In 1961 Windom et al. first identified a link between skeletal muscle disease and convergent acne. in 1978 Bjorksten et al. suggested a link between chronic recurrent multifocal osteomyelitis and palmoplantar pustulosis. in 1987 Chamot et al. analyzed the clinical data of 85 patients and proposed for the first time to name a specific group of syndromes after SAPHO syndrome. In 2009, only 450 cases were reported in the global literature; currently, more than 20 cases are reported in China; with the deepening of the understanding of the disease, the number of cases will also increase, and this paper provides the following review of SAPHO in anticipation of a better understanding of the disease. I. Epidemiology, pathogenesis and histopathology There is a lack of large-scale epidemiological studies, and the literature reports mostly from Europe and Japan, Europe reported that the incidence of Caucasians does not exceed 1/10000; while Japan reported the incidence of 0.00144/100000. The age of onset was mostly before 30 years old and was more common in females, while Yabe et al [5] reported 11 cases with an age of onset mostly in middle age. It is considered that the incidence and age of onset may vary depending on the ethnicity. The pathogenesis of the disease is unclear. There are two hypotheses: one suggests that the disease may be triggered by humoral immune and precellular inflammatory responses induced by Propionibacterium acnes infection in a genetic background to stimulate SAPHO syndrome; the other suggests that SAPHO syndrome belongs to seronegative spondyloarthropathies, similar to seronegative spondyloarthropathies, especially psoriatic arthritis, with serum rheumatoid factor negative, relatively high prevalence of sacroiliac arthritis, spondylotic lesions as characteristics, but neither hypothesis has been confirmed. In 2002, Golla et al. identified a mutated gene in a rat model of CRMO, which is located on chromosome 18 and is associated with the immune response and apoptosis of the organism, and found that the mutation is an important cause of the occurrence of CRMO in rats, and speculated that this gene may In 2008, Ferguson et al. studied a family with a SAPHO syndrome-like phenotype, and the results suggested that the disease is a natural immune abnormal disease in a certain genetic background, suggesting a genetic susceptibility to the disease. Secondly, infection induces an immune response, which may be an important cause of pathogenesis. In recent years, several papers have reported that Propionibacterium acnes has been isolated from patients with SAPHO syndrome. It is believed that Propionibacterium acnes infection can trigger abnormal activation of the body’s own nonspecific T-cell immune response to eliminate the governing microorganism, causing a persistent inflammatory state, resulting in high expression of the inflammatory cytokines IL-1, IL-8, and TNF-a high expression, thus causing non-specific inflammatory damage. Clinically, high expression of TNF-a was found in the patient’s mandibular lesion. The effectiveness of TNF-a antagonist treatment also provides a basis for this view. The pathological features of SAPHO syndrome are not specific. Bone biopsies in the acute phase are characterized by edema with large numbers of multinucleated neutrophils and plasma cells and significant periostitis; in the chronic phase, osteosclerosis and fibrosis are the main features. Propionibacterium acnes could be cultured in some cases. Skin biopsies are characterized by pseudo-abscesses and negative bacterial cultures. Clinical manifestations, imaging and laboratory tests Clinically, it mainly includes skin changes and skeletal and joint changes. The characteristic skeletal joint changes are osteitis and bone hypertrophy. The main clinical manifestations are pain and limitation of movement at the involved areas. The sternum, clavicle, sternoclavicular joint and ribs are most commonly involved, in 70-90% of cases, showing pain at the anterior upper chest wall; the spine, sacroiliac joint, long bones and flat bones can also be involved. The typical skin changes are mainly impetigo and sequestrum. Pustulosis is predominantly female, with palmoplantar pustulosis (manifested as yellow intradermal sterile pustules on the palms of the hands and feet) being more common and pustular psoriasis less common. Severe pemphigus, which is more common in males, may manifest as convergent acne, violaceous acne, and purulent sweat gland inflammation. Skin changes and skeletal and joint changes can occur simultaneously or before or after (months to years apart), and even in some patients there are no skin changes at all, making the diagnosis of the disease difficult. The long-term course of the disease can lead to hypertrophy or even fusion of the clavicle and ribs, as well as compression of adjacent nerves and vascular structures causing limb pain and edema, called “thoracic outlet syndrome”. The incidence of inflammatory bowel disease is about 8%, with Crohn’s disease being the most common. Imaging is the main method to detect skeletal damage, mainly manifested as osteophytes and osteitis, mainly characterized by bone hypertrophy caused by chronic periosteal reaction and cortical hyperplasia. 1, anterior upper chest wall: the anterior upper chest wall is the most easily involved site, with an incidence of 60-95%, and is also a characteristic manifestation of the disease. If SAPHO is suspected clinically, a whole-body bone scan should be performed as early as possible. 99Tcm-MDP whole-body bone scan can detect bone destruction at an early stage, with a sensitivity of 88% as reported abroad. Bone scan suggests abnormal foci of radioactive concentration in the anterior upper chest wall, and the typical image is the “bull’s head” sign (there is also involvement of the sternal stalk connection with the bilateral sternoclavicular joints and the first rib-thoracic junction, the lesion of the bilateral sternoclavicular joints and the first rib-thoracic junction is equivalent to the bull’s horn, and the sternal stalk is equivalent to the upper part of the bull’s skull). The sensitivity of our data is 94%, but the typical bull’s head sign is only 20%. 2, the spinal joint: the spine is the second affected part, the incidence of 32-52%. Clinically, the thoracic spine is most commonly involved, followed by the lumbar and cervical spine. Isolated vertebral involvement is most common, with an incidence of about 58%, but multiple continuous involvement is also seen. The main imaging features are as follows: vertebral body edge erosion, vertebral body endplate erosion and sclerosis, paravertebral ossification, narrowing of the vertebral space, and vertebral body wedge shape changes. 3, sacroiliac joint: the incidence of sacroiliac joint involvement in 13-52%, usually unilateral onset, mostly manifested as osteosclerosis and bone hypertrophy on the iliac side, but also can appear erosive changes, such as the discovery of moderate unilateral onset of sacroiliac arthritis, clinical should be highly suspected of SAPHO syndrome, but also to identify seronegative spondyloarthropathy. 4, other: the incidence of long bone lesions in the 30%, the prevalence of young people and children, mostly in the distal femur and proximal tibia, fibula, humerus, ulna and radius can also be involved. The incidence of flat bone lesions is 11%, mostly in the mandible and iliac bone. The damage to the mandible usually presents as unilateral osteosclerosis with extensive periosteal reaction and painful swelling due to peripheral soft tissue edema, which can involve the temporomandibular joint. Laboratory tests are mostly non-specific. Rheumatoid factor and antinuclear antibodies are negative. It may show mild elevation of blood leukocytes; elevated blood sedimentation and C-reactive protein; may be accompanied by mild anemia and mild elevation of serum IgA; HLA-B27 may be positive. In 1994, Kahn MF and Khan MA proposed three diagnostic criteria for SAPHO syndrome: 1. multifocal osteomyelitis with or without skin manifestations; 2. acute and chronic aseptic arthritis with pustular psoriasis, palmoplantar pustulosis, or acne; 3. aseptic osteitis with pustular psoriasis; 4. 3, aseptic osteitis with a characteristic skin lesion. The diagnosis of SAPHO syndrome is made when one of the three conditions is met. The majority of the literature also follows this criterion, but it is too strict for early diagnosis, especially in patients without skin changes, and was revised by Kahn MF at the 2003 ACR Annual Meeting as follows: (1) bone and/or joint disease with palmoplantar pustulosis; (2) bone and/or joint disease with severe type of acne; (3) isolated aseptic bone hypertrophy or osteitis in adults (4) chronic recurrent polymorphic osteomyelitis in children; (5) bone and/or joint disease with inflammatory bowel disease. However, the diagnosis of SAPHO syndrome is made by excluding reactive arthritis and tumor bone metastases. The disease should be differentiated from bone infectious diseases, tumor bone metastases, ankylosing spondylitis, diffuse idiopathic bone hypertrophy, rheumatoid arthritis, and other diseases. Bone infectious diseases often have dead bone and soft tissue formation in the area of bone destruction. Tumor bone metastases, usually imaging can find the primary focus. Ankylosing spondylitis, which occurs mostly in young men, is HLA-B27 positive, mostly without skin changes, and usually does not accumulate in the sternum, clavicle, or sternoclavicular joint. Diffuse idiopathic hypertrophy, with involvement of the cervical, thoracic and lumbar spine with bone bridge formation, is easily confused with SAPHO; however, diffuse idiopathic hypertrophy is rarely associated with cutaneous lesions and osteomyelitis. In rheumatoid arthritis, peripheral symmetrical small joint involvement is predominant, and rheumatoid factor positivity is not difficult to differentiate. In view of the clinical rarity of this disease, the etiology is still unclear, and the treatment is mostly empirical and small sample clinical trials, lacking uniform standards and guidelines. The goal of treatment should be based on the alleviation of the patient’s systemic symptoms and not on imaging abnormalities alone. Non-steroidal anti-inflammatory drugs (NSAIDs) are usually used as the first choice of symptomatic treatment drugs, but the response has been mixed. The application of antibiotic drugs, especially lincomycin, tetracyclines, and macrolides, has achieved better clinical outcomes in patients with mandibular involvement according to the hypothesis of Propionibacterium acnes infection. For the possible immune response caused by this disease, glucocorticoids and disease-modifying antirheumatic drugs (DMARD): such as cyclophosphamide, methotrexate, lorazepam, cyclosporine A, thalidomide, etc. have also been seen reported to achieve good results. Anti-tumor necrosis factor-a antagonists have also shown good clinical efficacy in response to the high expression of anti-tumor necrosis factor-a observed clinically. Diphosphonates are also increasingly used in this disease because of their ability to inhibit osteoclasts, and they have also achieved some efficacy. Surgical treatment is not currently advocated because of the high recurrence rate after simple osteocortical debridement. There is a lack of long-term clinical observation of the prognosis of this disease in a large sample. However, the prognosis of this disease is considered to be good. 120 patients observed by Hayem et al [4] did not develop serious skeletal and joint complications or disability, and only 2 patients observed by Colina M et al developed skeletal and joint complications during the long-term follow-up of 71 patients. IV. Outlook SAPHO syndrome is difficult to diagnose early because of the non-specific clinical presentation, the diversity of imaging features, and the lack of knowledge about the disease, which requires comprehensive analysis by dermatologists, internists, radiologists, and surgeons, accurate and timely diagnosis and treatment, and avoidance of unnecessary invasive tests and surgery. There is a lack of large randomized double-blind controlled clinical trials on treatment, and the side effects of glucocorticoids and DMARD are also a concern for many patients; the long-term treatment with anti-tumor necrosis factor-a antagonist drugs remains to be observed; Chinese medicine has also achieved some efficacy in the treatment of this disease, which is expected to further complement the treatment of this disease.