Long-term clinical course of two rare cases of synovitis-acne-pustulosis-hyperostosis-osteomyelitis syndrome involving only unilateral femur.

Synovitis-acne-pustulosis-hyperostosis-osteomyelitis (SAPHO) syndrome is characterised by aseptic osteitis and is often complicated by pustular dermatitis, such as palmoplantar pustulosis or acne. Although bone lesions are most found in the anterior thoracic region or spine, femoral lesions are not well documented in the literature. There is no established treatment for this condition, and few reports have described its long-term course. Here, we describe two cases of SAPHO syndrome involving the femur and discuss their long-term follow-up. A 40-year-old man (Case 1) presented with right thigh pain. Fifteen years after the initial diagnosis, the pain could be controlled with minomycin, salazosulfapyridine, and methotrexate. X-rays of the femur showed gradual cortical thickening. Although there were waves of pain, it gradually improved with the adjustment of drugs 25 years following the initial diagnosis. A 35-year-old man (Case 2) with right thigh pain was prescribed salazosulfapyridine and methotrexate; however, these were ineffective. Alendronate and guselkumab also proved ineffective. Ultimately, infliximab was started 9 years following disease onset, and pain became manageable. X-rays of the femur showed cortical thickening. SAPHO syndrome can be managed with drug therapies, such as nonsteroidal anti-inflammatory drugs, methotrexate, and conventional synthetic disease-modifying antirheumatic drugs; however, there are occasional treatment-resistant cases.

Anterior Chest Wall Non-traumatic Arthropathies: A Crucial but Often Overlooked Site.

OBJECTIVE: The purpose of this study was to describe the distribution of Anterior Chest Wall (ACW) arthropathies in a tertiary care center and identify clinical, biological and imaging findings to differentiate osteoarthritis (OA) from non-osteoarthritis (N-OA) etiologies. METHODS: Search from medical records from January 2009 to April 2022, including patients with manubriosternal and/or sternoclavicular and/or sternocostal joint changes confirmed by ultrasonography, computed tomography or magnetic resonance imaging. The final study group was divided into OA and N-OA subgroups. RESULTS: A total of 108 patients (34 males and 74 females, mean age: 47.3 ± 13 years) were included. Twenty patients had findings of OA, while 88 were diagnosed with N-OA pathologies. SpA was the most common etiology in the N-OA group (n = 75). The other N-OA etiologies were less common: rheumatoid arthritis (n = 4), Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome (n = 3), infectious arthritis (n = 3) and microcrystalline arthropathies (n = 3). Regarding the distinctive features, ACW pain was the inaugural manifestation in 50% of patients in OA group and 18.2% of patients in N-OA group (p = 0.003); high inflammatory biomarkers were more common in N-OA group (p = 0.033). Imaging findings significantly associated with OA included subchondral bone cysts (p < 0.001) and intra-articular vacuum phenomenon (p < 0.001), while the presence of erosions was significantly associated with N-OA arthropathies (p = 0.019). OA was independently predicted by the presence of subchondral bone cysts (p = 0.026). CONCLUSION: ACW pain is a common but often underestimated complaint. Knowledge of the different non-traumatic pathologies and differentiation between OA and N-OA etiologies is fundamental for appropriate therapeutic management.

Unusual cause of inflammatory backache: SAPHO syndrome.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) is a rare chronic inflammatory disease that develops in adults. We present a case of SAPHO syndrome in a 37-year-old male presenting with gradually worsening back and neck pain for a 7-year period. The episodes were preceded by a history of pustular skin eruptions, which first appeared on the upper trunk and then involved his face and were pustular and scarring. The purpose of presenting this case report from Iraq is to raise awareness about this rare condition, which is frequently misdiagnosed and under-recognized.

Sexual function assessment in patients with SAPHO syndrome: a cross-sectional study.

INTRODUCTION: SAPHO syndrome is a group of special syndromes characterized by synovitis, acne, pustulosis, hyperostosis and osteitis. Skin lesions and joint damage are the main clinical manifestations. Among them, females mostly present with palm toe pustulosis, while males have severe acne as the main external manifestation. The bone and joint damage characterized by bone hypertrophy and osteitis is the core manifestation of SAPHO and affects all parts of the body. SAPHO syndrome causes great physical and mental suffering to patients, and it also brings a huge financial burden to the family. The purpose of this study is to explore the impact of SAPHO on the quality of sexual life of patients. METHODS: We screened and included 249 SAPHO patients (169 women and 80 men) from Peking Union Medical College Hospital (Beijing, China). First, we recorded the basic situation of the patient through questionnaires (including gender, age, SAPHO duration, BMI, smoking, drinking, marital status, educational level, occupational status and work status.). Then, the patient needed to fill in the Short Form-36 quality of life questionnaire (SF-36 QoL) to record the quality of life. For Sexual dysfunction (SD), female patients needed to fill in the Female Sexual Function Index (FSFI) to assess the quality of sexual life; while the International Index of Erectile Function (IIEF) was used to assess the SD of male patients. At the same time, we used self-esteem and relationship questionnaire (SEAR) to analyze the psychological state of SAPHO patients. Finally, we performed statistical analysis on the data obtained, and then explored the connection between SAPHO and SD. RESULTS: In this cross-sectional study, a total of 249 patients completed the questionnaire and constituted the study population. We found that among 169 female patients, 124 patients had FSD (73.4%); while 45 patients did not have FSD (26.6%); and among 80 male patients, 45 (56.3%) had ED; However, 35 patients did not have ED (43.7%). The results of the quality of life and mental state assessment showed that female patients with SD showed lower scores in terms of mental state. Among all male participants, we found no significant difference in quality of life and mental state among participants with or without SD. In addition, there was no significant difference in the duration of SAPHO between female and male participants with or without SD. CONCLUSION: This study is the first to evaluate the SD of SAPHO patients. The incidence of SD in female SAPHO patients is higher than that in male patients; the cause of female SD may be mainly psychological factors. These results prove that it is particularly important to focus on regulating their psychological state while diagnosing and treating SAPHO patients in clinical practice.

Synovitis, acne, pustulosis, hyperostosis, osteitis syndrome with invisible organizing pneumonia: A case report.

We report the case of a 59-year-old female patient, presenting with pustular rash on both hands and pain in the lumbosacral part and left lower limb. A magnetic resonance imaging examination of the left leg was undertaken and the result showed that a malignant lesion with bone destruction of the left femoral shaft could not be excluded. Subsequently, bone tumor was excluded by pathological examination. Lung computed tomography scan showed patchy consolidation and cord shadow in the middle left lung. Subsequently, lung cancer was excluded by pathological examination, and the histopathological changes of lung were consistent with those of organized pneumonia. Blood tests revealed elevated C-reactive protein and erythrocyte sedimentation rate. Antinuclear antibody, rheumatoid factor, and human leukocyte antigen-B27 were unremarkable. Whole body bone scintigraphy via technetium 99m-methyl diphosphonate showed increased radionuclide uptake in the left middle femur. Based on her clinical manifestations, imaging results and bone scintigraphy, the patient was diagnosed as having synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. Loxoprofen and Tripterygium wilfordii Hook F led to impressive clinical and radiologic improvement.

A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome with isolated lesions of the thoracic spine.

We report a case of isolated lesions of the thoracic spine attributed to synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. A 55-year-old woman who suffered from 6 months of back pain had vertebral osteomyelitis on magnetic resonance imaging (MRI). There were no laboratory findings suggestive of infection, malignancy, or autoimmune disease. Radiography, computed tomography (CT), and MRI of the thoracic spine showed mixed lesions of sclerosis and erosion, whereas bone scintigraphy did not show accumulation at any site except the thoracic spine. No lesions in the anterior chest wall or sacroiliac joints were apparent from CT and MRI. No lesions other than at the thoracic spine were observed. As the isolated lesions of the thoracic spine were considered not to have resulted from infection, malignancy, or autoimmune disease, the patient was referred to our department for differential diagnosis. Given that isolated sterile hyperostosis/osteitis among adults is included in the modified diagnostic criteria for SAPHO syndrome, we suspected that the mixed lesions of sclerosis and erosion of the thoracic spine in this case may reflect SAPHO syndrome with chronic non-bacterial osteitis (CNO) of the thoracic spine. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was initiated and led to alleviation of her back pain, although the thoracic spine lesions remained on the 6-month MRI. Based on the CNO of the thoracic spine and the rapid response to NSAIDs, the final diagnosis was SAPHO syndrome with isolated lesions of the thoracic spine.

Destructive cervical spondylitis due to Cutibacterium acnes with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome: A case report.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a spectrum of heterogeneous diseases commonly recognised by skin and osteoarticular lesions. There have been reports of some surgical cases of the progressive, destructive spondylitis associated with SAPHO syndrome, wherein the destructive spondylitis was considered to have developed due to the progression of spondylitis with SAPHO syndrome as the pathogenic bacteria were not isolated. We herein report a surgical case of destructive cervical spondylitis associated with SAPHO syndrome. A 54-year-old woman with a history of palmoplantar pustulosis suffered severe neck pain for 6 months. Radiography and computeed tomography showed sclerosed and collapsed cervical vertebrae, and the patient was referred to our hospital for further evaluation and management upon suspicion of infection or spondylitis with SAPHO syndrome. For the severe neck pain and progressive destruction of cervical vertebrae, we performed posterior fusion surgery with subsequent anterior fusion. Cutibacterium acnes (C. acnes) was isolated by enrichment culture with thioglycolate broth from both the anterior and the posterior tissue samples. We diagnosed pyogenic spondylitis secondary to C. acnes infection and administered doxycycline for 6 weeks after the first surgery. The neck pain was resolved and cervical fusion was achieved one year postoperatively. C. acnes infection could elicit destructive spondylitis. An enrichment culture should be performed to isolate the pathogenic bacteria in cases of destructive spondylitis with SAPHO syndrome.

Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome with mandibular involvement: Would surgical operation help?

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare autoinflammatory disease; its primary manifestation includes osteoarthropathy with skin involvement. Janus kinase (JAK) inhibitors, such as tofacitinib, were used for rheumatoid arthritis; however, due to its downregulation of immune cytokines including interleukin (IL)-6 and IL-8, it might be effective for SAPHO patients. CASE SUMMARY: We report the 1st case of mandibular-related SAPHO syndrome treated with tofacitinib. The patient underwent mandibular resection surgery twice and postoperative pathology showed "osteomyelitis". The patient developed sclerosing osteomyelitis in the left wrist 9 months after surgery and SAPHO syndrome was diagnosed. The patient was administered nonsteroidal anti-inflammatory drugs and corticosteroids therapy without much remission. A 3-month tofacitinib therapy provided remission from both systemic inflammation status and peripheral osteoarticular symptoms and no significant recurrence was observed during follow-up in this case. CONCLUSION: Mandibular involvement in SAPHO syndrome is easily misdiagnosed due to its rarity. Mandibular resection surgery should be applied carefully; after systemic treatment with tofacitinib, the patient had remission. We provide a successful experience for the treatment of mandibular-related SAPHO syndrome.

Tumor necrosis factor inhibitors for pediatric patients with SAPHO syndrome associated with acne conglobata.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease with osteoarticular and cutaneous involvements as its main manifestations. Acne conglobata as a severe acne form may affect adolescent patients. Tumor necrosis factor inhibitors are usually used as a second-line therapy for refractory SAPHO syndrome and has been reported to treat acne conglobata successfully. We herein report three cases of adolescent patients with SAPHO syndrome associated with acne conglobata who were successfully treated with TNFi therapy.

68Ga-DOTA-FAPI-04 PET/CT Imaging in a Case of SAPHO Syndrome.

ABSTRACT: A 66-year-old woman presented with anterior chest wall and knee joints pain and multiple skin lesions. 99mTc-MDP bone scintigraphy showed increased bone density in the sternal angle with abnormal bone metabolism. The patient was enrolled in a 68Ga-DOTA-FAPI-04 PET/CT tumor clinical trial, and it showed increased tracer uptake in the sternum and right knee joint. Subsequently, ultrasound of the right knee joint confirmed the existence of synovitis, and no malignant components were found in sternal biopsy. The patient's final diagnosis was synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. The case confirmed that 68Ga-DOTA-FAPI-04 imaging is helpful for evaluating the involved sites of SAPHO syndrome.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome of femoral neoplasm-like onset: a case-based review.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an umbrella term covering a constellation of bone lesions and skin manifestations, but has rarely been clarified in the clinic. We report a 28-year-old woman who had initial onset of SAPHO syndrome with involvement of the femur, and she experienced a tortuous diagnostic course. We also performed a literature review of SAPHO syndrome cases involving the femur and summarize several empirical conclusions by integrating previous findings with our case. Furthermore, we propose our perspective that ailment of the skin caused by infection of pathogens might be the first hit for triggering or perpetuating the activation of the immune system. As a result, musculoskeletal manifestations are probably the second hit by crosstalk of an autoimmune reaction. The skin manifestations preceding bone lesions can be well explained. Current interventions for SAPHO syndrome remain controversial, but drugs aiming at symptom relief could serve as the first preference for treatment. An accurate diagnosis and appropriate treatment can cure patients in a timely manner. Although the pathogenesis of SAPHO syndrome remains to be determined, physicians and surgeons still need to heighten awareness of this entity to avoid invasive procedures, such as frequent biopsies or nonessential ostectomy.

[SAPHO syndrome with chronic tonsillitis: a case report and literature review].

SAPHO syndrome is a rare disease which affects the bones, joints, and skin. It is often misdiagnosed and treated mistakenly because of various clinical manifestations and general lack of awareness about the disease. The pathogenesis is inadequately understood, as a result, current therapy is empirical and aimed to control inflammatory process and alleviate pain. This paper summarizes the clinical manifestations and diagnosis and treatment scheme of SAPHO syndrome, and presents a case of patient with SAPHO syndrome who was treated in our department for bilateral tonsillectomy due to repeated pharyngalgia and fever for 10 years. Interestingly, the patient is getting better after the operation. The case is reported so as to provide reference for the diagnosis and treatment of SAPHO syndrome.

Pustular Psoriasis and Associated Musculoskeletal Disorders.

Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement.Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic non-bacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints.

Metastatic Carcinoma of Prostate as a Mimicker of SAPHO Syndrome.

Paraneoplastic arthritides are a group of immune-mediated inflammatory arthropathies associated with occult or manifest malignancy. Musculoskeletal spread of an underlying malignancy may also mimic many rheumatologic conditions. Distinguishing primary rheumatologic condition from paraneoplastic arthritides versus direct musculoskeletal spread of malignancy can be challenging especially in individuals with prior history of cancer and new musculoskeletal complaints. SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is an uncommon, although under recognized autoimmune disorder. Two musculoskeletal manifestations, namely inflammatory osteitis and hyperostosis of anterior chest wall with or without dermatologic manifestations, constitute a unifying feature of SAPHO syndrome. However, diagnosis of SAPHO syndrome is one of exclusion, and a wide variety of disorders including infections, malignancy (chondrosarcoma/osteosarcoma/metastasis), metabolic bone disorders (Paget's disease), osteoarthritis, seronegative spondyloarthropathy (spA) and osteonecrosis form part of a broad differential diagnosis. We present the case of a man, aged 72 years, with signs and symptoms of SAPHO syndrome and skin findings. Detailed history, radiological imaging, dermatology appearance, and role of immunohistochemical markers, especially staining for NKX3.1 protein with a novel antibody, led to a diagnosis of metastatic prostate adenocarcinoma. To our knowledge, this is the first case of metastatic adenocarcinoma of the prostate manifesting as SAPHO syndrome and cutaneous metastasis.

[SAPHO syndrome : An overview and nosological differentiation of 35 disease cases]. / SAPHO-Syndrom : Ein Überblick und nosologische Differenzierung von 35 Krankheitsfällen.

The SAPHO syndrome is not a single entity but an inhomogeneous, nosologically heterogeneous complex of symptoms with unknown etiology and heterogeneous pathogenesis. Clinically subacute, recurrent or chronic disease processes and a common skin-bone association (skibo disease) can be found. Under the acronym SAPHO, chronically recurrent multifocal osteomyelitis (CRMO) is the most common disease that can occur in youth as well as adolescence. Spondylarthritis hyperostotica pustulo-psoriatica with the triad palmoplantar pustulosis, sternoclavicular hyperostosis and ossifying spinal manifestations is the most common SAPHO form found in adults. Abortive disease forms are the inflammatory anterior chest wall syndrome, extended sternoclavicular hyperostosis syndrome of the clavicle bone, acne CRMO and acne spondylarthritis. The SAPHO disease usually heals with a relatively favorable prognosis but there are also unfavorable courses with functional limitations. The diagnosis should be made based on clinical examination, imaging (x-ray, scintigraphy, magnetic resonance imaging) and/or histological bone biopsy analysis. Treatment should be interdisciplinary. Antibiotic treatment is obsolete. This article provides an overview of the SAPHO syndrome and a clinical-rheumatological imaging differentiation as well as classification of 35 cases at first presentation.