REVIEW ARTICLE
Achalasia: A Review of Etiology,
Pathophysiology, and Treatment
Nor Hedayanti, Supriono
Division of Gastroentero-hepatology, Department of Internal Medicine
Faculty of Medicine, University of Brawijaya/Dr. Saiful Anwar Hospital, Malang
Corresponding author:
Supriono. Division of Gastroentero-hepatology, Department of Internal Medicine, Dr. Saiful Anwar
General Hospital. Jl. Jaksa Agung Suprapto No. 2 Malang Indonesia. Phone/facsimile: +62-341-348265.
E-mail: gastro_mlg@yahoo.com
ABSTRACT
Achalasia was a condition marked by peristaltic movement absent in lower esophageal sphincter and segment
that hypertonic result in imperfect relaxation during food ingestion. Achalasia incidence did not differ between
men and women, account for 1 in 100,000 people every year with prevalence of 10 in 100,000 people, unrelated
VSHFL¿FDOO\ZLWKHWKQLFDQGKDVLWVKLJKHVWLQFLGHQFHRQDJHJURXS
Based on its etiology, it was divided into primary and secondary Achalasia, while based on its motility, it was
into hypermotil, hypomotil, and amotil achalasia. Until present, several therapeutic modalities were available
to treat Achalasia, among them was pharmacology therapy, botulinum toxin injection via endoscopy, pneumatic
dilatation, Heller myotomy surgery, and per oral endoscopy myotomy (POEM).
Keywords : achalasia, patophysiology, therapy
ABSTRAK
Akalasia merupakan suatu keadaan yang ditandai dengan tidak adanya peristaltik di esofagus bagian bawah
dengan spingter esofagus bagian bawah (LES) yang hipertonik sehingga tidak terjadi relaksasi sempurna saat
menelan makanan. Angka kejadian akalasia pada perempuan dan laki laki adalah sama, yaitu 1 dari 100.000
orang per tahun dengan prevalensi 10 pada 100.000 orang, tidak didapatkan pada ras khusus dan angka kejadian
tertinggi pada usia 30-60 tahun.
Berdasarkan etiologi terdapat dua jenis akalasia, yaitu primer dan sekunder sedangkan berdasarkan motilitas
terdapat tiga jenis akalasia, yaitu akalasia hipermotil, akalasia hipomotil, dan akalasia amotil. Hingga saat ini,
terdapat beberapa modalitas terapi akalasia, antara lain intervensi farmakologi, injeksi toksin botulinum per
endoskopi, dilatasi pneumatik, bedah Heller myotomy, dan Per Oral Endoscopy Myotomy (POEM).
Kata kunci :DNDODVLDSDWD¿VLRORJLWHUDSL
INTRODUCTION
result in food static during ingestion and esophagus
$FKDODVLDZDV¿UVWO\GHVFULEHE\6LU7KRPDV:LOOLV dilatation. This condition will lead to several symptoms
in 1674 after he use whale bone to dilate his patients and complication, depend on its severity and duration.1,2
esophagus because of lower esophageal sphincter Some Literatures said that Achalasia was a primary
relaxation failure. Achalasia was progressive idiopathic GLVRUGHU RI HVRSKDJXV ZLWK UHOD[DWLRQ LQVXI¿FLHQF\
neural degeneration of Auerbach myenteric plexus, of lower esophageal sphincter as its etiology, with
32 The Indonesian Journal of Gastroenterology, Hepatology and Digestive Endoscopy
Achalasia: A Review of Etiology, Pathophysiology, and Treatment
UDGLRJUDSKLF ¿QGLQJV RI DSHULVWDOWLF HVRSKDJXV ZLWK DFLGUHÀX[EDUULHUWRHVRSKDJXVDQGQRUPDO\LQWRQLF
minimal openings, called bird-beak sign.3 or constriction state, except during food ingestion.
Incidence of Achalasia in men and women was Esophagus mucosa was base and not suitable for acid
similar, account for 1 from 100,000 people every from gastric secretion. Submucosal layer has secretory
year with prevalence of 10 in 100,000 people, did cells which produce mucus in order to help food
QRWVSHFL¿FIRUVRPHHWKQLFVDQGKLJKHVWLQFLGHQFH movement during ingestion process.4
was found in 30-60 age groups. In US, 2000 cases of At normal state, esophagus shown two types
Achalasia was reported every year, mostly at 25-60 of peristaltic: primary peristaltic and secondary
age groups, and rarely found in children. Otherwise, peristaltic. Primary peristaltic was only a movement
in Gastroentero-hepatology division, Internal Medicine following previous peristaltic movement in faring and
Department, Faculty of Medicine, University of continuing to esophagus during ingestion process.
Indonesia/Dr. Cipto Mangunkusumo Hospital, 48 This movement period start from faring to stomach
cases was found during 5 years period (1984-1988), was estimated for 8 to 10 seconds. But, food ingestion
mostly with the same age groups.2,3Achalasia was durin erect position result in faster food movement,
not a rare condition. This could be seen in middle- about 5-8 seconds, because of gravity effect. If primary
aged population, clinically marked with dysphagia, peristaltic movement fail to push all the food into
regurgitation, and epigastric discomfort. Clinically, stomach, secondary peristaltic movement than started.
Achalasia was divided into primary and secondary, This movement start from mienteric nerve and several
based on its etiology.2,3 UHÀH[HVIURPDIIHUHQWYDJDOQHUYHIURPHVRSKDJXVWR
American collage Gastroenterology Clinical medulla than back to esophagus.4
Guideline in Diagnosis and Management of Achalasia In the lower part of esophagus, about towo to
in 2013 recommended barium esophagogram ¿YH FHQWLPHWHU DERYH VWRPDFK HVRSKDJHDO FLUFXODU
to assess esophageal emptying, esophagogastric muscle functioned as gastroesophageal sphincter.
junction morphology both during gastric emptying Anatomically, this sphincter was not differ to other
and to evaluate its motility. Endoscopy procedure esophagus parts. Physiologically, sphincter will have
to see gastroesophageal junction and gastric cardia tonic constriction (with intraluminal pressure of 30
was recommended in all patients with Achalasia mmHg), differ from middle esophagus which in normal
to eliminate the possibility of pseudoachalasia. 3If condition was in relaxation state. When peristaltic
irreveribe functiona disorder happened, the main movement during ingestion process pass esophagus,
therapy for Achalasia was palliative treatment. receptive relaxation process will relax lower esophageal
Dominant symptoms of this disorder was progressive sphincter before peristaltic movement and allow food
dysphagia, regurgitation, chest pain, and weight loss.3 to enter stomach. Rarely, sphincter does not relax, so
that the condition called Achalasia happened.4
ETIOLOGY
Achalasia was divided into primary and secondary CLINICAL MANIFESTATION
Achalasia. In primary Achalasia, the exact etiology is
Dysphagia of both solid and liquid food was the
unknown, probably caused by neutropic virus infection
most common symptoms of achalasia, followed by
result in dorsal vagal nucleus lesion in brainstem and
regurgitation, chest pain, nausea, vomiting, weight
mesenteric ganglia in esophagus. Hereditary factor
loss, and night cough. Otherwise, chest pain was the
also has a role in this disorder. Otherwise, secondary
PDLQ V\PSWRPV RI JDVWURHVRSKDJHDO UHÀX[ GLVHDVH
Achalasia was caused by infection, intraluminar tumor
(GERD) caused by esophagus irritation from gastric
such as cardia tumor, extraluminal pressure from
acid. In patients with Achalasia, this symptoms could
pancreatic pseudocyst, anticholinergic drugs, or post
be caused by gastric acid retention or toxin produced
vagotomi operation.2
by fermented lactate by bacteria in esophagus.3
Achalasia was divided into three types (Figure
PATHOPHYSIOLOGY
1) based on its motility. First type is hypermotile
Esophagus main function is to deliver food ingested Achalasia, a vigorous Achaalasia, with pain dysphagia
from faring to stomach by peristaltic movement and regurgitation symptoms. Second type is hypomotile
ranged from 5-15 seconds. In upper and lower part Achalasia with dysphagia, pain, and regurgitation as its
of esophagus, a sphincter was important for gastric symptoms. The last type was amotile Achalasia with
Volume 17, Number 1, April 2016 33
Nor Hedayanti, Supriono
dysphagia and regurgitation symptoms. In amotile calcium channel blocker and long acting nitrate was
Achalasia, there were failure of normal peristaltic effective to lower pressure in LES and sometimes
so that esophagus was widely dilated in chronic reduce dysphagia, but did not improve its relaxation
Achalasia.5,6 ability or peristaltic movement of LES.7
There were several diagnostic modalities to evaluate Because of longer transit time and delayed in
esophagus emptying, which was a characteristic of
Achalasia, absorption and effectivity of any oral
drugs cannot be calculated. Those drugs was better
used via sublingual route, such as nifedipine 10-30
mg sublingual for 30-45 minutes before meals and
ISDN 5 mg sublingual 10-15 minutes before meals.
Those drugs reduce pressure in LES for about 50%.
Ong acting nitrate has a shorter time of action, 3-27
minutes, and showd a better clinical improvement in
53-87% case compared to nifedipine that works for
Figure 1. Types of Achalasia5 30-120 minutes with 0-75% effectivity.7
The main limit in those drugs is its short duration of
Achalasia, such as manometry, barium esophagogram, action that only reduce some symptoms and reduce its
esophagoduodenoscopy, and esophagus CT-scan.6 HI¿FDF\LQORQJWHUPXVH%HVLGHVLWVVLGHHIIHFWOLNH
peripheral edema, headache, and hypotension could
be found in 30% patients.7
TREATMENT
Drugs were used limited to patient in early
Since 17th century, achalasia therapy was started. condition without esophageal dilatation, or in patients
6XUJHRQVKDYHPDGHVLJQL¿FDQWLPSURYHPHQWLQ$FKDODVLD ZDLWLQJIRUGH¿QLWLYHWUHDWPHQWRUSDWLHQWLQKLJKULVN
therapy.1 Otherwise, until now, none of achalasia therapy that refuse to undergo invasive procedures. Drugs were
could change its pathology and all treatment was just a also indicated in severe Achalasia with chest pain
palliative of its clinical manifestation3 symptoms. Pharmacotherapy in this condition was
highly recommended.7
Pharmacology
Endoscopic Botolium Toxin Injection
Based on Society of American Gastrointestinal and
Endoscopic Surgeons in Guidelines for the Surgical Toxin botulinum is a neuro toxin works to inhibit
Treatment of Esophageal Akalasiain 2009,the goal of neurotransmitter in terminal cholinergic receptor.
pharmacotherapy was to help obstruction reduction Botulinum toxin-A that used for Achalasia therapy
and improve lower esophageal sphincter relaxation works by breaks SNAP-25 protein molecule in
function. Several pharmacological agents such as presynaptic membrane, so that acethylcholine relese
Figure 2. Botulinum toxin mechanism of action and injection location9,10
34 The Indonesian Journal of Gastroenterology, Hepatology and Digestive Endoscopy
Achalasia: A Review of Etiology, Pathophysiology, and Treatment
was blocked and inhibit acetylcholine exocytosis to was used in recent 30 years with the most succesfull
synaptic area. This will result in transient muscle rate of 75-85% after repeated dilatation. Complication
weakness by blocking cholinergic stimulation in LES VXFK DV HVRSKDJHDOUHÀX[ RU HVRSKDJHDOSHUIRUDWLRQ
(Figure 2).1 were rarely found. This special technique was not only
Botulinum toxin injection locally could reduce LES based on it size, but also based on its duration of LES
pressure and increase esophagus passive emptying. dilatation, range from seconds to 5 minutes. Balloon
Toxin injected via sclerotherapy during endoscopy.
In normal condition, 80 to 100 unit of Botulinum
toxin-A was injected in each LES quadrant to reduce
its pressure, increase esophageal opening, and improve
esophageal emptying.1,8
Clinical effect from single injection was short
term effect with relaps incidence more than 50% in 6
months. Otherwise, repeated injection could give more
effect in 70-90% patients. A report showed that 21% of
Figure 3. Pneumatic dilatation9
newly diagnosed Achalasia patients was treated using
botulinum toxin as early modalities with injection
was dilated perfectly in short time to get optimum
duration of 6 months. Good response from botulinum
LES dilatation. In 60 seconds, balon was reexpanded
toxin injection was found in patients aged less than 50
in several minutes, and in each procedure was using
years old and patients with severe Achalasia.1,8
maximum two ballon (Figure 3).2
This therapy was safe, only 10% complained chest
The use of dilator made from polyethylene has a
SDLQDIWHULQMHFWLRQEXWPRVWO\GLGQRWUHTXLUHVSHFL¿F
succesfull rate of 93% with lower complication during
therapy. But, repreated injeaction could make myotomy
4 years follow up. Fluoroscopy guided endoscopy was
procedure during surgery seems harder because of
effective to dilate balloon. Pneumatic dilatation was
adhesion of muscular layer and increase perforation
done using endoscopy in sedated patients, result in 60%
possibility in mucosa. Regarding to patient safety,
reduce in LES pressure and 79% symptos resolution. A
botulinum toxin injeaction could be given if no other
report from Cleaveland showed that 41% of new cases
choice present or if surgery correction contraindicated,
was treated with pneumatic therapy, result in clinical
and in patients with survival rate of 2 years.1
response of 86% and 54% esophagus emptying. 1,11
Pneumonic Dilatation
Pneumatic Dilatation vs. Botulinum Toxin Injection
Dilatation procedure was firstly done to treat
In randomized study involving 42 patiens,
achalasia. This principle of therapy is to weakend
botulinum injection and pneumatic dilatation was
/(6E\WHDULQJLWVPXVFOH¿EHUUDGLDOO\IURPLQVLGH
happened in 70% and 32%, respectively, in 12 months.
esophagus. Endoscopic dilatation was believed as the
A Cochrane database review in sic studies involving
most safe no surgical therapy for achalasia. Pneumatic
178 patients showed statistically indifferent after
dilator were preffered than stiff dilator in achalasia
four weeks of intervention. Three research, including
therapy because of its effect that widening and break
reviewer, showed a remisiion of about 33 cc per 47cc
muscle fibre in LES. Several pneumatic dilator
after pneumatic injection. This also happened in 11
DYDLODEOHWRGD\KDYHWKHVDPHHI¿FDF\DQGVDIHW\EXW
of 43 patients after both botulinum injection and
only few data could support it.1
pneumatic dilatation. Relative risk was 2,67. This
Dilatation treatment was slowly reduce its
showed that pneumatic dilatation was more effective
symptoms. The most simple treatment to done is Hurst
than botulinum injection in long term Achalasia3
plugging procedure, made from mercury-contained
rubber, have four different size in F (French) scale.
Laparoscopic Heller Myotomy (LHM)
It works principally based on gravitation using the
smallest radius plug to the biggest. Its effectivity only Surgical therapy in Achalasia was known as Heller
50% with no relaps case, 35% with relaps, and 15% myotomy, a procedure where muscle surrounding
failure to respond.2 esophagus was exposed and cut. Conventional surgery
The most recommended procedure was LES was using long incision in thorax. Recent years,
dilatation using pneumatic dilator. This procedure laparoscopic approach have been use as minimal
Volume 17, Number 1, April 2016 35
Nor Hedayanti, Supriono
invasive concept similar to open-surgery concept. This
PHWKRGZDVKDYLQJORWRIEHQH¿WEHFDXVHRILWVVKRUWHU
length of stay in hostpital, less pain, smaller operation
scar, and faster recovery time. Laparoscopic approach
was safe and effective in achalasia therapy, although
VRPHWLPHVDQDWRPLFDOYDULDWLRQPDGHLWVOLJKWGLI¿FXOW10
A meta-analysis that compare short term and
long term effect of LHM and balloon dilatation via
endoscopic was done. From 16 studies consist of 590
LHM procedure and balloon dilatation via endoscopy
with follw up in 12, 24, and 60 months, it can be
concluded an OR of 2,2 in 12 months, 5,06 in 24
months, and 29,83 in 60 months of LHM superiority
as the main choice of therapy. Besides, only 18 patients
reported having redilatation after LHM procedure,
while 110 patients in balloon dilatation, even 36 among
them should undergo myotomy as its retreatmen.12
LHM was found to be effective with long term
outcome. Most of its risk came from general anesthesia
procedure. Esopohageal perforation is one of the
complication, but could be detected during operation Figure 4. POEM procedure13
and repaired without serious further complication.9
CONCLUSION
Peroral Endoscopy Myotomy (POEM) There were several types of Achalasia based on
its etiology and motility. Modality choices to treat
POEM is a technique involving tunneling between
Achalasia was more various in recent years. But, there
esophageal muscle to treat achalasia, especially
were no therapy yet to change its pathology, so that
with Chagas disease. This procedure was done via
those therapies were just palliative therapies.
endoscopy so that no exterior incision was made.
POEM was effective to cure dysphagia symptom in
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