Esophageal contractions in Chagas' disease and in idiopathic achalasia

GOALS: The aim of this study was to compare the esophageal contractions in Chagas' disease and in idiopathic achalasia. BACKGROUND: It is suggested that the esophageal involvement caused by Chagas' disease and by idiopathic achalasia, although similar, shows some differences. STUDY: We studied the contractions at 2, 7, 12, and 17 cm below the upper esophageal sphincter in 25 patients with idiopathic achalasia (15 with dilatation), 52 with Chagas' disease (22 with dilatation), and 18 controls. Each subject performed 5 swallows of a 5-mL bolus of water alternated with 5 dry swallows. RESULTS: In the distal esophageal body, the amplitude was lower in patients than in controls. Among patients with esophageal dilatation, the proximal amplitude was lower in patients with idiopathic achalasia, and the time interval between the contractions at 2 and 7 cm was longer in patients with Chagas' disease, the number of failed contractions was higher in Chagas' disease, and simultaneous contractions were more frequent in idiopathic achalasia. The simultaneous isobaric pressure in the distal esophagus was associated with an increase in proximal pressure that was higher than distal but lower than proximal swallowing pressure. CONCLUSION: The results suggested that idiopathic achalasia and Chagas' disease cause similar impairment of distal esophageal motility, but in patients with esophageal dilatation the impairment of proximal motility may be not the same.     

Differences in response of the proximal esophagus to wet swallows in patients of Chagas'' disease and idiopathic achalasia

Chagas' disease and idiopathic achalasia have similar esophageal manifestations such as absent or incomplete lower esophageal sphincter relaxation and aperistalsis in the esophageal body (alterations seen mainly in the distal esophageal body). Our aim in this paper was to study the response of the proximal esophageal body to wet swallows in patients with Chagas' disease and patients with idiopathic achalasia. We retrospectively analyzed the time interval between the onset of the pharyngeal contractions 1 cm proximal to the upper esophageal sphincter, as well as 5 cm distal to the pharyngeal measurement. Amplitude, duration and area under the curve of contractions in the proximal esophagus were also determined in 42 patients with Chagas' disease (15 with associated esophageal dilatation), 21 patients with idiopathic achalasia (14 with concomitant esophageal dilatation) and 31 control subjects. The time between the onset of pharyngeal and proximal esophageal contractions was longer in patients with Chagas' disease and in those with esophageal dilatation (1.39 +/- 0.16 s) than in control subjects (0.86 +/- 0.04 s, P < 0.01). The amplitude of proximal esophageal contractions was lower in patients with idiopathic achalasia and esophageal dilatation (60.9 +/- 16.3 mmHg) than in control subjects (89.7 +/- 6.9 mmHg, P = 0.06). The authors conclude that in patients with advanced esophageal disease, the proximal esophageal contractions in Chagas' disease have a delayed response to wet swallows when compared with controls, and that the amplitude of proximal esophageal contractions was lower than expected in patients with idiopathic achalasia.     

Esophageal Motility of Patients with Chagas' Disease and Idiopathic Achalasia

Chagas' disease and idiopathic achalasia have the same neuropathic lesion—the loss of ganglion cells within the esophageal myenteric plexus—with similar clinical, radiologic, and manometric features. However, it is suggested that there are some differences between them. We studied the esophageal motility of 45 patients with Chagas' disease (seven with esophageal dilation), 27 patients with idiopathic achalasia (13 with esophageal dilation), and 40 asymptomatic volunteers. We used the manometric method with continuous perfusion. The lower esophageal sphincter (LES) pressure was measured by the rapid pull-through method. Esophageal contractions was evaluated at 5, 10, and 15 cm above the LES, after 10 swallows of a 5-ml bolus of water alternated with 10 dry swallows. LES pressure was higher in achalasia than in Chagas' disease patients and controls (P < 0.05). Amplitude of contraction was lower in all patient groups compared with controls (P < 0.01) and lower in patients with dilation compared with patients without dilation (P < 0.05). The contraction duration was longer in patients with achalasia than in patients with Chagas' disease and controls (P < 0.05). The percentage of failed contractions was higher in Chagas' disease than in achalasia and controls (P < 0.05), and the percentage of simultaneous contractions was higher in patients with idiopathic achalasia than in patients with Chagas' disease and controls (P < 0.05). The results suggest the possibility that the extent of impairment of esophageal innervation differs between Chagas' disease and idiopathic achalasia.     

Vigorous achalasia in Chagas'' disease

The study investigated the esophageal motility of 98 patients with Chagas' disease and 40 asymptomatic volunteers, with the objective of comparing patients with vigorous achalasia (distal amplitude contractions >/= 37 mmHg) and patients with classical achalasia (amplitude < 37 mmHg). The Chagas' disease patients had normal esophageal radiologic transit (n=60) or esophageal slow transit and retention without dilation (n=38). The manometric method with continuous perfusion was used to study esophageal motility. Comparison of classical and vigorous achalasia showed no difference in duration of contractions, lower and upper esophageal sphincter pressure, proportion of patients with dysphagia, or the number of multipeaked contractions. The number of failed contractions was higher in patients with classic achalasia than in patients with vigorous achalasia. We conclude that the distinction between classical and vigorous achalasia does not seem to be important for the classification of Chagas' disease.     

Etiopathological aspects of achalasia: lessons learned with Hirschsprung's disease

The etiology of primary esophageal achalasia is largely unknown. There is increasing evidence that genetic alterations might play an important but underestimated role. Current knowledge of the genetic base of Hirschsprung's disease in contrast is far more detailed. The two enteric neuropathies have several clinical features in common. This association may also exist on a cellular and molecular level. The aim of this review is to enlighten those etiopathogenetic concepts of Hirschsprung's disease that seem to be useful in uncovering the pathological processes causing achalasia. Three aspects are looked at: (i) the genetic base of Hirschsprung's disease, particularly its major susceptibility gene rearranged during transfection and its potential reference to achalasia; (ii) the altered motor functions in both conditions with loss of inhibitory innervation and interstitial cell pathology; and (iii) the involvement of these motility disorders in genetic syndromes.     

Hypocontraction of the esophagus in patients with Chagas' disease and with primary achalasia

The esophageal contraction amplitude is low in patients with Chagas' disease and patients with primary achalasia but not every swallow is followed by low contraction amplitude. We evaluated the number of low contraction amplitude in 40 normal volunteers, 99 Chagas' disease patients and 14 patients with primary achalasia. Each subject performed 10 swallows of a 5 mL bolus of water and the esophageal motility was measured at 5, 10 and 15 cm above the lower esophageal sphincter by the manometric method with continuous perfusion. The amplitude of contraction was considered to be low when its value was below 30 mm Hg. There was a hypotensive contraction when the amplitude was low or when the contraction failed. The number of hypotensive contractions was higher in patients with Chagas' disease and patients with achalasia than in healthy volunteers (P < 0.05). Patients with Chagas' disease and abnormal esophageal radiological examination but without dilation had more frequent hypotensive contraction than patients with normal esophageal radiologic examination (P < 0.01). The same results were obtained for subjects with three or more hypotensive contractions (P < 0.01). The patients with Chagas' disease and dysphagia had more hypotensive contractions than patients without dysphagia (P < 0.05). We conclude that patients with Chagas' disease and patients with primary achalasia have a higher number of hypotensive contractions following wet swallows than normal volunteers, a fact that should influence the symptomatology of the patients.     

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia

The human lower esophageal sphincter (LES) is believed to be innervated by nonadrenergic, noncholinergic inhibitory nerves, and cholinergic excitatory nerves. In idiopathic achalasia, LES relaxation is abnormal because the inhibitory nerves to the sphincter are either absent or functionally impaired. The integrity of cholinergic excitatory nerves to the LES, however, has not been thoroughly evaluated. In 27 patients with untreated idiopathic achalasia, and 21 healthy volunteers, we investigated the hypothesis that postganglionic cholinergic nerves to the LES are functionally intact in achalasia. The LES responses to atropine, edrophonium, methacholine, amyl nitrite, and pentagastrin were assessed. In 2 achalasia patients, patterns of fasting motor activity in the LES were investigated during overnight manometric studies. Resting LES pressure was significantly greater in the achalasia patients, 41 +/- 4 mmHg (mean +/- SE), than in the normal subjects, 20 +/- 2 mmHg. Atropine significantly reduced LES pressure in both groups by 30%-75%. Edrophonium increased LES pressure in the achalasia patients but had negligible effect on the normal subjects. The LES in achalasia patients exhibited an increased sensitivity to both methacholine and pentagastrin compared with the normal subjects. In both patients who underwent an overnight manometric study, the LES exhibited cyclic phasic contractile activity synchronous with gastric contractions during the migrating motor complex. We conclude that the study findings support the hypothesis that postganglionic cholinergic LES innervation in achalasia patients is either normal or only minimally impaired, in contrast to the marked impairment of the inhibitory nerves governing LES relaxation.     

Congenital achalasia: facts and fantasies

Achalasia, a poorly relaxing lower esophageal sphincter, produces a functional obstruction and the expected symptoms of dysphagia, regurgitation and eventually weight loss. The cause of achalasia remains largely unknown in Western countries, Chagas' disease being the most frequent etiology in Brazil. We report on two sets of monozygotic male twins with typical manifestations of achalasia. The majority of authors attribute a limited contribution unless achalasia is related to a multisystem disorder, like the triple-A or Allgrove's syndrome, an autosomal recessive disease characterized by the triad of adrenocorticotropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrima. The four cases reported demonstrated the genetic influence of achalasia in patients without multisystem disorders. We believe that idiopathic achalasia is a syndrome with similar clinical, pathological, radiological and manometric evolution, but with a great variety of etiological agents, one of them being the congenital form.     

Etiology and pathogenesis of achalasia: the current understanding

Idiopathic achalasia is an inflammatory disease of unknown etiology characterized by esophageal aperistalsis and failure of LES relaxation due to loss of inhibitory nitrinergic neurons in the esophageal myenteric plexus. Proposed causes of achalasia include gastroesophageal junction obstruction, neuronal degeneration, viral infection, genetic inheritance, and autoimmune disease. Current evidence suggests that the initial insult to the esophagus, perhaps a viral infection or some other environmental factor, results in myenteric plexus inflammation. The inflammation then leads to an autoimmune response in a susceptible population who may be genetically predisposed. Subsequently, chronic inflammation leads to destruction of the inhibitory myenteric ganglion cells resulting in the clinical syndrome of idiopathic achalasia. Further studies are needed to better understand the etiology and pathogenesis of achalasia-such an understanding will be important in developing safe, effective, and possibly curative therapy for achalasia.     

Lower esophageal sphincter pressure in idiopathic achalasia and Chagas disease-related achalasia

The most important etiologies of achalasia are idiopathic and related to Chagas' disease. The lower esophageal sphincter pressure (LESP) in idiopathic achalasia (Id Ach) is higher compared with a healthy group, but there are different reports in Chagasic achalasia (Ch Ach). We compared the LESP of patients with both forms of achalasia and a control group. The LESP of 213 achalasia patients without previous treatment and 32 healthy volunteers were assessed. In 126 patients, the etiology could be demonstrated using serologic tests (Id Ach, 94 and Ch Ach, 32). The LESP of 213 patients was 31.86+/-14.18 mmHg and in the control group was 17.92+/-7.03 mmHg (P < 0.0001). The LESP in Id Ach and Ch Ach was 33.28+/-13.63 mmHg and 23.5+/-12.09 mmHg (P < 0.0001), respectively. Only the Id Ach group achieved statistical difference in relation to the control group (P < 0.0001). In conclusion, the LESP of Id Ach patients was higher than in Ch Ach patients and the control group, but there was no LESP difference between the Ch Ach and control groups.     

Comparison of esophageal motility impairment caused by Chagas' disease in two age groups

BACKGROUND: Chagas' disease and the aging process cause loss of neurons of the esophageal myenteric plexus. AIM: To evaluate the esophageal motility impairment caused by Chagas' disease in two age groups. Our hypothesis was that the aging process may cause further esophageal motility impairment in patients with Chagas' disease. METHODS: We studied the esophageal motility of 30 patients with Chagas' disease and dysphagia, with esophageal retention of barium sulfate and an esophageal diameter within the normal range. Fifteen were 34 to 59 years old (younger group, median 51 years) and 15 were 61 to 77 years old (older group, median 66 years). As a control group we studied 15 subjects aged 33 to 58 years (median 42 years) and 7 subjects aged 61 to 73 years (median 66 years). The esophageal contractions were measured by the manometric method with continuous perfusion after five swallows of a 5 mL bolus of water at 2, 7, 12 and 17 cm below the upper esophageal sphincter. RESULTS: Patients with Chagas' disease had lower amplitude of contractions and fewer peristaltic, more simultaneous, and more non-conducted contractions than controls. Older patients with Chagas' disease had lower amplitude of contractions in the distal esophagus (mean +/- SE: 30.8 +/- 4.3 mm Hg) than younger patients (51.9 +/- 8.6 mm Hg). From 12 to 17 cm, older patients had more non-conducted (41%) and fewer peristaltic (8%) contractions than younger patients (non-conducted: 16%, peristaltic: 21%). CONCLUSION: Older patients with Chagas' disease with clinical and radiological examinations similar to those of younger patients had motility alterations suggesting that the aging process may cause further deterioration of esophageal motility.     

Effect of bolus volume on proximal esophageal contractions of patients with Chagas' disease and patients with idiopathic achalasia

Chagas' disease and idiopathic achalasia patients have similar impairment of distal esophageal motility. In Chagas' disease, the contractions occurring in the distal esophageal body are similar after wet or dry swallows. Our aim in this investigation was to evaluate the effect of wet swallows and dry swallows on proximal esophageal contractions of patients with Chagas' disease and with idiopathic achalasia. We studied 49 patients with Chagas' disease, 25 patients with idiopathic achalasia, and 33 normal volunteers. We recorded by the manometric method with continuous water perfusion the pharyngeal contractions 1 cm above the upper esophageal sphincter and the proximal esophageal contractions 5 cm from the pharyngeal recording point. Each subject performed in duplicate swallows of 3‐mL and 6‐mL boluses of water and dry swallows. We measured the time between the onset of pharyngeal contractions and the onset of proximal esophageal contractions (pharyngeal‐esophageal time [PET]), and the amplitude, duration, and area under the curve (AUC) of proximal esophageal contractions. Patients with Chagas' disease and with achalasia had longer PET, lower esophageal proximal contraction amplitude, and lower AUC than controls (P≤ 0.02). In Chagas' disease, wet swallows caused shorter PET, higher amplitude, and higher AUC than dry swallows (P≤ 0.03).There was no difference between swallows of 3‐ or 6‐mL boluses. There was no difference between patients with Chagas' disease and with idiopathic achalasia. We conclude that patients with Chagas' disease and with idiopathic achalasia have a delay in the proximal esophageal response and lower amplitude of the proximal esophageal contractions.     

Association of HLA-DR and -DQ alleles with idiopathic achalasia.

BACKGROUND & AIMS: Idiopathic achalasia is a motility disorder of the esophagus characterized by incomplete relaxation of the lower esophageal sphincter and a loss of normal peristaltic activity in the body of the esophagus. The loss of inhibitory neurons in the distal esophagus, as well as abnormalities in the vagus nerve, dorsal motor nucleus of the vagus nerve, and autonomic nervous system, have been described in achalasia. Although the underlying cause of idiopathic achalasia is unknown, the diffuse neuronal effects found suggest a possible viral or neurodegenerative mechanism. By use of serological methods, a significant association between the HLA-DQ1 phenotype and idiopathic achalasia has been found, suggesting a possible immunogenetic mechanism. To further define immunogenetics in the pathogenesis of idiopathic achalasia, we performed tissue typing in patients with achalasia to determine their specific HLA phenotypes. Methods: We prospectively studied 32 patients (23 white and 9 black) with idiopathic achalasia. Peripheral blood was collected, and HLA-DR and -DQ typing by polymerase chain reaction with sequence-specific primers was performed. Results were compared with those from 268 racially matched local controls. RESULTS: Idiopathic achalasia and the broad HLA-DQ1 allele were not significantly associated in either population, although a trend was found in white subjects (odds ratio [OR], 2.16; chi2 = 5.36, P corrected [Pc] = 0.0824). Further subtyping in white subjects revealed a significant association between idiopathic achalasia and the DQB1*0602 allele (OR, 3.10; chi2 = 7.32, Pc = 0.0408). A strong trend was also found with the DRB1*15 allele (OR, 2.83; chi2 = 8.11, Pc = 0.0572). In the black population, there was no association between idiopathic achalasia and DQB1*0602 or DRB1*15, but a trend was found with DRB1*12 (OR, 6. 19; chi2 = 5.19, P = 0.0227 uncorrected, Pc = 0.295). CONCLUSIONS: Idiopathic achalasia is associated with HLA alleles in a race-specific manner. These results support an immunogenetic mechanism in the pathogenesis of idiopathic achalasia.     

A rare case of multiple myeloma initially presenting with pseudoachalasia

Pseudoachalasia is a rare clinical entity with clinical, radiographic, and manometric features often indistinguishable from achalasia. Primary adenocarcinomas arising at the gastroesophageal junction or a tumor of the distal esophagus are the most frequent causes of pseudoachalasia. Rarely, processes other than esophagogastric cancers including chronic idiopathic intestinal pseudo-obstruction, amyloidosis, sarcoidosis, Chagas' disease, vagotomy, antireflux surgery, pancreatic pseudocysts, von Recklinghausen's neuroinomatosis, gastrointestinal stromal tumor, and other malignancies and rare genetic syndromes, may lead to the development of pseudoachalasia. Secondary achalasia is extremely rare, with less than 100 cases reported in the literature so far. Gastrointestinal manifestations in primary or secondary amyloidosis include abdominal pain, diarrhea, constipation, malabsorption, obstruction, motility disturbance, intestinal infarction, perforation, and hemorrhage; however, gastrointestinal tract involvement is asymptomatic in most instances. We present here a rare case of multiple myeloma initially presenting with dysphagia because of esophageal amyloidosis and manometric findings typical of achalasia.     

Clinical and manometric findings on elderly patients with achalasia

Introduction: Data regarding the age impact on the clinical presentation and esophageal motility in adults with idiopathic achalasia are scarce. Objective: To asses the clinical and manometric features of elderly patients with idiopathic achalasia. Methods: The medical charts of 159 patients diagnosed with achalasia were divided into two groups according to the patients' age: ?60 years (n = 123) and >60 years (n = 36). Clinical and manometric findings [esophageal body aperistalsis, basal lower esophageal sphincter (LES) pressure and abnormal LES relaxation] of both groups were compared upon diagnosis. Patients with previous esophageal interventions were excluded. Results: Only chest pain was more common in the ?60 year-old group (51.2% vs. 22.2%, p <0.003). This difference remained when comparing the group of men ?60 years. Other presenting features (including sex, weight loss, and presence of dysphagia, regurgitation and heartburn) did not differ between the groups. The LES relaxation was incomplete in 70.4% of the cases. No differences on the basal LES pressure, residual LES pressure or the amplitude of the esophageal body contractions between both groups were found. Considering only the classic achalasia cases, symptomatic time before diagnosis was greater in ?60 years compared with older patients: 24 vs. 12 months (p <0.05), respectively. Conclusions: These results suggest that chest pain is more common in younger male achalasia patients and residual LES pressure decreases with age.     

Lower esophageal sphincter pressure in Chagas' disease

It is known that lower esophageal sphincter (LES) pressure in patients with idiopathic achalasia is higher than in normal subjects, but in patients with Chagas' disease, who have esophageal disease with similar clinical, manometric, and radiologic results, studies of LES pressure show contradictory findings. We measured the LES pressure in 118 patients with chronic Chagas' disease, 14 patients with idiopathic achalasia, and 50 control subjects using a perfused catheter and the stationary pull-through (SPT) technique. The patients with Chagas' disease had normal esophageal radiologic examination (group A, N=50), delay in esophageal clearance without dilatation (group B, N=41), or delay in esophageal clearance with dilatation (group C, N=27). The LES pressure of Chagas' disease patients of group A (18.6 ±9.1 mm Hg, mean ±SD), group B (17.8 ±9.7mm Hg), and group C (21.6 ±10.1 mm Hg) was lower (P<0.001) than the LES pressure of the controls (24.9 ±10.2 mm Hg). In patients with idiopathic achalasia, the LES pressure (40.7 ±17.8 mm Hg) was higher than in control subjects (P<0.01) and Chagas' disease patients (P<0.001). We conclude that the LES pressure of patients with Chagas' disease tended to be lower than that of control subjects and achalasia patients.Presented in part at the 8th World Congress of Gastroenterology, September 1986, São Paulo, Brazil, and published in abstract form inDig Dis Sci 31:273, 1986.     

Family case of achalasia cardia: Case report and review of literature

Achalasia cardia is an idiopathic disease that occurs as a result of inflammation and degeneration of myenteric plexi leading to the loss of postganglionic inhibitory neurons required for relaxation of the lower esophageal sphincter and peristalsis of the esophagus.The main symptoms of achalasia are dysphagia,regurgitation,chest pain and weight loss.At present,there are three main hypotheses regarding etiology of achalasia cardia which are under consideration,these are genetic,infectious and autoimmune.Genetic theory is one of the most widely discussed.Case report given below represents an inheritable case of achalasia cardia which was not diagnosed for a long time in an 81-year-old woman and her 58-year-old daughter.     

The Spectrum of Esophageal Motor Disorders in Chagas' Disease

Objective : To determine the patterns of esophageal motility found in patients with Chagas' disease. Methods : Clinical, manometric, and scintigraphic data were obtained from 43 subjects with positive serological tests for Chagas' disease and nondilated esophagus and 10 patients with Chagasic megaesophagus. Results : Twenty (46.5%) of the seropositive subjects with nondilated esophagus were asymptomatic, and 23 (53.5%) had dysphagia, but only 12 (27.9%) had persistent dysphagia, a feature typical of Chagasic megaesophagus; only two (4.6%) had chest pain. Manometric findings within the seropositive group were: normal motility in 16 subjects, peristaltic multipeaked contractions in three, aperistalsis of the esophagus with relaxing lower esophageal sphincter in nine, and aperistalsis with nonrelaxing lower esophageal sphincter in 15 subjects. All of 10 megaesophagus patients had aperistalsis of the esophagus plus nonrelaxing lower esophageal sphincter. Scintigraphy was as sensitive as manometry in detecting esophageal dysmotility, but the erect scintigraphy was abnormal in subjects with complete aperistalsis only. Conclusion: In Chagas' disease, megaesophagus appears to be a disorder at the most severe end of a spectrum encompassing classical achalasia and its milder variants. Other esophageal motility disorders are rare, but normal esophageal function is common.     

Autoimmune comorbidity in achalasia patients

Background and Aim

Idiopathic achalasia is a rare esophageal motor disorder. The disease state manifests local and systemic inflammation, and it appears that an autoimmune component and specific autoantibodies participate in the pathogenesis. The study aims to determine the prevalence of autoimmune and chronic inflammatory diseases in patients with achalasia and compare the results with those from patients with gastroesophageal reflux disease (GERD).

Methods

It was a cross‐sectional and included 114 patients with idiopathic achalasia and 114 age‐matched and sex‐matched control patients with GERD. Data on the presence of autoimmune and inflammatory diseases, the time of presentation, and any family history of autoimmune disease were obtained from the hospital's medical records.

Results

Seventy three (64%) were female patients (mean age: 42.3 ± 15.5; median disease duration: 12 months). We identified the presence of autoimmune disease in 19 patients with achalasia (16.7%), hypothyroidism was the main diagnosis, and it was present in 52.6% of patients compared with 4.2% in controls. Thirteen of the 19 achalasia patients (68.4%) with autoimmune disease had history of familial autoimmunity. We identified 11 achalasia (9.6%) and 5 GERD patients (4.16%) with an inflammatory condition. Compared with the GERD, the achalasia group was 3.8 times more likely to have an autoimmune disease (95% CI: 1.47–9.83), 3.0 times more likely to have thyroidopathies (95% CI: 1.00–9.03), and 3.02 times more likely to suffer from any chronic inflammatory disease (95% CI: 1.65–6.20).

Conclusions

The non‐negligible number of patients with autoimmune diseases identified among the patients with idiopathic achalasia supports the hypothesis that achalasia has an autoimmune component.