Causes and Symptoms of Pyrexia of Unknown Origin
Learn about pyrexia of unknown origin (PUO), its possible causes, symptoms, and diagnostic approaches to identify underlying conditions and guide effective treatment.
Written by Dr. Rohinipriyanka Pondugula
Reviewed by Dr. M L Ezhilarasan MBBS
Last updated on 1st Sep, 2025
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Fever is a common symptom that most of us experience from time to time, often due to infections like the flu or a cold. However, when a fever persists for weeks without a clear cause, it can be concerning. This condition is known as Pyrexia of Unknown Origin (PUO).
If you or a loved one has been experiencing a prolonged fever without an obvious reason, this article will help you understand PUO, its possible causes, symptoms, and ways to manage it.
What is Pyrexia of Unknown Origin (PUO)?
PUO is defined as a fever that:
- Lasts for more than three weeks.
- Remains above 38.3°C (101°F) on multiple occasions.
- Has no clear diagnosis despite thorough medical evaluation.
Unlike typical fevers that resolve with treatment, PUO requires deeper investigation to identify the underlying cause.
Consult a Top Specialist
Common Causes of PUO
PUO can result from various conditions, broadly categorized into four groups:
1. Infections (Most Common Cause)
- Bacterial infections: Tuberculosis (TB), abscesses, endocarditis (heart infection).
- Viral infections: Epstein-Barr virus (EBV), cytomegalovirus (CMV), HIV.
- Parasitic or fungal infections: Malaria, toxoplasmosis, histoplasmosis.
2. Autoimmune & Inflammatory Diseases
- Rheumatoid arthritis, lupus, vasculitis.
- Inflammatory bowel disease (IBD) like Crohn’s disease.
3. Cancers & Blood Disorders
- Lymphoma, leukemia, kidney cancer, liver cancer.
- Blood clotting disorders like deep vein thrombosis (DVT).
4. Miscellaneous Causes
- Drug-induced fever (certain antibiotics, anti-seizure medications).
- Thyroid disorders (hyperthyroidism).
- Heat-related illnesses (heatstroke).
Sometimes, despite extensive testing, the exact cause remains unknown, requiring ongoing monitoring.
Symptoms Associated with PUO
Since PUO itself is a symptom, it is often accompanied by other signs depending on the underlying cause:
General Symptoms
- Persistent high-grade fever (above 101°F).
- Chills and night sweats.
- Fatigue and weakness.
- Loss of appetite and weight loss.
Infection-Related Symptoms
- Swollen lymph nodes (TB, HIV).
- Persistent cough (pneumonia, TB).
- Joint pain (viral or autoimmune diseases).
Autoimmune & Cancer-Related Symptoms
- Skin rashes (lupus, vasculitis).
- Unexplained bruising or bleeding (leukemia).
- Abdominal pain (lymphoma, liver disease).
If you experience any of these symptoms along with a prolonged fever, consult a doctor for further evaluation.
How is PUO Diagnosed?
Since PUO has no single cause, doctors use a step-by-step approach to diagnose it:
- Detailed Medical History – Travel history, exposure to infections, medications, family history.
- Physical Examination – Checking for swollen lymph nodes, rashes, organ enlargement.
- Blood Tests – Complete blood count (CBC), liver/kidney function, inflammatory markers (ESR, CRP).
- Imaging Tests – Chest X-ray, CT scan, MRI, or PET scan to detect infections or tumors.
- Specialized Tests – Tuberculosis tests, autoimmune markers (ANA, RF), bone marrow biopsy (if cancer is suspected).
In some cases, doctors may recommend hospitalization for closer monitoring.
Managing PUO: What Can You Do?
While the treatment depends on the underlying cause, here are some general tips to manage PUO:
1. Stay Hydrated
- Fever increases fluid loss. Drink plenty of water, coconut water, or oral rehydration solutions.
2. Monitor Your Temperature
- Keep a fever diary to track temperature patterns, which helps doctors identify the cause.
3. Rest & Nutrition
- Eat a balanced diet rich in proteins, vitamins, and minerals to support immunity.
- Avoid processed foods and excessive sugar.
4. Avoid Self-Medication
- Do not take antibiotics or steroids without a doctor’s prescription, as they can mask symptoms.
5. Follow Up with Your Doctor
- If tests are inconclusive, repeat evaluations may be needed.
When to Seek Immediate Medical Help?
Consult a doctor urgently if you experience:
- Fever above 104°F (40°C).
- Severe headache, confusion, or seizures.
- Difficulty breathing or chest pain.
- Unexplained weight loss (more than 10% of body weight).
How Apollo24|7 Can Help
If you or someone you know is suffering from persistent fever without a clear cause, Apollo24|7 offers:
- Expert consultations with specialists in infectious diseases, rheumatology, and oncology.
- Advanced diagnostic tests (blood tests, imaging, biopsies).
- Personalized treatment plans based on your condition.
You can book an online consultation or schedule lab tests easily through the Apollo24|7 app or website.
Final Thoughts
PUO can be frustrating and worrisome, but with the right medical guidance, most cases can be diagnosed and treated effectively. If you have a prolonged fever, don’t ignore it and seek medical advice early to rule out serious conditions.
Consult a Top Specialist
Consult a Top Specialist
Dr. Mohamed Azeem
General Physician/ Internal Medicine Specialist
2 Years • MBBS,MD(Internal Medicine) CCEBDM
Karaikudi
Apollo Hospitals Karaikudi, Karaikudi
Dr. Dhanraj K
General Physician/ Internal Medicine Specialist
25 Years • MBBS, MD Internal Medicine - Osmania Medical College, Hyderabad
Hyderabad
Apollo Hospitals Jubilee Hills, Hyderabad
(375+ Patients)
Dr. Anand Ravi
General Physician
2 Years • MBBS
Bengaluru
PRESTIGE SHANTHINIKETAN - SOCIETY CLINIC, Bengaluru
Dr Syed Mateen Pasha
General Physician
2 Years • MBBS
Bengaluru
PRESTIGE SHANTHINIKETAN - SOCIETY CLINIC, Bengaluru
Dr P Sai Avinash
General Physician/ Internal Medicine Specialist
5 Years • MBBS
Bengaluru
Apollo Medical Center, Marathahalli, Bengaluru
Consult a Top Specialist
Dr. Mohamed Azeem
General Physician/ Internal Medicine Specialist
2 Years • MBBS,MD(Internal Medicine) CCEBDM
Karaikudi
Apollo Hospitals Karaikudi, Karaikudi
Dr. Dhanraj K
General Physician/ Internal Medicine Specialist
25 Years • MBBS, MD Internal Medicine - Osmania Medical College, Hyderabad
Hyderabad
Apollo Hospitals Jubilee Hills, Hyderabad
(375+ Patients)
Dr. Anand Ravi
General Physician
2 Years • MBBS
Bengaluru
PRESTIGE SHANTHINIKETAN - SOCIETY CLINIC, Bengaluru
Dr Syed Mateen Pasha
General Physician
2 Years • MBBS
Bengaluru
PRESTIGE SHANTHINIKETAN - SOCIETY CLINIC, Bengaluru
Dr P Sai Avinash
General Physician/ Internal Medicine Specialist
5 Years • MBBS
Bengaluru
Apollo Medical Center, Marathahalli, Bengaluru
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