Approach to Pyrexia of unknown origin

Question 1

What is the definition of pyrexia of unknown origin?

Answer 1

Fever > 38.3°C on several occasions

Duration > 3wks (because >3 weeks, we will not expect common viral infections eg URTI)

Uncertain diagnosis after 1wk of study (inpatient/outpatient) including

• Clinical 🡪 history, physical examination
• Labs 🡪 FBC, blood culture (3 sets, different sites, several hrs w/o antibiotics), routine biochemistries, UFEME, urine culture
• Imaging 🡪 Chest X-ray

Question 2

What are the infectious causes of pyrexia of unknown origin (PUO)?

Answer 2

Infective Endocarditis – Hx of IVDU
Osteomyelitis – any bone pain, painful WB, immunocompromise, trauma
Abscess – any swinging fevers
Tuberculosis
Atypical Pneumonia
Meningitis (esp subacute causes of meningitis)
HIV – sexual Hx

Question 3

What are inflammatory causes of PUO? What is the relevant hx to take?

Answer 3

Any rheumatological / vasculitis disorders – RA, SLE, GCA, PMR etc

To ask:

• Any joint / back / buttock pain, rashes, redness in eye, yellowing of skin, rashes
• Any ulcers, loss of hair
• LOW, LOA, FHx

Question 4

What are the malignant causes of PUO? What is the relevant hx to take?

Answer 4

Haematological 🡪 lymphoma (esp. NHL), leukaemia, MDS, MM’

Solid organ 🡪 esp renal cell carcinoma, hepatocellular carcinoma

Question 5

What are iatrogenic causes of PUO? What is the relevant hx to take?

Answer 5

Iatrogenic causes of fever, esp SJS, TEN

Note: if patient is receiving chemoTx, always check for central line / PICC site infection (erythema, bleeding, discharge)

Question 6

What are endocrine causes of PUO? What is the relevant hx to take?

Answer 6

Thyroid -> hyperthyroidism, subacute thyroiditis

Adrenocortical -> pheochromocytoma, adrenal insufficiency

Question 7

What are other causes of PUO? What is the relevant hx to take?

Answer 7

Chronic DVT / PE

Hematoma w/ inflammation

Hypothalamic dysfunction (e.g. central fever) -> stroke, anoxic injury

Question 8

What are the important hx to take in a patient with fever?

Answer 8

• Do you have any skin rash?
• Do you have any abdominal pain or diarrhea?
• Do you have any neck stiffness or difficulty looking when it is bright?
• Do you come for a NEA-identified dengue hotspot?
• Have you travelled out of Singapore for the past 12 months?
• Do you have any pets or animal exposure?
• Have you come into contact with anyone sick recently?
• Did you have any recent viral illness or URTI symptoms?
• Is there a pattern to your fever? Are there fever spikes? How many per day>
• Is the fever associated with chills and rigor?
• Did you medicate yourself to reduce the fever or associated symptoms?
• Is it a notifiable problem?

Question 9

What are infective causes of a nosocomial fever?

Answer 9

• Pneumonia (new cough, desaturation, new crackles)
• PICC or CICC infection (check for tenderness at insertion site) ie Central Line Infection
• Wound or surgical site infection (check for tenderness, discharge and cellulitis, consider pressure ulcers too: refer to NHS staging)
• Clostridium difficile infection -> diarrhea (check for C. diff toxins in stool)
• Urinary tract infection (catheter-associated UTI is generally a diag

Question 10

What are non infective causes of a nosocomial fever?

Answer 10

• Drug fever (check for rash, edema and eosinophilia)
• Blood-related (e.g. transfusion-related)
• Thrombus (e.g. DVT, consider septic thrombus also, consider risk factors)
• Malignancy
• Herpes zoster flare (consider that patients are in state of stress)

Question 11

What is the definition of a nosocomial fever?

Answer 11

Patient hospitalised for >24 hrs, with no fever on admission

Question 12

What is the definition of a immunodeficient fever?

Answer 12

• Temp >38.3 degrees
• Neutrophil count <500 per mm3
• Evaluate at least 3 days