Chapter 35 Oral mucosal and salivary gland 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 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’.
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:
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.
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).
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.
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).
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.
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.
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.
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 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.
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:
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 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.
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).
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.
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 cancer-phobic. In this event, reassurance is essential.
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 the latter group. Although Candida are 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.
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.
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.
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.
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.
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).