Pyrexia of Unknown Origin (PUO)

What is Pyrexia of Unknown Origin (PUO)?

Pyrexia of Unknown Origin (PUO) is a condition in which an individual has elevated body temperature, but despite investigations, no cause or explanation is found for this condition.

Alternate names

• Pyrexia of Unknown Origin
• Fever of Unknown Origin

Is PUO a Medical Emergency?

Pyrexia of Unknown Origin (PUO) is not a medical emergency.

Types

PUO can be of the following types:

• Classical PUO
• Hospital-acquired PUO
• Immunocompromised or neutropenic PUO
• HIV related PUO

Causes

• A temperature greater than 101°F on several occasions
• More than 3 weeks duration of the condition
• Failure to reach a diagnosis despite admission to hospital and inpatient investigations

The causes of PUO are numerous and differ according to the geographic regions, economic index, etc.
Some of the causes of PUO may include:

• Non-infectious causes of PUO:
  • Giant cell (temporal) arteritis
  • Adult still disease (juvenile rheumatoid arthritis)
  • The systemic lupus erythematosus (SLE)
  • Periarteritis nodosa/microscopic polyangiitis (PAN/MPA)
  • Rheumatoid arthritis (RA)
  • Antiphospholipid syndrome (APS)
  • Gout
  • Pseudogout
  • Behçet disease
  • Sarcoidosis
  • Felty syndrome
  • Takayasu arteritis
  • Kikuchi disease
  • Periodic fever adenitis pharyngitis aphthous ulcer (PFAPA) syndrome
• Infectious causes of PUO:
  • Tuberculosis (TB)
  • Q fever (parturient animals)
  • Brucellosis (hooved mammals, raw dairy)
  • HIV infection
  • Abdominopelvic abscesses
  • Cat scratch disease (CSD)
  • Epstein-Barr virus (EBV) infection
  • Cytomegalovirus (CMV) infection
  • Enteric (typhoid) fever
  • Toxoplasmosis
  • Extrapulmonary TB
  • Organ-based infectious causes of PUO are as follows:
  • Subacute bacterial endocarditis (SBE)
  • Tooth abscess
  • Chronic sinusitis/mastoiditis
  • Chronic prostatitis
  • Discitis
  • Vascular graft infections
  • Whipple disease
  • Multicentric Castleman disease (MCD)
  • Cholecystitis
  • Lymphogranuloma venereum (LGV)
  • Histoplasmosis
  • Leptospirosis
  • Visceral leishmaniasis
  • Rat-bite fever
• Malignancy and cancer-related:
  • Lymphoma
  • Renal cell carcinoma
  • Acute myelogenous leukemia
  • Myeloproliferative disorders
  • Multiple myeloma
  • Breast cancer
  • Liver cancer
  • Pancreatic cancer
  • Metastases to the brain or liver.
• Miscellaneous causes:
  • Thyroiditis
  • Cirrhosis
  • Crohn disease
  • Familial periodic fever syndrome
  • Pulmonary emboli

Symptoms & signs

In most cases of PUO, no symptoms other than the persistence of fever are seen.
The following, if present, may indicate an underlying cause:

• Pulse temperature deficit - Low pulse rate despite the high fever
• Unequal pulse in the upper extremities
• Oral ulcers
• Tender teeth
• Enlarged or tender thyroid
• Enlarged lymph nodes
• The enlarged liver without an enlarged spleen
• Enlarged spleen without enlarged liver
• Tenderness of the sternum to touch
• Tenderness of the spine
• Nodules of swelling of the scrotum
• Tender and red nodules on the legs

Investigations

The following investigation may be done:

• Laboratory tests:
  • CBP & ESR
  • Peripheral blood smear
  • Tuberculosis screening tests - PPD or Mantoux
  • Complete metabolic panel
  • Complete urine examination
  • Renal function tests
  • Liver function tests
  • Blood cultures
  • HIV serology
  • Naproxen test
• Imaging tests:
  • Chest x-ray - Posteroanterior (PA) and lateral views
  • Thoracic CT angiography
  • Echocardiography
  • CT scanning of the abdomen and pelvis
  • FDG PET - CT - Whole body
  • Radionucleotide studies
  • Bone scanning
• Diagnostic procedures:
  • Endoscopy
  • Biopsies and tissue sampling - CSF, pleural fluid, peritoneal fluid, liver, bone marrow, and lymph nodes.

Diagnosis

A diagnosis of the underlying cause of Pyrexia of Unknown Origin (PUO) may be established based on careful medical history, travel history, sexual history, clinical evaluation, and investigation results.

Treatment options

The treatment of PUO is based on identifying the underlying cause and its management.

Medical management

The medical management of Pyrexia of Unknown Origin (PUO) depends on the diagnosed underlying cause.

Complications

Most cases of PUO do not lead to any serious complications.

Prognosis

The prognosis of Pyrexia of Unknown Origin is directly dependent on the prognosis of the underlying cause.

When to contact the doctor or hospital? / How to identify the emergency or complications?

It is advisable to seek medical attention if there is a persistent fever despite taking over the counter medications.

Indications for hospitalization if required

Hospitalization may be required for the initial evaluation of (PUO).

Suggested clinical specialist/ Departments to consult for this condition

Specialists from the departments of infectious diseases, haematology, oncology, rheumatology, pulmonology, gastroenterology, endocrinology, interventional radiology, and general surgery will attend it.