Achalasia/Chagas Achalasia/Chagas DiseaseDisease

Kunwar Sohal, PGY 3Kunwar Sohal, PGY 3

April 20, 2010April 20, 2010

AchalasiaAchalasia

Greek term that means "does not relax" Greek term that means "does not relax" Loss of peristalsis in the distal esophagus Loss of peristalsis in the distal esophagus

(whose musculature is comprised (whose musculature is comprised predominantly of smooth muscle) and a failure predominantly of smooth muscle) and a failure of LES relaxation of LES relaxation

Histologic examination reveals decreased Histologic examination reveals decreased numbers of neurons (ganglion cells) in the numbers of neurons (ganglion cells) in the myenteric plexuses myenteric plexuses

Degeneration preferentially involves the nitric Degeneration preferentially involves the nitric oxide-producing, inhibitory neurons that effect oxide-producing, inhibitory neurons that effect the relaxation of esophageal smooth muscle; the relaxation of esophageal smooth muscle; the cholinergic neurons that contribute to LES the cholinergic neurons that contribute to LES tone by causing smooth muscle contraction are tone by causing smooth muscle contraction are relatively spared relatively spared

EtiologyEtiology

Etiology of primary achalasia is not Etiology of primary achalasia is not known, however certain recognized known, however certain recognized diseases can cause esophageal motor diseases can cause esophageal motor abnormalities similar or identical to abnormalities similar or identical to those of primary achalasia those of primary achalasia – Chagas DiseaseChagas Disease– Malignancy: most common cause of Malignancy: most common cause of

pseudoachalasia in most populations, pseudoachalasia in most populations, through invasion of plexus or as through invasion of plexus or as paraneoplastic syndromeparaneoplastic syndrome

– Achalasia like motor Achalasia like motor abnormalities: amyloidosis, sarcoidosis, abnormalities: amyloidosis, sarcoidosis, neurofibromatosis neurofibromatosis

DiagnosisDiagnosis

  A barium swallow is the primary screening A barium swallow is the primary screening test when achalasia is suspected on clinical test when achalasia is suspected on clinical groundsgrounds

Diagnostic accuracy of barium swallow for Diagnostic accuracy of barium swallow for achalasia is approximately 95 percent achalasia is approximately 95 percent

Manometry: required for confirmation in Manometry: required for confirmation in virtually all casesvirtually all cases– Elevated resting LES pressure, above 45mm HgElevated resting LES pressure, above 45mm Hg– Incomplete/absent LES relaxation: in response to a Incomplete/absent LES relaxation: in response to a

swallow swallow – Aperistalsis of the smooth muscle portion of the Aperistalsis of the smooth muscle portion of the

body of the esophagus body of the esophagus

TreatmentTreatment

Nitrates and CCBsNitrates and CCBs Botulinum toxin injection: poisons the Botulinum toxin injection: poisons the

excitatory (acetylcholine-releasing) neurons excitatory (acetylcholine-releasing) neurons that increase LES smooth muscle tone that increase LES smooth muscle tone – Initial success rates of close to 80 percent are Initial success rates of close to 80 percent are

similar to those seen with endoscopic balloon similar to those seen with endoscopic balloon dilation and surgery dilation and surgery

– Symptom relief wanes with time (70 percent at 3 Symptom relief wanes with time (70 percent at 3 months, 53 percent at 6 months, and 41 percent at months, 53 percent at 6 months, and 41 percent at 12 months 12 months

Dilation of LES: for poor surgical candidatesDilation of LES: for poor surgical candidates Surgical MyotomySurgical Myotomy

Heller Myotomy and Heller Myotomy and Toupet fundoplicationToupet fundoplication Myotomy: cut musclesMyotomy: cut muscles Toupet (posterior) fundoplication, Toupet (posterior) fundoplication,

the fundus is wrapped around the the fundus is wrapped around the back of the esophagus back of the esophagus

Chagas’ DiseaseChagas’ Disease

Caused by the protozoan parasite, Trypanosoma cruzi Caused by the protozoan parasite, Trypanosoma cruzi Humans can become infected with resulting acute or Humans can become infected with resulting acute or

chronic disease chronic disease Found only in Central and South America, Mexico and the Found only in Central and South America, Mexico and the

southern United States southern United States WHO has estimated that 16 to 18 million people are WHO has estimated that 16 to 18 million people are

infected with T. cruzi, with an estimated annual infection infected with T. cruzi, with an estimated annual infection rate of 300,000 and an annual mortality rate of >50,000 rate of 300,000 and an annual mortality rate of >50,000 patients patients

Prevalence estimates are largely based upon results of Prevalence estimates are largely based upon results of testing in blood banks. Between 1960 and 1989, the testing in blood banks. Between 1960 and 1989, the prevalence of infected blood in selected cities of South prevalence of infected blood in selected cities of South America ranged from 1.7 percent in Sao Paulo, Brazil, to America ranged from 1.7 percent in Sao Paulo, Brazil, to 53 percent in Santa Cruz, Bolivia 53 percent in Santa Cruz, Bolivia

70 to 90 percent of infected individuals are asymptomatic 70 to 90 percent of infected individuals are asymptomatic carriers of T. cruzi and never develop any symptoms carriers of T. cruzi and never develop any symptoms

Chagas’, contdChagas’, contd

Vector for this infection is the Vector for this infection is the reduviid bug, also known as the reduviid bug, also known as the "kissing bug" "kissing bug"

Once a bug is infected, it remains Once a bug is infected, it remains so for life and can transmit so for life and can transmit infection for several years infection for several years

Chronic Chagas’Chronic Chagas’ DiseaseDisease Pathogenesis of chronic Chagas' disease is unclearPathogenesis of chronic Chagas' disease is unclear Extensive debate over whether the complications that Extensive debate over whether the complications that

arise are due directly to parasite invasion or to arise are due directly to parasite invasion or to secondary autoimmune mechanisms secondary autoimmune mechanisms

Approximately 50 percent of infected individuals Approximately 50 percent of infected individuals develop cardiac and/or digestive forms of the develop cardiac and/or digestive forms of the diseasediseasetypically demonstrate cardiomegaly, typically demonstrate cardiomegaly, megaesophagus, and megacolon megaesophagus, and megacolon

DilationDilationmore R sided, signs of systemic congestion more R sided, signs of systemic congestion (ascites, hepatomegaly) predominate over pulm edema(ascites, hepatomegaly) predominate over pulm edema

The most characteristic cardiac anatomic lesion is the The most characteristic cardiac anatomic lesion is the ventricular apical aneurysm which, in one series, was ventricular apical aneurysm which, in one series, was noted in 52 percent of 1078 autopsied chagasic noted in 52 percent of 1078 autopsied chagasic patients patients

Histologic examination shows chronic mild myocarditisHistologic examination shows chronic mild myocarditis

AcuteAcute

Most patients are asymptomatic during Most patients are asymptomatic during the acute stage of infection the acute stage of infection

In a minority, acute infection may be In a minority, acute infection may be associated with a persistent local associated with a persistent local reaction, or either Chagoma (swelling reaction, or either Chagoma (swelling and local lymphadenopathy) or for bites and local lymphadenopathy) or for bites involving the orbit involving the orbit

Microscopic examination shows intense Microscopic examination shows intense parasitism in virtually every organic parasitism in virtually every organic system, with prominent inflammatory system, with prominent inflammatory changes in the vicinity of ruptured changes in the vicinity of ruptured infected cells  infected cells 

DiagnosisDiagnosis

Diagnosis is generally made by Diagnosis is generally made by testing with at least two different testing with at least two different serologic tests serologic tests

CDC recommends ELISA and IFA CDC recommends ELISA and IFA (immunofluorescence assay)(immunofluorescence assay)

TreatmentTreatment

If confirmatory testing is positiveIf confirmatory testing is positive The treatment is indicated for patients with The treatment is indicated for patients with

the acute form of the disease or in congenital the acute form of the disease or in congenital disease, no good studies in chronic disease, no good studies in chronic

Recommendations do suggest that adults Recommendations do suggest that adults aged 19-50 yrs without advanced Chagas aged 19-50 yrs without advanced Chagas cardiomyopathy, that antitrypanosomal drug cardiomyopathy, that antitrypanosomal drug treatment should generally be offerred (Bern treatment should generally be offerred (Bern et al, JAMA 2007) et al, JAMA 2007)

Nifurimox is typically their first line treatment Nifurimox is typically their first line treatment (easier to release by CDC under current (easier to release by CDC under current protocols), for 90 daysprotocols), for 90 days