Autoinflammatory Diseases

Understanding Autoinflammatory Diseases

Autoinflammatory diseases are mediated by hyperactivation of the innate immune system and driven by dysregulated cytokine production^1,2

Many of these diseases are characterized by^3,4:

Recurrent fevers
Fatigue

Rash
Gastrointestinal, neurologic, musculoskeletal, and dermatologic manifestations

The awareness of autoinflammatory diseases is still limited, and as a result, it may take years or even decades to reach a diagnosis.³

Many autoinflammatory diseases start in early childhood and can present with considerable quality-of-life impairment. These diseases may present in several members of a family. Other autoinflammatory diseases appear to be acquired, perhaps due to the interplay of genetic and environmental factors, and can present at any time during childhood or adulthood.^3,4

Autoinflammatory diseases are divided into 2 categories: monogenic or polygenic^5-7

At a Glance: Monogenic Diseases

Monogenic autoinflammatory diseases are caused by a mutation that occurs in a single gene. Several periodic fever syndromes (PFS) are examples of monogenic diseases, including^5-7:

Familial Mediterranean fever (FMF)
Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD)
Tumor necrosis factor receptor–associated periodic syndrome (TRAPS)
Cryopyrin-associated periodic syndrome (CAPS):
- Familial cold autoinflammatory syndrome (FCAS)
- Muckle-Wells syndrome (MWS)
- Neonatal-onset multisystem inflammatory disease (NOMID)
Additional examples of monogenic diseases include⁶:
- NALP-associated periodic fever
- Deficiency of the interleukin-1 receptor antagonist (DIRA)
- Blau syndrome
- Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome
- Majeed syndrome

At a Glance: Polygenic Diseases

Polygenic or multifactorial autoinflammatory diseases are complex systemic disorders. These disorders share an autoinflammatory and sometimes an autoimmune background. Still’s disease is one example of polygenic disease and includes⁸:

Systemic juvenile idiopathic arthritis (SJIA)
Adult-onset Still’s disease (AOSD)
Additional examples of polygenic diseases include⁶:
- Behçet’s disease
- Sweet’s disease
- Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome
- Chronic recurrent multifocal osteomyelitis (CRMO)

Autoinflammatory diseases are divided into 2 categories

LEARN ABOUT MONOGENIC DISEASEs

LEARN ABOUT POLYGENIC DISEASES

AOSD=adult-onset Still’s disease; CAPS=cryopyrin-associated periodic syndromes; CRMO=chronic recurrent multifocal osteomyelitis; DIRA=deficiency of the interleukin-1 receptor antagonist; FCAS=familial cold autoinflammatory syndrome; FMF=familial Mediterranean fever; HIDS=hyperimmunoglobulin D syndrome; IL-1β=interleukin 1 beta; MKD=mevalonate kinase deficiency; MWS=Muckle-Wells syndrome; NOMID=neonatal-onset multisystem inflammatory disease; PAPA=pyogenic arthritis, pyoderma gangrenosum, and acne; PFAPA=periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis; PFS=periodic fever syndromes; SJIA=systemic juvenile idiopathic arthritis; TRAPS=tumor necrosis factor receptor–associated periodic syndrome.

References: 1. Shaw PJ, McDermott MF, Kanneganti T-D. Inflammasomes and autoimmunity. Trends Mol Med. 2011;17(2):57-64. doi:10.1016/j.molmed.2010.11.001 2. Rossi-Semerano L, Koné-Paut I. Is Still’s disease an autoinflammatory syndrome? Int J Inflam. 2012;2012:480373. doi:10.1155/2012/480373 3. Bonnekoh H, Krause K. How to diagnose and manage systemic autoinflammatory diseases in childhood. Curr Treat Options Allergy. 2015;2:235-245. doi:10.1007/s40521-015-0061-1 4. Cush JJ. Autoinflammatory syndromes. Dermatol Clin. 2013;31(3):471-480. doi:10.1016/j.det.2013.05.001 5. Federici S, Gattorno M. A practical approach to the diagnosis of autoinflammatory diseases in childhood. Best Pract Res Clin Rheumatol. 2014;28(2):263-276. doi:10.1016/j.berh.2014.05.005 6. Ciccarelli F, De Martinis M, Ginaldi L. An update on autoinflammatory diseases. Curr Med Chem. 2014;21(3):261-269. doi:10.2174/09298673113206660303 7. Glaser RL, Goldbach-Mansky R. The spectrum of monogenic autoinflammatory syndromes: understanding disease mechanisms and use of targeted therapies. Curr Allergy Asthma Rep. 2008;8(4):288-298. doi:10.1007/s11882-008-0047-1 8. Figueras-Nart I, Mascaró JM Jr, Solanich X, Hernández-Rodríguez J. Dermatologic and dermatopathologic features of monogenic autoinflammatory diseases. Front Immunol. 2019;10:2448. doi:10.3389/fimmu.2019.02448

Autoinflammatory Diseases

Understanding Autoinflammatory Diseases