Anterior Chest Wall Non-traumatic Arthropathies: A Crucial but Often Overlooked Site.

OBJECTIVE: The purpose of this study was to describe the distribution of Anterior Chest Wall (ACW) arthropathies in a tertiary care center and identify clinical, biological and imaging findings to differentiate osteoarthritis (OA) from non-osteoarthritis (N-OA) etiologies. METHODS: Search from medical records from January 2009 to April 2022, including patients with manubriosternal and/or sternoclavicular and/or sternocostal joint changes confirmed by ultrasonography, computed tomography or magnetic resonance imaging. The final study group was divided into OA and N-OA subgroups. RESULTS: A total of 108 patients (34 males and 74 females, mean age: 47.3 ± 13 years) were included. Twenty patients had findings of OA, while 88 were diagnosed with N-OA pathologies. SpA was the most common etiology in the N-OA group (n = 75). The other N-OA etiologies were less common: rheumatoid arthritis (n = 4), Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome (n = 3), infectious arthritis (n = 3) and microcrystalline arthropathies (n = 3). Regarding the distinctive features, ACW pain was the inaugural manifestation in 50% of patients in OA group and 18.2% of patients in N-OA group (p = 0.003); high inflammatory biomarkers were more common in N-OA group (p = 0.033). Imaging findings significantly associated with OA included subchondral bone cysts (p < 0.001) and intra-articular vacuum phenomenon (p < 0.001), while the presence of erosions was significantly associated with N-OA arthropathies (p = 0.019). OA was independently predicted by the presence of subchondral bone cysts (p = 0.026). CONCLUSION: ACW pain is a common but often underestimated complaint. Knowledge of the different non-traumatic pathologies and differentiation between OA and N-OA etiologies is fundamental for appropriate therapeutic management.

The clinical characteristics and prognosis of patients with SAPHO syndrome--a real-world cohort study.

OBJECTIVES: We aimed to analyze the clinical characteristics and outcomes of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: The clinical records of 64 patients with SAPHO syndrome were collected, and the treatment and outcomes of 27 patients were followed up. The patients were divided into three groups according to the site of bone lesions: only anterior chest wall (ACW) involvement, only spinal involvement, and bone lesion involvement at both sites. The clinical characteristics and outcomes were compared. The clinical characteristics of the patients with and without peripheral joint involvement were compared. RESULTS: Among all patients, 31.25% (20/64) had only ACW involvement, 15.63% (10/64) had only spinal involvement, and 53.12% (34/64) had both ACW and spinal involvement. Peripheral joint involvement was observed in 25.00% (16/64) of the patients. Patients with only spinal involvement were older than those with only ACW involvement (p = 0.006). Patients with both ACW and spinal involvement were older than those with only ACW involvement (p = 0.002) and had a longer diagnosis delay (p = 0.015). Patients with peripheral joint involvement were younger than those without peripheral joint involvement (p = 0.028). During follow-up, 88.89% (24/27) of patients had good outcomes. Twenty-two patients were treated with non-steroidal anti-inflammatory drugs + Iguratimod (IGU), and the outcomes of 90.91% (20/22) improved. CONCLUSIONS: A relationship may exist between the sites of bone lesions and clinical characteristics of patients with SAPHO syndrome. The clinical outcomes of these patients may be good, and IGU may be effective in treating SAPHO syndrome. Key Points • This study is the first long-term follow-up on the effectiveness of iguratimod in treating patients with SAPHO. • This study revealed that patients with SAPHO and different bone lesion sites may present with different clinical characteristics.

Pro and contra: is synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) a spondyloarthritis variant?

PURPOSE OF REVIEW: The purpose of this review is to present the up-to-date evidence on the epidemiology, pathogenesis, musculoskeletal manifestations, and imaging of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and to discuss its relationship with spondyloarthritis (SpA). RECENT FINDINGS: SAPHO is a rare inflammatory disorder of bone, joints, and skin, with a worldwide distribution that predominantly affects the middle-age adults. The hallmark of the syndrome is a constellation of sterile inflammatory osteitis, hyperostosis, and synovitis involving the anterior chest wall, associated with acneiform and neutrophilic dermatoses, such as palmoplantar pustulosis and severe acne. The axial skeleton, sacroiliac, and peripheral joints can be involved in a similar fashion to SpA. The pathogenesis of the syndrome is multifactorial. The diagnosis is mainly based on the clinical and typical radiological features. The treatment approach is based on the off-label use of antibiotics, bisphosphonates, disease-modifying antirheumatic drugs, and anticytokine biologics. SUMMARY: The SAPHO syndrome shares common features with SpA-related diseases, yet also shows some unique pathogenetic and clinical features. The nosology of SAPHO remains a subject of controversy, awaiting further research into the pathogenetic and clinical aspects of this syndrome. A better understanding of these aspects will improve the diagnostics and clinical care of patients with SAPHO.

Does SAPHO syndrome exist in dermatology?

In the late 1960s, palmoplantar pustulosis (PPP) with sternocostoclavicular arthropathy was first described in Japan, predominantly affecting women in the perimenopausal age. In the 1970s, the chronic non-bacterial osteomyelitis and chronic recurrent multifocal osteomyelitis were initially observed in paediatric patients with approximately 70% girls. Acne fulminans accompanied by polyarthralgia have been observed since early 1970s, which almost exclusively occurs in adolescent boys. Report on spondyloarthropathy associated with hidradenitis suppurativa can be traced back to 1982. The SAPHO syndrome was coined in 1987 to lump together synovitis, acne, pustulosis, hyperostosis and osteitis to conceptualize a group of inflammatory osteocutaneous diseases of unclear etiopathogenesis and ill-defined associations spanning disparate age and gender groups. From historical view, Sasaki syndrome is proposed to replace SAPHO syndrome to represent PPP with sternocostoclavicular arthropathy in the absence of other skin manifestations. Hidradenitis suppurativa is folliculitis in pathogenesis and no longer classified as acne. PPP accompanied by psoriasis vulgaris is more likely psoriasis pustulosa palmoplantaris in dermatological aspect, and the associated arthritis is part of psoriatic arthropathy. Pathophysiology of these disorders is incompletely understood. To echo the advancement of high-throughput sequencing, splitting but not lumping of clinical findings would be a better strategy to decipher these multigenic complex inflammatory disorders.

Rapid induction of clinical remission in SAPHO syndrome using high-dose Tripterygium glycosides: A case report.

RATIONALE: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disease without standard treatments. Tripterygium wilfordii hook f (TwHF) is a traditional Chinese herb with anti-inflammatory effect, and 1.0 mg/(kg·d) dose of Tripterygium glycosides has been reported to significantly improve the disease activity of a SAPHO patient in a case report. However, the optimal dose of TwHF is still unclear. Here, we report the first case of SAPHO patient who achieved rapid remission in clinical symptoms after receiving 1.5 mg/(kg·d) dose of Tripterygium glycosides treatment. PATIENT CONCERNS: A 67-year-old woman noted palmoplantar pustulosis and pain in the anterior chest wall and waist. Bone scintigraphy demonstrated the typical tracer accumulation feature and magnetic resonance images showed bone marrow edema in lumbosacral vertebra. DIAGNOSES: The diagnosis was made by dermatological and osteoarticular manifestations and classical signs in bone scintigraphy in accordance with the diagnostic criteria proposed in 2012. INTERVENTIONS: Tripterygium glycosides was given with a primary dose of 1.5 mg/(kg·d) for 1 month and then reduced at a rate of 10 mg every 2 weeks until 1.0 mg/(kg·d) for a long-term maintenance. OUTCOMES: Fast-induced remission on clinical manifestations was achieved and magnetic resonance imaging abnormality was improved significantly. Additionally, no apparent side effects were observed. LESSONS: 1.5 mg/(kg·d) dose of Tripterygium glycosides seems to have fast-induced remission than 1.0 mg/(kg·d) with reliable safety. Besides, Tripterygium glycosides may also have a pharmacological effect of inhibiting osteolysis and enhancing bone strength.

Imaging features in patients with SAPHO/CRMO: a pictorial review.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and chronic recurrent multifocal osteomyelitis (CRMO) have been described as disorders of chronic osteoarthritic inflammation frequently associated with skin manifestations, and SAPHO and CRMO (SAPHO/CRMO) are rare autoinflammatory disorders of unknown etiology. SAPHO tends to occur in adults and CRMO predominantly occurs in children and adolescents. SAPHO/CRMO can affect any skeletal region (e.g., anterior chest wall, spine, or long bones). As SAPHO/CRMO are diagnoses of exclusion, the diagnoses might be difficult if skin manifestations are not clearly evident. However, knowledge of the imaging findings of skeletal disorders is helpful for correcting the diagnosis and avoiding unnecessary invasive procedures, as well as in facilitating early diagnosis and adequate treatment. This pictorial review describes the appearance of increased skeletal uptake for SAPHO/CRMO on bone scintigraphy along with findings from radiography, computed tomography, and magnetic resonance imaging.

Demographic, clinical, and scintigraphic comparison of patients affected by palmoplantar pustulosis and severe acne: a retrospective study.

OBJECTIVE: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome encompasses heterogeneous dermatological manifestations, mainly palmoplantar pustulosis (PPP) and severe acne (SA). This study aims to explore the necessity of stratified management according to skin lesions. METHODS: In a cohort of SAPHO patients, we compared the demographic, clinical, and scintigraphic characteristics of the SAPHO patients whose skin lesion was PPP or SA. RESULTS: A total of 249 patients were included (227 affected by PPP and 22 affected by SA). Patients with SA were younger at onset (20, interquartile ranges (IQR) 15-30 vs. 37, IQR 30-46 years old; p < 0.001) and enrollment (35, IQR 25-38 vs. 41, IQR 33-50 years old; p = 0.001), and they had a prolonged disease duration (88.5 months, IQR 18.7-216.0 vs. 16.0, IQR 7.0-48.0 months; p < 0.001) and time needed for diagnosis (7.5, IQR 2.0-19.0 vs. 1.0, IQR 1.0-4.0 years; p < 0.001). Adjusted by age, sex, and disease duration, SA was significantly associated with more disease-modifying anti-rheumatic drug (DMARD) use (adjusted odds ratio (OR) 3.72; 95% confidence interval (CI) 1.23, 12.62; p = 0.019) and more sternoclavicular joint involvement (adjusted OR 5.91; 95% CI 1.17, 61.3; p = 0.030) in two separate Firth's logistic regression models. CONCLUSION: SAPHO patients affected by PPP or SA as the only skin lesion may have different epidemiologic features, osteoarticular manifestations, and treatment history.Key Points• SAPHO patients with PPP or SA were heterogenous in both demographic, clinical, and imaging features.• SAPHO patients with SA were mainly male and had a significantly younger age and longer duration of symptoms before diagnosis.• SA in SAPHO patients was significantly associated with more sternoclavicular involvement and more DMARD use history.

Images of the month 3: The 'bull's head' sign of SAPHO syndrome.

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare, chronic, inflammatory disorder with cutaneous and osteoarticular manifestations.1 The aetiology of SAPHO syndrome is unknown and therefore treatment is tailored towards the individual. Non-steroidal anti-inflammatory drugs, bisphosphonates, corticosteriods, antibiotics, disease modifying anti-rheumatic drugs and biologics have all been used with variable success.

SAPHO syndrome with enthesopathy.

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome was first described as chronic recurrent multifocal osteomyelitis. Because of its rarity, a thorough description of its clinical manifestations is lacking. Herein, we describe the clinical manifestations and imaging features, especially the enthesopathy in bilateral Achilles tendons, of a middle-aged Asian woman with SAPHO syndrome, who improved after diclofenac treatment.

Failure of tocilizumab in treating two patients with refractory SAPHO syndrome: a case report.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disease with no standard treatment. Interleukin (IL)-6 inhibitors represent a novel therapeutic option for rheumatoid arthritis and some autoinflammatory diseases. However, the clinical utility of IL-6 inhibitors in treating SAPHO syndrome has been poorly investigated. In the present report, we describe two patients with SAPHO syndrome that was unresponsive to conventional treatment. Tocilizumab, an anti-IL-6 receptor monoclonal antibody, was putatively administered according to positive IL-6 immunohistochemical staining in biopsied bone tissues. However, the disease continued to progress, and new-onset or worsening skin lesions were noted with transient neutropenia. These cases demonstrate that tocilizumab may not be an ideal option for treating SAPHO syndrome.

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.

Successful treatment of SAPHO syndrome with apremilast.

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a rare disease with inflammatory osteoarticular and skin involvement. The pathogenesis of SAPHO syndrome remains unclear, but evidence suggests it may be an autoinflammatory disease triggered upon exposure to infectious agents in genetically predisposed individuals. Induction of the interleukin (IL)-23/T helper 17 axis in addition to neutrophil activation seem to play a key role, and therapies targeting these immunological pathways, including tumour necrosis factor (TNF) inhibitors, ustekinumab, secukinumab and the IL-1 inhibitor anakinra, are potential treatment options that need further investigation. Here we report a case of a 24-year-old woman with SAPHO syndrome who presented at our clinic with palmoplantar pustulosis and sternoclavicular joint involvement. Previous treatments with topical steroids and keratolytics combined with nonsteroidal anti-inflammatory drugs, intravenous methylprednisolone, methotrexate and sulfasalazine had all failed to improve symptoms. Therapy with etanercept was not tolerated, and because of a previous demyelinating peripheral neuropathy, further treatment with TNF inhibitors was avoided. We initiated ustekinumab 45 mg, which improved skin manifestations but not joint pain. Dose escalation to 90 mg initially improved joint pain, but the dose had to be reduced to 45 mg again because of increased infections. During subsequent 45-mg ustekinumab treatment, joint pain exacerbated so we switched to adalimumab which caused an exacerbation of the disease, so we switched to secukinumab, which improved skin and joint symptoms significantly but was associated with a pustular hypersensitivity reaction. Finally, we began treatment with apremilast, a pan-cytokine approach, resulting in stabilization of the skin and joint symptoms without side-effects. To our knowledge, this is the first case report of apremilast as a treatment for SAPHO syndrome.

[About a case of laryngeal location of SAPHO]. / À propos d'un cas de SAPHO de localisation laryngée.

INTRODUCTION: Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) is a syndrome that combines dermatological, articular and osseous inflammatory manifestations. Bilateral laryngeal immobility relative to cricoarytenoid joint origin is very uncommon. This article presents a case of bilateral cricoarytenoid joint ankylosis in a SAPHO syndrome context. CASE REPORT: A 53-year-old patient presenting with a two year history of intermittent bouts of dyspnea. A SAPHO syndrome was discussed on repeated thoracic CT-scan. The link between dyspnea and SAPHO syndrome had not been made immediately given the absence of any known anteriority. However, having ruled out other etiologies and after having had to perform a tracheotomy due a worsening of the respiratory condition, this diagnosis was considered. Treatment by corticosteroids and infliximab permitted a clinical improvement of the patient. CONCLUSION: This clinical case report should increase awareness of possible cricoarytenoid joint involvement in SAPHO.

Síndrome de SAPHO como diagnóstico diferencial de metástasis / SAPHO syndrome in the differential diagnosis of metastasis

El síndrome de SAPHO fue propuesto a finales de los años 80 para agrupar diversas manifestaciones osteoarticulares con hallazgos radiológicos propios como la hiperostosis de la pared anterior del tórax. La prevalencia, la causa y la patogénesis de la enfermedad son desconocidas. El diagnóstico se realiza tanto por la clínica como por la imagen específica gammagráfica de «asta de toro» en la articulación esternoclavicular. Se presenta el caso de una mujer de 64 años diagnosticada de carcinoma ductal infiltrante de mama derecha pT1N0Mx. En el estudio de extensión de la enfermedad se evidenció imagen gammagráfica de lesión blástica, difusa, en manubrio esternal, sospechosa de enfermedad de Paget o lesión metastásica. Se completó el estudio con TC torácica en la que se evidenció esclerosis del manubrio esternal, sugerente de metástasis. Por el resultado de los estudios se pensó en el síndrome de SAPHO como opción diagnóstica más probable. El bajo estadio tumoral de la paciente hizo pensar en posibles alternativas diagnósticas. Conocer esta entidad clínica puede evitar errores a la hora de clasificar en estadios tumorales más avanzados a un sujeto y, por tanto, evitar tratamientos quimioterápicos y radioterápico más agresivos (AU)

SAPHO syndrome was proposed in the late 80s in order to group different osteoarticular manifestations with specific radiological findings such as the hyperostosis of the front part of the chest wall. Prevalence, etiology and pathogenesis of the disease are unknown, while diagnosis is made both clinically and by the specific gammagraphic image of «bull horn» in the sternoclavicular joint. The following case of a 64-year-old woman diagnosed with infiltrating ductal carcinoma of the right breast pT1N0Mx is reported. When studying the extent of the disease, a gammagraphic image of diffuse blast injury in the sterna manubrium was evidenced, which allowed the suspicion of Paget's disease or metastatic injury. Study was completed with a chest CT in which manubrium sclerosis was evidenced, suggesting metástasis. Res ults of the studies pointed out SAPHO syndrome as the most likely diagnostic option. The low tumor stage of the patient prompted the idea of possible alternative diagnoses. A deeper knowledge of this clinical condition may be crucial to avoid mistakes when classifying a subject in more advanced tumor stages, and consequently, to prevent the use of more aggressive chemotherapy and radiotherapy treatment (AU)

SAPHO Syndrome: Imaging Findings of Vertebral Involvement.

BACKGROUND AND PURPOSE: Imaging findings in patients with a combination of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) are often misinterpreted as discitis/osteomyelitis or metastases, resulting in multiple biopsies and delayed diagnosis. We have incidentally noted a semicircular morphology in vertebral body imaging in several cases of SAPHO syndrome with vertebral involvement. Our goal was to evaluate the prevalence of this distinctive morphology in these patients. MATERIALS AND METHODS: A retrospective review of patients with SAPHO syndrome diagnosed between July 1998 and August 2013 was conducted. A descriptive analysis of MR imaging, CT, radiography, bone scanning, and PET imaging was performed for the presence and distribution of vertebral body signal intensity or attenuation changes and/or enhancement; contiguous vertebral body involvement; vertebral body collapse; endplate irregularity; disc space, facet, and spinous process involvement; subligamentous thickening; and paraspinal soft-tissue involvement. RESULTS: Eighteen patients (16 women [89%]; mean age, 52.9 years) with SAPHO and spine involvement were included. Contiguous involvement of ≥2 vertebral bodies was found in 16 patients (89%), with a curvilinear or "semicircular" pattern involving portions of adjacent vertebral bodies in 10 (63%, P = .14). Most intervertebral discs demonstrated absence of abnormal T2 hyperintensity (73%) and enhancement (89%). Subligamentous thickening was present in 12 (67%). Paraspinal soft-tissue involvement was present in 6 (33%). CONCLUSIONS: SAPHO syndrome should be included in the differential diagnosis in a patient with a curvilinear or semicircular pattern of vertebral involvement, contiguous vertebral body involvement, and absence of intervertebral disc edema and enhancement.

Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome: a single centre study of a cohort of 164 patients.

OBJECTIVE: The aim was to assess the clinical, laboratory and radiological features of SAPHO syndrome. METHODS: We recruited all patients presenting to Peking Union Medical College Hospital from 2004 to 2015 diagnosed with SAPHO syndrome. The medical data, laboratory test results and imaging were collected for all patients. RESULTS: One hundred and sixty-four patients (111 women and 53 men) were recruited to our cohort. The mean age of the patients was 40.71 years. Nine patients had osteoarticular symptoms without skin involvement. One hundred and forty-three and 25 patients had palmoplantar pustulosis and severe acne, respectively. Psoriasis vulgaris was accompanied by palmoplantar pustulosis or severe acne in 24 patients. One hundred and sixty-four patients suffered from pain in the anterior chest wall, followed by spine (12 in the cervical region, 36 in the thoracic region and 111 in the lumbosacral region) and peripheral joint (136 patients) involvement. None of the patients had IBD. The hs-CRP level was increased in 70.8% patients. Only 2.4% were HLA-B27 positive. CT scan indicated osteolysis, sclerosis and hyperostosis in the anterior chest wall and spine in SAPHO syndrome patients. The bull-horn sign was the typical characteristic of SAPHO syndrome seen in bone scintigraphy images. One hundred and thirty-one (79.9%), 85 (51.8%), 100 (61%) and 54 (32.9%) patients took NSAIDs, CSs, DMARDs and oral bisphosphonates, respectively. CONCLUSION: SAPHO syndrome is predominant in middle-age women, characterized by dermatological and osteoarticular manifestations with unknown aetiology. CT scan and bone scintigraphy are useful for diagnosis. There is still no standard treatment to control the disease.