What diseases cause recurrent fevers?

September 25, 2025 •

4 min read

According to the Cleveland Clinic, systemic autoinflammatory diseases (SAIDs), formerly known as periodic fever syndromes, are a group of disorders that cause frequent, recurring fevers. Determining what diseases cause recurrent fevers involves a careful look at a wide range of possibilities, from infections to autoimmune conditions and even certain cancers.

Quick Summary

Recurrent fevers can be triggered by a variety of medical conditions, including chronic or lingering infections like tuberculosis, autoimmune diseases such as lupus or rheumatoid arthritis, and a category of genetic conditions known as periodic fever syndromes. In some cases, certain cancers like lymphomas can also manifest with repeated fever episodes. The cyclical nature and accompanying symptoms can offer crucial clues to the underlying cause.

Key Points

Infections Are Common Culprits: Chronic or relapsing infections from viruses (like EBV, CMV), bacteria (tuberculosis), or parasites (malaria) can cause fevers to return repeatedly.
Genetic Syndromes Exist: Periodic fever syndromes like FMF and PFAPA are genetic disorders that cause predictable, recurring fever episodes alongside other symptoms like rashes or joint pain.
Autoimmune Conditions Trigger Fevers: Systemic autoimmune diseases such as Lupus and Adult-onset Still's Disease can cause recurrent fevers as a symptom of widespread, chronic inflammation.
Malignancies Can Cause Fever: Certain cancers, particularly lymphomas and leukemias, can cause a type of fever called a paraneoplastic syndrome, where the tumor itself induces fever.
Diagnosis is Often Complex: Determining the cause of a recurrent fever involves a process of elimination using physical exams, blood tests for inflammatory markers, imaging, and sometimes genetic testing.
Management Depends on the Cause: Treatment options vary widely depending on the underlying diagnosis, from anti-inflammatory drugs and targeted biologics for autoinflammatory diseases to managing the underlying infection or malignancy.

Common Infectious Causes

While most common viral illnesses resolve within a few days, some infections can cause a fever to come and go over a longer period. A fever is a natural immune response, and a recurrent pattern can signal that the body is struggling to fully eradicate an underlying infectious agent. Infections can be particularly stubborn or persistent, especially if the patient is immunocompromised.

Chronic Bacterial and Viral Infections

Several infections are known to cause recurring or prolonged fevers:

Epstein-Barr Virus (EBV): This virus is a common cause of infectious mononucleosis and can sometimes lead to prolonged, relapsing fevers that last for weeks or months.
Cytomegalovirus (CMV): Another common virus, CMV can also cause a mono-like illness with long-lasting, recurrent fevers.
Tuberculosis (TB): A persistent bacterial infection that can cause systemic symptoms, including a classic pattern of recurrent fevers, along with weight loss and night sweats.
Malaria: Especially relevant for individuals with a history of travel, malaria is caused by a parasite and is characterized by cyclic fevers with a predictable pattern.
Lyme Disease: A tick-borne illness that, if not treated early, can lead to recurrent symptoms, including fevers.

Autoinflammatory Diseases and Periodic Fever Syndromes

These are genetic conditions characterized by unprovoked episodes of fever and inflammation. Unlike autoimmune diseases, which involve the adaptive immune system, autoinflammatory disorders stem from a dysregulation of the innate immune system.

Genetically-Driven Inflammatory Responses

Familial Mediterranean Fever (FMF): The most common periodic fever syndrome, FMF is an inherited disorder that causes recurrent attacks of fever along with painful inflammation in the abdomen, chest, or joints.
PFAPA Syndrome (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis): This is a common condition in young children, featuring recurrent high fevers, mouth sores, sore throat, and swollen neck glands. The episodes follow a regular cycle.
Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS): A rare genetic disorder that can present with prolonged fevers lasting for weeks, along with muscle aches and a migratory skin rash.
Mevalonate Kinase Deficiency (MKD): Also known as Hyperimmunoglobulin D syndrome, this disorder causes recurrent, irregular fever attacks often accompanied by gastrointestinal issues and swollen lymph nodes.

Autoimmune and Chronic Inflammatory Conditions

Systemic autoimmune diseases can cause recurrent fevers as a symptom of chronic inflammation. The immune system mistakenly attacks healthy tissue, leading to widespread inflammation throughout the body.

Conditions Associated with Systemic Inflammation

Systemic Lupus Erythematosus (SLE or Lupus): A systemic autoimmune disease that can cause a wide range of symptoms, including fever, joint pain, rashes, and fatigue.
Adult-onset Still's Disease (AOSD): This is the adult form of systemic juvenile idiopathic arthritis and is characterized by daily high fevers, a salmon-colored rash, and joint pain.
Rheumatoid Arthritis (RA): In some cases, severe RA can cause systemic inflammation and fever, especially during flares.
Inflammatory Bowel Disease (IBD): Conditions like Crohn's disease and ulcerative colitis can cause systemic inflammation and fever, particularly during severe flare-ups.

Malignancy-Related Fevers (Neoplastic Fevers)

In some cases, a recurring fever, particularly one of unknown origin, can be a symptom of an underlying cancer. This is known as a paraneoplastic syndrome, where the tumor itself or the body's immune response to it causes fever.

Common Cancers Associated with Recurrent Fever

Lymphoma: Both Hodgkin's and non-Hodgkin's lymphomas are well-known causes of neoplastic fever. The classic Pel-Ebstein fever, though rare, is a cyclical pattern of high fever followed by an afebrile period, typically associated with Hodgkin's lymphoma.
Leukemia: Cancers of the blood, such as acute leukemias, can cause recurrent fevers.
Renal Cell Carcinoma: This type of kidney cancer is sometimes associated with neoplastic fever, often correlated with the tumor's size.

Comparison of Recurrent Fever Causes


Cause	Common Characteristics	Typical Onset	Potential Triggers
Chronic Infections	Persistent or relapsing fever, often with other infection-specific symptoms (e.g., cough with TB)	Varies greatly	Exposure to pathogens, immunocompromised state
Periodic Fever Syndromes	Regularly-spaced fever episodes, genetic component, other inflammatory symptoms (rash, mouth sores)	Often in childhood	Stress, surgery, vaccination (MKD)
Autoimmune Disorders	Chronic inflammation, joint pain, rashes, accompanying systemic symptoms	Varies (childhood or adult)	Disease flares, stress
Malignancies	Intermittent fever, often responsive to NSAIDs, sometimes with night sweats and weight loss	Usually in adults	Cancer progression, tumor release of pyrogens

The Diagnostic Process

For a recurrent fever of unknown origin, a systematic diagnostic approach is necessary. A doctor will begin with a thorough history and physical exam, looking for clues to the underlying cause. Several tests may be performed to rule out common culprits and identify more serious conditions.

Blood and Urine Tests: These are used to detect markers of infection (complete blood count) and inflammation (C-reactive protein, erythrocyte sedimentation rate), as well as to check for specific autoimmune antibodies.
Imaging: X-rays, CT scans, and MRIs can help locate infections, tumors, or other sources of inflammation.
Genetic Testing: For suspected periodic fever syndromes, genetic testing can confirm the presence of a specific gene mutation.
Medication Trials: In cases of suspected neoplastic fever, a doctor might use a trial of anti-inflammatory medication like naproxen to see if it reduces the fever, which can be a diagnostic indicator.

Conclusion: Recognizing the Underlying Cause is Key

Recurrent fevers are a complex medical symptom that should never be ignored. While many cases are linked to self-limiting infections, persistent or cyclic fevers require careful investigation to rule out more serious underlying conditions, such as autoinflammatory disorders, autoimmune diseases, or malignancies. The pattern of the fever, its accompanying symptoms, and the patient's medical history are all critical pieces of the puzzle for a proper diagnosis. Accurate identification of the cause is the first step toward effective management and resolution of this distressing symptom. For more information on fever management, you can visit the Centers for Disease Control and Prevention.

Frequently Asked Questions

The most common periodic fever syndrome in young children is PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis) syndrome, which causes episodes of high fever, mouth sores, a sore throat, and swollen lymph nodes.

While not a direct cause of a true infectious fever, extreme stress can affect the immune system and has been noted as a potential contributing factor to fluctuating body temperature in some individuals.

A fever of unknown origin is a diagnosis given when a person has a persistent fever lasting more than three weeks that does not have a clear cause despite extensive medical evaluation.

Yes, although it is a less common cause, some cancers, such as lymphomas, can cause recurrent fevers. This is known as a paraneoplastic syndrome, where the tumor causes the fever directly.

Treatment for periodic fever syndromes can vary but often involves managing symptoms and preventing complications. Options may include anti-inflammatory drugs like NSAIDs and corticosteroids, or targeted biologics, depending on the specific syndrome.

Autoimmune diseases like lupus and rheumatoid arthritis can cause recurrent fevers that are related to periods of heightened inflammatory activity, or 'flares,' where the immune system is mistakenly attacking the body's own tissues.

It is recommended to see a doctor for any persistent, unexplained, or recurrent fevers, especially if they last longer than a few days. Accompanying symptoms like weight loss, chills, or rashes also warrant medical evaluation.