Study of the Pathophysiological Mechanisms Involved in the SAPHO Syndrome: Genetic Component and Immune Response

SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is a chronic inflammatory rheumatism associating bone or joint lesions and dermatological manifestations dominated by severe acne and palmar and palmoplantar pustulosis. Prevalence of SAPHO syndrome is estimated at 1/50000 in France, but this figure is probably underestimated due to frequent misdiagnosis. Osteoarticular manifestations form a rheumatic picture very similar to that of other forms of spondyloarthritis (SpA). The latest French recommendations do not distinguish SAPHO syndrome from other forms of SpA. As a result, the management of SAPHO remains fairly heterogeneous, essentially based on the local experience of rheumatologists. Delays in diagnosis and difficulties in finding effective treatment can result in significant disability and reduced quality of life, particularly detrimental in a young population (age at diagnosis is usually between 30 and 40). The wide spectrum of clinical presentations of SAPHO syndrome explains the complexity of managing this condition. Understanding the pathophysiological mechanisms underlying these different forms of the disease is a major challenge for personalized medicine. SAPHO syndrome is a multifactorial disease that is a result of interaction of genetic, environmental, immunological and infectious factors. In the classification of immune-mediated inflammatory diseases, SAPHO syndrome lies midway between autoinflammatory diseases involving the innate immune response and spondyloarthritis associated with abnormalities in the adaptive immune response. Indeed, while the clinical phenotype may resemble spondyloarthritis in certain aspects, the identification of genetic forms of chronic relapsing osteitis, such as DIRA syndrome or Majeed syndrome, argues in favor of an autoinflammatory origin of SAPHO syndrome. Although osteitis is reputed to be sterile, an infectious initiating factor has long been suspected in this disease. Among the bacterial agents, antigens antigens from Cutibacterium acnes were detected in bone biopsies from patients with SAPHO syndrome. It has been suggested that this bacterium may play a role in triggering a systemic inflammatory response systemic inflammatory response mediated in particular by IL-1β.

NCT Number	NCT07081880
Lead Sponsor	Fondation Hôpital Saint-Joseph
Conditions	SAPHO Syndrome
Enrollment	100 participants
Start Date	2025-07-15
Primary Completion	2028-07-15 (estimated)
Study Completion	2035-05-15 (estimated)
Updated on ClinicalTrials.gov	2025-12-24