Inherited Periodic Fever Syndrome: Recurrent Fever and More

What Is Inherited Periodic Fever Syndrome?

Inherited periodic fever syndromes are a collection of conditions that result in repeated fevers. The syndromes are autoimmune illnesses. The majority of these illnesses are inherited and caused by a gene mutation. The symptoms associated with inherited periodic syndromes are various, but they all produce fever, skin rashes, joint pains, and abdominal pains and can develop into chronic problems, including amyloidosis. Treatment varies depending on the type of recurrent fever syndrome, although it frequently entails lifetime medication.

What Causes Inherited Periodic Fever Syndrome?

Genetic alterations are considered the main reason for the incidence of inherited periodic fever. The majority of autoinflammatory illnesses are inherited and manifest during childhood.

The types of inherited periodic fever syndrome and their genetic causes are given below.

• Familial Mediterranean Fever (FMF) - MEFV gene.

• Muckle-Wells Syndrome - NLRP3 gene.

• Hyperimmunoglobulinemia D with Recurrent Fever - MVK gene.

• TNF Receptor-Associated Periodic Syndrome (TRAPS) - TNFRSF1A gene.

• Neonatal Onset Multisystem Inflammatory Disease (NOMID) - NLRP3 gene.

• Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome (PFAPA) - Not yet identified.

What Are the Different Conditions That Come Under Inherited Periodic Fever Syndromes?

• Familial Mediterranean Fever (FMF) - Familial Mediterranean fever (FMF) is the most frequently inherited periodic fever. It is characterized by brief episodes of fever, stomach discomfort, and serositis lasting less than 72 hours. It can cause repeated fevers and painful inflammation in the child's abdomen, chest, and joints. Typically, FMF incidents begin in childhood. As the child grows older, the frequency and severity of their attacks may decrease.

• Hyperimmunoglobulin D syndrome (HIDS) - Hyperimmunoglobulin D syndrome (HIDS) is characterized by episodes of high fever, swollen lymph nodes in the neck, abdominal pain, arthritis, skin rashes, vomiting, and diarrhea. The condition usually manifests itself before the age of one year. The condition gets its name from the fact that most babies produce a lot of immunoglobulin type D.

• Periodic Fever, Aphthous-Stomatitis, Pharyngitis, and Adenitis (PFAPA) - Periodic fevers with mouth sores, a sore throat (pharyngitis), and enlarged lymph nodes in the child's neck are the symptoms of PFAPA. It affects children in their early childhood, usually before the age of four. After the age of ten, the frequency of episodes normally decreases and resolves.

• Neonatal Onset Multisystem Inflammatory Disease (NOMID) - NOMID causes fever and a skin rash. The symptoms of NOMID appear at birth or within the first few weeks of life. Two more disorders are caused by the same gene mutation associated with NOMID. They are Muckle-Wells syndrome and familial cold autoinflammatory syndrome. These three conditions are referred to as cryopyrin-associated autoinflammatory disorders.

• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) - In addition to fever, TRAPS can cause gastrointestinal pain, skin rashes, diarrhea, muscle aches, and swelling around the child's eyes. TRAPS usually appear from early childhood to late childhood or even into adulthood. This syndrome was previously known as familial Hibernian fever.

Is Inherited Periodic Fever Syndrome a Common Condition?

Inherited periodic fever syndrome is a rare condition. There are various types of diseases that fall under the category of inherited periodic fever syndrome. The frequency (that is, how frequently someone experiences the illness) of some conditions is unknown. The majority of the diseases under the umbrella of inherited periodic fever syndrome are extremely rare, but some are common. TNF receptor-associated periodic syndrome (TRAPS) affects one in one million people. However, one in 200 people in Mediterranean and Middle Eastern regions suffers from familial Mediterranean fever.

What Are the Symptoms Associated With Inherited Periodic Fever Syndrome?

Recurrent episodes of fever without any infection, autoimmune illness, or other underlying causes are the one common symptom that all inherited periodic fever syndromes share. The frequency of febrile episodes may vary depending on the syndrome and range from daily episodes to once per 10 years. The duration of a fever during an attack might range from hours to almost continuous, but it is usually typical for a certain syndrome. The temperature may rise to exceed 40 degrees Celsius at the peak of the fever. Between attacks, the affected person may feel fine and exhibit no symptoms. Only 10 percent of cases of inherited periodic fever syndrome occur in adulthood.

The common symptoms associated with inherited periodic fever syndrome are the following.

• Severe joint pain.

• Skin rashes.

• Swollen lymph nodes.

• Headaches.

• Loss of appetite.

• Abdominal pain.

• Premature birth.

• Muscle pain.

• Chills.

• Flu-like symptoms.

• Mouth sores.

What Are the Diagnostic Tests Used for Inherited Periodic Fever Syndrome?

• Clinical Examination - When a patient exhibits recurring fever episodes together with other inflammatory signs, inherited periodic fever syndromes need to be clinically suspected. However, if the attacks are persistent or very uncommon, the diagnosis may be challenging. A family history of such incidents is useful if it is known.

• Laboratory Tests - Inflammation can be detected using laboratory tests like a complete blood count (CBC) or a CRP (C-reactive protein). These tests turn positive during the attack and become negative thereafter (returning to normal or very close to normal).

• Genetic Testing -If genetic testing is positive, it can often be conclusive. However, not all mutations are known or easily tested for. A negative test does not rule out the possibility of a diagnosis. In these circumstances, a clinical diagnosis must be made. In 20 % of patients with clinical symptoms suggestive of an inherited periodic fever syndrome, genetic testing of the MEFV, MVK, and genes reveals a mutation.

What Are the Treatment Options Available for Inherited Periodic Fever Syndrome?

• Treatment for inherited fever syndrome varies depending on the type. Although there is no cure for the illnesses, treatment focuses on relieving the child's symptoms with medication.

• Hereditary recurrent fever syndrome acute attacks are often managed with bed rest, anti-inflammatory medications, analgesics, and occasionally systemic corticosteroids. Aspirin or Paracetamol has no effect on the fever.

• When recognized triggers are avoided, the frequency of attacks can be reduced. Patients with familial cold-associated syndrome (FCAS) frequently relocate to temperate locations to avoid triggers.

• Continuous treatment may be required for some types to prevent febrile episodes. Aside from Colchicine for familial Mediterranean fever, biological medicines such as Canakinumab are used to treat inherited periodic fever syndrome.

Conclusion

Inherited periodic fever syndromes are hereditary disorders that cause recurrent episodes of fever. If the child has a family history of any of the conditions under inherited periodic fever or has repeated fevers, contact a healthcare provider as soon as feasible. The child must have an accurate diagnosis to receive appropriate treatment. To avoid the development of life-threatening consequences in inherited periodic fever syndromes, treatment should be initiated as soon as possible.