A system for the infectious diseases examination

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Chapter 16 A system for the infectious diseases examination

As it takes two to make a quarrel, so it takes two to make a disease, the microbe and its host.

Charles Chaplain (1856–1941)

We have selected two important presentations to be covered in this chapter to show how infectious diseases can be approached in a systematic manner.

Pyrexia of unknown origin (PUO)

This condition is defined as documented fever (>38 °C) of more than 3 weeks’ duration, where no cause is found despite basic investigations.¹^,² The most frequent causes to consider are tuberculosis, occult abscess (usually intra-abdominal), osteomyelitis, infective endocarditis, lymphoma or leukaemia, systemic-onset juvenile rheumatoid arthritis, giant cell arteritis and drug fever (drug fever is responsible for 10% of fevers leading to hospital admission³). In studies of fever of unknown origin, infection is found to be the cause in 30%, neoplasia in 30%, connective tissue disease in 15% and miscellaneous causes in 15%; in 10% the aetiology remains unknown (Table 16.1). Remember, the longer the duration of the fever, the less likely there is an infectious aetiology. The majority of patients do not have a rare disease but rather a relatively common disease presenting in an unusual way.⁴

TABLE 16.1 Common causes of pyrexia of unknown origin

1 Neoplasms

• Hodgkin’s and non-Hodgkin’s lymphoma, leukaemia, malignant histiocytosis

• Other tumours: hepatic, renal, lung, disseminated carcinoma, atrial myxoma

2 Infections

• Bacterial: e.g. tuberculosis, brucellosis and other bacteraemias, abscess formation (especially pelvic or abdominal), endocarditis, pericarditis, osteomyelitis, cholangitis, pyelonephritis, pelvic inflammatory disease, prostatitis, syphilis, Lyme disease, borreliasis, cat scratch disease, dental abscess

• Viral: e.g. infectious mononucleosis, cytomegalovirus infection, hepatitis B or C, human immunodeficiency virus (HIV) infection, Ross River virus

• Parasitic, rickettsial and others: e.g. malaria, Q fever, toxoplasmosis

• Fungal: e.g. histoplasmosis, cryptococcosis, blastomycosis

3 Connective tissue diseases

• Juvenile rheumatoid arthritis, systemic lupus erythematosus

• Vasculitis, e.g. giant cell arteritis, polyarteritis nodosa

4 Drug fever 5 Miscellaneous

Inflammatory bowel disease, alcoholic liver disease, granulomatous disease (e.g. sarcoid), multiple pulmonary emboli, thyroiditis, adrenal insufficiency, phaeochromocytoma, familial Mediterranean fever and other hereditary periodic fever syndromes, factitious fever

6 Uncertain

History

The history may give a number of clues in these puzzling cases. In some patients a careful history may give the diagnosis where expensive tests have failed. See Questions box 16.1.

The time course of the fever and any associated symptoms must be uncovered. Symptoms from the various body systems should be sought methodically.

Examples include:

1. The gastrointestinal system—diarrhoea, abdominal pain, recent abdominal surgery (inflammatory bowel disease, diverticular disease, cholangitis).

2. The cardiovascular system—heart murmurs, dental procedures (infective endocarditis), chest pain (pericarditis).

3. Rheumatology—joint symptoms, rashes.

4. Neurology—headache (meningitis, cerebral abscess).

5. Genitourinary system—history of renal disease or infection, dysuria.

6. Respiratory system—old tuberculosis (TB) or recent TB contact, chest symptoms.

Details of any recent overseas travel are important. Find out also about hobbies and exposure to pets. Occupational exposure may be important. Take a drug history. Find out if the patient is involved in behaviour posing a risk of HIV infection. Patients who are already in hospital may have infected cannulas or old cannula sites.

Fever due to bacteraemia (the presence of organisms in the bloodstream) is associated with a higher risk of mortality. It is present in up to 20% of hospital patients with fever.⁵ Certain clinical findings modestly increase the likelihood of the presence of bacteraemia (Good signs guide 16.1).

GOOD SIGNS GUIDE 16.1 Clinical findings and bacteraemia

Risk factors	Likelihood ratio if
Risk factors	Present	Absent
Age > 50	1.4	0.3
Temperature >38.5	1.2	NS
Rigors	1.8	NS
Tachycardia	1.2	NS
Respiratory rate >20	NS	NS
Hypotension	2.0	NS
Chronic kidney disease	4.6	0.8
Hospitalisation for trauma	3.0	NS
Terminal disease	2.7	NS
Indwelling urinary catheter	2.4	NS
Central venous catheter	2.0	NS
‘Toxic appearance’	NS	NS

From McGee S, Evidence-based physical diagnosis, 2nd edn. St Louis: Saunders, 2007.

Examination

General

Look at the temperature chart to see whether there is a pattern of fever that is identifiable. Inspect the patient and decide how seriously ill he or she appears. Look for evidence of weight loss (indicating a chronic illness). Note any skin rash (Table 16.2). The details of the examination required will depend on the patient’s history.

TABLE 16.2 Differential diagnosis of prolonged fever and rash

1 Viral: e.g. infectious mononucleosis, rubella, dengue fever

2 Bacterial: e.g. syphilis, Lyme disease

3 Non-infective: e.g. drugs, systemic lupus erythematosus, erythema multiforme (which may also be related to an underlying infection)

Hands

Look for the stigmata of infective endocarditis or vasculitic changes. Note whether there is clubbing. The presence of arthropathy or Raynaud’s phenomenon may point to a connective tissue disease.

Arms

Inspect for drug injection sites suggesting intravenous drug abuse (see Figure 4.41). Feel for the epitrochlear and axillary nodes (e.g. lymphoma, other malignancy, sarcoidosis, focal infections).

HIV infection and the acquired immunodeficiency syndrome (AIDS)

This syndrome, first described in 1981, is caused by the human immunodeficiency virus (HIV).⁶^,⁷ This is a T-cell lymphotrophic virus, which results in T4 cell destruction and therefore susceptibility to opportunistic infections and the development of tumours, notably Kaposi’s sarcoma^a and non-Hodgkin’s lymphoma.

HIV infection should be suspected particularly if the patient falls into a high-risk group (e.g. male homosexual, intravenous drug abuser, sexual tourist, sexual partner of HIV-infected person, haemophiliac, blood transfusion or blood product recipient, prostitute, or sexual contact with one of these). Examine the patient as follows.

Examination

General inspection

Take the temperature. The patient may appear ill and wasted due to chronic ill-health or chronic opportunistic infection. Mycobacterium avium complex (MAC) presents with fever and weight loss.

Look at the skin for rashes:

• The maculopapular rash of acute HIV infection (5- to 10-mm maculopapular lesions on the face and trunk and rarely on the palms and soles).

• Herpes zoster (shingles, which may involve more than one dermatome in this disease and is more commonly seen in early rather than in advanced HIV infection).

• Oral herpes simplex (cold sores) or genital herpes (20%).

• Oral and flexural candidiasis (once the CD4 level is below 200/mm³).

• Molluscum contagiosum (10%), impetigo, seborrhoea (occurs in up to 80% of patients at some time) or other non-specific exanthems.

• Kaposi’s sarcoma: red-purple vascular non-tender tumours. These present typically on the skin but can occur anywhere.

• Skin lesions resembling Kaposi’s sarcoma may also be seen. These are called bacillary angiomatosis and are caused by Bartonella henselae and Bartonella quintana (Figures 16.1 and 16.2).

Figure 16.1 Angry red nodule of bacillary angiomatosis

Figure 16.2 Late nodules of Kaposi’s sarcoma

Adverse drug reactions are more common in patients with HIV infection and may be the cause of a rash. Look for hyperpigmentation. Patients taking the drug clofamizine for MAC infection usually become deeply pigmented. Areas of peripheral fat atrophy—lipodystrophy— on limbs, cheeks and buttocks may be seen in 20%–30% of patients treated with the protease inhibitor drugs. Some of these patients have fat redistribution with central obesity.

Hands and arms

Look for nail changes including onycholysis. Feel for the epitrochlear nodes; a node 0.5 cm or larger may be characteristic.⁸ Note any injection marks.

Face

Inspect the mouth for:

• candidal plaques

• angular stomatitis

• aphthous ulcers

• tongue ulceration (e.g. herpes simplex, cytomegalovirus or candidal infections) or gingivitis.⁹

Periodontal disease is very common. Kaposi’s sarcoma (Figures 16.3 and 16.4) may also occur on the hard or soft palate (in which case associated lesions are almost always present elsewhere in the gastrointestinal tract). Oral squamous cell carcinoma and non-Hodgkin’s lymphoma are more common in AIDS.

Figure 16.3 Kaposi’s sarcoma

From McDonald FS, ed., Mayo Clinic images in internal medicine, with permission. © Mayo Clinic Scientific Press and CRC Press.

Figure 16.4 Oral candidiasis

From McDonald FS, ed., Mayo Clinic images in internal medicine, with permission. © Mayo Clinic Scientific Press and CRC Press.

Parotidomegaly is sometimes seen as a result of HIV-associated Sjögren’s syndrome. These patients may have dry eyes and mouth for this reason.

Hairy leucoplakia is a unique raised or flat, white, painless, and often hairy-looking lesion typically present on the lateral surface of the tongue; it is caused by Epstein-Barr virus infection in HIV-infected persons and is almost diagnostic of HIV infection.

Palpate over the sinuses for tenderness (sinusitis). Examine the cervical and axillary nodes. There may be generalised lymphadenopathy, and all lymph node groups should be examined.

Chest

Note any tachypnoea or dry cough. Chronic cough, either dry or productive of purulent sputum, is common. On auscultation crackles may be present at the bases due to bronchiolitis obliterans. There are often, however, no chest signs despite the presence of pulmonary infiltrates on chest X-ray due to Pneumocystis jiroveci (formerly carinii) or other opportunistic infections.

Abdomen

Examine for hepatosplenomegaly (e.g. infection, lymphoma). Perform a rectal examination (e.g. perianal ulceration from herpes simplex) and a sigmoidoscopy looking for Kaposi’s sarcoma or proctitis (e.g. cytomegalovirus, herpes simplex, amoebic dysentery or pseudomembranous colitis from antibiotic use). Examine the genitals for herpes simplex, warts, discharge or chancre.

Nervous system

Look for signs of meningism (e.g. cryptococcal meningitis). There may be focal signs due to a space-occupying intracranial lesion (e.g. toxoplasmosis, non-Hodgkin’s lymphoma).

Look in the fundi for cottonwool spots (common in AIDS patients), scars (e.g. toxoplasmosis—Figure 16.5) or retinitis (e.g. cytomegalovirus-induced retinitis with perivascular haemorrhages and fluffy exudates, which can cause blindness of rapid onset—Figure 16.6).¹⁰ There may be signs of dementia (AIDS encephalopathy).