Oesophageal candidiasis

This infection usually occurs in patients receiving prolonged courses of antibiotics or who are immunosuppressed by therapy with systemic corticosteroids or other immunosuppressive drugs. It can be seen in patients using inhaled steroids, taken for nasal or respiratory conditions. Conditions commonly associated with oesophageal candidiasis include diabetes, AIDS, lymphoma and other malignancies particularly during chemotherapy when these patients are neutropenic. The oesophageal infection may be accompanied by an oral or pharyngeal candidiasis, particularly in the context of AIDS.

The endoscopic features are white plaques on an erythematous mucosa, which can progress to necrosis and ulceration. Diagnosis is confirmed by brushings and biopsy demonstrating hyphae and tissue invasion by the organism. The features can be similar to those of infections due to herpes simplex virus (HSV) or cytomegalovirus (CMV), and biopsy is necessary to distinguish these conditions.

Therapy is aimed at treating the underlying disease or conditions that predispose to the infection. Modification of drug therapy such as corticosteroids or antibiotics may be relevant, or the control of diabetes if present. The first-line treatment for oesophageal candidiasis is fluconazole, either oral or intravenous depending upon symptoms and tolerance for oral intake.

Herpes simplex oesophagitis

Malignancy, immunosuppressive drugs and immunodeficiency states are predisposing factors, but herpetic oesophagitis can occur spontaneously in the apparently healthy, immunocompetent individual. The causative agent is the herpes simplex virus type 1. The endoscopic appearances can vary from discrete, punched-out ulcers to confluent, extensive ulceration. Whitish plaques can also be a feature making differentiation from Candida by endoscopic inspection difficult. Endoscopic biopsy will confirm the diagnosis. Treatment involves suspension, if possible, of drugs such as corticosteroids or cytotoxic agents. The antiviral agent acyclovir is active against this virus.

Cytomegalovirus oesophagitis

This oesophageal infection is seen most frequently in patients with AIDS, bone marrow transplantation and other immunodeficiency states. Endoscopic features are of extensive ulceration, and characteristic inclusion bodies and giant cells are seen on biopsy.

Is it true dysphagia?

Dysphagia is defined as difficulty with the act of swallowing. The purely sensory symptom of globus can be equated inappropriately with difficulty swallowing by the patient. Globus is a non-painful sensation of a lump or fullness in the throat in which deglutitive food bolus transport is unimpaired. Indeed, globus sensation is usually alleviated by eating and is most noticeable between meals. The patient with globus sensation generally only requires otolaryngological evaluation to exclude local inflammatory or infiltrative disorders followed by explanation and reassurance. Some cases can be reflux-related and a trial of proton pump inhibitor therapy is reasonable although response rates to this approach are modest and variable.

Age of onset, duration of dysphagia, frequency and progression

The duration of symptoms is often an important clue to whether the underlying cause is benign or malignant or whether it is due to a recent, acute event such as a stroke. Malignant dysphagia usually presents with a short history of progressive dysphagia over weeks or a few months and is frequently associated with weight loss. A sudden onset of dysphagia, often in association with other neurological symptoms or signs, usually indicates a neurological cause such as stroke. Frequent dysphagia, which is progressive and predominantly for solids, is more likely to indicate an underlying structural disorder such as a peptic stricture or tumour.

A long history of intermittent, non-progressive, solid bolus obstruction is the hallmark of an oesophageal mucosal ring. In a patient over the age of 40 years, this is generally due to a single mucosal (Schatzki’s) ring at the squamocolumnar junction. In a young male this is commonly due to eosinophilic oesophagitis.

Intermittent dysphagia, for both liquids and solids, is characteristic of a motility disorder such as achalasia, diffuse oesophageal spasm or scleroderma oesophagus.

Perceived site of bolus hold-up

The reported site of bolus hold-up can be helpful in finding the location of the underlying cause, but the patient’s perception of the site of hold-up can be misleading. In cases of pharyngeal dysphagia, hold-up is reported in the neck. However, distal oesophageal pathology causing dysphagia can give rise to a sensation of the bolus catching either in the cervical or retrosternal region. Hence, a perception by the patient of apparent bolus hold-up in the neck does not help the clinician distinguish between pharyngeal and oesophageal causes of dysphagia. However, perceived hold-up in the low retrosternal region excludes a pharyngeal cause for the dysphagia.

An algorithmic approach to determine site and likely aetiology of dysphagia

With the abovementioned information to hand, the next logical step is to define more precisely the anatomical location of the problem. This can be achieved in most instances from the history (Fig 2.5).

Figure 2.5 An algorithmic approach in taking a history from the patient with dysphagia. The first step is to determine whether the problem arises from the pharynx or from the oesophagus. The italicised text boxes on the left denote the questions to ask the patient. The text boxes in the centre represent patient responses. Having determined that the likely source of the problem is oesophageal rather than pharyngeal in origin, the second step is to determine, on the basis of history, whether the problem is structural or whether it is due to dysmotility (refer to text).

More specific symptoms for oropharyngeal dysfunction

Four symptoms are highly specific for oropharyngeal dysfunction: (1) delayed or absent oropharyngeal swallow initiation; (2) deglutitive postnasal regurgitation or egress of fluid through the nose during swallowing; (3) deglutitive cough indicative of aspiration; and (4) the need to swallow repetitively to clear swallowed material from the hypopharynx. If one or more of these symptoms is experienced, the cause of the dysphagia is probably oropharyngeal—either structural or neuromyogenic—and further history and investigation of a likely oropharyngeal problem should proceed accordingly (see below). Supportive but less specific symptoms of oropharyngeal dysphagia include bolus hold-up perceived in the neck, piecemeal swallows, oral spill or drooling, dysphonia, throat clearing and garbled voice. Immediate expectoration (rather than regurgitation) of an offending bolus is indicative of bolus retention in the hypopharyngeal or cricopharyngeal region. Delayed regurgitation of old food is typical of a large pharyngeal diverticulum.

Symptoms specific for oesophageal dysphagia

If, based on the above, one strongly suspects an oesophageal cause for dysphagia, the next step is to determine whether the cause is a structural lesion or a motor disorder (Fig 2.5). Again, this can be achieved by the line of questioning in the following step-wise fashion.

Figure 2.6 The endoscopic finding of fluid or salivary residue within the oesophagus, particularly if it is dilated (left), is highly suggestive of achalasia. Note the typical radiographic findings of achalasia (right): a dilated oesophagus with food and fluid retention, an air-fluid level (arrow) and the ‘bird beak’ tapering at the cardio-oesophageal junction (arrow head).

Is the dysphagia for solids or liquids? Typically a motor disorder (e.g. achalasia, diffuse spasm) will cause dysphagia for both liquids and solids whereas a structural disorder will cause dysphagia for solids only. As the calibre of the oesophagus narrows, the size of the solid bolus required to cause obstruction becomes progressively smaller.

If the problem is likely to be a structural oesophageal disorder, the following enquiry will define the likely cause:

If the problem is likely to be an oesophageal motility disorder, the following enquiry will define the likely cause.

The three cardinal features of oesophageal dysmotility are dysphagia (for solids and liquids), chest pain and regurgitation:

If oesophageal dysmotility is strongly suspected, distinction between achalasia and oesophageal spasm can be difficult at times. Achalasia is much more common than spasm. In achalasia, chest pain is more prominent early in the disease, but over the years tends to diminish and may disappear as dysphagia and regurgitation worsen. Due to oesophageal dilatation and poor clearance, regurgitation is frequently more impressive in achalasia than it is in the case of spasm.

Is there an underlying related or causative disease?

Oral-pharyngeal dysphagia usually has a neurological basis. A prior history of stroke is often obtained. Symptoms of bulbar muscle dysfunction or other brain stem symptoms (such as vertigo, nausea, vomiting, hiccup, tinnitus, diplopia or drop attacks) should be sought. The patient may complain of tremor, ataxia or unsteadiness, which might indicate an underlying movement disorder or may describe muscular weakness suggestive of myopathy (Box 2.2).

Oesophageal dysphagia may present on a background of reflux; hence, history of heartburn and antacid use is relevant. Smoking, alcohol and prior caustic ingestion are risk factors for oesophageal carcinoma. Oesophageal dysmotility can be associated with connective tissue disease, particularly scleroderma when Raynaud’s phenomenon and typical skin changes may be present. Eosinophilic oesophagitis is frequently associated with a history of atopy and asthma.

Hands and skin

Changes consistent with Raynaud’s phenomenon, with or without sclerodactyly, are features commonly found in patients with scleroderma oesophagus. Calcinosis and telangiectasia, if present, complete the features of CREST syndrome, which is always associated with oesophageal dysmotility and reflux. The lilac-coloured (heliotrope) skin changes, typically around the nail beds, bridge of the nose and cheeks and forehead is a feature of dermatomyositis, which can cause severe pharyngeal dysfunction and, to a lesser extent, oesophageal dysfunction as well. Rarely, other skin disorders can cause oesophageal disease and include lichen planus, pemphigus, epidermolysis bullosa, Bechet’s syndrome and acanthosis nigricans.

Sweating, tremor and tachycardia of thyrotoxicosis may be present in patients with thyrotoxic myopathy causing pharyngeal dysfunction. The typical features of thyrotoxicosis, however, may not be present in the elderly or individuals taking beta-adrenergic antagonists.

Head and neck

The examiner should palpate the neck for masses, lymph nodes or a goitre. Rarely, a pharyngeal pouch can be felt, nearly always on the left, and may be compressed causing regurgitation of a small amount of food residue into the pharynx with an audible ‘gurgle’. Signs of prior surgery, tracheostomy and radiotherapy are obvious and should be noted. The oral cavity (including natural dentition or dentures, tongue and oropharynx) should be inspected.

Eyes

Thyrotoxic eye signs should be looked for. Ptosis might indicate a myopathy or myasthenia. Unilateral ptosis, if associated with Horner’s syndrome (descending sympathetic tract), is typical of lateral medullary infarction causing pharyngeal dysphagia. In addition to dysphagia, the lateral medullary (Wallenberg’s) syndrome typically involves hoarseness (10th nerve), vestibular dysfunction (nystagmus, vertigo, vomiting, diplopia and tinnitus), cerebellar limb ataxia, contralateral loss of pain and temperature sensation over half the body (spinothalamic tract), and hiccups.

Neuromuscular function

Careful examination of cranial nerve function will sometimes detect bulbar muscle dysfunction, but normal palatal motion and an intact gag reflex does not exclude significant bulbar muscle dysfunction in a patient with pharyngeal dysphagia. Tremor and gait disturbances may reflect an extrapyramidal movement disorder such as Parkinson’s. Muscle fasciculation, wasting and weakness or fatigueability should be sought to detect underlying motor neurone disease, myopathy or myasthenia.

Watch and listen to the patient swallow. With the index and middle fingers resting lightly on the hyoid and laryngeal cartilages respectively, the axial motion of the larynx and hyoid bone should be noted while the patient swallows a mouthful of water. Inadequate laryngeal ascent is frequently seen in neurogenic dysphagia, impairs airway protection during the swallow and can be associated with aspiration. Aspiration will often (but not invariably) cause coughing or choking during the swallow.

Respiratory and nutritional sequelae

The patient’s general nutritional state and body weight are important. The degree of weight loss is a good indicator of the severity of the disease and is most profound in malignant disease. Examination of the chest may reveal signs of respiratory infection, suggesting significant aspiration, which is common in patients with pharyngeal dysphagia.

Investigation of suspected oral-pharyngeal dysphagia

The initial investigation should be a dynamic, radiographic examination—the videoradiographic swallow study of the oral-pharyngeal phase. This examination should be complemented by static films, but video recordings are mandatory as the motor events of the oral-pharyngeal phase are too complex and too rapid to be resolved by simple observation of fluoroscopy or x-ray films. Static films are important in detecting mucosal defects and structural lesions such as strictures, rings, pouches, webs (Fig 2.1) and tumours.

In cases of oral-pharyngeal dysfunction where the cause is not clear, the videoswallow study is a sensitive means of confirming the site of dysfunction; establishing whether a pharyngeal motor problem exists; defining the mechanisms of dysfunction; and detecting the presence and timing of aspiration. A clear idea of the mechanisms of dysfunction and severity of the disorder is vital in tailoring therapy. In the context of a recent stroke, head or neck surgery or radiotherapy, the underlying cause may be obvious. Nevertheless, in such cases an understanding of the patient’s swallow mechanics is vital in deciding on the advisability and safety of oral feeding and the choice of therapy. For example, recognition of timing of aspiration has therapeutic implications. Preswallow aspiration results from poor tongue control and premature spill of the bolus over the back of the tongue before laryngeal protective reflexes have been elicited. Intraswallow aspiration frequently accompanies pharyngeal weakness. Postswallow aspiration is seen when residual bolus pools in the hypopharynx and spills over into the airway as it reopens following the swallow. Pharyngeal bolus transport abnormalities may be due to defective triggering of the pharyngeal motor response, pharyngeal peristaltic weakness or a combination of both. Pharyngeal muscle weakness may be seen as postswallow pooling in the pyriform sinuses. If weakness is unilateral, pooling is confined to the paretic side and is associated with pharyngeal bulging on the affected side. In such cases bolus transport can be facilitated by therapeutic strategies such as head turning towards the paretic side. Diminished upper oesophageal sphincter opening can be due to local stricture, inadequate pharyngeal propulsive forces or incomplete sphincter relaxation. Depending upon the relative contribution of one or more of these features, such patients may benefit from cricopharyngeal dilatation or myotomy.

Laboratory tests are useful in confirming suspected underlying primary diseases that may cause oral-pharyngeal dysphagia. Serum creatine phosphokinase level, erythrocyte sedimentation rate, antinuclear antibodies, acetylcholine receptor antibodies and thyroid function tests will give a clue to most acquired myopathies, but electromyogram and muscle biopsy may also be necessary as 20% of cases of myositis will have normal biochemistry.

Endoscopy will be required in most patients with pharyngeal dysfunction and certainly all cases in whom it is uncertain whether the problem is oesophageal or pharyngeal. Videoradiography should precede endoscopy as it may detect a problem that would make endoscopy hazardous or difficult (e.g. pharyngeal pouch, cricopharyngeal stricture or tumour). Furthermore, radiology may detect a structural lesion that is better appreciated radiologically than it is by the endoscopist and that may be successfully treated endoscopically (e.g. cricopharyngeal stricture or postcricoid web).

If the cause for pharyngeal dysfunction is not apparent after the above investigation, careful ear, nose and throat evaluation is required to exclude pharyngolaryngeal malignancy. Tumours in the region can be easily overlooked by the radiologist, and lesions in some locations can be missed by the endoscopist using a standard gastroscope. Features highly suggestive of local malignancy, such as recent onset of throat pain on swallowing and hoarseness with dysphagia, should prompt early laryngoscopy.

Investigation of suspected oesophageal dysphagia

With a few exceptions, endoscopy should be the first investigation in cases of suspected oesophageal dysphagia. Endoscopy is more sensitive than radiology in detecting mucosal disease. It also provides an opportunity to obtain biopsies and to combine a diagnostic with therapeutic procedure in cases where dilatation is required. One of the deficiencies of endoscopy in the assessment of dysphagia is that it cannot reliably diagnose motility disorders, although the endoscopic finding of a dilated oesophagus containing fluid or salivary residue is highly suggestive of dysmotility (Fig 2.6). Endoscopy does not always reliably pick up all benign structural abnormalities capable of causing dysphagia. This is because an accurate estimation of the narrow calibre oesophagus is not always possible at endoscopy. Hence, a negative endoscopy does not always exclude a structural cause of dysphagia. If a structural oesophageal abnormality is suspected strongly on history and the oesophagus has a normal macroscopic appearance, oesophageal biopsies should be taken to check for eosinophilic oesophagitis, which is commonly associated with one or more mucosal rings (Fig 2.8).

In the investigation of oesophageal dysphagia, there are two situations in which a barium swallow should precede endoscopy—a suspected oesophageal ring and suspected oesophageal dysmotility. Preliminary barium swallow findings in these circumstances may permit definitive treatment of a ring or achalasia at the initial endoscopy, or dictate manometry prior to endoscopy if achalasia is suspected (Fig 2.6). In the patient with a typical history of an oesophageal ring (see above), a barium swallow can be an extremely useful adjunct to endoscopy, because mucosal rings are frequently not apparent endoscopically. An appropriately tailored barium swallow study, including prone-oblique views and if necessary a marshmallow swallow, will usually clearly demonstrate a ring and/or the site of bolus hold-up causing the patient’s symptoms. The ring can then be dilated, even if it is not visible to the endoscopist, at the subsequent endoscopy.

Oesophageal manometry is usually reserved for cases in whom endoscopy and radiology have failed to achieve a diagnosis. Manometry is the only way to diagnose achalasia with certainty; its manometric features are oesophageal aperistalsis, hypertonia and failure of the lower oesophageal sphincter relaxation during swallowing (Fig 2.7). The manometric hallmark of diffuse oesophageal spasm is synchronous oesophageal contractions in at least 10% of water swallows in an oesophagus, which can demonstrate peristalsis. Additional features present to a variable extent include repetitive waves (swallow-induced or spontaneous); high amplitude contractions; and prolonged contractions (of more than 6 seconds). The scleroderma oesophagus demonstrates complete aperistalsis and absent lower oesophageal sphincter tone, both being due to profound smooth muscle degeneration in the distal oesophagus.

Figure 2.7 Manometry tracing from patient with oesophageal achalasia. Shown are pressures at 5 cm intervals along the oesophagus, and from the lower oesophageal sphincter and stomach, during a 5 mL water swallow. Note the hypertensive sphincter (pressure 30 mmHg) and the failure of lower oesophageal sphincter relaxation (circled). There is a complete loss of peristalsis. In its place is a synchronous low amplitude pressure wave (dashed line) with identical waveform along the entire oesophageal length, indicative of lack of lumen occlusion of a dilated oesophagus (as seen in barium radiograph, Fig 2.6).

Treatment of oesophageal dysphagia

Oesophageal strictures, rings and webs are generally successfully treated by endoscopic dilatation. This is most commonly achieved by passing graduated sizes of Silastic™ (e.g. Savary-Gilliard®) or balloon dilators over an endoscopically placed guide wire. The underlying cause of the stricture must also be treated. Severe reflux disease causing stricture should be managed with potent acid suppression with a proton pump inhibitor. The more refractory cases may require antireflux surgery. Difficult strictures often require repeated dilatations.

In the case of one or more oesophageal rings, eosinophilic oesophagitis must always be considered and diagnosis is achieved with endoscopic biopsies. Eosinophilic oesophagitis should be treated in the first instance with the topical (swallowed) steroid fluticasone. Controlled trials have shown comparable efficacy between topical and systemic steroids in eosinophilic oesophagitis, but the former is preferred as it has fewer systemic effects. Steroid therapy in eosinophilic oesophagitis may obviate the need for oesophageal dilatation. However, a proportion of cases, particularly with longstanding disease, may still require dilatation to achieve adequate symptomatic relief and avoid episodic complete bolus impaction. Great care must be exercised in these cases as the rings are often relatively tight and significant postdilatation tears are not infrequent (Fig 2.8).

Figure 2.8 Case of a 23-year-old male with longstanding, intermittent dysphagia for solids. The barium swallow (A) shows multiple mucosal rings and a dominant narrowing in the proximal third of the oesophagus. The endoscopic appearance of the multi-ringed oesophagus (B) is typical of eosinophilic oesophagitis (proven on biopsy). Note also the mucosal tear following endoscopic oesophageal dilatation (C).

The management of oesophageal malignancy requires relief of dysphagia and, where appropriate, ablation of the tumour either by surgery, chemo- or radiotherapy, or laser ablation. Due to the advanced nature of the disease at the time of diagnosis, the aim of therapy is palliative in the majority although surgery is an option in early cases. Relief of dysphagia in difficult circumstances can be achieved by placement of an expanding oesophageal stent. Covered stents are also useful in treating associated oesophagotracheal fistulae if they occur.

Oesophageal achalasia is best treated by mechanical disruption of the non-relaxing lower oesophageal sphincter. This can be achieved either by surgical cardiomyotomy or by endoscopic, balloon (pneumatic) dilatation. The incidence of posttreatment gastro-oesophageal reflux is greater in those treated surgically; hence, surgical myotomy should be combined with fundoplication. Although smooth muscle relaxants, including the calcium channel blocker nifedipine, do reduce lower oesophageal sphincter pressure, therapeutic results are disappointing. Botulinum toxin (Botox) is simple and safe to infiltrate into the lower oesophageal sphincter at endoscopy with short-term efficacy approaching that of pneumatic dilatation. However, because Botox has limited durability requiring repeated injections it is reserved for the very elderly or those with significant associated comorbidity.

Diffuse oesophageal spasm is best treated with smooth muscle relaxants such as nitrates and calcium channel blockers. If symptoms are relatively infrequent, sublingual nitrates to abort an episode of chest pain can be useful. Refractory cases with debilitating symptoms can be treated surgically by long oesophageal myotomy, which is effective in 50–70% of cases.

Treatment of oral-pharyngeal dysphagia

Identification and treatment of an underlying cause, if present, should be the primary aim. Thyrotoxic myopathy responds well to treatment of the thyroid disorder. Inflammatory myopathies (systemic lupus erythematosus and polymyositis) respond variably to steroids with or without other immunosuppressive agents. Dysphagia due to myasthenia, and to a lesser extent to Parkinson’s disease, is also responsive to specific drug therapy. Avoidance of implicated drugs such as phenothiazines can be helpful, but the effects of these drugs are not always reversible.

Structural disorders such as webs and some pharyngeal or cricopharyngeal strictures can be successfully dilated endoscopically. The dysphagia associated with the posterior pharyngeal pouch is almost invariably successfully treated by surgery (cricopharyngeal myotomy with or without pouch excision or suspension). Head and neck tumours causing dysphagia generally require surgery or radiotherapy.

Pharyngeal dysphagia due to cerebrovascular accident is more difficult to treat. However, substantial spontaneous recovery can also be expected in many cases. Expert treatment of oral-pharyngeal dysphagia requires close cooperation with a speech pathologist and careful assessment of the dynamics of swallowing as has been outlined. The aims of therapy are to establish a safe means of nutrition by avoiding or minimising aspiration and to promote swallowed bolus clearance from the pharynx by manipulation of food consistency, swallow technique or the use of prosthetic devices or surgery. The reader is referred to a detailed review of this topic. If aspiration is absent or minimal, oral feeding of modified food consistencies can continue safely. However, introduction of non-oral (enteral) feeding by nasogastric tube in the short term, or percutaneous endoscopic gastrostomy in the longer term, may be necessary to optimise nutrition if feeding via the oral route is considered unsafe. With the help of a speech pathologist, compensatory strategies can be implemented to minimise the symptoms of aspiration and dysphagia by manipulating the manner in which the food bolus flows through the oral and pharyngeal regions. These techniques involve manipulation of the position of the head and/or the body; or altering the characteristics of administered food boluses including volume, rate and viscosity.

Disorders of upper oesophageal sphincter opening may be amenable to cricopharyngeal myotomy, which disrupts the upper oesophageal sphincter and permits it to open more widely. The results from myotomy have been variable, however, and there is no current consensus on who should be selected for myotomy.