REVIEW

Approach to the Patient with Dysphagia

Ala’ A. Abdel Jalil, MD,a David A. Katzka, MD,b Donald O. Castell, MDaaEsophageal Disorders Program, Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston;bDepartment of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minn.

Funding: NonConflict of InAuthorship: A

writing this manusRequests for r

Esophageal DisordDoughty St, Room

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0002-9343/$ -seehttp://dx.doi.org/1

ABSTRACT

Dysphagia is a fascinating symptom. It is ostensibly simple when defined by trouble swallowing, yet itssubtleties in deciphering and its variations in pathophysiology almost mandate a thorough knowledge ofmedicine itself. With patience and careful questioning, a multitude of various disorders may be suggestedbefore an objective test is performed. Indeed, the ability to diligently and comprehensively explore thesymptom of dysphagia is not only rewarding but also a real test for a physician who prides himself orherself on good history taking.� 2015 Elsevier Inc. All rights reserved. � The American Journal of Medicine (2015) 128, 1138.e17-1138.e23

KEYWORDS: Diagnosis; Dysphagia; Eosinophilic esophagitis; Motility disorders

DEFINITION

ObjectiveDysphagia is defined objectively as an abnormal delay intransit of a liquid or solid bolus during the oropharyngealor esophageal stages of swallowing. This delay can betransient, lasting seconds, or at its most severe manifest as afixed delay, as in a food impaction. The periodicity also mayvary widely, occurring yearly or with every swallowattempt. Nevertheless, if a test of esophageal transit such asbarium radiography, nuclear scintigraphy, or multichannelimpedance was performed, there should be clear evidence ofabnormally slow bolus transport in a point between themouth and the stomach. Likewise, a test of anatomicor motility assessment of the oropharynx and esophaguswould demonstrate a finding that is associated clearly withobjective dysphagia.

SubjectiveDysphagia as defined subjectively is the sensation of adelay in transit of a liquid or solid bolus during the

e.terest: None.ll authors had access to the data and played a role incript.eprints should be addressed to Ala’ A. Abdel Jalil, MD,ers Program, Medical University of South Carolina, 114249, MSC 290, Charleston, SC 29425.: ala79md@gmail.com

front matter � 2015 Elsevier Inc. All rights reserved.0.1016/j.amjmed.2015.04.026

oropharyngeal or esophageal stages of swallowing(oropharyngeal and esophageal dysphagia, respectively).This could be distinctly different from the objective mea-surement of dysphagia because various mechanisms ofesophageal sensory function may account for the sensationof dysphagia without apparent delay in bolus transit. Forexample, in patients with functional dysphagia, symptomsmay reflect a feeling of the passage of a bolus through theesophagus, even with normal transit. Likewise, a symptomthat is generated from a true delay in bolus transit may bepotentiated or attenuated through sensory neural dysfunc-tion to seem out of proportion or outlast, respectively,a short-lived delay in bolus transit.1 Conversely, otherdisorders may manifest with hyposensitive function of theesophagus, such that patients feel neither the severity northe duration of bolus impaction as occurs in the late stagesof achalasia.2

QuestionnairesSeveral research groups have devised questionnaires to aidin the measurement and interpretation of dysphagia in apatient.3 These questionnaires serve several purposes. Thefirst is a standardization of questions, which may be appliedto research as a measurable tool. The second is to complete athorough characterization of dysphagia. For example, thesequestionnaires commonly seek additional information aboutthe dysphagia, such as chronicity, frequency, severity, andassociated symptoms. The third is to tailor the dysphagia tothe clinical situation in which it is being applied. For

Abdel Jalil et al Approach to Dysphagia 1138.e18

example, some of these questionnaires,4 such as the MayoDysphagia Questionnaire5,6 and Northwestern Question-naire,7 have been developed for the general population.Others are disease specific, such as those developed forpatients who have eosinophilic esophagitis or sustainedstrokes.8

CLINICAL SIGNIFICANCE

� To perform a well-done dysphagia eval-uation, it is necessary to recognize alarmsymptoms.

� Order barium esophagram early if yoususpect oropharyngeal or motilitydisorder.

� If dysphagia persists, or the diagnosisremains unclear despite initial work up,consider referring to the appropriatespecialist (GI, ENT, Neurology) at anearly stage.

� Eosinophilic esophagitis is an emergingcause of dysphagia, especially to solids,with food impaction in advanced cases.

CATEGORIES

Motility Versus AnatomicAnatomic causes of dysphagia areusually those that compromise theesophageal lumen. These pro-cesses may be benign or malig-nant, oropharyngeal or distalesophageal, mucosal, intramural,or extrinsic to the esophagus.Common mechanical causes ofdysphagia may include reflux-induced esophageal strictures,head and neck or esophageal can-cer, and extrinsic compressionfrom mediastinal lymph nodes orlung cancer. The general clinicalprincipal related to anatomic cau-ses of dysphagia is that symptomsprimarily occur with ingestion of

solids and not liquids and are more likely with larger solidsand those of denser consistency (Figure 1).

In contrast, motility causes of dysphagia are more likelyto occur with both solids and liquids as the neuromuscularforces required to propel the bolus affect both liquid andsolid transport. Some motility disorders may start withsolids, which require greater esophageal contractile ampli-tude, thus unmasking an esophageal muscular disorderearlier in the pathogenesis of the neuromyopathy, but withprogression will involve liquids. In motility disorders of theoropharynx, liquids may be more problematic than solidsbecause of easier entry to the airway with failure of theepiglottis to cover and of elevation of the laryngeal struc-tures to protect the laryngeal vestibule. Typical disorders offoregut motility are achalasia or oropharyngeal dysfunctionsecondary to a cerebrovascular accident.

Upper Esophageal Versus Mid- and LowerEsophagealDetermining the location of esophageal dysfunction relativeto where the patient feels the symptoms is not reliable. Thishas been found not only clinically but also through experi-mentation in which balloon distention of the esophagus orduplication of symptoms by radiographic impaction of amarshmallow in the distal esophagus9-11 leads to a highlyvariable symptom location among individuals. One factorthat may help determine location is detecting a perturbationof other oropharyngeal functions accompanying dysphagia.For example, because cranial nerve deficits commonly affect

other functions in addition to swallowing, patients withoropharyngeal dysphagia may note voice changes, nasalregurgitation (failure to seal off the nasopharynx), or pran-dial coughing (failure to protect the airway). If dysphagialeads to regurgitation, the volume of regurgitant also maybe helpful. For example, the esophageal body is capable

of holding a larger volume offood with obstruction than theoropharynx.

Organ-Specific VersusInvolvement by AnotherDiseaseIn a patient with dysphagia, onealso has to determine whether thesymptom derives from an esoph-ageal specific disorder or a moregeneralized disorder affecting theesophagus. For example, systemicneuromuscular diseases, such asscleroderma, may cause dysphagiaof the lower esophagus, whereasamyotrophic lateral sclerosis ormyasthenia gravis may affectoropharyngeal function. Otherdiseases may lead to stricture for-mation, such as lichen planus or

Crohn’s disease, whereas others may lead to extrinsiccompression, such as dysphagia aortica or dysphagia luso-ria. Furthermore, diseases such as breast or lung cancer maycause an achalasia-like syndrome without clear evidence ofthe cancer on initial evaluation. As a result, detection of anesophageal disorder leading to dysphagia may not just stopat the esophagus. This is emphasized further by the fact thatmany of the disorders described and other systemic disor-ders may present with esophageal symptoms.

DIAGNOSTIC APPROACH

Initial EvaluationFurther History. In addition to the routine characteriza-tions of a symptom, such as chronicity, frequency, andseverity, further history needs to be pursued to determine thecategory of dysphagia under which it falls (as describedearlier) and, if possible, the specific cause or disease in thatcategory that is causing the dysphagia (Figures 1 and 2).Because specific diseases and locations commonly areassociated with symptoms in addition to dysphagia, it isimportant to elicit these symptoms in the history. Forexample, because individual cranial nerves innervatemuscles pertinent to multiple aspects of normaloropharyngeal function, such as mouth closing, sealing offof the nasal cavities, and protection of the airway andvoice, cranial neuropathies may cause drooling, nasal

Figure 1 Symptom differential of common causes of esophageal dysphagia. Overlap existsamong the features. Persistent dysphagia represents more severe disease that requires earliermedical attention. EoE ¼ eosinophilic esophagitis; IEM ¼ ineffective esophageal motility.

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regurgitation, pulmonary aspiration, and voice dysfunction,respectively, in addition to dysphagia.

It is important to appreciate that patients with chronicdiseases commonly learn techniques and strategies to adaptto their symptom and thus ease the difficulty that attends thisproblem. This is particularly true in patients with dysphagia.As a result, it is important in collecting further history to

Figure 2 Disorders causing oropharyngeal dysphagia.Several disorders may manifest with more than 1 cause ofdysphagia, such as head and neck surgery or radiation injury.Zenker’s diverticulum arises from dysmotility but then givesrise to further dysphagia by esophageal compression. CNS ¼central nervous system.

inquire about compensatory mechanisms that reduce thefrequency and severity of dysphagia. Such adaptationsinclude eating slowly, manifest by being the last to finisha meal in company. Another adaptation is avoiding prob-lematic foods. Indeed, some patients state they do not havedysphagia, but a careful dietary history may reveal theavoidance of hard solids such as meat or bread in thesepatients.

Patients will also learn techniques to facilitate boluspassage. For example, patients with solid food dysphagiamay drink fluids with every bite to facilitate bolus passage.When patients sustain episodes of complete bolus obstruc-tion, they may also learn to regurgitate as a method ofclearing the bolus. As a result, patients may avoid socialsituations in which they fear occurrence of and embarrass-ment at their dysphagia, such as meals at restaurants andbusiness affairs. Finally, another important aspect in elicit-ing a history of dysphagia is asking an accompanying familymember about the symptom. Often, they will note the sloweating and struggle at mealtime better than the patient whohas both consciously and subconsciously adapted to thedisorder.

Physical Examination. Examination of the patient mayplay a strong role in determining the cause of dysphagia.This is particularly true in patients with a suspected neuro-muscular cause of difficulty swallowing. As a result, asimple examination of cranial nerves should be performed,

Abdel Jalil et al Approach to Dysphagia 1138.e20

which can easily be accomplished in a brief time. Likewise,more generalized involvement of these disorders shouldbe sought, such as proximal or asymmetric extremityweakness, dysarthria, fasciculations, tremor, and cognitivedysfunction.

An oral examination is also necessary. Clues to the causeof dysphagia might include poor dentition, buccal lesionssuch as lichen planus, tongue fasciculations, asymmetricpalate elevation, and labial droop. A neck examination maybe helpful if a mass or adenopathy is detected, such as aVirchow’s node associated with esophageal cancer.

Bedside Testing. One of the easiest and potentiallyimportant parts of the physical examination is watching thepatient swallow in the office. Observation of deglutition of asimple glass of water or bite of a solid food can give aplethora of information on the patient’s dysphagia. Patientscommonly underestimate their degree of difficulty, but itmay be revealed by observations such as multiple swallowsrequired for a single bolus, the use of small sips of fluid orsmall bites of a solid, post-deglutitive throat clearing, and ageneral fear of swallowing.

Barium Swallow Versus Endoscopy. The first importantconsideration of these 2 tests is in realizing they are com-plementary and not duplicative (Figure 3).12 The decisionon which test to order initially depends in large part onwhich is most likely to yield the diagnosis. Becauseendoscopy gives accurate information on esophageal anat-omy, it is used commonly as the first test to evaluate solidfood dysphagia. It allows for more precise mucosalinspection and the ability to biopsy. Endoscopy also servesas a potential therapeutic tool because dilation may beperformed if needed at the time of the diagnostic study.

On the other hand, barium esophagography gives fargreater information for motility disorders. As a result, for

Figure 3 Barium esophagram of (A) mid-esopAchalasia (characterized by dilation and sigmoidiclassic bird’s beak sign).

oropharyngeal dysphagia (which is mostly attributable todysmotility), a video modified barium swallow is the initialdiagnostic test of choice.13-15 This approach not only allowsfor direct visualization of muscular strength and coordina-tion but also usually includes different food consistencies totest or duplicate the patient’s symptoms. Furthermore, thistest is performed commonly with a speech and swallowingtherapist, who not only has expertise in swallowing disor-ders but also may start to implement effective therapywith key compensatory maneuvers based on the study. Forsuspected distal esophageal motility disorders such asachalasia16 or scleroderma17 involving the esophagus,barium evaluation has been shown to be superior toendoscopy. Barium esophagography is more sensitive thanendoscopy for detection of esophageal strictures.18-20

Another advantage of an initial esophagogram is the abil-ity to plan the endoscopy. For example, identification of atight esophageal stricture may help determine the type ofdilation needed and the potential need for fluoroscopy toaid in the dilation. Likewise, an extant diagnosis of achalasiaby barium may allow for pneumatic dilation or injection ofintrasphincteric botulinum toxin during endoscopy. Finally,for the purposes of finding an esophageal fistula or perfo-ration in a patient with dysphagia, radiography is the safestand most accurate approach. It is our belief that the diag-nostic approach to all patients with dysphagia should beginwith a barium study, although performing endoscopy,particularly for patients with suspected mechanical causes ofdysphagia, is reasonable.

High-Resolution Impedance Manometry. High-resolutionimpedance manometry is a modern adaptation of traditionalesophageal manometry but with greater accuracy and visu-alization based on having 32 pressure transducers thatspan the esophaguseas opposed to the limitations of only afew transducers in the past.21,22 As a result, a clear

hageal stricture (arrow) and (B) advancedzation of esophagus with arrow pointing to

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panesophageal pressure tracing can be generated and thendescribed through a colorimetric graphic presentation (theClouse plot) (Figure 4).23 This gives a far clearer reading onperistaltic and sphincter function. Impedance measurementalso has been added to this technique such that catheter-based electrodes measure the conductivity of a substancebased on the characteristics and speed of the bolus.24 Aswallow of a liquid-based bolus will conduct electricitybetter and therefore generate a low impedance signalconcordant with esophageal peristalsis. Because direction offlow is measured easily, reflux of content from the stomachinto the esophagus also may be easily seen. Ideally, thiscombination of manometry and impedance measurement issuited for assessing esophageal motility disorders. Thereis recent evidence that abnormal bolus transit detectedby impedance during test swallows is the most sensitiveindicator of abnormal esophageal motility. Ordering theappropriate diagnostic test by the referring physician helpsin eliciting the next step in management of the patient’sdysphagia.

SPECIFIC DISORDERS

Neuromuscular DiseasesControl of oropharyngeal function is mediated by cerebral,brain stem, cranial nerve, and striated muscle function.Thus, numerous neural or muscular disorders may involveor even manifest with oropharyngeal dysphagia. Forexample, centrally mediated diseases that may cause

Figure 4 Normal high-resolution impedance manometry. LES ¼ lo

dysphagia include cerebrovascular accidents, Parkinson’sdisease, or progressive supranuclear palsy. Diseases thataffect the brain stem and cranial nerve function includebotulism, amyotrophic lateral sclerosis, and supranuclearpalsy. Examples of primary striated muscle disease areinclusion body myositis, myasthenia gravis, and polymyo-sitis. The important aspect of these diseases, as discussedearlier, is that multiple stages of the oropharyngeal portionof the swallow may be affected.

Stricturing DiseasesDiseases that lead to fibrotic change and luminal narrowingof the esophagus are common entities that cause dysphagia.They all uniformly lead to solid food dysphagia. Esophagealstrictures due to gastroesophageal reflux are most common,although some data suggest that with increasing use ofproton pump inhibitors, these may be decreasing in inci-dence.25,26 These strictures may manifest as mildly symp-tomatic focal distal annular narrowing to severelysymptomatic long distal esophageal strictures involving alarge portion of the esophagus. The treatment rests inadequate control of reflux and mechanical dilation of thestrictures. Of note, as in location, the severity of solid fooddysphagia does not always belie the severity of luminalnarrowing because patients commonly adapt with avoidingcertain foods, chewing carefully, and using fluids copiouslywith solid meals.

Another common stricturing disease is eosinophilicesophagitis.27 Initially thought uncommon, this disease is

wer esophageal sphincter; UES ¼ upper esophageal sphincter.

Abdel Jalil et al Approach to Dysphagia 1138.e22

estimated to occur in 0.4% of the population.28 It typicallyaffects children, adolescents, and young adults but isbecoming increasingly recognized in middle-aged patients.Eosinophilic esophagitis manifests typically in adults withyears of dysphagia, sometimes punctuated by food impac-tions. Its pathophysiology centers on a T-helper 2-mediatedfood allergy of the esophagus, which leads to chroniceosinophilic infiltration, inflammation, and fibrogenesis.Treatment is aimed at identification and elimination ofcausative foods or medical control of the allergic responseby using topical or systemic steroids. The need for dilationis also common in this disease.

Other stricturing diseases include iatrogenic causes, suchas radiation therapy or caustic medications (eg, bisphosph-onates, doxycycline, or potassium supplements), skindiseases (eg, lichen planus or pemphigus syndromes),caustic ingestion, and Crohn’s disease.

Esophageal CancerAdenocarcinoma is one of the most rapidly increasingcancers in Western society, now far outnumbering the pre-viously common squamous cell carcinoma.29 Theories thatmight explain this increasing incidence include increasinggastroesophageal reflux disease and central obesity (whichmechanically and chemically may contribute to increasingesophageal neoplasia),30 decreasing Helicobacter pyloriinfection (which may allow for more patients with higherlevels of gastric acid secretion),31,32 and dietarychanges.33,34 Barrett’s esophagus is the most dominantprecursor to adenocarcinoma. Dysphagia symptoms may beinsidious, starting intermittently with hard solids such asbread and meats and then progressing. Patients maycommonly have advanced lesions with marked luminalnarrowing yet mild symptoms. Whether this reflects ac-commodation or a generalized esophageal hyposensitivity tosymptoms is unclear. Other alarm symptoms that mayaccompany progressive dysphagia include weight loss,anorexia, and hematemesis.

AchalasiaAchalasia is the prototype esophageal motility disordercharacterized manometrically by aperistalsis and anincompletely relaxing lower esophageal sphincter.35

Although often considered typical, a hypertensive loweresophageal sphincter may not be present. A new mano-metric profile, the Chicago Classification,36 based on high-resolution impedance manometry, has been proposed tobetter characterize these variants. On radiography, patientshave a dilated esophagus with an incompletely openinglower esophageal sphincter. The underlying cause seems tobe an autoimmune esophageal ganglionitis with relative lossof inhibitory input possibly initiated by a viral infection.37

Although dysphagia to liquids and solids is the most com-mon symptom, patients may have a wide variation insymptoms, including chest pain, unresponsive heartburn,

weight loss, and regurgitation.38 Treatment is aimed atmechanical disruption of the lower esophageal sphincterthrough pneumatic dilation or laparoscopic, and morerecently, endoscopic myotomy.

Functional DysphagiaAt the beginning of this review, dysphagia was definedspecifically as an abnormal delay in bolus transit. Thisobjective definition is stated because patients may note asense of dysphagia despite normal radiographic or mano-metric measures of normal transit. These patients are theo-rized to have a sensory disorder in which they sense thenormally passing bolus due to augmented afferent esopha-geal sensation.39 Whether this is a disorder or peripheral orcentral sensory processing is unclear. These patients will“feel” the bolus going down. Conversely, they may stillsense food or fluid in their esophagus for prolonged periodsafter the meal, although they may still eat and drink withoutdifficulty. Radiography is an excellent means of making thisdiagnosis in which ingestants, such as barium-coated foodsor tablets, may reproduce symptoms yet demonstrate normaltransport. Another clue to this disorder in younger patients isthe association of dysphagia with other functional disordersof the gastrointestinal tract, including dyspepsia, bloating,early satiety, and belching.40 Treatment may include phar-macologic, behavioral, or cognitive therapy.

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