Chapter 30 Fevers of Unknown Origin Flashcards
Mechanisms of fever.
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.
Pyrogenic cyotkines (IL-1, TNF, IL-6 from mononuclear cells) –> Anterior hypothalamus by way of?
via circulation
Anterior hypothalamus –> Change in Temperature setpoint by way of?
Remember, Anterior Hypothalamus –> Change in temperature setpoint –> Alteration in autonomic heat loss/preservation mechanisms –> Fever
PGE2
Definition of Fever of Unknown Origin
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?
Classical FUO
Fever (>38.3°C) on several occasions and more than 3 weeks’ duration
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
Nosocomial (healthcare-associated) FUO
Fever (>38.3°C) on several occasions in a healthcare setting; infection not present or incubating on admission
Diagnosis
Uncertain after 3 days despite appropriate investigations, including at least 2 days’ incubation of microbiological cultures
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
Diagnosis
Uncertain after 3 days despite appropriate investigations, including at least 2 days’ incubation of microbiological cultures
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
Diagnosis
Uncertain after 3 days despite appropriate investigations, including at least 2 days’ incubation of microbiological cultures
What is the most common cause of FUO?
Infection
important non-infectious causes of fever, most notably are:
- malignancies
* collagen–vascular diseases
Investigating FUO
Step 1
Stage 1 comprises careful history taking, physical examination and screening tests:
in particular, the skin, eyes, lymph nodes and abdomen should be examined and the heart should be auscultated.
Investigating FUO
Stage 2 involves reviewing the history, repeating the physical examination, specific diagnostic tests and non-invasive investigations:
As the most common cause of unexplained fever is infection, collection and careful examination of appropriate specimens are essential.
Investigating FUO
Stage 3 comprises invasive tests:
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.
Investigating FUO
Stage 4 involves therapeutic trials:
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.
Main difference between Classic FUO & other forms of FUO such as:
nosocomial FUO
neutropenic FUO
HIV-associated FUO
Time course
With respect to time course, classically, an FUO may exist for
weeks or months before a diagnosis is made
With respect to time course, a healthcare-associated (nosocomial) FUO and in neutropenic patients
the time course is hours to days.
Infective Endocarditis
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.
Although any organism can cause Infective Endocarditis native valves are infected by?
native valves are usually infected by oral streptococci (such asStreptococcus sanguinis,Strep. oralisandStrep. mitis),Staphylococcus aureus,and coagulase-negative staphylococci
GRAM POSITIVE COCCI
Native valve infection pathogenesis
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.
Infective Endocarditis symptoms
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,
4 ongoing processes associated with infective endocarditis are?
What may also be evident in terms of peripheral manifestations?
- 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
Outward signs of endocarditis may be helpful in suggesting the diagnosis.
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.
What is the most important test for Infective Endocarditis?
Mortality rate?
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
Blood culture of Infective Endocarditis is processed?
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.
Antiobiotic resistance for infective endocarditis can be associated with what 2 factors?
- 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.
People with heart defects need prophylactic antibiotics during invasive procedures
Such as dental surgery and any other invasive procedures that are likely to cause a transient bacteremia.
Most people with an FUO have a treatable disease presenting in an unusual manner
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.
