Dysphagia (2023) 38:596–608

https://doi.org/10.1007/s00455-022-10435-3

REVIEW

Update on the Diagnosis and Treatment of Achalasia

Wojciech Blonski1,2 · Samuel Slone2 · Joel E. Richter2,3

Received: 16 April 2021 / Accepted: 4 March 2022 / Published online: 18 May 2022
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022

Abstract
Achalasia is a rare disease of the esophagus with impaired relaxation of the lower esophageal sphincter and aperistalsis.
The etiology is unknown but speculations include a viral or autoimmune etiology. All specialists dealing with swallowing
and esophageal diseases should recognize the classic symptoms of dysphagia for solids/liquids, regurgitation, and choking,
especially at night. High-resolution manometry is critical for the diagnosis with endoscopy and barium esophagram having
a supportive role. The disease cannot be cured but most can return to near normal swallowing and a regular diet with appro-
priate therapy. Treatment includes smooth muscle relaxants, botulinum toxin injections to the lower sphincter, pneumatic
dilation, Heller myotomy, and peroral endoscopic myotomy. One treatment does not fit all and a tailored approach through
a multidiscipline team will give the best long-term outcomes.

Keywords Achalasia · High-resolution esophageal manometry · Botulinum toxin · Pneumatic dilation · Heller surgical
myotomy · Peroral endoscopic myotomy · Deglutition · Deglutition disorders

Introduction Epidemiology

Achalasia is a rare motility disorder of the esophagus with
impaired relaxation of the lower esophageal sphincter (LES)
and aperistalsis. It was first described in 1674 by Sir Thomas
Willis and treated with a whale bone dilator. The “spasm” of
the LES results in impaired flow of ingested foods into the
stomach with stasis of food and secretions in the esophagus.
These motor abnormalities are due to loss of myenteric neu-
rons that coordinate esophageal peristalsis and LES relaxa-
tion [1]. Achalasia cannot be cured, but good treatments are
available which can be tailored to the individual person. This
review will highlight the newer aspects of the diagnosis and
treatment of achalasia and how to identify this disease by
physicians, surgeons, and speech and swallowing specialists.
* Joel E. Richter
Jrichte1@usf.edu
1
Division of Gastroenterology, James A. Haley VA Hospital,
Tampa, FL, USA
2
Division of Gastroenterology and Nutrition, Morsani College
of Medicine, University of South Florida, 12901 Bruce
B. Downs Blvd, MDC 72, Tampa, FL 33612, USA
3
Joy McCann Culverhouse Center for Esophageal Diseases,
Morsani College of Medicine, University of South Florida,
Tampa, FL, USA
The incidence of achalasia (new diagnosis) ranges from
0.3 to 3.0/100,000 adults and the prevalence (patients
with the diagnosis in the community) ranges from 1.8 to
12.6/100,000 [2]. There is equal frequency between men
and women and in whites and non-whites [1]. The inci-
dence of achalasia increases with age and the majority of
diagnoses occur after the age of 50 [1]. The prevalence of
achalasia is increasing in time whereas the incidence seems
to be remaining constant, most likely due to achalasia being
a chronic disease with a low disease-related mortality rate.
A recent study by Samo et al. at Northwestern University
sought to better define the incidence and prevalence of acha-
lasia. They found the rates were 2–3 times higher than previ-
ously reported and attributed this to the growing availability
of high-resolution manometry (HRM) permitting achalasia
to be diagnosed more accurately [2]. At the University of
South Florida Swallowing Center, the gastroenterologists
see at least 6–10 new cases of achalasia a month and the
swallowing specialists about one per month masquerading
as upper esophageal problem.

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W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia
Pathophysiology
The etiology of achalasia is unknown. This inflammatory
disease is characterized by esophageal aperistalsis and
failure of LES relaxation due to loss of inhibitory nitrin-
ergic neurons in the esophageal myenteric plexus [1].
The somatic efferent cholinergic fibers of the vagus
nerve originating from the nucleus ambiguous directly
innervate the striated muscle of the proximal esophagus,
whereas pre-ganglionic vagus nerve fibers from the dor-
sal motor nucleus innervate smooth muscle of the distal
esophagus. The latter release acetylcholine as the neuro-
transmitter that affects two types of postganglionic neu-
rons in the myenteric plexus: excitatory cholinergic neu-
rons which release acetylcholine and inhibitory nitrinergic
neurons which release nitric oxide (NO) and vasoactive
intestinal polypeptide (VIP) [3] (Fig. 1). Acetylcholine
causes esophageal and LES contractions, whereas NO and
VIP cause esophageal and LES relaxations and promote
esophageal peristalsis.
The major pathophysiologic mechanism in achalasia
is loss of NO and VIP releasing inhibitory neurons [4,
5]. A case–control study of 24 achalasia patients and 39
non-achalasia controls showed that intravenous adminis-
tration of cholecystokinin–octapeptide (CCK-OP) caused a
paradoxical increase in LES pressure in achalasia patients
due to the absence of inhibitory neurons with net unop-
posed direct excitatory effect of CCK-OP on the LES
Fig. 1  Esophageal motor
innervation. The striated muscle
of the proximal esophagus
is innervated directly by the
somatic efferent cholinergic fib-
ers of the vagus nerve originat-
ing from the nucleus ambiguus.
On the other hand, smooth
muscle of the distal esophagus
is innervated by the pre-gan-
glionic vagus nerve fibers from
the dorsal motor nucleus. They
release acetylcholine as the
neurotransmitter affecting two
types of postganglionic neurons
in the myenteric plexus: excita-
tory cholinergic neurons and
inhibitory nitrinergic neurons.
From [3]
597
smooth muscle [6] (Fig. 2). On the other hand, adminis-
tration of CCK-OP in the control group caused excitation
of both inhibitory neurons and LES smooth muscle lead-
ing to the net effect of LES relaxation. This mechanism
was explained by the overriding effect of the inhibitory
neurons over the direct CCK-OP stimulation of the LES
smooth muscle [6].
Several studies propose a possible association between
achalasia and parasitic or viral infections [7–11]. For exam-
ple, the pathophysiology of Chagas’s disease caused by
Trypanosoma cruzi resembles that of primary achalasia
[7]. In addition, achalasia patients were found to have an
increased prevalence of serum viral antibodies for herpes
simplex virus- 1 (HSV-1), human papilloma virus, Varicella-
Zoster virus, and measles virus compared to control patients
in several studies [8–11]. Other studies have detected HSV-1
DNA (viral infection), RNA (active replication), and virus in
surgical myotomy samples from patients with achalasia by
PCR (polymerase chain reaction amplification) [8–11]. The
contribution of human leukocyte antigen class II genes in the
susceptibility of achalasia was proposed in multiple small
case–control studies [12–14] and a large genetic association
study in 1,068 achalasia cases and 4242 controls [15].
An autoimmune component of achalasia has also been
proposed [16]. In one study, myenteric antiplexus autoan-
tibodies were detected in 50/92 achalasia patients and
in 3/40 healthy controls (p < 0.001) [17]. A retrospec-
tive chart review of 193 achalasia patients found that
compared to the general population data from published
13
598
Fig. 2  Both LES smooth muscle and inhibitory neurons of the myen-
teric plexus have cholecystokinin receptors. In normal esophagus,
administration of cholecystokinin–octapeptide (CCK-OP) results in
LES relaxation because the inhibitory neurons override the direct
epidemiological studies, achalasia patients were 3.6 times
more likely to have any autoimmune condition (95% CI
2.5–5.3), such as diabetes mellitus type 1, hypothyroidism,
Sjögren’s syndrome, systemic lupus erythematosus, or
uveitis [16]. Most recently, a cohort study of 2593 subjects
with achalasia matched to 10,402 controls showed an asso-
ciation between achalasia and autoimmune conditions such
as psoriasis, type 1 diabetes mellitus, pernicious anemia,
inflammatory bowel disease, autoimmune thyroid disease,
or rheumatoid arthritis (OR 1.39; 95% CI 1.02–1.90) and
atopic conditions such as eczema, allergic rhinitis, asthma,
or allergic conjunctivitis (OR 1.40; 95% CI 1.00–1.95) in
patients younger than 40 years [18].
An observational cross-sectional study comparing 26
specimens obtained from LES muscle of 32 achalasia
patients with 5 esophagectomy biopsies obtained from
patients with proximal esophageal squamous cell carci-
noma suggested that achalasia is associated with important
local and systemic inflammatory autoimmune components
[11]. LES muscle specimens from achalasia patients were
characterized by abundant perineural inflammatory infil-
trates and an increase in endoneural connective tissue and
myopathic changes. The highest inflammatory response
was observed among patients with type III achalasia when
compared with types I and II. In addition all achalasia
13
W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia
excitation of the LES smooth muscle. However, in achalasia, the LES
smooth muscle excitation is unopposed due to the loss of the inhibi-
tory neurons in the myenteric plexus. As a result, CCK-OP causes
LES contraction. From [3].
patients and none of the controls were positive for both
anti-myenteric antibodies and HSV-1 infection.
Clinical Presentation
The most common presentation of achalasia is dysphagia
for solids and liquids which can be seen in up to 100% and
85% of patients, respectively [19]. Other common symp-
toms include weight loss (30–91%), chest pain (17–95%),
regurgitation (59–64%), nocturnal cough (11–46%), and
heartburn (72%) [19]. With regards to the dysphagia, onset
can be gradual and initially the dysphagia may only be for
solid foods. By the time of presentation, most patients will
have dysphagia for both solids and liquids. Many patients
describe this sensation as food sticking or a “fullness in
the chest” [20]. Usually, they localize their symptoms to
the cervical esophagus and when associated with cough-
ing and choking, these complaints may be confused with
oropharyngeal dysphagia. The frequency of dysphagia can
range from infrequently to daily to each meal as the disease
progresses. As the disease worsens, the esophagus becomes
more dilated, regurgitation of saliva or undigested food can
become a more frequent complaint. This symptom typi-
cally occurs after meals or at night when the patient is in
W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia
the supine position and can awake the patient from sleep due
to coughing or choking. Chest pain occurs primarily at night
via unknown mechanisms [20]. It is more typical in patients
with mild disease where the esophagus is minimally dilated.
Chest pain is more common in younger patients [20]. Heart-
burn is a common symptom and is thought secondary to
retention of acidic beverages or lactic acid production from
retained food products [1].
The Eckardt score and the Achalasia-Specific Quality-
of-Life questionnaire (achalasia DSQoL or ASQ) are two
instruments used to assess the quality of life and symptom
severity before and after treatment for achalasia. The Eckardt
score (range 0–12) is a 4 question survey which addresses
the frequency of the following symptoms of achalasia: dys-
phagia, regurgitation, weight loss, and retrosternal pain [21].
The ASQ (range 10–31) is a survey in which patients can
quantify and qualify symptoms of achalasia such as dyspha-
gia to both solids and liquids and overall health in relation to
achalasia [22]. A recent study identified that an Eckardt, cut-
off of 4, and ASQ, cutoff of 15, were 94% and 87% accurate
in defining treatment successes versus failures in achalasia
[23].
Diagnosis of Achalasia
The three commonly used tests to help make a diagnosis
of achalasia are upper endoscopy, barium esophagram, and
esophageal manometry. Upper endoscopy is the first recom-
mended diagnostic test for all types of esophageal dysphagia
[24]. Barium studies are readily available in the community
but unfortunately are a “dying art” as training in the nuances
of the barium examination is being replaced by high-revenue
low radiation exposure tests, such as computed tomography
scans (CT) and magnetic resonance imaging [25]. High-res-
olution manometry is widely available but the transnasal test
is perceived as uncomfortable and community physicians
have limited training with this new technology.
Upper Endoscopy
In the community, upper endoscopy is nearly always the
first test performed in the patient complaining of dyspha-
gia. Endoscopy may reveal an alternative diagnosis (cancer,
stricture, eosinophilic esophagitis), but in early achalasia
over 50% of the cases find an entirely normal esophagus
[26]. In more advanced cases of achalasia, endoscopic find-
ings can include a dilated esophageal body with retained
saliva and food. The LES has a “puckered” appearance and
typically allows passage of the endoscope with gentle pres-
sure. An LES that is excessively tight may indicate an infil-
trate process or cancer that needs further evaluation with
endoscopic ultrasound or CT of the chest and abdomen. A
599
troubling observation we recently made was that 25% of
achalasia patients were having multiple esophageal dilations
for poorly described strictures. This persistent dysphagia not
responding to esophageal dilation has a high likelihood of
being achalasia [27].
High‑Resolution Manometry (HRM)
The gold standard test for diagnosing achalasia is high-res-
olution manometry (HRM) of the esophagus. In the perfect
scenario when achalasia is suspected, HRM should be the
next test after endoscopy has excluded mechanical obstruc-
tion. Achalasia can be divided into 3 subtypes (type I, type
II, and type III) by the Chicago Classification based on
parameters from HRM [28–31]. All three types are associ-
ated with aperistalsis and impaired LES opening as meas-
ured by the integrated relaxation pressure (IRP) The first
version of the Chicago Classification was published in 2009
[28] and since then it has been updated three times [29–31],
most recently in January 2021 as version 4.0 [31]. The most
recent 4.0 version of the Chicago Classification was based
on 10 wet swallows in the primary testing position (either
supine or upright).
Achalasia type I is defined as an increased median IRP,
100% failed esophageal peristalsis, and no panesophageal
pressurization. Achalasia type II is defined as an increased
median IRP, 100% failed esophageal peristalsis, and pres-
ence of panesophageal pressurization in ≥ 20% of swallows.
Achalasia type III is defined as increased median IRP, pres-
ence of ≥ 20% swallows with premature/ spastic contraction,
and no evidence of peristalsis (Fig. 3). It should be empha-
sized that achalasia is defined as 100% absent peristalsis
which includes failed or premature contractions.
Integrated relaxation pressure (IRP) varies with manom-
etry equipment and body position. Abnormal median IRP
for Medtronic HRM systems was set as ≥ 15 mmHg in the
supine position and ≥ 12 mmHg in the upright position; for
Laborie/Diversatek HRM systems ≥ 22 mmHg in the supine
position and ≥ 15 mmHg in the upright position [31]. The
diagnosis of achalasia does not require an abnormal median
IRP in both supine and upright positions [31].
Additional supportive testing with timed barium esopha-
gram (TBE) or functional lumen imaging probe (FLIP) has
been recommended in patients presenting with dysphagia
who have inconclusive diagnosis of achalasia on their HRM
[31]. Because of the association between opioid use and
achalasia type III, the most recent Chicago Classification
guidelines recommend performing HRM with opioids held
prior to motility testing based on medication half-life [31].
Evidence of upper esophageal sphincter (UES) dysfunc-
tion may be found in up to 60% of patients with achalasia
[32]. As shown in Fig. 4, this most commonly is a high rest-
ing UES pressure and sometimes incomplete relaxation. This
13
600 W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia

Fig. 3  High-resolution manometry pattern for the 3 types of achalasia. See text for more details based on Chicago classification. Courtesy of
USF Swallowing Center

Fig. 4  High-resolution
manometry topography of
patient with Type II achalasia.
Upper esophageal sphincter
(UES) is at top of graph with
more prominent red colors.
Panesophageal pressurization is
seen with green bars extending
from UES to non-relaxing lower
esophageal sphincter. When
this pressurization pattern is
seen, the UES hypercontacts
(blue arrows) as a protective
compensatory mechanism to
prevent aspiration. Courtesy of
USF Swallowing Center

is most commonly seen with panesophageal pressurization
classic for Type II achalasia. Most likely this is a compensa-
tory protective mechanism due to poor esophageal clearance
and/or increased intraesophageal pressure to protect from
aspiration. Interestingly, the UES abnormalities disappear
after pneumatic dilation [33].
Although the gold standard test for achalasia, some
patients find the nasal intubation intolerant, most patients
do not like repeated testing, and the LES may be difficult to
intubate in up to 10% of patients. In this setting, the motility
catheter can be placed during sedated endoscopy. Although
widely available in most communities, good training in the
performance and interpretation of HRM is limited and we
recently found underutilized compared to EGD and barium
studies [27, 34].
Barium Esophagram and Timed Barium Esophagram
The barium esophagram is considered the best test for
evaluating patients with dysphagia due to its simplicity
and low cost [34]. The classic appearance of achalasia on
barium esophagram includes esophageal dilation with poor

13
W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia 601

Fig. 5  Barium esophagram in patients with achalasia. Left: Type 1 Right: Type III achalasia with minimally dilated esophagus, tertiary
achalasia with megaesophagus, left elbow bend in lower esophagus, contractions occluding the lumen at multiple sites, and abrupt nar-
and bird beak (arrow) from non-relaxing LES and food retention. rowing at LES. Courtesy of USF Swallowing Center

emptying, absent peristalsis, and narrowing of the distal
esophagus, referred to as “bird’s beak” (Fig. 5). However,
in early cases of achalasia (up to 40%), esophageal dilation
may be absent, the narrowing of the distal esophagus mis-
interpreted as a peptic stricture, and esophageal peristalsis
either not assessed or misinterpreted as barium reflux due
to-and-from bolus movement [34]. The latter two diagnos-
tic errors are especially common in the community setting
where comprehensive barium esophagrams are infrequently
performed [25, 27].
Therefore, in order to avoid these drawbacks of the
traditional barium esophagram, the timed barium swallow
(TBS) was developed. TBS was initially described by de
Oliveira and the group of researchers at Cleveland Clinic
led by Dr Joel Richter in 1997 [35]. This simple test was
designed to assess esophageal emptying in patients with
achalasia before and after therapy (pneumatic dilatation
or surgical myotomy). In this technique, the patient drinks
100–200 ml of low-density (45% weight in volume) bar-
ium sulfate over one minute in the upright position fol-
lowed by frontal spot films of the esophagus obtained
at 1, 2, and 5 min after drinking barium. The degree of
esophageal emptying is estimated either qualitatively
by comparing 1 min and 5 min films or by measuring
height and width for both films, calculating rough area
for both and determining the percentage of change in the

Fig. 6  Timed barium esopha-

gram to assess esophageal
emptying at 1, 2, and 5 min in
patient with untreated acha-
lasia. Easy to identify moder-
ate esophageal dilation with
bird beak. Height of column
of barium is excessive (greater
than 5 cm) and does not change
over 5 min, consistent with
symptoms of dysphagia for
every meal. This study is rou-
tinely repeated after treatment
to assess for improved emptying
which correlates with long-
term improvement. Courtesy of
Cleveland Clinic-Ohio Swal-
lowing Center and previously
published in reference #55

13
602
area (Fig. 6). With time, the TBS has become part of the
standard workup at our Swallowing Center in all dyspha-
gia cases due to the fact that it is easy to perform (can be
performed by technicians rather than radiologists), has
minimal radiation exposure, and it gives details on esoph-
ageal anatomy as well as emptying of liquids and a tablet
(Figs. 5 and 6). The protocol has been modified by elimi-
nating the 2-min film and adding ingestion of a 13-mm
barium tablet 5 min after ingestion of liquid barium. The
13-mm barium tablet was added as a simple assessment
of swallowing solids. The test now is more appropriately
called the timed barium esophagram (TBE) as the key
measurements are esophageal emptying and anatomy.
Until recently the data regarding the predictive role
of TBE in untreated achalasia were very limited. A
recent retrospective study from our Swallowing Center
of 309 treatment naïve patients (achalasia, n = 117) who
underwent TBE for dysphagia established the diag-
nostic role and predictive value of TBE in this patient
population [36]. We determined that the barium column
height ≥ 5 cm at 1 min showed a sensitivity of 94% and
specificity of 71% and barium column height ≥ 2 cm at
5 min showed a sensitivity of 85% and specificity of 86%
in differentiating untreated achalasia from esophago-
gastric junction outflow obstruction (EGJOO) and non-
achalasia. In addition, the combination of liquid barium
and 13-mm barium tablet retention after 5 min increased
the diagnostic yield from 79.5 to 100% in untreated acha-
lasia patients. Based on our data, we proposed a barium
height ≥ 2 cm at 5 min be used as cutoff point for identify-
ing untreated achalasia [36]. With this accuracy, the TBE
can be used as a surrogate for esophageal manometry in
untreated achalasia patients unable to tolerate this test
or when the studies are of poor quality or unclear (for
example when it is not possible to pass the manometry
catheter through the LES).
Improvement in esophageal emptying after treatment
can also predict long-term outcome [37, 38]. The most
recent data from our Swallowing Center have shown that
as little as a 3% improvement in pre-post barium height
at 5 min (usually in range of 50 to 90%) has an accu-
racy of 94% compared to 71% accuracy of an absolute
cutoff of post-treatment barium height < 5 cm at 5 min
in predicting treatment success based on analysis of 81
achalasia patients followed for 3-year post-treatment [39].
Therefore, the most accurate parameter predicting treat-
ment success in achalasia patient is at least a 3% improve-
ment in pre–post-treatment barium height at 5 min [39].
Alternatively, we recommended use of the absolute cut-
off < 5 cm at 5 min on post-treatment TBE as a predictor
of treatment success only if pre-treatment TBE was not
performed [37].
13
W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia
EndoFLIP
Recent data suggested that assessment of esophagogastric
junction (EGJ) distensibility with endoscopic functional
luminal imaging probe (EndoFLIP, Medtronic, Minneapolis,
MN) is a better parameter than LES pressure for evaluating
the efficacy of treatment of achalasia [40].
The EndoFLIP probe is passed through the endoscope
channel and positioned across the EGJ [41]. The probe con-
sists of a 240-cm catheter with a 14-cm bag attached to its
distal end. The bag is compliant to a maximal diameter of
25 mm. There are 17 electrodes placed at 4-mm intervals
inside the bag. Cross-sectional areas (CSAs) are determined
for the 16 balloon cross-sections during volume-controlled
distensions using impedance planimetry. There are 2 pres-
sure sensors on the probe to determine intrabag pressure
which allows for assessment of EGJ distensibility. The cut-
off for normal EGJ distensibility has been set at ≥ 2.9 ­mm2/
mmHg based on data from 15 healthy volunteers [42].
EGJ distensibility measured by EndoFLIP was reduced
in untreated patients with achalasia when compared with
healthy controls (0.7 vs 6.3 m ­ m2/mmHg, p < 0.001) [40].
Interestingly, EGJ distensibility demonstrated a strong cor-
relation with the height of barium retention on the TBE at
5 min (r = 0.72, p < 0.001), whereas LES pressure showed a
poor correlation with the height of barium stasis (r = 0.25,
p = 0.26). In addition, EGJ distensibility was found to be
inversely strongly correlated with esophageal emptying
(r = − 0.72, p < 0.01) and moderately correlated with acha-
lasia symptoms (r = 0.61, p < 0.01). These data were further
supported by Pandolfino et al. who observed that the EGJ
distensibility was greatest in 20 healthy controls and the low-
est in the 23 untreated achalasia patients (8.2 vs. 0.7 m ­ m 2/
mmHg, p < 0.001) [43]. In addition, 17 achalasia patients
with good treatment response had significantly greater EGJ
distensibility when compared with either 23 patients with
untreated achalasia or 14 poor responders to achalasia treat-
ment (3.4 vs 0.7 vs. 1.5 ­mm2/mmHg p < 0.001).
Recent data from 13 patients with typical symptoms sug-
gestive of achalasia (median Eckardt score of 7), barium
stasis at 5 min on TBE (range of barium height 2.7–6.9 cm),
and HRM features of aperistalsis but an IRP < 15 mm Hg
(IRP range: 6.1–12 mm Hg) have shown that EndoFLIP can
identify an achalasia subgroup with normal IRP on HRM
[44]. EGJ distensibility was significantly reduced in patients
compared to historical healthy subjects (median 0.8 m ­ m 2/
mmHg vs. 6.3 ­mm2/mmHg, p < 0.001). Treatment of acha-
lasia resulted in significant improvement in EGJ distensibil-
ity (median pre-treatment 0.8 ­mm2/mmHg vs. median post-
treatment 3.5 ­mm2/mmHg).
It is recommended that achalasia patients should be moni-
tored using either EndoFLIP or TBS following treatment
[37, 40]. However, EndoFLIP is an invasive test using very
W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia 603

expensive equipment ($75,000 for system and $500 for each
probe) and requires another endoscopy and some technology
expertise, whereas the TBE is a simple non-invasive test
that assesses esophageal emptying. Therefore, TBE seems
an economical surrogate for EGJ distensibility. On the other
hand, intraoperative use of EndoFLIP may help determine
the appropriate length and adequacy of the myotomy in real
time during Heller myotomy or peroral endoscopic myotomy
(POEM) [43].
treated by a multidisciplinary team of specialists (gastro-
enterologists, surgeons, and swallowing therapists) where
the team can select the best treatment based on age, type of
achalasia, and comorbid diseases, rather than using the same
treatment approach for all patients.
Nitrates, Calcium Channel Blockers, and Botulinum
Toxin

The two most common oral pharmacological therapies for

Treatment Options for Achalasia
There are no curative options for achalasia. All treatments
are directed at improving quality of life, attempting to pre-
serve esophageal function and preventing esophageal sta-
sis. Current treatments reduce the obstruction at the LES
by some degree of disruption of the LES while trying not
to worsen symptoms with a new disease—gastroesophageal
disease (GERD). As shown in Table 1, the various treat-
ments of achalasia have different advantages and disadvan-
tages. We believe patients with achalasia are currently best
achalasia are long-acting nitrates (isosorbide dinitrate) and
calcium channel blockers (CCB) (nifedipine) [45]. These
medications cause smooth muscle relaxation of the lower
esophageal sphincter (LES) and decrease the sphincter
muscle tone which facilitates esophageal emptying. They
are typically taken 10–15 min before meals for the best
response. However, the effect is transient and these medica-
tions have multiple potential side effects. The most com-
mon side effects of long-acting nitrates are headache and
hypotension. The most common side effects for CCB are
bradycardia, hypotension, and pedal edema. This limits their

Table 1  Tailoring therapy for achalasia

Botulinum toxin
Outpatient procedure, popular in community
Easy to administer by endoscopy, safe
Best response in older patients and those with Type II and III achalasia, good treatment if high co-morbidities
Frequent symptom recurrence in young patients
Niche use in pregnancy and those on short-term aggressive anti-coagulation therapy
Pneumatic dilation
Outpatient procedure
Low complication risk (1–2%) and much cheaper than surgery
Best results in older patients and women
About 25% will require repeated procedures
Equal to Heller myotomy in RCT for Type I and II achalasia
Minimal GERD risk
Limited number of gastroenterologists are comfortable doing pneumatic dilations
Heller myotomy
The “gold” standard surgical treatment—widely available
Effective across all ages and sexes, but especially young men
Preferred in patients with megaesophagus, epiphrenic diverticulum, or hiatal hernia
Most effective in Type I and Type II achalasia
Modest increased risk of GERD (20–30%)
Peroral endoscopic myotomy
Increasingly available but technically demanding requiring > 100 procedures for best outcomes
Preferred treatment for Type III achalasia, equal to others in Type I and II achalasia
Endoscopic approach may be preferred with history of multiple abdominal surgeries, peritonitis, or mediastinitis
No incision, minimal pain, and rapid recovery
High risk of GERD (> 40%)—all will need to be on proton pump inhibitors
Insurance issues are improving

13
604
use to patients who are not candidates for other, more defini-
tive therapies [46].
Botulinum toxin (BTX) injected into the LES via upper
endoscopy is another treatment option for achalasia. Typi-
cally, 100 units of toxin are injected in four quadrants just
superior to the squamocolumnar junction using a needle.
Botulinum toxin works by blocking the presynaptic release
of acetylcholine. This counterbalances the loss of inhibi-
tory neurons allowing prolonged reduction of LES pres-
sure [37]. On average, the LES pressure decreases by 50%.
The response rate to botulinum toxin can be as high as 82%
although 50% of patients will have symptom recurrence
by 6 months [37]. Symptomatic responders decrease with
repeated injections thought secondary to antibody produc-
tion. The patients who are most likely to respond to BTX
are older patients (> 50 years) and those with Type II and
III achalasia with an IRP > 15 mmHg [37].
BTX is the most popular community endoscopic therapy
for achalasia where it is easy to administer and has a high
initial success rate and excellent safety profile. A survival
analysis suggests that BTX can approximate the efficacy of
pneumatic dilation (PD) in patients with a life expectancy
less than 2 years [47]. Other novel temporary uses for BTX
include achalasia in the pregnant patient (BTX does not
cross the placenta) and patients requiring strong anti-coag-
ulation after stent placement for 6–12 months [48].
Pneumatic Dilation
Pneumatic dilation (PD) is considered the most effective
non-surgical treatment option of achalasia according to
current guidelines by the American College of Gastroen-
terology (ACG) [49]. All patients undergoing PD should
be a surgical candidates due to the 1–2% risk of esophageal
perforation which may require surgical intervention [50].
PD is performed using noncompliant air-filled balloons
which come in 3 diameters 30, 35, and 40 mm (Rigiflex—
Boston Scientific, Boston, MA). PD is a graduated process
with the first treatment usually using the 30-mm size bal-
loon. However, in our Swallowing Center we may start with
a 35-mm balloon in some patients, such as young men due
to difficulties in disrupting the LES or patients after prior
myotomy due to scarring at the LES. During upper endos-
copy, the balloon is placed across the LES under fluoro-
scopic guidance and gradually inflated until the waist (due
to the non-relaxing LES), is flattened, and then is held for 15
to 60 s. The patient is discharged following 1 to 2 h obser-
vation after a negative barium esophagram for perforation
[51]. Subsequent PDs with increasing sizes balloons are per-
formed every to 2 to 4 weeks based on symptom relief and
presence of barium stasis at 5 min on TBE.
PD is an effective treatment for achalasia. According
to data from 1144 patients from 24 studies, symptomatic
13
W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia
relief was found in 74%, 86%, and 90% of patients treated
with 30, 35, and 40 mm balloons, respectively, with an aver-
age follow-up time of 37 months [51]. The factors predic-
tive of post- PD symptomatic relapse include young age
(< 40 years), male gender, single dilation with 30 -m bal-
loon, post-PD LES pressure greater than 10–15 mmHg, and
increased height of the barium column at 5 min on post-PD
TBS [21, 38, 52–55].
A prospective randomized comparative European trial
including 201 achalasia patients assigned to either PD
(n = 95) or laparoscopic Heller myotomy (LHM) (n = 106)
and followed up for a mean time of 43 months found compa-
rable efficacy between both treatments [56]. Patients in the
PD group underwent at least two PDs, the first with 30-mm
balloon and the second with 35-mm balloon 1 to 3 weeks
later. The third PD with 40-mm balloon was performed
4 weeks later if the Eckardt score was > 3. The rates of thera-
peutic success (primary outcome defined as decrease in the
Eckardt score to ≤ 3 annually) were not different between PD
and LHM after 1 year (90% vs. 93%, p = 0.46) and 2 years
(86% vs. 90%, p = 0.46) [56]. Predictors of treatment failure
with PD included pre-existing daily chest pain, age younger
than 40 years, and barium height > 10 cm at 5 min on post-
treatment TBE [56]. Recurrence of symptoms requiring
redilation occurred in 23 patients which was not successful
in 5 of 17 patients who underwent repeat PD. Subsequent
reanalysis of data from the European trial showed that the
efficacy of PD was superior to LHM in patients with acha-
lasia type II (n = 114, 100% vs. 93%; p < 0.05), equal to
LHM in patients with achalasia type I (n = 44; 81% vs. 85%;
p = 0.84), and inferior to LHM in patients with achalasia
type III (n = 18; 86% vs. 40%; p = 0.12, difference was not
statistically significant due to small number of patients) [57].
The 5-year follow-up data from the European trial showed
no significant difference in therapeutic success rates between
PD and LHM (82% vs. 84%, p = 0.92) [58]. Of note, redila-
tion was needed in 25% of PD patients. GERD may occur
in 15–35% of patients after PD [51, 56]. However, no sig-
nificant difference was found in abnormal distal esophageal
acid exposure between patients after PD vs. LHM (15% vs.
23%, p = 0.28) [56].
Laparoscopic Heller Myotomy
Surgical myotomy of the muscle layers of the lower esopha-
gus and LES, known as the Heller myotomy after a German
surgeon, is the traditional surgical treatment for achalasia.
The operation has been done laparoscopically since 1992,
allowing better visualization of the distal esophageal muscle
layers and gastric sling fibers of the upper stomach, result-
ing in a shorter operation and recovery time. The key com-
ponents of the operation are (1) a myotomy at least 6 cm
onto the esophagus and 2–3 cm onto the upper stomach to
W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia
eliminate the gastric sling fibers and (2) an anti-reflux fun-
doplication (Dor or Toupet) to reduce subsequent GERD
after destroying the LES [59, 60].
The LHM is a remarkably safe and effective operation. In
a large systematic review [61], the mean success was 89%
(range 76–100%) with average follow-up of nearly 4 years
[3]. A recent large European study randomly assigned 109
patients to LHM with Dor fundoplication and 112 patients
to peroral endoscopic myotomy (POEM) and accessed clini-
cal success at 2 years [62]. Resolution of dysphagia symp-
toms and improvement in esophageal function was similar in
both groups: 81.7% for LHM and 83% for POEM. However,
GERD and esophagitis were twice as high in the POEM
group (44%) compared to the LHM (29%). The operative
mortality rate for LHM is less than 0.1% and the most com-
mon complication is esophageal perforation in less than 5%
of cases.
Predictors of success for LHM include young age
(< 40 years), LESP greater than 30 mmHg, and a straight,
non-tortuous sigmoid esophagus [1]. Type I and II acha-
lasia patients do equally well with LHM because the single
site of obstruction at the LES is easily eliminated. Type III
achalasia patients with multi-sites of obstruction do less
well but better than PD. In this setting, POEM surgery is
definitely superior. Over 10–20 years, 10 to 20% after LHM
will relapse and need further treatment [1]. The main factors
are incomplete myotomy, usually on the stomach side, tight
or dysfunctional anti-reflux wrap, and late scarring of the
myotomy site [63]. Despite the fundoplication, GERD does
worsen over time after LHM in the range of 10 to 32%, but
these results are 2–3fold less than with POEM (46). Over
30 cases of Barrett’s esophagus and 6 cancers have been
reported 6 to 37 years after surgical myotomy [64].
Peroral Endoscopic Myotomy
Peroral endoscopic myotomy (POEM) was developed in
2010 by Dr. Inoue, a Japanese surgeon, to provide a less
invasive treatment of achalasia [65]. During upper endos-
copy, a mucosal incision 10–15 cm proximal to the LES
is made followed by creation of a long-submucosal tunnel
followed by endoscopic myotomy of a circular muscle bun-
dles within the distal esophagus and cardia (2 cm) [65, 66].
The length of myotomy within the distal esophagus can be
adjusted as desired. No fundoplication is performed, thus
there is a risk of developing GERD. On the other hand, the
advantages of this endoscopic procedure are lack of scar,
minimal pain, and availability on an outpatient basis. In
addition, POEM allows for performing a longer myotomy
if desired due to avoidance of mediastinal dissection, avoid-
ance of vagal nerve injury, and lack of intra-abdominal adhe-
sions that might affect future surgeries [67]. The procedure
is safe; serious adverse events are rare (0.5%) and include
605
esophageal leak, bleeding, empyema, or pneumonia [68].
Although the initial observations suggested that performance
of at least 40 procedures are required to achieve efficiency
and 60 procedures to achieve mastery [69], the most recent
data show that performance of at least 100 procedures are
required to decrease the risk of technical failure, adverse
events, and clinical failures [70].
A recently published randomized multicenter trial com-
pared the treatment efficacy of achalasia between POEM
(n = 67) and PD with a 30-mm and a 35-mm balloons
(n = 66) [71]. Patients assigned to PD group underwent no
more than two PDs, the first with 30-mm balloon and the
second with 35-mm balloon if Eckardt score was > 3 or
if repeat HRM in patients with Eckardt score ≤ 3 showed
IRP ≥ 10 mmHg. The intention-to-treat groups included 63
patients in POEM and 63 patients in PD groups. The rates
of treatment success (Eckardt score ≤ 3 and the absence of
severe complications or re-treatment) at the 2-year follow-up
were significantly greater in the POEM group when com-
pared with PD group (92% vs. 54%, p < 0.001). The limita-
tion of this clinical trial was that patients treated with PD
were not treated with third dilation using 40-mm balloon
before being declared treatment failures. Nonetheless, some
patients did undergo 40-mm balloon dilation with therapeu-
tic success of PD improved from 54 to 76% on the post hoc
analysis. However, the treatment success rate of POEM was
still significantly greater (92%, p = 0.008).
Finally, recent meta-analysis of 20 studies including 1575
achalasia patients determined that POEM was associated
with greater therapeutic success rates than LHM for acha-
lasia type I (OR 2.97, 95% CI 1.09–8.03; p = 0·032) and
type III (OR 3.50, 95%CI 1.39–8.77; p = 0.007) achalasia
[72]. On the other hand, POEM and LHM were associated
with similar rates of therapeutic success for type II achalasia
(OR 1.31, 95% CI 0.48 to 3.55; p = 0.591). This confirms the
efficacy of POEM in all types of achalasia, but it is particu-
larly superior in type III achalasia when a long myotomy is
required.
The major drawback of POEM is the risk of GERD.
A systematic review with meta-analysis of 17 studies of
1542 achalasia patients treated with POEM and 28 stud-
ies of 2581 achalasia patients treated with LHM found the
greater incidence of GERD among those treated with POEM
vs. LHM [73]. The pooled rate of postprocedural GERD
symptoms was 19.0% (95% CI 15.7–22.8%) after POEM vs.
8.8% (95% CI 5.3–14.1%) after LHM, the rate estimate of
abnormal acid exposure on esophageal pH monitoring was
39.0% (95% CI 24.5–55.8%) after POEM vs. 16.8% (95%
CI 10.2–26.4%) after LHM, and the rate of esophagitis was
29.4% (95% CI 18.5–43.3%) after POEM vs. 7.6% (95% CI
4.1–13.7%) after LHM.
Therefore, the recent expert review and best practice
advice from the American Gastroenterological Association
13
606
has recommended that achalasia patients after POEM should
be considered high risk of developing reflux esophagitis
and counseled prior to undergoing POEM about potential
post-POEM need for indefinite use of proton pump inhibitor
therapy and/or surveillance endoscopy [67]. Uncontrolled
GERD post-POEM may lead to development of Barrett’s
esophagus and potentially adenocarcinoma. This latter event
has now been reported in a single well-documented case
report 4-year post-procedure [74].
Opioid‑Associated Achalasia
A relatively new observation is that Type III achalasia along
with esophagogastric junction outflow obstruction (EGJOO)
are more likely to be associated with the use of opioids,
compared with Types I and II achalasia. Studies suggest that
11–13% of Type III and 13–37% of EGJOO may be due
to activation of mu and kappa receptors by opiates which
impair LES relaxation [75–77]. The most commonly incrim-
inated narcotics are oxycodone, hydrocodone, and tramadol
[78]. It is suggested but not known that studying patients off
their opioids for variable times based on drug half-life will
reduce this potential confusion [31]. Although an interesting
observation, there are no good data that patients on opioids
with Type III achalasia/EGJOO will not do well with tradi-
tional therapies, if the opioids cannot be discontinued.
Tailoring Therapy for Achalasia
Despite being a relatively rare disease, the wide availability
of HRM has increased the diagnosis of achalasia in both aca-
demic medical centers and the community. However, ease of
diagnosis does not mean that all gastroenterologists or sur-
geons can adequately treat these patients. We advocate the
treatment of achalasia be tailored to the individual achalasia
patient and one treatment does not fit all [48, 79] (Table 1).
Furthermore, the endoscopic and surgical expertise for
these multiple treatments are not available everywhere and
complex cases should be referred to Esophageal Centers
of Excellence. Just to give some brief examples. BTX is
best for the older patient, with comorbid diseases or a short
life expectancy, and should not be a preferred treatment for
healthy individuals [80]. Pneumatic dilation is a very effec-
tive outpatient treatment for achalasia, but unfortunately
fewer and fewer young gastroenterologists are being trained
in this procedure and thus is may not be available in many
communities [81]. The Heller myotomy is now encountering
strong competition from the POEM procedure, but long-
term success is highly dependent on surgical volume and the
risk of GERD and its complications (even cancer) are high
with POEM. Therefore, we strongly believe a multidiscipline
approach with weekly conferences to discuss these cases will
give our patients the best opportunity for long-term success.
13
W. Blonski et al.: Update on the Diagnosis and Treatment of Achalasia
Summary
Although a rare disease, achalasia is being increasingly
diagnosed with the wide availability of high-resolution
manometry. All specialists dealing with esophageal and
swallowing problems should recognize the classic symp-
toms of dysphagia for solids and liquids (often in the
cervical area), regurgitation, and coughing/choking usu-
ally at night. Although achalasia cannot be cured, most
patients can be returned to near normal swallowing and
a regular diet. Treatment options are multiple, including
medical, endoscopic, and surgical therapies. We believe
that the best outcomes for our achalasia patients comes
from a multidiscipline approach tailoring treatment to each
patient’s clinical situation, rather than one treatment fits
all.
Authors Contributions Invited review. Subject headings equally
divided up among 3 authors who did literature search and wrote their
sections. Senior author (JR) put the entire manuscript together.
Declarations
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical Approval The authors did not receive support from any organi-
zation for the submitted work.
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Wojciech Blonski MD
Samuel Slone MD
Joel E. Richter MD