Osteitis Syndrome Research Articles

Assessment ofclinical andradiological characteristics ofJapanese patients with synovitis, acne, pustulosis, hyperostosis, andosteitis syndrome.

This study aimed to analyse the radiological characteristics and clinical diversity of Japanese patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a heterogeneous disorder. Radiographs and clinical information from 115 Japanese patients (female/male: 81/34; mean age at onset: 48.7 years) diagnosed with SAPHO syndrome between January 2007 and December 2020 were retrospectively reviewed. Additionally, the treatment for SAPHO syndrome was explored. Among the 115 patients, 70 patients had complications, including palmoplantar pustulosis, acne, or psoriasis. Imaging studies included bone scintigraphy, magnetic resonance imaging, computed tomography, and positron emission tomography in 71, 58, 70, and 23 patients, respectively. The most frequent lesions were arthritis and hyperostosis of the sternoclavicular joints in 96 patients; spinal lesions, including sacroiliac arthritis, were observed in 85 patients. Peripheral aseptic osteitis was observed in 22 patients, and the tibia was involved in 12. The treatments consisted of analgesics, bisphosphonates, conventional synthetic disease-modifying antirheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively. Sternoclavicular hyperostosis and pustulosis are frequently observed in patients with SAPHO syndrome. Biological agents were more frequently used in patients with peripheral osteitis and arthritis.

Diagnostic and therapeutic practices in adult chronic nonbacterial osteomyelitis (CNO)

BackgroundChronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans.MethodsA primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring.Results36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2–3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNFα), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNFα and were considered the most effective treatments.ConclusionsFollowing from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNFα are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline.

Prospective Comparison of the Imaging Value of 99m Tc-MDP Bone Scan and 68 Ga-FAPI-04 PET/CT in Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome.

This study aimed to explore the imaging value of 68 Ga-FAPI-04 PET/CT in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and compare it with that of 99m Tc-MDP bone scan. Nineteen participants with SAPHO syndrome underwent 68 Ga-FAPI-04 PET/CT and 99m Tc-MDP bone scan. Demographic data and clinical features were recorded, SAPHO imaging features were analyzed, and the osteoarticular lesion detection rate in both methods was calculated. This prospective study recruited 4 men and 15 women aged 52.4 ± 8.6 years. The anterior chest wall was involved in all participants (100%). Palmoplantar pustulosis was the most common (36.8%) skin symptom. 99m Tc-MDP bone scan and 68 Ga-FAPI-04 PET/CT together detected 84 osteoarticular lesions, of which 91.7% (77/84) were detected by the former and 96.4% (81/84) by the latter. Furthermore, 68 Ga-FAPI-04 PET/CT detected 5 cases of knee and hip joint synovitis. 68 Ga-FAPI-04 PET/CT was more sensitive than 99m Tc-MDP bone scan when evaluating osteoarticular lesions in SAPHO syndrome and could also evaluate synovial lesions. 68 Ga-FAPI-04 PET/CT could be a good imaging method for SAPHO syndrome but requires further verification in a more extensive research cohort.

Imaging of Osteoarticular Lesions in SAPHO Syndrome: A Case Report

Introduction: Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is an acronym for a variety of osteoarticular and dermatologic manifestations. Although the incidence and prevalence are probably underestimated, the syndrome is considered rare. Observation: A 45-year-old female patient, without any particular pathological history, presented with anterior chest pain, spinal pain and palmar pustulosis. The symptoms had been evolving for six months, in a context of apyrexia and conservation of the general state. The diagnosis of SAPHO syndrome was retained in view of the young age, the clinical presentation and the axial osteoarticular involvement on imaging. In addition, bone scintigraphy objectified the "bull's head sign". Discussion: The osteoarticular manifestations of SAPHO syndrome are characterized by osteosclerosis, hyperostosis, erosions, synovitis and synostosis. Some locations, especially the anterior chest wall, and some topographical associations are very suggestive. Clinical symptoms are non-specific, hence the interest of imaging. CT is the modality of choice to determine the extent of osteoarticular lesions. Magnetic resonance imaging has an important place. It allows to establish a correlation between the stage of the disease and the clinical symptoms. Conclusion: Knowledge of clinical manifestations and radiological features allows for early diagnosis and prevention of osteoarticular progression.

Chronic Recurrent Multifocal Osteomyelitis (CRMO) and Juvenile Spondyloarthritis (JSpA): To What Extent Are They Related?

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease occurring mainly in the pediatric age group (before 16 years) and generally presents as a separate entity. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome combines osteoarticular and cutaneous involvement, similar to CRMO, and falls into the spectrum of spondyloarthritis (SpA). The fact that a patient can progress from one disease to another raises the question of whether CRMO, like SAPHO, could fall within the spectrum of SpA, ranging from a predominantly osteoarticular form to an enthesitic form with more or less marked skin involvement. In this review, we set out to discuss this hypothesis by highlighting the differences and similarities between CRMO and juvenile SpA in clinical, radiological and pathophysiological aspects. A common hypothesis could potentially consider intestinal dysbiosis as the origin of these different inflammatory diseases. Interindividual factors such as gender, environment, genetics and/or epigenetic background could act as combined disease modifiers. This is why we suggest that pathophysiology, rather than clinical phenotype, be used to reclassify these diseases.

Clinical and imaging features of six Han patients with SAPHO syndrome.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune disease characterized by skin or osteoarticular damage. SAPHO syndrome is often misdiagnosed or missed diagnosis due to lack of overall understanding of the disease by clinicians. To analyze the clinical symptoms and imaging features of six Han patients with SAPHO syndrome in order to provide reference for doctors to diagnose SAPHO syndrome. This study retrospectively analyzed the clinical data of six Han patients with SAPHO syndrome. All six Han patients with SAPHO syndrome had severe acne or pustulosis of the hands and feet, and all of them had osteoarticular damage, including five cases involving the sternoclavicular joint. Some patients showed a specific and typical "bull's head" sign on 99mTc-labeled methylene diphosphonate bone imaging. Among the six patients recruited, there was one thoracic vertebra, one cervical vertebra, one sacroiliac joint, and one peripheral joint involvement. Two patients had limited activity due to severe osteoarticular damage. Due to the atypical clinical symptoms of SAPHO syndrome, most patients will experience a tortuous and long diagnostic process, while a correct understanding and timely intervention of SAPHO syndrome are essential to improve the prognosis of patients.

Work productivity and activity in patients with SAPHO syndrome: a cross-sectional observational study

BackgroundOur understanding of work productivity impairment among patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is limited. The purpose of this study was to provide an overview of work productivity loss in SAPHO syndrome patients through the use of the work productivity and activity impairment (WPAI) questionnaire, as well as to investigate the relationship between the WPAI and other disease-related indicators.MethodsPatients for this cross-sectional study were recruited from Peking Union Medical College Hospital (Beijing, China). The questionnaires incorporating the WPAI were administered, along with the inclusion of demographic data, disease-specific measures, and general health variables. The construct validity of the WPAI was evaluated via the correlations between WPAI outcomes and other measures. Wilcoxon rank-sum tests and nonparametric Kruskal‒Wallis tests were used for the comparison of the WPAI outcomes between known groups.ResultsA total of 376 patients were included, and 201 patients (53.5%) were employed. The medians (interquartile range [IQR]) of absenteeism, presenteeism, work productivity loss, and activity impairment were 0% (0–13%), 20% (0–40%), 20% (0–52%), and 30% (0–50%), respectively. All of the WPAI outcomes showed moderate to strong correlations with other generic and disease-specific measures (|r| = 0.43–0.75), except for absenteeism. Increasing disease activity and worse health status were significantly associated with increased impairments of work productivity and activity.ConclusionThis study highlights the negative effects of SAPHO syndrome on the work productivity and activity of patients, thus indicating good construct validity and discriminative ability of the WPAI. To reduce the economic burden, it is important to improve the work productivity and daily activity of patients by ameliorating clinical care.

P43 A complicated road to diagnosis: Auto inflammatory bone disease

Introduction/BackgroundAuto inflammatory bone disorders are characterized by chronic non-infectious osteomyelitis and inflammation-induced bone resorption. It results from aberrant activation of components of the innate immune system. The auto inflammatory bone disorder includes chronic non-bacterial osteomyelitis (CNO) and its severe form chronic recurrent multifocal osteomyelitis (CRMO); synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome; Majeed syndrome; deficiency of interleukin-1 receptor antagonist (DIRA) and cherubism. The most common among this is CRMO/CNO. The disease can affect any part of the body but the metaphyseal region of the long bones, clavicle, and vertebra are the most commonly affected site.Description/MethodA 9 year old girl presented with five month history of swelling over right periocular and temporal region, associated with skin discoloration and difficulty in opening her eyes. She also reported headache more in the right frontal region. She had on and off exacerbations of skin discoloration and headaches. There was no history of fevers, weight loss, night sweats, skin lesions or arthritic symptoms. She did not have a personal or family history of inflammatory or autoimmune disorders. She is under ophthalmology elsewhere since the age of 3 months with a right divergent squint and history of right squint surgery at 6 years.Physical examination revealed swelling involving right infraorbital and temporal region, which was soft and not tender to touch with associated erythema in the same site. There were no signs of meningism or altered mental status. Musculoskeletal examination was unremarkable.Her blood test results showed mild increase in platelets (476 * 109), CRP 8mg/L, ESR (18mm/hr). IgG4 titres were mildly raised (1.16g/L). Other immunologic markers including rheumatoid factor, human leukocyte antigen B27, antinuclear antibody and anti-neutrophil cytoplasmic antibody were normal.Histopathological examination of bone and soft tissue of her right orbital rim showed low grade non-specific chronic inflammation with extensive appositional remodelling of bone suggestive of CRMO/SAPHO. No evidence of malignancy/infection.Later whole body MRI was performed to identify the extent of disease. MRI whole body was performed which showed multiple areas of bone marrow oedema and periostitis within the appendicular and axial skeleton, bilateral gluteal enthesitis and sacroilitis. There are some features that are atypical for CRMO (asymmetrical involvement, transphyseal involvement including epiphyseal involvement of the left humerus). Also noted to have right-sided periorbital oedema, oedema of the right masticator muscles and temporalis. Further planned to do dedicated MRI of left humerus with contrast.Discussion/ResultsIt can be difficult to consider what the problem is when a health care provider is presented with a group of seemingly disparate signs and symptoms with a history and time course that do not match classic (or commonly atypical) disease presentations. Common things happen commonly, so when symptoms occur without the usual co-occurring symptoms, unusual symptoms or time courses, it can be challenging.The current patient presented with periocular swelling with headache and skin discolouration. The differentials can be Langerhans cell histiocytosis, IgG4-related disease, osteoblastoma, and osteosarcoma. There were no hepatosplenomegaly, lymphadenopathy, also the mass was soft to palpate, and hence the above differentials were unlikely. Patient was initially evaluated at tertiary oncology centre and malignancy ruled out. The histopathology slides were reviewed and reported as mentioned above. In view of no skin manifestations, CRMO was the likely diagnosis considered. Hence MRI whole body performed.Barrani et al reported a similar type of unusual case of a 12-year-old girl with CRMO arising with recurrent episodes of left supraorbital headache, followed by the appearance of a periorbital dyschromia. Magnetic resonance imaging (MRI) of the skull and orbits revealed an important subacute inflammatory process. However, a few months later, the child presented a painful swelling of the left clavicle; the histological examination of the related biopsy allowed us to establish the diagnosis of CRMO.The follow up with our patient is quite a short duration and she might evolve later in the disease course giving more clarity!Key learning points/ConclusionIn evaluating a diagnostic dilemma, starting the laboratory evaluation helps to begin the process of trying to find an answer and can also help the families as “something is being done.”Chronic recurrent multifocal osteomyelitis can present with unifocal lesions, atypical locations or absence of recurrence.A high level of suspicion is paramount to avoid unnecessary biopsies and repeated antibiotic regimens.Families will often be quite concerned and support for them is also necessary and close communication and follow up is appropriate.

Rapid Progression of Sternocostoclavicular Hyperostosis (SCCH) Observed after Anti-TNF-a Therapy for Polyarthritis: A Case Report

Sternocostoclavicular hyperostosis (SCCH) is a chronic osssifying diathesis affecting mostly juxtasternal structures and the inflammatory osteitis is mostly part of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome with Cutis Verticis Gyrata: Case Report and Review of Literature

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare disease clinically characterized by a wide range of cutaneous and osteoarticular manifestations. Here, we report a case of SAPHO syndrome with cutis verticis gyrata (CVG) and investigated the genetic causes in the four members of this pedigree. After failure of conventional treatments, a recombinant human TNF-α receptor II:IgG Fc fusion protein (rhTNFR:Fc, YISAIPU®) achieved good control of the disease at the 2-year follow-up. We did not identify any pathogenic mutation in this pedigree. We also summarized the clinical and therapeutic characteristics of 83 patients with SAPHO syndrome through the China National Knowledge Infrastructure (CKNI) database from 2016 to 2021. Patients with acne were young and predominantly male. About 45.8% patients were treated with biological therapies or traditional Chinese medicine (TCM), 84.2% of which showed positive effects against cutaneous and osteoarticular manifestations. We report a case of SAPHO syndrome with CVG that was successfully treated with rhTNFR:Fc. Our results reveal the genetic heterogeneity involved. Biologics and TCM are likely alternative options for the treatment of SAPHO syndrome.

Pro and contra: is synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) a spondyloarthritis variant?

The purpose of this review is to present the up-to-date evidence on the epidemiology, pathogenesis, musculoskeletal manifestations, and imaging of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and to discuss its relationship with spondyloarthritis (SpA). SAPHO is a rare inflammatory disorder of bone, joints, and skin, with a worldwide distribution that predominantly affects the middle-age adults. The hallmark of the syndrome is a constellation of sterile inflammatory osteitis, hyperostosis, and synovitis involving the anterior chest wall, associated with acneiform and neutrophilic dermatoses, such as palmoplantar pustulosis and severe acne. The axial skeleton, sacroiliac, and peripheral joints can be involved in a similar fashion to SpA. The pathogenesis of the syndrome is multifactorial. The diagnosis is mainly based on the clinical and typical radiological features. The treatment approach is based on the off-label use of antibiotics, bisphosphonates, disease-modifying antirheumatic drugs, and anticytokine biologics. The SAPHO syndrome shares common features with SpA-related diseases, yet also shows some unique pathogenetic and clinical features. The nosology of SAPHO remains a subject of controversy, awaiting further research into the pathogenetic and clinical aspects of this syndrome. A better understanding of these aspects will improve the diagnostics and clinical care of patients with SAPHO.

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.

New Insights in the Treatment of SAPHO Syndrome and Medication Recommendations.

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by dermatological disorders and osteoarticular inflammatory lesions. This article reviews the application of biologics and other treatments based on the therapeutic target and the size of molecules in SAPHO syndrome. We found that drugs, especially biologics, have different effects on bone, joint, and skin damage. This may relate to the different inflammatory pathways involved in the osteoarticular and cutaneous symptoms in SAPHO patients. In this study, we provide stratified medication recommendations for SAPHO syndrome. Patients with osteoarticular symptoms can consider tumor necrosis factor blockers, JAK inhibitor, interleukin (IL)-1 inhibitor, and IL-17 inhibitor. Patients with cutaneous symptoms should consider IL-17 and JAK inhibitors. Apremilast, Tripterygium wilfordii Hook F, and bisphosphonates are other effective treatments.

Diagnostic challenge of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome in pediatric age: A monocentric case series

SAPHO syndrome is a rare disease that typically begins in the third-fifth decade of life, and is characterized by osteoarticular and dermatologic features [1]. The acronym summarizes the key clinical features: synovitis, acne, palmoplantar pustulosis, hyperostosis and osteitis [2]. The prevalence of this condition is estimated to be less than 1 per 10,000 people [3]. Several cases have been described in childhood, mostly in adolescents, some associated with other comorbidities. Indeed, the SAPHO clinical spectrum encompasses a wide range of different manifestations which overlap with other autoimmune or autoinflammatory disorders, thus often challenging the diagnosis, particularly in paediatric age [4–6]. If promptly recognized and adequately treated, SAPHO syndrome shows a favourable course. Herein we present a case series of 5 children affected by SAPHO syndrome, diagnosed at our Rheumatology Unit from March 2015 to June 2020, experiencing an excellent response to anti-TNFα. Five Caucasian patients (3 males) with a median age of 12 years and 5 months (range 132-192 months) received a diagnosis of SAPHO syndrome (Table 1). The median time between disease onset and diagnosis was 6 months (range 3–22 months). Patient #1 and #2 had a previous diagnosis of Inflammatory Bowel Diseases (IBD) – Crohn disease (CD) and Ulcerative colitis (UC), respectively; no other previous or concomitant relevant medical conditions were reported for the other patients.

SAPHO Syndrome: An Unusual Cause of Dysphagia.

Case PresentationThis case describes a 51-year-old male who presented to the emergency department with a complaint of two weeks of progressively worsening dysphagia as well as the emergence of superficial fluid collections on the anterior chest and leg during the same period. Computed tomography showed retropharyngeal and paratracheal fluid collections with adjacent vertebral osteitis; however, biopsies were negative for any infectious or mycobacterial source, and instead showed chronic inflammatory changes.DiscussionSynovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is a rare rheumatic disorder that presents with multifocal osteitis and sterile neutrophilia. SAPHO syndrome may be easily mistaken for a diffuse infectious process on initial evaluation and imaging; however, it is treated with anti-inflammatory medications, including non-steroidal anti-inflammatory drugs and corticosteroids. Although most patients achieve remission of symptoms with treatment, the location of the fluid collections and resultant bony destruction may be life-threatening if undiagnosed.

The Synovitis, Acne, Pustulosis, Hyperostosis, And Osteitis (SAPHO) syndrome: A two-center study of 23 patients

IntroductionThe Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) syndrome is a rare autoinflammatory disease. The clinical presentation is heterogeneous, hence the difficulty of making the diagnosis. Aim of the workTo assess clinical, laboratory parameters and radiological features, and to detail the therapeutic options of SAPHO syndrome. Patients and methodsPatients diagnosed with SAPHO syndrome were retrospectively studied from two rheumatology centres in Tunisia. The epidemiological, clinical, radiological, and therapeutic data were collected from patients’ medical records. ResultsTwenty-three patients were enrolled. The mean age was 44.7 ± 16.9 years (14–76 years). Skin involvement was found in a third of patients. Osteoarticular manifestations involved anterior chest wall damage in 56% of cases and axial skeletal lesions in 93% of patients. Ten (43%) patients had peripheral joint involvement, and one reported bone pain in the forearm. HLA-B27 was positive in a third of the patients. All patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) with variable clinical responses. Antibiotic therapy with doxycycline was prescribed in 3 cases, with no clinical improvement. Sulfasalazine was used in 4 cases after therapeutic failure of NSAIDs. Methotrexate was prescribed in 4 cases. Tumor necrosis factor (TNF) inhibitors (Etanercept) were provided for 2 with a good clinical response, and were planned for two others. Pamidronate was given to a patient with bone involvement with pain relief and clinical improvement. ConclusionPatients with SAPHO were relatively young. Skin lesions were not common. The involvement of the anterior chest wall and the axial skeleton was predominant.

Recent advances in palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic inflammatory condition where crops of sterile pustules with erythematous keratotic lesions causing bleeding and pain appear on the palms and soles. Recently, the European Rare and Severe Expert Network considered PPP as a variant of pustular psoriasis with or without psoriasis vulgaris.The prevalence of PPP varies from 0.050 to 0.12%. PPP occurs more frequently in women and the highest prevalence occurred between the ages of 50 and 69 years. Nail psoriasis seems to be frequent in PPP, ranging from 30 to 76%, and psoriatic arthritis in 8.6 to 26% of PPP patients.Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and pustulotic arthro-osteitis are considered PPP-associated disorders. PPP has been reported with other co-morbidities such as psychiatric disorders, thyroid-associated disease, altered calcium homeostasis, gluten sensitivity diabetes, obesity, and dyslipidemia, but larger studies are required to prove such associations. Environmental exacerbating factors might contribute to the onset or worsening of PPP such as cigarette smoking, stress, focal infections, metal allergies, and drug intake. Genetic predisposition plays an important role in PPP.In PPP, both the innate and the adaptive immune systems are activated. The acrosyringeal expression of IL-17 has been demonstrated, indicating that the eccrine sweat gland is an active component of the skin barrier and an immune-competent structure. Increased levels of several inflammatory molecules, including IL-8, IL-1α, IL-1β, IL-17A, IL-17C, IL-17D, IL-17F, IL-22, IL-23A, and IL-23 receptor, have been detected in PPP biopsies. Increased serum levels of TNF-α, IL-17, IL-22, and IFN-γ have been detected in patients with PPP in comparison to healthy subjects, suggesting a similar inflammatory pattern to psoriasis vulgaris. Oral and tonsillar infections serve as trigger factors for PPP.Long-term therapy is required for many patients, but high-quality data are limited, contributing to uncertainty about the ideal approach to treatment.

Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is known as a rare disease characterized by inflammatory lesions on bones and skin. Polymorphism of clinical manifestation and lack of molecular biomarkers have both limited its diagnosis. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of long noncoding RNA (lncRNA)-messenger RNA (mRNA) profile in patients with SAPHO syndrome and healthy controls. A total of 4,419 differentially expressed (DE) mRNAs and 2,713 lncRNAs were identified (p < 0.05, fold change > 2) and a coexpression network was constructed to further investigate their regulatory interactions. The DE lncRNAs were predicted to interact with mRNAs in both cis and trans manners. Functional prediction found that the lncRNA-targeted genes may function in SAPHO syndrome by participating in biological process such as adipocytokine signaling pathway, ErbB signaling pathway, FoxO signaling pathway, as well as production and function of miRNAs. The expression levels of three pairs of coexpressed lncRNA-mRNAs were validated by qRT-PCR, and their relative expression levels were consistent with the RNA-seq data. The deregulated RNAs GAS7 and lnc-CLLU1.1-1:2 may serve as potential diagnostic biomarkers, and the combined receiver operating characteristic (ROC) curve of the two showed more reliable diagnostic ability with an AUC value of 0.871 in distinguishing SAPHO patients from healthy controls. In conclusion, this study provides a first insight into long noncoding RNA transcriptome profile changes associated with SAPHO syndrome and inspiration for further investigation on clinical biomarkers and molecular regulators of this inadequately understood clinical entity.

Pharmacological Management of Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome Syndrome: A Proposal of a Treatment Algorithm.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic disease with marked clinical and radiological heterogeneity. It is characterized by a combination of dermatological and osteoarticular manifestations. The treatment of SAPHO syndrome is not yet codified. It includes several therapeutic options such as anti-inflammatory drugs, bisphosphonates, antibiotics, conventional disease-modifying antirheumatic drugs, and biological treatment.This article aims to provide an updated review of the different pharmacological options for SAPHO syndrome. We also propose a therapeutic algorithm for the management of this disease.

Chronic Nonbacterial Osteomyelitis of the Sternocostoclavicular Region in Adults: A Single-Center Dutch Cohort Study.

ABSTRACTSternocostoclavicular hyperostosis (SCCH) is a rare autoinflammatory bone disorder caused by chronic nonbacterial osteomyelitis (CNO), which is associated with sclerosis and hyperostosis primarily affecting the sternum, the medial end of the clavicles, and the first ribs. Other areas of the axial skeleton may also be affected. The more severe synovitis–acne–pustulosis–hyperostosis–osteitis (SAPHO) syndrome is additionally associated with dermatoses and joint manifestations. This Dutch retrospective cross‐sectional single‐center cohort study characterizes the spectrum of clinical features in adult CNO/SCCH patients at the time of diagnosis. The only inclusion criteria was the availability of complete sets of clinical and imaging data systematically collected over three decades using in‐house protocols. Data from 213 predominantly female patients (88%) with a median age of 36 years at presentation were studied. The mean diagnostic delay was 5 ± 5 years. The main symptoms were chronic pain (92%), bony swelling (61%), and restricted shoulder girdle function (46%); 32% had palmoplantar pustulosis and 22% had autoimmune disease. The majority (73%) had isolated SCCH; 59 (27%) had additional localizations in vertebrae (19%), the mandible (9%), or both (2%); 4 had SAPHO. The prevalence of current or past smoking was high (58%), particularly for patients with palmoplantar pustulosis (76%). There was a significant relationship between delay in diagnosis and both the extent of affected skeletal sites (p = 0.036) and erythrocyte sedimentation rate levels (p = 0.023). Adult‐onset CNO is characterized by distinctive clinical and radiological features, but diverse aspects of its spectrum are currently not fully captured by a comprehensive classification. Delayed diagnosis is still common and potentially associated with irreversible structural changes and debilitating chronic symptoms, increasing the burden of illness and negatively impacting on quality of life. It is hoped that findings from this study will dispel confusion about nomenclature and classification of adult‐onset CNO and increase awareness of its distinctive clinical and radiological features, and thus facilitate early diagnosis and referral for treatment, which should positively impact prognosis by preventing disease progression, although this remains to be established. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.