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.

Serum IgG4 elevation in SAPHO syndrome: does it unmask a disease activity marker?

OBJECTIVES: SAPHO syndrome is a rare inflammatory disorder with multiple phenotypes, including synovitis, acne, pustulosis, hyperostosis, and osteitis. IgG4 is a subclass of immunoglobulin G, and the elevation of IgG4 has been found in different autoimmune diseases. In the present study, we explored the clinical significance of serum IgG4 levels in patients with SAPHO syndrome. METHODS: Fifty-two patients who met the classification criteria of SAPHO syndrome were included in this study. Clinical data and disease activity markers were collected including erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hsCRP), pain visual analogue scale (VAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Serum immunoglobin (IgA, IgM, and IgG) and IgG subclass (IgG1, IgG2, IgG3, and IgG4) levels were determined using the immunonephelometric assay. RESULTS: Raised serum IgG4 levels (>1400 mg/dL) were detected in 23% (12/52) of patients. Patients with elevated sIgG4 levels had significantly higher pain VAS (5.42±2.76 vs. 3.08±1.78, p=0.02), BASMI (1.80±1.64 vs. 0.38±0.94, p=0.03) and ASDAS (3.20±0.65 vs. 1.74±0.58, p<0.001) levels compared with patients with normal sIgG4 levels. This difference was also observed for ESR (38.2 vs. 22.2 mm/h, p=0.01) and serum CRP (21.0 vs. 2.2 mg/L, p=0.04) levels, which also positively correlated with sIgG4 levels. We also included 4 patients whose IgG4 levels decreased and correlated with the decrease in hsCRP and ESR levels after treatment. CONCLUSIONS: Elevated sIgG4 levels are common in patients with SAPHO syndrome and are associated with high disease activity. Further investigations are needed for this phenomenon.

Serum levels of proinflammatory, anti-inflammatory cytokines, and RANKL/OPG in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

OBJECTIVE: To measure the expression of proinflammatory, anti-inflammatory cytokines, and receptor activator NK-κB ligand (RANKL)/osteoprotegerin (OPG) in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, and to assess the relationship between those factors and disease activity. METHODS: We studied 30 cases of SAPHO syndrome and 15 healthy controls. According to the Visual Analogue Scale (VAS) pain scores and Bath Ankylosing Spondylitis Activity Index (BASDAI), patients were divided into active group and stable group. The serum levels of IFN-γ, TNF-α, TGF-ß1, IL-1ß, IL-4, IL-6, IL-8, IL-17A, IL-22, RANKL, and OPG were determined by ELISA. RESULTS: The active group IL-6 (2.34 ± 1.31 pg/ml), IL-8 (36.41 ± 12.93 pg/ml), and IL-17A (29.17 ± 4.01 pg/ml) levels were significantly higher than those in the stable group (p < .01) and healthy controls (p < .01). RANKL in active group (73.43 ± 57.07 pg/ml) was significantly higher than the ones in other groups (p < .0001), with increased RANKL/OPG ratio in the active group compared with other groups (p < .05). While the level of TGF-ß1 in the active group was significantly lower than that in the stable and control groups (p < .0001). There was no significant difference with clinical significance were found in IFN-γ, TNF-α, IL-1ß, IL-4, IL-22, and OPG. CONCLUSION: In active SAPHO patients, there was an anomaly of proinflammatory and anti-inflammatory cytokines balance in SAPHO syndrome.

Reduction of peripheral natural killer cells in patients with SAPHO syndrome.

OBJECTIVES: Little is known about the roles of peripheral immune cell subsets in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. Up to now, just a few studies have focused on this issue. We aimed to analyse the distribution and phenotype of T cell subsets and natural killer (NK) cells in the peripheral blood of patients with SAPHO syndrome. METHODS: The proportion and absolute counts of circulating immune cells were assessed in 19 patients diagnosed as SAPHO syndrome and 19 healthy controls. CD4+T cell subsets were also analysed in 9 untreated SAPHO patients and 9 healthy volunteers by flow cytometry. RESULTS: The proportion and absolute counts of NK cells were significantly reduced in SAPHO patients in comparison with the controls (proportion, 10% vs. 18%, p<0.001; absolute counts, 231/µl vs. 307/µl, p=0.014). Conversely, the proportion and absolute counts of Th17 cells in untreated SAPHO patients were significantly higher than that in the healthy controls (proportion, 1.49% vs. 0.93%, p=0.004; absolute counts, 14.36/µl vs. 5.14/µl, p<0.001). Similarly, Th17/Th1 cells were significantly increased (proportion, 0.45% vs. 0.33%, p=0.024; absolute number, 5.47/µl vs. 1.98/µl, p<0.001), but there was no significant difference between the percentage and number of Treg cells in patients with SAPHO syndrome and healthy controls. Thus, the ratio of Th17/Treg was increased in SAPHO patients (0.68 vs. 0.17, p=0.004). CONCLUSIONS: Our data suggested that the immune inflammation in SAPHO patients may be related to the depletion of NK cells and the imbalance of Th17 and Treg cells. A reduction of peripheral NK cells may exacerbate the disease progression by not being inhibited Th17 cells.

Pulmonary high-resolution computed tomography findings in patients with synovitis, acne, pustulosis, hyperostosis and osteitis syndrome.

OBJECTIVE: To characterize the high-resolution computed tomography (HRCT) pulmonary abnormalities in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: Pulmonary HRCT images were reconstructed from whole-spine computed tomography (CT) images of 67 patients with SAPHO syndrome. HRCT images of 58 healthy controls were also obtained and reviewed. Patients with pneumonia and tuberculosis were excluded. Demographic and clinical data such as gender, age, onset age, disease duration, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hs-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were collected from the SAPHO syndrome patients. Demographic characteristics, ESR and hs-CRP data from the healthy controls were also recorded. Student's t test, Mann-Whitney U test, chi-squared test and logistic regression were employed to compare the HRCT findings of the two groups of patients. RESULTS: The median age of the SAPHO syndrome patients was 47.0 years, interquartile range [38.0-53.0]; that of the healthy controls was 37.0[30.8-53.8]. From the detailed HRCT evaluations, abnormalities were identified in 45 patients. We found irregular linear opacities in 29 (43.3%) patients, opacities in 22 (32.8%), ground-glass opacity in 11 (16.4%), pleural thickening in 9 (13.4%), solitary nodules in 6 (9%), bronchiectasis in 3 (4.5%), pulmonary bulla in 2 (3%), multiple nodules in 1 (1.5%), and reticular patterns in 1 (1.5%). Compared to the healthy controls, the SAPHO syndrome patients had a significantly higher rate of opacities but a significantly lower percentage of nodules (especially multiple nodules), although the overall rates of abnormal HRCT findings were similar in the two groups. According to the multivariate logistic regression analysis, increased age and BASDAI < 4 were significant predictors of abnormal HRCT findings. CONCLUSION: Our study is the first to address HRCT pulmonary abnormalities in SAPHO syndrome patients. SAPHO syndrome patients have a significantly higher percentage of opacities and a significantly lower rate of pulmonary nodules than healthy controls. BASDAI and age are possible good predictors of abnormal HRCT pulmonary findings.

F-18 FDG PET/CT in 26 patients with SAPHO syndrome: a new vision of clinical and bone scintigraphy correlation.

BACKGROUNDS: Whole-body bone scintigraphy (WBBS) and MRI are widely used in assessment of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. However, the value of F-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) in SAPHO syndrome was unclear. The aim of this study was to characterize the manifestation of SAPHO syndrome on 18F-FDG PET/CT and explore its relationship with clinical symptoms and WBBS. METHODS: Twenty-six patients who suffered from SAPHO syndrome and had undergone whole-body 18F-FDG PET/CT were recruited in Peking Union Medical College Hospital from 2004 to 2016. Clinical manifestations and laboratory findings were recorded for all patients. Imaging data on 18F-FDG PET/CT and WBBS were collected and analyzed retrospectively. RESULTS: All the 26 patients (20 females and 6 males) exhibited skeletal abnormalities on 18F-FDG PET/CT. Multiple skeletal lesions affecting the anterior chest wall or spine with low to moderate 18F-FDG uptake and coexistence of osteolysis and osteosclerosis presented as the typical features of SAPHO syndrome. Sixteen (61.5%) patients had abnormal 18F-FDG uptake outside the osteoarticular system. PET scan had moderate to substantial agreement with CT and WBBS in revealing lesions in the anterior chest wall and axial skeleton. Nonetheless, the correlation between increased 18F-FDG uptake and clinical symptoms was weak. CONCLUSIONS: SAPHO syndrome exhibits characteristic features on 18F-FDG PET/CT. It showed comparable capacity in revealing skeletal lesions with bone scintigraphy.

Serum Interleukin-18, Fetuin-A, Soluble Intercellular Adhesion Molecule-1, and Endothelin-1 in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome.

To examine serum interleukin 18 (IL-18), fetuin-A, soluble intercellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) levels in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and Synovitis Acne Pustulosis Hyperostosis Osteitis syndrome (SAPHO). We studied 81 AS, 76 PsA, and 34 SAPHO patients. We measured serum IL-18, fetuin-A, sICAM-1, ET-1, IL-6, IL-23, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). IL-18 levels were higher in AS (p = 0.001), PsA (p = 0.0003), and SAPHO (p = 0.01) than in controls, and were positively correlated with CRP (p = 0.03), VEGF (p = 0.03), and total cholesterol (TC, p = 0.006) in AS and with IL-6 (p = 0.03) in PsA. Serum fetuin-A levels were lower in AS (p = 0.001) and PsA (p = 0.001) than in controls, and negatively correlated with C-reactive protein (CRP) in AS (p = 0.04) and SAPHO (p = 0.03). sICAM-1 positively correlated with CRP (p = 0.01), erythrocyte sedimentation rate (ESR, p = 0.01), and IL-6 (p = 0.008) in AS, and with IL-6 (p = 0.001) in SAPHO. Serum ET-1 levels were lower in AS (p = 0.0005) than in controls. ET-1 positively correlated with ESR (p = 0.04) and Disease Activity Score 28 (DAS28, p = 0.003) in PsA. In spondyloarthritis, markers of endothelial function correlated with disease activity and TC.

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.

Extra-Articular Symptoms in Constellation with Selected Serum Cytokines and Disease Activity in Spondyloarthritis.

Objectives. In this study, we assessed the extra-articular symptoms in constellation with selected serum cytokines and disease activity in spondyloarthritis (SpA). Patients and Methods. We studied 287 SpA patients: 131 had AS, 110 had PsA, and 46 had SAPHO. We assessed extra-articular symptoms in all cases. In 191 SpA patients, we measured serum interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-23 (IL-23), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). Results. Patients with acute anterior uveitis (AAU) had higher VAS (P = 0.0008), BADSDAI (P = 0.0001), ASDAS-ESR (P = 0.04), CRP (P = 0.006), IL-6 (P = 0.02), and IL-18 (P = 0.03) levels. Patients with inflammatory bowel disease (IBD) had higher VAS (P = 0.03), CRP (P = 0.0009), and IL-6 (P = 0.0003) levels. Patients with skin psoriasis had lower VAS (P = 0.001) and BASDAI (P = 0.00007) levels. Patients with psoriatic onycholysis had lower VAS (P = 0.006), BASDAI (P = 0.00001), and CRP (P = 0.02) and higher IL-23 (P = 0.04) levels. Patients with PPP had lower BASDAI (P = 0.04) and higher ET-1 (P = 0.001) levels. Conclusions. SpA patients with increased serum IL-18 and decreased serum ET-1 had an increased risk of extra-articular symptoms. In SpA patients, increased disease activity was associated with an increased risk of AAU and IBD and a decreased risk of skin psoriasis, psoriatic onycholysis, and PPP.

Serum IL-6 and IL-23 Levels and Their Correlation with Angiogenic Cytokines and Disease Activity in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome.

OBJECTIVES: To assess serum interleukin-6 (IL-6) and interleukin-23 (IL-23) and their correlation with angiogenic cytokines and disease activity in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and SAPHO syndrome. PATIENTS AND METHODS: We studied 152 spondyloarthritis (SpA) patients: 69 PsA, 61 AS, 22 SAPHO, and 29 controls. We recorded age, sex, disease duration, and treatment. We assessed BASDAI, VAS, and PASI scores. Serum IL-6, IL-23, VEGF, EGF, FGFb, and FGFa levels were determined using ELISA. We estimated ESR and CRP. RESULTS: Serum IL-6 and IL-23 levels were higher in SpA than in control (P < 0.00001 and P = 0.0004, resp.). There was a positive correlation between serum IL-6 and CRP in AS (P = 0.000001), PsA (P = 0.000001), and SAPHO (P = 0.0003) patients. There was a positive correlation between serum IL-6 and ESR in AS (P = 0.000001), PsA (P = 0.002), and SAPHO (P = 0.02) patients. There was no correlation of serum IL-6 and IL-23 with VAS, BASDAI, and angiogenic cytokines in SpA. CONCLUSIONS: Serum IL-6 but not serum IL-23 correlated with ESR and CRP in SpA. No correlation was found of serum IL-6 and IL-23 with VAS, BASDAI, and angiogenic cytokines.

TH17 cells are increased in the peripheral blood of patients with SAPHO syndrome.

To assess whether the immune derangement previously observed in SAPHO syndrome could be linked to variations in blood TH1, TH2 or TH17 lymphocytes frequency. Seven SAPHO patients with a protracted course of the disease were studied ex-vivo for intracellular cytokines production by means of flow-cytometry and compared with matched groups of Psoriatic Arthritis patients and healthy controls. The Kruskal-Wallis test on the median of the three categories showed that there is a significant association between the TH17 levels and the category (p value = 0.02474). The mean and variance for the proportion of IL-17 producing CD4+ cells were compared between groups showing significant differences between SAPHO versus PsA subgroup (p = 0.05) and SAPHO versus healthy controls (p = 0.008). Interestingly, activation of TH17 axis, but not of TH1 and TH2, has been found, and can be observed both in patients with different activity of the disease or treated with different drugs. The TH17 increase in peripheral blood of our SAPHO subjects resembles the one recently found in patients with different AIDs. Novel therapeutic options in these patients may therefore include IL-17 blockade.

Serum levels of angiogenic cytokines in psoriatic arthritis and SAPHO syndrome.

INTRODUCTION: Angiogenesis is involved in the pathogenesis of arthritis. OBJECTIVES: The aim of the study was to assess the serum levels of selected angiogenic cytokines and their association with clinical presentation in patients with psoriatic arthritis (PsA) and SAPHO syndrome. PATIENTS AND METHODS: We studied 98 patients: 80 with PsA and 18 with SAPHO syndrome. The following data were recorded: age, sex, disease duration, joint involvement, type of psoriasis, nail involvement, and treatment. The following indices used to assess the activity of PsA and SAPHO were measured: PASI, BASDAI, BASFI, BASMI, BASG, and VAS pain. We determined erythrocyte sedimentation rate, C­reactive protein (CRP), and platelet count. The serum levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic and acidic fibroblast growth factors (FGFb and FGFa) were determined using an enzyme­linked immunosorbent assay. RESULTS: In patients with PsA, VEGF levels were positively correlated with CRP (P = 0.04), BASFI (P = 0.03), and disease duration (P = 0.007). No differences were found between patients with and without nail psoriasis in the VEGF or EGF levels (P = 0.32 and P = 0.85, respectively). There were no differences between patients with the peripheral and axial forms of arthritis in VEGF or EGF levels (P = 0.56 and P = 0.28, respectively). No significant correlations were observed between EGF and FGF levels and clinical presentation in patients with PsA. In patients with SAPHO, no significant correlations were found between angiogenic cytokine levels and clinical presentation. CONCLUSIONS: Our data suggest a role of VEGF in the pathogenesis of PsA. Further studies are required to better understand the role of angiogenic cytokines in PsA.

Biologics for rare inflammatory diseases: TNF blockade in the SA PHO syndrome.

INTRODUCTION: SAPHO is an invalidating syndrome characterised by Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis. The low prevalence and heterogeneous presentation often leads to a significant diagnostic delay. Here, we provide an up-to-date overview of current insights into the pathogenesis and different treatment options. In addition, we describe the effects of anti-TNF treatment in three refractory cases. CASE REPORTS: Patient A is a 25-year-old female with hidradenitis suppurativa, inflammatory back pain and painful joints. After diagnosis, anti-TNF treatment was started resulting in clinical improvement. Patient B is a 44-year-old woman who presented with acne, palmoplantar pustulosis and anterior chest wall pain. Bone scintigraphy showed increased uptake at the anterior chest wall. Treatment with bisphosphonates resulted in temporary improvement and subsequent treatment with anti-TNF induced long-term clinical improvement. Patient C is a 37-year-old woman with palmoplantar psoriasis, relapsing hidradenitis and inflammatory back pain. MRI revealed osteitis of the pubic bone. Anti-TNF was started for SAPHO syndrome. However, despite a clinical response, our patient discontinued treatment, resulting in rapid deterioration. Anti-TNF treatment was re-introduced followed by clinical improvement. CONCLUSION: These case reports illustrate, consistent with the current literature, that TNF blockers can be considered for treatment of refractory SAPHO syndrome.

Prevalence of autoantibodies in SAPHO syndrome: a single-center study of 90 patients.

OBJECTIVE: To determine the prevalence of the most often tested autoantibodies in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: We identified 90 patients seen in our unit between June 2002 and June 2009, and diagnosed according to the proposed criteria for SAPHO syndrome. Demographic and clinical data were collected as well as immunological results, including antinuclear, antithyroid peroxydase (TPO), antithyroid globulin (Tg), antigastric parietal cell, antismooth muscle, antimitochondria, and anti-liver-kidney microsome (LKM) antibodies. Anticyclic citrullinated peptide (CCP) antibodies were analyzed in 69 patients, antibodies to soluble extractable nuclear antigens in 43, anti-double-stranded DNA (dsDNA) antibodies in 22 [depending on the type of fluorescence of antinuclear antibody (ANA)], and antiendomysium antibodies in 55. RESULTS: Autoantibodies were found in 20 patients (22.2%): 14 patients (15.5%) had positive ANA (titer >/= 1/160); among them, 10 (11%) patients never took a lupus-inducing drug. Antithyroid antibodies (anti-TPO and/or anti-Tg antibodies) were found in only 3 patients (3.3%). Three patients (3.3%) were positive for antigastric parietal cell antibodies and 4 (4.4%) were weakly positive for antismooth muscle antibodies. Antimitochondria and LKM antibodies were negative in all 90 patients. Anti-CCP and anti-dsDNA antibodies were negative in the 69 and 22 patients tested, respectively. One out of 43 patients (2.3%) had anti-SSA antibodies. Antiendomysium antibodies were negative in the 55 patients tested. CONCLUSION: Our study indicates an increased prevalence of autoantibodies in SAPHO syndrome, with no specific profile. We failed to confirm the reports of an increased prevalence of antithyroid antibodies. These results tend to support a link between autoimmunity and SAPHO syndrome.

Clinical and radiologic evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a single center study of a cohort of 71 subjects.

OBJECTIVE: To assess the basic features and outcomes of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: We identified all patients seen in our unit between 1990 and 2008 diagnosed according to the proposed inclusion criteria with SAPHO syndrome, who had a followup of at least 2 years. RESULTS: Seventy-one patients (48 women, 23 men) with SAPHO syndrome were identified. The median disease duration at the end of followup was 10 years (interquartile range [IQR] 7-15 years), and the median followup duration was 11 years (IQR 6-11.5 years). Six patients were diagnosed with Crohn's disease. Fourteen patients had never had cutaneous involvement, but 8 patients presented >1 skin manifestation. Nine patients (13%) presented a limited (<6 months) monophasic disease course, 25 cases (35%) had a relapsing-remitting course, and 37 patients (52%) had an acute painful phase with a prolonged course lasting >6 months. A total of 4% of the patients were HLA-B27 positive. Female sex (odds ratio [OR] 7.2, 95% confidence interval [95% CI] 2.2-22.9) and the presence at onset of anterior chest wall (ACW) involvement (OR 5.7, 95% CI 1.8-18.1), peripheral synovitis (P = 0.0036), skin involvement (OR 10.3, 95% CI 3.4-31.1), and high values of acute-phase reactants (OR 7.7, 95% CI 2.7-22) were correlated with a chronic disease course and involvement of new osteoarticular sites. CONCLUSION: A chronic course is the more common evolution of SAPHO syndrome. Female sex, elevated erythrocyte sedimentation rate and C-reactive protein values, ACW involvement, peripheral synovitis, and skin involvement at the onset seem to be associated with a chronic course.

The usefulness of bone remodelling markers in predicting the efficacy of pamidronate treatment in SAPHO syndrome.

OBJECTIVES: Pamidronate has recently been used in SAPHO syndrome due to its anti-osteoclastic effect. The aim of this study is to determine the usefulness of bone remodelling markers for determining the efficacy of pamidronate treatment. METHODS: Thirteen patients with SAPHO syndrome were treated with pamidronate. The treatment evaluation was done using a visual analogue scale (VAS) and also erythrocyte sedimentation rate, C-reactive protein, serum crosslaps (sCTX) and osteocalcin initially and after 3 months. A relevant clinical response was defined as an improvement in VAS of at least 40%. RESULTS: At 3 months, 7 of 13 patients had a good clinical response, as previously defined. Five of the seven patients maintained the good response over 6 months. Before the first perfusion 6 of the 13 patients had increased sCTX (upper 3250 pmol/l). In this small cohort we tried to analyse whether the increase in bone remodelling markers was associated with a good clinical response. In the responders group the mean levels of sCTX and osteocalcin at baseline were 6783.17 and 24.66, respectively, and in the non-responders group the levels were 2152 and 11.8, respectively. There was a significant difference in sCTX between the responders and the non-responders (P = 0.0044). CONCLUSION: Infusion of pamidronate is effective in SAPHO in some patients. Increased sCTX might be a prognostic marker for a good clinical response but results have to be confirmed in a larger cohort.