An integrated transcriptomics and network pharmacology approach to explore the mechanism of Wang-Bi tablet against SAPHO syndrome.

BACKGROUND: SAPHO syndrome is recognized as a rare entity with damage to skin and bones due to inflammation. Currently, the treatment for SAPHO syndrome is still a challenge in clinical practice. In this study, an integrated transcriptomics and network pharmacology approach was applied to explore the therapeutic effect and mechanism of Wang-Bi tablet (WBT) on SAPHO syndrome. METHODS: The main components of WBT and their targets, as well as the targets of SAPHO syndrome, were collected from databases. Network visualization was performed using Cytoscape software. The GO and KEGG enrichment analysis was executed by David dataset. Then, the molecular mechanism of WBT improving SAPHO syndrome was validated by transcriptomics of peripheral blood neutrophils in SAPHO syndrome. Finally, the above results were validated by molecular docking. RESULTS: The Network Pharmacology results showed there are 152 core targets for WBT treatment on SAPHO syndrome. RNA-seq data showed 442 differentially expressed genes (DEGs) in peripheral blood neutrophils of SAPHO patients. Intriguingly, NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway were included in the enrichment results of network pharmacology and RNA-seq. Moreover, we verified that the core components of WBT have good affinity with the core targets of NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway by molecular docking. CONCLUSIONS: This study illustrated that the possible mechanisms of WBT against SAPHO syndrome may be related to NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway, and further experiments are needed to prove these predictions.

Tripterygium wilfordii Hook F. in the treatment of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a clinical trial.

OBJECTIVE: This study aimed to investigate the efficacy and safety of Tripterygium wilfordii Hook F. (TwHF) in the treatment of osteoarticular lesions in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: Eligible SAPHO patients were recruited to this single-center trial to receive 12-week TwHF treatment. Two dose groups (1.0-mg/kg/day group and 1.5-mg/kg/day group) were designed and patients were allocated (1:1) to these two groups. The primary endpoint was the change from baseline in Ankylosing Spondylitis Disease Activity Score on the basis of C-reactive protein level (ASDAS) at week 12. RESULTS: All the 30 included patients completed the trial. At week 12, both dose groups showed significant change from baseline in ASDAS (1.0-mg/kg/day group: - 1.34 (1.10), p = 0.000; 1.5-mg/kg/day group: - 1.53 (1.19), p = 0.000). Similar improvement was also found in the Visual Analogue Scale in global osteoarticular pain, Bath Ankylosing Spondylitis Disease Activity Index, and other efficacy measures. The results showed a fast-acting characteristic of TwHF that the maximum efficacy was achieved within the first 2-4 weeks and maintained at a stable level for the rest of the study. No significant differences were observed between the two dose groups under the current sample size. TwHF was well tolerated that no severe adverse events or irregular menstruation were recorded, except for one patient who developed severe alanine aminotransferase elevation at the last follow-up and has stopped the TwHF treatment after the 12-week follow-up. CONCLUSIONS: TwHF should be considered for the treatment of osteoarticular lesions in SAPHO syndrome in clinical practice because of significant efficacy, reliable safety, and high socioeconomic value. TRIAL REGISTRATION: ChiCTR1900025912 Key points • This is the first clinical trial to evaluate Tripterygium wilfordii Hook F. (TwHF) in the treatment of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. • Twelve-week TwHF treatment in both dose groups designed (1.0-mg/kg/day group and 1.5-mg/kg/day group) was well tolerated and could lead to significant disease remission of SAPHO syndrome. • No significant differences were observed between the two dose groups under the current sample size. • TwHF should be considered for the treatment of osteoarticular lesions in SAPHO syndrome in clinical practice because of significant efficacy, reliable safety, and high socioeconomic value.

Biologic Therapy for Hidradenitis Suppurativa Plus Conglobate Acne Associated with SAPHO Syndrome: A Case Report.

is missing (Short Communication).

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.

[Clinical Observation of Chaihu Guizhi Decoction in Treating SAPHO Syndrome].

Objective To evaluate the clinical efficacy and safety of Modified Chaihu Guizhi De- coction on SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome. Methods Totally 40 patients with SAPHO syndrome were randomized to the treatment group(20 cases) and control group(20 cases). The treatment group was treated with Modified Chaihu Guizhi Decoction, and the control group with alendronate sodium 70 mg each week. The therapeutic course for all was 12 weeks. The Visual Analogue Scale (VAS) pain scores, bath ankylosing spondylitis activity index (BASDAI) , bath ankylosing spondylitis functional index(BASFI) , erythrocyte sedimentation rate(ESR) and hypersensitivity C reactive protein (hs-CRP) were measured before and after treatment. Adverse events were observed. Results The VAS, BASDAI, and BASFI score significantly improved compared with baseline in the treatment group (P <0. 01 , P <0. 05). The VAS and BASDAI score of the treatment group improved compared with the control group after treatment (P <0. 05). Three patients in the control group reported adverse events with digestive tract symptoms, while there was no obvious adverse drug reactions in the treatment group. Conclusions Modified Chaihu Guizhi Decoction was superior to alendronate sodium in the treat- ment of SAPHO syndrome without obvious adverse drug reactions.

Case report: remarkable remission of SAPHO syndrome in response to Tripterygium wilfordii hook f treatment.

RATIONALE: SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is an autoinflammatory disease with no standardized treatment. Tripterygium wilfordii hook f (TwHF) is a Chinese herb with immunosuppressive effects and has been used to treat some chronic inflammatory diseases. However, it has not been reported as a therapeutic option in SAPHO syndrome. Here we present the first report in which a remarkable remission of SAPHO syndrome was achieved in response to TwHF. PATIENT CONCERNS: A 57-year-old female patient noted swelling and pain at the anterior chest wall and scattered rashes like psoriasis vulgaris. Bone scintigraphy demonstrated the classic "bull's head" sign and magnetic resonance images indicated bone marrow edema on T5. DIAGNOSES: The diagnosis was made by dermatological and osteoarticular manifestations and classical "bull's head" sign in bone scintigraphy. INTERVENTIONS: TwHF with a priming dose of 20 mg 3 times per day and a gradual dose reduction of 20 mg per day in every 3 months. Four months later, methotrexate was added with 10 mg per week. OUTCOMES: Osteoarticular symptoms and radiological abnormalities were improved dramatically. LESSONS: This case illustrates a promising strategy to treat SAPHO syndrome.

Biologic therapy in refractory chronic non-bacterial osteomyelitis of childhood.

OBJECTIVE: To date there is no uniformly effective treatment for either chronic recurrent multifocal osteomyelitis (CRMO) or synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. We report on our clinical experience of using biologic therapy to treat children with these conditions. METHODS: Retrospective descriptive case series of four children with refractory disease treated with biologics. Disease activity was assessed at predetermined time points (T = 0, T = 6 weeks and T = 12 months after the start of biologic therapy, and at latest follow-up) using a combination of clinical examination and radiological findings: a 10 cm pain and physician visual analogue scale; the Childhood Health Assessment Questionnaire as an assessment of disability; and changes in markers of systemic inflammation. RESULTS: There was an initial improvement in all parameters assessed for all three children treated with TNF-alpha blockade, although the third case had to discontinue the therapy due to a suspected (but unconfirmed) fungal skin infection. Anakinra treatment alleviated the symptoms in the fourth patient at 6 weeks, but there was no sustained response to treatment at 1-year follow-up. CONCLUSION: We present our preliminary experience of using biological therapies to treat children with CRMO and SAPHO in conjunction with other immunosuppression. Further studies are needed to establish the role of these therapies in refractory CRMO and SAPHO.