Essential Microbiology for Dentistry. 5th ed.

Chapter 35. Oral mucosal and salivary gland infections

Oral mucosal infections

The oral mucosa, which covers a significant proportion of the oral cavity, is affected by a number of infectious diseases. The majority of these are of fungal (candidal) and viral origin and are similar to infections seen in other superficial mucosal surfaces of the body, such as the vagina. In this section, candidal infections are discussed first, followed by viral infections.

Oral candidiasis (synonym: oral candidosis)

Oral candidiasis or candidosis is mainly caused by the yeast Candida albicans, although other Candida species often cause infection. All forms of oral candidiasis are considered to be opportunistic infections, and the epithet 'disease of the diseased' has been applied to these infections, which are seen mainly in the 'very young, the very old and the very sick'.


Oral candidiases can be classified as follows (Fig. 35.1):

1. Primary oral candidiases: localized candidal infections present only in the oral and perioral tissues.

2. Secondary oral candidiases: candidal infections that manifest in a generalized manner both in the oral cavity and in other mucous and cutaneous surfaces (systemic mucocutaneous candidal infections). These are due to rare disorders (except perhaps in candidiasis of human immunodeficiency virus (HIV) infection) such as thymic aplasia and chronic endocrine diseases.

The classic triad of (either primary or secondary) oral candidiases are:

1. pseudomembranous variant

2. erythematous (atrophic) variant

3. hyperplastic variant.

In addition, there are a number of other Candida-associated lesions where the aetiology is multifactorial. These are primary oral candidiases restricted to the oral cavity only. Antifungal therapy alone will not cure these diseases, and underlying cofactors that perpetuate the disease need to be evaluated and eradicated for disease resolution. These diseases are:

 Candida-associated denture stomatitis

 angular cheilitis or angular stomatitis

 median rhomboid glossitis

 linear gingival erythema (the microbiological aetiology is not conclusive).

Pseudomembranous candidiasis

Pseudomembranous candidiasis, classically termed 'thrush' (Fig. 35.2), is an acute infection but may persist intermittently for many months or even years in patients using corticosteroids topically or by aerosol, in HIV-infected individuals, and in other immunocompromised patients. It may also be seen in neonates and in the terminally ill, particularly in association with serious underlying conditions such as leukaemia.

Clinical features

Characterized by white membranes on the surface of the oral mucosa, tongue and elsewhere. The lesions develop to form confluent plaques that resemble milk curds and can be wiped off to reveal a raw, erythematous and sometimes bleeding base. Hence, some consider pseudomembranous and the erythematous variants a continuum and a single entity (i.e., two stages of the same disease).

Microbiology and pathology

The white patches consist of necrotic material and desquamated parakeratotic epithelium, penetrated by yeast cells and hyphae, which invade as far as the stratum spinosum. Oropharyngeal thrush may sometimes spread into the adjacent mucosa, particularly that of the upper respiratory tract and the oesophagus. The combination of oral and oesophageal candidiasis is particularly prevalent in HIV disease.

Fig. 35.1 Classification of oral candidiasis.

Fig. 35.2 Pseudomembranous candidiasis (thrush) of the palate in a human immunodeficiency virus (HIV)-infected individual.

Fig. 35.3 Erythematous candidiasis of the palate in a human immunodeficiency virus (HIV)-infected individual.


Topical antifungal preparations, mainly containing the polyene drugs nystatin and amphotericin, are given as lozenges or pastilles.

Erythematous (atrophic) candidiasis

Erythematous candidiasis is a poorly understood condition associated with corticosteroids, topical or systemic broad-spectrum antibiotics, or HIV disease. It may arise as a consequence of persistent acute pseudomembranous candidiasis when the pseudomembranes are shed, or may develop de novo. Erythematous candidiasis of the palate is a common Candida-associated lesion frequently observed in elderly people wearing full dentures (Candida-associated denture stomatitis; see below).

Clinical features

The clinical presentation is of one or more asymptomatic erythematous areas, generally on the dorsum of the tongue, palate or buccal mucosa (Fig. 35.3). Lesions on the dorsum of the tongue present as depapillated areas; red areas are often seen on the palate in HIV disease.

There can be associated angular stomatitis, especially in Candida-associated denture stomatitis.

Fig. 35.4 Chronic hyperplastic candidiasis at the commissures of the mouth.


Not much is known of the role of yeasts in this condition, although antifungal therapy leads to resolution of the lesions.


Topical antifungal treatment, mainly nystatin and amphotericin, is given as lozenges or pastilles. Azole group agents, such as oral fluconazole tablets, are useful in HIV disease.

Hyperplastic candidiasis (Candida leukoplakia)

The lesions in hyperplastic candidiasis present as chronic, discrete raised areas that vary from small, palpable, translucent, whitish areas to large, dense, opaque plaques (Fig. 35.4), hard and rough to the touch (plaque-like lesions). Homogeneous areas or speckled areas that do not rub off (nodular lesions) can also be seen. The lesions are often asymptomatic and usually occur on the inside surface of one or both cheeks (retrocommissural area). Oral cancer supervenes in 9%-40% of cases of hyperplastic candidiasis, as compared with the 2%-6% risk of malignant transformation cited for oral white patches in general. Therefore, patients with recalcitrant hyperplastic candidal lesions resistant to therapy should be kept under regular surveillance.

Microbiology and histopathology

Parakeratosis and epithelial hyperplasia occur, with candidal invasion restricted to the upper layers of the epithelium (Fig. 35.5). The condition has been associated in a minority with iron and folate deficiencies and with defective cell-mediated immunity. Biopsy is important as the condition is premalignant and shows varying degrees of dysplasia.

Fig. 35.5 Histopathological section of a chronic hyperplastic candidiasis lesion showing numerous candidal hyphae (pink) infiltrating the superficial layers of the oral epithelium.

Fig. 35.6 Candida-associated denture stomatitis showing the erythematous and oedematous denture-bearing (palatal) mucosa (Newton’s type 2 lesion).


Topical antifungal treatment, mainly nystatin and amphotericin, is given as lozenges or pastilles. Azole group agents, such as oral fluconazole tablets, may help resolve chronic infections. Because of the possibility of malignant transformation, patients should be followed up if the condition is chronic.

Candida-associated lesions

Candida-associated denture stomatitis

Candida-associated denture stomatitis, also called denture sore mouth or chronic atrophic candidiasis, is one of the most common ailments in wearers of full dentures; in some areas such as Scandinavia, 60% of wearers over 60 years old were reported to suffer from the condition. It is also associated with patients wearing orthodontic appliances or obturators for cleft palate. The characteristic presenting signs are erythema and oedema of the mucosa that is in contact with the fitting surface of the upper denture. The mucosa below the lower dentures is hardly ever involved.

Clinical features

The patient may occasionally experience slight soreness but is usually free from symptoms; the only presenting complaint is sometimes an associated angular stomatitis. Depending on the severity of inflammation, the lesions may appear as:

 pinpoint erythema of the denture-bearing mucosa (Newton's type 1)

 diffuse and confluent erythema and oedema of the denture-bearing mucosa (Newton's type 2; Fig. 35.6)

 papillary hyperplasia and inflammation, commonly involving the central part of the hard palate and the alveolar ridge (Newton's type 3; Fig. 35.7).


1. Local factors: poor denture hygiene, ill-fitting dentures, traumatic dentures, carbohydrate-rich diets, xerostomia (e.g., Sjogren's syndrome).

2. Systemic factors: iron and folate deficiency, diabetes mellitus, immune defects.

Microbiology and histopathology

Generally considered to be due to accumulation of plaque biofilms with yeasts and bacteria on the fitting surface of the denture and the underlying mucosa. In the papillary hyperplastic variety, Candida species do not invade the epithelium. Other aetiological factors, such as mechanical irritation or an allergic reaction to the denture base material, may be involved.


The condition is treated by:

 scrupulous denture hygiene and removal of dentures at night (these measures alone, without antifungals, are adequate in the majority of cases)

 regular disinfection of dentures by steeping them in sodium hypochlorite or chlorhexidine to eradicate the reservoir of candidal cells in the prosthesis

 review of the denture fitness to relieve trauma, if any

 a diet with a low content of fermentable carbohydrates

 polyene antifungals—nystatin, amphotericin (lozenges, pastilles, etc.).

Angular stomatitis (perleche, angular cheilitis)

The lesions of angular stomatitis are seen in one or both angles of the mouth (Fig. 35.8), especially as a complication of Candida- associated denture stomatitis.

Clinical features

Characterized by soreness, erythema and fissuring, this condition is commonly associated with denture-induced stomatitis. Both yeasts and bacteria (especially Staphylococcus aureus) are involved as interacting predisposing factors. However, angular stomatitis is very occasionally an isolated initial sign of anaemia or vitamin deficiency, such as vitamin B12 deficiency, and resolves when the underlying disease has been treated. The condition is also seen in HIV-associated disease (Fig. 35.9).


Candida spp. are present with or without co-infection with Staphylococcus aureus. The presence of yellow crusting may indicate staphylococcal infection.


1. Elimination of the intraoral reservoir of infection in concurrent denture stomatitis.

2. Adjustment of vertical dimension of the dentures to prevent saliva retention, and moisture at the angles of the mouth (note: moist body surfaces encourage the growth of Candida).

3. Topical antifungal therapy with nystatin, amphotericin B or miconazole (miconazole has both antifungal and antistaphylococcal activity and is useful for mixed infections); antistaphylococcal preparations (dictated by microbiological investigation) include fusidic acid and neomycin/chlorhexidine.

4. Investigate for possible underlying disease: iron or vitamin B12 deficiency; HIV infection.

Fig. 35.7 Candida-associated denture stomatitis showing palatal papillary hyperplasia (Newton’s type 3 lesion).

Fig. 35.8 Angular cheilitis in a denture-wearer. Note the yellow crusting due to staphylococcal infection.

Fig. 35.9 The aetiological factors implicated in angular cheilitis. AIDS, Acquired immune deficiency syndrome.

Fig. 35.10 Median rhomboid glossitis showing the characteristic diamondshaped lesion.

Median rhomboid glossitis

Midline glossitis, or glossal central papillary atrophy, is characterized by an area of papillary atrophy that is elliptical or rhomboid in shape and symmetrically placed centrally at the midline of the tongue, anterior to the circumvallate papillae (Fig. 35.10). Occasionally, median rhomboid glossitis presents with a hyperplastic exophytic or even lobulated appearance. In addition to fungal infection, a number of predisposing cofactors, including smoking, steroid inhalation and remnants of the tuberculum impar, have been proposed.

Microbiology and management

The condition frequently shows a mixed bacterial-fungal microflora and responds to antifungals and/or improvement in oral hygiene. The lesion may also spontaneously remit. Patients are often worried about the appearance and are cancer-phobic. In this event, reassurance is essential.

Linear gingival erythema

This condition, defined as a localized or generalized erythematous band extending along the gingival margins (between adjacent gingival papillae), was first described in HIV-infected individuals; it is however not confined to this group. Although Candida is implicated in the pathogenesis, and lesions resolve after antifungal therapy in some cases, it is likely that other cofactors such as oral hygiene play an equally important role.

Candidiasis and immunocompromised hosts

A few patients have chronic candidiasis from an early age, sometimes with a definable immune defect, e.g., chronic mucocutaneous candidiasis (Figs 35.11 and 35.12). Candidal infections in these patients are seen in the oral mucosa, skin and other body parts. These secondary oral candidal infections have increased recently because of the high prevalence of attenuated immune response, consequent to diseases such as HIV infection, haematological malignancy and treatment protocols, including aggressive cytotoxic therapy.

Fig. 35.11 Candidal paronychia in a patient with chronic mucocutaneous candidiasis. (Note: this patient also had scalp and oral involvement.)

Fig. 35.12 Chronic mucocutaneous candidiasis: hyperplastic lesions of the tongue in the same patient shown in Fig. 35.11.

Oral candidiasis in HIV disease

Candidal infections, with oral thrush and oesophagitis as frequent clinical manifestations, are the most common opportunistic infections encountered in acquired immune deficiency syndrome (AIDS). It has also been shown that the occurrence of an otherwise unexpected mycosis (typically oral candidiasis) in an HIV-infected individual is a poor prognostic indicator of the subsequent development of full-blown AIDS (see also Chapter 30). However, in HIV-infected populations on antiretroviral therapy, the incidence of oral candidiasis has significantly declined.

Systemic candidiasis

Candidiasis is usually restricted to the skin and mucous membranes but may occasionally spread and manifest systemically (multisystem involvement). Systemic forms of candidiasis may affect only one organ or be disseminated (candidal septicaemia, candidaemia). This occurs mainly in compromised patients, e.g., up to 30% of all patients with acute leukaemia die with systemic candidal infections.

Laboratory diagnosis

A summary of the specimens required for the laboratory diagnosis of oral candidal infections is given in Table 35.1.

Oral manifestations of systemic mycoses

A number of systemic fungal infections may manifest as oral ulcerations or granulomas. Many of these are caused by dimorphic fungi and are uncommon in the West, but are seen in developing countries. These oral lesions are usually secondary diseases, the primary lesions being confined to the lungs and/or the skin. Because the primary lesion is internal, it may go unnoticed until the secondary oral lesion presents as the apparently initial manifestation of the infection (e.g., histoplasmosis). Usually, the lesions heal without causing illness, but in progressive disease, sometimes related to lung cavitation, infection can disseminate to the skin, mucosae and internal organs. In a majority of patients, the initial lesion heals, often asymptomatically, and delayed hypersensitivity develops, with a positive skin test reaction to the appropriate antigen. Almost all these infections present in the oral cavity as ulcerations.


Direct demonstration of yeast-like forms of the fungi in exudate, sputum or biopsy specimens; isolation in appropriate culture media and/or serology.

Table 35.1 Specimens required for the laboratory diagnosis of oral candidal infections





Pseudomembranous candidiasis




Erythematous candidiasis




Denture stomatitis









Hyperplastic candidiasis




Angular cheilitis




Median rhomboid glossitis




+, useful; ±, may be useful; -, inappropriate.

Note: an oral rinse (with 10 ml saline) for 1 min is required to evaluate the oral carriage of Candida in terms of colony-forming units per millilitre (CFU/ml).


Almost all dimorphic fungi are sensitive to amphotericin; fluconazole may be an alternative.

Some examples of these infections are given below.

Examples of systemic fungal infections



Histoplasma capsulatum, a dimorphic fungus.

Main oral sites affected

Oral mucosa, tongue, palate, gingiva, periapical region.

Clinical features

Nodular indurated or granular masses and ulceration; tissue destruction with bone erosion.

Frequency of oral infection

In 40%-50% of cases.



Paracoccidioides brasiliensis, a dimorphic fungus (more common in western countries than in Asia).

Main oral sites affected

Tongue, hard and soft palate, gingiva.

Clinical features

Papules or vesicles leading to ulceration.

Frequency of oral infection




Penicillium marneffei, a dimorphic fungus, common in South-East Asia.

Main oral sites affected

Palate, gingiva, labial mucosa, tongue, oropharynx.

Clinical features

Erosions or shallow ulcers covered with a white slough.

Frequency of oral infection

Very common.

Oral viral infections

The majority of virus infections of the oral mucosa are due to the herpes group of viruses. Occasionally, other viruses, such as coxsackieviruses, papillomaviruses and paramyxoviruses (which cause measles and mumps), may manifest with oral symptoms (see Chapter 21).

Primary herpes simplex infection: herpetic stomatitis

Herpetic stomatitis is the most common viral infection to affect the mouth; it is caused by human herpesviruses 1 and 2 (HHV-1 and HHV-2). The incubation period is about 5 days, and the virus is transmitted by contact with skin lesions or infected saliva. Children may carry the virus asymptomatically, or as convalescent carriers, in saliva for several months, but the virus is rarely isolated from adults once the primary lesion heals. The early-childhood infection is usually subclinical, frequently dismissed as 'teething', but if the infection occurs in adults, the symptoms are obvious and severe. In countries with high standards of hygiene, there is an increasing frequency of adults presenting with primary herpes.

Clinical features

In the initial stages, there is mild to severe fever and enlarged lymph nodes, with pain in the mouth and throat; then, a variable number of vesicles develop haphazardly on the oral mucosa, the tongue and gingivae. These vesicles rupture quickly to form small round or irregular superficial ulcers with erythematous haloes and greyish-yellow bases. The gingivae are inflamed, and the infection may be confused with acute necrotizing ulcerative gingivitis (ANUG) of bacterial origin. In some, ANUG may develop secondary to primary herpetic stomatitis. The mouth is very painful and eating and swallowing may be difficult. The lesions resolve without scarring within 5-10 days.

Secondary herpes simplex infection: herpes labialis (HHV-1 and HHV-2)

About a third of the patients who have had primary infection develop herpes labialis (cold sore) in later life as a result of reactivation of the latent virus, which usually resides in the trigeminal ganglion. The stimulus for reactivation could be:



 exposure to sunlight


 debilitating disease.

The lesion develops at the mucocutaneous junction of the lip or on the skin adjacent to the nostrils. Characteristically, the lesions are preceded, some 24 h before, by a premonitory sign of itching, prickling or a burning sensation. Blisters then develop, enlarge, coalesce, rupture, become encrusted and heal within 10-14 days (see Fig. 21.3).

Intraoral recurrent herpetic infections are infrequent; they involve the hard palate, alveolar ridges and gingiva. These lesions develop in a similar manner to those of the lips, and appear as a cluster of small, shallow ulcers with red, irregular margins. Pain is not a common feature, and the intraoral lesions may or may not recur intermittently for years.

Herpetic dermatitis and herpetic whitlow (HHV-1 and HHV-2)

Primary herpetic dermatitis is localized and characterized by pruritus, burning and pain. Multiple vesicles appear, persist for 4-5 days and burst, with resultant crusting scabs that heal within 2-3 weeks. Dentists who escaped exposure in childhood may contract herpetic dermatitis from patients who have either primary or secondary herpes. Infection may take the form of a herpetic whitlow on the finger, resulting in an intensely painful lesion (see Fig. 21.2). Herpetic whitlow may recur, but less frequently than the perioral infection.

Laboratory diagnosis of herpetic infection

See also Chapter 6.

Direct examination

Smears should be stained with monoclonal fluorescent antisera to herpes simplex virus type 1 or 2 (HHV-1 or HHV-2). This technique is specific and rapid.


Herpes simplex virus is readily isolated from samples of oral lesions in a variety of tissue culture systems.


In primary infection, a fourfold or greater increase in antibody titre between the acute and convalescent sera is indicative of recent infection with herpes simplex virus. The demonstration of immunoglobulin M (IgM) antibodies by immunofluorescence techniques in a single sample can also be used in diagnosis.


Moderate to severe primary herpetic stomatitis is treated with oral and topical aciclovir, together with symptomatic measures. However, the use of aciclovir in recurrent herpetic infections should be limited to immunocompromised patients and those who have a past history of severe, extensive or frequently recurring lesions. The patients should apply the drug before vesicles form to obtain the best results.

Varicella and zoster (HHV-3)

Primary infection with the varicella-zoster virus causes chickenpox. Zoster or shingles is the secondary (synonym: post-primary, reactivation) infection due to the reactivation of the virus hiding in the latent form in sensory ganglia (e.g., the trigeminal ganglion for the facial region; see Fig. 21.3).


Chickenpox is a common infectious disease and is usually contracted in childhood.

Oral manifestations

Before the typical skin rash develops, lesions may be found in the mouth, especially on the hard palate, pillars of the fauces and uvula, although any area of the oral mucosa may be involved. The characteristic skin rash, which is centripetal, and progresses from macular to papular, vesicular and pustular forms before scabbing, helps to differentiate chickenpox from other causes of oral ulceration. The oral lesions consist of small ulcers surrounded by an area of erythema. The vesicles are quickly ruptured in the mouth and therefore rarely noticed. The lesions may be painful in adults, but children rarely complain of discomfort.

Shingles (zoster)

Shingles is a localized eruption due to the reactivation of the herpes zoster virus. It involves an area of skin supplied by one or more sensory ganglia in which the virus is residing. In some 10% of cases, zoster reflects an underlying immune-deficiency state, possibly a neoplasm such as lymphoma or HIV disease.

Oral manifestations

The trigeminal nerve is affected in about 15% of cases, with the ophthalmic, maxillary and mandibular divisions involved in that order of precedence. The lesions of shingles may be found on the skin, on the oral mucosa or both. Severe localized oral pain often precedes the rash and mimics the pain of toothache. The most common intraoral sites affected are the anterior half of the tongue, the soft palate and the cheek. The vesicles break down intraorally within a few hours to give very painful ulcerated areas with a yellowish-grey surface and erythematous borders. The oral lesions heal more quickly than the skin lesions and rarely scar.

Laboratory diagnosis of chickenpox and shingles

The clinical presentation is characteristic, but in unusual circumstances, the disease can be confirmed in the laboratory by submitting:

 vesicle fluid for electron microscopy and virus isolation

 smears from an ulcer for immunofluorescence

 acute or convalescent sera to test for the presence of specific IgM antibodies by immunofluorescence.


Chickenpox is self-limiting; but an effective vaccine is available to prevent infection. For zoster, high-dose aciclovir (800 mg five times daily) should be prescribed as soon as possible, especially in immunocompromised patients.

Epstein-Barr virus infections (HHV-4)

Epstein-Barr virus is the agent of a number of infections, including infectious mononucleosis, nasopharyngeal carcinoma, Burkitt's lymphoma, oral hairy leukoplakia and post-transplant lymphoproliferative diseases.

Infectious mononucleosis

Infectious mononucleosis is an acute infectious disease, mainly of children and young adults. The agent, the Epstein-Barr virus, is present in the oropharyngeal secretions of patients suffering or convalescing from infectious mononucleosis; the disease is transmitted by kissing. The virus has also been demonstrated in the oropharynx of healthy carriers.

Oral manifestations

At the onset, the throat is painful and congested but exudate is absent. An enanthem consisting of clusters of fine petechial haemorrhages may be seen at the junction of the hard and soft palates (these lesions are also found in other virus infections of the respiratory tract). Subsequently, a white pseudomembrane may develop on the tonsil and on other parts of the oral mucosa, and oral ulceration may occur. Other presenting signs may be submandibular lymphadenitis and mild fever.

Laboratory diagnosis

The diagnosis of infectious mononucleosis may be possible on the typical clinical presentation. Laboratory tests required to confirm the diagnosis include:

 haematology: differential white blood cell count to demonstrate the lymphocytosis and atypical mononuclear cells (20%)


 testing an acute serum sample for the presence of IgM antibodies to the Epstein-Barr virus capsid antigen (using an immunofluorescence technique)

 the monospot or Paul-Bunnell tests.

Hairy leukoplakia

See Chapter 30.

Oral manifestations of other herpesviruses (HHV-5 to HHV-8)

Other herpesvirus infections are generally of minor consequence, except for Kaposi's sarcoma caused by HHV-8 (see Chapter 21).

Coxsackievirus infections

Two diseases caused by group A coxsackieviruses produce oral signs and symptoms:

 hand, foot and mouth disease, caused mainly by coxsackievirus A16 and, less commonly, by types A4, A5, A9 or A10

 herpangina, caused by coxsackieviruses A2, A4, A5, A6 and A8.

Oral manifestations of herpangina

This febrile disease is characterized by sore throat, dysphagia, anorexia and occasionally a stiff neck. Accompanying oral signs and symptoms are small, papulovesicular lesions about 1-2 mm in diameter, with a greyish-white surface surrounded by red areolae, especially in the palate. The disease lasts for about 3-4 days, the fever abates and the oral lesions heal promptly.

Paramyxovirus infections

Measles, mumps, parainfluenza and respiratory syncytial viruses are categorized as paramyxoviruses. Of these, measles and mumps are of concern in dentistry as they commonly manifest with oral signs or symptoms. Measles is discussed in Chapter 21; mumps is described later under salivary gland infections.

Oral manifestations of bacterial infections


Syphilis is re-emerging as a relatively common disease due to the HIV pandemic and the increasing promiscuity associated with affluence worldwide. As oral manifestations are the early signs of the disease, dental practitioners should pay particular attention to these.

Fig. 35.13 Mucous patches of secondary syphilis on the tongue (A) and soft palate (B).

Primary syphilis

Chancre is the characteristic sign of primary syphilis and normally appears in the genitalia, but extragenital lesions, mostly in the oral cavity, occur in some 10% of cases. The common sites affected are the lips and tongue, and, to a lesser extent, the gingival and tonsillar area. The lesions heal spontaneously about 5 weeks after appearing. The regional lymph nodes are usually enlarged.

Secondary syphilis

Oral manifestations are slightly raised, greyish-white glistening patches on the mucosa—the so-called 'mucous patches' of the tonsils, soft palate, tongue and cheek (Fig. 35.13); gingivae are rarely involved. The surface membrane covering the lesions is grey and easily removed, and contains many spirochaetes. The mucous patches may later coalesce to produce a serpiginous lesion ('snail-track' ulcer). The cervical lymph nodes are enlarged and rubbery in consistency. The lesions heal spontaneously 2-6 weeks after appearing. However, typical lesions may not always be present because of unrelated antibiotic therapy.

Tertiary syphilis

The characteristic sign of this stage is the gumma. The most common oral site of gumma formation is the hard palate, but the soft palate, lips and tongue may be involved (Table 35.2). The lesion starts as a small, pale, raised, painless area that ulcerates and rapidly progresses to a large, necrotic zone with exposure of bone and, in the case of the palate, may eventually perforate into the nasal cavity. The palatal lesions are usually midline; in rare cases, the soft palate may be involved. No spirochaetes are found in gummata.

Table 35.2 Oral manifestations and infectivity of syphilis


Orofacial manifestations



Chancre of lip, tongue, gingiva



Mucous patches on tonsil, tongue, soft palate, cheek; ‘snail-track’ ulcers; rubbery, enlarged cervical lymph nodes



‘Gumma’ of palate; rarely osteomyelitis; syphilitic leukoplakia leading to carcinoma



Hutchinson’s incisors; ‘mulberry’ molars; facial deformities with open bite or dish face


Atrophic or interstitial glossitis is another oral manifestation of tertiary syphilis. Clinically, there is atrophy of the filiform and fungiform papillae, which results in a smooth, sometimes wrinkled, lingual surface. Subsequent leukoplakia may develop.

Late and quaternary syphilis

The quaternary stage of syphilis, which may develop 10-20 years after primary syphilis, is characterized by two main clinical forms: cardiovascular syphilis and neurosyphilis. No specific oral manifestations are seen at this stage.

Congenital syphilis

The dental lesions are a result of infection of the developing tooth germ by Treponema pallidum. The deciduous teeth are minimally affected; the permanent teeth may be malformed or fail to develop. The most common dental manifestations of congenital syphilis are Hutchinson's incisors and 'mulberry' molar teeth. In the former, upper central incisors are mostly involved; the teeth are barrel-shaped and have a crescentic notch at the incisal edge. In the latter, the first permanent molar teeth have a roughened dirty, yellow, hypoplastic occlusal surface, with poorly developed cusps resembling the surface of a mulberry. Other manifestations of congenital syphilis include frontal bossing and saddle nose.


Oral lesions of tuberculosis are usually secondary to primary infection elsewhere, commonly the lungs. Primary infections of the oral mucosa by Mycobacterium tuberculosis are rare. In the case of secondary infection, the sources of infection are contaminated sputum or blood-borne bacilli. Lesions are found more commonly in the posterior area of the mouth, and it has been suggested that this may be due to the relative propensity of lymphoid tissue in this region. The major oral lesions are:

 oral ulceration

 tuberculous lymphadenitis

 periapical granulomas and bone infections.

Oral ulceration

There is a wide spectrum of tuberculous lesions of the oral mucosa, including indolent ulcers, diffuse inflammatory lesions, granulomas and fissures; pain may be mild or absent. The tongue is most commonly affected but lesions have been noted on the buccal mucosa, gingivae, floor of the mouth, lips, and the hard and soft palates. Primary tuberculosis of the oral mucosa is more common in children and adolescents than in adults and usually presents as a single, painless indolent ulcer, commonly on the gingiva, with enlarged cervical lymph nodes, or as a white patch.

Tuberculous lymphadenitis

The cervical glands are most commonly affected, and in patients with pulmonary tuberculosis, the route of infection is probably by lymphatic or haematogenous spread, or via an abrasion of the mouth. In patients with no evidence of systemic infection the route is probably via the tonsils or oral mucosa. The typical presentation is a lump in the neck, which may be painful. The size may vary, and in the early stages, the swelling is firm but mobile. Later, the mass becomes fixed, with the formation of an abscess and sinus—a cold abscess. The lesions may be unilateral, bilateral, single or multiple.

Periapical granuloma and bone infections

In patients with active tuberculosis, tubercle bacilli are seen in periapical granulomas. Tooth extraction may lead to delayed healing of the socket, which fills with 'tuberculous granulations'.

Bone infections are not uncommon in tuberculosis: secondary tuberculous osteomyelitis may involve the maxilla or mandible. Here, the bacilli may gain access to the bone by:

 haematogenous spread

 direct spread from an oral lesion

 infected saliva entering an extraction socket or fracture. Tuberculous osteomyelitis of the jaws is chronic in nature, usually with severe pain and the production of bony sequestra.

Tuberculosis of the salivary glands

See below.


Leprosy, a granulomatous disease caused by Mycobacterium leprae, is of two main types: the tuberculoid and the lepromatous variants (see Chapter 19).

Tuberculoid leprosy

Tuberculoid leprosy does not directly affect the oral mucosa, but the associated neurological features may affect the mouth and face. Such manifestations vary from loss of eyebrows to nodular involvement of all facial cutaneous and subcutaneous structures. If the trigeminal nerve is involved, hyperaesthesia or paraesthesia of the face, lips, tongue, palate, cheeks or gingiva may be present; secondary ocular changes may occur, with subsequent corneal and conjunctival sensory loss. The facial lesions of tuberculoid leprosy comprise dry, hairless, anaesthetic plaques, with a well-defined and raised border, which are red on white skin and hypopigmented on dark skin.

Lepromatous leprosy

In lepromatous leprosy, M. leprae is present in many tissues of the body, and multiple, erythematous, bilateral and symmetrical lesions are found on the skin of the face, arms and legs. The lesions are anaesthetic. The nasomaxillary complex is the primary area of destruction in the facial region. Facial skeletal changes, such as saddle nose, atrophy of the anterior nasal spine and premaxillary bone recession, are common, with or without tooth loss (see Fig. 19.3). Dental deformities are limited to a pink discoloration of the upper incisors due to invasion of the pulp by infected granulomatous tissue, which can produce pulpitis and pulp death.

The incidence of oral lesions in lepromatous leprosy varies from 10% to 60%. Intraoral nodules have been described as yellowish-red, soft to hard, sessile, single or confluent lesions, which tend to ulcerate. Healing is by secondary intention with fibrous scars. The sites most commonly involved are the premaxillary gingivae, the hard and soft palates, the uvula and tongue. Tongue lesions, particularly on the anterior two-thirds, consist of single or multiple nodules, giving a 'cobblestone' appearance, or in some instances may resemble a geographic tongue with erythematous areas denuded of papillae. As the saliva of patients with oral lesions commonly contains M. leprae, this could be a possible source of infection.

Salivary gland infections

Inflammation of the salivary glands (sialadenitis) due to infective causes is not an uncommon phenomenon. Sialadenitis can be:

 viral (in the majority)

 bacterial (in the minority).

The parotid glands are more commonly infected than the submandibular glands, and infections of the accessory salivary glands are very rare (Table 35.3). Apart from mumps, the majority of salivary gland infections are seen in adults.


Initiation and progression of salivary gland infections depend on the decrease in host resistance to infection:

 general: debility, dehydration

 local: obstruction of ducts due to sialoliths (salivary stones), strictures or other pathology and the virulence of the causative organism. Factors important in salivary gland infections are shown in Fig. 35.14.

Viral infections of salivary glands

Mumps (endemic parotitis)

Mumps is caused by an RNA paramyxovirus, which infects circulating lymphocytes, especially activated T cells. These spread in the blood, 'targeting' salivary duct epithelial cells and replicating in them, leading to acinar disintegration, periductal oedema and a mononuclear infiltrate (Fig. 35.15). Subsequently, the virus is shed in saliva and spreads into the blood stream, causing a viraemia.

Table 35.3 Classification of salivary gland infections

Fig. 35.14 Factors important in the pathogenesis of salivary gland infections.

Fig. 35.15 Mumps virus multiplication in salivary duct and shedding into saliva.


The disease is frequently seen in winter and spring. Clinical or subclinical infection may occur at all ages but is most common in childhood.

Incubation period and infectivity

Approximately 14-28 days; the saliva of patients incubating mumps (during the prodromal period) is infectious for a few days before parotitis develops and up to 2 weeks after the onset of clinical symptoms. Mumps is transmitted by direct contact with saliva and by droplet spread, and hence, the disease may be contracted in the dental clinic environment.

Clinical features

These include:

 pyrexia, sore throat, furred tongue, trismus and earache, commonly

 pain on chewing and/or pain and tenderness on upward pressure beneath the angle of the lower jaw (pain may be acute during salivation)

 reddening of the opening of the parotid duct

 increase in glandular size, and varying consistency of the gland from normal to very hard

 low salivary flow rate leading to non-specific stomatitis and halitosis

 trismus and earache due to parotid involvement

 either one or both parotid glands may be involved, with a delay of up to 5 days in between; salivary glands other than the parotid may be enlarged in some 10% of cases

 the clinical course of mumps varies widely, from a mild upset lasting a day or two to a severe illness with high fever lasting up to 2 weeks; complete recovery is usual.


Complications are due to involvement of other glands or tissues, leading to meningoencephalitis (30%) and orchitis (25% of adult males); rarely, thyroiditis, neuritis, myocarditis and nephritis.


Diagnosis is normally made on clinical grounds. On unusual clinical presentation, laboratory investigations may be required and include:

 serology: to demonstrate antibodies to mumps virus antigens using serological tests, e.g., the detection of IgM antibodies using immunofluorescence

 electron microscopy: saliva (pure parotid saliva collected by cannulation) may be examined for typical virus particles.

Salivary gland disease in HIV infection

Salivary gland disease may occur in a minority of HIV-infected individuals. Xerostomia and/or enlargement of the major salivary glands are the two main presentations: xerostomia is present in some 10% of cases, while major gland enlargement may be accompanied by illness resembling Sjogren's syndrome.

The histological picture is variable, with lymphocytic sialadenitis, hyperplasia of salivary lymph nodes, Kaposi's sarcoma or lymphoma. The aetiology of HIV-induced salivary gland disease is not clear.

Other viral infections

Mumps is the most common viral cause of sialadenitis, but a member of the herpesvirus group, cytomegalovirus, can also cause a clinical disease, cytomegalic inclusion disease (salivary gland inclusion disease), which affects newborns, children and adults, and has multiple systemic manifestations, including salivary gland enlargement. The disease is so called because of the large, doubly contoured 'owl-eye' inclusion bodies seen within the nucleus or cytoplasm of duct cells of the parotid gland.

Rarely, other viruses such as parainfluenza virus types 2 and 3, echoviruses and coxsackieviruses have been implicated in non-suppurative sialadenitis.

Bacterial infections of salivary glands

Acute suppurative parotitis (bacterial sialadenitis)

Acute suppurative parotitis is seen mostly in adults with salivary gland abnormalities. In the past, it was primarily a disease of dehydrated or post-operative patients, but with the introduction of proper fluid balance and antibiotic prophylaxis, suppurative parotitis in these groups is now rare.

Aetiology and pathogenesis

In health, potential oral pathogens cannot ascend the salivary ducts and invade the glandular tissue because of the flushing action of saliva. However, if the flow of saliva is greatly reduced or stopped, a retrograde infection via the salivary duct may ensue. Predisposing factors include:

 drugs that reduce salivary flow, e.g., diuretics, certain anti-histamines, tranquillizers and anticholinergics

 localized salivary gland abnormalities, e.g., calculus, mucus plug or benign strictures

 generalized sialectasis, e.g., in patients who become dehydrated after gastrointestinal surgery or patients with Sjogren's syndrome (a progressive degenerative disease affecting salivary gland tissue).

Clinical features

1. Unilateral or bilateral swelling of the parotid glands may be present for days or weeks. Swelling may be limited

to the gland or, in more severe infections, extend locally, involving the pre- and post-auricular areas. The earlobes may be displaced laterally.

2. Purulent salivary secretions occur at the duct orifice.

3. Trismus results from pain and swelling.

4. Usually, there are no systemic symptoms, but occasionally fever, chills and leukocytosis may be seen.

5. In chronic infection, recurrent bouts of acute exacerbation of infection followed by periods of remission may lead to replacement fibrosis.


 If possible, pus should be aspirated through a fine, smallbore, polythene catheter attached to a syringe, or collected aseptically on a cotton-wool swab by 'milking' the duct, and sent immediately to the laboratory. The ductal orifice and the subjacent mucosa should be decontaminated with an antiseptic such as chlorhexidine prior to swab collection of pus.

 Catheter collection of pus should not be performed during the acute stage.

 Pus should be collected before antibiotics are prescribed.


Both monomicrobial and polymicrobial infections may occur. The organisms most commonly isolated are a-haemolytic streptococci; the frequency of isolation of Staphylococcus aureus is gradually diminishing (Table 35.4).


The treatment of choice is parenteral antibiotic therapy, guided by culture of pus and sensitivity tests. Amoxicillin is the agent of choice, or erythromycin in patients hypersensitive to penicillins. A Gram-stained smear of the pus is useful in deciding initial antibiotic therapy.

Thorough oral hygiene is extremely important. Salivation should be encouraged by increased fluid intake (rehydration) and the use of sialagogues (e.g., lemon juice). In severe cases, consider surgical drainage of pus.

Once the acute condition has resolved, the patient should be referred for sialographic investigation of the affected gland or glands to identify correctable salivary gland abnormalities (e.g., mucus plugs, benign strictures and calculi), which lead to recurrence of infection. Note: sialography should never be attempted during the acute phase of the illness.

Table 35.4 Bacteria commonly isolated from bacterial parotitis

Common isolatesa

a-Haemolytic streptococci

Staphylococcus aureus

Less common isolates

Haemophilus spp.

Eikenella corrodens

Bacteroides spp.

Anaerobic streptococci

Rare isolates

Neisseria gonorrhoeae

Mycobacterium tuberculosis

Actinomyces spp.

Treponema pallidum

aPolymicrobial infections are common.


Subsequent treatment options include duct dilation, removal of ductal obstructions or surgical revision of ducts.


If acute bacterial parotitis is untreated, severe complications may ensue, especially in debilitated patients. These are:

 extension of inflammation and oedema into the neck and resultant respiratory obstruction

 cellulitis of the face and neck

 osteomyelitis of adjacent facial bones

 rarely, septicaemia and death.

Submandibular sialadenitis

Submandibular sialadenitis is less common than acute suppurative bacterial parotitis. Most bacterial infections of the submandibular glands are associated with obstructive ductal disease (e.g., sialoliths and ductal strictures). The aetiology, microbiology and management of submandibular (submaxillary) sialadenitis are similar to those of bacterial parotitis.

Neonatal suppurative parotitis and recurrent parotitis of childhood

These rare diseases, with unknown aetiology, are confined to the first decade of life. In recurrent parotitis, the child experiences repeated acute episodes of painful parotid gland enlargement. The suggested predisposing factors include congenital abnormalities of the ductal system, preceding mumps and, foreign bodies in the parotid duct. Management includes removal of the aetiological agent, symptomatic therapy and antibiotics, if necessary.

Rare bacterial infections of salivary glands

Salivary gland infections by organisms such as T. pallidum, Neisseria gonorrhoeae, Actinomyces israelii and M. tuberculosis have been rarely described. These may be due to:

 endogenous, ascending infection via salivary ducts (e.g., A. israelii)

 infection via an adjacent, contiguous focus (e.g., T. pallidum)

 reactivation of an old lesion (e.g., M. tuberculosis).

Key facts

 Oral candidiasis, an opportunistic infection, is the most common oral fungal infection in humans, and is usually seen in the very young, the very old and the very sick.

 Oral candidiasis, classified as a superficial (as opposed to systemic) mycosis can be broadly subdivided into primary and secondary disease: primary infection is strictly confined to the oral cavity, whereas the secondary disease is present in both the oral and other superficial body sites.

 The classic disease triad of oral candidiasis comprises pseudomembranous (thrush), erythematous and hyperplastic variants.

 Other common Candida-associated lesions are denture stomatitis, angular cheilitis and median rhomboid glossitis.

 Herpesviruses (eight are now recognized) cause the majority of oral viral infections.

 In general, herpes simplex viruses types 1 and 2 (human herpesviruses 1 and 2 (HHV-1 and HHV-2)) cause infections above and below the belt, respectively (i.e., oral and genital infections).

 Herpetic gingivostomatitis is the primary infection, and herpes labialis is the reactivation infection caused by HHV-1.

 Varicella-zoster virus (HHV-3) causes chickenpox (primary infection) and zoster/shingles (reactivation infection) affecting well-defined dermatomes (‘belt of roses from hell’).

Epstein-Barr virus (HHV-4) causes infectious mononucleosis or glandular fever, common in young adults and a number of other diseases.

Group A coxsackieviruses cause hand, foot and mouth disease of children and herpangina; oral lesions are papulovesicular, small and greyish-white.

Oral manifestations of syphilis are chancre (primary syphilis), mucous patches and snail-track ulcers (secondary), and gumma and interstitial glossitis (tertiary).

Mulberry (moon) molars and Hutchinson’s incisors can be seen in congenital syphilis, due to infection of the tooth germ by Treponema pallidum; other manifestations are frontal bossing and saddle nose.

Oral ulceration, lymphadenitis, periapical granulomas and bone infection are the common oral manifestations of tuberculosis; these are secondary to primary infection of the lungs.

Leprosy, a chronic granulomatous disease, manifests as tuberculous and lepromatous variants; intraoral nodules, which ulcerate and heal with fibromatous scars, and gross facial disfiguration are seen in the lepromatous variant.

The most common salivary gland infection is caused by the mumps virus; bacterial infections of salivary glands are relatively uncommon.

 Mumps is characterized by the enlargement and inflammation of one or both parotid glands, reddening of the parotid duct orifice, pyrexia and (sometimes) earache.

 Xerostomia and enlargement of major salivary glands are seen in HIV infection.

 Acute suppurative parotitis, caused mainly by a-haemolytic streptococci and Staphylococcus aureus, is exquisitely painful.

 Management of bacterial parotitis entails antibiotic therapy, good oral hygiene, rehydration, sialagogues and, if necessary, surgical drainage.

 Less commonly, salivary gland infections are caused by Mycobacterium tuberculosis, Actinomyces spp., Neisseria gonorrhoeae and Treponema pallidum.

Review questions (answers on p. 367)

Please indicate which answers are true, and which are false.

35.1 A 70-year-old asthmatic who is on inhaled budesonide (a steroid) for the last 15 years presents with a white patch on the buccal mucosa that could be easily removed, revealing a red patch underneath. Which of the following statements are true?

A. it is likely that this patient is having an opportunistic infection

B. culturing a swab from the white patch on blood agar will aid in the diagnosis

C. the drug treatment to his medical condition is likely to have caused the white/red patch

D. administration of amoxicillin might worsen the condition

E. nystatin lozenges are the treatment of choice

35.2 Seeing a patient with mucocutaneous candidiasis with oral lesions should prompt you to:

A. look for a cause for immunodeficiency

B. start antiretroviral therapy

C. isolate the patient as he/she may spread the infection to others

D. enquire about the family history of the disease

E. start topical antifungal treatment for the oral lesions

35.3 Candida-associated denture stomatitis (synonym: chronic atrophic candidiasis):

A. is usually symptomatic

B. frequently presents with angular stomatitis

C. can be treated by improving denture hygiene and not wearing dentures at night

D. is common on both the upper and the lower denture-bearing mucosa

E. palatal papillary hyperplasia may be seen in advanced cases

35.4 Which statements about infections of the oral cavity due to human herpesviruses are true?

A. infection with human herpesvirus 2 (HHV-2) is common in children

B. reactivation leads to herpes stomatitis in one-third of patients

C. infection with HHV-8 may cause Kaposi's sarcoma

D. severe toothache may follow oral herpes zoster infections

E. palatal petechiae are pathognomonic of Epstein-Barr virus (EBV) infections

35.5 Match the stage of syphilis that will demonstrate the appropriate clinical feature:

A. chancre primary/secondary/tertiary/congenital

B. gumma of hard palate primary/secondary/tertiary/congenital

C. snail-track ulcer primary/secondary/tertiary/congenital

D. mulberry molar teeth primary/secondary/tertiary/congenital

E. mucous patches primary/secondary/tertiary/congenital

F. saddle nose


35.6 Which of the following statements related to infections of the salivary glands are true?

A. mumps is common among children

B. acute suppurative parotitis is common among post-operative patients

C. in mumps, parotid glands are primarily involved

D. mumps might lead to orchitis and pancreatitis

E. P-haemolytic streptococci are the major aetiological agent for acute bacterial parotitis

Further reading

Kibber, C. C., MacKenzie, D. W. R., & Odds, F. C. (Eds.), (1996).

Principles and practice of clinical mycology. Chichester: John Wiley.

Lamey, P. J., Boyle, M. A., MacFarlane, T. W., et al. (1987). Acute suppurative parotitis in out-patients: Microbiological and post-treatment sialographic findings. Oral Surgery, Oral Medicine, and Oral Pathology, 63, 37-41.

Odds, F. C. (1988). Candida and candidosis (2nd ed.). London: Baillière Tindall.

Reichart, P., Samaranayake, L. P., & Philipsen, H. P. (2000). Pathology and clinical correlates in oral candidiasis and its variants: A review. Oral Diseases, 6, 85-91.

Samaranayake, L. P., Cheung, L. K., & Samaranayake, Y. H. (2002). Candidiasis and other fungal diseases of the mouth. Dermatologic Therapy, 15, 252-270.

Samaranayake, L. P., & MacFarlane, T. W. (Eds.), (1990). Oral candidosis. London: Wright.

Scully, C., Flint, S. R., & Porter, S. R. (1996). Oral diseases (2nd ed.). London: Martin Dunitz.

Sitheeque, M., & Samaranayake, L. P. (2003). Chronic hyperplastic candidiasis (candidal leukoplakia). Critical Reviews in Oral Biology and Medicine, 14, 253-267.

Soysa, N. S., Samaranayake, L. P., & Ellepola, A. N. B. (2008).

Antimicrobials as a contributory factor in oral candidosis - A brief overview. Oral Diseases, 14, 138-143.

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