Current and Emerging Therapeutic Approaches in SAPHO Syndrome: A Narrative Review

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare inflammatory disorder characterised by heterogeneous osteoarticular and cutaneous manifestations. Its variable clinical presentation, fluctuating disease course, and limited high-quality evidence complicate therapeutic decision-making. This narrative review critically examines established and emerging treatment strategies, with particular emphasis on phenotype-informed management and differences between skeletal and cutaneous responses. A targeted narrative review of the literature was conducted, incorporating clinical studies, observational cohorts, case series, and individual reports addressing therapeutic interventions in SAPHO syndrome. The available evidence was evaluated with consideration of study design, treatment outcomes, follow-up duration, safety, and methodological limitations. Nonsteroidal anti-inflammatory drugs remain the principal initial symptomatic treatment, while intravenous bisphosphonates and tumour necrosis factor inhibitors have the most extensive clinical evidence in persistent osteoarticular disease. Conventional synthetic disease-modifying antirheumatic drugs may be useful in patients with predominant peripheral arthritis. The emerging evidence supports further investigation of interleukin-targeted therapies, Janus kinase inhibitors, and iguratimod, particularly in refractory or mixed phenotypes. However, treatment responses frequently differ between skeletal and cutaneous manifestations, and paradoxical skin reactions may complicate biologic therapy. Most available studies are small, uncontrolled, and heterogeneous, limiting conclusions regarding comparative efficacy and optimal treatment sequencing. SAPHO syndrome requires an individualised, multidisciplinary therapeutic approach guided by the dominant active phenotype, treatment response, and safety considerations. Separate assessment of osteoarticular and cutaneous outcomes is essential. Prospective multicentre studies using standardised outcome measures are needed to establish optimal treatment strategies, long-term efficacy, and safety.