To Explore The Pathogenesis Of SAPHO Syndrome And Clinical Study Of SAPHO Syndrome From Helper T Cells And RANKL / OPG System

PART1:Serum levels of cytokines and RANKL/OPG in synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) SyndromeObjective:The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is a rare disease which characterized by the association of skin lesions and osteoarticular disorder. The abnormal condition of immunology is concerned with its etiology. The goal of this study was to investigate T helper cells correlated cytokines, pro-inflammation cytokines as well as RANKL and OPG levels in serum of SAPHO syndrome patients.Patients and Methods:30 patients with SAPHO syndrome were enrolled,15 healthy volunteers were recruited as healthy controls. BASDAI (Bath Ankylosing Spondylitis Activity Index) and VAS (Visual Analogue Scale) pain scores were used to assess the activity of SAPHO syndrome, thereupon the SAPHO syndrome patients were divided into active and stable groups. In addition, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were tested. The serum levels of IFN-γ, IL-4, IL-17, IL-22, TGF-β, TNF-α, IL-1β, IL-6, IL-8 and RANKL (receptor activator NK-κB ligand) as well as OPG (osteoprotegerin) were determined by ELISA.Results:Compared with stable group, the active group of SAPHO syndrome was associated with elevated serum levels of IL-17(P< 0.0001), IL-1β(P=0.022), IL-6(P=0.021), IL-8(P< 0.0001) and RANKL(P< 0.0001), while decreased with TGF-β1(P< 0.0001). There was no difference with serum levels of IFN-γ, TNF-α, IL-4, IL-22 as well as OPG between active and stable group.Conclusions:The inflammation level was closely associated with disease activity of SAPHO syndrome. The imbalance between inflammatory and anti-inflammatory system, as well as the imbalance of osteoblast and osteoclast may play important role in SAPHO syndrome.PART2:The imbalance of Thl7 and Treg cells in patients with active synovitis, acne, pustulosis, hyperostosis, osteiti (SAPHO) syndromeObjective:Amplified inflammation persists in the patients with active SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis). Nevertheless, the underlying mechanism remains unclear. Th17/T regulatory cells (Treg) imbalance may contribute to this abnormal inflammation of active phases of SAPHO syndrome.Patients and Methods:According to the VAS (Visual Analogue Scale) pain score and BASDAI (Bath Ankylosing Spondylitis Activity Index),22 SAPHO syndrome patients were divided into active group (n=11) and stable group (n=11), meanwhile 11 healthy volunteers were enrolled as control groups.By means of flow cytometry, the expression of Th17 and Treg cells in peripheral blood mononuclear cell were tested.Results:The mean percentages of Th17 cells was markedly higher in active group of SAPHO syndrome than in stable group (P< 0.0001) and healthy controls(P< 0.0001). Also the ratio of Th17 cells to Treg cells was markedly higher in active group than in the other two groups(P< 0.0001). There were no differences of Treg cells among the three groups (P=0.3394). In addition, the ratio of Th17/Treg cells was positively correlted with the values of VAS in SAPHO syndrome patients (P< 0.0001, r=0.7527)Conclusions:The results demonstrated that the development of SAPHO syndrome is closely related to the imbalance of Th17/Treg ratio, which suggests a defect in anti-inflammatory homeostasis in SAPHO syndrome.PART 3.1.Clinical analysis of 99 cases of SAPHO syndromeObjective:This paper analyzes the reasons of misdiagnosis of SAPHO syndrome, and aims to improve the level of clinical knowledge of SAPHO syndrome and diagnosis.Methods:99 SAPHO syndrome patients were collected between January 2004 and July 2014 in our hospital. Their general situations were retrospectively analyzed including clinical manifestations, Laboratory examination, imaging features, invasive operation and operation.Results:99 definite diagnosed cases were retrospectively analyzed,32 cases were misdiagnosed as palmoplantarpustular,16 cases as rib cartilage inflammation,12 cases as arthritis,7 cases as ankylosing spondylitis,6 cases as periarthritis of shoulder, 5 cases as bone tuberculosis,5 cases as prolapse of lumbar intervertebral disc,4 cases as chronic osteomyelitis,4 cases as suspected bone tumors,2 cases as cervical spondylosis,1 case as rheumatoid arthritis, aseptic osteitis, reactive arthritis, mandibular inflammation, metabolic bone disease, condensing osteitis respectively.Conclusion:Familiar with the clinical features and diagnositic criteria of SAPHO syndrome and early bone scan can improve the diagnosis of the disease, reduce unnecessary invasive operation and operation.PART 3.2 Tumor necrosis factor-alpha blockers in SAPHO syndrome—8 cases report and literaturereview.Objective:Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a very rare disease and still lack standardized therapy. We analyzed the clinical efficacy of anti-tumor necrosis factor-α (TNF-α) inhibitor therapy in treatment of SAPHO syndrome.Methods:We analyzed 8 patients with refractory SAPHO syndrome treating with anti-TNF-a inhibitors, and reviewed cases treating with anti-TNF-α inhibitors reported in the literature.Results:8 patients were all female:7 of them had palmoplantar pustulosis, the other one was free of skin lesions. Their osteoarticular manifestations included anterior chest wall involving in 8 patients, peripheral joints involving in 6 patients, sacroiliac joints involving in 6 patients, and vertebral joints involving in 2 patients. All patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs) as the first-line therapy, and corticosteroid and/or disease modifying anti-rheumatic drugs (DMARDs) as the second-line drug, but the symptoms cannot be ameliorated. Patients received anti-TNF-α inhibitors as the third-line therapy, and each of them had their symptoms improved. During the treatment of anti-TNF-α inhibitors, skin rash of 1 patient aggravated, and 1 patient developed submandibular sialadenitis.4 patients had disease relapse after cessation of anti-TNF-α inhibitor therapy.3 patients received Chinese traditional medicine as additional therapy, and had symptoms improved further.Conclusion:Anti-TNF-α inhibitors can ameliorate symptoms of SAPHO syndrome patients significantly, but skin rash in some patients aggravate during the treatment. The risk of infection is the most potential side-effect of anti-TNF-α therapy. Relapse of disease is not unusual after the cessation of treatment. Chinese traditional medicine is proved to be valid in SAPHO syndrome, and would be developed into the potential new therapy of this rare disease.PART 3.3 The clinical observation of traditional Chinese medicine Chaihu Guizhi Tang treatment of SAPHO syndromeObjective:To evaluate the clinical efficacy and safety of traditional Chinese medicine Chaihu Guizhi Tang in adjunctive treatment of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome through a 12-week open study.Patients and Methods:40 patients with SAPHO syndrome were enrolled in line with inclusive criteria and assigned to the treatment group and control group according to random digit table,20 patients in each group. Patients in the control group took alendronate sodium 70mg each week. Patients in the treatment group took Chaihu Guizhi Tang. The therapeutic course for all was 12 weeks. The VAS (Visual Analogue Scale) 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 12 weeks of treatment. And evaluate the efficacy of the two groups of treatment.Results:40 patients completed the study, including 20 cases in treatment group and control group 20 cases. Compared with before treatment, the treatment group in the ESR, VAS, BASDAI, BASFI score were significantly improved (P<0.05). According to the control group only BASDAI score improved significantly(P<0.05). Comparison between the two groups after treatment, the treatment group in the VAS score and BASDAI score is better than the control group(P<0.05). In the ESR, hs-CRP and BASFI scores, comparing the two groups have no statistical significance.3 patients in the control group have digestive tract symptoms of adverse reactions, the treatment group has no obvious adverse drug reactions.Conclusions:The traditional Chinese medicine Chaihu Guizhi Tang treatment curative effect than alendronate sodium in SAPHO syndrome patients, and no obvious adverse drug reactions.