Autoinflammatory syndrome

Autoinflammatory Syndrome

Autoinflammatory syndromes are a group of disorders characterized by recurrent episodes of systemic inflammation without the high-titer autoantibodies or antigen-specific T cells that are typical of autoimmune diseases. These syndromes are primarily caused by genetic mutations that affect the innate immune system, leading to inappropriate activation and inflammation.

Overview

Autoinflammatory syndromes are distinct from autoimmune diseases in that they do not involve the adaptive immune system. Instead, they are caused by dysregulation of the innate immune system, which is the body's first line of defense against pathogens. The innate immune system includes cells such as neutrophils, macrophages, and dendritic cells, as well as proteins like cytokines and the complement system.

Pathophysiology

The pathophysiology of autoinflammatory syndromes involves mutations in genes that regulate the innate immune response. These mutations lead to the overproduction of pro-inflammatory cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). This results in episodes of fever, rash, joint pain, and other inflammatory symptoms.

Some of the key genes involved in autoinflammatory syndromes include:

• MEFV: Mutations in this gene cause Familial Mediterranean Fever (FMF), which is characterized by recurrent fevers and serositis.
• NLRP3: Mutations in this gene are associated with Cryopyrin-Associated Periodic Syndromes (CAPS), which include conditions such as Muckle-Wells syndrome and Chronic Infantile Neurological Cutaneous Articular syndrome (CINCA).
• TNFRSF1A: Mutations in this gene lead to Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS).

Clinical Features

Patients with autoinflammatory syndromes typically present with recurrent episodes of fever, rash, and joint pain. Other symptoms may include abdominal pain, chest pain, and fatigue. The frequency and severity of these episodes can vary widely among individuals and different syndromes.

Diagnosis

Diagnosis of autoinflammatory syndromes is based on clinical presentation, family history, and genetic testing. Laboratory tests may show elevated inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) during episodes.

Treatment

Treatment of autoinflammatory syndromes often involves the use of anti-inflammatory medications. Colchicine is commonly used for FMF, while IL-1 inhibitors such as anakinra and canakinumab are effective for CAPS. TNF inhibitors may be used for TRAPS.

Also see

• Autoimmune disease
• Innate immune system
• Cytokine
• Genetic mutation