Monogenic autoinflammatory diseases: concept and clinical manifestations

Abstract

The objective of this review is to describe the clinical manifestations of the growing spectrum of monogenic autoinflammatory diseases including recently described syndromes. The autoinflammatory diseases can be grouped based on clinical findings: 1. the three classic hereditary "periodic fever syndromes", familial Mediterranean Fever (FMF); TNF receptor associated periodic syndrome (TRAPS); and mevalonate kinase deficiency/hyperimmunoglobulinemia D and periodic fever syndrome (HIDS); 2. the cryopyrin associated periodic syndromes (CAPS), comprising familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID) or CINCA, and; 3. pediatric granulomatous arthritis (PGA); 4. disorders presenting with skin pustules, including deficiency of interleukin 1 receptor antagonist (DIRA); Majeed syndrome; pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome; deficiency of interleukin 36 receptor antagonist (DITRA); CARD14 mediated psoriasis (CAMPS), and early-onset inflammatory bowel diseases (EO-IBD); 5. inflammatory disorders caused by mutations in proteasome components, the proteasome associated autoinflammatory syndromes (PRAAS) and 6. very rare conditions presenting with autoinflammation and immunodeficiency.

Figure 1

A1 – Urticarial rash in neonatal-onset multisystem inflammatory disease, (NOMID), A2 – Severe hydrocephalus in NOMID syndrome, A3 – Papilledema in NOMID syndrome, B1 – Anterior synechiae in Blau syndrome chronic uveitis, B2 – Left arm ichthyosis-like exanthema in Blau syndrome, C1 – Generalized pustulosis in deficiency of interleukin-1 receptor antagonist (DIRA), C2 – Amplified image of DIRA skin rash, D1 – Sagittal image in fat suppressed T1 sequence showing synovial thickening and enhancement with moderate fluid in the right elbow joint in pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome, D2 - Extense left lower leg pyoderma gangrenosum lesion in (PAPA) syndrome, E – Generalized psoriasis in CARD14 mediated psoriasis (CAMPS), F1 – Erythematous, annular and nodular rash in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome, F2 - Lipodystrophy (black arrows) and acanthosis nigricans (red arrow) in CANDLE syndrome