SAPHO Syndrome (Acquired Hyperostosis Syndrome, Pustulosis, Hyperostosis and Osteomyelitis, Synovitis acne pustulosis hyperostosis osteitis) is described as any combination of Synovitis (inflammation of the joints), with acne, Pustulosis (thick yellow blisters containing pus) often in the palms and soles, Hyperostosis (increase in bone substance) and Osteitis (inflammation of the bone). The cause of Sapho syndrome is unknown, but not fully understood and the treatment is focused on managing symptoms.
This is a variety of inflammatory bone disorder associated with skin changes coupled to various clinical, radiologic and pathologic conditions. In 1972, orthopedists considered this entity as a Chronic Recurrent Multifocal Osteomyelitis. Later in 1978 It was noted a closed association with blisters in the palms and soles named palmoplantar pustulosis, existed. Since, numerous skin conditions with osteoarticular disorders were reported bringing a variation in the name of the pathology as sternoclavicular Hyperostosis, pustulotic arthro-osteitis and acne associated spondyloarthropathy.
The term SAPHO Syndrome (Synovitis, Acne, pustulosis, Hyperostosis osteitis) was coined in 1987 by Chamot to describe this spectrum of inflammatory bone disorder, often but not always associated with dermatologic lesions.
Symptoms will vary from person to person. People diagnosed with the disease may have different symptoms based on the human phenotype ontology (HPO). The information collected is updated regularly with bone pain, arthralgia, chest pain, cranio-fascial osteosclerosis, Enthesitis (SC Joints).
60-90% of patients suffering from this condition will present with anterior chest wall hyperostosis, sclerosis or bone hypertrophy involving especially the sternoclavicular joint. We all know well the predilection of the SC joint to tuberculosis and syphilis in our country of Haiti. The spine is commonly affected in 32-50% of cases in which most of the lesions are in the thoracic spine demonstrating spondylodiscitis, osteosclerosis, paravertebral ossifications and sacroilliac joint involvement. 30% of patients will have long bone involvement at the metaphyseal-diaphyseal junctions, around the knee joint: distal femur and proximal tibia.
These lesions tend to mimic osteomyelitis without the acute or chronic signs of abcess formation, involucrum and further sequestrum formation. 10% of the patients suffering of the condition will also have flat bone involvement like the ilium or the mandibula. If the disease is seen in children, the metaphysis of the long bone is generally involved in the process, followed by the spine and the clavicle. The aseptic skeletal inflammatory manifestation often mimic osteomyelitis, lymphomas, Ewing sarcoma and even can give the appearance of metastasis to bone.
SAPHO Syndrome occurs also in other spondyloarthropathies like psoriatic arthritis, idiopathic ankylosing spondyloarthropathy, spondylopathy associated with inflammatory bowel syndrome. Psoriatic arthritis with axial skeletal involvement and pustular arthritis can be like SAPHO but radiologic signs of osteitis with hyperostosis are not seen in psoriatic arthritis. Generally psoriatic arthritis is asymmetric and remain associated with only sacroiliitis and sparing of the facet joints while in ankylosing spondylitis the sacroilliac joints are typically involved until ankylosis is fully established.
Reactive spondyloarthritis is believed to be a component of a systemic autoimmune response following an infection of the conjunctivae, or the bowels or the urethral-genital system, two to four weeks prior but involving larger joints asymmetrically. Enteropathic spondyloarthritis is generally associated to two major chronic inflammatory diseases: Ulcerative Colitis and Chrohn disease which also have radiologic spondylitis sacroilliac joint involvement like Ankylosing Arthritis.
We have already discussed that the most common site of skeletal involvement in SAPHO Syndrome is the anterior chest followed by the spine with osteosclerosis and hyperostosis. It becomes logical to use imaging studies to differentiate them.
Technetium 99m bone scanning demonstrates an increase tracer uptake for the active and chronic lesions. Pet scanning maybe used to differentiate acute from chronic healed inflammatory lesions mandating a biopsy to rule out any possible metastatic lesions.
MRI imaging will demonstrate bone marrow edema in any active lesion. Recently a curvilinear or semicircular pattern was described in the vertebral body segments helping in differentiating SAPHO Syndrome from Metastatic disease of the spine. Another finding is an anterior vertebral corner erosion suggesting of enthesis. 30% of patients with the syndrome can rule out osteomyelitis or discitis.
SAPHO Syndrome cannot be diagnosed hystopathologically. Biopsy can only rule out the possibility of infection. As we have already stated, the pathogenesis is not completely understood but appears to have genetic, immunologic and infectious components. Some studies have demonstrated a relation to Ankylosing Spondylitis with the Human Lymphocyte Antigen (HLA-B27). Infectious origins have been postulated because of isolation of Propionibacterium acnes in some skin lesions.
There is no specific treatment to this SAPHO syndrome. It can be chronic or heal suddenly. Joint pain may be managed with anti-inflammatory drugs (NSAIDS) and Bisphosphonates as a first line of treatment, but Vitamin A, Serotonin has been suggested for the treatment of acne as well as Corticosteroids (Psoralen) and Ultraviolet therapy with retinoids.
Physical therapy has been used as an adjunct to musculoskeletal symptoms but there are questionable evidences that such treatment is beneficial. Surgical treatment of deformity to relieve pain and discomfort may have also a role in progressively destructive spondylitis requiring stabilization.
We have seen patients undergoing serologic testing with subsequent antibiotic therapy. Many may have had prior biopsies before a diagnosis is made. The skin manifestations like Acne Fulminans, Pustular Psoriasis, Palmoplantar Pustulosis usually occur simultaneously with the bone lesions. Typically, a patient will have 2 or 3 months of progressive mi-thoracic pain exacerbated by exercises but no history of fever, no swollen joints, often no other signs of infection.
Laboratories tests will reveal a normal white blood cell count as well as a normal C-reactive protein level. CT Scan or MRI of the thoracic spine may show sclerosis or edema. Lymphoma can be suspected but Bone biopsies of the thoracic spine remained in the normal limit ruling out that diagnosis. Core biopsy do show chronic inflammatory process at the thoracic vertebrae level. Bacterial cultures are often inconclusive or negative for fungi or bacteriae. Serologic test are also generally negative for Human Leucocyte Antigen (HLA) B27. Neoplasm and Infection can be, at once eliminated.
One may conclude that the SAPHO syndrome is a diagnosis of exclusion. Often when MRI studies are often repeated, demonstrating no changes to the previous lesions reported or no resolution to the inflammatory process year after.
I tried to present the evidences that diagnosing the SAPHO Syndrome can be challenging and tricky when dealing with clinical, radiologic and serologic studies but at least one of the osteoarticular manifestations added to dermatologic lesions like Acne or Palmoplantar pustules with or without chronic recurrent osteomyelitis or any other dermatosis are enough to assure the diagnosis.
In conclusion, SAPHO Syndrome is indeed, a diagnosis of exclusion even if cutaneous manifestations are not present. It is important to differentiate it from other conditions. Unfortunately, treatment remains ill-defined but Bisphosphonates and NSAIDs have been suggested as the first-choice drugs in the treatment of this condition, controlling symptoms. Other have tried Tumor Necrosis Factor alpha antagonist (TNF inhibitors), Topical Corticosteroids, Colchicine, Ciclosporin, Sulfonamide, Calcitonin, Methotrexate, Leflunomide, Infliximab, Etanercept and have shown some effects in reducing symptoms. Finally, Antibiotics to treat Propionibacterium infection have also been used in the treatment of the SAPHO syndrome, once biopsies or cultures have proven this pathogen to be responsible of the infection.
Always keep in mind that a Differential diagnosis between Osteomyelitis or Arthritis, Langerhans cell histiocytosis and/or Bone Tumors such as Ewing sarcoma, Osteoblastoma and Osteoid Osteoma need always to alert the clinician.
Maxime Coles MD
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