Autoinflammatory syndromes.

What are they autoinflammatory syndromes?

Autoinflammatory syndromes are defined as conditions caused by an exaggerated response of the innate immune system that results in spontaneous episodes inflammation affecting multiple organs. An autoinflammatory syndrome can only be diagnosed when there are infectious conditions, malignancy, allergic and immunodeficiency conditions have been excluded. Compared to the classic autoimmune diseases, autoinflammatory syndromes lack pathogen autoantibodies and antigen-specific T cells.

Classification of autoinflammatory syndromes.

Autoinflammatory syndromes can be inherited through mutations to a single gene (monogenic autoinflammatory syndromes) or, more commonly, are polygenic immune conditions that resemble autoimmune collagen disorders The number of conditions included increases as molecular and genetic Studies reveal the mechanisms of the disease.

A classification system is presented below, with examples of syndromes with dermatological manifestations.

Hereditary fever syndromes

• Family Mediterranean fever (FMF)
• Tumor necrosis factor receiverassociated periodic fever syndrome (TRAPS)
• Hyper-IgD syndrome (HIDS)

Other monogenic autoinflammatory syndromes

• Cryopyrin-associated periodic syndromes (CAPS)

  • Familial cold autoinflammatory syndrome (FCAS)
  • Muckle-Wells syndrome (MWS)
  • Neonatal multi-system startup inflammatory disease/chronic Child neurological cutaneous arthropathy syndrome (NOMID / CINCA)
• Syndrome of pyogenic arthritis, pyoderma gangrenosum and acne (PAPA syndrome, PAPAS, PAPGA syndrome)
• Youth systemic granulomatosis (Blau syndrome, early-onset sarcoidosis)
• Deficiency of interleukin-1 receptor antagonist (DIRA)
• Mevalonic aciduria
• Majeed syndrome

Non-hereditary or polygenic disorders.

• Schnitzler's syndrome
• Crohn's disease
• Behcet's disease
• Hidradenitis suppurativa
• Psoriasic arthritis
• Periodic fever syndrome, foot and mouth stomatitis, pharyngitis and adenitis (PAPAS, PFAPA syndrome)
• Juvenile systemic onset idiopathic arthritis
• Adult-onset disease

Innate immune system

The innate immune system is a primitive inherited system to recognize danger in the form of injury or infection. Macrophages and dendritic cells carry receivers that bind to pathogenassociated molecular patterns (PAMPs), which are components of the microbial cell wall that are consistently expressed by bacteria and viruses, or hazard-associated molecular patterns (DAMPs), that are produced by the body in response to injury or infection. Pattern recognition receptors are inherited and do not adapt or change with experience. The binding of these receptors coordinates an initial inflammatory response that involves neutrophils and monocytes and the production of cytokines such as interleukin 1 (IL-1). IL-1 is activated within the cytoplasm of neutrophils and monocytes by inflammasomes, large protein complexes that include the activation enzyme caspase-1. Activated IL-1 is the strongest known trigger for fever. Also activates lymphocytes and promotes white blood cells infiltration at sites of injury or infection.

Genetic mutations affecting components of the inflammasome or the inflammatory response activated by IL-1 have been found in several of the monogenic autoinflammatory syndromes. Mutations can cause inflammation of the inflammasome or fail to limit IL-1-mediated inflammation. Autoinflammatory diseases that are not considered genetic are associated with inherited diseases. polymorphisms of proteins such as gamma-secretase and Notch-associated proteins, resulting in deregulation of inflammasome when exposed to certain triggers. These include hormones, smoking, adipokines associated with insulin resistance and obesity.

In autoinflammatory syndromes, the effector pathways are hypersensitive to endogenous (DAMP) or exogenous (PAMP) molecular patterns, or are constitutively hyperactive, resulting in uncontrolled cytokine-mediated inflammation.

What is the treatment for autoinflammatory syndromes?

Treatment varies with the actual syndrome. In many ways, systemic corticosteroids have only a modest effect. Biological agents such as anakinra (which targets IL-1) result in dramatic and consistent improvement in syndromes where a clear link to IL-1 has been demonstrated. There is less consistent benefit in other conditions where a direct link to IL-1 has not been found.