Chapter 30 Fevers of Unknown Origin

Question 1

Mechanisms of fever.

Answer 1

Fever may be induced either by exogenous pyrogens such as pathogens or their toxins or by endogenous pyrogens released in the host, and may have a protective effect.

Question 2

Pyrogenic cyotkines (IL-1, TNF, IL-6 from mononuclear cells) –> Anterior hypothalamus by way of?

Answer 2

via circulation

Question 3

Anterior hypothalamus –> Change in Temperature setpoint by way of?

Remember, Anterior Hypothalamus –> Change in temperature setpoint –> Alteration in autonomic heat loss/preservation mechanisms –> Fever

Answer 3

PGE2

Question 4

Definition of Fever of Unknown Origin

Answer 4

Cause of this fever is usually immediately apparent or is discovered within a few days, or the temperature settles spontaneously.

Patient’s fever is >38.3°C (101°F) on several occasions and continues for more than 3 weeks despite 1 week of intensive evaluation, a provisional diagnosis of?

Question 5

Classical FUO

Fever (>38.3°C) on several occasions and more than 3 weeks’ duration

Answer 5

Diagnosis
Uncertain despite appropriate investigations after at least three outpatient visits or 3 days in hospital, including at least 2 days’ incubation of microbiological cultures

Question 6

Nosocomial (healthcare-associated) FUO

Fever (>38.3°C) on several occasions in a healthcare setting; infection not present or incubating on admission

Answer 6

Diagnosis
Uncertain after 3 days despite appropriate investigations, including at least 2 days’ incubation of microbiological cultures

Question 7

Neutropenic FUO
Fever (>38.3°C) on several occasions; neutrophil count <500 / mm3in peripheral blood, or expected to fall below that number within 1–2 days

Answer 7

Diagnosis
Uncertain after 3 days despite appropriate investigations, including at least 2 days’ incubation of microbiological cultures

Question 8

HIV-associated FUO
Fever (>38.3°C) on several occasions; fever of more than 4 weeks’ duration as an outpatient or more than 3 days’ duration as an inpatient; confirmed positive HIV serology

Answer 8

Diagnosis
Uncertain after 3 days despite appropriate investigations, including at least 2 days’ incubation of microbiological cultures

Question 9

What is the most common cause of FUO?

Answer 9

Infection

Question 10

important non-infectious causes of fever, most notably are:

Answer 10

• malignancies

* collagen–vascular diseases

Question 11

Investigating FUO
Step 1
Stage 1 comprises careful history taking, physical examination and screening tests:

Answer 11

in particular, the skin, eyes, lymph nodes and abdomen should be examined and the heart should be auscultated.

Question 12

Investigating FUO
Stage 2 involves reviewing the history, repeating the physical examination, specific diagnostic tests and non-invasive investigations:

Answer 12

As the most common cause of unexplained fever is infection, collection and careful examination of appropriate specimens are essential.

Question 13

Investigating FUO

Stage 3 comprises invasive tests:

Answer 13

Biopsy of liver and bone marrow should always be considered in the investigation of classic cases of FUO, but other tissues such as skin, lymph nodes and kidney may also be sampled.

Question 14

Investigating FUO

Stage 4 involves therapeutic trials:

Answer 14

Trials of corticosteroids or prostaglandin inhibitors may be indicated if a non-infectious cause has been essentially eliminated. There are few indications for empirical antimicrobial or cytotoxic chemotherapy in the management of classic FUO.

Question 15

Main difference between Classic FUO & other forms of FUO such as:
nosocomial FUO
neutropenic FUO
HIV-associated FUO

Answer 15

Time course

Question 16

With respect to time course, classically, an FUO may exist for

Answer 16

weeks or months before a diagnosis is made

Question 17

With respect to time course, a healthcare-associated (nosocomial) FUO and in neutropenic patients

Answer 17

the time course is hours to days.

Question 18

Infective Endocarditis

Answer 18

infective endocarditis is an uncommon disease that historically has often presented as an FUO which is fatal if untreated. The infection involves the endothelial lining of the heart, usually including the heart valves. It may occur as an acute, rapidly progressive disease or in a subacute form. The majority of these patients have a pre-existing heart defect, either congenital or acquired (e.g. as a result of rheumatic fever), or a prosthetic heart valve in situ. However, the patient may be unaware of any defect before the infection.

Question 19

Although any organism can cause Infective Endocarditis native valves are infected by?

Answer 19

native valves are usually infected by oral streptococci (such asStreptococcus sanguinis,Strep. oralisandStrep. mitis),Staphylococcus aureus,and coagulase-negative staphylococci

GRAM POSITIVE COCCI

Question 20

Native valve infection pathogenesis

Answer 20

Bacteria circulating in the bloodstream adhere to, and establish themselves on, the heart valves. Multiplication of the pathogens is associated with destruction of valve tissue and the formation of vegetations, which interfere with, and may severely compromise, the normal function of the valve.

Question 21

Infective Endocarditis symptoms

Answer 21

A patient with infective endocarditis almost always has a fever and a heart murmur and may also complain of non-specific symptoms such as anorexia, weight loss, malaise, chills, nausea, vomiting and night sweats,

Question 22

4 ongoing processes associated with infective endocarditis are?
What may also be evident in terms of peripheral manifestations?

Answer 22

• the infectious process on the valve and local intra-cardiac complications
• septic embolization to virtually any organ
• bacteremia, often with metastatic foci of infection
• circulating immune complexes and other factors

Peripheral manifestations may also be evident in the form of splinter hemorrhages and Osler’s nodes

Question 23

Outward signs of endocarditis may be helpful in suggesting the diagnosis.

Answer 23

These result from the host’s response to infection in the form of immune-complex-mediated vasculitis, focal platelet aggregation and vascular permeability. (A and B, different views.) Splinter hemorrhages in the nailbed and petechial lesions in the skin. (C) Osler’s nodes. These are tender nodular lesions that tend to affect the palms and fingertips.

Question 24

What is the most important test for Infective Endocarditis?

Mortality rate?

Answer 24

Blood culture is the most important test for diagnosing infective endocarditis
The mortality rate of infective endocarditis is approximately 20–50% despite treatment with antibiotics

Question 25

Blood culture of Infective Endocarditis is processed?

Answer 25

Ideally, three separate samples of blood should be collected within a 24-h period and before antimicrobial therapy is administered.
Isolation of the causative organism is essential so that antibiotic susceptibility tests can be performed and optimum therapy prescribed.

Question 26

Antiobiotic resistance for infective endocarditis can be associated with what 2 factors?

Answer 26

• relative inaccessibility of the organisms within the vegetations both to antibiotics and to host defenses
• the organism’s high population density and relatively slow rate of multiplication.

Question 27

People with heart defects need prophylactic antibiotics during invasive procedures

Answer 27

Such as dental surgery and any other invasive procedures that are likely to cause a transient bacteremia.

Question 28

Most people with an FUO have a treatable disease presenting in an unusual manner

Answer 28

Although classically a patient with FUO presents with a long history (weeks or months of fever), patients also present with fevers that are not immediately diagnosed by routine laboratory investigations.

Definitions of FUO have also been proposed for these groups (nosocomial, neutropenic and HIV associated).
The list of pathogens causing fever in these patients is growing.

The clinician’s aim in the investigation of every patient with FUO should be to discover the cause (i.e. to change a FUO to a fever of known origin) and to initiate appropriate treatment.