What Is Pyrexia Of Unknown Origin (PUO): Types, Causes, Symptoms, Treatment, Diagnosis

Pyrexia of unknown origin, also known as fever of unknown origin, is an unexplained fever despite basic investigations.^(2,4) Patients under this category are difficult to diagnose as they have already resisted classification during the baseline investigations.⁽²⁾

Unexplained fevers are worrisome to the patient and the doctors as well, most of which are diagnosed often within a week.

Pyrexia of unknown origin is of four types,

Classical PUO ⁽¹⁾: The cause of a classic type of pyrexia of unknown origin is infections, malignancy, collagen and vascular diseases. The patient has a temperature of 38.3 C for duration of more than 3 weeks.^(1,4) The classic type of pyrexia of unknown origin affects previously healthy people.

Nosocomial PUO ⁽¹⁾: Nosocomial pyrexia of unknown origin is a fever, which occurs as a result of hospitalization. The patient is usually admitted for some other condition, but begins to run a fever, the cause of which is difficult to detect. The causes of Nosocomial pyrexia of unknown origin can be enterocolitis, drug-induced, pulmonary embolism, sinusitis or septic thrombophlebitis.

Immune Deficient PUO: People with a compromised immune system are at risk of infection and this can lead to pyrexia of unknown origin. It can occur due to bacterial infection, aspergillosis, candidiasis or herpes virus.

HIV-Associated PUO ⁽¹⁾: HIV can lead to fever in the patient. It can also make a person susceptible to infections, which can cause fever of unknown origin. The patient can easily become affected by viral or bacterial infections.

If the doctor recognizes the type of pyrexia of unknown origin (PUO), determining the cause is easy. The various causes are categorized as follows:

• Giant cell arteritis
• Juvenile rheumatoid arthritis
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Polyarteritis nodosa

• Tuberculosis
• Q fever
• Brucellosis
• HIV infection
• Abdominopelvic abscesses
• Cat scratch disease
• Typhoid fever
• Extrapulmonary tuberculosis

• Lymphoma
• Leukemia
• Pancreatic carcinoma
• Sarcoma
• Other types of cancers

• Drug abuse
• Hyperthyroidism
• Hepatitis
• Thyroiditis
• Crohn’s disease
• Factitious fever

Pyrexia of unknown origin presents fever with few other symptoms, which can help the physician determine the related cause.

The most common symptoms of Pyrexia Of Unknown Origin (PUO) are:

• A temperature of more than 100.3 F.
• Chills accompanied by fever.
• Sweating.
• Headaches.
• Body aches.
• Fatigue.
• Weakness.

Other symptoms of Pyrexia Of Unknown Origin (PUO) include:

• Sore throat.
• Cough.
• Joint pain.
• Rash.
• Sinus congestion.
• Diarrhea.

If the fever does not present any emergency symptom, the doctor generally waits for it to subside on its own before prescribing any tests.

Medical History ⁽³⁾: If the fever lasts long, then the doctor may run some tests to determine the cause. During the medical history, the doctor enquires about travel, any changes in the daily environment or any other environmental exposure which can lead to pyrexia of unknown origin.

Physical Examination ⁽³⁾: The doctor would also do a physical examination and check for sign of pallor, rash or jaundice to diagnose pyrexia of unknown origin.

Blood Tests ⁽³⁾: The doctor may also advice blood tests to check for certain conditions including the autoimmune diseases, which generally have no obvious symptoms. Blood cultures and sputum test are done to check for bacterial, fungal and viral infections.

Chest X-ray ⁽³⁾: Chest x-ray can be performed to inspect the lungs.

Most of the cases of pyrexia of unknown origin (PUO) are discharged without any definitive diagnosis and in most cases, it resolves on its own.⁽³⁾ As the mortality rate of pyrexia of unknown origin (PUO) is very low, the doctor does not go with the therapeutic trials, as the early use of antipyretics and antimicrobial may delay the diagnosis of pyrexia of unknown origin.⁽³⁾

The treatment of pyrexia of unknown origin (PUO) depends on the cause.

NSAIDs: Non-steroidal anti-inflammatory drugs and antihistamines are used to treat pyrexia of unknown origin, if no underlying cause is detected.⁽³⁾ This help in reducing fever.

Antibiotics: Broad-spectrum antibiotics are given in case of pyrexia of unknown origin has an immune-deficient cause.

Antivirals: In HIV cases, the treatment of pyrexia of unknown origin focuses on treating HIV with antiviral drugs.

In spite of greater understanding of the diseases and an increased access to the diagnostic tests, pyrexia of unknown origin (PUO) remains a clinical challenge. A good understanding of the patient’s medical history and examination plays a big role in reaching the diagnosis for the patient.

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