Home Economics American Trypanosomiasis Chagas Disease, Second Edition: One Hundred Years of Research
The digestive form of Chagas disease is characterized by alterations in the motor, secretory, and absorptive functions of the gastrointestinal tract. Lesions of the enteric nervous system are pivotal in the pathogenesis of Chagas digestive megasyndromes. The myoenteric plexus of Auerbach, which is located between the longitudinal and circular muscular layers of the digestive tract, is the main one affected.41 Although most of the damage to the neurons of this plexus and the nervous fibers occurs during acute infection, further neuronal loss occurs slowly over an extended period of the chronic phase. There is a marked reduction in the number of nervous cells of the Auerbach’s plexus as demonstrated by Koberle42 in quantitative studies performed on several segments of the digestive tract, in humans, and in experimental animals infected with T. cruzi. Denervation occurs to variable degrees, is irregular and noncontinuous, and probably depends on both parasite and host factors.
Variations in T. cruzi strains related to the pathogenicity for the enteric nervous system probably explain the regional differences associated with Chagas disease (i.e., why the digestive form is seen only in some geographical areas), its unpredictable evolution, and its multiplicity of clinical manifestations.
The medical literature indicates a higher prevalence of the digestive form in the central region of Brazil. It has also been described in other countries of South America, but is not seen in countries above the equatorial line, where only a few cases with esophageal motor alterations have been described.43
Prevalence studies of the chagasic digestive form in Brazil (the country with the highest rates) have been performed based on radiological findings of the esophagus as an indicator of the involvement of the digestive tract. In seven radiological surveys performed in endemic areas and blood banks by abreugraphy (roentgenpho- tography, a radiograph of 35 or 70 mm, used as screening for tuberculosis), the prevalence rates of esophagopathy ranged from 7.1% to 18.3% (mean 8.8%) among 3073 infected individuals.44
Although intrinsic denervation can be found along the entire digestive tract, with variable intensity and distribution, the esophagus and the distal colon, because of their physiology, are the most frequently involved segments. As a consequence of denervation, motor uncoordination and achalasia of the sphincters occur, making it difficult for these segments to empty semisolid material, and leading to dilatation with time; this is the pathophysiological mechanism underlying chagasic megaesophagus and megacolon.
It has been observed that the frequency of megaesophagus is higher than that of megacolon in outpatient clinics or institutions caring for chagasic patients.
A survey conducted at the Hospital das Clinicas of the Federal University of Goias, between 1976 and 1997, showed that 1761 patients had megaesophagus at the first consultation (56.8% males and 43.2% of females; ages ranging from 2 to 102 years, of whom 75% were 20—70 years old). The association with megacolon was investigated by barium enema in 765 patients, and 365 of them (45.5%) also had megacolon.45
Serological tests for Chagas disease were performed on 1271 sera from patients with megaesophagus, including 362 with associated megacolon. Positive results were found in 91.3% of patients with megaesophagus and in 99.4% of patients with associated megacolon.44
Association of the cardiac and digestive form may vary according to peculiarities in each region and these data have limited value. In a region of central Brazil, this association was evaluated in 1313 patients. A normal ECG was found in 48.2% (n = 633), nonspecific ECG alterations were found in 21.1% (n = 277), and characteristic alterations (i.e., CRBBB) in 30.7% (n = 403). Only 14 out of 403 patients had severe alterations. The more frequent ECG abnormalities were CRBBB with or without left anterior fascicular block and ventricular premature beats.44
The clinically more interesting entities in the digestive form are esophagopathy and colopathy. In those cases with higher denervation, evolution is to ectatic forms of megaesophagus and megacolon.
The main complaints presented by patients at consultation are dysphagia, regurgitation, and esophageal pain. Other less frequent symptoms are hiccups, pyrosis, and hypersalivation accompanied by parotid hypertrophy. Malnutrition is observed with the progression of the disease.
Dysphagia is often the first and the most frequent symptom in the natural history of idiopathic achalasia or chagasic megaesophagus. It may be mild, moderate, or severe, and the intensity varies with type of food ingested, its temperature, and the emotional status of the patient.
Regurgitation may be active, occurring during or immediately after meals with the conscious participation of the patient, or passive, when the patient is lying in bed sleeping, generally at night. The regurgitated material is expelled through the
mouth and narines and may enter the respiratory tract, causing coughing and suffocation. Regurgitation is a common cause of pulmonary complications, mainly aspirative bronchopneumonia.
Esophageal pain may be spontaneous or associated with food ingestion, when it is called odynophagia. Spontaneous pain is localized at the level of the xiphoid appendix or below the sternum and propagates in an ascending direction up to the base of the neck, and radiates to the interscapulovertebral region and upper limbs. The pain is of the burning type, constrictive, tearing, or colicky, and is alleviated or abolished with the ingestion of water or other liquids.
Radiological examination is essential to confirm the diagnosis and to stage the disease (based on the morphofunctional characteristics of the esophagus), which is very important for the selection of the most appropriate therapy. Although there are several radiological classifications, we recommend the one by Rezende et al.,46 which identifies four groups (Fig. 28.12).
Group I: Normal diameter of esophagus; minimal contrast retention; presence of a residual air column above the contrast
Group II: Moderate dilatation, with some contrast retention; increase in uncoordinated motor activity; relative hypertony of the inferior third of the esophagus Group III: Large increase in diameter and great contrast retention; hypotonic esophagus with weak or absent motor activity
Group IV: Large increase in volume, atonic, elongated esophagus, lying on the right diaphragmatic dome.
Radiological examination should be combined with fluoroscopy to assess esophageal motility and emptying. The examination is performed with the patient in the upright position, preferentially at right anterior oblique view. In this position, the cardiac shadow projects to the front and the column to the back, allowing for better discrimination of the contrasted esophageal image.
Figure 28.12 Radiological classification of chagasic megaesophagus in four groups according to the stage of disease.46
The amount of contrast medium should be sufficient to generate an ideal height and pressure column that promotes the passage of contrast to the stomach, when the shape, diameter, wall contour, and mainly the contractile activity of the esophagus can be clearly seen. It is also important to search for eventual tertiary waves, which are uncoordinated and nonpropulsive contractions. The distal esophagus should be carefully observed. The last X-ray should be done after all the contrast medium has passed through the cardia.
For the detection of cases in group I, in which the diameter of the esophagus is normal, a special technique, known as retention test (analysis of two consecutive radiographs, the first immediately after ingestion of barium, and the second 1 min later), is recommended. The test is positive when incomplete emptying is observed on the second radiograph producing a level of residual contrast, and the esophagus remains open by the presence of an air column. A differential diagnosis should be established with other diseases that may display the same image, such as presbyeso- phagus, hiatus hernia, esophagitis, systemic sclerosis, neoplasia, and the use of anticholinergic drugs before the barium swallow.
There is significant correlation between symptoms and the evolution of megaesophagus. In group I, dysphagia is generally the only complaint. In group II, besides more severe dysphagia, there is active regurgitation and esophageal pain. In groups III and IV, passive regurgitation and malnutrition are frequent.
The evolution of chagasic esophagopathy to worsening of symptoms and progression of radiological and manometric parameters is not uniform in all cases; and if it occurs, it evolves slowly over time.
In a longitudinal study performed in an endemic area (Mambai, Goias State, Brazil) the prevalence of megaesophagus was assessed in 1006 individuals with positive serology. A chest abreugraphy (roentgenphotography, 70 mm) was taken after a barium meal of 75 mL contrasted the esophagus; a second abreugraphy was done 1 min later. Megaesophagus was detected in 71 (7%) of these patients: 43 were classified as group I, 18 as group II, 5 as group III, and 5 as group IV. Twenty-one patients with megaesophagus were reexamined 25 years later with the same technique. Progression was observed in 10 cases.47
Esophagealgastroduodenal endoscopy should be routinely performed after the radiological examination of the esophagus for evaluation of the mucosa and detection of associated lesions, mainly esophageal cancer, and cancer of the esopha- gealcardiotuberosity region.
For the differential diagnosis of chagasic megaesophagus with other esophagopa- thies, if there are any doubts, esophageal manometry is indicated using at least three pressure channels. The abnormalities seen in patients with chagasic megaesophagus vary depending on the stage of the disease. There is a loss of peristaltic activity at the body of the esophagus (aperistalsis), with synchronic waves and failure or incomplete aperture of the lower esophageal sphincter with ingestion (achalasia). In groups III and IV contractions are of low amplitude.
Manometry is particularly useful in the differential diagnosis of the hyperkinetic forms of megaesophagus and diffuse esophageal spasm, and for evaluation of the basal pressure of the lower sphincter of the esophagus before and after dilatation or surgery.
Idiopathic achalasia and chagasic megaesophagus are both risk factors for the development of esophageal cancer, because of chronic irritation of the mucosa caused by residual food. The prevalence of this association varies widely from 0.4% to 9.3%.45 The duration of the disease may be more important than the age of the patient. Higher prevalence of megaesophagus has been described by surgical services, probably because patients who need surgery are those with more advanced disease.
Treatment of chagasic megaesophagus and idiopathic achalasia may be clinical, instrumental, or surgical. Clinical treatment is indicated only for group I, or when other types of treatment are contraindicated for groups II, III, or IV. Clinical treatment is based on hygiene and dietary measures, and, eventually, the use of drugs such as isosorbitol dinitrate or nifedipine given before meals to relax the lower esophageal sphincter.
Instrumental treatment may be performed by dilatation of the cardioesophageal junction with a mercury-filled dilator (bougies of Hurst or Maloney) to temporarily alleviate the dysphagia, or by a pneumatic or hydrostatic balloon that reduces the pressure of the lower esophageal sphincter and usually shows satisfactory results. For older patients, the injection of botulinum toxin into the muscular layer of the esophagus—gastric transition may be performed as an alternative procedure and has an effect that lasts, on average, for 1 year.
The preferential treatment for groups II and III is surgery, using the Heller extramucosal cardiomyotomy technique via videolaparoscopy. For group IV, different types of surgery, including resection of the esophagus with cervical esophagogastric anastomosis, are indicated.
The prevalence of megacolon is hard to estimate, because of difficulties related to its diagnosis, which involves the realization of a barium enema. Megacolon is seldom the only manifestation of the digestive tract; in most cases it is associated with megaesophagus.
The most common symptoms are constipation, meteorism, dyskesia, and less often, abdominal colicky pain. Constipation may even be absent in 25—30% of individuals who have radiological dilatation of the colon.44,48
On physical examination, an increase in the abdominal volume is observed. Since the distal colon is the most affected segment, the distended sigmoid occupies a large part of the abdominal cavity and may be localized by palpation and percussion outside its normal topography.
Prolonged retention of feces in the distal colon leads to formation of fecaloma, which may be diagnosed by simple abdominal palpation, as an elastic tumor that can be molded by pressure. Rectal examination will detect a fecaloma at the rectal ampulla. Radiological examination is necessary to confirm the diagnosis, and should begin with a noncontrasted plain abdominal radiograph, which may show increased intestinal air and, if fecaloma is present, a bread-like image. After the noncontrasted X-ray, a barium enema is performed, which usually involves the use of intestinal cleansing or purgatives, as well as the introduction of air into the colon to achieve double contrast. These maneuvers, however, modify the original morphology of the colon and may induce false results. The colon is an elastic organ with capacity for distension or contraction, depending on the fecal contents as well as the endogenous or exogenous stimuli. Purgatives are irritants and increase the tonus and enterocolic contractility. The introduction of air into the colon causes distension of its wall that is proportional to the injected pressure, increasing the diameter of the distal colon, mainly the sigmoid colon. As a result, a false picture of the anatomical dimensions of the distal colon is obtained.
To avoid these pitfalls, a simplified technique is recommended, which has been shown to be satisfactory for the diagnosis of chagasic megacolon in endemic regions.49 Barium enema is performed without previous preparation and double contrast, using 300 mL of barium sulfate diluted up to 1200 mL with water. This preparation is delivered at a height of 1 m with the patient in ventral decubitus position, without any pressure effect. Then the patient moves to the right lateral decubitus position for 5 min. The first radiograph is taken in the dorsal decubitus position, and the second in the ventral decubitus position, using a 30 X 40 mm X-ray film. Another film, 24 X 30 mm, is taken with the patient in the right lateral decubitus position to image the rectum. The distance between the source of X-rays and the film (focus-film distance) should be 1 m. The presence of fecaloma is not an obstacle to this simplified technique. If there is suspicion that another disease of the colon is present, enema should be repeated with the conventional technique.
When the colon is largely dilated, the diagnosis is easy. When it is not, doubts may arise, because there is no clear-cut division among normal and abnormal patterns. The diameter and the dimension of sigmoid and rectal ampoule as well as the total length of the colon varies widely in normal subjects and in infected people. For this reason, the limits of normality need to be established for a given population. In an endemic region of Central Brazil, the application of the technique mentioned above in 72 nonchagasic individuals allowed to establish the following values as the upper limits of normal for radiological films: 7 cm for the diameter of sigmoides in an anteroposterior view; 11 cm for rectum diameter; and 70 cm for the length of distal colon, including rectum and sigmoides. By employing these parameters, the prevalence of megacolon in 225 infected individuals in this area was 6.2%.50
Dilation is usually located at the distal colon, including sigmoid and rectum (Fig. 28.13A). Rarely a dilatation is found in other segments or in the entire colon (Fig. 28.13B). Very often dilatation is associated with an increase in colon length, the dolicomegacolon.
Obviously, diagnosis of the nondilated colopathy cannot be performed by radiological examination and requires other methods, such as manometry and pharmacological tests of denervation.
Differential diagnosis should be made with other colonic dilatations of obstructive or functional origin, such as neoplasias, stenosis, extrinsic compressions, and rectosigmoid endometriosis. Among dilatations of functional origin, the psychogenic megacolon of the infancy, the andine megacolon (without lesions of the myoenteric plexus), the toxic megacolon that occurs as a complication of inflammatory bowel
Figure 28.13 Chagasic megacolon. (A) Dilatation is mainly at the rectum and sigmoid. (B) Total megacolon (rare).
diseases, and the atonic colon due to the action of drugs leaving to a secondary dilatation should always be remembered.
Differential diagnosis with Hirschsprung disease, also called congenital megacolon, is usually easy because chagasic megacolon is exceptional in low-age children.
Two other complications, apart from fecaloma formation, may occur: the fecal impactation and sigmoid volvulus, both with a clinical syndrome of intestinal occlusion. Fecal impactation may be solved with fecaloma emptying. Volvulus, depending on the degree of torsion and the aspect of the mucosa, may be treated by endoscopy distortion. If signals of suffering of mucosa are present at the local of torsion, surgical treatment is indicated.
Differently from megaesophagus, cancer of colon is rarely seen in patients with megacolon.
Treatment of megacolon may be clinical or surgical. In oligosymptomatic patients, when constipation is mild to moderate, a treatment based on osmotic laxatives (saline, lactulose, macrogol 3350) or emollients (mineral oil) is indicated, together with appropriate hygienic and dietary measures. An additional aid may be the inclusion of glycerol in enemas or in suppositories. The same conservative procedure is indicated for patients waiting for surgery and for those with a high surgical risk.
Surgical treatment is indicated in symptomatic patients with persistent constipation and clear evidence of dilatation of the distal colon in the radiological examination, as well as in those with previous complications. There are several surgical techniques, but the most frequently used (because of the results) is the resection of the dilated segment and lowering of the retrorectal portion of colon, leaving the rectum without function (technique of Duhamel—Haddad).
Other organs of the digestive tract
Other segments and organs of the digestive system may be compromised in Chagas disease, causing functional alterations that may be detected by different investigation methods, but with a lower impact than the lesions involving esophagus and colon.45
Chagasic gastropathy was initially suspected based on clinical evidence only.51 Gastric involvement is found in nearly 20% of patients with megaesophagus. On radiological examination the gastric volume is extremely variable, and the absence of air in the stomach of patients with advanced megaesophagus is very typical (Fig. 28.14).
In patients with the digestive form, hypersensitivity of the muscle layer of the gastric wall in response to cholinergic pharmacological stimuli, as well as alterations in both motility and secretion, may be detected by several methods. In these cases there is rapid gastric emptying for liquids and delayed for solids. A lower adaptative relaxation of the stomach in response to distension is also usually found. An alteration of the gastric electric rhythm has recently been demonstrated by electrogastrography.52
Another alteration seen in patients with Chagas disease is a lower basal and stimulated (under different stimuli such as histamin, histalog, pentagastrin, and calcium ion infusion) gastric acid secretion. However, when a stimulus with a cholinergic substance is added, an increase of hydrochloric acid or pepsin secretion
Figure 28.14 (A) megaesophagus group IV associated with megastomach; (B) Megaesophagus of group III associated with dilatation of stomach, bulb, and duodenal archade.
is obtained. This demonstrates that hyposecretion is mainly due to intrinsic denervation of the stomach and not due to reduction in the number of secretory cells. Fast and postprandial hypergastrinemia is another finding.
Besides these secretory and motor alterations, chronic gastritis of variable intensity is frequently found. Multiple etiopathogenic factors may be involved, such as biliary duodenogastric reflux and infection by Helicobacter pylori.
Hypertrophy of pyloric muscle is usually seen in cases with severe difficulty in gastric emptying, formerly known as pylorus achalasia. In these cases pyloroplastia is indicated as a complement to cardiomyotomy for the surgical treatment of megaesophagus.
Duodenum is, after the esophagus and colon, the segment that most often shows dilatation (Fig. 28.15).
Megaduodenum is nearly always associated with other visceromegaly. The dilatation may be localized only at the bulb (megabulb), at the second and third segments, or involve the entire duodenal arcade. Even when no dilatation is present, dyskinesia and hyperreactivity to cholinergic stimuli are common, due to enteric denervation. Symptoms caused by megaduodenum may be confused with dyspepsia of gastric origin, of the dysmotility type.
Histopathological studies have shown less degree of denervation at the small intestine than at esophagus and colon. Dilatation of jejunum or ileum characterizing megajejunum or megaileum is rare, with few published cases (Fig. 28.16).
Figure 28.15 Chagasic megaduodenum.
Figure 28.16 Megajejunum in a patient with megaesophagus of group II.
The evidence of chagasic enteropathy is not readily apparent by clinical means, but may be detected using specific investigations. Motor alterations have been described in radiological and manometric studies. Patients with other manifestations of the digestive form usually show abnormalities in the interdigestive motor migratory complex. As a consequence, it is possible to have an increase in bacterium flora growth, which in some cases is similar to that seen in the syndrome of stagnant loop.
Studies in patients with the digestive form have also demonstrated an abnormal increase in the absorption of glucose and other sugars. As a consequence, the tolerance to glucose oral test may show abnormal glycemic curves, with transitory hyperglycemia in the first hour. In association with hyperabsorption of glucose a modest hypoabsorption of fats may be seen, although not sufficient to reduce the fecal fat excretion rate. Both alterations are partially due to abnormalities in gastric emptying.
An intrinsic denervation of the gallbladder may also be observed, leading to motor alterations in gallbladder filling and emptying. Manometric alterations were also described at the Oddi sphincter. Nevertheless, colecistomegaly and choledocho dilatation are not frequent (Fig. 28.17).
A higher prevalence of colelithiasis in chagasic patients with megaesophagus and/or megacolon has been described.
Salivary glands, mainly parotids, are hypertrophic in patients with megaesophagus, a common finding in any obstructive esophageal disease as a consequence of the esophageal—salivary reflex that produces hypersalivation. Chagasic patients also have a higher sensitivity of salivary glands to mechanical stimuli of mastication and to the pharmacological stimuli by pilocarpin. Interestingly, the
Figure 28.17 Colecistomegaly in a chagasic patient.
Figure 28.18 Hypertrophic parotids in a patient with chagasic megaesophagus.
hypersalivation and parotid hypertrophy persist in esophagectomized patients, showing that these alterations are not exclusively due to the esophagus—salivary complex, but that there may also be some inervation involvement of salivary glands in Chagas disease (Fig. 28.18).
Regarding the exocrine pancreas, its functional capacity is preserved in relation to direct stimuli of the organ. However, in consequence of alterations in the delivery of duodenojejunal hormones, a secretory deficiency by indirect stimuli may be found.
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