Classification

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

Fig. 35.1 Classification of oral candidiasis.

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

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

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.

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

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.

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

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

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.

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

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 infiltrating the superficial layers of the oral epithelium.

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).

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

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

Aetiology

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.

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

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).

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

Treatment

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.

Fig. 35.10 Median rhomboid glossitis showing the characteristic diamond-shaped lesion.

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 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.

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.

Histoplasmosis

Paracoccidioidomycosis

Penicilliosis