Tripterine ameliorates monosodium urate crystal-induced gouty arthritis by altering macrophage polarization via the miR-449a/NLRP3 axis.

OBJECTIVE: Tripterine (Trip) is frequently applied to alleviate inflammation in various diseases such as rheumatoid arthritis. Macrophages have both anti-inflammatory and pro-inflammatory functions. However, whether Trip can inhibit cell inflammation in gouty arthritis (GA) remains undiscovered and whether the mechanism involved in macrophage polarization is also undetermined. This paper aims to study the effects of Trip on inflammation and macrophage polarization in GA. METHODS: Monosodium urate (MSU) crystals were used to establish GA mouse models, and bone marrow-derived macrophages (BMDMs) were induced to construct GA cell models. Pretreatments of Trip and injection of Antagomir-449a/Agomir-449a were performed on mice for 6 days. The effects of Trip and miR-449 on toe swelling, joint damage of GA mouse were examined. The alternations on cell morphology, cell proliferation marker Ki67, inflammatory cytokines, NLRP3 inflammasome, and NF-κB signaling-related proteins were also determined both in vivo and in vitro. Dual-luciferase reporter gene assay and RIP assay were adopted to estimate the targeting relationship between miR-449a and NLRP3. RESULTS: GA mouse model had increased M1 macrophage, intensified inflammation response, along with suppressed miR-449a expression. Following administration of Trip attenuated cell inflammation, promoted macrophage polarize to M2 phenotype, elevated miR-449a expression, repressed the phosphorylation levels of NF-κB signaling-related proteins, and diminished IκBα expression in vivo and in vitro. However, inhibition of miR-449a hindered the favorable effect of Trip on GA and increased NLRP3 inflammasome expression. MiR-449a directly targeted NLRP3. Overexpression of NLRP3 partially eliminated the biological effects of miR-449a agonist. CONCLUSION: Trip regulates macrophage polarization through miR-449a/NLRP3 axis and the STAT3/NF-κB pathway to mitigate GA. The elucidation on the molecular mechanism of Trip in GA may provide theoretical guidance for clinical therapy of GA.

Treatment of Dactylitis and Enthesitis in Psoriatic Arthritis with Biologic Agents: A Systematic Review and Metaanalysis.

OBJECTIVE: Biologic agents with different mechanisms of action [inhibitors of tumor necrosis factor-α (TNF-α), interleukin (IL)-12/23, and IL-17] showed efficacy in randomized controlled trials (RCT) in the treatment of psoriatic arthritis. We conducted a pooled metaanalysis of these agents for treatment of dactylitis and enthesitis and compared results with the American College of Rheumatology 20 (ACR20) response and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. METHODS: A systematic literature search was performed and a pooled metaanalysis of RCT with anti-TNF-α (infliximab, golimumab, adalimumab), anti-IL-12/23 (ustekinumab), and anti-IL-17 (secu kinumab, ixekizumab) was conducted using the random-effects model. Bias was assessed using the Cochrane risk-of-bias tool. RESULTS: Eighteen RCT were included in the pooled analysis (n = 6981). Both TNF-α inhibitors and novel biologics (ustekinumab, secukinumab, ixekizumab) demonstrated significant resolution of dactylitis at Week 24 with pooled risk ratios (RR) versus placebo of 2.57 (95% CI 1.36-4.84) and 1.88 (95% CI 1.33-2.65), respectively. For resolution of enthesitis at Week 24, RR for TNF-α inhibitors was 1.93 (95% CI 1.33-2.79) versus 1.95 (95% CI 1.60-2.38) for novel biologics. Both biologic categories showed overlapping ranges of ACR20 responses (TNF-α inhibitors: RR = 2.23, 95% CI 1.60-3.11; pooled IL-12/23 and -17: RR = 2.30, 95% CI 1.94-2.72) and similar quality of life improvement scores with mean HAQ-DI score changes of -0.29 (95% CI -0.39 to -0.19) and -0.26 (95% CI -0.31 to -0.22), respectively. CONCLUSION: The pooled analysis demonstrated that anti-TNF-α agents have the same efficacy as novel agents (ustekinumab, secukinumab, and ixekizumab) in dactylitis and enthesitis.

Psoriatic Nail Dystrophy Is Associated with Erosive Disease in the Distal Interphalangeal Joints in Psoriatic Arthritis: A Retrospective Cohort Study.

OBJECTIVE: To assess whether the association between psoriatic nail dystrophy and radiographic damage in the hands of patients with psoriatic arthritis (PsA) is specific to the distal interphalangeal (DIP) joints. METHODS: A convenience sample of patients was collated from the Bath longitudinal PsA cohort. All patients had PsA according to the ClASsification for Psoriatic ARthritis criteria (CASPAR) criteria, scored radiographs of their hands, and documented nail scores as measured by the Psoriatic Nail Severity Score. Chi-square tests were performed to examine for association between features of nail dystrophy and radiographic damage in the DIP joints, and proximal interphalangeal or metacarpophalangeal (non-DIP) joints of the corresponding digits. RESULTS: There were 134 patients included, with a median age of 53 years (interquartile range; IQR 44-61) and disease duration of 7 years (IQR 3-17). The presence of any form of psoriatic nail dystrophy was associated with erosion at the DIP joints of the corresponding digit (OR 1.9, 95% CI 1.23-2.83; p < 0.004) and this association was primarily driven by the presence of nail onycholysis (OR 1.72; 95% CI 1.12-2.62; p = 0.02). Nail subungual hyperkeratosis was more strongly associated with joint space narrowing, erosions, and osteoproliferation at the corresponding DIP joint compared to non-DIP joints (p < 0.001). Nail pitting was not associated with erosions or osteoproliferation. CONCLUSION: The presence of psoriatic nail dystrophy, particularly onycholysis, is associated with erosive disease at the DIP joints. Subungual hyperkeratosis is more strongly associated with erosive damage at the DIP than non-DIP joints. These findings support the anatomical and pathological link between nail and DIP joint disease.

Bone change after surgical treatment of mucous cyst at the interphalangeal joint of the great toe in a patient with rheumatoid arthritis.

Digital mucous cysts are a type of benign cysts of the digits, typically located at the distal interphalangeal joints or in the proximal nail fold, which usually occur on the hands. The diagnosis of digital mucous cysts is relatively easy because of its light-transmitting property, but the treatment is often difficult because of complications including recurrence, infection, diminished range of motion, and nail deformity. We report a case of rheumatoid arthritis (RA) showing good course after surgical treatment of mucous cyst at the interphalangeal joint of the great toe. In a case of RA, combination of synovectomy with surgical treatment of mucous cyst might be effective.

Enthesitis and Dactylitis in Psoriatic Disease: A Guide for Dermatologists.

Psoriatic arthritis (PsA) is an inflammatory arthritis that is estimated to affect approximately 30% of patients with psoriasis. Enthesitis and dactylitis, two hallmarks of PsA, are associated with radiographic peripheral/axial joint damage and severe disease. Clinical symptoms of enthesitis include tenderness, soreness, and pain at entheses on palpation, whereas dactylitis is recognized by swelling of an entire digit that is different from adjacent digits. Both ultrasound and magnetic resonance imaging can be used to diagnose enthesitis and dactylitis, especially in patients in whom symptoms may be difficult to discern. Delayed treatment of PsA can result in irreversible joint damage and reduced quality of life. Thus, it is recommended that dermatologists monitor patients with psoriasis for these two early and important manifestations of PsA.

A Novel Method of Synovitis Stratification in Ultrasound Using Machine Learning Algorithms: Results From Clinical Validation of the MEDUSA Project.

Ultrasound is widely used in the diagnosis and follow-up of chronic arthritis. We present an evaluation of a novel automatic ultrasound diagnostic tool based on image recognition technology. Methods used in developing the algorithm are described elsewhere. For the purpose of evaluation, we collected 140 ultrasound images of metacarpophalangeal and proximal interphalangeal joints from patients with chronic arthritis. They were classified, according to hypertrophy size, into four stages (0-3) by three independent human observers and the algorithm. An agreement ratio was calculated between all observers and the standard derived from results of human staging using κ statistics. Results was significant in all pairs, with the highest p value of 3.9 × 10-6. κ coefficients were lower in algorithm/human pairs than between human assessors. The algorithm is effective in staging synovitis hypertrophy. It is, however, not mature enough to use in a daily practice because of limited accuracy and lack of color Doppler recognition. These limitations will be addressed in the future.

Evidencia científica del tratamiento ortopodológico en pie afectado por artritis reumatoide / Evidence of orthopodiatric treatment affected by rheumatoid arthritis on foot

Antecedentes: La artritis reumatoide afecta más a mujeres. La prevalencia en nuestro país es de 0.5%. Se debe abordar mediante un equipo multidisciplinar. Los signos característicos en el pie son sinovitis de las articulaciones, entesitis, nódulos reumatoides y vasculitis. Las modalidades de tratamiento conservador son: ortesis, calzado, estiramientos, terapia manual e incluso ejercicios terapéuticos mediante Tai-chi. Objetivos: Valorar la evidencia científica sobre el tratamiento conservador del pie reumático mediante ortesis plantares y calzado terapéutico. Conocer los últimos avances y que opción es la más indicada para tratar esta patología que afecta al pie. Material y métodos: Se ha realizado una revisión bibliográfica de los últimos 15 años en Pubmed. Resultados: Se ha encontrado relación entre el dolor de antepié, subluxación metatarsofalángica y erosión del cartílago articular con el aumento de presión a nivel metatarsal plantar lo que justifica la realización de tratamiento ortopodológico encaminado a reducir la misma. El tratamiento conservador está enfocado a la utilización de ortesis y de zapato terapéutico para mejorar el dolor, la marcha y la funcionalidad. Hay evidencia científica para tratar la metatarsalgia con diferentes tipos de ortesis, que no solo ayudan a mejorar el dolor sino que además reducen el nº de articulaciones inflamadas. La combinación con zapato terapéutico con o sin modificaciones externas produce mejores resultados. Conclusión: Existe escasa evidencia científica sobre el uso de tratamiento ortopodológico para el pie reumático pero se han encontrado algunos artículos que avalan su eficacia, por lo que es imprescindible realizar estudios en este campo (AU)

Background: Rheumatoid arthritis affects more women. The prevalence in our country is 0.5%. It should be approached by a multidisciplinary team. Characteristic foot signs' are synovitis of joints, enthesitis, rheumatoid nodules and vasculitis. The conservative treatment modalities are: orthotics, footwear, stretching, manual therapy and therapeutic exercises even by Tai-chi. Objectives: To evaluate the scientific evidence on the conservative treatment of rheumatoid foot with orthotics and therapeutic footwear. Aware of progress and that is the most suitable option for treating this disease that affects the feet. Material and methods: We carried out a literature review of the past 15 years in Pubmed. Results: We found the relationship between pain forefoot metatarsophalangeal subluxation and erosion of articular cartilage with increasing pressure to plantar metatarsal level which justifies conducting orthosis treatment aimed at reducing it. Conservative treatment is aimed at the use of orthoses and shoe therapy to improve pain, gait and functionality. There is scientific evidence for treating metatarsalgia with different types of orthotics that not only help improve the pain but also reduce the number of swollen joints. The combination with therapeutic shoe with or without external changes produces better results. Conclusion: There is little scientific evidence on the use of orthosis treatment for rheumatoid foot but found some articles that support its effectiveness, so it is essential to carry out studies in this field (AU)

The impact of transferred vascularized toe joint length on motion arc of reconstructed finger proximal interphalangeal joints: a cadaveric study.

Vascularized toe joint transfer for finger proximal interphalangeal joint reconstruction can result in sub-optimal arc of motion and extension lag due to inappropriate intercalated bony segment length. We investigated the impact of intercalated segment length on passive arc of motion and extension lag of the reconstructed proximal interphalangeal joint. Cadaveric intercalated joint grafts were harvested from lesser toes and transferred to cadaveric fingers. The pre-determined finger proximal interphalangeal joint defect size was 2 cm. Three different intercalated segment lengths were inserted and resulting proximal interphalangeal joint arc of motion and extension lag were measured. The average arc of motion of finger proximal interphalangeal joints was 81° and 54° for toe proximal interphalangeal joints. Long intercalated segments had an average arc of motion of 30° with 32° extension lag. Equal-length intercalated segments had an average 49° arc of motion with 15° extension lag. Short intercalated segments had an average arc of motion of 71° with 8° extension lag. Shorter intercalated segments provide the greatest reduction in extension lag.

Proximal interphalangeal joint ankylosis in an early medieval horse from Wroclaw Cathedral Island, Poland.

Animal remains that are unearthed during archaeological excavations often provide useful information about socio-cultural context, including human habits, beliefs, and ancestral relationships. In this report, we present pathologically altered equine first and second phalanges from an 11th century specimen that was excavated at Wroclaw Cathedral Island, Poland. The results of gross examination, radiography, and computed tomography, indicate osteoarthritis of the proximal interphalangeal joint, with partial ankylosis. Based on comparison with living modern horses undergoing lameness examination, as well as with recent literature, we conclude that the horse likely was lame for at least several months prior to death. The ability of this horse to work probably was reduced, but the degree of compromise during life cannot be stated precisely. Present day medical knowledge indicates that there was little likelihood of successful treatment for this condition during the middle ages. However, modern horses with similar pathology can function reasonably well with appropriate treatment and management, particularly following joint ankylosis. Thus, we approach the cultural question of why such an individual would have been maintained with limitations, for a probably-significant period of time.

Underlying Adenocarcinoma of the Lung Metastasizing to the Proximal Phalanx of the Foot Causing Complex Regional Pain SyndromeA Case Report.

We report an unusual case of adenocarcinoma of the lung metastasizing to the proximal phalanx of the third digit in a 56-year-old woman with overlying complex regional pain syndrome. The patient was initially treated for neuroma, fracture, and neuropathic pain with no improvement over a 4-month period before presenting to the emergency department for left third digit pain. Radiographic imaging showed substantial osteopenia and mottling; magnetic resonance imaging demonstrated an aggressive lesion to the proximal phalanx. The patient underwent excision of the lesion, revealing metastatic moderately differentiated adenocarcinoma.

Dactylitis in enteropathic spondyloarthritis.

OBJECTIVES: Dactylitis has long been recognised as one of the significant features of spondyloarthropathies. In the literature, the prevalence of dactylitis in enteropathic spondyloarthritis (EASpA) ranges between 2% and 4%. The aim of this study was to identify the prevalence of dactylitis in EASpA patients and to investigate its association with clinical subset and with articular and bowel disease activity. METHODS: 78 EASpA patients and 78 controls were enrolled for this study. All patients and controls underwent a rheumatological and a gastroenterological clinical examination. Demographic and clinical features were recorded. Diagnosis of dactylitis was made by physical examination and was evaluated using the Leeds Dactylitis Instrument (LDI). RESULTS: In our study the prevalence of dactylitis in EASpA was 15.38%, mainly in patients with Crohn's disease (CD) and peripheral arthritis. A significantly higher articular and bowel disease activity was found in patients with dactylitis compared to those without it. The family history of psoriasis represented a predictor of occurrence of dactylitis. Finally, a significant correlation between disease activity and LDI score was found in EASpA. CONCLUSIONS: The results of our study showed a high prevalence of dactylitis in EASpA. It was more frequent in patients with CD and peripheral involvement with a higher articular disease activity, confirming that dactylitis may be a severity marker and a prognostic factor for EASpA. The significant correlation between disease activity and LDI score could address LDI as a potential tool of assessment of dactylitis.

Vascularized transfer of two coherent toe joints in simultaneously reconstructing MCP and PIP of a mutilated finger.

BACKGROUND: The reconstruction of metacarpal- and interphalangeal joints after severe hand injuries has been proven to be challenging. Commonly used procedures like arthrodesis, amputation or ray resection of the finger compromise the functionality of the injured finger. Especially for young patients, the restoration of all functions of the fingers is a priority. Local tissue transfers for finger joint reconstructions is not an option due to inacceptable donor site morbidity; microsurgical tissue transfers in terms of free toe joint transfers have proven to be a valuable method. METHODS: We present the case of a patient who suffered an excessive injury from a circular saw to his dominant hand. The MCP Joints of D2-D4 were fully destroyed, along with the PIP joint of a subtotally amputated D4. Arteries, nerves and tendons could be coapted directly, while primarily reconstructing of the finger joints was impossible. To ensure a possible regain of full functionality, two coherent joints, the MTP and the PIP of one toe, were transferred to the ring finger as a single transplant, reconstructing the MCP and the PIP joints of the injured finger in a one step procedure. Additionally the MCP joint of the D2 was reconstructed by the use of a free PIP-joint transfer, further the MCP joint of the D3 was replaced by an MCP endoprosthesis. RESULTS: After a follow up of 3 years the patient displayed full function of his dominant hand including sensitivity, and has gone back to manual work without limitations. The result was cosmetically acceptable and the donor site defect was easily being tolerated by the patient who is playing soccer in the regional soccer league. CONCLUSION: Free double toe joint transfer has been proven feasible in this patient. While transferring a single toe joint to reconstruct a finger joint is a well-established method, our review of the latest literature showed no case of a free transfer of two coherent joints and three transplanted joints in one hand. The applied microsurgical technique should be considered by microsurgically trained hand surgeons for the treatment of comparable severe hand injuries. In comparison to the most common procedures described for the repair and reconstruction of severely injured finger joints this method showed superior results.

Relationship between pedographic analysis and the Manchester scale in hallux valgus.

OBJECTIVE: The aim of this study was to evaluate the correlation between the Manchester scale and foot pressure distribution in patients with hallux valgus deformity. METHODS: The study included 152 feet of 87 patients with hallux valgus and a control group of 391 feet of 241 individuals without hallux valgus deformity. The severity of hallux valgus was determined using the Manchester scale grading system. Plantar loading patterns in 10 foot areas were determined for all participants. RESULTS: According to the Manchester scale, 72% of the participants had no, 12.9% mild, 10.7% moderate and 4.4% severe deformity. The Manchester scale grade was highly correlated with both hallux valgus angle and first intermetatarsal angle (p=0.00). Significant differences between the four grades were present for mean pressure under the hallux and the first and second metatarsal heads only (p=0.00). The load distribution under these areas was higher as the hallux valgus progressed from mild to more severe. In all groups, the highest pressure was observed under the second metatarsal head. CONCLUSION: The Manchester scale was strongly associated with both the hallux valgus angle and the first intermetatarsal angle. The progression from mild to moderate and severe deformation is associated with peak pressure raise at the hallux, first and second metatarsal heads. The Manchester scale appears to be a useful tool to provide information for the degree of deformity and the pressure under painful foot areas.

Enthesitis as a component of dactylitis in psoriatic juvenile idiopathic arthritis: histology of an established clinical entity.

CONTEXT: Imaging of dactylitis in adult psoriatic arthritis suggests a pathophysiological role for enthesitis. However, histological definition of the dactylitic digit is unavailable. OBJECTIVE: We evaluated the role of enthesitis in dactylitis associated with psoriatic juvenile idiopathic arthritis (psJIA) in a child who underwent detailed imaging and histologic evaluation. DESIGN: Radiographs, ultrasound and high-resolution magnetic resonance imaging were employed to define the locus of disease in two dactylitic digits from a 14-year-old girl with psJIA. Biopsies were stained with hematoxylin and eosin, CD3, CD20, CD4, CD8 and CD117 and examined via light microscopy. RESULTS: Radiologic features of dactylitis included enhanced signal at digital entheses without accompanying synovitis or tenosynovitis. Histologically, finger and toe tissue exhibited hypervascular tenosynovium with a fibromyxoid expansion of fibrous tissue. This was accompanied by sparse to moderate perivascular lymphocytic inflammation consisting predominantly of T cells, with occasional admixed B cells and mast cells. Neutrophils and plasma cells were absent. Fibrocartilage exhibited reactive features including increased extracellular myxoid matrix, binucleation, and focal necrosis, without cellular inflammation. Fibrinous synovitis and mild reactive synoviocyte hyperplasia were seen. CONCLUSIONS: Dactylitis in psJIA bears a radiographic resemblance to the condition in adult psoriatic arthritis. Histologic hallmarks include an expanded mast cell-populated extracellular myxoid matrix, cartilage degeneration, and a T cell-rich perivascular inflammatory infiltrate. These findings help to define enthesitis as a clinicopathologic entity.

High-resolution MRI assessment of dactylitis in psoriatic arthritis shows flexor tendon pulley and sheath-related enthesitis.

OBJECTIVE: Dactylitis is a hallmark of psoriatic arthritis (PsA) where flexor tenosynovitis is common. This study explored the microanatomical basis of dactylitis using high-resolution MRI (hrMRI) to visualise the small entheses around the digits. METHODS: Twelve patients with psoriatic dactylitis (4 fingers, 8 toes), and 10 healthy volunteers (6 fingers, 4 toes) had hrMRI of the digits using a 'microscopy' coil and contrast enhancement. All structures were evaluated including the tendons and ligaments, related enthesis organs, pulleys, volar/plantar plates and tendon sheaths. RESULTS: In dactylitis, collateral ligament enthesitis was seen in nine digits (75%), extensor tendon enthesitis in six digits (50%), functional enthesitis (5 digits, 42%), abnormal enhancement at the volar plates (2/5 joints, 40%) and the plantar plate (1/5 joints, 20%). Nine cases (75%) demonstrated flexor tenosynovitis, with flexor tendon pulley/flexor sheath microenthesopathy observed in 50% of all cases. Less abnormalities which were milder was observed in the normal controls, none of whom had any signal changes in the tendon pulleys or fibrous sheaths. CONCLUSIONS: This study provides proof of concept for a link between dactylitis and 'digital polyenthesitis' including disease of the miniature enthesis pulleys of the flexor tendons, further affirming the concept of enthesitis in PsA.

Comparison between palpation and ultrasonography for evaluation of experimentally induced effusion in the distal interphalangeal joint of horses.

OBJECTIVE: To ultrasonographically quantify experimentally induced effusion of the distal interphalangeal (DIP) joint of horses and compare results with those obtained with palpation. SAMPLE: 8 forelimbs from equine cadavers and forelimbs of 5 mares. PROCEDURES: Preliminary ex vivo experiments were performed to validate the methods. Then, the DIP joints of the forelimbs of standing horses were serially distended with saline (0.9% NaCl) solution (1, 4, and 10 mL) by injection through an intra-articular catheter. Two ultrasonographers measured distension of the dorsal recess of the DIP joint, and 2 surgeons, who were not aware of the volume injected, graded joint effusion by palpation. RESULTS: Intraobserver and interobserver repeatability was excellent for ultrasonographic measurements. Interobserver agreement for use of palpation to detect joint distension was moderate (κ = 0.45). There was an overall increase in the palpation distension grade with an increase in injected volume. Sensitivity for detection with palpation of larger volumes (4 and 10 mL) was high (92% and 100%, respectively). However, sensitivity was lower (57%) for detection with palpation of minimal distension (1 mL). CONCLUSIONS AND CLINICAL RELEVANCE: Although palpation provided a reliable clinical assessment of DIP joint effusion for volumes of 4 to 10 mL, ultrasonographic measurements were easy to obtain, more accurate, and able to detect smaller amounts of distension. This may be clinically relevant for the assessment of effusion of the DIP joint that can arise in horses with early osteoarthritis or infectious arthritis with concomitant soft tissue swelling that precludes accurate assessment with palpation.

Accuracy of low-field magnetic resonance imaging versus radiography for guiding injection of equine distal interphalangeal joint collateral ligaments.

Desmopathy of the distal interphalangeal joint collateral ligament is a common cause of lameness in the horse and carries a variable prognosis for soundness. Intralesional treatment has been proposed for improving outcome; however, limited reports describe methods for injecting this ligament. The purpose of this study was to compare accuracy of low-field magnetic resonance imaging (MRI) vs. radiography for injecting the collateral ligament of the distal interphalangeal joint. Equine cadaver digit pairs (n = 10) were divided by random assignment to injection of the ligament by either technique. An observer unaware of injection technique determined injection success based on postinjection MRI and/or gross sections acquired from the proximal, middle, and distal portions of the ligament. McNemar's test was performed to determine statistical difference between injection techniques, the number of injection attempts, and injection of the medial or lateral collateral ligament. Magnetic resonance imaging guided injection was successful more frequently than radiographic-guided injection based on postinjection MRI (24 of 30 vs. 9 of 30; P = 0.0006) and gross sections (26 of 30 vs. 13 of 30; P = 0.0008). At each level of the ligament (proximal, middle, and distal), MRI-guided injection resulted in more successful injections than radiographic guidance. Statistical significance occurred at the proximal aspect of the collateral ligament based on postinjection MRI (P = 0.0143) and the middle portion of the ligament based on gross sections (P = 0.0253). Findings supported future testing of standing, low-field MRI as a technique for delivering intralesional regenerative therapy in live horses with desmopathy of these collateral ligaments.