NOD2-associated granulomatous autoinflammatory syndromes – a short update for clinicians

Abstract

NOD2 (nucleotide-binding oligomerization domain-2), a pattern recognition receptor, is involved in innate immune defense against pathogens, intestinal mucosal barrier integrity, gut microbiota composition, autophagy, immune homeostasis and inflammation. NOD2 mutations have been associated primarily with childhood diseases (Blau syndrome and sarcoidosis with early-onset, monogenic Crohn’s disease), but also with adult diseases (NOD2-associated autoinflammatory syndrome – NAID, also called Yao syndrome etc.). Intermediate forms between Blau syndrome and NAID have also been described. Blau’s disease and early-onset sarcoidosis are the familial and the sporadic forms respectively of a dominantly inherited rare monogenic autoinflammatory disease. Blau’s syndrome starts in early childhood, evolving with non-caseating granulomatous arthritis with prominent tenosynovitis, dermatitis with a “bronzed”, maculo-papular or scaly skin rash, and intermittent fever. Periodic fever, generalized lymphadenopathy, and granulomatous visceral involvement may be present. Therapy consists in systemic steroids, immunosuppressants and biologic drugs. In adults the NAID or Yao’s syndrome evolves with bouts of systemic inflammation with lower limbs swelling, tenosynovitis and non-erosive arthritis, fever and dermatitis. We discuss the differential diagnosis with other granulomatous diseases. Increased awareness is necessary regarding these rare diseases which may alter the quality of life or lead to disability, in order to improve their prognosis.