Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome: a single centre study of a cohort of 164 patients

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1 RHEUMATOLOGY Rheumatology 2016;55: doi: /rheumatology/kew015 Advance Access publication 25 February 2016 Original article Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome: a single centre study of a cohort of 164 patients Chen Li 1, *, Yuzhi Zuo 2, *, Nan Wu 2, *, Li Li 3, Feng Li 3, Weihong Zhang 4, Wenrui Xu 4, Xue Zhao 4, Hongli Jing 5, Qingqing Pan 5, Weixun Zhou 6, Xiaohua Shi 6, Yu Fan 2, Jianyi Wang 2, Sen Liu 2, Zhenlei Liu 2, Fengchun Zhang 7, Xiaofeng Zeng 7, Hui Chen 8, Siya Zhang 8, Jinhe Liu 1, Guixing Qiu 2, Zhihong Wu 2,9, Zhenhua Dong 1 and Wen Zhang 7 Abstract 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 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. Key words: SAPHO syndrome, clinic and radiologic features, treatment. Rheumatology key messages. SAPHO syndrome is a rare disease characterized by dermatologic and osteoarticular manifestations.. The prevalence of SAPHO syndrome may be underestimated. 1 Department of Traditional Chinese Medicine, 2 Department of Orthopedic Surgery, 3 Department of Dermatology, 4 Department of Radiology, 5 Department of Nuclear Medicine, 6 Department of Pathology, 7 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 8 Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology and 9 Department of Central Laboratory, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China Submitted 19 August 2015; revised version accepted 25 January 2016 Correspondence to: Wen Zhang, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing , P.R. China. zhangwen91@sina.com *Chen Li, Yuzhi Zuo and Nan Wu contributed equally to this study. CLINICAL SCIENCE! The Author Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please journals.permissions@oup.com

2 Chen Li et al. Introduction The SAPHO syndrome is a rare disease with chronic inflammatory osteoarticular symptoms and dermatological lesions such as palmoplantar pustulosis and severe acne (SA) [1]. Windom et al. [2] first reported an association between musculoskeletal symptoms and acne conglobata in Since then, more than 50 different names have been used to describe the combination of osteoarticular and dermatological manifestations, such as pustulotic arthro-osteitis, sternocostoclavicular hyperostosis, acneassociated spondyloarthropathy and chronic recurrent multifocal osteomyelitis (CRMO) [1]. In 1987, Chamot et al. [3] first introduced the concept of SAPHO syndrome to describe the osteoarticular and dermatological lesions, and in 1994, Kahn and Khan [4] proposed the diagnostic criteria of SAPHO syndrome. The most commonly affected skeletal site is the anterior chest wall (ACW), including sternoclavicular, manubriosternal and costosternal joints, while the axial skeleton, including the spine and sacroiliac joints, is another common site involved in SAPHO syndrome [5, 6]. The appendicular skeleton is a less frequently affected site, but iliac, femoral and mandibular osteitis have also been reported [7 10]. Palmoplantar pustulosis (PPP) and SA are the main dermatological manifestations of SAPHO syndrome. The SA usually presents as acne conglobata, acne fulminans and hidradenitis suppurativa. Psoriasis vulgaris (PV) has also been seen in association with the SAPHO syndrome. Nonetheless, inclusion of PV as the only dermatological manifestation is still controversial [11]. Nowadays, SAPHO syndrome is considered to be a rare disease. To our knowledge, there are only a few large cohorts comprising 600 cases [3, 6, 12 17], and most of them are from Europe and Japan, with no reports from Chinese population. Kahn and Khan [4] reported that the prevalence was <1 in in Caucasians, and Schilling [18] estimated that the prevalence in Germany was 0.04%. Epidemiological data from China are still unknown. The real prevalence may be underestimated owing to lack of recognition or an atypical clinical manifestation [19]. The aetiology, pathogenic mechanism, target therapy and long-term prognosis of this disease are still not fully understood. Although most patients seem to have a good prognosis, the effects of disease burden and deleterious treatment on quality of life are still a major challenge [20]. In addition, some patients are reported to be refractory to all treatments. New therapeutic strategies are necessary to avoid potentially irreversible skeletal lesions [21]. The purpose of this study was to describe the clinical, laboratory and radiological features of a Chinese SAPHO syndrome cohort observed in a single centre from 2004 to Methods Patients who met the criteria for SAPHO syndrome proposed by Kahn and Khan [4] were recruited in Peking Union Medical College Hospital from 2004 to Inclusion criteria were as follows: osteoarticular manifestations with acne conglobata, acne fulminans or hidradenitis suppurativa; osteoarticular manifestations with PPP; hyperostosis (of the ACW, limbs or spine) with or without dermatosis; and CRMO involving the axial or peripheral skeleton with or without dermatosis. The exclusion criteria were as follows: septic osteomyelitis; infectious chest wall arthritis; infectious PPP; palmoplantar keratodermia; diffuse idiopathic skeletal hyperostosis except for fortuitous association and osteoarticular manifestations of retinoid therapy. All patients medical data were collected, including the onset and course of dermatological and osteoarticular manifestation; age at onset of symptoms and SAPHO diagnosis. Laboratory evaluation included ESR, hypersensitive CRP (hs-crp), RF, ANA and HLA-B27. Biopsy or surgery was performed when it was necessary for exclusion. Imaging data, including 99m Tc bone scintigraphy, whole spinal CT or CT of symptomatic sites, were collected. Therapy and the effect of treatment were also recorded. The effect of a drug was evaluated based on the patient s feeling of pain reflected by a visual analog scale score. We took those whose visual analog scale score was below 4 as reporting a good effect. Informed written consent was obtained from each patient. The Ethics Committee of Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences approved this study (Number of Ethics documents: ZS-944). Results Clinical manifestations of SAPHO patients One hundred and sixty-four patients (111 women and 53 men) who met the inclusion criteria were recruited to our cohort. The mean age of the patients was years and the mean age at onset of symptoms was years. The mean duration of diagnosis was 3.61 years. Interestingly, most of the patients were misdiagnosed with other diseases, such as costochondritis and AS, when they first presented to the doctors (supplementary Table S1, available at Rheumatology Online). Details of demographic characteristics of this cohort are shown in Table 1. Among them, 155 patients had both osteoarticular symptoms and dermatological manifestations, whereas nine patients had only osteoarticular symptoms without skin involvement. Among those with dermatological manifestations, 54.2% (84/155) patients had dermatological manifestations before osteoarticular symptoms, whereas 18.7% (29/155) and 27.1% (42/155) had dermatological manifestations after and at the same time as osteoarticular symptoms, respectively. Clinical features of osteoarticular symptoms were insidious and variable, from slight to severe inflammatory pain in different locations with or without swelling. In our cohort, all patients suffered from pain in the ACW, and the percentage of patients suffering from pain in the cervical, thoracic and lumbosacral regions was 7.3, 22.0 and 67.6%, respectively. Interestingly, 82.9% had pain in peripheral joints, such as the shoulder, wrist, hip or knee, and four patients had

3 A cohort study of SAPHO syndrome TABLE 1 Demographic and clinical characteristics of the 164 patients with SAPHO syndrome Demographic and clinical characteristics (n = 164) Demographic characteristics Sex, female/male 111/53 Age, mean (S.D.), years (10.49) Age at onset of symptoms, m (10.84) ean (S.D.), years Duration of diagnosis, mean (S.D.), years 3.61 (5.88) Clinical characteristics, a number of patients with symptoms/total number of patients (%) Osteoarticular symptoms Cervical region pain 12/164 (7.3) Thoracic region pain 36/164 (22.0) Anterior chest pain 164/164 (100) Lumbosacral region pain 111/164 (67.7) Peripheral joint pain 136/164 (82.9) Skin manifestations PPP 143/155 (92.3) SA 25/155 (16.1) PPP only 108/155 (69.7) SA only 11/155 (7.1) PV only 0/155 (0) PPP and PV 23/155 (14.8) PPP and SA 13/155 (8.4) SA and PV 2/155 (1.3) Other manifestations IBD 0/164 (0) Laboratory tests ESR 93/163 (57.1) hs-crp 114/161 (70.8) ANA 12/164 (7.3) RF 2/164 (1.2) HLA-B27 4/164 (2.4) a Only positive or elevated associations are expressed. hs-crp: hypersensitive CRP; PPP: palmoplantar pustolosis; PV: psoriasis vulgaris; SA: severe acne. pain in the temporomandibular joint. Dermatological manifestations include PPP, SA and PV. In our study, 143 and 25 patients had PPP and SA, respectively. Twenty-four patients had PV, which was accompanied by PPP or SA (Fig. 1). Biopsy was performed in 37 patients (12 of them had skin biopsy and the remainer had bone biopsy or surgery). All the histopathological results showed neutrophil granulocyte infiltration without infection or malignant disease. Dermatological biopsy indicated hyperkeratosis of the stratum corneum and hyperproliferation of the stratum spinosum, with neutrophil granulocyte, lymphocyte and plasma cell infiltration in the dermis, whereas bone biopsy indicated aseptic inflammation in the bone marrow, with neutrophil granulocyte and lymphocyte infiltration. None of the patients in our cohort had IBD. Laboratory findings Laboratory evaluation included ESR, hs-crp, ANA, RF and HLA-B27. The ESR level was elevated (ESR > 20 mm/h) in 57.1% of patients, whereas 70.8% of patients had an increased hs-crp level. Only 7.3% of patients had a low titre of ANA, and 1.2 and 2.4% were RF and HLA- B27 positive, respectively. The details can be found in Table 1. Imaging features of SAPHO patients CT scans of the whole spinal column with multiplanar reconstructions were performed in 53 patients at the radiology department in our hospital. The disorders of the osteoarticular involvement observed on CT images are shown in Table 2. The ACW, which consists of the sternocostal joint, sternoclavicular joint and manubriosternal joint, is the most common target area involved in SAPHO syndrome, with 90.6% (48/53) of patients affected. Imaging findings of ACW lesions, including osteolysis, sclerosis and hyperostosis (Fig. 2A), were detected by CT scan. Spinal disorders, which mainly included vertebral lesions and paravertebral ossifications, could be detected in 79.2% (42/53) and 71.7% (38/53) patients, respectively. Vertebral lesions manifested as cortical erosion, sclerosis in the surrounding cancellous bone and subsequent syndesmophytes of the vertebral corner, with or without intensive involvement of the neighbouring endplate (Fig. 2B and C). The ligamentous ossifications were delicate and segmental (Fig. 2D), mostly located on the supraspinous ligament. Sacroiliitis could be found in 45.3% (24/53) of patients, 26.4% (14/53) laterally and 18.9% (10/53) bilaterally. On CT images, sacroiliac disorders manifested as osteolysis, sclerosis and ankylosis in a progressive process. All these disorders described above could be depicted clearly and accurately on CT images because of their superiority in demonstrating osteoarticular lesions and high resolution. Bone scintigraphy was carried out in 157 patients, and all of them had ACW involvement, including the sternoclavicular joint, manubriosternal joint and costosternal joint. The vertebrae and peripheral joints were proved to be involved in 71 and 54 patients, respectively. The bull-horn sign was seen in bone scintigraphy images, which is the typical characteristic of SAPHO syndrome (Fig. 3). Treatment and response The major drugs used of NSAIDs, antibiotics, CSs, biphosphonates and DMARDs, including MTX, SSZ, HCQ, CSA, LEF and CYC. Biologic therapy was also used in some patients. NSAIDs were the most frequently prescribed drugs for initial treatment. In our cohort, 131 (79.9%) patients took NSAIDs, and 113 of them (86.3%) had disease improvement. CS therapy, which was common for those who did not repond in a satisfactory manner with NSAIDs, were used in 85 (51.8%) patients, and 69 of them (81.2%) described pain relief. CS (prednisone or equivalent) was administered at an initial dosage of mg/kg/day, with an average dosage of 30 mg/day, tapered by 5 mg every week, and was gradually reduced to 10 mg/day after 4 weeks. DMARDs were used in 100 (61%) patients to control peripheral synovitis, of whom 58, 39, 34, 5, 7 and 3 patients took MTX, SSZ, IEF, HCQ, CYC and CSA, respectively. Among them, 63 patients had more than one

4 Chen Li et al. FIG. 1Skin manifestations of SAPHO syndrome (A and B) The palmoplantar pustulosis. (C) Psoriasis vulgaris with involvement of nails. (D) Severe acne in the neck of the patient. TABLE 2 Involved lesions of SAPHO syndrome by whole spine CT scan and bone scintigraphy CT scan, number of patients with lesions/total number of patients who had the imaging evaluation (%) (n = 53) Sternoclavicular joint 35/53 (66.0) Manubriosternal joint 26/53 (49.1) Costosternal joint 46/53 (86.8) Sacroiliac joint 24/53 (45.3) Vertebrae 42/53 (79.2) Paravertebral ossifications 38/53 (71.7) Peripheral joints 3/53 (5.7) Bone scintigraphy, number of patients with lesions/total number of patients who had the imaging evaluation (%) (n = 157) Sternoclavicular joint 128/157 (81.5) Manubriosternal joint 49/157 (31.2) Costosternal joint 11/157 (7) Sacroiliac joint 46/157 (29.3) Vertebrae 71/157 (45.2) Peripheral joints 54/157 (34.4) Craniofacial bone and joints 16/157 (10.2) kind of DMARD. Only 49 patients considered DMARDs were effective enough. Oral bisphosphonates were used in 54 (32.9%) patients for severe bone pain, but only 16 (29.6%) patients were considered to respond effectively. Forty-one (25%) patients had tried anti-tnfa agents, and 28 (68.3%) patients had a good result. Discussion SAPHO syndrome was first introduced in 1987 to describe the bone, joint and skin lesions [3]. To date, SAPHO syndrome is considered as a rare disease whose real prevalence may be underestimated [3, 6, 12, 13, 15, 20]. According to our knowledge, we have reported the largest cohort of SAPHO syndrome, with 164 patients. A comparison of the features from some well-known cohorts is presented in Table 3 [6, 13 15, 20]. The aetiology of SAPHO syndrome is still unknown. Two hypotheses are most popular according to previous articles. One is that SAPHO syndrome is caused by a lowvirulence pathogen or an autoimmune response triggered by a viral or bacterial pathogen, such as Propionibacterium acnes [22]. Propionibacterium acnes can activate complement and induce IL-1, IL-8 and TNF-a, possessing strong immunomodulatory activities [23]. The other hypothesis suggested that SAPHO syndrome is related to seronegative spondyloarthropathies, especially PsA [11, 24]. The infectious theory was not supported by our study, as all the biopsy results showed neutrophil granulocyte infiltration. Our data showed no association with HLA-B27, which is consistent with other

5 A cohort study of SAPHO syndrome FIG. 2Multiple lesions were detected in different patients with SAPHO syndrome by CT scan Skeletal disorders of SAPHO patients. (A) Axial CT image of the first sternocostal joint showing focal cortical erosion with marked sclerosis and hyperostosis of the sternum and costal cartilage. (B) Oblique/coronal CT image of the sacroiliac joint demonstrating unilateral sacroiliitis on the left. (C) Sagittal CT image of the thoracic spine depicting cortical erosion and sclerosis in the manubrium, sternum and multiple thoracic vertebrae. (D) Sagittal CT image of the lumbar spine showing cortical erosion and sclerosis in multiple vertebrae and a coarse bony bridge across L2 L3. FIG. 3Bone scintigraphy of the SAPHO patients (A) Abnormal absorption in bilateral sternoclavicular joints (bull-horn sign). (B) Abnormal absorption in right clavicle and bilateral fifth rib. (C) Abnormal absorption in lumbar vertebrae and right tibia

6 Chen Li et al. TABLE 3 Comparison with other large cohorts Cohort Italy ( ) [13] Spain ( ) [6] France ( ) [15] Japan ( ) [14] Germany [20] Demographic characteristics Sex, female/male 48/23 26/26 70/50 37/17 52/12 Age, years Median (IQR) 45.5 ( ) 42 (12) 37.7 (12.9) Mean 48.4 b 48.1 (11.7) Age at onset of symptoms, years Median (IQR) 38.5 ( ) 37 (13) 28.6 (13.7) NA 35.8 (11.1) Duration of diagnosis, years Median (IQR) 4.6 ( ) 4.5 (5.6) Mean 9.1 b NA 3.8 (5.3) Follow-up, years Median (IQR) 11 (6 11.5) NA Mean 15.4 b NA NA Clinical characteristics, a number of patients with symptoms/total number of patients (%) Osteoarticular symptoms, n Anterior chest pain 50/71 (70) 38/52 (73) 76/120 (63) 50/53 (94.3) 49/63 (77.8) Lumbosacral region pain 17/71 (24) 24/52 (46) NA 21/53 (39.6) NA Peripheral pain 8/71 (11) 29/52 (55.8) 41 (34) 17/53 (32.1) NA Dermatological manifestations, n Patients without 31/71 19/52 19/120 NA 8/63 skin involvement, n PPP, n 26/40 (65) 17/33 (51.5) 66/101 (65) NA 42/63 (66.7) SA, n 16/40 (40) 13/33 (39.4) 30/101 (33) NA 9/63 (14.3) Psoriasis 3/40 (8) 11/33 (33) 37/101 (37) NA 16/63 (25.4) PPP only 20/40 (50) NA 38/101 (38) NA 26/63 (41.3) SA only 9/40 (23) NA 22/101 (22) NA 6/63 (9.5) PV only 3/40 (8) NA 12/101 (12) NA 2/63 (3.2) PPP and SA 5/40 (12) NA 7/101 (7) NA 2/63 (3.2) PPP and PV 0/40 (0) NA 21/101 (21) NA 13/63 (20.6) SA and PV 0/40 (0) NA 4/101 (4) NA 0/63 (0) Other manifestations, n IBD, n 2/71 (3) 2 (3.6) 9 (8) NA NA Laboratory tests, n ESR 15/71 (21) NA 66/101 (65) NA NA CRP 12/71 (17) NA 13/23 (57) NA NA RF 0/54 (0) NA NA NA 7/52 (13.5) ANA 0/39 (0) NA NA NA NA HLA-B27 0/71 (0) 8/45 (17.7) 11/83 (13) 0/36 (0) 7/45 (15.6) a Only positive or elevated associations are expressed. b S.D. of values not available in original publication. IQR: interquartile range; NA: not available. reports [6, 13 15, 20]. However, we noticed that >15% patients had psoriasis in our cohort, which may support the seronegative spondyloarthropathy hypothesis. Interestingly, none of the patients had been diagnosed with IBD, which was different from other cohorts [6, 13, 15]. Given that none of our patients had undergone colonoscopy, IBD could be a miss diagnosis or overlooked. In our study, SAPHO syndrome was a disease with young to middle-aged patients. Women were predominant (67.7%). This result was consistent with cohorts in France, Germany, Italy and Japan, whereas no difference in sex was reported for the Spanish cohort. In the present SAPHO cohort, the duration of diagnosis in our study was 3.6 years was much shorter than for other cohorts [6, 13, 15]. This may because of a better recognition of this disease these days in addition to the wide use of bone scintigraphy, which is a sensitive test for early diagnosis of SAPHO syndrome. Osteoarticular symptoms existed in all patients with different locations. The most commonly affected skeletal site was the ACW, which is consistent with the result of bone scintigraphy, followed by the axial skeleton, including vertebrae and the sacroiliac joint. Most patients (82.9%) complained about pain in the peripheral joints, but only 34.4% had increased uptake in peripheral joints on bone scintigraphy. In our study, only 5.5% of patients did not have dermatological manifestations, which is less than for other cohorts [6, 13, 15, 20]. PPP was the most common manifestation, followed by SA. PV usually accompanied other manifestations, such as PPP and SA. The proportion of patients affected with PPP only in our cohort was much higher than in other cohorts. No patients in our cohort presented with PV only, whereas several such cases presented in the European cohorts [6, 13, 15, 20]. The diverse race or genetic background may contribute to the unequal phenotype in different reports. Based on our histological results, neutrophil granulocyte infiltration was found in skin and bone lesions. Also,

7 A cohort study of SAPHO syndrome IL-1 and Th17 cells were found to be increased in SAPHO syndrome patients [25, 26], both of which indicate an inflammatory condition in SAPHO syndrome. ESR and hs- CRP/CRP are common inflammatory condition parameters. However, it seems that there are no correlations between ESR and clinical symptoms. In our study, almost half the patients who complained of an obvious progression of symptoms did not have elevated ESR. According to other cohorts, CRP had the same problem as ESR. In contrast, in our study, 70.8% of patients had an increased hs-crp level, which may be a better parameter to monitor the disease activity. In our study, 95.7% of patients had bone scintigraphy. All of them had increased uptake in one or more locations, and 10.2% of them had the bull-horn sign. Bone scintigraphy has been reported to be a sensitive and accurate early diagnostic test for bone lesions of SAPHO syndrome [27, 28]. Compared to CT scan, it could detect multiple involved skeletal sites, especially the ACW, whereas CT scan is more sensitive and elaborate in depicting spinal and osteoarticular lesions, which is especially significant in the absence of ACW involvement. Bone scintigraphy also has some other limitations. Firstly, it cannot determine whether the lesion is benign or malignant. Secondly, the symmetric uptake can be seen in some cases, which is confusing for diagnosis. Last but not least, scintigraphy cannot distinguish physiological and pathological changes in these cases. Therefore, CT or MRI scan is necessary to differentiate these lesions [15]. SAPHO syndrome usually has a good prognosis, but the pain often has an extreme influence on the quality of life of patients. To date, there is no standard treatment for SAPHO syndrome because of the unknown aetiopathological mechanism. According to our study, NSAIDs, CS and anti-tnf-a agents are effective for controlling the disease, especially for pain relief. But symptoms are recurrent, especially with drug discontinuation. In addition, patients often take more than one drug to control the disease, making it hard to evaluate the effect of a single drug. In conclusion, SAPHO syndrome is predominant in middle-aged women and characterized by dermatological and osteoarticular manifestations with unknown aetiology. Its prevalence may be underestimated because of lack of recognition. There is no standard treatment to control the disease. Acknowledgements The authors thank the patients who were involved in this study. And the authors thank the National Natural Science Foundation of China [ to G.Q., to Z.W.], Beijing Natural Science Foundation [ to N.W.] and Peking Union Medical College for supporting this study. Funding: This work was supported in part by grants from Foundation of Academic creative training plan of Peking Union Medical College [2015zlgc0609 to Y.Z]. Disclosure statement: The authors have declared no conflicts of interest. Supplementary data Supplementary data are available at Rheumatology Online. References 1 Nguyen MT, Borchers A, Selmi C et al. The SAPHO syndrome. Semin Arthritis Rheum 2012;42: Windom RE, Sanford JP, Ziff M. Acne conglobata and arthritis. Arthritis Rheum 1961;4: Chamot AM, Benhamou CL, Kahn MF et al. Acnepustulosis-hyperostosis-osteitis syndrome. Results of a national survey. 85 cases. Rev Rhum Mal Osteoartic 1987;54: Kahn MF, Khan MA. The SAPHO syndrome. Baillieres Clin Rheumatol 1994;8: Toussirot E, Dupond JL, Wendling D. Spondylodiscitis in SAPHO syndrome. A series of eight cases. Ann Rheum Dis 1997;56: Sallés M, Olivé A, Perez-Andres R et al. The SAPHO syndrome: a clinical and imaging study. 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