Osteitis Syndrome Research Articles

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome manifested as a mass on the chest wall: a case report

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disorder characterized by a variety of osseous and cutaneous symptoms. We presented a case of a middle-aged female presenting with a mass on the right chest wall. Respiratory specialists were unfamiliar with the condition and were unable to make a definitive diagnosis. The case outlined the diagnostic and treatment process and summarized the clinical characteristics of the syndrome, with the aiming of improving the diagnostic skills of respiratory specialists and reducing cases of missed diagnosis and misdiagnosis.

Current and future advances in practice: SAPHO syndrome and chronic non-bacterial osteitis (CNO).

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare, underdiagnosed disease with a wide clinical spectrum. Sterile bone inflammation, predominantly of the anterior chest, and skin manifestations (palmoplantar pustulosis, psoriasis vulgaris and acne) are the key features of SAPHO, which shares certain similarities with SpA. SAPHO is closely related to paediatric chronic non-bacterial osteitis (CNO), a spectrum of autoinflammatory bone diseases. The aetiology of SAPHO is considered multifactorial based on a complex interplay of genetic, immune and infectious factors. Despite the increasing awareness of SAPHO/CNO, diagnostic delay is common, as validated classification and diagnostic criteria are lacking. Treatment of SAPHO represents a challenge and includes anti-inflammatory drugs, antibiotics, bisphosphonates, synthetic conventional DMARDs and off-label use of anti-cytokine biologics and Janus kinase inhibitors. This review summarizes the current diagnostic and practical treatment approach to SAPHO/CNO and highlights the ongoing research endeavours concerning the definition and validation of diagnostic criteria, core domains and treatment.

Lincoln Sign in Synovitis, Acne, Pustulosis, Hyperostosis, and Osteomyelitis Syndrome.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is characterized by skin lesions and osteomyelitis. Although the pathogenesis of SAPHO syndrome remains unclear, chronic focal infection may play a role in the development of excessive immune responses.

Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis, Palmoplantar Pustulosis, and Neutrophilic Dermatoses: A GRAPPA 2023 Annual Meeting Update.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and chronic nonbacterial osteomyelitis (CNO) are rare autoinflammatory/autoimmune conditions seen in adults and children. Although osteoarticular manifestations are the primary distinguishing features of SAPHO, over half of patients also have palmoplantar pustulosis (PPP). These and other associated disorders such as acne, inflammatory bowel disease, and hidradenitis suppurativa are characterized, at least in the early stages, by neutrophilic infiltration. The bone and skin manifestations exhibit both innate and adaptive immune responses and therefore share similar pathogenic molecules and overlapping treatment targets. At the Group for Research and Assessment for Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, a 3-part presentation provided an overview of current efforts at establishing consensus on diagnosis/classification, treatment, and core outcome sets for SAPHO/CNO; an overview of PPP in SAPHO and as a standalone condition; and finally, an overview of the role of the neutrophil in these disorders.

Pediatric SAPHO syndrome with pleural effusion: case report of a unique finding in a rare disease.

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by bone inflammation and skin manifestations including acne, palmoplantar pustulosis, psoriasis, or hidradenitis suppurativa. SAPHO syndrome is considered on the same spectrum as chronic nonbacterial osteomyelitis/chronic recurrent multifocal osteomyelitis (CNO/CRMO), the former often being the nomenclature in adults and the latter in children. The diagnosis is made on patterns of clinical manifestations and is a diagnosis of exclusion. While skin and bone manifestations are commonly described with SAPHO syndrome, pleural involvement is rare, and few cases have been described in the literature, especially in pediatric patients. Herein we present a 14-year-old female with a past medical history of hidradenitis supprtiva, eczema, psoriasis, and a prior episode of culture-negative osteomyelitis who presented to the emergency room with chief complaints of right sided pain with inspiration and back pain. Exam revealed palmoplantar pustulosis, hidradenitis supprativa, psoriasis, and tenderness of vertebrae. Imaging showed a right sided pleural effusion and multiple sites of osteitis. Laboratory evaluation revealed elevated inflammatory markers, an exudative pleural effusion with neutrophilic predominance, and no evidence of malignancy, infection, or immunodeficiency. The patient was diagnosed with SAPHO syndrome and treated with naproxen, methotrexate, and golimumab with significant improvement including resolution of the pleural effusion. Pediatric SAPHO syndrome is a rare disease that classically causes osteitis and skin manifestations. This case highlights that pleural effusion can be a rare manifestation of pediatric SAPHO syndrome. Patients with suspected SAPHO syndrome with respiratory symptoms should be evaluated for pleural effusion.

TNF-alpha blockade in Primary Chronic Non-Bacterial Osteomyelitis of the Mandible.

Primary chronic Non-Bacterial Osteomyelitis of the jaw is a rare auto-inflammatory disease of unknown aetiology that bears pathophysiological resemblance to both the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome in adults and chronic recurrent multifocal osteomyelitis (CRMO) in children. Both SAPHO and CRMO respond to TNF-alpha blockade. Previously reported treatment regimens in CNOM including non-steroidal anti-inflammatory drugs, corticosteroids, antibiotics, anti-resorptive therapy, and surgery all bear disappointing results. TNF- α blockade is suggested as a treatment option by some experts but this is not backed by any clinical data.We sought to retrospectively and exhaustively report our experience of anti-TNF alpha therapy in refractory CNOM. Fifteen patients with refractory CNOM and high disease burden were referred to our centre. TNF- α blockade was attempted in 10 cases, given its efficacy in neighbouring diseases, its good tolerance profile and failure of previous treatment strategiesWe herein retrospectively report detailed outcomes for all patients having received anti-TNF alpha therapy for this indication in our centre. TNF-α-targeting therapy resulted in a rapid and sustained remission in a majority of patients with CNOM, without serious adverse events. Treatment was tapered and stopped without relapse in some patients despite a refractory course of several years. Male sex seems to be associated with a poorer outcome. Our results suggest that blocking TNF-α is efficient and safe in CNOM.

The comparison of clinical and pathological features between patients of SAPHO syndrome with different microbiological findings in bone biopsy.

To elucidate the existence of bacteria in situ and its influence on the clinical and pathological features of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. A total of 34 patients diagnosed with SAPHO syndrome were allocated to two groups (bacterial positive and bacterial negative) based on next-generation sequencing (NGS) and microbiological culture through CT guided percutaneous puncture. The clinical characteristics, biochemical markers, imaging data, and pathological results of the patients were analysed and compared between the two groups. And 32 infectious suppurative osteomyelitis patients were also included in this study to compare the pathological results with SAPHO syndrome patients. The positive rate of bacteria by NGS and bacterial culture were 41.2%, respectively. And the two methods detected a wide variety of bacterial species, including cocci, bacilli, and others. The difference of clinical symptoms (such as pain, swelling, and warmth), biochemical markers, imaging findings and pathological findings were not statistically significant between the bacteria positive and the bacteria negative groups. Moreover, patients with SAPHO syndrome had less inflammatory cell infiltration and increased granulation tissue formation compared with infectious suppurative osteomyelitis patients. NGS and bacterial culture expand the variety of detectable bacteria and improve the detection rate of bacteria in SAPHO syndrome. The bacteria in SAPHO patients may be low-virulence colonising bacteria presented in the skin or in the body. The less inflammatory cell infiltration in tissue may reflect a damaged ability to clear low-virulence bacteria in patients with SAPHO syndrome. The presence of low-virulence bacteria may provide a new therapy choice for refractory SAPHO patients.

Severe respiratory failure secondary to unilateral phrenic nerve injury: A case report

AbstractPatients with unilateral phrenic nerve paralysis are usually asymptomatic at rest. We present a 77‐year‐old woman with a chest wall osteoarthropathy associated with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome that developed severe hypercapnic respiratory failure following cryoballoon ablation for the management of atrial fibrillation. Her right phrenic nerve injury (PNI) was confirmed by chest radiography, phrenic nerve conduction studies, and diaphragmatic ultrasonography. We conclude that unilateral PNI during ablation invalidated the diaphragmatic compensation for pre‐existing reduced thoracic expansion, resulted in severe hypoventilation. Clinicians should be careful of the fact even unilateral PNI could cause catastrophic respiratory failure in patients with restricted thoracic expansion.

Profiles of Circulating Exosomal Mirna in Patients with SAPHO Patients by High-Throughput Sequencing.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disease that is characterized by autoinflammatory lesions on both bones and skin. The diverse manifestations and limited understanding of its etiology have hindered the diagnosis and treatment of this condition. SAPHO syndrome is also classified as a primary inflammatory osteitis. The onset of osteoarticular involvement in this disease is typically gradual, and the identification of associated biomarkers may be crucial for accurate diagnosis, effective treatment, and a better understanding of its underlying mechanisms. We enrolled a total of 6 SAPHO patients and 3 healthy volunteers for this study. The miRNA expression profile in circulating exosomes was analyzed using next-generation sequencing. A total of 45 miRNAs were found to be differentially expressed in SAPHO patients. Linear discriminant analysis effect size analysis and Wilcoxon rank-sum test were employed to identify biomarkers based on these differentially expressed miRNAs. Among them, we selected 4 miRNAs as biomarkers for SAPHO syndrome, resulting in an area under the receiver operating characteristic curve of 1. The differentially expressed miRNAs indicated enrichment in immune system and endocrine system-related KEGG pathways, as well as infectious diseases and cancers. Furthermore, the most significantly enriched molecular functions in GO analysis were protein binding and catalytic activity. The exosomal miRNA profile in SAPHO syndrome exhibited significant changes, suggesting its potential as a candidate biomarker for diagnostic assistance, although further investigation is warranted to elucidate their role in the pathology.

Chronic Nonbacterial Osteomyelitis, Hidradenitis Suppurativa, and SAPHO Syndrome

Introduction: Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome may represent one side of a spectrum of disease that also includes chronic nonbacterial osteomyelitis. Case: A 23-year-old male with bone pain in the anterior chest, shoulder, clavicles, left elbow, and left ankle presented to rheumatology clinic after multiple evaluations for infectious osteomyelitis. Imaging and deep bone biopsies of affected areas were consistent with chronic osteomyelitis, with labs notable for elevated erythrocyte sedimentation rate, C-reactive protein, and positivity for HLA-B27. A full skin exam was consistent with hidradenitis suppurativa, and he was started on infliximab and methotrexate with improvement in both his osteoarticular and skin symptoms. Conclusions: Patients presenting with features of follicular occlusion or neutrophilic dermatoses in conjunction with bone pain should be evaluated for SAPHO/CNO. In patients with SAPHO/CNO with vertebral involvement, bisphosphonates in addition to anti-inflammatory medications (such as methotrexate and TNF-inhibitors) can be effective.

Dramatic response of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome to tofacitinib monotherapy: a case report

IntroductionThe synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare condition. Its treatment remains a challenge for clinicians, and often yields mixed results.CaseWe report the case of a 51-year-old Caucasian woman who presented with SAPHO syndrome with mainly axial involvement. She had been treated with sulfasalazine and anti-inflammatory drugs for many years without any success. A few weeks after starting treatment with tofacitinib, both clinical and biological parameters dramatically improved. Imaging also showed considerable regression of the vertebral and pelvic lesions. However, tofacitinib had to be discontinued due to the occurrence of pulmonary embolism. Consequently, recurrence of bone pain and biologic inflammation was rapidly observed.ConclusionsAnti-JAKs are an interesting treatment option in the management of SAPHO syndrome that need further clinical trials and assessment for validating response.

Stellate ganglion block in the treatment of SAPHO syndrome: A case report.

Synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare and refractory autoinflammatory disease, and there is no consensus on its treatment. Stellate ganglion block (SGB) blocks sympathetic nerves, ameliorates immune dysfunction, and alleviates stress response, which has been used to treat various chronic pain syndromes, arrhythmias, and post-traumatic stress disorder (PTSD). Also, the SGB has been reported to be successfully used to treat certain skin diseases, autoinflammatory diseases, and menopausal symptoms. In this study, over 3 years of follow-up, we found that SGB successfully intervened the symptoms of SAPHO syndrome, including sternoclavicular joint arthritis and palmoplantar pustulosis.

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

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. 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. 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). 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.

A young woman with generalized pustular psoriasis and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome treated successfully with upadacitinib

A young woman with generalized pustular psoriasis and synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome treated successfully with upadacitinib

SAPHO Syndrome in Crohn’s Disease Successfully Treated with Ustekinumab: Case Report and Review of the Literature

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

SAPHO Syndrome in Crohn’s Disease Successfully Treated with Ustekinumab: Case Report and Review of the Literature

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

Family aggregation and prevalence of other autoimmune diseases in SAPHO syndrome

ObjectiveSAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) syndrome is a heterogeneous disease that clinically manifests as chronic inflammatory osteoarticular and dermatological lesions. Few reports have described familial clustering of SAPHO syndrome cases. This research aimed to illustrate the family aggregation of SAPHO syndrome and investigate the prevalence of autoimmune disorders among SAPHO syndrome patients and first-degree relatives in a large cohort. MethodsWe retrospectively reviewed the medical records of 233 SAPHO patients diagnosed at Peking Union Medical College Hospital. Direct phone calls were made to each first-degree relatives. All relatives of the patients who reported SAPHO syndrome were asked for a detailed outpatient evaluation. ResultsA total of 233 patients and 1227 first-degree relatives were recruited. Six (2.6 %) patients had positive SAPHO family history, including four mother-daughter pairs and two sister pairs. Twenty-one (9.0 %) patients presented at least one kind of autoimmune disease, including 12 rheumatoid arthritis and 4 ulcerative colitis cases. Fifty-eight (24.9 %) SAPHO syndrome patients had 68 (5.5 %) first-degree relatives with at least one autoimmune disorder. The palmoplantar pustulosis, psoriasis vulgaris, and rheumatoid arthritis prevalence in our subjects were each higher than reference rates. ConclusionThis is the first evaluation of familial aggregation for SAPHO syndrome in a large cohort. SAPHO syndrome has a weak familial aggregation. There is a relatively high prevalence of coexisting autoimmune disease among patients with SAPHO syndrome and their first-degree relatives. These results would prompt physicians to screen SAPHO syndrome patients and their family members for concomitant autoimmune diseases. KeypointsThis study suggesting a potential genetic component in the pathogenesis of SAPHO syndrome. This study is the first to evaluate the family aggregation of SAPHO syndrome in a large cohort.

Extracorporeal Shock Wave Therapy for the Treatment of Musculoskeletal Pain: A Narrative Review.

Extracorporeal shock waves have been used for pain treatment for various sub-acute and chronic musculoskeletal (MSK) problems since 2000. The aim of this article is to update information on the role of extracorporeal shock wave therapy (ESWT) in the treatment of various pathologies that cause MSK pain. Given that in the last two years, articles of interest (including systematic reviews and meta-analyses) have been published on less known indications, such as low back pain, nerve entrapments, osteoarthritis and bone vascular diseases, a literature search was conducted in PubMed, the Cochrane Database, EMBASE, CINAHL and PEDro, with the aim of developing a narrative review of the current literature on this topic. The purposes of the review were to review possible new mechanisms of action, update the level of evidence for known indications and assess possible new indications that have emerged in recent years. Although extracorporeal shock waves have mechanical effects, their main mechanism of action is biological, through a phenomenon called mechanotransduction. There is solid evidence that supports their use to improve pain in many MSK pathologies, such as different tendinopathies (epicondylar, trochanteric, patellar, Achilles or calcific shoulder), plantar fasciitis, axial pain (myofascial, lumbar or coccygodynia), osteoarthritis and bone lesions (delayed union, osteonecrosis of the femoral head, Kienbock's disease, bone marrow edema syndrome of the hip, pubis osteitis or carpal tunnel syndrome). Of the clinical indications mentioned in this review, five have a level of evidence of 1+, eight have a level of evidence of 1-, one indication has a level of evidence of 2- and two indications have a level of evidence of 3. The current literature shows that ESWT is a safe treatment, with hardly any adverse effects reported. Furthermore, it can be used alone or in conjunction with other physical therapies such as eccentric strengthening exercises or static stretching, which can enhance its therapeutic effect.

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

We aimed to analyze the clinical characteristics and outcomes of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. 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. 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 olderthan those with only ACW involvement (p = 0.002) and had a longerdiagnosis 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. 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.

Involvement of knee and foot pathology presenting as an accompanying sign in a soldier of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is expressed as chronic multifocal osteomyelitis. There is no report to show a knee/foot lesions accompanying with SAPHO syndrome. We herein present a case of SAPHO syndrome with involvement of pathology of knee and foot, which was confirmed by obtaining the images of skeletal scintigraphy. We also described the clinical indicators and imaging features.