Septic arthritis is a severe infection associated with significant morbidity and mortality. Despite eradication of the microorganisms, persistent inflammation may lead to substantial long-term functional joint sequelae. The use of corticosteroids could reduce this inflammation, thereby improving functional joint outcomes and facilitating first-line medical treatment. The hypothesis of this study is that corticosteroid administration, in addition to antibiotic therapy, reduces persistent inflammation and improves functional joint prognosis in adult patients with acute septic arthritis.

Septic arthritis is a severe infection with a mortality rate of 10-15% and morbidity up to 25% due to rapid joint destruction. Despite antibiotic treatment, persistent intra-articular inflammation increases the risk of long-term joint damage. Standard care includes antibiotics and joint drainage, either surgically (arthrotomy or arthroscopy) or by repeated bedside aspiration. Surgery carries risks of nosocomial infections and complications, and aspirations are not always feasible.

Corticosteroids are currently not recommended in adult septic arthritis due to concerns that their anti-inflammatory effects might worsen infection. However, corticosteroids have shown benefits in other infections, improving outcomes in meningitis and pneumonia. Animal studies suggest that host inflammatory responses, particularly activation of CD4+ lymphocytes and macrophages, drive joint damage, and corticosteroids reduce this inflammation, preserving cartilage.

In children with septic arthritis, corticosteroids have been shown to reduce long-term joint damage, symptom duration, and hospital stay without increasing infection risk. To date, no randomized controlled trials have evaluated corticosteroids in adult septic arthritis.

This study aims to assess the efficacy and safety of adjunctive corticosteroid therapy with antibiotics in adults with septic arthritis, focusing on reducing joint sequelae, pain, hospital stay, and surgical interventions.

Inclusion Criteria:

• Age ≥ 18 years
• Documented septic arthritis (microorganism identified intra-articularly by culture or PCR, or by turbid synovial fluid with positive Gram stain, or positive blood cultures)
• Effective antibiotic therapy initiated within ≤ 3 days
• Effective contraception for women of childbearing age during treatment period
• Signed informed consent
• Affiliation to the French national health insurance system
• Ability to read, write, and understand French

Exclusion Criteria:

• Polyarticular septic arthritis (≥ 2 joints)
• Septic arthritis of small joints (e.g., fingers: proximal interphalangeal joint (PIP), distal interphalangeal joints (DIP), MetaCarpoPhalangeal (MCP); toes: MTP)
• Systemic sclerosis
• Pyomyositis
• Diabetic foot infection
• Current corticosteroid therapy for another indication
• Inability to take oral medication
• Contraindication to corticosteroids
• Associated endocarditis
• Presence of prosthetic joint or osteosynthesis material in the affected joint
• Septic shock
• Severe soft tissue wound overlying the joint
• Aplastic chemotherapy
• Neutropenia (defined as neutrophils < 500/mm³)
• Mycobacterial infection
• Fungal infection
• Sickle cell disease
• Current pregnancy
• Breastfeeding women
• Patients under legal protection (e.g., guardianship)
• Participation in another interventional clinical trial
• Uncontrolled diabetes
• Unstable psychiatric disorders
• Adults unable to provide informed consent
• Contraindication to corticosteroid therapy

Experimental arm: Standard antibiotic therapy combined with oral prednisone at a dose of 60 mg per day for 7 days Control arm: Standard antibiotic therapy combined with an oral placebo matching prednisone for 7 days.