30 Fever of unknown origin

Question 1

Fever defined as temperature > 38.0
(sometimes defined >37.8)

Why does fever arise?

Answer 1

Produced in response to -

Exogenous pyrogen such as endotoxin gram neg cell walls

Endogenous pyrogen such as IL1, IL6, TNF released from phagocytic cells - protective to host

Move via circulation to anterior hypothalmnus

PGE2 produced which changes temperature setpoint

Results in alteration in autonomic heat loss/ preservation mechanisms

Question 2

What is definition of fever of unknown origin?

Answer 2

Fever >38.3 on several occasions

Continues for more than 3 weeks, despite 1 week of intensive evaluation

Question 3

What are broad causes of FUO?

Answer 3

Infection - most common 40%

Malignancy - lymphoma/ leukaemia 30%

Collagen-vascular disease - AI 20%

Drug associated/ device associated

Inherited - Familial Mediterranean fever/ Familial Hibernian Fever (Irish descent)

Endocrine - hyperthyroidism, subacute thyroiditis

Question 4

What are broad classes FUO can be divided into?

Answer 4

Classical

Nosocomial - infection not present or possibly incubating on admission

Neutropenic FUO

HIV-associated FUO

The bottom three do not necessarily take 3 weeks, as can progress rapidly. So require more prompt investigation.

Question 5

What are causes of FUO in the following categories?

Bacteria

Answer 5

TB
Salmonella typhi
S. aureus - osteomyelitis/ IE
HACEK organisms - IE
Chlamydia/ coxiella/ bartonella - IE
Brucellosis
Anaerobes- abscess
Lyme disease - borrelia burgdorferi
Relapsing fever - borrelia recurrentis
Leptospirosis
Rate bite fever - streptobacillius moniliformis
Typhus - rickettsia prowazekii
Spotted fever - rickettsia rickettsii
Psittacosis 
Q fever
Oral cavity - dental abscess

Question 6

What are causes of FUO in the following categories?

Parasitic

Answer 6

Malaria
Trypanosomiasis
Amoebic abscess
Fascioliasis
Toxoplasmosis

Question 7

What are causes of FUO in the following categories?

Fungal

Viral

Answer 7

Candidiasis
Cryptococcosis
Histoplasmosis

HIV
EBV
CMV
Viral hepatitis

Question 8

What are important parts of history taking?

Answer 8

Routine systemic enquiry - including sexual
Travel history
Occupation
Hobbies
Exposure to animals/ pets
Substance misuse
Infectious hazards

Question 9

What are initial investigations for FUO?

Answer 9

Routine bloods
Blood culture
ANA/ ANCA/ RF
Blood film

HIV/ EBV/ CMV
IGRA

Urinalysis/ culture

CXR
CT whole body
ECHO

Question 10

What steps are required after initial investigations for FUO do not return answer?

Answer 10

Whole body PET/CT scan

Biopsies of anything on scans

Trial of therapy e.g anti-TB agents, or steroids

Question 11

What are initial investigations for FUO?

Answer 11

Routine bloods
Blood culture
LDH
Ferritin

ANA/ ANCA/ RF
HIV/ EBV/ CMV
IGRA
Syphilis

Protein electrophoresis

Urinalysis/ culture

CXR
CT whole body
ECHO

Question 12

What steps are required after initial investigations for FUO do not return answer?

Answer 12

Whole body PET scan/ Gallium scan

Biopsies of anything on scans - e.g bone marrow

Trial of therapy e.g anti-TB agents, or steroids

Question 13

What are common AI disease to cause FUO?

Answer 13

Temporal arteritis

PMR

PAN - higher risk in HBV/ HCV

Stills disease - 16-35

Juvenile RA

Sarcoidosis

Wegner’s granulomatosis

Takayasu’s arteritis

Cryoglobulinaemia

Kikuchi’s disease - necrotising lymphadenitis. Usually woman under 40, Asian

Question 14

65 year old intermittent fever, generalised aches and pains. Takes allopurinol.

ESR 97
CRP 121
FBC/ U+E/ LDH normal

What is diagnosis?

Allopurinol related drug fever
IE
Lymphoma
PMR
TB

Answer 14

PMR

Allopurinol rarely causes drug related fever

IE - no peripheral stigmata

Lymphoma - normal LDH, no lymphadenopathy

TB - no risk factors