In the UK, 60% of HIV-infected patients have characteristic oral lesions. Lesions strongly associated with HIV infection include candidiasis (with erythema and/or white exudates), erythematous candidiasis, oral hairy leucoplakia, Kaposi’s sarcoma, non-Hodgkin’s lymphoma, necrotizing ulcerative gingivitis, and necrotizing ulcerative periodontitis.

Oral hairy leucoplakia is almost pathognomonic of HIV infection and may be an early sign. It is more common in HIV-infected homosexual men than in any other high-risk group. It is characterized by white vertical corrugations on the lateral borders of the tongue, and immunostaining shows Epstein-Barr virus.

Kaposi’s sarcoma presents as a red, purple or blue macule or nodule, most commonly on the palate. It is diagnostic of AIDS. The lesion is associated with herpesvirus 8.

All lesions are much less common since the introduction of HAART.

Box 2.4 Common causes of infection in immunocompromised patients

Deficiency	Causes	Organisms
Neutropenia	Chemotherapy	Escherichia coli
	Myeloablative therapy	Klebsiella pneumoniae
	Immunosuppressant drugs	Staphylococcus aureus
		Staph. epidermidis
		Aspergillus spp.
		Candida spp.
Cellular immune defects	HIV infection	Respiratory syncytial virus
	Lymphoma	Cytomegalovirus
	Myeloablative therapy	Epstein-Barr virus
	Congenital syndromes	Herpes simplex and zoster
		Salmonella spp.
		Mycobacterium spp. (esp. M. avium-intracellulare)
		Cryptococcus neoformans
		Candida spp.
		Cryptosporidium parvum
		Pneumocystis carinii
		Toxoplasma gondii
Humoral immune deficiencies	Congenital syndromes	Haemophilus influenzae
	Chronic lymphocytic leukaemia	Streptococcus pneumoniae
	Corticosteroids	Enteroviruses
Terminal complement deficiencies (C5-C9)	Congenital syndromes	Neisseria meningitidis N. gonorrhoeae
Splenectomy	Surgery	Strep. pneumoniae
	Trauma	N. meningitidis
		H. influenzae
		Malaria

Relatively few patients with infectious disease present a serious risk to healthcare workers (HCW) and other contacts. However, the appearance of diseases like severe acute respiratory syndrome (SARS), the occasional importation of zoonoses like Lassa fever, and concerns about the bioterrorist use of agents such as smallpox mean that there is still the potential for unexpected outbreaks of life-threatening disease. During the world-wide SARS outbreak in 2003, scrupulous infection control procedures reduced spread of infection. However, in the ‘inter-epidemic’ period it is difficult to maintain the same level of ‘alert’. HCWs should remain vigilant because the early symptoms of many of these diseases are non-specific.

In some infections such as chickenpox the clinical presentation is so distinctive that no investigations are normally necessary to confirm the diagnosis. Other cases require investigation.

Box 2.1 Infections commonly associated with a rash

Macular/maculopapular Measles Rubella Enteroviruses Human herpesvirus 6 Epstein-Barr virus Cytomegalovirus Parvovirus Human immunodeficiency virus (HIV) Dengue Typhoid Secondary syphilis Rickettsia – spotted fevers Vesicular Chickenpox (herpes zoster virus) Shingles (herpes zoster virus) Herpes simplex virus Hand, foot and mouth disease (Coxsackie virus) Herpangina (Coxsackie virus) Petechial/haemorrhagic Meningococcal septicaemia Any septicaemia with disseminated intravascular coagulation (DIC) Tick typhus Viruses (Table 2.23) Erythematous Scarlet fever Lyme disease (erythema chronicum migrans) Toxic shock syndrome Urticarial Toxocariasis Strongyloidiasis Schistosomiasis Cutaneous larva migrans Others Tick typhus (eschar) Primary syphilis (chancre) Anthrax (ulcerating papule)

General investigations (to assess health and identify organ(s) involved)

These will vary depending on circumstances:

• Blood tests. Routine blood count, ESR and C-reactive protein, biochemical profile, urea and electrolytes are performed in the majority of cases (Box 2.2).
• Imaging. X-ray, ultrasound, echocardiography, CT and MR scanning are used to identify and localize infections. Biopsy or aspiration of tissue for microbiological examination may also be facilitated by ultrasound or CT guidance.
• Radionuclide scanning after injection of indium- or technetium-labelled white cells (previously harvested from the patient) may occasionally help to localize infection. It is most effective when the peripheral white cell count is raised, and is of particular value in localizing occult abscesses.

Viral exanthem

This, probably the commonest type of virally induced rash, presents clinically as a widespread non-specific erythematous maculopapular rash. It probably arises because of circulating immune complexes of antibody and viral antigen localizing to dermal blood vessels. The rash can be caused by many different viruses (e.g. echo-, parvo-, human herpes virus-6, Epstein-Barr virus;) and so is rarely diagnostic. The rash will resolve spontaneously in 7-10 days.

Diet

Dietary factors have been attributed to account for a third of cancer deaths, although it is often difficult to differentiate these from other epidemiological factors. For example, the incidence of stomach cancer is particularly high in the Far East, while breast and colon cancers are more common in the western, economically more developed countries. Many associations have been observed without a causative mechanism being identified between the incidence of cancer and the consumption of dietary fibre, red meat, saturated fats, salted fish, vitamin E, vitamin A and many others.

Environmental/occupational

Ultraviolet light is known to increase the risk of skin cancer (basal cell, squamous cell and melanoma). The incidence of melanoma is therefore particularly high in the white Anglo-Celtic population of Australia, New Zealand and South Africa, where exposure to UV light is combined with a genetically predisposed population.

Occupational factors.

In 1775, Percival Pott described the association between carcinogenic hydrocarbons in soot and the development of scrotal epitheliomas in chimney sweeps.

The principal causes now are asbestos (lung and mesothelial cancer) and combustion of fossil fuels releasing polycyclic hydrocarbons (skin, lung, bladder cancers). Organic chemicals such as benzene may cause molecular abnormalities associated with the development of myeloid leukaemia.

Infectious agents

The geographical distribution of a rare malignancy may suggest that it might be caused by, or associated with, an infective agent. For example, a specific type of T-cell leukaemia, seen almost exclusively in residents of the southern island of Japan and in the West Indies, is caused by infection with the retrovirus, HTLV-1 (human T-cell leukaemia virus) which is endemic in these areas.
Hepatocellular carcinoma occurs in patients with hepatitis B and C virus infections, and Burkitt’s lymphoma and nasopharyngeal carcinoma are associated with the Epstein-Barr virus. EBV is also linked with Hodgkin’s lymphoma (p. 508). Patients with HIV infection or immunosuppression from organ transplantation have an increased incidence of EBV-related lymphoma and herpesvirus-8-associated Kaposi’s sarcoma. The incidence of cervical cancer is increasing amongst younger women in association with human papillomavirus infection. Early sexual activity and multiple sexual partners have both been found to be associated with increased risk.

Bacterial infection with Helicobacter pylori predisposes to the development of gastric cancer and gastric lymphoma, while Schistosoma japonicum infection predisposes to the development of squamous carcinomas in the bladder.

Iatrogenic
Drugs.

Oestrogens have been implicated in the development of vaginal, endometrial and breast carcinoma. Alkylating agents and radiotherapy given, for example, for Hodgkin’s lymphoma (see later) are themselves associated with an increased incidence of secondary acute myelogenous leukaemia (AML), bladder and lung cancer. The epipodophyllotoxin drug, etoposide, has also been shown to be associated with the development of secondary AML.

Radiation.

The nuclear disasters of Hiroshima, Nagasaki and Chernobyl led to an increased incidence of leukaemia after 5-10 years in the exposed population. Increased incidences of thyroid and breast cancer have also been reported. Radiotherapy used, for example, in ankylosing spondylitis and Hodgkin’s lymphoma, has led to increased incidences of cancer.

Geographical distribution

The incidence of specific tumours varies with geographical location but the cause varies; for example England, Scotland and Wales have the highest death rate from malignant disease in the world, mainly because of the very high incidence of lung cancer due to smoking. India also has the highest incidence of cancers of the gall bladder, mouth and lower pharynx. Breast, colon and prostatic cancer have a relatively low incidence in Asian countries. Liver cancer occurs world-wide but is rare in Europe and North America where the HBV carrier rate is low. Stomach cancer is particularly prevalent in Japan and is thought to be due to dietary factors.
Environmental factors have been clearly implicated. For example, subsequent generations of people moving from countries with a low incidence to those with a high incidence of breast or colon cancer acquire the cancer incidence of the country to which they have moved. This suggests that for these specific cancers, environmental factors are more significant than genetic ones.