Periodic fever syndromes are inflammatory conditions that cause recurrent fevers. Doctors use treatment to manage symptoms, avoid complications, or, in some cases, attempt to cure the syndrome. Treatment often takes the form of medication, with mixed results.

Healthcare professionals define periodic fever syndromes as inheritable autoinflammatory conditions that cause recurring fevers.

There are many periodic fever syndromes. Common examples include periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, familial Mediterranean fever (FMF), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS).

This article provides an overview of the treatments available for periodic fever syndromes and explores their outcomes. After explaining what these syndromes involve, it will look at treatments for specific periodic fever syndromes, assessing risks and benefits.

Healthcare professionals walking up the stairs and discussing the treatment options for periodic fever syndrome.Share on Pinterest
Dean Mitchell/Getty Images

The goal of treatment for periodic fever syndromes may vary from condition to condition. Sometimes, treatment aims to cure the condition. Other treatment options aim to manage symptoms or prevent complications.

Treatment for periodic fever syndromes commonly includes pharmaceutical interventions. These include:

  • Corticosteroids: These medications can help reduce inflammation. They can also reduce immune system responses.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs): As the name suggests, these anti-inflammatory drugs work differently from steroids.
  • Colchicine: Another anti-inflammatory drug, colchicine is neither a corticosteroid nor NSAID. Research suggests it may be useful for treating periodic fever syndromes.
  • Biologics: Scientists define biologics as medications that originate from biological sources. Because they are biologically sourced, they are typically more complex than wholly synthesized medications. This can allow them to address inflammation very effectively.

Doctors sometimes use tonsillectomy to treat some periodic fever syndromes. A tonsillectomy is the surgical removal of the tonsils.

Side effects of treatment

Pharmaceutical treatments always come with potential side effects. These may include:

  • Corticosteroids: There is evidence that corticosteroids can have a wide variety of side effects, such as adrenal suppression, cardiovascular problems, and diabetes. Adrenal suppression is when the adrenal glands cannot produce enough hormones.
  • NSAIDs: Scientists have documented several side effects of NSAID usage. These medications can harm the kidneys, stomach, and cardiovascular system.
  • Colchicine: Research suggests that the most common side effects of colchicine are diarrhea, vomiting, and nausea. It is rare for colchicine to produce other effects, such as gastrointestinal problems.
  • Biologics: Scientists have found that people generally respond quite well to biologics. Typical symptoms include minor reactions to injections of biologics and minor infections.

Benefits and risks of treatment

Opting for surgical interventions could mean avoiding side effects from medications. However, tonsillectomy is not helpful for many periodic fever syndromes. Additionally, surgery always comes with its own risks.

Common complications of tonsillectomy include:

Individuals will need to consider the pros and cons of available treatment options for different periodic fever syndromes.

According to a 2021 review, PFAPA syndrome involves episodes of high fever that usually last 3–7 days and recur every 2–8 weeks. Often, the condition arises in children and resolves by adulthood.

Treatment often involves managing symptoms, which can be severe. In some cases, the treatment also aims to cure the condition.

There are two main forms of treatment for PFAPA syndrome: pharmaceutical and surgical.

Pharmaceutical options include:

  • colchicine
  • cimetidine
  • corticosteroids
  • NSAIDs

Tonsillectomy can sometimes help with PFAPA syndrome. Scientists do not understand why this might be.

Treatment outcomes

The 2021 review states that:

  • NSAIDs can be fairly effective in lowering fevers, but they will not shorten the episode of fever or the duration of the fever cycle.
  • Colchicine can increase the gaps between fevers.
  • Corticosteroids can be extremely effective in lowering fevers.
  • Tonsillectomy may sometimes put the condition into remission.

According to a 2022 review, FMF involves episodes of fever and pain. These may last between 6 hours to 4 days, with weeks, months, or years between episodes.

FMF typically develops before 20 years of age, and attacks often become less common with time.

FMF treatment involves using medications to manage symptoms and avoid complications. Possible complications include amyloidosis, a group of conditions that refer to the buildup of amyloid, a type of protein, in the body.

Doctors can recommend several medications for FMF. These include colchicine and interleukin inhibitors, which are a type of biologic.

TNF alpha (TNF-α) inhibitors, a type of biologic, may also help. Examples include:

Additionally, selective serotonin reuptake inhibitors may reduce the frequency of episodes.

Treatment outcomes

The authors of the 2022 review suggest that lifelong colchicine treatment is highly effective at stopping fevers, reducing inflammation, and preventing amyloidosis.

They also suggest that interleukin inhibitors can prove effective at reducing fevers but may not prevent amyloidosis.

A 2020 review states that TRAPS involves episodes of fever and multiple-organ inflammation. These episodes typically last between 5 days to 3 weeks and recur every 4–6 weeks. TRAPS usually develops in childhood.

Treatment for TRAPS involves medications. As with FMF, the aim is to manage symptoms and avoid complications, including amyloidosis.

Doctors use many medications to treat TRAPS, including:

  • colchicine
  • corticosteroids
  • interleukin inhibitors
  • TNF-α blocking agents

Treatment outcomes

The authors of the 2020 review suggest that:

  • Colchicine is not very useful for managing TRAPS symptoms.
  • At higher doses, corticosteroids can help reduce inflammation.
  • Some interleukin inhibitors can help manage TRAPS symptoms and may reduce the risk of complications.
  • Etanercept, a TNF-α blocking agent, can greatly reduce symptom intensity, frequency, and duration.
  • The TNF-α blocking agents adalimumab and infliximab can worsen symptoms.

There is no scientific evidence of safe and effective natural treatments for periodic fever syndromes.

However, as with many conditions, anecdotal evidence suggests that caregivers can offer comfort and support to help.

When speaking with a doctor about treatment for periodic fever syndromes, it can be useful to ask questions about the following:

  • the likely outcomes
  • possible side effects
  • possible allergies or intolerances to the treatment
  • pharmaceutical interactions with other medications

In some cases, doctors might be unable to answer these questions with complete certainty. However, discussing such issues can help make treatment as safe and stress-free as possible.

Periodic fever syndromes include several auto-inflammatory conditions. They often begin in childhood and can cause recurrent severe fevers.

To treat periodic fever syndromes, a healthcare professional may prescribe medications, including corticosteroids, NSAIDs, colchicine, and biologics.

Surgery to remove the tonsils may help treat one type of periodic fever syndrome called PFAPA syndrome.