The autoinflammatory disorders are a group of immune-mediated inflammatory conditions that mimic infections and allergic conditions in their clinical presentation. These conditions (previously known also as "periodic fever syndromes") result from dysregulated activity of, intracellular molecular complexes, known as inflammasomes, that sense "danger" to the body and coordinate an initial immune response(1).

The primary associated morbidity is systemic amyloidosis (abnormal deposition of certain proteins called amyloids in various bodily areas), with a risk for kidney damage. Diagnostic testing is mostly limited to genetic testing(2).

Familial Mediterranean fever (FMF), mevalonate kinase deficiency (also known as hyper-IgD syndrome), and tumor necrosis factor (TNF) receptor-associated disease are characterized by periodic or recurrent episodes of systemic inflammation causing fever, rash, serositis (inflammation of serous tissues lining the lungs, heart), lymphadenopathy (enlargement of the lymph nodes) and arthritis. Although FMF affects mainly Jews, Turks, Arabs and Armenians, recent population studies suggest that other ethnic groups such as Italians and Greeks may be affected as well(3).

Cryopyrin is a protein essential for inflammasome activation and abnormalities of cryopyrin result in cryopyrin-associated periodic syndromes(CAPS). The mildest form is familial cold-associated syndrome, a more severe form is Muckle-Wells syndrome, and the most severe is neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome. These are characterized by chronic or recurrent episodes of systemic inflammation presenting with urticaria-like rash, arthritis, deafness and central nervous system and bone involvement.

Other disorders are dominated by the presence of sterile abscesses (with no associated pathogen e.g. bacteria) in the skin, joints, and bones (e.g. pyogenic sterile arthritis, pyoderma gangrenosum and acne syndrome, and Majeed syndrome).

Finally, some autoinflammatory syndromes present with noncaseating granulomatous inflammation affecting the joints, skin, and eyes (e.g. Blau's syndrome) (4). Treatment options of autoinflammatory syndromes include colchicin, TNF-alpha inhibitors and novel IL-1-targeted drugs(5,6).

1. Goldbach-Mansky R, Kastner DL. Autoinflammation: the prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. J Allergy Clin Immunol 2009;124:1141-1149.

2. Hoffman HM, Simon A. Recurrent febrile syndromes: what a rheumatologist needs to know. Nat Rev Rheumatol 2009;5:249-256.

3. Samuels J, Ozen S. Familial Mediterranean fever and the other autoinflammatory syndromes: evaluation of the patient with recurrent fever. Curr Opin Rheumatol 2006;18:108-117.

4. Gattorno M, Federici S, Pelagatti MA, Caorsi R, Brisca G, Malattia C et al. Diagnosis and management of autoinflammatory diseases in childhood. J Clin Immunol 2008;28 Suppl 1:S73-S83.

5. Farasat S, Aksentijevich I, Toro JR. Autoinflammatory diseases: clinical and genetic advances. Arch Dermatol 2008;144:392-402.

6. Hoffman HM. Therapy of autoinflammatory syndromes. J Allergy Clin Immunol 2009;124:1129-1138.