What are the other Names for this Condition? (Also known as/Synonyms)

• Familial Hibernian Fever
• TNF Receptor-Associated Periodic Syndrome (TRAPS)
• Tumor Necrosis Factor Associated Periodic Syndrome

What is Tumor Necrosis Factor Receptor-Associated Periodic Syndrome? (Definition/Background Information)

• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is a rare autoinflammatory disorder characterized by recurrent episodes of inflammation and fever. It belongs to a group of conditions known as hereditary periodic fever syndromes
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome is caused by mutations in the TNFRSF1A gene, which provides instructions for producing the tumor necrosis factor receptor 1 (TNFR1) protein. Tumor necrosis factor (TNF) is a cytokine involved in the body's immune response and inflammation regulation. In TRAPS, mutations in the TNFRSF1A gene lead to dysfunctional TNFR1 proteins, resulting in uncontrolled or excessive inflammation
• The episodes of inflammation in Tumor Necrosis Factor Receptor-Associated Periodic Syndrome can vary in duration, from days to weeks, and are typically accompanied by fever. The common signs and symptoms include abdominal pain, muscle and joint pain, rash, and swelling in various body parts, such as the extremities, face, and lymph nodes
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome can present at any age, but symptom onset typically occurs during childhood. The severity and frequency of episodes can vary among individuals, with some experiencing milder and less frequent episodes while others may have more severe and frequent manifestations
• Early diagnosis of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome is important to guide appropriate management and prevent complications. The treatment aims to control inflammation, alleviate symptoms during episodes, and reduce the frequency and severity of episodes. Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and biologic agents targeting TNF, such as etanercept or adalimumab, are commonly used therapeutic options
• While Tumor Necrosis Factor Receptor-Associated Periodic Syndrome is a lifelong condition, with proper management and treatment, many individuals can lead productive lives with improved symptom control and reduced frequency of episodes. Regular monitoring and collaboration with healthcare professionals experienced in managing autoinflammatory disorders, such as rheumatologists or immunologists, are essential for ongoing care and treatment optimization
• Early diagnosis of TRAPS is crucial to initiate appropriate treatment and prevent complications. Regular monitoring and follow-up with healthcare professionals experienced in managing TRAPS are essential for ongoing care and treatment optimization

Who gets Tumor Necrosis Factor Receptor-Associated Periodic Syndrome? (Age and Sex Distribution)

• Although rare (prevalence estimated at less than 1 in 1 million individuals), Tumor Necrosis Factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) is considered to be the second most common of the inherited periodic fever syndromes. More than 1000 cases have been reported
• TRAPS can affect individuals of any age, including children and adults. However, the onset of symptoms typically occurs during childhood, with most cases presenting in the first year of life or early childhood
• No clear gender bias is observed, and both males and females can be affected by the condition

Due to its rarity, there may be underdiagnosis or misdiagnosis of TRAPS, and the exact age and gender distribution may vary among reported cases.

What are the Risk Factors for Tumor Necrosis Factor Receptor-Associated Periodic Syndrome? (Predisposing Factors)

The primary risk factor for Tumor Necrosis Factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) is having a specific genetic mutation (in the TNFRSF1A gene). Inheriting a mutated copy of this gene from one or both parents increases the risk of developing TRAPS.

• TRAPS follows an autosomal dominant inheritance pattern, meaning that an affected individual has a 50% chance of passing the mutated gene on to each of their children. However, it's important to note that not all individuals with the TNFRSF1A mutation will develop TRAPS, and the severity of symptoms can vary even among family members with the same mutation.
• While the TNFRSF1A gene mutation is the primary risk factor for TRAPS, the presence of the mutation alone is insufficient to guarantee the condition's development. Other factors, such as genetic modifiers or environmental triggers, may contribute to disease expression variability and severity.
• Not all cases of TRAPS occur within a family kindred. Spontaneous mutations in the TNFRSF1A gene occur after the original DNA pattern of an individual has been established at conception.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome? (Etiology)

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is caused by mutations in the TNFRSF1A gene. The TNFRSF1A gene provides instructions for producing the tumor necrosis factor receptor 1 (TNFR1) protein. Mutations in this gene lead to dysfunctional TNFR1 proteins, which regulate inflammation and the immune response.

• The exact mechanism by which mutations in TNFRSF1A lead to the development of TRAPS is not fully understood. However, these mutations are believed to result in abnormal functioning or reduced levels of the TNFR1 protein, leading to an impaired ability to control inflammation. This results in episodes of excessive or uncontrolled inflammation in affected individuals.
• TNFR1 normally interacts with tumor necrosis factor (TNF), a cytokine involved in inflammation and immune responses. The dysfunctional TNFR1 protein in TRAPS may disrupt the normal signaling pathway, leading to an exaggerated immune response and the characteristic symptoms of the condition.
• Genetic mutations in the TNFRSF1A gene primarily cause TRAPS, and the disorder is unrelated to external factors or environmental triggers. The condition follows an autosomal dominant inheritance pattern, meaning that a person with a mutated TNFRSF1A gene has a 50% chance of passing the mutation to each of their children. Spontaneous mutations occur in some individuals with no genetic family members carrying the defective TNFRSF1A gene.
• Further research is ongoing to understand better the underlying mechanisms of TRAPS and how specific genetic mutations contribute to the development of the condition.

What are the Signs and Symptoms of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome?

Tumor Necrosis Factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) is characterized by recurrent episodes of inflammation and fever. The signs and symptoms of TRAPS can vary among individuals, but common features include:

• Fever: Recurrent episodes of prolonged fever, typically lasting for several days to three weeks. Chills and general malaise may accompany the fever.
• Abdominal Pain: Abdominal pain is a common symptom in TRAPS. It can be severe and migratory, which may move from one area to another within the abdomen. The pain is often associated with inflammation of the abdominal lining (peritonitis) and can mimic conditions such as appendicitis.
• Muscle and Joint Pain: Individuals with TRAPS may experience muscle and joint pain during episodes of inflammation. The pain can affect multiple joints and muscles, possibly migratory or persistent.
• Skin Manifestations: Skin symptoms are observed in some individuals with TRAPS. These can include rash, redness, or swelling in various body areas, such as the limbs or face. Some skin lesions appear urticarial (like hives). One characteristic of the rash of TRAPS is associated with severe deep pain, seemingly greater than would be expected from the appearance of the rash. This may reflect myalgia beneath and associated with the rash.
• Eye Involvement: Eye inflammation, uveitis and/or conjunctivitis are seen in a subset of individuals with TRAPS. It may present as redness, pain, sensitivity to light, or blurred vision. In addition, periorbital edema (swelling of the tissues around the eyes) is a relatively specific feature of TRAPS.
• Swelling and Lymph Node Enlargement: Swelling, particularly in the extremities, such as the hands and feet, may occur during TRAPS episodes. Lymph nodes may also become enlarged.
• The tissues surrounding and enfolding the heart and lungs, the pericardium, and the pleura may become inflamed. This produces chest pain and fluid accumulation, compromising heart and lung function.

After the disease has been present for a long time, secondary amyloid proteins can build up in the kidneys and liver, causing poor function of these organs.

The episodes of symptoms in TRAPS can vary in duration, with asymptomatic intervals between episodes. The frequency and severity of episodes can also vary among individuals, with some experiencing more frequent and severe manifestations while others have milder episodes.

How is Tumor Necrosis Factor Receptor-Associated Periodic Syndrome Diagnosed?

Diagnosing Tumor Necrosis Factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) involves a combination of clinical evaluation, genetic testing, and exclusion of other possible causes of recurrent fever and inflammation. The signs and symptoms of TRAPS can overlap with other conditions, making diagnosis challenging.

The steps involved in diagnosing the disorder include:

• Medical History and Physical Examination: A detailed medical history is taken to assess the pattern, frequency, and duration of symptoms, such as recurrent fever, abdominal pain, and joint/muscle pain. A thorough physical examination is conducted to identify any characteristic signs or symptoms of TRAPS, including skin manifestations or lymph node enlargement.
• Genetic Testing: Genetic testing plays a crucial role in diagnosing TRAPS. It involves analyzing the TNFRSF1A gene for mutations. A blood sample is collected, and DNA sequencing is performed to identify mutations in the TNFRSF1A gene. The presence of a mutation confirms the diagnosis of TRAPS. However, not all individuals with TRAPS have identifiable mutations, and some genetic variants may require further evaluation to determine their significance.
• Exclusion of Other Conditions: Since the symptoms of TRAPS can overlap with other conditions, it is important to exclude other potential causes of recurrent fever and inflammation. This may involve additional laboratory tests, imaging studies, or consultations with specialists based on the specific presentation.
• Clinical Criteria: In the absence of genetic testing or in cases where genetic testing does not identify mutations, the diagnosis of TRAPS can be made based on clinical criteria. These criteria include recurrent episodes of fever lasting longer than three days and at least one of the following: abdominal pain, muscle/joint pain, skin manifestations, or eye involvement.
• Family History: A family history of TRAPS or other hereditary periodic fever syndromes can also support the diagnosis, although it may not be present in all cases.

Diagnosing TRAPS can be challenging due to its rarity and variability in symptoms. Therefore, consulting with a healthcare professional or a rheumatologist experienced in diagnosing and managing autoinflammatory diseases is recommended. They can guide the diagnostic process, interpret genetic testing results, and consider other relevant factors to establish an accurate diagnosis.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome?

Tumor Necrosis Factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) can be associated with various complications, which may vary among individuals. Some possible complications include:

• Amyloidosis: One of the most significant complications of TRAPS is the development of secondary amyloidosis. Amyloidosis occurs when abnormal protein deposits called amyloids accumulate in organs and tissues, leading to organ damage and dysfunction. The kidneys are commonly affected, resulting in renal impairment.
• Joint Damage: Recurrent episodes of joint inflammation in TRAPS can lead to progressive joint damage over time. Persistent inflammation can result in cartilage destruction, joint deformities, and functional limitations.
• Ocular Complications: Eye inflammation (uveitis) is a known complication of TRAPS. If left untreated or inadequately managed, uveitis can lead to various complications, including vision loss, glaucoma, cataracts, and other eye-related issues.
• Skin Manifestations: Severe skin manifestations in TRAPS, such as rash, swelling, or skin ulcers, may result in scarring, pigmentation changes, or disfigurement. Skin complications can affect the individual's self-esteem and quality of life.
• Secondary Infections: During episodes of inflammation and compromised immune function, individuals with TRAPS may be more susceptible to secondary infections. Prompt infection management is crucial to prevent complications and minimize the risk of severe infections.
• Psychosocial Impact: The chronic and unpredictable nature of TRAPS, along with its impact on daily life and activities, can lead to psychological and emotional challenges. Individuals with TRAPS can experience anxiety, depression, social isolation, and reduced quality of life.

Not all individuals with Tumor Necrosis Factor Receptor-Associated Periodic Syndrome will experience the above complications. The severity and occurrence of complications can vary among individuals, and early diagnosis, appropriate management, and regular monitoring can help minimize the risk and impact of these complications. Prompt recognition and management of complications are important to optimize long-term outcomes and quality of life for individuals with TRAPS.

How is Tumor Necrosis Factor Receptor-Associated Periodic Syndrome Treated?

The treatment of Tumor Necrosis Factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) aims to control inflammation, reduce the frequency and severity of episodes, alleviate symptoms, and prevent complications. The treatment approach may vary depending on the individual's symptoms, disease severity, and therapy response. Some common treatment strategies for TRAPS:

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): NSAIDs, such as ibuprofen or naproxen, may be prescribed to help manage pain, reduce inflammation, and alleviate symptoms during TRAPS episodes. They can be used as a first-line treatment for mild to moderate symptoms.
• Corticosteroids: Corticosteroids, such as prednisone, may be prescribed during severe episodes or if NSAIDs are insufficient to control inflammation. They can help reduce inflammation and alleviate symptoms. However, their long-term use is generally avoided due to potential side effects.
• Disease-modifying Antirheumatic Drugs (DMARDs): DMARDs, such as methotrexate or sulfasalazine, may be prescribed for individuals with more severe or refractory TRAPS. These medications help modulate the immune system and reduce inflammation. DMARDs are typically used in combination with other therapies and under the guidance of a rheumatologist.
• Biologic Agents: Biologic therapies targeting tumor necrosis factor (TNF), such as etanercept or adalimumab, may be used in individuals with moderate to severe TRAPS symptoms or those who do not respond adequately to other treatments. These medications specifically block the action of TNF, reducing inflammation and preventing episodes. Biologic agents are typically reserved for individuals with more severe disease manifestations and are prescribed under the care of a rheumatologist. The most commonly used have been anakinra and canakinumab (FDA-approved), decreasing inflammation from Interleukin-1 beta. A case resistant to these two medications responded to tocilizumab, an Interleukin-6 inhibitor.
• Supportive Care: Supportive measures, such as physical therapy, occupational therapy, or joint protection techniques, can help manage pain, improve mobility, and enhance overall quality of life. Adequate pain management, counseling, and psychosocial support are important components of supportive care.

Treatment for TRAPS is often individualized based on the specific needs and symptoms of the individual. Regular monitoring, follow-up appointments, and communication with healthcare professionals experienced in managing autoinflammatory disorders, such as rheumatologists, are crucial for ongoing care, treatment adjustments, and evaluation of treatment response.

Tumor Necrosis Factor Receptor-Associated Periodic Syndrome is also a chronic condition, and treatment may require long-term management. Collaboration with healthcare professionals and adherence to treatment recommendations are key factors in managing the condition and improving outcomes.

In addition to medical treatment, individuals with TRAPS may benefit from lifestyle measures such as stress management, regular exercise, a balanced diet, and maintaining a supportive network. These measures can help optimize overall well-being and potentially reduce the impact of TRAPS on daily life.

How can Tumor Necrosis Factor Receptor-Associated Periodic Syndrome be Prevented?

Tumor Necrosis Factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) is a genetic condition caused by mutations in the TNFRSF1A gene. As such, it is not currently possible to prevent the development of TRAPS, as the underlying genetic mutations are inherited.

However, there are strategies to manage and minimize the impact of TRAPS on an individual's life. These strategies focus on early diagnosis, prompt treatment, and preventive measures to reduce the frequency and severity of episodes, prevent complications, and enhance overall well-being. Here are some measures that can be taken:

• Early Diagnosis and Treatment: Prompt recognition and diagnosis of TRAPS are crucial to initiating appropriate treatment and preventing complications. If you experience symptoms consistent with TRAPS, such as recurrent fever, abdominal pain, or joint/muscle pain, it is important to consult a healthcare professional or rheumatologist experienced in diagnosing and managing autoinflammatory disorders.
• Regular Monitoring and Follow-up: Regular monitoring and follow-up appointments with healthcare professionals are essential for ongoing care and treatment optimization. Regular assessments can help identify any changes in disease activity, adjust treatment plans as needed, and prevent complications.
• Treatment Adherence: Adhering to the prescribed treatment plan is important for managing TRAPS effectively. This includes taking medications as directed, attending follow-up appointments, and communicating any changes or concerns to your healthcare team.
• Lifestyle Measures: Leading a healthy lifestyle can support overall well-being and potentially reduce the impact of TRAPS. This includes maintaining a balanced diet, exercising regularly, managing stress levels, getting adequate sleep, and avoiding known triggers that may exacerbate symptoms.
• Infection Prevention: During TRAPS episodes, the immune system may be compromised, making individuals more susceptible to infections. Practicing good hygiene, such as regular handwashing, avoiding close contact with individuals with infectious illnesses, and staying up to date with vaccinations, can help reduce the risk of secondary infections.
• Genetic Counseling: If you have a family history of TRAPS or other hereditary periodic fever syndromes, genetic counseling can provide information about the condition, assess the risk of passing on the mutation, and guide family planning decisions.

While these measures can help manage Tumor Necrosis Factor Receptor-Associated Periodic Syndrome and reduce the impact of the condition, TRAPS is a lifelong condition, and complete prevention of episodes or complications may not be possible. Collaboration with healthcare professionals experienced in managing TRAPS and adherence to recommended treatment and lifestyle measures are essential for optimizing outcomes and maintaining the best possible quality of life.

What is the Prognosis of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome? (Outcomes/Resolutions)

The prognosis of Tumor Necrosis Factor (TNF) Receptor-Associated Periodic Syndrome (TRAPS) varies among individuals and can range from mild to severe. The long-term outcomes of TRAPS depend on factors such as the severity and frequency of episodes, response to treatment, and complications. A few considerations regarding the prognosis of TRAPS include:

• Variable Disease Course: The course of TRAPS can vary significantly among individuals. Some individuals may experience relatively mild and infrequent episodes, while others may have more frequent and severe manifestations. The disease course can also change over time, with periods of remission and relapse.
• Quality of Life: TRAPS can significantly impact an individual's quality of life during episodes of inflammation and fever. The unpredictable nature of the condition, along with associated symptoms such as abdominal pain, joint/muscle pain, and skin manifestations, can disrupt daily activities and affect overall well-being.
• Response to Treatment: Early diagnosis and appropriate treatment can significantly improve outcomes for individuals with TRAPS. With the right treatment approach, many individuals can achieve symptom control, reduce the frequency and severity of episodes, and lead productive lives.
• Complications: The occurrence of complications, such as amyloidosis, kidney, liver, or heart dysfunction, or joint damage, can influence the long-term prognosis of TRAPS. Prompt diagnosis, timely management, and regular monitoring are important to detect and manage complications early, minimizing their impact on overall health.
• Psychological Impact: The chronic and unpredictable nature of TRAPS, along with its impact on daily life and activities, can contribute to psychological and emotional challenges. Anxiety, depression, and reduced quality of life are potential outcomes that may require supportive care and appropriate management.

The prognosis of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome can vary among individuals, and early diagnosis and appropriate management are crucial for optimizing outcomes. Regular monitoring and follow-up with healthcare professionals experienced in managing autoinflammatory disorders, such as rheumatologists, are important for ongoing care, treatment optimization, and evaluation of treatment response.

Collaboration with healthcare professionals, adherence to treatment recommendations, and proactive management of symptoms and complications are key factors in managing TRAPS and improving the prognosis and quality of life for individuals with the condition.

Ongoing research and medical advancements contribute to a better understanding of TRAPS and may lead to improved treatments and outcomes in the future.

Additional and Relevant Useful Information for Tumor Necrosis Factor Receptor-Associated Periodic Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/