Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis Syndrome Research Articles

SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis); A Case of Backache in an Adolescent in Pakistan

SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) syndrome is a group of rare auto-inflammatory disorders with a wide range of dermatological and osteoarticular manifestations. Different nomenclatures, like Chronic Recurrent Multifocal Osteoarthritis (CRMO) and Chronic Non-Bacterial Osteomyelitis (CNO), have been used in the past for the same disease, but SAPHO Syndrome has been the accepted terminology since 1990. An adolescent, 17 years of age, with a six-month history of inflammatory backache and fatigue, reported to a rheumatology clinic. His health assessment questionnaire- disability indexcame out to be two. Acne on physical examination raised inflammatory markers, and characteristic findings of SAPHO syndrome on bone scan suggest the disease. The patient was treated with an excellent response to bisphosphonates. The report highlights the importance of the evaluation of inflammatory backache in adolescents. SAPHO syndrome is an underdiagnosed disease. Therefore, more awareness of this disease among healthcare physicians is required.

Colitis induced by IL-17A-inhibitors

BackgroundInterleukin (IL)-17A is essential for intestinal mucosal integrity, contributing to the prevention of detrimental immunity such as infectious colitis and inflammatory bowel disease (IBD). Indeed, neutralization of IL-17A has been abandoned as a therapeutic principle in IBD because of increased disease activity. However, it is controversial whether IL-17A inhibitors increase the risk of developing colitis in patients who do not have underlying IBD. Here, we present two cases of different forms of colitis that occurred during treatment with two IL-17A inhibitors, secukinumab and ixekizumab.Case presentationsWe report the case of a 35-year-old female with SAPHO (synovitis–acne–pustulosis–hyperostosis–osteitis) syndrome who was admitted due to severe colitis with bloody diarrhea, fever, abdominal pain and weight loss after receiving secukinumab for 3 months as well as the case of a 41-year-old male with psoriatic arthritis who presented himself to the outpatient clinic with bloody stools, abdominal pain and nausea 5 months after changing his therapy from secukinumab to ixekizumab. In both patients, treatment with IL-17A-inhibitors was stopped and tumor necrosis factor inhibitors were started. Both patients recovered, are clinically stable and show no more signs of active colitis.ConclusionThe role of IL-17A inhibitors in the pathogenesis of infectious colitis and new-onset IBD is not fully understood and requires further research. Patients receiving IL-17A-inhibitor therapy should be carefully screened and notified of the possible side effects.

SAPHO Syndrome in Crohn’s Disease Successfully Treated with Ustekinumab: Case Report and Review of the Literature

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

SAPHO Syndrome in Crohn’s Disease Successfully Treated with Ustekinumab: Case Report and Review of the Literature

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

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.

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.

Bull’s head sign in the scintigraphy of a young female with recurrent chest pain

In this case we report a 38-year-old female patient with history of recurrent retrosternal chest pain lasting almost 5 years. Standard X-rays of chest and spine revealed no abnormalities. In a physical examination tenderness of anterior chest wall was observed, especially in sternoclavicular areas. SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome was taken into consideration despite of lack of typical skin lesions (acne, pustulosis). We decided to implement 99mTc scintigraphy. Increased osteoblastic activity (intense 99-technetium intake) in manubriosternal and both sternoclavicular regions represents bull’s head sign which is a rare finding, but pathognomonic to SAPHO syndrome. After a 3-month therapy with aceclofenac 100 mg, total remission was reached. If we rule out this rare condition like SAPHO based on lack of abnormalities in X-rays, the reason of symptoms could be still unrecognized. 99mTc scintigraphy is valuable to show even subclinical areas of involvement and to monitor treatment response in 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.

Cranial osteomyelitis associated with SAPHO syndrome: An underdiagnosed cause of chronic headache

AbstractA 50‐year‐old woman having palmoplantar pustulosis was admitted with a headache accompanied by occipital bulge. She had a history of cryptogenic cervical spondylitis which had not completely remitted despite treatment with nonsteroidal anti‐inflammatory drugs. Head magnetic resonance imaging revealed enhanced swelling in the soft tissues of the right occipital region corresponding to the bulging locus. Bone scintigraphy demonstrated increased uptake in the parieto‐occipital bone, cervical spine, and sternoclavicular joints. Considering the negative results of the culture tests, she was diagnosed with aseptic cranial osteomyelitis induced by synovitis‐acne‐pustulosis‐hyperostosis‐osteitis (SAPHO) syndrome; cervical osteitis might induce her unidentified spondylitis. This syndrome is unrecognized as a cause of secondary headache. Based on our review of previous reports and the current case, we suggest that a painful bulge, which is demonstrated as an enhanced swelling in the cephalic soft tissue, may be a diagnostic cue for SAPHO syndrome.

Pulmonary Vasculitis on Dual-Phase 18F-FDG PET/CT in SAPHO Syndrome.

Pulmonary vasculitis is an uncommon type of vasculitis that may cause pulmonary artery stenosis with ensuing ischemic damage to lung tissue. 99mTc-macroaggregated albumin scintigraphy and iodine lung perfusion mapping are useful imaging modalities for assessment of lung perfusion but are not useful for assessing disease activity. On the other hand, 18F-FDG PET/CT is widely used for assessment of vasculitis activity but cannot provide perfusion information. We reported the clinical utility of dual-phase 18F-FDG PET/CT for pulmonary vasculitis in patients with SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome.

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.

Otras espondiloartritis

Spondyloarthritis (SpA) conditions include axial and peripheral SpA. However, there are others such as reactive arthritis (ReA), arthritis conditions linked to inflammatory bowel disease (IBD) or synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome; these are common in rheumatology consultations, although less frequent than cases of ankylosing spondylitis (AS) or psoriatic arthritis (PsA). These conditions can present with either axial or peripheral signs and symptoms, and with extra-articular such as, ophthalmological or cutaneous manifestations. The most frequent form of ReA presentation is oligoarthritis of the lower limbs, with axial involvement being more infrequent. In IBD-associated arthropathy, symptoms can appear at any level. Axial symptoms predominate in SAPHO syndrome. Diagnosis is principally based on the symptoms and radiological findings, without any unanimous diagnostic criteria. For joint symptoms, the first line of treatment is non-steroidal anti-inflammatory drugs, although with restrictions in the case of IBD-associated arthropathy, with the use of systemic or local corticoids also being possible (systemic corticoids should not be used if there is axial involvement). If the first line of treatment is not successful, the treatment indicated is disease-modifying drugs such as sulfasalazine and, if necessary, biological drugs (especially anti-tumour necrosis factor —TNF— therapy); these have been used in these pathologies with varied responses.

Carotid Ulceration in a Young Woman with SAPHO Syndrome

A 25 year old woman was recently diagnosed with SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome. On magnetic resonance imaging, performed for chronic left sternoclavicular pain, incidental left common carotid artery (CCA) occlusion was diagnosed. During further diagnostic work up, duplex ultrasound also revealed newly appeared but asymptomatic intima-media ulceration of the contralateral CCA, (A, arrow), confirmed by computed tomography (B, right CCA ulceration, arrow; left CCA occlusion, asterisk). Characteristic arterial involvement associated with recurrent oral ulceration and skin lesions indicated Behçet's disease. Treatment included steroids, methotrexate, and infliximab. Duplex ultrasound after two weeks revealed healing of the ulcerated right CCA, with intimal regeneration clearly noted.Image 1

Genetic variants in FBLIM1 gene do not contribute to SAPHO syndrome and chronic recurrent multifocal osteomyelitis in typical patient groups

BackgroundSyndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) and chronic recurrent multifocal osteomyelitis (CRMO) present two diseases of a dermatologic and rheumatologic spectrum that are variable in manifestation und therapeutic response. Genetic risk factors have long been assumed in both diseases, but no single reliable factor has been identified yet. Therefore, we aimed to clinically characterize a patient group with syndrome of synovitis acne pustulosis hyperostosis osteitis (SAPHO) (n = 47) and chronic recurrent multifocal osteomyelitis (CRMO)/ chronic non-bacterial osteomyelitis (CNO) (n = 9) and analyze a CRMO candidate gene.MethodsClinical data of all patients were collected and assessed for different combinations of clinical symptoms. SAPHO patients were grouped into categories according to the acronym; disease-contribution by pathogens was evaluated. We sequenced coding exons of FBLIM1.ResultsPalmoplantar pustular psoriasis (PPP) was the most common skin manifestation in CRMO/CNO and SAPHO patients; most SAPHO patients had sterno-costo-clavicular hyperostosis. The most common clinical category of the acronym was S_PHO (n = 26). Lack of pathogen detection from bone biopsies was more common than microbial isolation. We did not identify autosomal-recessive FBLIM1 variants.ConclusionsS_PHO is the most common combination of symptoms of its acronym. Genetic analyses of FBLIM1 did not provide evidence that this gene is relevant in our patient group. Our study indicates the need to elucidate SAPHO’s and CRMO/CNO’s pathogenesis.

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Copy Number Variation of Multiple Genes in SAPHO Syndrome.

SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome is a type of rare chronic aseptic inflammation of unknown etiology. To date, no research to our knowledge has reported copy number variation (CNV) of genes that could affect predisposition to SAPHO syndrome. We investigated the association between CNV profile and SAPHO syndrome. We used array comparative genomic hybridization (CGH) to screen for CNV in a nuclear family including 2 patients and a healthy control. We then validated the copy numbers of candidate genes found in the array CGH assay and other candidate genes by TaqMan real-time PCR in 360 case and control samples. Ten regions from 8 chromosomes were found to have abnormal gene copies in the nuclear family, so the CNV of candidate genes (ADAM5, CSF2RA, IL3RA, and 9 other genes) were tested by TaqMan PCR. Significant copy number loss of CSF2RA (p = 0.000) and NOD2 (p = 0.005), and significant copy number gain of MEGF6 (p = 0.002) and ADAM5 (p = 0.000) were seen in patients with SAPHO compared with controls at the a = 0.05 level. There were no differences in the other 8 candidate genes between patient and control samples (p > 0.05). Our study established the first association between CNV in CSF2RA, NOD2, MEGF6, and ADAM5 and SAPHO syndrome. These findings may offer insight into the pathogenesis of SAPHO and provide the basis for improved diagnosis and treatment.

Clinical Characteristics of Japanese Patients with Palmoplantar Pustulosis.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles. The purpose of this review was to describe the characteristics of Japanese PPP patients as PPP is frequently observed within the Japanese population. Most Japanese dermatologists consider PPP a distinct entity, and co-existence of PPP and psoriasis is rare; however, outside Japan, PPP is often considered to be palmoplantar psoriasis, and an extra-palmoplantar lesion associated with PPP is considered to be psoriasis. PPP frequently develops or exacerbates following focal infections such as tonsillitis, odontogenic infection, and sinusitis, either with or without arthralgia. Pustulotic arthro-osteitis (PAO) is a major comorbidity of PPP, most often affecting the anterior chest wall. In Japanese patients, PAO is frequently seen, whereas cases of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome with symptoms other than PPP and sternocostoclavicular joint pain are extremely rare. A difference in incidence depending on race suggests that different genetic backgrounds may be responsible for susceptibility to these disorders. The treatment of focal infections often results in dramatic effects on cutaneous lesions, as well as joint pain. The characteristics of Japanese patients with PPP are female predominance, mostly smokers, rare co-existence with psoriasis, frequent association with PAO, almost no accompanying celiac disease, and closely associated with focal infection. PPP should be separately considered from palmoplantar psoriasis.

A Case of Pyoderma Gangrenosum as Skin Manifestation of SAPHO Syndrome in an IBD Patient

A 39 year old Caucasian male with a history of rectosigmoid ulcerative colitis (UC) was transferred to our hospital with joint pain, skin lesions, and fevers. He was initially diagnosed with UC in 2015 after experiencing hematochezia, abdominal pain and weight loss. He was started on budesonide and oral mesalamines. Given his refractory symptoms, he was started on adalimumab. However he developed rapid formation of high antibody levels, so he was transitioned to vedolizumab and azathioprine a year later. Until the time of presentation, he reported good control of his symptoms. He presented to the outside hospital in June 2018 with chest and back pain. In addition, he reported painful skin “pimples” throughout his chest, back and axilla which began to express pus. I&D's were performed of multiple lesions with purulent drainage; however they increased in size after incision. MRI showed findings concerning for osteomyelitis involving T4-6 and L2 vertebral bodies. He was placed on broad spectrum antibiotics, and his azathioprine was held. Despite antibiotic therapy, he developed fevers and was transferred to our hospital. Upon arrival, physical examination revealed multiple crusted, erythematous 1 cm pustules on his sternum (Fig. 1) and back. There was also a 6x3 cm ulcerated plaque on his left buttock with fibrinous necrotic material surrounded by an indurated rim of gray tissue (Fig. 2). In addition, there was a large ulcerated wound with necrotic center with surrounding violaceous erythema in his right axilla. A shave biopsy of his left buttock revealed a dense neutrophilic infiltrate throughout the dermis. Upon further review of imaging, osteomyelitis was ruled out but there was concern for osteitis (Fig. 3). Based on the clinical and histopathological findings, the diagnosis of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome was made in addition to pyoderma gangrenosum (PG). Antibiotics were discontinued, and he was started on IV steroids with resolution of his fever and improvement in his skin lesions.2055_A Figure 1. Subcutaneous 1 cm pustule with surrounding inflammation and central incision from prior I&D2055_B Figure 2. 6x3 cm ulcerated plaque on his left buttock with fibrinous necrotic material surrounded by an indurated rim of gray tissue with erythema2055_C Figure 3. Pattern of marrow edema and enhancement in T4-T6 and L2, without disc or epidural enhancement, consistent with osteitis.SAPHO syndrome is a rare disease, with an estimated prevalence of 1:10,000 in the Caucasian population. There are only a few cases of PG presenting as a skin manifestation of SAPHO syndrome. This is a rare case highlighting the association between SAPHO syndrome and PG in a patient with well-controlled IBD. Further investigation is warranted regarding the overlap of these conditions and its correlation with IBD.

Swellings of the sternoclavicular joint: review of traumatic and non-traumatic pathologies.

The sternoclavicular joint (SCJ) is an integral part of the shoulder girdle that connects the upper limb to the axial skeleton.Swelling of the SCJ is commonly due to trauma, degeneration, infections and other disease processes that affect synovial joints.This review also focuses on uncommon conditions that could affect the SCJ, including SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, Friedrich’s disease and Tietze syndrome.The scope of this review is limited to the analysis of the current evidence on the various conditions affecting the SCJ and also to provide an algorithm to manage these conditions.Cite this article: EFORT Open Rev 2018;3:471-484. DOI: 10.1302/2058-5241.3.170078

A case of bronchiolitis obliterans organising pneumonia associated with SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome

A 57-year-old woman with SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome presented with recurrent episodes of pneumonia. She was treated with multiple courses of antibiotics with no success. The transbronchial biopsy undertaken via bronchoscopy...