Synovitis Acne Pustulosis Hyperostosis Osteitis (SAPHO) Syndrome

The SAPHO syndrome was given its name based upon the presence of synovitis, acne, pustulosis, hyperostosis, and osteitis in the patients described in early reports. It is a rare inflammatory disorder of bone, joints, and skin, which was first described as a syndrome in 1987.

It is an auto-inflammatory disease, mainly characterized by the association of neutrophilic cutaneous involvement (skin lesions with intense inflammatory infiltration of neutrophils) and chronic osteomyelitis (rare condition in which the bones have lesions, inflammation, and pain).

Most of these are coincident with CRMO, although skin involvement plays a larger role in SAPHO. For this reason, it is often suggested that the two syndromes lie along the same clinical spectrum.

 

Clinical presentation

SAPHO syndrome is characterized by a number of bone and joint findings that may present with symptoms of pain, swelling, and tenderness in involved areas. These features may be chronic or episodic and relapsing and focal or multifocal. The bone and joint features in individual patients include one or more of the following:

  • Synovitis, which is most often a nonerosive inflammatory arthritis, although periarticular osteopenia, joint space narrowing, and bony erosive changes associated with the synovitis and/or osteitis may occur.

  • Osteitis, with pain, tenderness, and sometimes swelling of the bone due to focal inflammation of the cortex, the medullary cavity, or both.

  • Hyperostosis (excessive growth of bone) is typically evident later in the disease course due to endosteal and/or periosteal proliferation. Sclerotic changes in the bone can result from trabecular and cortical thickening with narrowing of the medullary canal; concurrent osteolytic lesions may coexist when osteitis and hyperostosis are both present.

  • Changes consistent with axial spondyloarthritis, affecting the sacroiliac joints and spine, and enthesitis (ie, inflammation and resultant pathologic change at the site of tendinous and ligamentous insertion into bone). Diffuse idiopathic skeletal hyperostosis (DISH)-like nonmarginal enthesophytes may occur.

 

Bone and joint involvement may affect a variety of regions, especially the anterior chest wall; other parts of the axial skeleton, including the sacroiliac joint and spine; and medium to large lower-extremity joints.

 

Diagnosis

The diagnosis of SAPHO syndrome can be challenging, given the wide variety of clinical features that may occur in these patients. In general, SAPHO syndrome should be suspected in patients with bone and joint symptoms consistent with inflammatory arthritis and/or osteitis, especially when it involves the anterior chest wall, sacroiliac joints, or spine, and particularly when occurring in association with a neutrophilic dermatosis or acneiform eruption.

The diagnosis of SAPHO syndrome remains largely a clinical diagnosis that is based upon the presence of a combination of features; it is also a diagnosis of exclusion that requires an absence of evidence to support an infectious, malignant, or other etiology. Classic rheumatic diseases, such as rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis should also be excluded.

It is recommended to start with plain radiographs of the affected areas, followed by a bone scan (whole-body scintigraphy) if radiographs are unrevealing. Magnetic resonance imaging (MRI) of affected areas should be used for the detection of osteitis and better characterization of bone and soft tissue involvement.

Early SAPHO may be difficult to distinguish from osteomyelitis, as they may both present with a local site of bone pain, tenderness, warmth, and swelling, with an associated fever.

Malignant disorders of bone such as osteosarcoma and metastatic cancer should be considered. Both osteosarcoma and SAPHO may present with localized bone pain and surrounding swelling and without systemic symptoms. However, unlike SAPHO, osteosarcoma typically occurs in a single bone lesion, often affects the long bones, and has distinct radiographic features. A biopsy can establish a definitive diagnosis.

 

Lab tests

There are no pathognomonic laboratory findings of SAPHO. However, the following tests are recommended:

  • Complete blood count and hepatic and renal chemistries

  • Markers of inflammation, including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

  • Rheumatoid factor and anticyclic citrullinated peptide antibodies, which are often positive in patients with rheumatoid arthritis, and may be helpful if there is diagnostic uncertainty, depending upon the clinical findings.

  • Human leukocyte antigen (HLA)-B27 testing, which would be positive more often in patients with spondyloarthritis and may be helpful if there is diagnostic uncertainty, depending upon the clinical findings.

 

Genetics & epidemiology

The genetic bases of SAPHO syndrome remain largely unknown.

SAPHO syndrome is a rare disease, with limited data available regarding its prevalence, which has been estimated as 1 in 10,000 in Caucasian populations. Many reports are from Europe (eg, France, Germany, Spain, and the Netherlands), but African American, Latin American, Japanese, Chinese, Australian, and other patients are reported, suggesting a worldwide distribution.

Individuals between the ages of 30 and 50 seem most frequently affected, but children and young adults have also been reported, as have older adults, with one report of a woman diagnosed at 80 years of age. There is an apparent female predominance, particularly among patients less than 30 years of age at onset.

 

Treatment

CRMO can be treated with medications. The goals for treatment are to reduce the pain, improve the ability to move and to improve the quality of life.

Most attacks of CRMO can be managed with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are the first line of treatment. If NSAIDs are not effective, then these other drugs are often used:

  • corticosteroids (prednisone)

  • bisphosphonates (pamidronate)

  • methotrexate (MTX)

  • biologics (etanercept, infliximab, adalimumab, anakinra)

 

Colchicine and sulfasalazine are generally well-tolerated alternative second-line therapies that may be sufficient for patients with mild arthritis who fail to respond adequately to NSAIDs or cannot tolerate NSAIDs. These agents often are not adequate for patients with more severe symptoms.

 

In patients resistant to standard therapies, the following treatments may be useful:

  • Bisphosphonates

  • Anti-interleukin (IL)-1 therapy

  • Anti-IL-12/23 or anti-IL-17 therapies

 

Antibiotic therapy for SAPHO syndrome is primarily employed for patients with associated moderate to severe acne. Oral antibiotics are effective for acne and may also improve osteoarticular manifestations of SAPHO syndrome. The anti-inflammatory effects of antibiotics are postulated to contribute to improvement.

 

 

References:

- “An Update on Autoinflammatory Diseases”. Ginaldi et al. Curr Med Chem. 2013 Jan; 21(3): 261–269. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905709/

- “SAPHO syndrome: a review.” Rukavina, I. J Child Orthop. 2015 Feb;9(1):19-27. doi: 10.1007/s11832-014-0627-7. Epub 2015 Jan 14. https://www.ncbi.nlm.nih.gov/pubmed?term=25585872

-“The SAPHO syndrome.” Nguyen et al. Semin Arthritis Rheum. 2012 Dec;42(3):254-65. doi: 10.1016/j.semarthrit.2012.05.006. https://www.ncbi.nlm.nih.gov/pubmed?term=23153960

- “SAPHO: What radiologists should know.” Depasquale et al, Clin Radiol. 2012 Mar;67(3):195-206. doi: 10.1016/j.crad.2011.08.014. Epub 2011 Sep 21. https://www.ncbi.nlm.nih.gov/pubmed?term=21939963

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