Fever of Unknown Origin

Question 1

What is a pyrogen?

Answer 1

A substance that induces fever

Question 2

Types of pyrogens and what they release

Answer 2

■ Bacterial toxins (Eg. exotoxin)
■ Cytokines- Interleukin -1, Interleukin-6, TNF
○ These pyrogens lead to release of prostaglandin-E2 (PGE2)

Question 3

Fever helps support the immune response by _____

Answer 3

making the body less favorable for replication of bacteria, viruses, etc. Also,
increases WBC activity

Question 4

95% of normal population average oral body temp is ______

Answer 4

36-37.4 °C (96.8-99.3 °F)

Question 5

Rectal/vaginal temperature is 0.5 degrees Celsius ____ than oral

Answer 5

higher

Question 6

Axillary is 0.5 degrees Celsius _____ than oral

Answer 6

lower

Question 7

Peripheral thermometers such as tympanic, temporal artery, axillary, and oral have ____ sensitivity.

Answer 7

low

Question 8

T/F “Fever of Unknown Origin”, while a bit of an odd name, it is a specific diagnosis.

Answer 8

T

Question 9

Fever indicates _____

Answer 9

an increased set point via the hypothalamus, Indicates a controlled rise in body temperature

Question 10

Hyperthermia is _____

Answer 10

in response to external factor (Eg. Heat
stroke) or metabolic (Eg. Thyroid storm), drug or medication (Eg. Cocaine)
■ Bodies set point is unaltered
■ Elevated temp can lead to neuronal, liver, kidney injury

Question 11

FUO Level defined

Answer 11

● Temperature ≥ 100.9° F (38.3° C) on several occasions
● Illness lasting longer than three weeks
● Diagnosis has not been made after three outpatient visits or 3 days of hospitalization

Question 12

Persistent fever due to process not present upon admission ie neg cultures AND Dx remains unknown after 3 days of investigation is called___

Answer 12

Hospital-associated

Question 13

Persistent fever in patient with less than 500 neutrophils in whom cultures are negative AND Dx remains unknown after 3 days of investigation is called

Answer 13

Neutropenia-associated

Question 14

HIV positive patient who has persistent fever for 4 weeks or more outpatient OR 3 weeks as inpatient. 3 days of investigation also is called____

Answer 14

HIV-associated

Question 15

Subclasses of FUO

Answer 15

Hospital-associated
Neutropenia-associated
HIV-associated

Question 16

T/F you should Allow time for the usual diagnostic work-up to be performed before labeling the patient as having FUO

Answer 16

T

Question 17

Factors that can affect FUO

Answer 17

Age
Duration of fever
Immunologic status

Question 18

In adults ______ account for the majority of cases of FUO

Answer 18

infections and cancer

Question 19

Duration of fever

Answer 19

At 6 months or longer the etiology incidence changes significantly
■ Infection, cancer, and autoimmune disorders account
for only 20% of FUO in these type patients
■ Granulomatous diseases such as Inflammatory Bowel
Disease and Factitious fever become more prominent

Question 20

Common causes of FUO for Neutropenic patients

Answer 20

■ Fungal infections
■ Occult (hidden) infections
- Does not appear toxic
- No clear source of infection found
- Usually due to Streptococcal Pneumonia

Question 21

An example of an occult infection that can occur in a neutropenic patient to cause FUO

Answer 21

Streptococcal Pneumonia

Question 22

Causes of FUO in the patient taking immunosuppressive meds for example
organ transplant patients

Answer 22

Eg. Cytomegalovirus (CMV), Fungal, and Mycobacterial infections

Question 23

Five top suspects for FUO

Answer 23

❖ Infection
❖ Neoplasm
❖ Autoimmune Disorders
❖ Miscellaneous
❖ Undiagnosed FUO

Question 24

Most common systemic infections that can cause FUO

Answer 24

TB and endocarditis most common
systemic cause

Question 25

Most common localized infection for causing FUO

Answer 25

occult abscess
➢ Liver, spleen, kidney, brain, and bone
abscesses can be difficult to detect
➢ Osteomyelitis, cholangitis, paranasal
sinusitis, UTI, dental abscesses, etc

Question 26

Most common neoplasm causing FUO

Answer 26

➢ Lymphoma (both Hodgkin and Non
Hodgkin) and leukemia

Question 27

most common cause of automimmune
mediated FUO

Answer 27

Connective tissue diseases
● Adult Still disease
● Systemic lupus erythematosus (SLE)
● Polyarteritis nodosa

Question 28

Miscellaneous causes of FUO

Answer 28

➢ Thyroiditis-increases metabolic rate
➢ Recurrent pulmonary emboli-infarction releases noninfectious pyrogens
➢ Alcohol hepatitis-inflammation of the liver
➢ Familial mediterranean fever- rare
➢ Factitious fever-we talked about this
➢ Drug fever–will look at some examples of potential causes

Question 29

Important history questions for FUO

Answer 29

❖ Exposures-travel, occupational (TB exposure), family
❖ Family Hx-Autoimmune disorders ie SLE
❖ Medical Hx-immunosuppression, recent
medications, localizing symptoms
❖ Social Hx-IV drug abuse, sexual practices
❖ Surgical Hx-Thyroidectomy, joint replacement

Question 30

Labs to order for assessing FUO

Answer 30

➢ CBC with differential
➢ Blood cultures - Allow for 2 weeks for slow growers
➢ CMP-routine blood chemistries (LFTs and bilirubin)
➢ If LFTs abnormal then Hep A, B, and C serologies
➢ UA with micro analysis and culture
➢ Chest radiograph, additional studies when indicated
➢ If signs/symptoms point to a particular organ system, then
further work up is indicated (Eg. LP, Biopsy, etc)

Question 31

When to refer patients with FUO

Answer 31

❖ Any patient with FUO and progressive weight loss and other constitutional signs
❖ Any immunocompromised patient
(e.g. transplant recipients and HIV-infected patients)
❖ Conduct any specialized testing
and infectious disease can also coordinate with the CDC

Question 32

When to admit patients with FUO

Answer 32

❖ Any patient who is rapidly declining with weight loss where hospital admission may expedite work-up.
❖ If FUO is present in immunocompromised patients,
➢ Neutropenic from recent chemotherapy
➢ Post- transplantation (particularly in the previous 6 months)