What illness causes persistent fever? A guide to chronic fever causes.

September 27, 2025 •

3 min read

Persistent fever, sometimes referred to as fever of unknown origin (FUO), is defined by doctors as a body temperature above 101°F (38.3°C) that lasts for several weeks without an obvious cause. Knowing what illness causes persistent fever is a complex diagnostic challenge, requiring a thorough investigation beyond a simple cold or flu.

Quick Summary

A persistent fever can be a symptom of a variety of underlying health problems, including chronic infections like tuberculosis, inflammatory and autoimmune disorders such as lupus and rheumatoid arthritis, and certain cancers like lymphoma. Certain medications and conditions affecting the endocrine system can also be culprits.

Key Points

Diverse Causes: Persistent fever can be triggered by a wide array of conditions, including chronic infections, autoimmune disorders, and certain cancers.
Fever of Unknown Origin (FUO): If a fever lasts several weeks without a clear cause despite initial evaluation, it is termed FUO, necessitating a more intensive diagnostic process.
Common Infections: Chronic bacterial illnesses like tuberculosis, localized abscesses, or systemic viral infections such as EBV can be culprits behind a lingering fever.
Inflammation's Role: Autoimmune diseases like lupus and rheumatoid arthritis often cause persistent fevers due to the body's ongoing inflammatory response.
Malignancy Link: Certain cancers, especially blood cancers like lymphoma and leukemia, can directly cause fever, known as neoplastic fever.
Medication Effect: Drug fever is a documented cause, where a fever develops as a side effect of certain medications and resolves after they are discontinued.
Stress-Induced Fever: In rare cases, chronic emotional stress can cause a psychogenic fever, which doesn't respond to typical antipyretics.

Understanding the Complexities of Persistent Fever

Unlike an acute fever that resolves in a few days, a chronic or persistent fever indicates that the body is fighting a prolonged battle. The causes are diverse and can be organized into several broad categories, making a proper diagnosis crucial for effective treatment. Doctors will perform a series of tests and analyses to narrow down the possibilities, moving from more common conditions to rarer ones.

Potential Causes of Persistent Fever

A persistent fever can be a symptom of various underlying issues, ranging from infections to inflammatory conditions and even certain cancers. Understanding these potential causes is key to seeking appropriate medical evaluation.

Infections

Chronic infections are a common culprit for persistent fevers. These can be bacterial, such as tuberculosis (TB), which often causes a low-grade fever with night sweats and weight loss, or endocarditis, an infection of the heart lining. Localized infections like chronic sinusitis or abscesses, and even some UTIs in adults, can also lead to a prolonged fever. Viral infections like Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and even HIV can cause a persistent fever, sometimes mimicking mononucleosis-like symptoms.

Inflammatory and Autoimmune Disorders

Conditions where the immune system attacks the body's own tissues can trigger chronic inflammation and persistent fever. Autoimmune diseases such as Rheumatoid Arthritis and Lupus are well-known examples. Other inflammatory conditions like Adult-Onset Still's Disease, Inflammatory Bowel Disease, and various forms of vasculitis can also cause prolonged fevers.

Malignancies

Certain cancers, particularly those affecting the blood and lymphatic system like lymphoma and leukemia, can cause a persistent fever as a paraneoplastic syndrome. This fever can be a direct result of the cancer itself. Renal cell carcinoma has also been associated with persistent fever in some cases.

Other Causes

Beyond infections, inflammation, and cancer, other factors can contribute to a persistent fever. These include drug fever, a reaction to certain medications that resolves upon discontinuing the drug. Deep vein thrombosis (DVT) can cause a low-grade fever due to the inflammatory response from the blood clot. Thyroiditis, an inflammation of the thyroid gland, can also lead to a persistent low-grade fever. In some instances, chronic emotional stress is linked to psychogenic fever, which doesn't respond to typical fever reducers.

A Comparison of Common Persistent Fever Causes


Feature	Infectious Causes	Autoimmune/Inflammatory Causes	Malignancies	Drug Fever
Onset	Can be abrupt or gradual	Usually gradual	Often insidious	Variable, typically days to weeks after starting medication
Typical Fever Pattern	Sustained, intermittent, or relapsing, depending on the pathogen	Typically low-grade and persistent, but can spike	Can be intermittent, cyclic (Pel-Ebstein fever), or sustained	Variable pattern, may have a normal pulse rate relative to high temperature (Faget's sign)
Associated Symptoms	Fatigue, cough, swollen nodes, malaise	Joint pain, rash, muscle aches, organ-specific symptoms	Night sweats, weight loss, unexplained lumps, extreme fatigue	Often no other symptoms aside from potential rash; disappears upon drug withdrawal
Key Diagnostic Clues	Blood cultures, imaging (X-ray, CT), specific serology	Blood tests (ANA, ESR, CRP), imaging, biopsies	Blood tests (CBC, markers), imaging (CT, PET), biopsy	Resolution of fever upon medication cessation

Conclusion: Seeking Medical Expertise

A persistent or recurrent fever warrants medical evaluation to determine the underlying cause and ensure appropriate treatment. Self-diagnosis and treatment are not advisable due to the wide range of potential conditions. A doctor will conduct a thorough medical history, physical exams, and diagnostic tests to arrive at a diagnosis. For additional information on Fever of Unknown Origin, you can consult the American Academy of Family Physicians website.

Investigating a persistent fever is crucial for effective treatment and maintaining good health.

Frequently Asked Questions

A fever is generally considered persistent or chronic if it lasts for more than 10 to 14 days. If the cause remains unidentified after thorough testing, it may be classified as Fever of Unknown Origin (FUO).

Yes, you should be concerned. While a low-grade fever may seem mild, if it persists for an extended period, it can signal an underlying health issue such as an autoimmune condition, chronic infection, or a malignancy.

Yes, chronic emotional stress can lead to a condition known as psychogenic fever. This type of fever is typically low-grade and does not respond to standard fever-reducing medications like acetaminophen.

A doctor may order a range of tests, including a complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood cultures, urinalysis, imaging (such as CT or PET scans), and specific serology or biopsies, depending on other symptoms.

No. While certain cancers like lymphoma and leukemia can cause a persistent fever, it is a relatively rare cause compared to chronic infections and autoimmune diseases. It is a possibility that a doctor will consider, especially if other symptoms like weight loss or night sweats are present.

It is not recommended to simply take fever-reducing medication indefinitely. While it can offer temporary relief, it does not address the root cause and can mask symptoms. It is important to work with a doctor to find the underlying issue.

You should see a doctor if a fever lasts more than a few days, is accompanied by other concerning symptoms (like unexplained weight loss, night sweats, or confusion), or if it spikes to a very high temperature. Seeking medical advice is crucial for determining the underlying cause and proper treatment.