Distal esophageal spasm and hypercontractile esophagus

INTRODUCTION — Patients with esophageal dysmotility may present with dysphagia, noncardiac chest pain, heartburn and/or regurgitation. After inflammatory and structural abnormalities are excluded by performing an upper gastrointestinal endoscopy (esophagogastroduodenoscopy), esophageal manometry is often performed to assess esophageal motor function. Barium esophagram, videofluoroscopic swallow studies, and esophageal impedance planimetry may complement endoscopic assessment and obviate the need for esophageal manometry in specific instances (ie, oropharyngeal dysphagia, subtle esophageal stricture).

This topic will review the pathophysiology, clinical features, diagnosis, and management of the following disorders of esophageal peristalsis: distal esophageal spasm (DES; formerly diffuse esophageal spasm) and hypercontractile (formerly jackhammer) esophagus (HE). Absent esophageal contractility, which may be related to an underlying connective tissue disorder, is discussed separately. (See "Gastrointestinal manifestations of systemic sclerosis (scleroderma)".)

The approach to the evaluation of patients with dysphagia is discussed separately. (See "Approach to the evaluation of dysphagia in adults".)

The evaluation of chest pain of esophageal origin is discussed separately. (See "Evaluation of the adult with chest pain of esophageal origin".)

The evaluation of chest pain of nonesophageal origin is also addressed separately. (See "Outpatient evaluation of the adult with chest pain" and "Evaluation of the adult with chest pain in the emergency department".)

CLASSIFICATION BASED ON ESOPHAGEAL MANOMETRY — Based on high resolution manometry with esophageal pressure topography, esophageal motility disorders are classified according to the Chicago Classification [1-3]. (See "High resolution manometry", section on 'Overview'.)

The Chicago Classification categorizes esophageal motility disorders according to the deglutitive pressure (ie, pressure with swallowing) of the esophagogastric junction (EGJ) as measured by the integrated relaxation pressure (IRP). An esophageal manometry study that demonstrates impaired EGJ relaxation (ie, elevated IRP) and absent peristalsis is consistent with a diagnosis of primary or secondary achalasia. The clinical manifestations, diagnosis, and management of achalasia are discussed separately:

●(See "Achalasia: Pathogenesis, clinical manifestations, and diagnosis".)

●(See "Overview of the treatment of achalasia".)

●(See "Pneumatic dilation and botulinum toxin injection for achalasia".)

●(See "Surgical myotomy for achalasia".)

An elevated IRP in the presence of intact esophageal peristaltic function is consistent with the diagnosis of EGJ outflow obstruction (EGJOO), especially when combined with delayed esophageal emptying on a barium esophagram or impaired EGJ opening using impedance planimetry.

If the IRP is normal, motility disorders are then further categorized based on abnormalities in esophageal peristalsis. The major disorders of esophageal peristalsis are distal esophageal spasm, hypercontractile (jackhammer) esophagus, absent peristalsis, and ineffective esophageal motility. Absent esophageal peristalsis (often related to systemic sclerosis) is discussed separately. (See "Gastrointestinal manifestations of systemic sclerosis (scleroderma)".)

EPIDEMIOLOGY — Observational studies using diagnostic criteria from the Chicago Classification suggest that DES and HE are uncommon disorders among patients referred for motility testing [4-7]. In a study of 1070 patients with dysphagia and chest pain who were referred for esophageal manometry, 24 patients (2 percent) had manometric findings suggestive of DES [4]. In two studies including over 900 patients referred for esophageal manometry, the prevalence of HE ranged from 1 to 4 percent [6,7].

PATHOPHYSIOLOGY — The underlying pathology of DES and HE are not clearly understood, but theories for the potential mechanisms leading to disease manifestations have been described [8-16].

Distal esophageal spasm — DES is defined by premature and rapidly propagated contractions in the distal esophagus [8]. Premature and rapid contractions are associated with esophageal bolus retention. Similar to achalasia, DES is classified as a disorder of deglutitive inhibition with dysfunction of nitrinergic (nitric oxide) enteric neural innervation of the smooth muscle portion of the esophagus. This hypothesis is supported by in vitro and in vivo studies that demonstrate simultaneous esophageal contractions with inhibition of nitric oxide synthase [11,17]. Furthermore, in small case series including patients with DES, phosphodiesterase inhibitors (by increasing guanylate cyclase, the second messenger for nitric oxide) [9] and nitrates (as nitric oxide donors) [10] were associated with improving symptoms and esophageal motor function. This is further reinforced by the observation that the normal peristaltic pattern in asymptomatic individuals will change to a spastic pattern during administration of a nitric oxide scavenger, with some individuals experiencing chest pain [11]. Several case reports have described progression from DES to achalasia over time, and these observations support a shared pathophysiology [18].

Limited studies have demonstrated degeneration of vagal fibers, inflammatory infiltration of the myenteric plexus, hypertrophy of the muscularis propria and variable loss of enteric ganglion cells in the myenteric plexus [19,20].

While a cause of enteric neural dysfunction in DES has not been identified, esophageal spasm and dysmotility may also be induced by esophageal acid exposure and chronic opioid use [15,16,21,22].

Hypercontractile esophagus — The vigorous esophageal contractions seen in patients with HE (or nutcracker esophagus in older studies using conventional manometry) may be due to excessive excitatory enteric neural innervation and/or smooth muscle hypertrophy [12-14].

Both mechanical and physiologic obstruction of the EGJ may result in increased amplitudes of esophageal contractions. Thus, HE may be secondary to a mechanical or functional obstruction. Mechanical obstruction can be in the distal esophagus, esophagogastric junction, or proximal stomach (as described in patients with Roux-en-Y gastric bypass or magnetic sphincter augmentation). On the other hand, HE and esophagogastric junction outflow obstruction (EGJOO) may result from loss of deglutitive inhibition. An association between HE, with or without EGJOO, has been identified in patients with chronic opioid use [21,22]. HE has also been identified in some patients with eosinophilic esophagitis (eg, those with muscular involvement) [23].

CLINICAL FEATURES

Clinical manifestations — Most symptomatic patients with DES or HE present with dysphagia and/or chest pain [7,24]. Patients have esophageal dysphagia, which is characterized by difficulty swallowing and often a sensation of solid food or liquids getting stuck or passing slowly. The dysphagia may localize to the suprasternal notch or chest. Retrosternal, noncardiac chest pain may be the predominant symptom [25]. In some cases, patients have symptoms of heartburn and/or regurgitation, but these symptoms are usually accompanied by either dysphagia and/or noncardiac chest pain.

As an example, in a study of 34 patients with HE, 23 patients (67 percent) reported dysphagia and 16 patients (47 percent) had chest pain [24]. Dysphagia was associated with hypercontractile swallows on manometry, while chest pain was not associated with manometric findings. (See 'Diagnostic criteria' below.)

Gastroesophageal reflux disease may coexist with disorders of esophageal peristalsis. In a series of 108 patients with DES, 41 patients (34 percent) had pathologic acid reflux demonstrated by either pH monitoring or endoscopy [26]. (See 'Differential diagnosis' below.)

Imaging — DES and HE appear differently on imaging:

●Distal esophageal spasm – In patients with DES, simultaneous contractions may result in a "rosary bead" or "corkscrew" appearance of the esophagus on barium esophagram (image 1 and image 2). However, barium esophagram is neither sensitive nor specific for DES. In a study including 76 patients with DES who had a barium esophagram report available for review, 43 patients (57 percent) had nonspecific abnormalities (eg, tertiary contractions resulting in partial lumen obliteration), while only three patients (4 percent) had an esophagus with a corkscrew appearance [26].

●Hypercontractile esophagus – In patients with HE, barium esophagram shows normal sequential peristalsis. However, the esophagram may identify secondary causes of hypercontractility, including a distal mechanical obstruction, hiatal hernia, or extrinsic compression.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for DES and HE includes other causes of esophageal dysphagia and noncardiac chest pain:

●Gastroesophageal reflux disease (GERD)

●Esophageal stricture including Schatzki ring and peptic stricture (see "Esophageal rings and webs")

●Eosinophilic esophagitis with muscular involvement

●Nonreflux esophagitis (eg, infectious, medication-induced, graft-versus-host disease, lichen planus, radiation)

●Hiatus hernia, especially paraesophageal type (see "Hiatus hernia")

●Postoperative anatomy (eg, fundoplication, bariatric surgery) (see "Bariatric operations: Late complications with subacute presentations")

●Esophageal diverticula

●Functional gastrointestinal disorder (eg, functional dysphagia, functional chest pain)

●Opioid-induced esophageal dysmotility – Opioid-induced esophageal dysmotility is increasingly being reported in case series, and it can mimic primary motility disorders [21,22]. As an example, in an observational study of 4075 patients who underwent esophageal manometry, opioid use was associated with higher rates of a manometric diagnosis of esophageal dysmotility compared with no opioid exposure (DES: 11 versus 5 percent, and HE: 9 versus 3 percent) [22]. In addition, small case series have demonstrated impaired lower esophageal sphincter relaxation after administration of morphine [21].  

Management of opioid-associated esophageal dysmotility is uncertain. While cessation of opioids is optimal, tapering or discontinuing opioids may be challenging. Nevertheless, limited reports have shown improvement in esophageal motor dysfunction with discontinuation of opioids [21]. (See "Opioid tapering for patients with chronic pain".)

Data on the use of opioid receptor antagonists for symptomatic improvement are mixed. For patients with persistent symptoms who are unable to stop opioids, medical therapy or botulinum toxin injection are reasonable options.

Most of these conditions can be excluded by taking a history and by upper gastrointestinal endoscopy with esophageal biopsy, although barium esophagram can provide complementary information particularly for patients with postoperative anatomy and subtle mechanical strictures. (See "Evaluation of the adult with chest pain of esophageal origin" and "Approach to the evaluation of dysphagia in adults".)

Patients with GERD symptoms (heartburn, regurgitation) that are refractory to acid suppressive therapy can be further evaluated with esophageal pH or combined pH-impedance testing. The approach to the diagnosis and treatment of refractory GERD is discussed separately. (See "Approach to refractory gastroesophageal reflux disease in adults" and "Esophageal multichannel intraluminal impedance testing", section on 'Combined multichannel intraluminal impedance and pH'.)

Patients with noncardiac chest pain and/or dysphagia with a normal upper endoscopy including esophageal biopsy are often evaluated with esophageal manometry to exclude esophageal motility disorders (eg, achalasia). (See "High resolution manometry" and 'Classification based on esophageal manometry' above.)

DIAGNOSIS

Evaluation — The clinical diagnosis of DES and HE should be suspected in a patient presenting with suggestive symptoms including esophageal dysphagia or noncardiac chest pain.

Our approach to the diagnostic evaluation includes the following:

●We perform an upper gastrointestinal endoscopy with esophageal biopsy to rule out other esophageal disorders. For selected patients (eg, patients with history of radiation or caustic esophageal injury), we also often obtain a barium esophagram. (See "Approach to the evaluation of dysphagia in adults", section on 'Approach to diagnostic testing'.)

●If the above evaluation is negative or nondiagnostic (eg, tertiary contractions only on barium esophagram), we perform high resolution esophageal manometry to evaluate for an esophageal motility disorder. (See 'Diagnostic criteria' below.)

Patients with a normal structural evaluation and normal manometry study may have symptoms related to a functional gastrointestinal disorder (eg, functional dysphagia, functional chest pain), which is discussed separately. (See "Approach to the evaluation of dysphagia in adults", section on 'Functional dysphagia' and "Evaluation of the adult with chest pain of esophageal origin", section on 'Management'.)

Impedance planimetry is being incorporated into the diagnostic evaluation of dysphagia at some medical centers. Functional lumen imaging probe (FLIP) is an assessment tool that utilizes impedance planimetry to characterize esophageal contractility, and FLIP is being studied for evaluating patients with suspected DES and HE [27]. The use of FLIP is discussed in more detail separately. (See "Functional lumen imaging probe (FLIP) for adults with esophageal disorders".)

Diagnostic criteria — The diagnosis of DES or HE requires the following:

●Exclusion of other, more common conditions associated with symptoms of esophageal dysphagia or noncardiac chest pain. For most patients, the initial testing includes a structural evaluation of the esophagus (upper gastrointestinal endoscopy with esophageal biopsies). (See 'Diagnosis' above.)

●Identification of characteristic abnormalities on esophageal manometry (see "High resolution manometry"):

•Distal esophageal spasm – DES is characterized by spastic or premature contractions in the distal esophagus (figure 1). On high resolution manometry (HRM) with esophageal pressure topography (EPT), DES is defined as the occurrence of premature contractions in at least 20 percent of liquid swallows in the setting of normal relaxation of the esophagogastric junction (ie, normal IRP) [3,28]. A premature contraction is one that is simultaneous, usually with a distal latency (ie, time from onset of the upper esophageal sphincter relaxation to the contractile deceleration point) of less than 4.5 seconds in the setting of normal esophageal contractile vigor (distal contractile integral greater than 450 mmHg∙s∙cm). Loss of deglutitive inhibition during multiple rapid swallows may be observed. (See "High resolution manometry", section on 'Distal esophageal spasm (DES)' and "High resolution manometry", section on 'Distal latency (DL)'.)

While some studies suggest that patients with DES may be further characterized by different phenotypes, no formal classification of DES phenotypes has been validated [29,30].

•Hypercontractile esophagus – After excluding mechanical obstruction of the distal esophagus or esophagogastric junction (EGJ) with initial testing, HE is characterized by high pressure but normally sequential contractions in the smooth muscle esophagus. On HRM with EPT, criteria for HE are at least 20 percent liquid swallows with a distal contractile integral (DCI) >8000 mmHg∙s∙cm in the setting of normal relaxation of the EGJ (normal integrated relaxation pressure) (figure 1) [3,31].  

The DCI reflects the overall strength of the distal contraction (ie, amplitude, duration, and length between the proximal and distal troughs) [32]. Several subtypes of HE have been described including single-peaked hypercontraction, multi-peaked hypercontraction (ie, jackhammer esophagus), or hypercontraction of the lower esophageal sphincter following deglutition (figure 1). The jackhammer subtype of HE is characterized by higher DCI values and greater symptom association [31]. (See "High resolution manometry".)  

HE was previously referred to as "nutcracker esophagus" or "spastic nutcracker," based on conventional manometry studies [1]. Technical differences between conventional manometry and high resolution manometry are discussed separately. (See "Overview of gastrointestinal motility testing", section on 'Esophageal manometry'.)

Caution should be used when comparing data on nutcracker esophagus to HE because criteria for HE using the DCI are more specific with less overlap with healthy populations than the amplitude-based criteria used to define nutcracker esophagus (ie, >180 mmHg).

In addition, a clinically relevant diagnosis of DES or HE requires the presence of symptoms of esophageal dysfunction (mostly dysphagia and/or chest pain) in addition to the manometric features [3].

The findings on esophageal manometry may support another diagnosis such as achalasia or absent peristalsis, and these disorders are discussed separately. (See "Achalasia: Pathogenesis, clinical manifestations, and diagnosis" and "Gastrointestinal manifestations of systemic sclerosis (scleroderma)".)

MANAGEMENT

Goals and sequence of therapies — Because of a range of symptoms, heterogeneity in manometric features, and limited data on natural history and efficacy of therapies, our treatment approach for DES and HE is based on the following principles:

●Pretreatment evaluation involves excluding other conditions (eg, eosinophilic esophagitis [muscular variant], esophagogastric junction outflow obstruction [EGJOO], type 3 achalasia, opioid-associated dysmotility). (See 'Diagnosis' above and 'Differential diagnosis' above.)

●The goal of therapy is to provide relief of symptom(s) rather than normalization of manometric features.

●If gastroesophageal reflux disease (GERD) has not been excluded with pH testing, we typically begin with empiric antisecretory therapy. (See 'Initial measures' below.)

●Selection among other therapies is informed by the patient's response to prior therapy, symptom type (eg, dysphagia, chest pain), symptom severity, disease progression, risk of adverse effects, and patient preferences. For most patients, medical therapy or endoscopic therapy (eg, botulinum toxin injection) is associated with symptomatic improvement. For patients with limited symptom burden, observation alone may be appropriate. In such cases, clinical follow-up and repeat radiographic and/or manometric testing is reasonable.

Initial measures — The goals of initial therapy are to control symptoms (eg, heartburn, noncardiac chest pain, regurgitation).

●Control GERD symptoms – We begin a proton pump inhibitor (PPI) twice daily, especially if patients also have GERD symptoms (table 1). The use of PPIs for the treatment of GERD is discussed in more detail separately. (See "Medical management of gastroesophageal reflux disease in adults", section on 'Proton pump inhibitors'.)

For patients who respond to PPI, we continue therapy for three months. We gradually taper PPI therapy for patients who have been on PPI for three months or longer. If symptoms recur with tapering or discontinuing PPI, we restart it. Selection of PPI, duration of therapy, and tapering schedules are discussed separately. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Administration'.)

For patients with GERD symptoms or chest pain who do not respond to PPI therapy, subsequent management is based on symptoms and ambulatory pH study results. The approach to the evaluation and treatment of patients with refractory GERD is discussed elsewhere. (See "Approach to refractory gastroesophageal reflux disease in adults".)

We initially focus on controlling GERD symptoms for the following reasons [33] (see 'Pathophysiology' above and 'Clinical features' above):

•DES and HE may coexist with GERD [26]. As an example, in a study of 44 patients with HE by esophageal manometry, 19 patients (43 percent) had GERD-related symptoms [34]. In a small series of patients with DES who were treated with nitrates, clinical improvement was reported only in patients without coexisting GERD [35].

•Esophageal dysmotility may be induced by acid reflux, and thus, treatment of GERD may help alleviate symptoms of esophageal dysmotility [15,16].

•Some treatments for esophageal hyperperistalsis (ie, smooth muscle relaxants) may exacerbate GERD symptoms.

●Initial therapy to relax smooth muscle – For mildly symptomatic patients, we typically begin a trial of peppermint oil (two Altoids mints taken sublingually before each meal as needed). We use peppermint oil as initial therapy because it is generally well tolerated with minimal or no side effects and because smooth muscle relaxants can relieve symptoms in patients with hypercontractile esophageal peristalsis [36-38]. Peppermint oil improved manometric abnormalities in a case series of eight patients with DES [36]. Two patients also had improvement in chest pain.

Therapy for persistent symptoms

Pharmacologic therapy — For patients with persistent symptoms despite initial measures, we use pharmacologic therapy such as an antispasmodic or antihypertensive agent:

●Antispasmodic agents – We use an antispasmodic agent (eg, hyoscyamine, dicyclomine) based on clinical experience and limited published data [39,40]. As an example, hyoscyamine 0.25 mg, orally, three times daily as needed was associated with reduced esophageal contractility and lower esophageal sphincter (LES) pressure [39]. Dicyclomine 20 mg, four times daily as needed, modestly reduced esophageal contractile amplitudes in heathy individuals [40].

●Antihypertensive agents – We typically use a short-acting nitrate (ie, isosorbide dinitrate 5 to 10 mg, orally, twice or three times daily), although a calcium channel blocker is a reasonable alternative. For nitrate therapy, we begin with a lower dose (eg, isosorbide dinitrate 5 mg twice daily as needed) and caution patients about possible side effects (eg, headache). If the dose is well tolerated, it can be gradually titrated to achieve symptom response. (See "Nitrates in the management of chronic coronary syndrome", section on 'Adverse effects'.)

Although data to support the efficacy of antihypertensive agents for relaxing esophageal smooth muscle are limited, indirect data from studies in patients with achalasia suggested that nitrates provided greater reduction in esophageal contractile amplitudes compared with calcium channel blockers [41]. In addition, in two small trials including patients with DES, nitrate therapy was associated with greater symptom improvement compared with calcium channel blockers [10,35].

We infrequently use calcium channel blockers for treating esophageal hypercontractility because adverse effects generally limit their use. Adverse effects related to calcium channel blockers include headache, lightheadedness, hypotension, and constipation. However, extended-release formulations of calcium channel blockers may be better tolerated by some patients because of lower risk of adverse effects than the immediate-release formulations. (See "Major side effects and safety of calcium channel blockers".)

Data supporting the use of calcium channel blockers are mixed, and some studies included patients with nutcracker esophagus rather than HE [37,38,42]. In a trial of 22 patients with nutcracker esophagus, patients treated with diltiazem (60 to 90 mg four times daily) had greater relief of chest pain compared with placebo [37]. However, in another small trial, nifedipine showed improvement in esophageal contractile amplitudes but no significant difference in symptoms [42]. In a study evaluating calcium channel blockers in healthy individuals, nifedipine was associated with greater improvement in esophageal contractile pressure compared with verapamil or diltiazem, both of which had negligible effects [39].

●Tricyclic antidepressants — For patients with predominantly chest pain symptoms who cannot tolerate or do not have symptomatic improvement with initial measures and initial pharmacologic therapy, we begin a low-dose tricyclic antidepressant (TCA). The initial dose should be adjusted based upon tolerance and response. Due to the delayed onset of action of antidepressants, three to four weeks of therapy should be attempted before increasing the dose. We typically use either nortriptyline or amitriptyline with an initial dose of 10 to 25 mg daily at bedtime. We discuss potential adverse effects with the patient (ie, orthostatic hypotension, constipation, dry mouth, blurred vision, urinary retention). (See "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects", section on 'Side effects'.)

We instruct patients to take the TCA as prescribed rather than on an as-needed basis and to expect that response may not occur until four or more weeks have elapsed. If the TCA is well tolerated, we reassess the patient's symptoms after three months of treatment. If symptoms are improved, treatment is continued for 6 to 12 months, followed by a drug taper, which generally takes two to four weeks to avoid discontinuation symptoms (eg, agitation, anxiety, headache). The approach to discontinuing TCAs is discussed separately. (See "Discontinuing antidepressant medications in adults", section on 'Tricyclics'.)

TCAs have been shown to be effective in a small randomized trial for relief of chest pain in patients with esophageal motility abnormalities [43]. These results are likely due to the effect on visceral sensory perception as TCAs have not been demonstrated to improve dysmotility [29]. Older studies using conventional manometry suggest that visceral hypersensitivity may be a factor for some patients whose symptoms do not necessarily correlate with manometric abnormalities [44,45].

●Other pharmacologic options — Other antidepressant therapies that alter visceral pain perception can be used for hypercontractile esophageal motility disorders. Low-dose trazodone (eg, 25 to 50 mg at bedtime) and serotonin reuptake inhibitors (eg, citalopram 20 mg daily) can lower esophageal sensitivity, which results in symptomatic relief [46-51]. Venlafaxine may also be an option based on limited evidence [50,51]. However, we do not typically use sertraline or paroxetine because studies have not established their efficacy for treating esophageal dysmotility. (See "Evaluation of the adult with chest pain of esophageal origin", section on 'Management'.)

Phosphodiesterase inhibitors have been studied for treating esophageal motor disorders and as an alternative for patients who have not responded to other pharmacologic agents [52-54]. In an observational study of 11 patients with hypercontractile esophageal motility disorders, sildenafil was associated with manometric improvement in nine patients (81 percent) and symptom improvement in four patients (36 percent) [52]. However, two of four patients with symptom improvement discontinued treatment because of adverse side effects. Adverse effects associated with phosphodiesterase inhibitors are discussed separately. (See "Treatment of male sexual dysfunction", section on 'Initial therapy: PDE5 inhibitors'.)

Endoscopy-guided botulinum toxin injection — For patients with DES or HE and persistent symptoms that do not improve with initial measures or subsequent drug therapy, endoscopic therapy with botulinum toxin injection may provide symptom relief and improvement in manometric features [55-58]. (See 'Pharmacologic therapy' above.)

The dose and endoscopic delivery method for botulinum toxin is similar to use of botulinum toxin injection for achalasia, but the injection sites target the distal esophagus. The technique for botulinum toxin injection is discussed separately. (See "Pneumatic dilation and botulinum toxin injection for achalasia", section on 'Botulinum toxin injection'.)

Botulinum toxin injection typically provides short-term symptom relief (ie, approximately six months), while the risk of adverse effects is low. Evidence supporting use of botulinum toxin for DES and HE are limited by both heterogeneity in patient populations and small sample sizes [55-59]. In a trial including 22 patients with DES or nutcracker/jackhammer esophagus, botulinum toxin (injected endoscopically at 2 and 7 cm above the EGJ) resulted in greater improvement in dysphagia compared with saline injection [58]. However, there was no significant improvement in chest pain, regurgitation, or heartburn. Botulinum toxin also resulted in lower LES pressure, but there was no change in simultaneous or repetitive contractions or in contraction duration. In another trial including 23 patients with DES, HE, or type 3 achalasia, there were no significant differences in symptomatic improvement or contractile vigor following botulinum toxin therapy compared with a sham procedure [59].  

Myotomy — We reserve endoscopic and surgical myotomy for selected patients (eg, patients with complications of dysmotility such as impaired esophageal transit or symptomatic epiphrenic diverticula, patients with symptomatic improvement with botulinum toxin). The reported success of myotomy in observational studies is limited by the lack of randomized trials as well as possible inclusion of patients with EGJOO or type 3 achalasia. Evidence of coexisting EGJOO on manometry, impedance planimetry, and/or delayed transit on barium esophagram may support the use of more invasive interventions [60]. Randomized trials using well-defined, consensus-based outcome measures with long-term follow-up are needed before myotomy is routinely used for DES or HE, which both typically have a benign course. (See 'Prognosis' below.)

Peroral endoscopic myotomy — Peroral endoscopic myotomy (POEM) has been associated with symptomatic improvement in patients with hypercontractile esophageal motility disorders [61-64]. In a meta-analysis including 18 patients with DES and 37 patients with HE who underwent POEM, the reported clinical success rates were 88 and 72 percent, respectively, but the definition of clinical improvement varied among studies [61]. In a study including 25 patients with spastic motility disorders who underwent POEM, clinical success was achieved in 85 percent of patients after median follow-up of nine months, and manometric abnormalities resolved in 90 percent of patients [62]. The efficacy and safety of POEM, including adverse events such as symptomatic GERD are discussed in more detail separately. (See "Peroral endoscopic myotomy (POEM)".)

Surgical myotomy — Data from small case series and case reports have suggested that laparoscopic surgical myotomy was effective for treating DES and HE [65,66]. In a study of 20 patients with DES, extended surgical myotomy was associated with improvement in dysphagia in 18 patients (90 percent) and chest pain in all patients (100 percent) after median follow-up of 50 months [65]. However, technical limitations related to performing a laparoscopic long myotomy likely accounts for the greater use of POEM for patients with spastic esophageal motility disorders. (See "Surgical myotomy for achalasia".)

PROGNOSIS — Data on the natural history of DES and HE are limited, although observational studies describe a benign clinical course in most patients. There have been no reports of increased risk of mortality or esophageal carcinoma.

Data from small case series suggested that spastic esophageal disorders were associated with esophageal diverticula and with progression to achalasia. In a series of 19 patients with esophageal diverticula who had esophageal manometry, six patients (32 percent) had at least one hypercontractile swallow, two patients (11 percent) had jackhammer esophagus, and one patient (5 percent) had DES [67]. In a series of 12 patients with HE, three patients (25 percent) progressed to type 3 achalasia over a mean follow-up of 24 months [68]. In a series of 32 patients with DES, repeat manometry after a mean of 4.8 years demonstrated persistent DES in seven patients, achalasia in one patient, and normal motility in three patients [69]. These findings support evaluating patients for impaired deglutitive esophagogastric junction relaxation during the initial presentation and longitudinal follow-up. (See 'Evaluation' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dysphagia" and "Society guideline links: Esophageal manometry and pH testing".)

SUMMARY AND RECOMMENDATIONS

●Background – Major disorders of esophageal peristalsis include distal esophageal spasm (DES), hypercontractile esophagus (HE), absent esophageal peristalsis, and ineffective esophageal motility. (See 'Classification based on esophageal manometry' above and "High resolution manometry".)

●Pathophysiology – Although the pathophysiology of hypercontractile esophageal motility is not well understood, DES is thought to be a consequence of impaired inhibitory innervation, leading to premature and rapidly propagated contractions in the distal esophagus. Esophageal hyperperistalsis may also be induced by esophageal acid exposure. (See 'Pathophysiology' above.)

●Clinical features – Dysphagia and chest pain are the most common symptoms of DES and HE. Some patients also have symptoms of heartburn or regurgitation. (See 'Clinical features' above.)

●Diagnosis – The diagnosis of DES or HE requires the following (see 'Diagnosis' above):

•Exclusion of other conditions associated with symptoms of esophageal dysphagia or noncardiac chest pain. For most patients, the initial testing includes a structural evaluation of the esophagus (upper gastrointestinal endoscopy with esophageal biopsies).

•Identification of characteristic abnormalities on esophageal manometry (figure 1). (See "High resolution manometry".)

For patients with manometric criteria consistent with DES or HE, we exclude secondary causes of esophageal dysmotility including opioid-induced dysmotility, eosinophilic esophagitis, and impaired esophagogastric junction opening (esophagogastric junction outflow obstruction or mechanical obstruction).

●Management – The goal of initial therapy is to control gastroesophageal reflux disease (GERD) symptoms. For patients with DES or HE and who have GERD symptoms, we suggest initiating proton pump inhibitor (PPI) therapy (Grade 2C). The PPI is typically started with a standard dose taken twice daily (table 1).  

For patients who have either no GERD or well-controlled GERD, we suggest a trial of pharmacologic therapy to relax smooth muscle (Grade 2C). Treatment options include an antispasmodic agent (eg, hyoscyamine 0.25 mg three times daily as needed), a nitrate (eg, isosorbide dinitrate 5 to 10 mg twice to three times daily as needed), a calcium channel blocker (eg, nifedipine, extended release, 30 mg daily), or phosphodiesterase inhibitor (sildenafil 25 to 50 mg daily).

If therapy to relax esophageal smooth muscle is not effective or is not well tolerated, we begin a low-dose tricyclic antidepressant (eg, nortriptyline 10 to 25 mg at bedtime), especially for patients with pain-predominant symptoms. (See 'Therapy for persistent symptoms' above and "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects".)

For patients who do not have symptom relief or who do not tolerate pharmacologic therapy, endoscopy-guided botulinum toxin injection into the distal esophagus is a subsequent therapeutic option. (See 'Endoscopy-guided botulinum toxin injection' above.)

For selected patients (eg, those with complications of esophageal dysmotility), myotomy (ie, peroral endoscopic myotomy or surgical myotomy) is an alternative intervention because data suggest that myotomy was associated with improvement in symptoms and manometric features. (See 'Myotomy' above and "Peroral endoscopic myotomy (POEM)".)

●Prognosis – The prognosis for patients with DES or HE is favorable. There have been no reports of increased risk of mortality or esophageal carcinoma in patients with these disorders. Progression to achalasia and an association with esophageal diverticula have been reported in a subset of patients. (See 'Prognosis' above.)