Received: 9 April 2021 | Revised: 27 April 2021 | Accepted: 3 May 2021

DOI: 10.1111/nmo.14182

TECHNICAL NOTE

Chicago Classification update (version 4.0): Technical review on

diagnostic criteria for achalasia

Abraham Khan1 | Rena Yadlapati2 | Sutep Gonlachanvit3 | David A. Katzka4 |

Moo In Park5 | Michael Vaezi6 | Marcelo Vela7 | John Pandolfino8

1
Center for Esophageal Health, NYU
Langone Health, New York, NY, USA Abstract
2
Center for Esophageal Diseases, Division The recommended diagnostic criteria for achalasia have been recently updated by
of Gastroenterology & Hepatology,
University of California San Diego, La
Chicago Classification version 4.0 (CCv4.0), the widely accepted classification scheme
Jolla, CA, USA for esophageal motility disorders using metrics from high-­
resolution manometry
3
Center of Excellence on (HRM). CCv4.0 continued upon prior versions by subtyping achalasia into type I,
Neurogastroenterology and Motility,
Division of Gastroenterology, type II, and type III on HRM. The achalasia subgroup of the CCv4.0 Working Group
Chulalongkorn University, Bangkok, developed both conclusive and inconclusive statements for the HRM diagnoses of
Thailand
4 achalasia subtypes. Conclusive achalasia on HRM is defined as an abnormal median
Mayo Clinic, Rochester, MN, USA
5
Department of Internal Medicine, Kosin integrated relaxation pressure (IRP) in the primary position of wet swallows along with
University College of Medicine, Busan, 100% failed peristalsis, with type I achalasia having 100% failed peristalsis without
Korea
6 panesophageal pressurization (PEP), type II achalasia with PEP in at least 20% of swal-
Vanderbilt University Medical Center,
Nashville, TN, USA lows, and type III achalasia having at least 20% of swallows premature with no ap-
7
Mayo Clinic Arizona, Scottsdale, AZ, USA preciable peristalsis. An inconclusive HRM diagnosis of achalasia can arise when there
8
Division of Gastroenterology & is an integrated relaxation pressure (IRP) that is borderline or at the upper limit of
Hepatology, Northwestern University
Feinberg School of Medicine, Chicago, normal in at least one position, there is an abnormal IRP in both positions but evidence
IL, USA of peristalsis with PEP or premature swallows, or there is peristalsis in the secondary
Correspondence position after apparent achalasia in the primary position. In patients with dysphagia
Abraham Khan, Center for Esophageal and an inconclusive HRM diagnosis of achalasia, supportive testing beyond HRM such
Health, NYU Langone Health, New York,
NY, USA. as a timed barium esophagram (TBE) for functional lumen imaging probe (FLIP) is rec-
Email: Abraham.Khan@nyulangone.org ommended. The review recommends a diagnostic algorithm for achalasia, discusses
Funding information therapeutic options for the disease, and outlines future needs on this topic.
No funding declared.
KEYWORDS
Chicago Classification, dysphagia, high-­resolution manometry, hypercontractile esophagus,
jackhammer esophagus, non-­cardiac chest pain

1 | I NTRO D U C TI O N
The Chicago Classification has gained worldwide acceptance in catego-
rizing esophageal motility disorders using esophageal high-­resolution
manometry (HRM), with the first three versions published between
2009 and 2015.1–­3 The recently developed Chicago Classification
version 4.0 (CCv4.0) expanded upon prior adaptations with the as-
sistance of an international HRM Working Group composed of 52 di-
verse members using formal validated methodologies over two years.4
The 52 members were assigned to seven subgroups: standard HRM
protocol, achalasia, esophagogastric junction outflow obstruction
(EGJOO), distal esophageal spasm (DES), hypercontractile esophagus

Neurogastroenterology & Motility. 2021;33:e14182. wileyonlinelibrary.com/journal/nmo © 2021 John Wiley & Sons Ltd | 1 of 9
https://doi.org/10.1111/nmo.14182
2 of 9 | KHAN et al.
(HE), ineffective esophageal motility (IEM) and EGJ metrics. Two co-­
chairs led each subgroup, which additionally incorporated a non-­voting
member tasked with independent review of supportive literature and
assessment of level of evidence. This technical review details the work
of the achalasia subgroup in developing statements regarding the
manometric diagnosis of achalasia and the value of supportive testing
beyond HRM. This review also proposes a specific diagnostic algorithm
for achalasia, discusses clinical considerations and therapeutic options
for the disease, and emphasizes future needs on this topic.
2 | M E TH O D S
The achalasia subgroup of the CCv4.0 Working Group developed both
conclusive and inconclusive statements for the HRM diagnosis of acha-
lasia and statements regarding supportive testing and other relevant
clinical considerations. Each statement underwent a formal process to
assess the appropriateness of the statement and the level of support-
ive evidence, as outlined in the primary CCv4.0 document.4 The RAND
appropriateness method (RAM) evaluated each statement with two
rounds of independent ranking by the whole CCv4.0 Working Group,
with statements having ≥85% agreement being considered strong rec-
ommendations and those with 80%–­85% agreement considered con-
ditional recommendations. The statements without these categories
of agreement were discussed at working group meetings. Secondarily,
statements that met criteria for inclusion in the final CCv4.0, when
logistically possible, underwent a formal assessment regarding level
of supportive evidence using the Grading of Recommendations
Assessment, Development, and Evaluation (GRADE) process.5
3 | H R M M E TR I C S A N D D I AG N OS TI C
C R ITE R I A
CCv4.0 continued upon prior editions by subtyping achalasia into type
I, type II, and type III on HRM.6 The standard HRM protocol combined
with the hierarchical classification scheme of CCv4.0 establishes that
achalasia can be diagnosed with an abnormal median integrated re-
laxation pressure (IRP) in either a primary supine or upright position
with 10 wet swallows, as long as there is coinciding 100% absent peri-
stalsis (all swallows either failed or premature).4 Several statements in
CCv4.0 led to this overarching algorithmic scheme, and also served to
guide a practitioner when achalasia diagnostic dilemmas are observed.
4 | R ECO M M E N DATI O N S (S TATE M E NT S
W ITH AG R E E M E NT )
4.1 | Conclusive diagnosis of achalasia
Statement 1. A conclusive diagnosis of type I achalasia is defined as an
abnormal median IRP and absent contractility (100% failed peristalsis)
(strong recommendation, very low GRADE evidence).
Keypoints: What is new since the CCv3.0
• A conclusive diagnosis of type I, type II, and type III
achalasia can be made with metrics from one position
during wet swallows using the CCv4.0 standard proto-
col. Conclusive type III achalasia now mandates having
no appreciable peristalsis in addition to the necessary
premature swallows.
• An inconclusive diagnosis of type I or type II achalasia
consists of an IRP at the upper limit of normal from both
positions during wet swallows using the CCv4.0 stand-
ard protocol, or evidence of appreciable peristalsis with
changing position in the setting of type I or type II acha-
lasia in the primary position
• An inconclusive diagnosis of type III achalasia includes
an abnormal IRP with evidence of spasm and peristalsis,
and if EGJOO criteria are also met this diagnosis is rec-
ommended to be EGJOO with spastic features.
• An inconclusive diagnosis of achalasia on HRM in the
setting of dysphagia is strongly recommended to be fol-
lowed by TBE and/or FLIP to guide clinical decisions.
• Opioid use is associated with type III achalasia, and
there should be a consideration to evaluate these pa-
tients with HRM while off opioid medication.
Type I achalasia has historically been termed the classic presen-
tation of achalasia, and is typically a later state of disease progres-
sion than type II achalasia, with progressive functional neuronal cell
loss of both the myenteric ganglion cells of the distal esophagus and
the lower esophageal sphincter (LES), leading to moderate to severe
esophageal dilation of the esophageal body on barium studies.7
Figure 1 shows a representative swallow from a conclusive type I
achalasia HRM study, in which an abnormal IRP is combined with
failed peristalsis and a distal contractile integral (DCI) < 100 mmHg-­
s-­cm, with no panesophageal pressurization (PEP) observed (Table 1).
Statement 2. A conclusive diagnosis of type II achalasia is defined as
an abnormal median IRP and absent contractility (100% failed peristal-
sis) with panesophageal pressurization in 20% or more swallows (strong
recommendation, very low GRADE evidence).
Type II achalasia is considered an earlier stage of disease than
type I achalasia, and continues to be the most common subtype
seen on HRM. 8 PEP waves differentiate the two subtypes, with such
a wave characteristically believed to be akin to a filled water balloon
being squeezed.7 Nuanced pathophysiologic studies have shown
that the simultaneous pressurization in type II achalasia is due to
a cavity pressure in which there is an absence of luminal contact
during the pressure deflection. Further evidence details that this
cavity pressure may be from non-­lumen obliterating circular mus-
cle contraction and possibly longitudinal muscle contraction that
cause reduction in lumen size and/or volume, as opposed to sole
pressure from bolus trapping.9–­11 Figure 1 shows a representative
KHAN et al. | 3 of 9

Type I Achalasia Type II Achalasia Type III Achalasia

PEP Present

DCI 0 mmHg-s-cm

DL 3.5 s

IRP Elevated IRP Elevated IRP Elevated

Courtesy of Center for Esophageal Health at New York University Langone Health

F I G U R E 1 Representative swallows from conclusive type I, type II, and type III achalasia high-­resolution (HRM) studies. Type I achalasia:
integrated relaxation pressure (IRP) is abnormal with failed peristalsis (distal contractile integral (DCI) <100 mm Hg-­s-­cm) and without
panesophageal pressurization (PEP). Type II achalasia: IRP is abnormal with failed peristalsis and PEP. Type III achalasia: IRP is abnormal with
a normal DCI and evidence of spasm (distal latency (DL) below 4.5 s)

swallow from a conclusive type II achalasia HRM study, in which an
abnormal IRP is combined with failed peristalsis and a PEP wave
≥30 mm Hg.
Statement 3. A conclusive diagnosis of type III achalasia is defined
as an abnormal IRP and evidence of spasm (20% or more swallows with
premature contraction) with no evidence of peristalsis (strong recom-
mendation, very low GRADE evidence).
Type III achalasia is the least common subtype of the disease,
and may reflect a different pathophysiologic consequence than the
other subtypes, with less evidence of progressive neuronal cell loss
of the myenteric ganglion cells of the distal esophagus and LES.7,12
At least 20% of swallows having evidence of a premature or spastic
contraction, defined as a distal latency (DL) < 4.5 s in setting of a
DCI ≥ 450 mm Hg-­s-­cm, differentiates type III achalasia. There is
pathophysiologic evidence that these spastic contractions in type III
achalasia are not always truly simultaneous, but the motor pattern
in the distal esophagus still results in early luminal closure and resis-
tance to passage of bolus flow.11,13 Figure 1 shows a representative
swallow from a conclusive type III achalasia HRM study, in which an
abnormal IRP is combined with a premature contraction.
A refinement in definition that comes with this statement in
CCv4.0 focuses on the ambiguity in CCv3.0 that does not define
the characteristics of the swallows that are not premature in this
category. In CCv4.0, a conclusive diagnosis of type III achalasia re-
quires that the remaining swallows should be either failed, or failed
and associated with PEP. Thus, patients with evidence of peristalsis
should be defined as inconclusive for type III achalasia and may meet
criteria for EGJOO with spastic features if strict EGJOO criteria are
met (Figure 2).
4.2 | Inconclusive diagnosis of achalasia
Statement 4. An inconclusive diagnosis of type I or II achalasia includes
absent contractility with no appreciable peristalsis in the setting of IRP
values at the upper limit of normal in both positions, with or without
panesophageal pressurization in 20% or more swallows (strong recom-
mendation, very low GRADE evidence).
Statement 5. Evidence of appreciable peristalsis with changing po-
sition in the setting of a type I or II achalasia pattern in the primary po-
sition can shift the diagnosis toward an inconclusive diagnosis requiring
supportive testing (accepted clinical observation).
Statement 6. Supportive testing with a TBE, preferably with tablet,
and/or FLIP should be performed in patients with an inconclusive diag-
nosis of achalasia in the setting of dysphagia as a presenting symptom
(strong recommendation, very low GRADE evidence).
The CCv4.0 standard HRM protocol includes primary and sec-
ondary positions for wet swallows, though as mentioned achalasia
can be conclusively subtyped by utilizing just the primary position.
Inconclusive diagnoses of type I or type II achalasia result either
from an IRP at the upper limit of normal in both positions with no
appreciable peristalsis throughout the study, or alternatively from
diagnosis of type I or type II achalasia that becomes inconclusive
because appreciable peristalsis is observed in the secondary posi-
tion (Figure 2). In these diagnostic scenarios, the CCv4.0 Working
Group strongly recommends supportive testing with a timed bar-
ium esophagram (TBE), preferably with a tablet, and/or a functional
lumen imaging probe (FLIP) assessment.
A TBE is a simple test, with relatively low cost and radiation expo-
sure, in evaluating degree of esophageal emptying after a patient drinks
4 of 9 | KHAN et al.

TA B L E 1 Achalasia accepted
Percent Strength of Level of
recommendations
Recommended statement agreement recommendation evidence

A conclusive diagnosis of type I achalasia 98% Strong Very low

is defined as an abnormal median IRP
and absent contractility (100% failed
peristalsis)
A conclusive diagnosis of type II achalasia 98% Strong Very low
is defined as an abnormal median
IRP and absent contractility (100%
failed peristalsis) with panesophageal
pressurization in 20% or more swallows
A conclusive diagnosis of type III achalasia is 88% Strong Very low
defined as an abnormal IRP and evidence
of spasm (20% or more swallows with
premature contraction) with no evidence
of peristalsis
An inconclusive diagnosis of type I or II 91% Strong
achalasia includes absent contractility
with no appreciable peristalsis in the
setting of IRP values at the upper limit of
normal in both positions, with or without
panesophageal pressurization in 20% or
more swallows
Evidence of appreciable peristalsis with Accepted clinical
changing position in the setting of a type observation
I or II achalasia pattern in the primary
position can shift the diagnosis towards
an inconclusive diagnosis requiring
supportive testing
Supportive testing with a TBE, preferably 91% Strong Very low
with tablet, and/or FLIP should
be performed in patients with an
inconclusive diagnosis of achalasia in
the setting of dysphagia as a presenting
symptom
An inconclusive diagnosis of type III Accepted clinical
achalasia includes an abnormal IRP observation
with evidence of spasm and evidence
of peristalsis. If these cases fulfill strict
criteria for EGJOO (as detailed in the
EGJOO section) these patients should
be classified as EGJOO with spastic
features, which may represent an
achalasia variant.
The cutoff of spasm in 20% of swallows is Accepted clinical
arbitrary, and confidence in a diagnosis observation
of a type III achalasia variant may be
increased with a higher number of
premature/spastic swallows
Opioids are associated with type III 85% Conditional Low
achalasia and patients should be studied
off opioid medication if possible

100–­200 ml of low-­density barium sulfate.14 Different metrics have
been analyzed as being useful in this test, with a recent study reveal-
ing how a TBE can differentiate untreated achalasia, EGJOO, and non-­
achalasia dysphagia while acting as a potential surrogate for esophageal
manometry, with an additional diagnostic yield of adding a 13-­mm
barium tablet to each study. In this study of 309 patients, a barium
height >2 cm at 5 min on a TBE was the most accurate cutoff point
for identifying untreated achalasia from EGJOO and non-­
achalasia
disorders.15 The FLIP is a novel tool used during upper endoscopy
to simultaneously assess luminal diameter along with pressure in the
esophagus during planned volumetric distension.16 The apparatus can
assess the cross-­sectional area of the EGJ divided by the pressure in the
KHAN et al. | 5 of 9

IRP is measured to assess LES relaxa on and distal esophageal opening

IRP interpretaon should consider peristalc funcon

Abnormal median IRP in primary posi on with 10 wet swallows Abnormal median IRP in both posi ons Normal IRP in one posi on or both
With 100% failed peristalsis

Evidence of peristalsis Evidence of peristalsis Evidence of 100% failed

100% failed peristalsis 100% failed peristalsis with ≥20% of swallows premature with PEP or premature without PEP or premature peristalsis
without PEP PEP ≥20% of swallows with no peristalsis swallows* swallows

Consider TBE and/or FLIP if

Conclusive type Conclusive type Conclusive type Inconclusive Inconclusive IRP is borderline or
I achalasia II achalasia III achalasia* achalasia EGJOO abnormal in one posi on

Inconclusive
achalasia
Defini ve treatment op ons Tailored and long myotomy is Suppor ve tes ng with TBE and/or Follow EGJOO algorithm,
include LHM, PD, and POEM preferred treatment FLIP if pa ent presen ng with consider suppor ve tes ng
dysphagia with TBE and/or FLIP

If TBE supports reten on or

If TBE supports reten on or FLIP FLIP supports abnormal EGJ
supports abnormal EGJ opening - opening - defini ve
defini ve treatment is indicated treatment is indicated**

*Rarely paents with 100% failed peristalsis in the primary posion may undergo posion change and
exhibit evidence of appreciable peristalsis. This may decrease confidence in the diagnosis or be consistent
with early achalasia and confirmatory tesng with TBE and /or FLIP should be obtained before treatment.
**Care should be taken in paents with a known diagnosis of SSc as these paents may have retenon without an
obstrucon at the EGJ due to poor peristalsis and negave intrathoracic pressures.

F I G U R E 2 Diagnostic algorithm for suspected achalasia based on the CCv4.0. EGJOO, Esophagogastric junction outflow obstruction;
FLIP, Functional lumen imaging probe; IRP, Integrated relaxation pressure; LES, Lower esophageal sphincter; LHM, Laparoscopic Heller
Myotomy; PD, Pneumatic dilation; PEP, Panesophageal pressurization; POEM, Peroral endoscopic myotomy; SSc, Systemic sclerosis; TBE,
Timed barium esophagram

FLIP balloon to calculate the EGJ distensibility index (EGJ-­DI) in mm2/
mm Hg.17 Along with the EGJ-­DI, esophageal motility can be evaluated
and an overall FLIP panometry diagnosis suggested.18,19 A recent FLIP
consensus document addresses the current relationship of FLIP to
HRM and TBE in achalasia and EGJOO,20 and there is evidence that
FLIP panometry can accurately identify achalasia physiology and iden-
tify patients most likely to benefit from achalasia-­type therapy.21–­24
Supportive manometric measurements in the standard HRM
protocol of CCv4.0 can also assist with an inconclusive diagnosis of
achalasia in the setting of an IRP at the upper limit of normal. A spe-
cific example can be seen in patients with systemic sclerosis (SSc)
who present with HRM findings of a borderline IRP and 100% ab-
sent peristalsis, where the distinction between type I achalasia and
absent contractility may be challenging to interpret. The rapid drink
challenge (RDC), solid test swallows, a solid test meal, and pharma-
cologic provocation with either amyl nitrite or cholecystokinin all
can be useful in determining a relevant outflow obstruction at the
EGJ in inconclusive achalasia. 25–­28 However, CCv4.0 still supports
obtaining a TBE and/or FLIP in these cases as they remain inconclu-
sive. Figure 3 shows an example of an inconclusive HRM diagnosis of
type I achalasia with TBE supportive of an achalasia diagnosis.
Statement 7. An inconclusive diagnosis of type III achalasia includes
an abnormal IRP with evidence of spasm and evidence of peristalsis. If
these cases fulfill strict criteria for EGJOO (as detailed in the EGJOO sec-
tion) these patients should be classified as EGJOO with spastic features,
which may represent an achalasia variant (accepted clinical observation).
Statement 8. The cutoff of spasm in 20% of swallows is arbitrary,
and confidence in a diagnosis of a type III achalasia variant may be in-
creased with a higher number of premature/spastic swallows (accepted
clinical observation).
A key element of CCv4.0 was the more rigorous definition of con-
clusive EGJOO both by HRM metrics and necessary supportive testing
with TBE and/or FLIP, along with relevant clinical symptoms present.
EGJOO with evidence of premature or spastic contractions, along with
evidence of some peristalsis, is observed as an achalasia variant on the
spectrum of type III achalasia and is recommended to be classified as
EGJOO with spastic features. In line with this proposed continuity of
manometric findings, as the number of swallows in a conclusive type
III achalasia HRM diagnosis with spasm goes beyond 20%, there is
added confidence to the diagnosis and unique pathophysiologic sub-
type of type III achalasia.
Careful HRM with impedance studies and concurrent ultra-
sound images of type III achalasia patients have revealed a hetero-
geneity of pressurization patterns in patients with this subtype, as
well as unique periods of cavity and contact pressures in associa-
tion with augmented muscle thickness resulting in bolus segmenta-
tion.11 As further pathophysiologic studies are performed in type III
achalasia patients, a broader understanding of potential stages and
further categorization of this subtype can be gleaned. Currently,
as mentioned, FLIP and/or TBE can help distinguish inconclusive
HRM diagnoses of achalasia, and this can be relevant in type III
achalasia as well. 23 Figure 4 shows an example of an inconclusive
6 of 9 | KHAN et al.

Inconclusive type I achalasia

Example wet swallow Rapid drink challenge Timed barium esophagram

Median IRP 10.4 mmHg Panesophageal Pressurizaon > 20 mmHg

Courtesy of Center of Excellence on Neurogastroenterology and Molity, Chulalongkorn University

F I G U R E 3 Representative high-­resolution manometry (HRM) example swallows and a timed barium esophagram (TBE) for an
inconclusive HRM diagnosis of type I achalasia. HRM reveals 100% failed absent peristalsis without panesophageal pressurization (PEP) and
a borderline median integrated relaxation pressure (IRP). Rapid drink challenge (RDC) demonstrates PEP > 20 mm Hg. TBE indicates a mildly
dilated distal esophagus with tapering at the esophagogastric junction (EGJ) and delayed transit of barium. Supportive testing was consistent
with an achalasia diagnosis

Inconclusive type III achalasia on HRM with borderline IRP values, ≥ 20% with abnormal DL, and occasional swallows with borderline normal DL

Some swallows with borderline DL

Timed Barium Esophagram

Median IRP 15.4 mmHg with evidence of LES relaxaon and LES-CD separaon

FLIP Panometry suggesve of a spasc obstrucon

Bolus entrapment with obstrucon

at the EGJ and simultaneous
uncoordinated contracons

EGJ-DI 0.8mm2/mmHg; maximum EGJ diameter 11 mm and a spasc contracle response

Courtesy of Northwestern Esophageal Center

F I G U R E 4 Representative high-­resolution manometry (HRM), functional lumen imaging probe (FLIP) panometry, and a timed barium
esophagram (TBE) for an inconclusive HRM diagnosis of type III achalasia. HRM reveals borderline integrated relaxation (IRP) values and
≥20% of swallows with abnormal distal latency (DL) and evidence of spasm. FLIP panometry demonstrates an abnormal esophagogastric
junction distensibility index (EGJ-­DI) and maximum EGJ diameter, along with a spastic contractile response. TBE indicates simultaneous
uncoordinated contractions with obstruction at the EGJ. Supportive testing was consistent with an achalasia diagnosis
KHAN et al.
type III achalasia diagnosis with TBE and FLIP both supportive of
an achalasia diagnosis.
4.3 | Other statements
Statement 9. Opioids are associated with type III achalasia and patients
should be studied off opioid medication if possible (conditional recom-
mendation, low GRADE evidence).
Chronic daily opioid exposure is a known risk factor for type III
achalasia. 29 Opioid use within 24 h of HRM, compared with opioid
use stopped at least 24 h before HRM, has been associated with
findings of EGJOO and spastic peristalsis in a cohort of study pa-
tients mostly taking short-­acting opioids with a half-­life of no more
than 5 h.30 Practically, some patients on chronic daily opioids
may not have a straightforward avenue of stopping their medica-
tions, and patients with type III achalasia on opioids may have in-
distinguishable manometry patterns whether or not the pattern is
drug-­induced. Pharmacologic provocation with amyl nitrite and cho-
lecystokinin can provide findings during HRM that endorse a greater
chance of reversibility of a type III achalasia pattern if the opioids
31
are stopped. Overall, documenting whether patients are on or off
opioids during HRM is suggested, with the timing of opioid discon-
tinuation based on medication half-­life.
5 | A D D ITI O N A L CO N S I D E R ATI O N S
While the following statements did not meet criteria for agreement
as formal recommendations, they are important considerations de-
veloped by the achalasia subgroup.
• The cutoff for panesophageal pressurization is a guide. The distinc-
tion between type I and II is somewhat arbitrary and does not have
important clinical implications beyond the very low levels seen with
dilatation <15 mm Hg (48% agreement)
• Patients with panesophageal pressurization values above 70 mm Hg
may have embedded spasm and this may impact clinical outcome
(69% agreement)
The aforementioned transition from type II achalasia to type I
achalasia on HRM represents a pathophysiologic continuum. The
PEP definition based on the pressure deflection being ≥30 mm Hg
has been used since the first HRM subtyping of achalasia was re-
vealed in 2008.6 While this continued threshold has been useful
in categorizing patients by subtype and treatment response, more
work is needed to understand the clinical relevance of PEP patterns
with low pressure values when seen in patients with or without
esophageal body dilation.
Conversely, extremely high PEP values in the setting of type II
achalasia may denote embedded spastic physiology. Example case
reports of extremely high PEP findings have been reported, with
| 7 of 9
two patients undergoing peroral endoscopic myotomy (POEM) with
a successful outcome.32,33 Whether these patients should be treated
as having potential type III achalasia, or if supportive testing such
as FLIP can reveal specific embedded spastic patterns, is yet to be
confidently determined.
5.1 | Clinical
considerations and therapeutic options
Achalasia continues to be recognized as a disease which presents
with one of three distinct manometric subtypes. While much still
needs to be understood about the unique differences between the
continuum of pathophysiologic changes of type I and type II acha-
lasia when compared to the less common type III achalasia, this cat-
egorization has currently allowed for an assessment of treatment
response for each subtype across different modalities.
Laparoscopic Heller myotomy (LHM), pneumatic dilation (PD),
and POEM are considered potentially definitive treatment options
for achalasia. Botolinum toxin injection is reserved for patients who
are not candidates for the other therapies. In several outcome stud-
ies using definitive treatment options across achalasia subtypes,
type II achalasia began to show the best response rates, with type
III patients having less success with PD or short myotomies.34–­37
Several meta-­analyses have confirmed the prognostic value of sub-
typing achalasia when deciding upon definitive therapy, with no
clear significant differences in outcomes across LHM, PD, or POEM
for type II achalasia.38–­40 POEM, with the potential for a tailored and
longer myotomy, has been shown to have better treatment success
than LHM in type III achalasia.41 A meta-­analysis has also revealed
POEM to have a higher instance of gastroesophageal reflux disease
(GERD) metrics than LHM, which is typically combined with a Dor or
Toupet fundoplication.42 Two recent network meta-­analysis showed
LHM and POEM having comparable efficacy overall with achalasia,
and PD as performing less successfully.43,44
Recent national society guidelines have suggested that LHM,
PD, and POEM are effective treatment options for type I and type
II achalasia, with a preference for a tailored and longer myotomy for
type III achalasia.45,46 As the ability for HRM to subtype achalasia
continues to evolve, the potential for tailoring treatment for each
patient with this disease will undoubtedly advance as well.
6 | DISCUSSION
CCv4.0 has updated its diagnostic criteria for achalasia using HRM
based on a recommended standard protocol. While the subtyping
of achalasia into three distinct manometric patterns remains similar,
the advent of conclusive and inconclusive metrics can assist clini-
cians encountering diagnostic dilemmas surrounding this disease. A
proposed diagnostic algorithm for patients with suspected achalasia
based on the CCv4.0 is shown in Figure 2.
8 of 9 | KHAN et al.
Advances in HRM overall are expected to aid in future diagnostic
criteria for achalasia. While impedance sensors are commonly found
on manometry catheters allowing for HRM with impedance (HRIM)
and several potential roles in evaluating esophageal motility,47 the
role of impedance is not yet defined in the Chicago Classification.
Bolus flow time (BFT) is a metric using HRIM that has been shown to
be complementary to IRP in achalasia, and further studies may help
incorporate BFT into decisions regarding patients with borderline
IRP and inconclusive achalasia on HRM.48 Solid test swallows, a solid
test meal, and the RDC during HRM have all been shown to be useful
in understanding true outflow obstruction at the EGJ, 25,28 and these
supplemental metrics may also continue to strengthen clinical rele-
vance to current otherwise inconclusive HRM achalasia diagnoses.
Beyond HRM, FLIP technology has burgeoning evidence in
characterizing achalasia. The normal repetitive antegrade pattern
of esophageal motility seen in healthy controls during FLIP balloon
distension on endoscopy is disrupted in achalasia, and specific con-
tractile patterns of achalasia on FLIP continue to be elucidated.49 A
future priority regarding FLIP in achalasia is determining whether
subtypes of achalasia can be more succinctly defined by FLIP param-
eters. Future research should also correlate FLIP patterns in type I
and type II achalasia to PEP in HRM, as this will help define the op-
timal PEP level that predicts poor outcome as and the relevance of a
specific PEP threshold to any embedded spasm.
Coinciding with improvements in our understanding of diagnostic
testing and its implications for categorizing patients with achalasia is a
necessity for further work regarding the pathophysiology behind this
disease. A three-­dimensional pressure profile of the EGJ has shown
anatomical and functional abnormalities of the crural diaphragm in
achalasia which may have implications in understanding the onset of
the disease.50 A novel analysis of four-­dimensional impedance ma-
nometry was recently derived from HRIM who can assist in creating
a comprehensive characterization of bolus transit along with lumen
morphology and pressure in achalasia patients.51 Further subtyping
of achalasia is indeed possible, as continued advances in type II and
type III achalasia to evaluate differences in pressurization and bolus
flow patterns are ascertained.11 More investigation into the mecha-
nism of spasm and the overlap of opioids in type III achalasia may also
reveal alternative approaches to achalasia with spastic physiology.
Achalasia continues to be the most well-­described esophageal
motility disorder. The CCv4.0 has updated its definitions for the
subtypes of achalasia, and future research will continue to align
diagnostic considerations to pathophysiology in order to improve
treatment outcomes for this still incurable disease.
C O N FL I C T S O F I N T E R E S T
AK: Consulting: Medtronic. RY: Medtronic, Diversatek, Ironwood
(institutional consulting), Phathom Pharmaceuticals (consulting),
Ironwood (research grant), RJS Mediagnostix (advisory board with
stock options). SG: none. DK: Consulting: Adare, Celegene, Takeda,
Phathom. MP: none. MVaezi: Consulting: Diversatek, Phathom,
Ironwood; Speaker: Diversatek; Advisory Board: Diversatek,
Phathom, Ironwood; Research grants: Diversatek, Phathom,
Ironwood; Patent: Mucosal Integrity Testing. MVela: Consulting:
Medtronic. JP: Consulting: Medtronic, Ironwood Pharmaceuticals,
Diversatek; Research Support: Ironwood Pharmaceuticals, Takeda;
Advisory Board: Medtronic Diversatek; Stock Options: Crospon Inc.
DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing is not applicable to this article as no new data were cre-
ated or analyzed in this study.
ORCID
Abraham Khan https://orcid.org/0000-0002-8683-2320
Rena Yadlapati https://orcid.org/0000-0002-7872-2033
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How to cite this article: Khan A, Yadlapati R, Gonlachanvit S, et
al. Chicago Classification update (version 4.0): Technical review
on diagnostic criteria for achalasia. Neurogastroenterology &
Motility. 2021;33:e14182. https://doi.org/10.1111/nmo.14182