Synovitis,acne, pustulosis,hyperostosis, and osteitis syndrome with cranial bone involvement: Case report and literature review

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune inflammatory disease characterized by osteoarticular and dermatological manifestations. The most common osteoarticular manifestations involve the anterior chest wall, axial skeleton, and long bones. Cranial bone involvement is less reported in SAPHO syndrome. We herein present three cases of SAPHO syndrome with cranial bone involvement, and review the previous literature on similar manifestations. It was revealed that SAPHO syndrome could lead to cranial bone involvement, which could involve the dura mater, leading to hypertrophic pachymeningitis, but the outcome is usually good. Janus kinase inhibitors may be a potential treatment option.     

Diagnostic points and possible origin of osteomyelitis in synovitis,acne, pustulosis,hyperostosis and osteitis (SAPHO) syndrome: a radiographic study of 77 mandibular osteomyelitis cases

OBJECTIVES: To find diagnostic points and to identify the origin of osteomyelitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. METHODS: Fifty-two patients with mandibular suppurative osteomyelitis and 25 patients with mandibular osteomyelitis in SAPHO syndrome were included in the study. Radiographic patterns of the lesion, types of periosteal reaction and the presence of external bone resorption and bone enlargement were investigated in each case and compared between the two entities. RESULTS: Suppurative osteomyelitis demonstrated an osteolytic pattern and a lamellated type of periosteal reaction, whereas SAPHO syndrome revealed a mixed-pattern, solid-type periosteal reaction, external bone resorption and bone enlargement. CONCLUSIONS: Radiographic examination is suggested to be convenient and a useful diagnostic method of differentiating osteomyelitis in SAPHO syndrome from suppurative osteomyelitis. The periosteum is suspected to be the original site of osteomyelitic lesions in SAPHO syndrome.     

Ilium osteitis as the main manifestation of the SAPHO syndrome: response to infliximab therapy and review of the literature

OBJECTIVE: To analyze the clinical efficacy of anti-tumor necrosis factor (TNF)-alpha therapy in the SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. We describe 2 new cases with ilium osteitis as the main SAPHO syndrome feature and review reported cases treated with anti-TNF-alpha. METHODS: A literature search of SAPHO syndrome cases treated with TNF-alpha blocking therapy with special emphasis on osteoarticular and skin responses was performed. RESULTS: Eighteen cases were identified: 17 SAPHO syndrome and 1 chronic recurrent multifocal osteomyelitis, a juvenile variant of SAPHO syndrome. Sixteen were reported cases and 2 were nonreported cases seen in our arthritis unit. Sixteen patients received infliximab and 2 received etanercept, with an early, sustained clinical improvement in most cases. CONCLUSIONS: Anti-TNF-alpha therapies are effective treatment for patients with refractory SAPHO syndrome, not only for cutaneous lesions but also for persistent bone lesions such as osteitis.     

C1–C2 spondylodiscitis in an adult with SAPHO syndrome: an unusual presentation

The main advantage of recognition and diagnosis of SAPHO syndrome is the avoidance of unnecessary prolonged antibiotic treatment and repeated invasive procedures. The combination of synovitis, acne, pustulosis, hyperostosis and aseptic osteitis is known as SAPHO syndrome. The most common site of the disease is the upper anterior chest wall, characterized by predominantly osteosclerotic lesions, hyperostosis, and arthritis of the adjacent joints. Osteosclerosis of the vertebral bodies, hyperostosis, and erosions of the vertebral plates are rarely encountered. We present a case of SAPHO syndrome with C1–C2 spondylodiscitis. Diagnosis of SAPHO syndrome was established using Khan et al. criteria (Schilling, SAPHO syndrome, Encyclopedie Orphanet, 2004). CT showed osteosclerotic lesions of dens axis. MRI sequences reveal inflammatory bone marrow oedema. Radiologists should be aware of this unusual syndrome to avoid misdiagnosis (tumour/infection), unnecessary surgery, and antibiotic therapy.     

Sternoclavicular pustulotic osteitis (SAPHO). 20-year interval between skin and bone lesions

In 2 cases of palmoplantar pustulosis, a 20-year interval was observed between the skin lesion and the bone involvement. In one case, the bone lesion came first. In the other a skin lesion was seen for 3 weeks without subsequent relapse. The 2 cases underline the multifaceted presentation of the condition for which we have coined the name synovitis acne pustulosis hyperostosis osteitis (SAPHO) syndrome.     

Pulmonary adenocarcinoma associated with SAPHO syndrome difficult to differentiate from multiple bone metastasis

The patient was a 57-year-old man with a chief complaint of anterior chest pain who was diagnosed with clinical stage IV (c-T2N2M1) non-small-cell lung cancer (adenocarcinoma). Tenderness in the sternoclavicular joint, acne, periodontitis, and palmoplantar pustulosis were evident, and SAPHO syndrome was diagnosed. SAPHO syndrome is a rare disorder that results in synovitis, acne, pustulosis, hyperostosis, and osteomyelitis. Bone scintigraphy showed tracer accumulation in the costal cartilage, sternoclavicular joint, and cervical vertebrae 6-7. Although the bone lesions of SAPHO syndrome were difficult to differentiate from bone metastasis of pulmonary adenocarcinoma, metastatic bone tumors were ruled out by magnetic resonance imaging, computed tomography, and fluorodeoxyglucose positron emission tomography. There have been no previously reported cases of lung cancer with comorbid SAPHO syndrome. We report such a case and discuss the relevant literature, particularly that concerned with the evaluation of bone lesions.     

Coexistence of Sjögren syndrome in patients with synovitis,acne, pustulosis,hyperostosis, and osteitis syndrome: A retrospective observational study

To identify the prevalence and clinical characteristics of Sjögren syndrome (SS) in a Chinese single-center cohort of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.Patients diagnosed with SS were screened out from a cohort of 164 cases of SAHPO syndrome. Information regarding the patients’ gender, age at onset, clinical features, laboratory tests, bone scintigraphy, and treatment was reviewed.Five patients were screened out. The prevalence of SS in SAPHO patients was 3.05% The mean onset age of SS was 48.0 ± 12.0 years old and no apparent time order in the occurrence of SAPHO and SS was observed. Compared with the general SAPHO cohort, the 5 SS patients exhibited no significant difference in the SAPHO related clinical features or inflammatory markers, except for a higher prevalence of peripheral joints and bones involvement in bone scintigraphy. Objective evidence of dryness and positive salivary gland biopsy were found in all the patients. However, the positive rates of SSA and SSB antibody were only 20%. Anti-inflammatory treatment for SS was recorded in 3 patients (ESSDAI score: 3 in 2 patients; 12 in 1 patient) with extra-glandular manifestations, severe complications or poor response to the basic treatment.The prevalence of SS is higher in the SAPHO cohort than in the general Chinese population. Objective tests or biopsy might be more indicative than the antibody detection for SS diagnosis. Anti-inflammatory treatment should be prescribed in consideration of both the severity of SS and the demand for disease activity control of SAPHO.     

Synovitis,acne, pustulosis,hyperostosis, osteitis syndrome with invisible organizing pneumonia: A case report

We report the case of a 59-year-old female patient, presenting with pustular rash on both hands and pain in the lumbosacral part and left lower limb. A magnetic resonance imaging examination of the left leg was undertaken and the result showed that a malignant lesion with bone destruction of the left femoral shaft could not be excluded. Subsequently, bone tumor was excluded by pathological examination. Lung computed tomography scan showed patchy consolidation and cord shadow in the middle left lung. Subsequently, lung cancer was excluded by pathological examination, and the histopathological changes of lung were consistent with those of organized pneumonia. Blood tests revealed elevated C-reactive protein and erythrocyte sedimentation rate. Antinuclear antibody, rheumatoid factor, and human leukocyte antigen-B27 were unremarkable. Whole body bone scintigraphy via technetium 99m-methyl diphosphonate showed increased radionuclide uptake in the left middle femur. Based on her clinical manifestations, imaging results and bone scintigraphy, the patient was diagnosed as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Loxoprofen and Tripterygium wilfordii Hook F led to impressive clinical and radiologic improvement.     

New insights into synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome

In 1987, synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome was proposed as an umbrella term for a group of diseases with similar musculoskeletal manifestations, in particular hyperostosis of anterior chest wall, synovitis, and multifocal aseptic osteomyelitis, observed in association with dermatologic conditions such as palmoplantar pustulosis, severe acne, and hidradenitis suppurativa. Despite recent advances in our understanding of the epidemiologic, pathophysiologic, and immunogenetic mechanisms involved in SAPHO syndrome, etiopathogenesis remains poorly understood. Propionibacterium acnes, the microorganism associated with acne, has been recovered on bone biopsy in some patients, but the possible pathogenetic role of an infectious agent in a genetically predisposed individual, resulting in exaggerated inflammatory response as “reactive osteitis,“ is a largely unproven hypothesis. The newly available whole-body MRI will assist early diagnosis by detecting multifocal osteitis lesions, some of them asymptomatic, in axial (anterior chest wall, spine, and jaws) and nonaxial sites. Moreover, outcomes are vastly improved by treatment with bisphosphonates and tumor necrosis factor-α antagonists.     

Synovitis,acne, pustulosis,hyperostosis, osteitis (SAPHO), and chronic recurrent multifocal osteomyelitis (CRMO): A tale of two cases

BackgroundSAPHO (Synovitis Acne Pustulosis Hyperostosis Osteitis) and CRMO (Chronic Recurrent Multifocal Osteomyelitis) are chronic relapsing osteoarticular disorders with common dermatological manifestations.Aim of the workTo describe a case of SAPHO in an adult and CRMO in a child.Cases presentationCase 1: A 32-year old man presented with dull aching low back pain for 2 years with morning pain/stiffness. On examination there were acneform lesions on the face, tenderness over thoracic spine and swelling of left sternoclavicular joint. Plain x-rays showed sclerosis/widening/irregularity of sternoclavicular joint, sclerosis/irregularity of endplate, loss of disc space with syndesmophytes in mid/lower dorsal spine (D6-11) and sclerosis in middle of left tibia. Magnetic resonance imaging (MRI) spine showed cortical erosions and marrow edema (D6-L1) with findings suggestive of aseptic/inflammatory spondylodiscitis. A bone scan showed increased uptake D7-D12 and mid-third tibia (hyperostosis). Biopsy from D6/D7 showed normal histopathology. Case 2: A 10-year-old girl presented with pain/swelling of right foot for 2 months, pain/swelling of left shoulder and sternoclavicular joint with pustular acne on the face. There was swelling/tenderness over right 5th metatarsal base and left sternoclavicular joint as well as tenderness over proximal humerus. ESR was 65 mm/1^sthr. Plain x-rays showed punched-out lytic lesions surrounded by sclerosis in metatarsal base and metaphysis of humerus. Patient was diagnosed as CRMO.ConclusionSAPHO and CRMO are rare and their diagnosis is sometimes not easy. SAPHO can present as aseptic spondylodiscitis. Both conditions can be diagnosed with clinical and radiological features. A biopsy is necessary for ruling out other conditions.     

Intravenous pamidronate in the treatment of sternoclavicular hyperostosis

The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a rare clinical entity in which osteosclerosis and osteolysis are consistent radiological findings. We present a patient with SAPHO syndrome manifesting as painful sternoclavicular hyperostosis treated successfully with pamidronate. For the first time, a reduction in isotope bone scan activity was documented in parallel to a favourable clinical response. Bisphosphonates have potent antiosteoclastic and anti-inflammatory effects. By virtue of their dual effects on bone remodelling and inflammation, they seem an appropriate therapy in the management of SAPHO syndrome. This case demonstrates the efficacy of pamidronate, both clinically and radiologically, as first line therapy for patients with isolated hyperostosis.     

SAPHO syndrome in an adult with ulcerative colitis responsive to intravenous pamidronate: a case report and review of the literature

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare group of sterile, inflammatory osteoarticular disorders classically associated with skin lesions. It is occasionally associated with enteropathic disease such as ulcerative colitis. We present a 39-year-old patient with chronic ulcerative colitis who developed enteropathic SAPHO and responded well to pamidronate. We discuss the clinicopathological features with particular attention to bone pathology, and perform a literature review of this fascinating syndrome.     

SAPHO syndrome.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome put together osteoarticular lesions described separately under numerous denominations, such as multifocal osteomyelitis, pustulotic arthroosteitis, acne rheumatism. The association of sterile inflammatory bone lesions and neutrophilic skin eruptions is the cornerstone of this new syndrome, which also has links with spondyloarthropathies and plain psoriasis.     

Propionibacterium acnes and SAPHO syndrome: a case report and literature review

OBJECTIVE: To describe the presence of Propionibacterium acnes (P. acnes) in a series of patients with SAPHO syndrome in which a bone biopsy has been carried out and to discuss the results comparing them to the data described in the literature. METHODS: In 6 out of 56 patients with SAPHO syndrome, a bone biopsy from osteitic lesion was carried out. This invasive investigation was performed only in those cases in which it was necessary to clarify the diagnosis. RESULTS: Of the 6 biopsies processed, P. acnes was isolated in only one case. No other infectious agents were identified. CONCLUSION: P. acnes is not often found in bone lesions of SAPHO syndrome. A bone biopsy may represent a procedure useful for corroborating the diagnosis or for excluding other diseases only in specific cases.     

Successful treatment of a patient with Neuro-Behçet’s disease with low-dose weekly methotrexate

A 79-year-old man who had a history of recurrent oral ulcers, arthritis in the left knee joint and ileocecal ulcer was admitted to our hospital because of high fever, dysarthria and progressive dementia. Magnetic resonance imaging (MRI) examinations of the brain disclosed high signal intensity areas in the left pons, left midbrain, bilateral thalamus on T₂-weighted images. These lesions were detected as slightly low signal intensity areas on T₁-weighted images, some of which were ring-enhanced after the administration of gadolinium-DPTA. The cerebrospinal fluid (CSF) interleukin-6 activity was elevated remarkably (0.77 U/ml). A diagnosis of Neuro-Behçet’s disease (NB) was made and methotrexate (MTX) was started at a dose of 2.5 mg per week. After MTX therapy, MRI findings were improved and the IL-6 activity in the CSF was decreased significantly. In addition, the progression of neuropsychiatric symptoms was prevented without any side effects during MTX therapy over 3 years. It is suggested that low-dose MTX therapy might be effective in the treatment of NB.     

Pustulotic arthro-ostitis (SAPHO syndrome)

The sterile arthro-osteitis, especially in anterior chest wall, and also in spine and peripheral joints were observed in patients with pustulosis palmaris et plamtaris. These conditions were named pustulotic arthro-osteitis. Furthermore, the SAPHO syndrome, which stands for synovitis, acne, pustulosis, hyperostosis and osteitis, has been proposed in order to describe more varieties of bone, joints and skin lesions.     

Clinical features and radiological findings of 67 patients with SAPHO syndrome

Objectives: The purpose of this study was to facilitate the understanding of the SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis) syndrome by analyzing the clinical and radiological features of 67 Japanese patients with SAPHO syndrome.

Methods: Sixty-seven Japanese patients (female/male: 44/23, mean age at onset: 48.5 years) were diagnosed with SAPHO syndrome from 2002 to 2013 at our hospital. Medical records and radiological imaging of these patients were retrospectively reviewed.

Results: Among the 67 patients, 41 had dermatological manifestations, such as palmoplantar pustulosis, acne, and psoriasis. Initial symptom was local pain in all patients, and the most common initial site of the symptom was the anterior chest. Bacterial and fungal cultures from 20 bone biopsies were all negative. Histopathological diagnosis of the specimens was non-specific inflammation in all cases. Bone lesions were observed in 65 patients (97.0%). On the other hand, articular lesions including enthesitis were found in 31 patients (46.2%).

Conclusion: SAPHO syndrome had different clinical and radiological aspects. The clinical features were not remarkable, except the dermatological manifestations and the involvement of the anterior chest. Bone lesions including hyperostosis and osteitis were found radiographically in the majority of patients with SAPHO syndrome. These are the characteristics of the SAPHO syndrome, with the exclusion of other bone diseases.     

Ciliated foregut cyst in cirrhotic liver

We encountered a patient with a ciliated hepatic foregut cyst with accompanying liver cirrhosis, which was hard to distinguish from well-differentiated hepatocellular carcinoma. A lesion 2 cm in diameter was found in the subcapsular region of the medial segment of the liver. It was slightly hypoechoic on ultrasononraphy, of high attenuation on nonenhanced computed tomography (CT), of high intensity on T₁-weighted spin echo images of magnetic resonance imaging (MRI), and of isointensity on T₂-weighted spin echo images. It was not enhanced in the arterial phase images of MRI, and was shown as a complete perfusion defect on CT arterial portography. The cyst was enucleated and found to be filled with bloody mucinous fluid.     

In SAPHO syndrome anti-TNF-alpha therapy may induce persistent amelioration of osteoarticular complaints, but may exacerbate cutaneous manifestations

OBJECTIVES: SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a rare disease combining skin, bone and joint manifestations. In recent years new therapeutic strategies have been tried, among them TNF-alpha-blocking agents. We report our experience with infliximab in four cases of SAPHO syndrome refractory to conventional therapies. METHODS: Between 2002 and 2005, four cases of SAPHO syndrome (two females and two males; mean age 49.7 yr) responding poorly to conventional drugs were treated with infliximab. The dose was 5 mg/kg, according to the protocol used in spondyloarthropathies, with infusions at 0, 2 and 6 weeks followed by 6 weeks intervals. No active cutaneous manifestations were present at the time of starting therapy. RESULTS: Complete remission of osteoarticular involvement was achieved after the second or third infusion, and the positive response was maintained for up to 12 months. A patient relapsed after discontinuation of infliximab, because of infectious complication. Palmoplantaris pustulosis relapsed in two patients after three and six infusions, respectively; there was slight improvement after discontinuation of anti-TNF-alpha drugs. CONCLUSIONS: Infliximab seems to be a very effective therapy for osteoarticular complaints of SAPHO syndrome. Cutaneous involvement responded less favourably, palmoplantaris pustulosis relapse being a possible complication.