INTRODUCTION — Patients with esophageal dysmotility may present with dysphagia, noncardiac chest pain, heartburn and/or regurgitation. After a structural abnormality is excluded by performing an upper gastrointestinal endoscopy (esophagogastroduodenoscopy), esophageal manometry is obtained to assess esophageal motility and function. While it is clear that high resolution esophageal motility testing is an important part of the diagnostic evaluation, limited data are available for guiding management.

This topic will review the pathophysiology, clinical features, diagnosis, and management of the major disorders of esophageal peristalsis: distal esophageal spasm (formerly diffuse esophageal spasm), and hypercontractile (jackhammer) esophagus. Absent esophageal peristalsis (often related to systemic sclerosis) 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 non-esophageal 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 relaxation of the esophagogastric junction (EGJ), as measured by the integrated relaxation pressure. An esophageal manometry study that demonstrates impaired EGJ relaxation (ie, elevated integrated relaxation pressure) and absent peristalsis suggests a diagnosis of 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".)

If the integrated relaxation pressure is normal, motility disorders are then further categorized based on abnormalities in esophageal peristalsis. There are three major disorders of esophageal peristalsis: distal esophageal spasm, hypercontractile (jackhammer) esophagus, and absent peristalsis. 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 distal esophageal spasm (DES) and hypercontractile esophagus 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 hypercontractile esophagus ranged from 1 to 4 percent [6,7].

PATHOPHYSIOLOGY — The underlying pathology of hypercontractile esophageal motility disorders is not clearly understood, but theories for the potential mechanisms leading to disease manifestations have been described [8-16].

Distal esophageal spasm (DES) is thought to be a consequence of impaired inhibitory innervation, leading to premature and rapidly propagated contractions in the distal esophagus [8]. It has been hypothesized that patients with DES have a malfunction in endogenous nitric oxide synthesis and/or degradation. This hypothesis is supported by a dose-dependent decrease in the duration of swallow-induced contractions with intravenous glycerine trinitrate and improvement in symptoms with phosphodiesterase inhibitors [9] and nitrates [10]. This is further reinforced by the observation that the normal peristaltic pattern in asymptomatic volunteers will change to a spastic pattern during administration of a nitric oxide scavenger, with some subjects experiencing chest pain [11]. Ineffective esophageal transport in patients with DES results in dysphagia.

Esophageal spasm and dysmotility may also be induced by esophageal acid exposure, while prolonged esophageal contractions have been associated with heartburn [15,16].

In contrast with DES, the vigorous esophageal contractions seen in patients with hypercontractile (jackhammer) esophagus (or nutcracker esophagus in older studies using conventional manometry) may be due to excessive excitation, smooth muscle hypertrophy and/or smooth muscle response to excitatory nerves [12-14].

CLINICAL FEATURES

Clinical manifestations — Most patients with distal esophageal spasm (DES) or hypercontractile (jackhammer) esophagus are symptomatic and present with dysphagia for solids and liquids [7,17]. Patients have esophageal dysphagia, which is characterized by difficulty swallowing and often a sensation of food getting stuck in the esophagus. The dysphagia may occur in association with retrosternal, noncardiac chest pain, or noncardiac chest pain may be the predominant symptom [18]. 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 hypercontractile (jackhammer) esophagus, 23 patients (67 percent) reported dysphagia and 16 patients (47 percent) had chest pain [17]. Dysphagia was associated with hypercontractile swallows on manometry, while chest pain 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 [19]. (See 'Differential diagnosis' below.)

Imaging — DES and hypercontractile esophagus appear differently on imaging:

●DES - In patients with DES, severe non-peristaltic 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 [19].

●Hypercontractile esophagus - In patients with hypercontractile esophagus, barium esophagram shows normal sequential peristalsis.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for disorders of esophageal peristalsis includes other causes of esophageal dysphagia and noncardiac chest pain. These include:

●Gastroesophageal reflux disease (GERD)

●Esophageal stricture

●Eosinophilic esophagitis

●Nonreflux esophagitis (eg, infectious, medication-induced)

●Esophageal ring or web

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

Most of these conditions can be excluded by upper gastrointestinal endoscopy (esophagogastroduodenoscopy) with esophageal biopsy. (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 and 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'.)

Distal esophageal spasm and hypercontractile (jackhammer) esophagus are distinguished from other esophageal motility disorders that are associated with dysphagia (eg, achalasia, absent peristalsis) by esophageal manometry testing. (See "High resolution manometry" and 'Classification based on esophageal manometry' above.)

DIAGNOSIS

Evaluation — The clinical diagnosis of esophageal hyperperistalsis should be suspected in a patient presenting with suggestive symptoms such as 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 (algorithm 1). For selected patients (eg, patients with history of radiation or caustic esophageal injury), we also 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, we perform high resolution esophageal manometry to evaluate for an esophageal motility disorder. (See 'Diagnostic criteria' below.)

Patients with a normal structural evaluation and a manometry study that is not consistent with a major motility disorder 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 'Subsequent management'.)

Diagnostic criteria — The diagnosis of distal esophageal spasm (DES) or hypercontractile esophagus 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 increased simultaneous 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 swallows in the setting of normal relaxation of the esophagogastric junction [20]. A premature contraction is one that is simultaneous, usually with a distal latency (time from onset of the upper esophageal sphincter relaxation to the contractile deceleration point) of less than 4.5 seconds. (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 [21,22].

•Hypercontractile esophagus – Hypercontractile (jackhammer) esophagus is characterized by high pressure but normally sequential contractions in the smooth muscle esophagus [23]. On HRM with EPT, criteria for hypercontractile esophagus are at least two liquid swallows with a distal contractile integral (DCI) >8000 mmHg∙s∙cm with single or multi-peaked contraction in the setting of normal relaxation of the esophagogastric junction (figure 2). The DCI reflects the overall strength of the distal contraction (ie, amplitude, duration and length between the proximal and distal troughs) [24]. (See "High resolution manometry", section on 'Hypercontractile esophagus' and "High resolution manometry", section on 'Distal contractile integral (DCI)'.)

Hypercontractile esophagus 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'.)

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 the most effective treatment for distal esophageal spasm (DES) or hypercontractile (jackhammer) esophagus is not well defined, our treatment approach is based on the following principles:

●The goal of therapy is to provide relief of symptom(s).

●Our preference for therapies is based on limited data and clinical experience, and selection among them depends on the patient’s response to prior therapy, severity of symptoms, risk of adverse effects, and patient preferences.

●The therapeutic approach generally applies to patients with either DES or hypercontractile (jackhammer) esophagus.

Initial measures — The goals of initial therapy are to control gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation), if they are present, and to relax the hypercontractile smooth muscle of the esophagus without adverse effects by using a form of peppermint oil.

●Control GERD symptoms - We begin a proton pump inhibitor (PPI) twice daily for patients with GERD symptoms. PPIs are most effective when taken 30 minutes before meals, and they should be taken regularly rather than on-demand because continuous therapy provides better symptom control. 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 who do not experience relief of GERD symptoms after one to two months of PPI therapy, we add a bedtime histamine 2 blocker [25]. If the addition of histamine 2 blocker results in improvement of GERD symptoms, we continue it as long-term therapy. (See "Approach to refractory gastroesophageal reflux disease in adults", section on 'Residual acid reflux'.)

For patients with GERD symptoms who do not respond to combination therapy of PPI and histamine 2 blocker, 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 [26] (see 'Pathophysiology' above and 'Clinical features' above):

•Esophageal hyperperistalsis may coexist with GERD [19].

•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.

●Manage dysphagia/noncardiac chest pain - For patients with no GERD (or well-controlled GERD) who experience dysphagia and/or noncardiac chest pain, we begin therapy with peppermint oil (two Altoids mints taken sublingually before each meal). In the author's experience, peppermint oil taken as needed may also provide relief for attacks of DES-related chest pain.

We use peppermint oil as initial therapy because it relaxes esophageal smooth muscle and is generally well tolerated with minimal, if any, side effects.

Smooth muscle relaxants have been studied to provide symptomatic relief in patients with hypercontractile esophageal peristalsis [27-29]. Peppermint oil improved manometric abnormalities in a case series of eight patients with DES [27]. Two patients also had improvement in chest pain.

Therapy for persistent symptoms

Pharmacologic therapy — In patients with DES or hypercontractile esophagus who have either no GERD or well-controlled GERD and who do not experience improvement in symptoms (dysphagia, noncardiac chest pain) with peppermint oil, we use a calcium channel blocker. If the calcium channel blocker is not effective or is not well tolerated, we discontinue the calcium channel blocker and begin a low dose tricyclic antidepressant.

We use diltiazem 60 to 90 mg orally four times daily because limited data suggest that it is effective. We reassess the patient's symptoms after three months of treatment. Some patients will experience adverse effects related to calcium channel blockers (eg, headache, lightheadedness, hypotension, and constipation), and these effects limit their use for those patients. (See "Major side effects and safety of calcium channel blockers".)

If symptoms improve with a calcium channel blocker, we reduce the frequency of administration to twice daily. If symptoms resolve, we discontinue every-day dosing and give calcium channel blockers as needed (eg, diltiazem 60 mg taken once at the onset of symptoms such as dysphagia or noncardiac chest pain). While we monitor the patient’s symptoms, we do not obtain follow-up testing (eg, high resolution manometry).

For patients who cannot tolerate or do not have symptomatic improvement with calcium channel blockers, we discontinue the calcium channel blocker and begin a low dose tricyclic antidepressant (TCA) (eg, imipramine 25 to 50 mg 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'.)

If there is little or no improvement, we discuss an alternative therapy (eg, endoscopic injection of botulinum toxin). (See 'Endoscopic therapy for refractory symptoms' below.)

The approach to pharmacologic therapy with calcium channel blockers or TCA is supported by limited data. Therapy with calcium channel blockers is aimed at reducing the spastic and/or hypercontractile contractions in the distal esophagus; thus, smooth muscle relaxants have been studied to provide symptomatic relief [28,29]. In a trial of 22 patients with abnormal esophageal peristalsis (nutcracker esophagus), patients treated with diltiazem (60 to 90 mg four times daily) had greater relief of chest pain compared with patients given placebo [28].

Tricyclic antidepressants (imipramine, 25 to 50 mg once daily) have been shown to be effective in a small randomized trial for relief of chest pain in patients with esophageal motility abnormalities [30]. These results are likely due to the effect on visceral sensory perception as TCAs, for example, have not been demonstrated to improve dysmotility [21]. 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 [23,31].

Endoscopic therapy for refractory symptoms — For patients with hypercontractile esophageal peristalsis and persistent symptoms that do not improve with initial measures or subsequent drug therapy as described above, endoscopic therapy with botulinum toxin injection may be effective for relief of some symptoms (eg, dysphagia) [32-35]. The dose and endoscopic delivery method for botulinum toxin is similar to the use of botulinum toxin injection for achalasia, and this is discussed separately. (See "Pneumatic dilation and botulinum toxin injection for achalasia", section on 'Botulinum toxin injection'.)

In a trial including 22 patients with DES or nutcracker esophagus, treatment with botulinum toxin (injected endoscopically, 2 and 7 cm above the esophagogastric junction) resulted in greater symptomatic improvement for dysphagia compared with saline injection. However, there was no significant improvement in chest pain, regurgitation, or heartburn [35]. Disadvantages of botulinum toxin injection include the need for upper endoscopy and the limited duration of symptom relief (approximately six months) [33].

Other options — There are limited data to support the use of other therapies in patients with DES or hypercontractile (jackhammer) esophagus [27,36-41]. We do not use any of the following therapies routinely, but they could be potential options for patients who fail or cannot tolerate other therapies:

●Non-TCA antidepressants – Other antidepressant therapies that alter visceral pain perception can be used for hypercontractile motility disorders. Low dose trazodone (eg, 25 to 50 mg at bedtime) and serotonin reuptake inhibitors can lower esophageal sensitivity, which results in symptomatic relief [36,40-44]. Venlafaxine may be helpful but the evidence is weak, while sertraline and paroxetine may be of no clear benefit over placebo [43,44]. (See "Evaluation of the adult with chest pain of esophageal origin", section on 'Subsequent management'.)

●Phosphodiesterase inhibitors – Small case series suggest that phosphodiesterase inhibitors (eg, sildenafil 50 mg on an as needed basis for chest pain or dysphagia) relieve symptoms and improve manometric findings in patients with hypercontractile motility disorders [37,39]. In a series of 11 patients with nutcracker esophagus or DES, sildenafil (50 mg once daily as needed) was associated with symptom relief in four patients, but two patients discontinued treatment due to associated side effects [37]. In addition to adverse effects, use of sildenafil is limited due to issues of cost and coverage from payers.

●Nitroglycerin – Based on older, small case series, patients with well-controlled GERD (or no GERD) may have symptomatic improvement with a nitric oxide contributing drug (isosorbide 5 to 10 mg as needed for noncardiac chest pain), but its use may be limited by adverse effects such as headache [45,46].

●Peroral endoscopic myotomy (POEM) – Peroral endoscopic myotomy has demonstrated short-term relief in patients with hypercontractile esophageal motility disorders. However, given the absence of randomized, controlled trials and long-term follow-up data, in addition to potential complications (eg, postoperative dysphagia or reflux), POEM is not routinely used as therapy for DES or hypercontractile esophagus [38,47]. (See "Peroral endoscopic myotomy (POEM)".)

PROGNOSIS — The prognosis for patients with distal esophageal spasm (DES) or hypercontractile esophagus is good. There have been no reports of increased risk of mortality or esophageal carcinoma in patients with these disorders. If symptoms remain unchanged, no specific monitoring (eg, esophagogastroduodenoscopy or high resolution manometry) is required.

Limited data suggest that over time, many patients with DES will show symptomatic improvement [48]. Some studies also suggest that manometric findings may change over time [49]. Whether this variability is due to changes in esophageal motility over time or instead reflects the limitations of esophageal manometry testing is not clear. Approximately 5 percent of patients with DES subsequently develop achalasia that manifests as worsening dysphagia and regurgitation [50].

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

●There are three major disorders of esophageal peristalsis: distal esophageal spasm (DES), hypercontractile esophagus, and absent esophageal peristalsis. (See 'Classification based on esophageal manometry' above and "High resolution manometry".)

Absent esophageal peristalsis (often related to systemic sclerosis) is discussed separately. (See "Gastrointestinal manifestations of systemic sclerosis (scleroderma)".)

●Although the pathology of hypercontractile esophageal motility is not well understood, distal esophageal spasm 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.)

●Most patients with DES or hypercontractile esophagus are symptomatic and complain of dysphagia, which may occur in association with noncardiac chest pain. Some patients also have symptoms of heartburn or regurgitation. (See 'Clinical features' above.)

●The diagnosis of DES or hypercontractile esophagus requires the following (algorithm 1) (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 2) (see "High resolution manometry").

●The goal of initial therapy is to control gastroesophageal reflux disease (GERD) symptoms, if they are present, and to relax the hypercontractile smooth muscle of the esophagus by using a form of peppermint oil. For patients with disorders of esophageal hyperperistalsis and GERD symptoms, we suggest a proton pump inhibitor twice daily (Grade 2C). For patients with no GERD (or well-controlled GERD) who experience dysphagia and/or noncardiac chest pain, we suggest peppermint oil (eg, two Altoids mints taken sublingually before each meal) (Grade 2C). (See 'Initial measures' above.)

●For patients who have either no GERD or well-controlled GERD and who do not experience improvement in symptoms with peppermint oil, we suggest a calcium channel blocker (ie, diltiazem 60 to 90 mg orally four times daily) (Grade 2C). If the calcium channel blocker is not effective or is not well tolerated, we discontinue the calcium channel blocker and begin a low dose tricyclic antidepressant (eg, imipramine 25 mg at bedtime). (See 'Therapy for persistent symptoms' above and "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects".)

●The prognosis for patients with DES or hypercontractile esophagus is good. There have been no reports of increased risk of mortality or esophageal carcinoma in patients with these disorders. Limited data suggest that over time, many patients will experience symptomatic improvement. (See 'Prognosis' above.)