Introduction

Ludwig’s angina, first described by Wilhelm Frederick von Ludwig in 1836, is a rapidly progressive cellulitis (an infection of the soft tissues that spreads along tissue planes adjacent to each other) of the floor of the mouth and neck. Whilst rare, the condition is potentially fatal, with death usually occurring from obstruction of the airway following displacement of the tongue and swelling of the structures around the larynx (voice box). The infection develops in the submandibular space (beneath the tongue and above the hyoid bone), which is subdivided into the sublingual space (above the mylohyoid muscle) and the submaxillary space below the mylohyoid.¹

Most commonly, the origin of the infection is dental, usually involving the 2nd and 3rd lower molar teeth, however there are a wide variety of less common causes including infection of the salivary glands (sialadenitis), an open fracture of the jaw, quinsy (peritonsillar abscess), infected thyroglossal duct cysts, trauma from bronchoscopy or intubation, endotracheal lacerations, tongue piercing, oral lacerations, upper respiratory tract infections, and traumatic injury to the floor of the mouth.^1,2

Oral bacteria are the primary organisms implicated in the infection, predominantly Streptococcus viridans and Staphylococcus aureus, but numerous other organisms have been isolated. Whilst most cases occur in otherwise healthy patients, conditions which predispose to infection and compromise the immune system, such as diabetes, alcoholism, malnutrition, aplastic anaemia, HIV/ AIDS, and systemic lupus erythematosus, are recognised risk factors. In the pre-antibiotic era, when the condition was first described, mortality was as high as 50%, but modern surgical techniques and antibiotics have reduced this to 8%.² In addition to upper airway obstruction, Ludwig’s angina causes other serious, potentially fatal conditions such as descending mediastinitis, carotid sheath infection or rupture of the carotid artery, cavernous venous thrombosis, and aspiration pneumonia.²

Ludwig Angina is an aggressive and rapidly progressive condition, with the most common cause of death occurring from the obstruction of the upper airway.  In turn, early diagnosis is imperative. Securing the airway is the main priority, either by intubation (which may require fibre optic guidance) or surgically (either cricothyrotomy or tracheostomy). Intubation risks further swelling of the laryngeal and supraglottic tissues; therefore, it should preferably be attempted in the operating room with staff and facilities necessary to provide a surgical airway. In turn, early consultation with both an anaesthetist and an ENT (ear, nose, and throat) specialist is recommended. Awareness of the differential diagnosis in Ludwig’s angina is important in the assessment of the condition, as due to the importance of rapidly securing the airway, diagnosis is usually made on clinical grounds, rather than waiting for imaging tests such as CT scanning or MRI scanning, which can be performed once the airway is secured.^1,2,3

Key clinical features of ludwig’s angina

Clinical history

Frequently, there will be a history of dental symptoms such as dental pain, overall poor dentition, or a recent dental extraction. Patients are often septic and may exhibit fever, sweating, agitation, drowsiness, or confusion. Characteristically, there will be swelling in the floor of the mouth, and patients complain of difficulty swallowing, even their saliva, leading to drooling and pain on moving or flexing the neck. A hoarse voice accompanied by noisy and difficult breathing may develop, signalling impending airway obstruction.^1,2,3 

Clinical signs

The following clinical signs may be present:^1,2,3,8

• Poor dentition, dental caries (especially of the 2nd and 3rd molar teeth)
• Signs of Sepsis: fever, tachycardia, tachypnoea (rapid breathing), agitation, confusion, cold extremities, clammy skin
• A submandibular swelling, frequently accompanied by anterior (frontal) neck swelling. This is often described as having a “woody” induration.
• Dysphagia (difficulty swallowing)
• Odynophagia (painful swallowing) 
• Drooling of saliva
• Trismus (inability to fully open the mouth)
• Nuchal rigidity (stiff neck), the neck may be held in the “sniffing position” (jaw thrust forward and upwards, as if sniffing the air)
• Fetid breath
• Hoarseness of the voice
• Stridor (noisy breathing)
• Decreased air entry is heard with a stethoscope
• Cyanosis (blue lips)
• “Hot-potato” speech - sounds as if the patient has a hot potato in their mouth, a sign of potential airway crisis
• An absence of lymph node swelling as the infection spreads predominantly by local cellulitis, not the lymphatic system. 

Cyanosis, “hot-potato” speech, stridors, cyanosis, and reduced air entry are all signs of acute airway obstruction, indicating an impending airway crisis.

Differential diagnosis

Several other conditions may have similarities to the presentation of Ludwig’s angina, particularly in the early stages of presentation.

Infectious conditions

Peritonsillar abscess

With an overall incidence of 30 per 100,000 people per year, peritonsillar abscess (quinsy) is the most common of the parapharyngeal abscesses, predominantly found in young adults. This is an abscess that forms in the peritonsillar space (around the tonsil). This space is bounded by the tonsillar capsule to the middle and the superior constrictor muscle to the side, with the tonsillar pillars forming the front and back of this space. Usually, peritonsillar abscess occurs in the context of recent or current tonsillitis, in rarer cases it can occur without bacterial tonsillitis due to an infected tonsillar crypt, glandular fever, or infection in a remnant of tonsil left behind after a tonsillectomy operation.^4,5

Similar to Ludwig’s angina, sepsis, severe throat pain and odynophagia, thick, muffled (hot potato) speech, fetid breath, trismus, and drooling may be present. On examination of the pharynx, however, there is swelling of the anterior tonsillar pillar and soft palate, and the uvula is swollen and deviated away from the side of the abscess. Additionally, lymphadenopathy is frequent, and torticollis (wry-neck) is present (as opposed to the “sniffing position” in Ludwig’s angina). Occasionally, a peritonsillar abscess can lead to the development of Ludwig’s angina, in which both conditions coexist.^4,5 

Retropharyngeal abscess

Predominantly a disease of younger children (typically age 5 or younger), retropharyngeal abscesses usually occur in the context of viral upper respiratory tract infections but can also occur following oropharyngeal injury and dental infection. An abscess forms in the retropharyngeal space (behind the throat in front of the vertebrae of the neck) and is bounded at the front (anteriorly) by the buccopharyngeal fascia and at the back (posteriorly) by the alar fascia (connective tissue running in front of the cervical spine).⁶

Symptoms of retropharyngeal abscess again show many similarities to Ludwig’s angina. Fever, sepsis, throat pain, difficulty swallowing (dysphagia), and odynophagia are usually present. “Hot potato” speech and trismus may develop along with stridor, rapid breathing, and intercostal retractions, indicating airway compromise. What distinguishes it from Ludwig’s angina is a bulge in the posterior (back) pharyngeal wall (but only visible if the abscess is above the level of the tongue), and that the patient prefers to hold the neck flexed and will avoid extension of the neck. Additionally, cervical lymph node swelling is common but usually absent in Ludwig’s angina.⁶

Parapharyngeal abscess

Infections of the parapharyngeal space may also mimic Ludwig’s angina. The parapharyngeal space is an inverted cone-shaped space with the skull base at the base and the hyoid bone at the apex, lying lateral to the pharynx (throat). It is divided into two compartments - the pre-styloid space and the post-styloid space, separated by a sheet of fibrous tissue called the aponeurosis of Zuckerkandl and Teslut. Infections of the pre-styloid space, which contains fat, frequently present with abscess formation leading to prolapse of the tonsil, marked trismus, an external swelling behind the angle of the jaw, and marked odynophagia. Infections of the post-styloid space, which contains the carotid artery and the 9th, 10th, 11th, and 12th cranial nerves, typically present with bulging of the posterior pharyngeal wall, swelling in the parotid region, marked lymphadenopathy, but usually minimal trismus and minimal tonsillar prolapse. Paralysis of the 9th, 10th, and 11th cranial nerves may occur. Infections of both compartments present with sepsis, fever, torticollis and dysphagia, and odynophagia.^7,8

Cellulitis or abscess of the floor of the mouth

Cellulitis or a dental abscess affecting the lower teeth may mimic the early signs of Ludwig’s angina; however, the spread and the development of sepsis will be less aggressive, and the patient will not go on to develop the later signs seen in Ludwig’s angina.⁸

Non-infectious causes

Angiooedema

Angioedema is swelling of the face, lips, tongue, larynx, and often the hands and feet, although it can affect any part of the body. It is subdivided into several types based on differing pathology.

• Allergic (histaminergic): This is the type most people are familiar with. Usually occurring rapidly following exposure to a trigger eg, insect sting, food allergy, drug allergy. It is characterised by urticaria (hives), flushing, and itching^9,10
• Acquired angiooedema due to ACE-I (angiotensin-converting enzyme inhibitor drugs, used to treat high blood pressure and heart failure). Whilst swelling may occur in this form, there is no urticaria, and the symptoms are generally more severe. Other drugs are less commonly indicated, including proton pump inhibitors (used for stomach conditions and reflux), SSRI antidepressants, and the oral contraceptive pill⁹ 
• NSAID-induced angioedema - caused by NSAID drugs (such as ibuprofen and aspirin), this form typically causes urticaria and facial swelling^9,10
• Hereditary angioedema may present with a prodromal illness before the onset of angioedema associated with a rash (erythema marginatum). It frequently affects the gut, causing abdominal symptoms which may be misdiagnosed as gastroenteritis¹⁰
• Acquired angiooedema with C1 inhibitor deficiency - frequently associated with underlying leukaemia or other myeloproliferative disorder¹⁰

In Angioedema, there may be swelling of the tongue and floor of the mouth, but usually associated with the clinical picture of angioedema.  The airway may still become compromised. However, signs of infection and sepsis will not usually be present, and the history will be more in keeping with angioedema.

Neoplasms (e.g., oral cavity or submandibular/ sublingual tumours)

Tumours of the oral cavity, lips, and tongue are relatively common, with 450,000 cases of squamous cell mouth cancer being reported annually. If these are located under the tongue (sublingually) or in the floor of the mouth, they may present with a painful submandibular swelling, which may cause trismus and odynophagia. Tumours of the submandibular salivary gland may also occur; these are usually mucoepidermoid or adenoid cystic carcinomas or adenocarcinoma.^11,12

Symptoms caused by a tumour will usually be of gradual onset, and signs of fever and sepsis are not common. There may be swelling of the lymph nodes if local metastasis has occurred, and generalised symptoms may be present, such as weight loss and cachexia. The mass is usually firm and frequently non-tender as opposed to the findings of a tender mass with woody induration in Ludwig’s angina. CT scanning is the imaging modality of choice for these cancers.¹¹

Sialadenitis / Sialolithiasis / Submandibular gland abscess

Inflammation and infection of the submandibular salivary gland is termed submandibular sialadenitis. Dental infection, salivary gland stones (sialolithiasis), and dry mouth / poor oral hydration are common underlying causes. Sialadenitis may cause a painful swelling in the submandibular region, which typically develops over a period of several days and may become worse when eating. In some cases, there may be fever and abscesses in the submandibular salivary gland that may develop as a result. Ultrasound is particularly useful in differentiating it from Ludwig’s angina and helping define abscesses. Sialadenitis can occur due to bacterial or viral infection or autoimmune causes.¹³

Salivary gland stones (sialolithiasis) present with intermittent pain and swelling in the submandibular region, which is typically worse when eating. Often, the stone can be felt (palpated) in the floor of the mouth in the region of the submandibular duct. Fever and sepsis are not usual findings, unless there is accompanying sialadenitis or abscess formation.¹³

Sublingual haematoma

Bleeding under the tongue can occur after dental surgery, particularly if the patient is on anticoagulant drugs. It is important as it can cause airway obstruction. Fever and sepsis are absent. Rarely can these occur spontaneously with anticoagulant drugs such as Warfarin ¹⁴

Diagnostic tools

Because of the importance of ensuring airway patency, clinical examination and history are the most important bases for diagnosis in Ludwig’s angina. However, once airway patency is established, imaging can help aid diagnosis. Plain X-rays may show soft tissue swelling and the presence of gas if there are gas-forming organisms causing infection. Ultrasound is useful for suspected salivary gland abscesses, and stones may be seen on oral x-rays (OPG) or ultrasound. CT scanning, however, is the usual modality of choice. Blood tests may show a raised white cell count on a full blood count and raised inflammatory markers such as CRP, but these are not diagnostic. Blood cultures should be taken to try to identify the causative bacterial organism.^1,2,3

Summary

Ludwig’s angina is a rare and serious infection of the submandibular space, which can lead to rapid airway obstruction and death. Other infections of the deep spaces of the neck, most commonly peritonsillar abscess, but also including parapharyngeal and retropharyngeal abscesses, may mimic Ludwig’s angina and may occasionally give rise to Ludwig’s angina as these spaces communicate with each other. Angiooedema, of which there are several types, the most common being allergic angiooedema and acquired angiooedema due to ACE-inhibitor drugs, is another differential. Finally, infection, inflammation, or abscess formation in the submandibular salivary gland is an important possible differential. The main priority is to ensure a patent airway; thus, diagnosis is usually made on clinical grounds, with investigation by CT scanning performed once a patent airway is established.