Chapter 11 Oral implications of infection in compromised patients

The term ‘medically compromised’ is often misused. The definition of a medically compromised patient is one who by virtue of their medical condition, or its treatment, is susceptible to infection and other serious complications. Conditions which cause patients to be medically compromised can either be congenital or acquired. Medical compromise can be due to a whole variety of factors, some of which are illustrated in Table 11.1. The term ‘immunocompromised’ refers specifically to congenital or acquired alterations of the immune system, which may render an individual susceptible to infection. The number of immunocompromised individuals is increasing rapidly, mostly because of the AIDS pandemic, but also through intervention therapy (drugs which deliberately modify the immune system). A good example of the latter is deliberate suppression of the immune system with drugs to prevent rejection during and following solid organ transplantation. The oral microflora in immunocompromised patients is changed either by colonization with exogenous microorganisms which are not normally found in the mouth, or by the occurrence of opportunistic infection. It used to be believed that any person who was immunocompromised had to be given prophylactic antibiotics to prevent infection after surgery. This is not necessary unless there is a proven degree of impairment of immune defences which renders them susceptible to infection. The extent to which an immunocompromised patient is susceptible to infection can be measured by a variety of blood tests to assess the function of their immune system. These include simple tests on the number and proportion of their immunological cells (predominantly white cells), their function, or their degree of abnormality. Only where there is a proven loss of functional protective immunity is there a necessity to give prophylactic antimicrobials before surgery (Ch. 8).

Table 11.1 Orofacial infections that may occur in medically compromised patients

Disorder	Example	Orofacial infection
Endocrine disorders	Diabetes mellitus	Oral fungal infections
Respiratory disorders	Asthma	Oral fungal infections
Neurological disorders	Epilepsy	Gingival hyperplasia and periodontal disease
Neoplastic disease	Oral carcinoma	Dental caries and mucositis following radiotherapy
Chronic infection	Tuberculosis	Oral tuberculosis
Immunological disorders	HIV and AIDS	Oral viral and fungal infections
Haematinic deficiencies	Anaemia	Angular cheilitis and oral fungal infections

The status of the teeth and oral soft tissues is often a reflection of systemic health. Thus, opportunistic orofacial infection may be the presenting initial feature of systemic disease. In this chapter, the types of orofacial infection that are seen in medically compromised patients as a result of the presence of underlying disease or as a result treatment will be considered.

Osteoradionecrosis

Cancer in the oral region is treated usually by surgery, radiotherapy, chemotherapy or a combination of all three. Radiotherapy destroys the rapidly dividing cancer cells, but it also destroys surrounding bone. This bone is highly susceptible to secondary radiation as it absorbs a great deal of energy. Bone is affected by radiation in three ways; there is a decrease in the number of cells (hypocellularity) and reduction in blood vessels (hypovascularity) and, as a consequence, less oxygen in the tissue (hypoxia). As the bone heals after irradiation, fibrous tissue is generated instead of bone, especially in the mandible. The effects of radiation therapy are not transitory and the hypovascularity increases with time. A simple operation on tissues which have been irradiated, such as a tooth extraction, can result in spontaneous death of the surrounding bone (necrosis). Death of the bone after irradiation can be progressive and is called osteoradionecrosis and has been associated with oral ulceration caused by ill-fitting dentures, scaling of the teeth, facial bone fractures and root canal therapy. In the past, the radiation therapy was not so highly focussed (collimated) on the malignant tissue and the surrounding normal structures were also often affected. In these conditions, the incidence of osteoradionecrosis in oral bone varied from 17–37%. With careful collimation, shielding of surrounding tissues, use of small but effective repeated radiation doses (fractionation), the incidence of osteoradionecrosis has been reduced to 2–5%.

Osteoradionecrosis is likely to arise due to a combination of radiation, trauma and infection. However, extensive animal studies support a view that the microorganisms are contaminants and cause secondary infection of pre-existing necrosis. Interestingly, molecular techniques applied to necrotic tissue obtained from cases of osteoradionecrosis have detected a predominantly anaerobic microflora, including Porphyromonas spp. and Prevotella spp.. Osteoradionecrosis is a difficult condition to treat despite the provision of an antibacterial agent, such as metronidazole or clindamycin, combined with surgery.

Post-irradiation mucositis

Another of the consequences of irradiation of the oral region is non-specific inflammation of the oral mucosa, often called mucositis (Fig 11.1). This can be extensive and cause considerable pain with difficulties in feeding. Symptoms may be severe enough to influence the patient to abandon the radiation treatment. At first it was thought that radiation mucositis was due to infection by Candida spp., and other yeasts. However, provision of antifungal therapy has no effect, suggesting that yeasts are not causing the condition. More extensive sampling of the mucosa has shown that the microflora associated with mucositis is mainly composed of Gram negative aerobic and facultatively anaerobic bacteria such as Escherichia coli, pseudomonads, Klebsiella spp, and Acinetobacter spp.. Irradiation mucositis can be largely alleviated by selective decontamination of the oral cavity before and during irradiation therapy by applying topically a combination of non-absorbable antimicrobials onto the tissues to be protected. The usual combinations of antimicrobials are polymixin and tobramycin, and an antifungal is added to prevent yeast overgrowth. Two antimicrobials are used in order to prevent the selection of resistance in Gram negative bacteria. This combination can be used to ameliorate the effects of the mucositis.

Fig. 11.1 Post-irradiation mucositis on the lingual mucosa.

Bisphosphonate-associated osteonecrosis

Bisphosphonates are drugs used in the treatment of osteoporosis, a condition in which calcium is gradually lost from bone. Osteoporosis is a serious condition in which there can be spinal compression, long bone fracture and bone pain. The bisphosphonates are pyrophosphate analogues that can prevent osteoporosis by inhibiting osteoclast activity. Unfortunately some patients who take bisphosphonates can suffer from a failure of bone to heal especially after extractions. The bone around the socket dies and may remain exposed to the oral cavity and get secondarily infected particularly with anaerobes. The exact cause of this condition is not known, but it is likely that this may be similar to the hypovascularity seen in osteoradionecrosis. One other suggestion is that bisphosphonate-associated osteonecrosis is due to anaerobic infection of the bone, but this is unlikely to be the primary cause as it is not cured by antimicrobials or surgery. The risk of this condition developing is small and has been estimated to be about 1:100,000 in those taking bisphosphonates. The risk of the condition developing however increases with the length of time the bisphosphonates are taken. This condition may become a serious problem in the future as a total of 70 million people were taking bisphosphonates worldwide in 2008.

Staphylococcal mucositis

Recent surveys of data from oral samples processed in microbiology laboratories have shown that Staphylococcus spp. are frequently isolated. The predominant species isolated is Staphylococcus aureus with a minority of these being methicillin-resistant (MRSA). Many of these isolations have been obtained from patients who are debilitated, or are terminally ill. In addition, staphylococci have been isolated from orofacial granulomatosis, in particular within fissures of swollen lips (Fig. 11.2). The presenting features of orofacial granulomatosis are identical to those of Crohn’s disease, which is a chronic inflammatory condition of the gut. There is debate as to how frequently staphylococci infect or colonize the mouth. Recently, it has been proposed that there is a discrete condition called staphylococcal mucositis which occurs in debilitated individuals.

Fig. 11.2 Lip swelling in orofacial granulomatosis with mid-line split secondarily infected with Staphylococcus aureus.

Pyostomatitis vegetans

This condition is associated with the presence of active inflammatory bowel disease, in particular, ulcerative colitis or Crohn’s disease. The oral mucosa is diffusely inflamed, with fissured ulcers separating papillary projections (Fig. 11.3). Histological examination reveals suprabasal separation of the epithelium with the formation of eosinophilic abscesses. The severity of pyostomatitis vegetans often mirrors the bowel disease activity. Interestingly, the provision of metronidazole can relieve oral symptoms. Healing occurs when the underlying inflammatory bowel disorder is brought under control.

Fig. 11.3 Pyostomatitis vegetans presenting as mucosa erythema. This patient also had secondary infection of the mucosa with methicillin-resistant Staphylococcus aureus (MRSA).

Cancrum oris (noma, gangrenous stomatitis)

This is a severe form of necrotizing periodontal disease, and is seen occasionally in developing countries, in particular, sub-Saharan Africa (Ch. 6). The sufferer is characteristically less than 10 years of age, malnourished and has a history of a recent viral infection, such as measles (Ch. 10). The initial lesion spreads into the cheek, face and neck causing extensive tissue loss. Treatment is with a combination of antibiotics, such as benzylpenicillin with metronidazole, but each combination should include agents active against both Gram negative and Gram positive microorganisms.

Necrotizing fasciitis

Necrotizing fasciitis is a serious rapidly progressive infection that can result in death, particularly in immunocompromised individuals. The majority of cases of necrotizing fasciitis that occur in the cervical region of the neck are of dental origin, in particular, subsequent to an acute dentoalveolar abscess. Microbiological studies of this rare condition have implicated members of the anginosus group of streptococci as the most frequent pathogens, often in combination with strict anaerobes such as Prevotella spp.. Management involves provision of antibiotic therapy intravenously and surgical debridement; hyperbaric oxygen is also used.

Stroke and parkinson’s disease

Loss of control of oral musculature can occur following cerobrovascular accidents (strokes) and in conditions such as Parkinson’s disease. Loss of the oral musculature can result in changes in the oral microflora, but the reasons for this are not clear. The microflora becomes predominantly Gram negative with Enterobacter spp. and Acinetobacter spp. predominating. This change in the oral microflora is clinically significant as often the patient cannot swallow properly; oral microorganisms can also be aspirated into the lungs and cause pneumonia.

Xerostomia

Xerostomia means literally dry mouth and can be caused by a variety of conditions or treatments (Table 11.2). One of the consequences of xerostomia is overgrowth of dental plaque, with acidogenic oral streptococci and lactobacilli predominating within the biofilm. This can induce a dramatic increase in dental caries if teeth are present. Xerostomia predisposes to the development of mucositis and opportunistic Candida infections of the oral mucosa.

Table 11.2 Causes of xerostomia

Drug therapy (in particular antidepressants)

Sjögren’s syndrome (immunological destruction of salivary tissues)

Damage to salivary glands following radiotherapy

Undiagnosed or poorly controlled diabetes

Dehydration

Congential absence of salivary glands

Gingival hyperplasia and immunosuppressive agents

Following organ transplantation it is necessary to take immunosuppressive agents to prevent the immune system causing rejection of the transplant. One of the curious consequences of taking these antirejection agents is that the gingivae enlarge due to overgrowth of fibrous tissue (Fig. 11.4). The gingival overgrowth is worse if the oral hygiene of the mouth is poor. No plaque bacteria have been associated with this condition, which was thought to be directly due to the systemic action of the immunosuppressive agents. If the patient is treated with low doses of macrolide antimicrobials (e.g. azithromycin), then the overgrowth can be prevented or reduced. This evidence supports the contention that gingival hyperplasia is an infective inflammatory process but the infecting bacteria have still to be identified.