The pathogenesis of YAOS is unclear, but clinical manifestations are thought to be secondary to the overactivation of the innate immune system. NOD2 is a cytosolic receptor molecule that functions to initiate an inflammatory response following the recognition of bacterial cell wall components. Dysfunction of this pathway results in the overproduction of proinflammatory cytokines. Although the development of YAOS is secondary to a genetic mutation, only a small percentage of those affected have a family history of the disease. YAOS predominantly presents in adults aged 20-50 years with a female-to-male ratio of 2:1, but pediatric cases have also been reported.
YAOS is a chronic episodic disease that presents at an interval of several weeks to months and can last for several days. The clinical presentation can range greatly and affect multiple body systems. Patients most commonly experience prodromal flu-like symptoms followed by a high-grade fever and a rash comprised of minimally pruritic erythematous patches and plaques, primarily on the trunk, limbs, and face. The genitals and perianal area are typically spared. Skin lesions may last for hours to months but typically resolve in several days. Other common manifestations include musculoskeletal, gastrointestinal, and sicca-like symptoms (including dry eyes, blurred vision, eyelid swelling, and dry mouth). Episodes of inflammatory arthritic joint pain are common and may be accompanied by distal extremity swelling. All joints can be affected; the small and large joints of the lower extremities are more frequently involved. Gastrointestinal symptoms include non-bloody diarrhea and abdominal pain. Patients can experience weight loss, but there is typically no progression to malnutrition. Although YAOS is a systemic disease, it rarely affects solid organs.
M04.8 – Other autoinflammatory syndrome
768667002 – Nucleotide binding oligomerization domain containing 2-associated autoinflammatory disease
Differential Diagnosis & Pitfalls
- Familial Mediterranean fever
- Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
- Blau syndrome (BS) – Characterized by the triad of granulomatous dermatitis, uveitis, and inflammatory arthritis presenting in childhood. In YAOS, panuveitis, choroiditis, and pediatric presentation are rare.
- NLRP12 autoinflammatory syndrome
- Hyperimmunoglobulin D (IgD) syndrome (HIDS) / mevalonate kinase deficiency
- Cryopyrin-associated periodic syndrome
- Crohn disease (CD) – Cutaneous manifestations are erythema nodosum and pyoderma gangrenosum. In YAOS, bloody diarrhea is often absent.