. We sought to evaluate the predictors of underlying EMDs in patients presenting with EC.

Cases of EC at a single medical center between 2010 and 2021 were identified retrospectively based on the International Classification of Diseases, Ninth Revision code. Demographic, clinical, endoscopic, and manometric data were reviewed. The diagnosis of EC was based on typical endoscopic appearance.

In total, 130 EC patients were identified (mean age 69.5 ± 14.6; 66.2% male). Of these, 12 (9.2%) had an underlying EMD (11 cases of achalasia; 1 case of esophagogastric junction outflow obstruction). Five (41.7%) of these patients had previously been diagnosed as having an EMD, whereas 7 were newly diagnosed only after their presentation with EC. No significant differences were noted between those with or without EMDs in terms of demographics, medical comorbidities, or medication use. Patients with an EMD, however, were more likely to complain of dysphagia (91.7% vs 30.5%, P < 0.001), and on endoscopy, they were more likely to have residual food in the esophagus, residual fluid in the esophagus, a dilated esophagus, and resistance to traversing the esophagogastric junction (all P < 0.001). Sixty-one (46.9%) patients with EC died during follow-up (mean 58 months).

EMDs are present in approximately 10% of patients presenting with EC, with half being diagnosed only after presenting with EC. Similar to non-EC patients, patients with EC with dysphagia and the typical endoscopic findings of achalasia are more likely to have an EMD and warrant prompt manometric evaluation.

Achalasia cardia, type of esophageal dynamic disorder, is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter. Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia, and is more likely to occur in the elderly. Histological changes in the esophageal mucosa are considered pathogenic; however, studies have found that inflammation and genetic changes at the molecular level may also cause achalasia cardia, resulting in dysphagia, reflux, aspiration, retrosternal pain, and weight loss. Currently, the treatment options for achalasia focus on reducing the resting pressure of the lower esophageal sphincter, helping to empty the esophagus and relieve symptoms. Treatment measures include botulinum toxin injection, inflatable dilation, stent insertion, and surgical myotomy (open or laparoscopic). Surgical procedures are often subject to controversy owing to concerns about safety and effectiveness, particularly in older patients. Herein, we review clinical epidemiological and experimental data to determine the prevalence, pathogenesis, clinical presentation, diagnostic criteria, and treatment options for achalasia to support its clinical management.

Triple-A Syndrome (TAS) is a rare autosomal recessive disorder characterized by adrenal insufficiency, achalasia, and alacrimia. This disorder is caused by mutations in the AAAS gene. The aim of this study is to discuss the clinical, laboratory and molecular genetic analysis results of 12 patients with TAS.

We evaluated 12 patients from 8 families. Clinical and laboratory data were retrospectively collected from the medical records of the patients in the database for the period 2015-2020. All exons and exon-intron junctions of the AAAS gene were evaluated by next-generation sequencing method. Detected variants were classified according to American Collage of Medical Genetics criteria.

Alacrimia was found in all patients (100%); achalasia was found in 10 patients (83.3%) and adrenal insufficiency was found in 10 patients (83.3%). In addition, hyperreflexia(6/12), learning disability(5/12), hypernasal speech(5/12), muscle weakness(8/12), delayed walking(7/12), delayed speech(6/12), excessive sweating(7/12), optic atrophy(1/12), epilepsy(1/12), palmoplantar hyperkeratosis(5/12), multiple dental caries(9/12), atrophy of the thenar/hypothenar muscles(4/12) and short stature(4/12) were detected. The DHEA-S levels were measured in 10 patients and were found to be low in 8 of them. In all patients, the sodium and potassium levels were found to be normal. AAAS gene sequencing revealed four previously reported c.1066_1067del (p.Leu356fs*8), c.1432 C > T (p.Arg478*), c.688 C > T (p.Arg230*), and c.1368_1372del (p.Gln456fs*38) variants and two novel homozygous c.1250-1 G > A and c.398_399 + 2del variants in the AAAS gene.

We detected two novel variants in the AAAS gene. While the classic triad is present in 66.7% of the cases, neurological dysfunction, skin and dental pathologies also occur quite frequently. The earliest and most common finding of TAS is alacrimia. Therefore, adrenal insufficiency should be investigated in all patients with alacrimia and if necessary, genetic analysis should be performed for TAS. In addition, TAS should be followed up with a multidisciplinary approach since it involves many systems.

Esophageal motility disorders (EMDs) are the main etiology of nonobstructive dysphagia (NOD), but they are underestimated in Egypt. High-resolution manometry (HRM) with Chicago Classification version 3.0 (CC v3.0) is the current gold standard diagnostic modality to assess EMD in patients with NOD. In this HRM-based study, we aimed to classify EMD among Egyptian patients and explore the relationship between the severity of symptoms and the various groups of EMD. From January 2020 to January 2021, patients with dysphagia were subjected to diagnostic workup, which included symptom questionnaire for Eckardt score, esophagogastroduodenoscopy, barium esophagogram, and HRM. All patients were categorized based on the HRM results using CC version 3.0 after exclusion of those with obstructive esophageal lesions. Of 252 patients with dysphagia, 55 patients with NOD were analyzed according to CC version 3.0. Achalasia was diagnosed in 31 patients (56.4%) (type I: 18 [58.06%]; type II: 9 [29.03%], and type III: 4 [12.9%]), 3 patients (5.5%) with esophagogastric junction outflow obstruction, 2 patients (3.6%) with absent contractility, 4 patients (7.3%) with distal esophageal spasm, 7 patients (12.7%) with ineffective esophageal motility, and 8 patients (14.5%) with normal manometry. Patients with achalasia experienced significantly high regurgitation (96.8% vs 70.8%; P = .016) compared with those without achalasia. Achalasia was the most common EMD in Egyptian patients with NOD. Eckardt score was higher in patients with outflow obstruction and major motor disorder, but it could not differentiate different categories of CC of EMD. HRM is effective in characterization of EMD.

Africa comprises 54 countries with varying degrees of economic development. As with other healthcare systems, rare diseases such as adrenal insufficiency are neglected and poorly documented.

We wished to explore primary adrenal insufficiency (PAI) in Africa, its prevalence, aetiology, genetics, presentation, diagnosis, and treatment and to determine the unmet needs in clinical care, education, and research.

A narrative nonsystematic review of the literature was undertaken. We searched two online databases (PubMed and Google scholar) using the search terms "Addison's disease/PAI, primary adrenal insufficiency coupled with "Africa," "country names," and "genetic disorders." A total of 184 PAI records were reviewed. The exclusion of abstracts, conference proceedings, single case reports, and duplicate studies covering the same subject matter yielded 124 articles, of which 97 informed the final manuscript.

A wide range of aetiology of PAI was encountered, but their true prevalence is unknown. Aetiology varied with region and age of presentation as reflected by predominantly TB, HIV, and infective causes occurring in sub-Saharan Africa and more congenital forms described in North Africa associated with consanguinity. In Africa, the diagnostic criteria for PAI do not universally accord with conventional criteria, and there is a heavy reliance on clinical suspicion and biochemistry, including random cortisol of <400 nmol/L, rather than the tetracosactide test where stimulated cortisol <500-550 nmol/L confirms the diagnosis.

A high index of suspicion is warranted to diagnose PAI in resource-limited settings, especially where tetracosactide tests are not universally available.

Achalasia is a rare disease, with an incidence of one in 100 000. Genetic factors and autoimmune involvement have been reported in its etiology, and their involvement is strongly suspected, especially in patients with familial achalasia and those with comorbid hereditary or autoimmune diseases. However, these special types of achalasia are rare, and their frequency and clinical characteristics remain unclear.

This retrospective, multicenter cohort study included Japanese patients with a diagnosis of achalasia, treated between 2010 and 2019 across six tertiary centers in Japan. The frequency and clinical characteristics of special types of achalasia, namely, familial achalasia, achalasia with a comorbid hereditary disease, and achalasia with a comorbid autoimmune disease, were retrospectively investigated using a large-scale multicenter database.

During the study period, 1115 patients were treated for achalasia at six tertiary centers. Familial achalasia, achalasia with a comorbid hereditary disease, and achalasia with a comorbid autoimmune disease occurred in 7 (0.63%), 11 (0.99%), and 27 (2.4%) patients, respectively. Familial achalasia had a slightly younger age of onset (37.6 ± 12.1 years old) and a higher incidence in male patients (six patients; 85.7%). Down's syndrome was the most common hereditary comorbidity, and thyroid disease was the most common autoimmune comorbidity.

We clarified the frequency and clinical characteristics of special types of achalasia. Although special types of achalasia are rare, these comorbidities should be considered when treating patients with achalasia.

Acromegaly is a disorder associated with hypersecretion of growth hormone, most usually caused by a pituitary adenoma. Dysmotility of the gastrointestinal tract has been reported in acromegalic patients. Achalasia is a disorder characterized by aperistalsis of the oesophagus with incomplete lower oesophageal sphincter relaxation and whose aetiology remains unknown. Mutations in some genes have previously been associated with the development of acromegaly or achalasia. The study aims were to analyse mutations in selected genes in a woman having both of these diseases, to identify their aetiological factors, and to suggest explanations for the co-incidence of acromegaly and achalasia.

A female patient with acromegaly, achalasia, and a multinodular thyroid gland with hyperplastic colloid nodules underwent successful treatment of achalasia via laparoscopic Heller myotomy, a thyroidectomy was performed, and the pituitary macroadenoma was surgically excised via transnasal endoscopic extirpation. Germline DNA from the leukocytes was analysed by sequencing methods for a panel of genes. No pathogenic mutation in AAAS, AIP, MEN1, CDKN1B, PRKAR1A, SDHB, GPR101, and GNAS genes was found in germline DNA. The somatic mutation c.601C>T/p.R201C in the GNAS gene was identified in DNA extracted from a tissue sample of the pituitary macroadenoma.

We here describe the first case report to our knowledge of a patient with both acromegaly and achalasia. Association of acromegaly and soft muscle tissue hypertrophy may contribute to achalasia's development. If one of these diagnoses is determined, the other also should be considered along with increased risk of oesophageal and colorectal malignancy.

Esophageal achalasia is a primary esophageal motility disorder characterized by lack of peristalsis and by incomplete or absent relaxation of the lower esophageal sphincter in response to swallowing. The cause of the disease is unknown. The goal of treatment is to eliminate the functional outflow obstruction at the level of the gastroesophageal junction, therefore allowing emptying of the esophagus into the stomach. They include the laparoscopic Heller myotomy with partial fundoplication, pneumatic dilatation, and peroral endoscopic myotomy. Esophagectomy is considered as a last resort for patients who have failed prior therapeutic attempts. In this evidence and experience-based review, we will illustrate the technique and results of the surgical treatment of esophageal achalasia and compare it to the other available treatment modalities.

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the "2019 Seoul Consensus on Esophageal Achalasia Guidelines") were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.

Allgrove syndrome (OMIM 231550) is a rare autosomal recessive disease characterized by non-CAH primary adrenal insufficiency (non-CAH PAI), alacrima, and achalasia. It is caused by mutations in the AAAS gene. The syndrome is also associated with variable progressive neurological impairment and dermatological abnormalities.

We diagnosed 23 patients from 14 families with Allgrove syndrome, based on the presence of at least two characteristic symptoms, usually adrenal insufficiency and alacrima, between 2008 and 2018. A previously described nonsense variant of AAAS was detected in 19 patients from 12 families at homozygous state. Another novel homozygous mutation (c.394-397delCTGT) in AAAS was detected in four patients from two families. Presenting symptoms were alacrima (23/23; 100%), adrenal insufficiency (18/23; 78%), achalasia (13/23; 57%), short stature/growth retardation (16/23; 70%), hyperreflexia (15/23; 65%), palmoplantar hyperkeratosis (13/23; 57%), hyperpigmentation of the skin (10/23; 43%), hypoglycemia-induced convulsion (7/23; 30%), swallowing difficulty and vomiting (6/23; 26%). Serum DHEAS concentrations were low in all patients (23/23; 100%).

Clinical symptoms vary even among patients carrying the same mutation. Triple A syndrome should be considered in the etiology of non-CAH PAI in Arab populations and in Southeast Turkey. Any child with non-CAH PAI should be evaluated for the presence of alacrima and/or achalasia or family history of alacrima and/or achalasia. Children with alacrima and/or achalasia should also be investigated for adrenal insufficiency. Definitive molecular diagnosis is essential for early diagnosis and management of adrenal insufficiency, neurological symptoms, and growth retardation in patients and early diagnosis of as yet asymptomatic cases in the family, together with genetic counseling.

To systematically review clinical presentation, diagnosis, and therapy of achalasia, focusing on recent developments in high-resolution esophageal manometry (HREM) for diagnosis and peroral endoscopic myotomy (POEM) for therapy.

Systematic review of achalasia using computerized literature search via PubMed and Ovid of articles published since 2005 with keywords ("achalasia") AND ("high resolution" or "HREM" or "peroral endoscopic myotomy" or "POEM"). Two authors independently performed literature searches and incorporated articles into this review by consensus according to prospectively determined criteria.

Achalasia is an uncommon esophageal motility disorder, usually manifested by dysphagia to solids and liquids, and sometimes manifested by chest pain, regurgitation, and weight loss. Symptoms often suggest more common disorders, such as gastroesophageal reflux disease (GERD), thus often delaying diagnosis. Achalasia is a predominantly idiopathic chronic disease. Diagnosis is typically suggested by barium swallow showing esophageal dilation; absent distal esophageal peristalsis; smoothly tapered narrowing ("bird's beak") at esophagogastric junction; and delayed passage of contrast into stomach. Diagnostic findings at high-resolution esophageal manometry (HREM) include: distal esophageal aperistalsis and integrated relaxation pressure (trough LES pressure during 4 s) > 15 mmHg. Achalasia is classified by HREM into: type 1 classic; type 2 compartmentalized high pressure in esophageal body, and type 3 spastic. This classification impacts therapeutic decisions. Esophagogastroduodenoscopy is required before therapy to assess esophagus and esophagogastric junction and to exclude distal esophageal malignancy. POEM is a revolutionizing achalasia therapy. POEM creates a myotomy via interventional endoscopy. Numerous studies demonstrate that POEM produces comparable, if not superior, results compared to standard laparoscopic Heller myotomy (LHM), as determined by LES pressure, dysphagia frequency, Eckardt score, hospital length of stay, therapy durability, and incidence of GERD. Other therapies, including botulinum toxin injection and pneumatic dilation, have moderately less efficacy and much less durability than POEM.

This comprehensive review suggests that POEM is equivalent or perhaps superior to LHM for achalasia in terms of cost efficiency, hospital length of stay, and relief of dysphagia, with comparable side effects. The data are, however, not conclusive due to sparse long-term follow-up and lack of randomized comparative clinical trials. POEM therapy is currently limited by a shortage of trained endoscopists.

Recent reports show increasing incidence of achalasia in some populations. The aim of this study was to estimate incidence, prevalence, and healthcare costs of achalasia in a large cohort in The Netherlands.

Data were obtained from the largest Dutch healthcare insurance company (±4.4 million insured). Adult achalasia patients were identified between 2006 and 2014 when having an achalasia diagnosis code registered. A total of 907 achalasia patients were identified and included in our database, along with 9068 control patients (non-achalasia patients), matched by age and gender.

The mean incidence over the 9-year period was 2.2 per 100 000 persons and the mean prevalence was 15.3 per 100 000 persons. Mean age of achalasia patients was 54 (range 18-98) years. Male to female ratio was 1:1. Socio-economic status distribution was similar in achalasia patients and controls. Prior to the diagnosis, 74% of achalasia patients received proton pump inhibitors and 26% received anti-emetic medication. The first year after diagnosis median total direct medical costs of achalasia patients were €2283 (IQR 969-3044) per year. Patients above the 90th percentile of €4717 were significantly older than other patients below the 90th percentile (mean age 63 vs 57); P = .005.

In this large study that used a database comprising about 25% of all inhabitants of The Netherlands, it is confirmed that achalasia affects individuals of both genders and all ages. The costs associated with diagnosis and treatment of new cases of achalasia increase with increasing age.