R.A.G. Khammissa

Oral mucosal immunity

Oral keratinocytes and dendritic cells of the oral mucosa, through molecular pattern recognition receptors, distinguish between commensal and pathogenic microorganisms and mediate the generation of protective immunoinflammatory responses to potentially invading pathogens or mediate immune tolerance toward commensal microorganisms. Oral immune tolerance is the result either of lack of activation of T cells in response to immunogenic presentation of antigens or of suppression of activity of effector T cells by regulatory T cells. Secretory immunoglobulin A (sIgA) antibodies at oral mucosal sites contribute to oral immunity by limiting colonization of microorganisms and their invasion of the epithelium. Ig isotype class switching to IgA is either dependent on or independent of T helper cells and is facilitated by cytokines secreted by dendritic cells and monocytes.

Oral candidosis in relation to oral immunity

Symptomatic oral infection with Candida albicans is characterized by invasion of the oral epithelium by virulent hyphae that cause tissue damage releasing the inflammatory mediators that initiate and sustain local inflammation. Candida albicans triggers pattern-recognition receptors of keratinocytes, macrophages, monocytes and dendritic cells, stimulating the production of IL-1β, IL-6 and IL-23. These cytokines induce the differentiation of Th17 cells and the generation of IL-17- and/or IL-22-mediated antifungal protective immuno-inflammatory responses in infected mucosa. Some immune cells including NKT cells, γδ T cells and lymphoid cells that are innate to the oral mucosa have the capacity to produce large quantities of IL-17 in response to C. albicans, sufficient to mediate effective protective immunity against C. albicans. On the other hand, molecular structures of commensal C. albicans blastoconidia, although detected by pattern-recognition receptors, are avirulent, do not invade the oral epithelium, do not elicit inflammatory responses in a healthy host, but induce regulatory immune responses that maintain tissue tolerance to the commensal fungi. The type, specificity and sensitivity of the protective immune response towards C. albicans is determined by the outcome of the integrated interactions between the intracellular signalling pathways of specific combinations of activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL-17-mediated protective immune response is essential for oral mucosal immunity to C. albicans infection.

Noma (cancrum oris) in the South African context

Noma (cancrum oris) is a destructive necrotising disease affecting orofacial tissues predominantly of malnourished young children. It is characterised by a rapid acute onset which usually starts in the mouth, spreads intra-orally destroying soft tissue and bone and progresses to perforate the facial skin, causing disfigurement. Polybacterial anaerobic infection is critical too, but is not alone sufficient for the initiation of noma. Cofactors, first and foremost malnutrition, but also systemic viral and bacterial infections are crucial to the development of noma. A patient with necrotising stomatitis or noma must be admitted to hospital for antibiotic treatment, fluid and electrolytes as well as nutritional supplementation and general supportive treatment. The epidemiology of noma in the South African population is unknown, and the clinicopathological features are poorly characterised. Although worldwide there is no evidence that HIV infection is a strong risk factor for noma, HIV infection may play a substantial role in the pathogenesis of noma in South Africa.

Noma (Cancrum Oris): A Report of a Case in a Young AIDS Patient with a Review of the Pathogenesis

Noma (cancrum oris) is a mutilating necrotising disease of the orofacial tissues. It affects predominantly debilitated malnourished children, in whom the necrotic process may cause severe damage to mid-facial structures. Its aetiopathogenesis is uncertain, but its course is fulminating, and without timely intervention the disease may be fatal. Antibiotic treatment during any stage of necrotising stomatitis and of its sequel noma can stop progression of the disease; therefore detection and treatment of early intraoral necrotising lesions whether necrotising gingivitis, necrotising periodontitis or necrotising stomatitis are critical in preventing noma. We present an extreme case of noma in a malnourished HIV-seropositive child. There was an acute necrotic process affecting both the maxilla and the mandible with denudation of bone, spontaneous exfoliation of teeth, necrotising fasciitis and myonecrosis which destroyed the lips and cheeks and extended to the infra-orbital margins. There was severe disfigurement and severe impairment of function. Noma is primarily an anaerobic bacterial infection with secondary ischaemia leading to osteonecrosis and mid-facial destruction.

Oral squamous cell carcinoma in a South African sample: Race/ethnicity, age, gender, and degree of histopathological differentiation.

OBJECTIVES The purpose of this retrospective study was to investigate differences between black and white persons with oral squamous cell carcinoma (OSCC) with regard to age, gender, oral site affected, and histopathological degree of differentiation; and to compare these clinicopathological parameters between persons younger and older than 40 years in a South African population sample from the greater Johannesburg area. MATERIAL AND METHODS The histopathological reports of 510 cases of OSCC during the period 1995-2002 were retrospectively evaluated, and the data regarding age, gender, ethnicity/race, oral site affected, and degree of histopathological differentiation were recorded and statistically analyzed for differences between black and white persons, and between persons younger and older than 40 years of age. RESULTS Statistically significantly, black persons were diagnosed with OSCC at a younger mean age (57 years) than white persons (61 years) (P=0.0086). The difference between male: female (M:F) ratio in black (3.74:1) and white persons (1.96:1) was statistically significant (P=0.0041). White persons had a significantly higher proportion of SCC of the lower lip than black persons (P<0.0001). CONCLUSION OSCC was diagnosed at a younger age in black than in white persons; the proportion of black males in the black population group was greater than that of white males in the white population group; and the proportion of SCC of the lips was higher in younger than in older persons.