Treatment and monitoring of SAPHO syndrome: a systematic review.

BACKGROUND AND OBJECTIVES: Synovitis acne pustulosis hyperostosis osteitis (SAPHO) is a rare heterogeneous disease of unknown aetiopathology. Externally validated and internationally agreed diagnostic criteria or outcomes and, as a result, prospective randomised controlled trials in SAPHO are absent. Consequently, there is no agreed treatment standard. This study aimed to systematically collate and discuss treatment options in SAPHO. METHODS: Following 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' guidance, a systematic literature search was conducted using PubMed, Scopus and Web of Science databases. Prospective clinical studies and retrospective case collections discussing management and outcomes in SAPHO involving five or more participants were included. Articles not published in English, studies not reporting defined outcomes, and studies solely relying on patient-reported outcomes were excluded. RESULTS: A total of 28 studies (20 observational, 8 open-label clinical studies) reporting 796 patients of predominantly European ethnicity were included. Reported therapies varied greatly, with many centres using multiple treatments in parallel. Most patients (37.1%) received non-steroidal anti-inflammatory drugs alone or in combination. Bisphosphonates (22.1%), conventional (21.7%) and biological (11.3%) disease-modifying antirheumatic drugs were the next most frequently reported treatments. Reported outcomes varied and delivered mixed results, which complicates comparisons. Bisphosphonates demonstrated the most consistent improvement of osteoarticular symptoms and were associated with transient influenza-like symptoms. Paradoxical skin reactions were reported in patients treated with TNF inhibitors, but no serious adverse events were recorded. Most treatments had limited or mixed effects on cutaneous involvement. A recent study investigating the Janus kinase inhibitor tofacitinib delivered promising results in relation to skin and nail involvement. CONCLUSIONS: No single currently available treatment option sufficiently addresses all SAPHO-associated symptoms. Variable, sometimes descriptive outcomes and the use of treatment combinations complicate conclusions and treatment recommendations. Randomised clinical trials are necessary to generate reliable evidence.

Serum Sp17 Autoantibody Serves as a Potential Specific Biomarker in Patients with SAPHO Syndrome.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome shows a wide variability in musculoskeletal and cutaneous manifestations, and it is therefore underrecognized and misdiagnosed in the clinic due to a lack of specific markers. In this study, we aimed to identify specific biomarkers by screening serum autoantibodies in SAPHO patients with a 17K human whole-proteome microarray. The serum anti-Sp17 autoantibody was identified and verified to be a specific biomarker in patients with SAPHO syndrome. Indeed, the level of the anti-Sp17 autoantibody was significantly increased in patients with active SAPHO compared to patients with an inactive disease and healthy controls (P < 0.05). Additionally, serum anti-Sp17 autoantibody levels correlated with those of serum hypersensitive C-reactive protein (hsCRP), the erythrocyte sedimentation rate (ESR), and ß-crosslaps (ß-CTx) in patients with active SAPHO disease. Moreover, anti-Sp17 autoantibody levels were markedly decreased after anti-inflammatory treatment with pamidronate disodium, which downregulated levels of hsCRP and ESR in patients with active SAPHO. Thus, serum levels of the anti-Sp17 autoantibody might serve as a specific biomarker for the diagnosis of SAPHO syndrome or for monitoring the disease status.

Skin inflammation associated with arthritis, synovitis and enthesitis. Part 1: psoriatic arthritis, SAPHO syndrome, Still's disease, Behçet's disease.

The coincidence of skin and joint inflammation poses a challenge for both dermatologists and rheumatologists. Adequate management of such disorders requires that physicians of both specialties have sound knowledge of the other discipline. In case of suspected joint involvement, familiarity with the diagnostic options available to rheumatologists enables dermatologists to selectively refer their patients for a rheumatology consult. The objective of the present review is to familiarize the reader with the stepwise diagnostic workup performed by rheumatologists today, including laboratory tests, musculoskeletal ultrasound, X-ray studies, and magnetic resonance imaging. Subsequently, we will discuss a number of disorders characterized by the concurrence of skin and joint inflammation, highlighting aspects of epidemiology, etiology and pathogenesis, clinical presentation, diagnosis and treatment. These disorders include psoriatic arthritis as well as autoinflammatory disorders such as SAPHO syndrome, Still's disease and Behçet's disease.

Síndrome de SAPHO en pacientes sometidos a cirugía bariátrica: ¿relación causal o simple coincidencia? / SAPHO syndrome in patients undergoing bariatric surgery: Causality or coincidence?

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Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation.

Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro-IL)-1ß to its active isoform IL-1ß. The overproduction of IL-1ß triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well-known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.

SAPHO Syndrome: Current Developments and Approaches to Clinical Treatment.

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare autoimmune disease which, due to its clinical presentation and symptoms, is often misdiagnosed and unrecognized. Its main features are prominent inflammatory cutaneous and articular manifestations. Treatments with immunosuppressive drugs have been used for the management of SAPHO with variable results. To date, the use of anti-TNF-α agents has proved to be an effective alternative to conventional treatment for unresponsive or refractory SAPHO cases. TNF-α is a pro-inflammatory cytokine and pivotal regulator of other cytokines, including IL-1 ß, IL-6, and IL-8, involved in inflammation, acute-phase response induction, and chemotaxis. IL-1 inhibition strategies with anakinra have shown efficacy as first and second lines of treatment. In this review, we will describe the main characteristics of biological drugs currently used for SAPHO syndrome. We also describe some of the promising therapeutic effects of ustekinumab, an antibody against the p40 subunit of IL-12 and IL-23, after failure of multiple drugs including anti-TNF-α and anakinra. We discuss the use and impact of the new anti-IL-1 antagonists involved in the IL-17 blockade, in particular for the most difficult-to-treat SAPHO cases.

Current knowledge and future prospects for SAPHO syndrome.

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a complex disorder characterized by osteoarticular and cutaneous symptoms. Most patients experience bone pain and dermatologic manifestations. Diagnosis of SAPHO syndrome is based on exclusion of infectious arthritis and septic osteomyelitis with findings of hyperostosis or chronic recurrent multifocal osteomyelitis involving axial or peripheral skeleton, with or without skin manifestations. The pathophysiology of SAPHO is unclear, although several hypotheses exist. Some of these hypotheses have led to the ever growing treatment options of medications. Broad varieties of medications have been used, such as nonsteroidal anti-inflammatory drugs and disease-modifying agents. New therapeutic options, such as tumor necrosis factor inhibitors have evolved and have shown promising results.

[SAPHO syndrome]. / Le syndrome SAPHO.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a rare entity characterized by the association of heterogeneous osteoarticular and cutaneous manifestations that have for common denominator an aseptic inflammatory process. The etiopathogeny of this disease is still a matter of debate. Although it has been related to the spondylarthritis family, an infectious origin is suggested. Diagnosis is based on the presence of at least one of the three diagnostic criteria proposed by Kahn. The treatment includes NSAIDs, antibiotics, corticosteroids, methotrexate and more recently the bisphosphonates and the TNFα inhibitors.

Pustulotic arthro-osteitis associated with palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles of middle-aged women. PPP frequently develops or exacerbates following focal infections, such as tonsillitis, odontogenic infection and sinusitis, either with or without arthralgia and/or extra-palmoplantar lesions. Pustulotic arthro-osteitis (PAO) is a joint comorbidity of PPP, most often affecting the anterior chest wall. PAO is sometimes regarded as the same entity as synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome, and may be a subtype or incomplete type of SAPHO syndrome; however, there are several differences. In Japanese patients, PPP with PAO is frequently seen, whereas SAPHO syndrome in the true meaning is rare. A difference of incidence depending on race suggests that different genetic backgrounds may be responsible for susceptibility to these disorders. Bacterial infection, especially Propionibacterium acnes, is suggested to play an important role in the pathogenesis of SAPHO syndrome. P. acnes is responsible for acne, however, bacterium is unassociated with PPP skin lesions which are characterized by sterile pustules. On the other hand, PAO is frequently triggered by focal infection, and treatment of focal infection results in dramatic effects on the release of joint pain. This paper reviews current insights into the clinicopathophysiology of PAO, and discusses its possible mechanisms in comparison with SAPHO syndrome.

Clinical care of children with sterile bone inflammation.

PURPOSE OF REVIEW: To review the current literature of sterile bone inflammation in childhood and to evaluate the evidence for clinical care including diagnostic methods and treatment. RECENT FINDINGS: Chronic noninfectious osteomyelitis includes several different entities marked by sterile bone inflammation associated with histologic evidence of a predominant neutrophil infiltration in the absence of autoantibodies and autoreactive T cells, some of which are associated with a genetic mutation. Whole body MRI is helpful in detecting asymptomatic lesions. Initial treatment with NSAIDs is usually sufficient to control symptoms as the bone heals. However, if the lesions persist and do not respond to first-line treatment, or involve the spine or hip, treatment with bisphosphonate will usually lead to a resolution of symptoms. Rarely, treatment with anti-TNF agents is required. SUMMARY: This review summarizes recent information on diagnosis, treatment and prognosis of disorders involving sterile bone inflammation in childhood. It also addresses the evolving differential diagnosis for autoinflammatory disorders that include sterile bone inflammation and presents a treatment algorithm for management.

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-alpha antagonists.

Pancreatic hamartoma and SAPHO syndrome: a case report.

We report the first case of an association of pancreatic hamartoma with SAPHO syndrome mimicking disseminated bone metastases. A 46 year old male with intermittent back pain for 10 years, relieved by NSAIDs and desquamation erythemathous palmo-plantar eruption one year before, presented with symptoms of duodenal stenosis, a cystic tumor at the head of the pancreas and osteoformative (hyperostosis) and osteodestructive (osteitis) lesions of the clavicle, mandible, lumbar spine. The bone lesions resembled bone metastases, but an inflammatory infiltrate and fibrosis were found on the excisional biopsy of left clavicle, compatible with the SAPHO syndrome. The pancreatic tumor grew rapidly and showed a histological aspect of malignancy at laparoscopy. A cephalic duodenopancreatectomy was performed, but the histological findings established the diagnosis of pancreatic hamartoma. Several months later, the bone Tc99m scintigraphy was normal.

Síndrome SAPHO: entidade rara ou subdiagnosticada? / SAPHO syndrome: rare or under - diagnosed?

OBJETIVO: Descrever os achados clínicos, radiológicos e patológicos da síndrome SAPHO e sugerir que, apesar de ser considerada rara, esta síndrome deve estar sendo subdiagnosticada por clínicos e radiologistas, provavelmente em função do desconhecimento das suas características. MATERIAIS E MÉTODOS: Foi realizado estudo retrospectivo de seis casos confirmados desta síndrome, dando-se ênfase aos achados clínicos (idade, sexo e sintomas) e de imagem (cintilografia óssea, radiografia convencional, tomografia computadorizada e ressonância magnética). RESULTADOS: A manifestação clínica inicial de todos os pacientes foi dor na parede torácica ântero-superior há pelo menos quatro meses. Todos apresentavam achados de imagem de processo inflamatório e/ou osteíte e hiperostose nas articulações da parede torácica ântero-superior. As alterações cutâneas da síndrome, tipo pustulose palmoplantar, estiveram presentes em cinco dos seis pacientes. Em nenhum dos seis casos o diagnóstico foi sugerido na consulta clínica inicial ou na primeira interpretação das imagens feita por radiologistas não especialistas em sistema músculo-esquelético. CONCLUSÃO: Os nossos achados estão de acordo com os descritos na literatura, devendo ser considerado este diagnóstico em todo paciente que apresente quadro doloroso de parede torácica acompanhado de manifestações dermatológicas e/ou osteíte.

Stress in a case of SAPHO syndrome.

In this article, we describe a case of seemingly stress-induced SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome in a man who exhibited the central features of palmoplantar psoriasis and anterior chest involvement. We also review the etiology, pathogenesis, and treatment of SAPHO syndrome and emphasize the important differences between this syndrome and psoriatic arthritis.

Síndrome SAPHO (sinovitis, acné, pústulas, hiperostosis, y osteítis) con lesión esternal primaria inicial / Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome presenting as a primary sternal lesion

El síndrome SAPHO, acrónimo de Sinovitis, Acné, Pústulas, Hiperostosis y Osteítis, es una entidad nosológica que engloba múltiples afecciones que tienen un común compromiso osteoarticular y cutáneo. Se presenta una enferma de 59 años de edad que consulta por intenso dolor esternal y luego de un año padece exantema pustular palmo-plantar, acné y fiebre. Se le realiza una Tomografía computada, gamagrafía ósea y biopsia de las lesiones cutáneas, con lo cual se llega al diagnóstico de síndrome SAPHO. Se efectúa una reseña histórica de las distintas publicaciones sobre patologías encuadradas en el síndrome y se realiza una revisión bibliográfica de las teorías sobre su posible etiología, la cual continúa en discusión, aunque la tendencia actual es considerarla una artropatía seronegativa de similar fisiopatología al síndrome de Reiter (AU)