Sapho Syndrome

A rare, pyogenic autoinflammatory disease, characterized by the association of neutrophilic cutaneous involvement and chronic nonbacterial osteomyelitis.

Epidemiology

Although its incidence and prevalence are probably underestimated, SAPHO syndrome (acronym for Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is considered to be a rare disorder.

Clinical description

The age of onset ranges from adolescence to late adulthood, with a median age between 30 and 40 years. SAPHO syndrome encompasses a wide spectrum of anomalies characterized by variable combinations of osteoarticular and cutaneous manifestations of varying degrees of severity. The onset of bone and joint pain, stiffness and swelling is most often insidious. In adults, inflammation occurs mainly in the anterior chest wall but also in the spine, less frequently in the mandible and the iliac bones ; in children it shows a comparable distribution as chronic nonbacterial osteomyelitis (CNO/CRMO) (e.g. long bones, clavicle, spine). When synovitis occurs, it manifests most of the times in the sacro-iliac joint, hips or knees, or the sternoclavicular joints. Depending on severity of symptoms, a limited range of motion may be observed. Dermatological involvement includes severe acne, palmoplantar pustulosis, and pustular psoriasis. Skin manifestations often begin 1-2 years before osseous changes but may appear simultaneously or more than 20 years later. Patients may also suffer from abdominal pain, diarrhea, anal fissures or abscesses, suggesting the possible association with an inflammatory bowel disease (IBD). Most authors regard CNO/CRMO as the pediatric form of SAPHO syndrome. In fact, the frequent occurrence of dermatological disorders or IBD pleads for the inclusion of these two entities in the same spectrum.

Etiology

The etiology is unknown. SAPHO syndrome seems to have a multifactorial origin with genetic, environmental, immunologic, and infectious components. Slow-growing bacteria, such as Propionibacterium acnes, could act as a triggering factor.

Diagnostic methods

Diagnosis, suspected upon clinical examination, must be confirmed with imaging procedures (X-rays, CT, MRI) showing a combination of osteolysis and osteosclerosis with secondary hyperostosis, bone marrow edema, endosteal-periosteal inflammation, perifocal myositis, and adjacent arthritis. Bone biopsy often reveals an infiltrate of neutrophils in early stages, progressively replaced by mononuclear cells and associated with sclerosis in later stages. A bacteriological study is sometimes positive for Propionibacterium acnes. Synovial fluid culture is usually negative.

Differential diagnosis

Differential diagnosis includes infectious osteomyelitis or arthritis, Langerhans cell histiocytosis, and bone tumors such as Ewing sarcoma, osteoblastoma, and osteoid osteoma. Hypophosphatasia may mimic the bone phenotype of SAPHO syndrome.

Genetic counseling

Most cases are sporadic. Some familial cases have been reported.

Management and treatment

Treatment is mainly symptomatic and is based on non-steroidal anti-inflammatory drugs, sometimes replaced by corticosteroids (e.g. prednisone). In resistant cases, disease-modifying antirheumatic drugs (e.g. methotrexate) can also be used. Intravenous biphosphonates (pamidronate, zoledronate) can alleviate bone pain. More recently, TNF-inhibitors showed encouraging results in controlling both osteoarticular and cutaneous manifestations. The osteoarticular features may also be treated by sulfasalazine. Acne may be treated with systemic antibiotics, like doxycycline. Palmoplantar pustulosis or pustular psoriasis usually responds well to either topic corticosteroids or PUVA therapy. Physiotherapy is recommended.

Prognosis

The disease usually has a chronic evolution, with alternating periods of remission and relapse, sometimes with the appearance of new osteosclerotic lesions. Spontaneous resolution can occur. Complications include impairment of bone and joint function, vascular compression, chronic pain syndrome, and progression towards classical spondyloarthritis.