Table of ContentsView AllTable of ContentsTypesSymptomsCausesDiagnosisTreatmentPrognosis
Table of ContentsView All
View All
Table of Contents
Types
Symptoms
Causes
Diagnosis
Treatment
Prognosis
Periodic fever syndrome is the term given to a number of conditions that feature an unexplained fever that returns over and over again. Sometimes thesefeverscome with other symptoms, but not always. Periodic fever syndromes usually arise in childhood and may resolve before the adult years, but they don’t always.
These conditions are rarely fatal but may result in lifelong challenges and treatments. Keep reading to learn more about the different types of periodic fever syndromes and how to manage them.
Types of Periodic Fever Syndrome
The most common periodic fever syndromes are listed below.
Familial Mediterranean fever(FMF)Hyperimmunoglobulin D syndrome (HIDS)Muckle-Wells syndrome and familial cold autoinflammatory syndromeNeonatal-onset multisystem inflammatory disease (NOMID)Periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome (PFAPA)Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
Periodic Fever Syndrome Symptoms
While the most common symptom in this family of disorders is recurrent fever without an infectious cause, there are also a range of symptoms that go along with the fevers depending on which condition you may have:
When Is a Fever Too High?
Autoinflammatory diseases represent a sort of malfunction within the immune system. Instead of only attacking foreign threats like viruses or bacteria, gene mutations in people with these conditions cause their immune cells to attack their own bodies. This can result in a number of symptoms, including fevers.
The symptoms that present depend on what body system your immune cells are working against.In some cases, the genetic abnormality causes limited symptoms. In others, inflammation is more widespread, causing damage to other organs.
Diagnosis of periodic fever syndromes usually happens after months or years of unexplained fevers that occur without evidence of viral or bacterial infections. These diseases usually appear in infancy or childhood but can continue into adulthood, too.
Typically, the diagnosis will rely on family histories and the presence of certain symptoms.
Symptoms and EvaluationA formal diagnosis may accompany the following symptoms or evaluation:Observed patterns of recurrent fevers without infectionAbsence of other problems like cancers, infections, or other diseasesGenetic testing for known gene mutationsFamily historiesEthnicity—there is a higher prevalence of FMF in people of Mediterranean and Middle Eastern descentElevated inflammatory markers likeC-reactive protein
Symptoms and Evaluation
A formal diagnosis may accompany the following symptoms or evaluation:Observed patterns of recurrent fevers without infectionAbsence of other problems like cancers, infections, or other diseasesGenetic testing for known gene mutationsFamily historiesEthnicity—there is a higher prevalence of FMF in people of Mediterranean and Middle Eastern descentElevated inflammatory markers likeC-reactive protein
A formal diagnosis may accompany the following symptoms or evaluation:
Once again, specific treatments will depend on the specific disease, but generally medications that reduce inflammation or suppress the immune system may be used to manage these conditions.While there are treatments to manage symptoms of these disorders—and some may resolve with age—most periodic fever disorders are not curable.
There has also been some progress in usingbiologicslike Enbrel (etanercept), Ilaris (canakinumab), and Kineret (anakinra), which block certain immune functions to treat certain periodic fever syndromes.
Safe Ways to Treat a Fever
While recurrent fevers may cause significant symptoms, they are rarely fatal and can often be managed with medication. In PFAPA and HIDS, symptoms typically lessen throughout childhood, especially after age 10.
Mild symptoms may continue into adulthood or contribute to other conditions like arthritis. Mild symptoms may continue into adulthood or contribute to other conditions like arthritis. FMF is a lifelong condition that is manageable as long as colchicine treatment is continuous.
NOMID, on the other hand, often results in serious physical deformities and/or neurological damage. Many of these conditions, particularly Muckle-Wells, are also associated with a condition called amyloidosis.
Amyloidosisoccurs when abnormal proteins build up and cause damage to your organs—especially to the kidneys.This condition can even lead to kidney failure.
While these conditions can cause a range of symptoms from mild to serious, periodic fever syndromes are not fatal in most cases.
A Word From Verywell
What to Do if Your Child Has a Fever
19 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Lachmann HJ.Periodic fever syndromes.Best Practice & Research Clinical Rheumatology. 2017;31(4):596-609. doi. 10.1016/j.berh.2017.12.001Westwell-Roper C, Niemietz I, Tucker LB, Brown KL.Periodic fever syndromes: beyond the single gene paradigm.Pediatric Rheumatology. 2019;17(1):22. doi. 10.1186/s12969-019-0324-7National Organization of Rare Diseases.Familial Mediterranean Fever.MedlinePlus.Tumor necrosis factor receptor-associated periodic syndrome.National Organization of Rare Diseases.Mevalonate Kinase Deficiency.National Organization of Rare Diseases.Neonatal-Onset Multisystem Inflammatory Disease.National Organization of Rare Diseases.Familial Cold Autoinflammatory Syndrome.Cedars Sinai.PFAPA Syndrome.National Institute of Arthritis and Musculoskeletal and Skin Diseases.Autoinflammatory Diseases.Consolini R, Costagliola G, Gattorno M.The challenge of managing children with periodic fever syndromes in the era of covid-19.Front Pediatr. 2021;8:620621. doi. 10.3389/fped.2020.620621UpToDate.Familial Mediterranean fever: Epidemiology, genetics, and pathogenesis.UpToDate.The autoinflammatory diseases: An overview.Duke University Health System.Periodic Fever Syndromes.Columbia University Irving Medical Center.Periodic Fever Syndromes.Malcova H, Strizova Z, Milota T, et al.Il-1 inhibitors in the treatment of monogenic periodic fever syndromes: from the past to the future perspectives.Front Immunol. 2021;11:619257. doi. 10.3389/fimmu.2020.619257Li P, Zheng Y, Chen X.Drugs for autoimmune inflammatory diseases: from small molecule compounds to anti-tnf biologics.Front Pharmacol. 2017;0. doi. 10.3389%2Ffphar.2017.00460Wang A, Manthiram K, Dedeoglu F, Licameli GR.Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (Pfapa) syndrome: A review.World J Otorhinolaryngol Head Neck Surg. 2021;7(3):166-173Rigante D, Manna R.Familial mediterranean fever: assessing the overall clinical impact and formulating treatment plans.Mediterr J Hematol Infect Dis. 2019;11(1):e2019027. doi. 10.4084/mjhid.2019.027National Institute of Diabetes and Digestive and Kidney Diseases.Amyloidosis & Kidney Disease.
19 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Lachmann HJ.Periodic fever syndromes.Best Practice & Research Clinical Rheumatology. 2017;31(4):596-609. doi. 10.1016/j.berh.2017.12.001Westwell-Roper C, Niemietz I, Tucker LB, Brown KL.Periodic fever syndromes: beyond the single gene paradigm.Pediatric Rheumatology. 2019;17(1):22. doi. 10.1186/s12969-019-0324-7National Organization of Rare Diseases.Familial Mediterranean Fever.MedlinePlus.Tumor necrosis factor receptor-associated periodic syndrome.National Organization of Rare Diseases.Mevalonate Kinase Deficiency.National Organization of Rare Diseases.Neonatal-Onset Multisystem Inflammatory Disease.National Organization of Rare Diseases.Familial Cold Autoinflammatory Syndrome.Cedars Sinai.PFAPA Syndrome.National Institute of Arthritis and Musculoskeletal and Skin Diseases.Autoinflammatory Diseases.Consolini R, Costagliola G, Gattorno M.The challenge of managing children with periodic fever syndromes in the era of covid-19.Front Pediatr. 2021;8:620621. doi. 10.3389/fped.2020.620621UpToDate.Familial Mediterranean fever: Epidemiology, genetics, and pathogenesis.UpToDate.The autoinflammatory diseases: An overview.Duke University Health System.Periodic Fever Syndromes.Columbia University Irving Medical Center.Periodic Fever Syndromes.Malcova H, Strizova Z, Milota T, et al.Il-1 inhibitors in the treatment of monogenic periodic fever syndromes: from the past to the future perspectives.Front Immunol. 2021;11:619257. doi. 10.3389/fimmu.2020.619257Li P, Zheng Y, Chen X.Drugs for autoimmune inflammatory diseases: from small molecule compounds to anti-tnf biologics.Front Pharmacol. 2017;0. doi. 10.3389%2Ffphar.2017.00460Wang A, Manthiram K, Dedeoglu F, Licameli GR.Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (Pfapa) syndrome: A review.World J Otorhinolaryngol Head Neck Surg. 2021;7(3):166-173Rigante D, Manna R.Familial mediterranean fever: assessing the overall clinical impact and formulating treatment plans.Mediterr J Hematol Infect Dis. 2019;11(1):e2019027. doi. 10.4084/mjhid.2019.027National Institute of Diabetes and Digestive and Kidney Diseases.Amyloidosis & Kidney Disease.
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Lachmann HJ.Periodic fever syndromes.Best Practice & Research Clinical Rheumatology. 2017;31(4):596-609. doi. 10.1016/j.berh.2017.12.001Westwell-Roper C, Niemietz I, Tucker LB, Brown KL.Periodic fever syndromes: beyond the single gene paradigm.Pediatric Rheumatology. 2019;17(1):22. doi. 10.1186/s12969-019-0324-7National Organization of Rare Diseases.Familial Mediterranean Fever.MedlinePlus.Tumor necrosis factor receptor-associated periodic syndrome.National Organization of Rare Diseases.Mevalonate Kinase Deficiency.National Organization of Rare Diseases.Neonatal-Onset Multisystem Inflammatory Disease.National Organization of Rare Diseases.Familial Cold Autoinflammatory Syndrome.Cedars Sinai.PFAPA Syndrome.National Institute of Arthritis and Musculoskeletal and Skin Diseases.Autoinflammatory Diseases.Consolini R, Costagliola G, Gattorno M.The challenge of managing children with periodic fever syndromes in the era of covid-19.Front Pediatr. 2021;8:620621. doi. 10.3389/fped.2020.620621UpToDate.Familial Mediterranean fever: Epidemiology, genetics, and pathogenesis.UpToDate.The autoinflammatory diseases: An overview.Duke University Health System.Periodic Fever Syndromes.Columbia University Irving Medical Center.Periodic Fever Syndromes.Malcova H, Strizova Z, Milota T, et al.Il-1 inhibitors in the treatment of monogenic periodic fever syndromes: from the past to the future perspectives.Front Immunol. 2021;11:619257. doi. 10.3389/fimmu.2020.619257Li P, Zheng Y, Chen X.Drugs for autoimmune inflammatory diseases: from small molecule compounds to anti-tnf biologics.Front Pharmacol. 2017;0. doi. 10.3389%2Ffphar.2017.00460Wang A, Manthiram K, Dedeoglu F, Licameli GR.Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (Pfapa) syndrome: A review.World J Otorhinolaryngol Head Neck Surg. 2021;7(3):166-173Rigante D, Manna R.Familial mediterranean fever: assessing the overall clinical impact and formulating treatment plans.Mediterr J Hematol Infect Dis. 2019;11(1):e2019027. doi. 10.4084/mjhid.2019.027National Institute of Diabetes and Digestive and Kidney Diseases.Amyloidosis & Kidney Disease.
Lachmann HJ.Periodic fever syndromes.Best Practice & Research Clinical Rheumatology. 2017;31(4):596-609. doi. 10.1016/j.berh.2017.12.001
Westwell-Roper C, Niemietz I, Tucker LB, Brown KL.Periodic fever syndromes: beyond the single gene paradigm.Pediatric Rheumatology. 2019;17(1):22. doi. 10.1186/s12969-019-0324-7
National Organization of Rare Diseases.Familial Mediterranean Fever.
MedlinePlus.Tumor necrosis factor receptor-associated periodic syndrome.
National Organization of Rare Diseases.Mevalonate Kinase Deficiency.
National Organization of Rare Diseases.Neonatal-Onset Multisystem Inflammatory Disease.
National Organization of Rare Diseases.Familial Cold Autoinflammatory Syndrome.
Cedars Sinai.PFAPA Syndrome.
National Institute of Arthritis and Musculoskeletal and Skin Diseases.Autoinflammatory Diseases.
Consolini R, Costagliola G, Gattorno M.The challenge of managing children with periodic fever syndromes in the era of covid-19.Front Pediatr. 2021;8:620621. doi. 10.3389/fped.2020.620621
UpToDate.Familial Mediterranean fever: Epidemiology, genetics, and pathogenesis.
UpToDate.The autoinflammatory diseases: An overview.
Duke University Health System.Periodic Fever Syndromes.
Columbia University Irving Medical Center.Periodic Fever Syndromes.
Malcova H, Strizova Z, Milota T, et al.Il-1 inhibitors in the treatment of monogenic periodic fever syndromes: from the past to the future perspectives.Front Immunol. 2021;11:619257. doi. 10.3389/fimmu.2020.619257
Li P, Zheng Y, Chen X.Drugs for autoimmune inflammatory diseases: from small molecule compounds to anti-tnf biologics.Front Pharmacol. 2017;0. doi. 10.3389%2Ffphar.2017.00460
Wang A, Manthiram K, Dedeoglu F, Licameli GR.Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (Pfapa) syndrome: A review.World J Otorhinolaryngol Head Neck Surg. 2021;7(3):166-173
Rigante D, Manna R.Familial mediterranean fever: assessing the overall clinical impact and formulating treatment plans.Mediterr J Hematol Infect Dis. 2019;11(1):e2019027. doi. 10.4084/mjhid.2019.027
National Institute of Diabetes and Digestive and Kidney Diseases.Amyloidosis & Kidney Disease.
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