Clinical Research Directory

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.

Typological Study of Sleep Pathologies During Psoriatic Rheumatism and SAPHO Syndrome: Prospective Study Within the Paris Saint-Joseph Hospital Group"

Chronic inflammatory rheumatisms (CIR) are a source of motor disability and various comorbidities, particularly cardiovascular and metabolic. They also significantly impact patients' quality of life, including sleep disturbances. Among CIRs, psoriatic arthritis is a chronic inflammatory arthropathy associated with psoriasis, typically seronegative for rheumatoid factor. This heterogeneous disease affects peripheral and/or axial joints and can include extra-articular manifestations such as uveitis and chronic inflammatory bowel diseases. Its prevalence is estimated between 0.3% and 1% in the general population. SAPHO syndrome, similar to psoriatic arthritis, is characterized by specific bone involvement with a hypertrophic tendency, often affecting the axial skeleton and the anterior thoracic wall. Pain and inflammation are closely linked to sleep quality, creating a vicious cycle where pain disrupts sleep and poor sleep amplifies pain perception. Analgesic treatments, such as opioids, can also cause nocturnal respiratory pathologies, further disrupting sleep. Inflammatory processes are regulated by sleep, influencing plasma concentrations of CRP, IL6, and TNF production. Patients with psoriatic arthritis or SAPHO syndrome share common risk factors with Obstructive Sleep Apnea Syndrome (OSAS), such as obesity, hypertension, and metabolic syndrome. Sleep disorders are common in the general population and likely underdiagnosed in these patients. Several studies suggest a link between sleep disorders and these rheumatic conditions, affecting quality of life and exacerbating symptoms. Questionnaires like the Epworth and Pichot scales provide a more precise evaluation of these symptoms. However, objective sleep exploration through polysomnography has never been conducted in these patients. In summary, CIRs, particularly psoriatic arthritis and SAPHO syndrome, significantly impact patients' quality of life and sleep, necessitating appropriate evaluation and management of associated sleep disorders.

Study of the Efficacy and Safety of Etanercept Treatment in Patients With SAPHO Syndrome

The study includes adult patients with SAPHO syndrome (ORPHA: 793), meeting the modified classification criteria according to Kahn (2003), with the ineffectiveness of standard treatment (patient's global assessment of the disease on the VAS scale greater than or equal to 4 cm with accompanying pain on the VAS scale greater than or equal to 4 cm) treated with non-steroidal anti-inflammatory drugs in a stable dose for at least 4 weeks and/or classical disease-modifying antirheumatic drugs in stable doses for at least 12 weeks.