SAPHO Syndrome – A Pictorial Assay

Abstract

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a distinct clinical entity representing involvement of the musculoskeletal and dermatologic systems. It is well known to rheumatologists because of characteristic skin manifestations and polyarthropathy. However, few reports exist in the orthopaedic literature. It is important to be aware of sAPHO syndrome as it can mimic some of the more common disease entities such as infection, tumor, and other inflammatory arthropathies. Anterior chest wall pain centered at sternoclavicular and sternocostal joints is an important and characteristic clinical finding which can point to its diagnosis. A patient may undergo different diagnostic tests and invasive procedures such as biopsies before a diagnosis is made. Imaging can be helpful by offering a detailed evaluation of the abnormalities. More importantly it helps in revealing subclinical foci of involvement due to the polyostotic nature of the disease. The treatment is mostly nonsurgical. NSAIDS are the first line agents. However multiple new agents are being used for refractory cases. Surgery is reserved to treat complications.

Introduction

The association between musculoskeletal and skin lesions was first described by Windam et al in 1961 [1]. SAPHO stands for synovitis, acne, pustulosis, hyperostosis and osteitis. It is used to describe a combination of inflammatory conditions involving joints and characteristic skin lesions. The acronym was first coined by the French rheumatologist Chamot, in 1987, to describe a syndrome of acne, pustulosis and hyperostosis [2]. Since then it has been referred to by different names including sternoclavicular hyperostosis, non-bacterial osteitis, chronic recurrent multifocal osteomyelitis (CRMO), pustulotic arthro-osteitis, and spondyloarthritis hyperostotica pustulo-psoriatica [3, 4, 5, 6, 7]. It is important to be aware of different manifestations of this syndrome as it can have clinical features identical to more common and more recognized diseases such as infections, seronegative spondyloarthropathies, and tumors. A patient may undergo multiple diagnostic tests including biopsies before a correct diagnosis is made. SAPHO syndrome is well known to dermatologists and rheumatologists, but there are only few reports in the orthopaedic literature [8].

Clinical Features

SAPHO syndrome can affect all age groups from childhood to adulthood. There is a slightly higher incidence in the female population [3, 5, 6, 7]. Most of the reports have come from Japan and Europe. This may be due to increased awareness in these areas, rather than a higher incidence [8, 9]. Characteristic skin lesions include severe palmar and plantar pustulosis (PPP) along with severe acne (acne conglobata) which may represent a form of psoriasis. SAPHO has a variable clinical course with remissions and relapses. The skin manifestations and skeletal abnormalities may not coexist and may be separated by many years [14, 15].

The affected individuals usually present with pain, swelling, and limitations of movement in the affected joints. Although patients may present with a single site of involvement initially, a thorough search should be made to evaluate for the presence of subclinical foci due to the polyostotic nature of the disease. The characteristic and most common feature is anterior chest wall pain. Children can present with extremity pain due to involvement of long bones. Pain is usually subacute to chronic; however, it can be debilitating, can affect nighttime sleep, and can be accompanied by fever [7, 8, 9]. The lab tests can be normal or may show elevated inflammatory markers. Patients with spinal involvement can present with numbness and radicular pain. The spinal lesions in SAPHO syndrome generally have a good prognosis and rarely cause neurological deterioration [9]. However, vertebral destruction may result in a kyphotic deformity or quadriplegia in severe cases [9, 10]. There have been multiple reports of mandible and temporomandibular joint involvement presenting with recurrent pain, swelling and limitation of movement at the jaw progressing to ankylosis [11, 12, 13].

Imaging Findings

Imaging plays an important role due to the characteristic osteoarticular manifestations which can help in determining the diagnosis. Most patients show polyostotic involvement. The sternoclavicular junction is the most common site of involvement in adults, followed by the spine and sacroiliac joints. The sternoclavicular, costochondral and manubriosternal joints are involved in decreasing order of frequency [20–24].

Radiographs

On radiographs, there is bone expansion and medullary canal stenosis, which results in diffuse thickening of the periosteum, cortex and endosteum. There may be accompanying osteolysis and osteosclerosis [16,17]. Ossification of the costoclavicular ligament and hyperostosis at the sternal end of the first ribs are important early findings (Figure 1). The joint involvement is characterized by arthritis with joint space narrowing. There can be associated bone erosions and periarticular osteopenia. Ankylosis may be present and brings pain relief in some patients [17]. Sacroiliitis is seen in up to 50% of patients and is usually unilateral with erosions and sclerosis along the iliac side of the joint [17, 26] (Figures 2, 3). Although all the abnormalities can be seen on plain radiographs, CT is the modality of choice to determine the extent of the lesions.

Figure 1. Hyperostosis and osteitis of the left sternoclavicular and sternocostal joints.

35 year old female presented with chronic recurring jaw pain after tooth extraction. (a) CT sagittal reformatted image of the left mandible showing hyperostosis of the ramus and body. (b) Chest x-ray, (c) CT chest and (d) CT 3d reformatted images show hyperostosis and sclerosis involving the manubrium and proximal end of first rib on the left side. Involvement of sternocostal, sternoclavicular and manubriosternal joints is highly diagnostic of SAPHO syndrome. CT is much more sensitive in depicting the lesions as compared to radiographs. (e) Bone scan showing increased uptake in left sternoclavicular region. Scintigraphy is particularly useful in revealing subclinical areas of involvement. (f) MRI of the chest, axial T2 fat-saturated image show edema in the marrow and adjacent soft tissue edema at anterior end of the left first rib and adjacent manubrium. Water sensitive sequences on MR show high sensitivity and are helpful in detecting subclinical foci. (g) Follow up MRI shows reduced marrow edema suggestive of response to NSAIDS and methotrexate. (h) However CT chest a year later showed progression of abnormalities.

Figure 2. Multifocal spondylodiskitis and sacroiliitis confused for metastatic disease.

50 year old man presented with trauma and back pain. (a) Radiograph of the lumbar spine showed sclerotic areas in multiple vertebral bodies. These were initially suspected to be sclerotic metastases. (b) A bone scan obtained showed high uptake in the sacroiliac joints and lumbar spine. (c) A sagittal reformatted image of the lumbar spine showed sclerotic lesions and erosions centered on the corners of vertebral bodies and adjacent end plates. No associated soft tissue mass was seen. Corner erosions are one of the characteristic features of SAPHO. (d) to (f) MRI of lumbar spine including sagittal T1, T2 and T1 fat-sat contrast images showed corner lesions to be hypointense on T1, hyperintense on T2 with contrast enhancement. There is no abnormal signal in disc or any associated fluid col ection which rules out an infectious etiology. (g) MRI Pelvis axial T2 fat suppressed image centered at SI joints showed edema around the bilateral sacroiliac joints, more severe on right side.

Figure 3. Spondylodiskitis and sacroiliitis in SAPHO syndrome.

46 year old female presented to the emergency treatment center with acute chest pain and had a chest CT done to rule out pulmonary embolism. (a, b) There were multiple areas of hyperostosis and sclerosis in the manubrium, clavicle and first rib on the left side. (c) The sagittal reformatted image of the thoracic spine showed sclerotic lesions in the adjacent vertebral bodies. Disc spaces are well preserved. The spine is the second most common site of involvement in children and adults. These were earlier diagnosed as suspicious for metastatic disease. The patient had no history of cancer and further investigations revealed no focus of a primary tumor. (d) The Ferguson view of the sacroiliac joints and (e) a CT pelvis showed sclerosis and erosions in the bilateral sacroiliac joints, more severe on left side. Sacroiliac involvement in SAPHO is either unilateral or bilateral asymmetric, mainly involving the iliac side of the SI joint. This patient was also found to have palmar and plantar pustulosis.

In children and adolescents, the metaphyses of long bones, followed by the clavicles, are the most commonly involved areas. The femur and tibia are the most common sites for long bone involvement (Figure 4). The clavicle is the most common site of anterior chest wall involvement, starting medially and extending laterally.

Figure 4. Hyperostosis and osteitis involving the long bones in SAPHO syndrome.

21 year old female presenting with pain in both legs. (a) Radiograph of both knees showed bony expansion and new bone formation (hyperostosis) with sclerosis. Long bone involvement is more common in pediatric patients. (b) Bone Scan showed increased uptake in both the distal femur diaphysis. (c) and (d) MRI showed thick periosteal reaction along with marrow edema(osteitis) in both femora. (e) to (h) follow up imaging studies after an year including radiographs of both knees, a bone scan and MRI of both femora respectively; showed significantly decreased disease activity after anti-TNF factor treatment.

The spine is the second most common site of involvement in children and adults, with the thoracic spine most commonly affected [9, 10, 25]. The lesions may start at the vertebral body or end plates [17] (Figure 2, 3). Maugars et al. proposed that lesions begin with the enthesis and lead to osteolysis, erosion, synovitis, hyperostosis, and finally synostosis followed by ankylosis and reduction of hyperostosis [26]. Nonspecific spondylitis and diskitis are the most common imaging findings (Figures 2d to 2f).

Magnetic Resonance Imaging

MRI is helpful in revealing subclinical foci and to identify active lesions by the presence of bone marrow edema on water sensitive sequences such as T2 weighted and STIR. The bony changes may extend to involve adjacent soft tissues on MRI (Figures 1f and 1g).

In the spine, high T2 signal in the disc, vertebral sclerosis, hyperostosis, and paravertebral ossification can be seen. Vertebral body corner erosions may be seen which appear low on T1 and high on T2 weighted sequences and with gadolinium enhancement [27, 28]. Loss of vertebral body height may result in a kyphotic deformity. Lack of abscess formation, sequestra, or paravertebral soft tissue involvement helps differentiate SAPHO from pyogenic spondylodiskitis [27, 28].

Scintigraphy

Whole body scintigraphy can also be useful for identifying subclinical foci [18]. 18FDG PET/CT has been used to differentiate active and inactive lesions. It can also distinguish lesions in SAPHO from bony metastases [19]. Symmetric high radionuclide uptake in the sternocostoclavicular joints can be seen on bone scan termed as “bull's head sign” [20].

Etiology and pathogenesis

Various hypotheses have been proposed to explain the cause of SAPHO syndrome. The foremost among them is an infectious etiology. Propionibacterium acnes, an anaerobic saprophyte found in human skin has been isolated from the biopsy specimens of bone and synovium [23, 24, 29]. Despite these few case reports, antibiotic trials have been found to be ineffective [18].

There have been suggestions in the literature of a possible link to seronegative spondyloarthropathies [9, 17, 24, 29]. Paravertebral ossification along with palmar plantar pustulosis point to an association with psoriasis [26, 27, 28]. HLA B27 may be positive in up to 30% of SAPHO patients [17].

Differential Diagnosis

The clinical findings of SAPHO can resemble other diseases such as osteomyelitis, osteosarcoma, Ewing Sarcoma, Paget's disease, metastases, osteitis conden-sans of the clavicle, and POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) [30, 31]. However there are some characteristic features which can raise the suspicion and help in reaching a proper diagnosis. SAPHO should be strongly suspected in patients with multiple areas of bony abnormalities which may include joints, axial and appendicular skeleton along with anterior chest wall pain, with unremarkable lab tests and no history of inflammatory arthropathy or primary cancer. Imaging studies are the best next step to further evaluate the lesions and reveal subclinical foci.

Treatment

The treatment of SAPHO syndrome is empirical and is mainly symptomatic. NSAIDS are the mainstay of treatment [6,7,8,14]. Corticosteroids, colchicines, sulfasala-zines, and methotrexate are used as secondline agents. Antibiotics, calcitonin, and anti-TNF agents are used for refractory cases including persistent bone lesions including osteitis. Oral and intravenous bisphophonates have been tried successfully [32]. The spondylitis in SAPHO syndrome generally has a good prognosis treated conservatively. However, it may cause severe destruction rapidly, which may be best treated surgically [9]. Mandibular involvement has been treated with hyperbaric oxygen therapy and minor surgical procedures such as decortication and curettage. Wide resection is reserved for patients with deformity, loss of function, increasing pain, and failure of conservative treatments [33].

Conclusion

SAPHO is a distinct clinical entity with characteristic imaging features. It is crucial to be aware of its manifestations so as to diagnose it and differentiate it from other diseases. It is important to remember that the skin manifestations and bony involvement may not be present at the same time.