Joint Manifestations Research Articles

33 Oligoarticular juvenile idiopathic arthritis-associated uveitis

BackgroundOligoarticular juvenile idiopathic arthritis (JIA) is a rare inflammatory disease that occur in children under the age of 16. JIA associated uveitis is the most frequent extra-articular manifestation. The uveitis can be sight-threatening and may be associated with disabling morbidity. The uveitis seen in JIA is chronic anterior uveitis which is always asymptomatic in the initial stage.ObjectiveTo report the incidence of uveitis in oligoarticular JIA and to determine the potential risk factors for the occurrence of uveitis in children with oligoarticular JIA.ResultsWe retrospectively evaluated 95 consecutive pediatric patients with oligoarticular JIA in the paediatric emergency and outpatient department of the children's hospital in Tunisia between January 2005 and December 2021. 70 patients were included in this study. A total of 12 cases (17.1%) with oligoarticular JIA associated uveitis where identified. The incidence of uveitis in these children was 0.7 cases per year.The uveitis had occurred before the joint manifestations in only one patient. The average time between the onset of symptoms and the occurrence of uveitis was 1.7 years with a maximum time interval of 5 years. Management of JIA-associated uveitis involved use of topical agents in half of our patients and systemic agents in the other half.JIA-associated uveitis has led to ocular complications such as cataracts (n = 5), glaucoma (n = 6), anterior/posterior synechiae (n = 8), and ultimately a visual impairment and blindness (n = 1). Eleven of the twelve patients with uveitis had acceptable visual acuity. The presence of antinuclear antibody (ANA) was identified as a risk factor for the occurrence of uveitis (p = 0.03).ConclusionCollateral damage of oligoarticular JIA include growth failure, muscle atrophy and intraocular damage. The main challenge during the management of oligoarticular JIA is the early detection of uveitis. Multidisciplinary management by the rheumatologist and the ophthalmologist is essential to optimize outcome.

Clinical profile of patients with lupus psychosis in a Colombian cohort.

The objective of this study is to describe the frequency and the clinical, paraclinical, and treatment profile of patients with lupus psychosis in a Colombian cohort of patients with systemic lupus erythematosus (SLE). This retrospective cohort study evaluated epidemiological and clinical characteristics, results of neuroimaging, analysis of the cerebrospinal fluid, treatment, and disease evolution in patients with lupus psychosis. Among 2,479 patients with SLE, six female patients aged between 20 and 50 years with a diagnosis of lupus psychosis were identified. In two patients, psychosis was present at disease onset and in the other four, SLE was already present, although the majority of them were diagnosed less than two years prior to the onset of psychosis. The entire cohort had high disease activity as measured by SLEDAI-2K. We found concomitant cutaneous, joint, and hematological alterations. Cerebrospinal fluid data were obtained in half of the patients and were normal. We performed brain tomography on most of our patients, which was almost always described as normal. In 5 out of 6 patients, the induction therapy to treat psychosis was based on steroids, and in the majority of them, a resolution of psychiatric symptoms was observed after initiating treatment. Lupus psychosis is a rare event that usually occurs early in the course of the disease and is associated with other manifestations of SLE. This investigation mainly found concomitant cutaneous, joint, and hematological manifestations, with a favorable outcome after treatment, as described in the literature.

Henoch-Schönlein purpura following COVID-19 vaccine in a child: a case report

BackgroundHenoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis, typical of childhood. It’s a self-limiting disease and it affects different systems. HSP is characterized by dermatological, abdominal, joint and renal clinical manifestations. This condition usually occurs upon infections, mainly upper respiratory tract ones, medications, vaccinations and malignancies.Case presentationWe describe the case of a 11 year-old girl who developed a urticarial rash 12 days after the first dose of Pfizer-BioNTech BNT16B2b2 mRNA vaccine and a clear picture of Henoch Schönlein purpura 5 days after administration of the second dose of the same vaccine.ConclusionTo our knowledge, this is the first description of a pediatric patient with Henoch-Schönlein purpura occurring in association with vaccination against COVID-19.

Evidence-Based Treatment of Severe Psoriasis by Individualised Homoeopathy: Case Reports

AbstractPsoriasis is a chronic skin disease with manifestations in skin, nails and joints. The disease usually runs a long course of remission and relapses, and is usually worse in winters. Psoriasis Area and Severity Index (PASI) score above 15 is considered to be an independent criterion for classifying a case as severe psoriasis. The conventional systemic therapy controls the symptoms but is costly and has known adverse effects. Individualised homoeopathic treatment has a potential role in providing safe and cost-effective treatment in psoriasis. In this article, three cases of severe psoriasis vulgaris treated with Homoeopathy at Bakson Homoeopathic Medical College and hospital are presented. Two cases were under treatment for a period of 20 months and one case received treatment for 24 months. Significant reduction (60–100%) in PASI score was observed with individualised homoeopathic treatment.

Graft versus host disease-related eosinophilic fasciitis: cohort description and literature review

BackgroundChronic graft versus host disease (cGVHD) simulating eosinophilic fasciitis (EF) is an underdiagnosed and challenging complication due to the lack of knowledge about its pathogenesis, refractoriness to traditional immunosuppressive agents and their negative impact on the physical function and quality of life. The aim of this study is to describe the clinical-biological characteristics and response to treatment of a case series and to provide a comprehensive literature review on cGVHD related EF involvement.MethodsProspective observational study to describe the clinical and diagnostic evaluation characteristics of patients with EF-like follow-up as part of our multidisciplinary cGVHD consultations. In addition, the literature on joint and/or fascial musculoskeletal manifestations due to cGVHD was comprehensively reviewed.Results118 patients were evaluated in multidisciplinary cGVHD consultations, 39 of whom (33%) developed fasciitis. Notably, 11 patients had isolated joint contractures without sclerotic skin. After a median of three lines of treatment, the vast majority of patients achieved some degree of response. 94 potentially eligible articles were identified by the search strategy, with 17 of them, the majority isolated case reports, making the final selection. The validated staging scales used for the assessment were the Joint and Fascial Score and the Photographic Range of Motion.ConclusionFascial/articular involvement needs to be recognized and evaluated early. To our knowledge, our cohort is the second largest series to have been reported. Literature addressing fascial/joints complications related to cGVHD is scarce. The search for new biomarkers, the use of advanced imaging techniques and multidisciplinary approach may help improve the prognosis of patients with cGVHD.

UNIFIED ALGORITHM OF REHABILITATION OF PATIENTS WITH OCCLUSIONAL DISORDERS OF IATROGENIC GENESIS COMBINED WITH VERTICAL MALOCCLUSION

Malocclusion is common dental diseases. According to epidemiological studies, occlusal pathology in the vertical plane is 5-7% among all anomalies. Occlusial problems contribute to the violation of basic body functions such as breathing, speech, chewing, which significantly impairs the quality of life of patients.Orthodontic treatment of adult patients has its own characteristics associated with the presence of concomitant pathology, as well as the inability to correct some pathologies only by orthodontic treatment. In the case of severe occlusion, complicated by tooth loss, a combination of surgical, orthodontic and prosthetic methods can achieve the best results. The key to successful treatment of such patients is a detailed diagnosis and a well-developed rehabilitation plan. Occlusive disorders, especially those that have arisen or been provoked as a result of dental treatment, usually lead to changes in all parts of the dental system and a number of complications. These structural changes usually make it difficult or sometimes impossible to conduct orthodontic treatment without the use of a set of special preparatory measures.
 The aim of our study: to propose a unified algorithm for complex dental rehabilitation of patients with occlusive disorders of iatrogenic origin in combination with vertical malocclusion and to prove its effectiveness.
 During 2019-2020, 55 patients with occlusive disorders of iatrogenic genesis in combination with pathology of occlusion in the vertical plane aged 23 to 47 years (mean age 36.1 ± 5.2 years) were examined, including 32 women and 23 men. Depending on the complaints and clinical manifestations, patients were divided into three groups. The first included 16 people with muscular manifestations, the second - 18 with disorders of the temporomandibular joint (TMJ) manifestations, the third - 21 people who, in addition to manifestations of TMJ and muscles, had primary neuritic disorders. All patients before and 6 months after treatment underwent clinical and laboratory examinations, radiography, electromyography and digital occlusion analysis of T-scan.
 There was a complete disappearance or significant reduction of complaints and symptoms after 6 months of rehabilitation in all 3 groups of patients. The implementation of our complex rehabilitation algorithm has led to the normalization of the bioelectrical activity of the masticatory muscles according to electromyography research, which is one of the most important criteria for the transition to the next stage of treatment and replacement of temporary restorations with permanent ones. Positive dynamics in the position of the TMJ condyles (tested with Computed Tomography) after the use of occlusal splints was observed in all patients and served as a marker for deciding to move to the next stage of dental treatment, including orthodontic correction. Also, occlusal balancing and normalization of the balance of occlusal contacts under the control of digital occlusal analysis T-Scan III was achieved in all patients in the preparatory stage and then monitored and maintained at all subsequent stages of comprehensive rehabilitation.
 Our study showed that the proposed algorithm for comprehensive rehabilitation of patients with iatrogenic occlusive disorders in combination with vertical malocclusion increases the effectiveness of orthodontic treatment of such patients and significantly reduces the duration of treatment in all 3 groups. This sequence of diagnostic and therapeutic measures provides the best opportunities for the patient to achieve maximum functional and aesthetic results.

Clinical and Laboratory Characteristics of Chronic Prostatitis / Chronic Pelvic Pain Syndrome

Chronic prostatitis / chronic pelvic pain syndrome is a common urological disease that is the most common clinical form of chronic prostatitis. The combination in its pathogenesis of chronic inflammation of the prostate and chronic pain creates difficulties in diagnosis and treatment. This review aims to highlight modern approaches and diagnostic tools most commonly used in the practice of urology. The article presents the main clinical manifestations, modern classification and methods of research of patients with chronic prostatitis / chronic pelvic pain syndrome. Clinical and laboratory signs of certain forms of prostatitis with emphasis on the joint manifestations of chronic bacterial prostatitis and chronic prostatitis / chronic pelvic pain syndrome are considered. Diagnostic criteria, bases of laboratory and differential diagnosis of chronic prostatitis are considered. Particular attention is paid to the difficulties of laboratory diagnosis of chronic prostatitis / chronic pelvic pain syndrome, in particular, evaluation of the results of repeated microscopic and cultural examinations of the secretion of the prostate, ejaculate and post-massage urine. The actual questionnaire of patients for objectification and monitoring of their complaints is presented; the possibility of individualization of treatment according to the patient’s phenotype and the implementation of a multimodal approach to the provision of medical care for prostatitis. The peculiarities of communication with the patient and the most common scales for assessing the condition of patients as a tool for objectifying complaints are presented. The place of instrumental methods in the diagnostic algorithm for chronic prostatitis is presented.

Expressions and difficulty of clinical manifestations in the early diagnosis of psoriatic arthritis

Objectives. Study of clinical manifestations in psoriatic arthritis: enthesitis, dactylitis, peripheral arthritis, axial arthritis, skin manifestations, for early diagnosis, which would allow the establishment of an adjusted treatment and the elaboration of measures to prevent complications. Materials and methods. The performed clinical study has an analytical-observational retrospective and included the patients who were hospitalized in the Rheumatology and Arthrology departments of the “Timofei Moşneaga” Republican Clinical Hospital during 2015-2021. The study included 103 patients with psoriasis (47 men and 56 women) with various clinical forms of psoriasis and different ages. Results. The clinical examination of primary or referred patients with cutaneous manifestations, revealed peripheral arthritis in 15 patients (24.6%), dactylitis – in 37 (60.7%), heel pain was detected in 32 (52.5%), axial arthritis – in 30 (49.2%), enthesitis, distal interphalangeal arthritis and tendonitis were not detected. Those who primary or referred with joint manifestations, in 35 (57.4%) of patients was present peripheral arthritis, dactylitis in 40 (65.6%), enthesis of the elbow joints in 11 (18%), knee joints - in 8 (13.1%), the calcaneal region - to 25 (41%), arthritis of the distal interphalangeal joints was detected in 21 (34.4%), tendinitis - to 13 (21.3%). Discussions. The obtained results allow us to state that one of the directions in improving the diagnosis of PsA consists in the use of ultrasound examination and MRI imaging of the joints of the hands and feet. This makes it possible to effectively identify the characteristic of enthesopathy, edema of tissues, as well as destructive changes in the joints of the hands and feet. Conclusions. In the study group of patients with psoriasis, in 25 (24.2%) no joint damage was detected. The frequency of detection of psoriatic arthritis and other rheumatic diseases (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis etc.) was 59.2% and 16.6%, respectively, 32 (52.5%) out of 61 (59.2%) patients with PsA were primarily diagnosed. The sensitivity and specificity of the mPEST (Psoriasis Epidemiology Screening Tool) questionnaire in relation to the CASPAR criteria were 77% and 69% respectively. The highest indicators of sensitivity, specificity and accuracy in the diagnosis of PsA has ultrasound and MRI: 88%, 92%, 89% and respectively, 89%, 94%, 91%.

A novel variant of DeSanto-Shinawi Syndrome with joint manifestations

The clinical features associated with WAC haploinsufficiency include recognizable dysmorphic facial features, variable degrees of developmental delay and intellectual disability that were recently delineated as DeSanto-Shinawi syndrome (OMIM 616708). We describe a patient with DeSanto-Shinawi syndrome caused by a novel frameshift variant in WAC gene (NM_016628.4(WAC):c.1689del (p.Phe563Leufs*6)). As noted in cases previously reported, our patient phenotype included facial dysmorphism, intellectual disability, behavioral problems, feeding difficulties, hirsutism, constipation and astigmatism. She also had limited range of motion of joints since birth and Juvenile Idiopathic Arthritis diagnosed at eleven years old. Although in the last years some additional features were reported in DeSanto-Shinawi syndrome, joint manifestations have not been previously described. As limited range of motion of joints was reported since birth with no correlation with arthritis onset, it could be a new clinical feature. Polyarthritis in this patient can be only a coincidence, since there is a first degree relative with psoriasis, or might be related to WAC mutation. Indeed, WAC encodes a protein that plays a vital role in autophagy. It has already been demonstrated that WAC haploinsufficiency leads to increased autophagy and, according to different authors, increased autophagy may display a pathogenic role in several autoimmune disorders such as Rheumatoid Arthritis and Juvenile Idiopathic Arthritis. Thus, WAC haploinsufficiency may have contributed to autoimmune disorder in this patient.

Lichen planus-lupus erythematosus overlap syndrome

The combination of lichen planus and lupus erythematosus is rare: the number of overlap syndrome cases described in the world literature does not exceed 50. The clinical picture of the overlap syndrome is variable: patients have discoid lesions of lupus erythematosus and typical flat-topped polygonal papules of lichen planus, as well as joint manifestations in the form of livid-red plaques with central atrophy and superficial desquamation. Laboratory testing reveals positive antinuclear antibody. The histopathological picture is characterized by a combination of histological signs of lichen planus and lupus erythematosus. In some cases, clinical and immunological signs of systemic lupus erythematosus are found in patients with the overlap syndrome. We describe two cases of lichen planussystemic lupus erythematosus overlap syndrome.

Formulation d’une pommade antalgique et anti-inflammatoire à base d’un extrait hydroalcoolique des écorces de racines de Securidaca longepedunculata Fresen (Polygalaceae)

Securidaca longepedunculata is a plant commonly used by African populations. Previous works have identified the main bioactive constituents; study the toxicity, analgesic, anti-inflammatory, antioxidant activities of the root barks. This work aims at developing an Improved Traditional Medicine (ITM) in ointmentbased on the hydroethanolic extract of the root barks. The plant material was analyzed to determine the physicochemical parameters. The hydroethanolic extract was used to formulate ointments with shea butter. The quality parameters of the ointment were determined and the primary irritability was checked in albino rabbits. The local anti-inflammatory activity was evaluated against croton oil and xylem inflammation in mice. It exhibited stability at a temperature of 30°C and showed no skin irritation. It inhibited 27% of the inflammation to croton oil. Triterpenic saponins and antiradical constituents were the main chemical markers identified. These results and the existing data can be used for the development of “SECUDOL ointment”, an ITM against painful and inflammatory joint manifestations.

POS0005 BASELINE BIOMARKERS PREDICT BETTER RESPONSES TO DEUCRAVACITINIB, AN ORAL, SELECTIVE TYROSINE KINASE 2 (TYK2) INHIBITOR, IN A PHASE 2 TRIAL IN PSORIATIC ARTHRITIS

BackgroundDeucravacitinib (DEUC) is a novel, oral, selective TYK2 inhibitor with a unique allosteric mechanism of action that has demonstrated efficacy in patients with psoriasis (PsO)1 and psoriatic arthritis (PsA).2 TYK2 mediates signalling of select immune cytokines, eg, interleukin (IL) 23, IL-12, and Type I interferons, whereas the related Janus kinases (JAK) 1/2/3 mediate signalling of a wider array of cytokines and mediators involved in inflammatory, developmental, metabolic, and hematopoietic pathways. DEUC reduced inflammatory markers associated with skin and joint manifestations but did not result in laboratory abnormalities associated with inhibition of JAK1/2/3 in a PsA trial.3ObjectivesTo identify baseline biomarkers that predict response to DEUC in patients with PsA.MethodsThe double-blind Phase 2 trial (NCT03881059) enrolled 203 patients with PsA randomised 1:1:1 to placebo (PBO), DEUC 6 mg once daily (QD), or 12 mg QD.2 Molecular profiling of baseline serum samples was performed by immunoassays. Clinical response at Week 16 was measured by ≥20% improvement from baseline in American College of Rheumatology Improvement Criteria (ACR 20) and ≥75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) scores.ResultsBiomarkers of the IL-23/T helper cell type 17 pathway, including IL-17A, IL-17‒induced β-defensin 2 (BD2), and IL-19, were associated with higher PASI but not Psoriatic Arthritis Disease Activity Scores overall at baseline. PASI 75 responders in DEUC-treated groups had higher baseline levels of IL-17A compared with nonresponders. In contrast, PASI 75 responders in PBO-treated patients had lower baseline expression of IL-17A, BD2, and IL-19 compared with nonresponders. In patients treated with DEUC 12 mg QD, greater reductions in BD2 were observed in the PASI 75 responder group compared with nonresponder group. When patients were dichotomised by median baseline biomarker level, higher clinical responses in both PASI 75 and ACR 20 were achieved in those with higher baseline overall biomarker levels in the DEUC-treated groups compared with the PBO group. Higher baseline expression of IL-23 biomarkers IL-17A, IL-19, and BD2 enriched ACR 20 response in patients treated with DEUC compared with PBO (OR=5.64, 6.68, and 4.99, respectively). While greater benefit was observed in high-biomarker groups, the low-biomarker populations still manifested clinical responses although not significant (Figure 1).ConclusionPatients who had higher expression of IL-23 pathway biomarkers were more likely to benefit from DEUC compared with placebo in skin and joint manifestations of PsA. These results reinforce the value of TYK2 inhibition in patients with IL-23‒mediated diseases. The potential value of IL-23-pathway markers in predicting higher responses to DEUC should be further explored in larger trials.

POS1361 THE CANADIAN RESEARCH GROUP OF RHEUMATOLOGY IN IMMUNO-ONCOLOGY (CanRIO): A NATIONWIDE MULTI-CENTER PROSPECTIVE COHORT

BackgroundImmune Checkpoint Inhibitors (ICI) have altered the landscape of cancer therapy. However, toxicities are common and up to 80% of patients will develop immune-related adverse events (irAE), including rheumatic irAEs (Rh-irAE), which can often limit their cancer treatment. Our knowledge of clinical manifestations and optimal management of patients with Rh-irAE continues to evolve as these agents are being used to treat a wider variety of cancers. Currently available data is limited to retrospective case series and case reports. There is also scarce data on the use of ICI in patients with pre-existing autoimmune disease (PAD) as these patients are often excluded from clinical trials.ObjectivesTo describe the clinical presentation, management and early outcomes of patients exposed to ICI with Rh-irAE or PAD recruited and followed prospectively from multiple sites across Canada.MethodsAdult patients with Rh-irAE from cancer immunotherapy (CTLA-4, PD-1 or PDL-1 inhibitors) or those with PAD exposed to cancer immunotherapy are prospectively recruited across 9 academic sites in Canada. Standardized clinical and biologic data are also collected. We describe clinical characteristics and management of patients recruited between January 2020 and October 2021, stratified based on the presence or absence of PAD.Results103 patients were recruited from 9 sites. From those, 85 had Rh-irAE, 47 had pre-existing musculoskeletal and rheumatic diseases, and 20 had other PAD. The most frequent Rh-irAE were joint manifestations (n = 73). Other Rh-irAE included muscle symptoms (n = 7), connective tissue disease (n = 6), vasculitis (n=2) and sarcoid (n = 3). Prednisone was the most common treatment (n = 53). Intraarticular corticosteroids were used in 7 patients. Eleven patients required conventional synthetic disease-modifying anti-rheumatic drugs (DMARD) and only one required biologic DMARD to control the Rh-irAE. Anti-PD-1 therapies were the most used ICI (56.3%), followed by combination therapy (35.9%). Response to index immunotherapy at 6 months was available for 21 patients. Most patients had partial response (57.1%) and only 4 patients had tumor progression (19.1%). The ICI was permanently discontinued due to an irAE in 21 patients (38.1% with PAD and 61.9% without PAD). There were no deaths related to Rh-irAE.ConclusionThe initial sample of the CanRIO prospective national cohort suggests that demographic characteristics and tumor representation in people with PAD and without PAD is similar. Patients with PAD are less likely to receive combination therapy (n= 12 vs. n=25) and are less likely to have tumor progression on ICI (n=1) compared to those without PAD (n=3). Selection bias is noted in this initial sample since half of recruited patients have PAD. The CanRIO cohort provides valuable insight into real-world spectrum and management of Rh-irAE secondary to immunotherapy for cancer.Disclosure of InterestsShahin Jamal Grant/research support from: CanRIO has received financial support from BMS and Organon, Lourdes Gonzalez Arreola: None declared, Julia Tan: None declared, Carrie Ye: None declared, Janet Roberts: None declared, Aurore Fifi-Mah: None declared, Marie Hudson: None declared, Sabrina Hoa: None declared, Janet Pope: None declared, Ines Colmegna: None declared, C. Thomas Appleton: None declared

POS0863 ANTI-NOR90 ANTIBODIES IN THE SETTING OF CONNECTIVE TISSUE DISEASE: CLINICAL SIGNIFICANCE AND COMPARISON WITH A COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS

BackgroundAnti-NOR90 antibodies are directed against a 90-kD nucleolar protein located in the nucleolus organizing regions (NORs), mainly described in systemic sclerosis (SSc) [1, 2, 3] but reported also in other rheumatologic and oncologic diseases [4, 5, 6]. The clinical correlates of anti-NOR90 antibodies are still to be defined because the cohorts described thus far include a low number of patients.ObjectivesTo describe the characteristics of a large cohort of anti-NOR90 antibodies positive patients and compare them with a matched cohort of SSc patients negative for anti-NOR90 antibodies.MethodsA retrospective analysis was performed on patients positive for anti-NOR90 antibodies referring to participating centres. The concomitant positivity for anti-RNA polymerase III, Th/To, PM-Scl, Ku, and PDGFR antibodies was an exclusion criterion. In all cases the diagnoses, the different organ involvement and related clinical, instrumental and laboratory characteristics were evaluated. The EUROLINE SystemicSclerosisProfile kit from Euroimmun (Lübeck, Germany) was used to detect anti-NOR90 antibodies.ResultsWe included 101 patients positive for anti-NOR90 (M/F=13/88, mean age 52.5 years). They were mainly classified as SSc (n=38), undifferentiated connective tissue disease (UCTD) (n=21), interstitial pneumonia with autoimmune features (IPAF) (n=11) (graph 1). The most frequent clinical manifestations were arthralgias (n=72), Raynaud’s phenomenon (RP) (n=58), sicca syndrome (n=49), ILD (n=40), puffy fingers (n=32), arthritis (n=30), and limited skin sclerosis (n=24). Anti-NOR90 antibodies were associated with anti-Ro52 antibodies in the 16% of cases, with anticentromere antibodies in the 7% of cases, and with anti-Scl70 in the 5% of cases. After excluding these patients, and considering the isolated anti-NOR90 positivity, 12 patients had SSc, 35 UCTD, and 11 IPAF. The most frequent clinical manifestations were arthralgias (n=40), RP (n=37), and sicca syndrome (n=21). Compared to 242 matched SSc without anti-NOR90 antibodies, patients with anti-NOR90 had more frequently joint manifestations and sicca syndrome and less frequently all vasculopathic manifestations (RP, telangiectasias, pitting scars, acral ulcers), dysphagia and fibromyalgia.ConclusionOur study shows that anti-NOR90 antibodies are more commonly observed in females, and clinically associated with the occurrence of arthritis/arthralgias, sicca syndrome and RP. In more than the 50% of cases they may be found with other autoantibodies, such as the anti-Ro52, the anticentromere, and the anti-Scl70 antibodies. Anti-NOR90 seems to play an accompanying role in the context of CTDs, without strong influence on the clinical phenotype expression of the underlying CTD.

OP0024 DIFFERENTIATION BETWEEN IL-6 AND IL-17 PATHWAY INHIBITION IN RELATIONSHIP WITH CLINICAL OUTCOMES IN NON-BIOLOGICAL DMARD-IR AND BIOLOGICAL DMARD-IR PSORIATIC ARTHRITIS PATIENTS TREATED WITH UPADACITINIB IN SELECT-PsA 1 AND SELECT-PsA 2 STUDIES

BackgroundThe differential contribution of IL-6 and IL-17 pathways to the pathogenesis of psoriatic arthritis (PsA) is not fully understood. Upadacitinib (UPA), an oral JAK inhibitor, was more effective than placebo (PBO) in improving key clinical manifestations of PsA in two global phase 3 trials, SELECT-PsA 1 (non-biological DMARD-IR, nbDMARD-IR) and SELECT-PsA 2 (biological DMARD-IR, bDMARD-IR).1,2 Targeted proteomic analysis suggested that UPA modulates multiple biological pathways in innate and adaptive immune systems via direct and indirect inhibition of key regulators, including IL-6 and IL-17 pathways, with a possible shift from Th1 predominance in nbDMARD-IR PsA to a more Th17 bias in bDMARD-IR PsA.3ObjectivesWe assessed the relationship between IL-6 and IL-17 pathway modulation and different clinical outcomes after UPA treatment in nbDMARD-IR and bDMARD-IR PsA patients.MethodsA subset of patients was randomly selected from SELECT-PsA 1 (n=74 of UPA 15 mg QD, n=74 of PBO) and PsA 2 studies (n=90 of UPA 15 mg QD, n=81 of PBO). Serum levels of IL-6, IL-17A, IL-17F, and beta-defensin 2 (BD2) proteins were measured at baseline, week 2, and week 12 by validated immunoassays. The quantitative cytokine measurements were transformed as log10, and PASI score was transformed as log10 (x+1) prior to analysis. A Repeated Measure Mixed Linear Model was used to compare UPA versus PBO treatment effects in overall selected patients and between responders and non-responders defined by PASDAS score ≤ 3.6 (Minimal Disease Activity, MDA)4 and PASI75 at week 12, respectively. The relationships between cytokines and clinical outcomes (PASI and DAS28-CRP) were assessed by Pearson’s correlation at baseline and after treatment.ResultsIn nbDMARD-IR PsA patients, baseline IL-17A, IL-17F, and BD2 levels correlated with each other and with PASI, while IL-6 appeared independent from the IL-17 pathway and correlated with DAS28-CRP. At week 12, UPA treatment significantly decreased IL-6 and BD2. The decrease of IL-6 was more pronounced in PASDAS MDA responders and correlated with DAS28-CRP improvement, but the decrease of BD2 was significant in PASI75 responders and correlated with PASI improvement. In contrast, IL-17A and IL-17F were not significantly changed after UPA treatment, neither correlated with clinical outcomes at week 12.In bDMARD-IR PsA patients, baseline IL-17A level was significantly elevated compared to nbDMARD-IR patients but weakly correlated with other cytokines and show no correlation with PASI. At week 12, the reduction of IL-6 after UPA treatment was not different between responders and non-responders (PASDAS MDA or PASI75) and did not correlate with DAS28-CRP improvement, while the reduction of BD2 remained significant in PASI75 responders and correlated with PASI improvement. Further, UPA treatment significantly reduced IL-17A in PASDAS MDA responders and IL-17F in PASI75 responders compared to non-responders, respectively. The reduction of IL-17F correlated with PASI improvement at week 12.ConclusionIL-6 and IL-17 pathway inhibition after UPA treatment showed different profiles in relationship with clinical outcomes in nbDMARD-IR versus bDMARD-IR PsA patients. IL-6 decrease was more pronounced in nbDMARD-IR PsA patients and associated with joint manifestation improvement, while IL-17A and IL-17F decreases were only observed in bDMARD-IR PsA patients and associated with psoriasis improvement. BD2, a biomarker of Th17-associated skin pathology, significantly decreased after UPA treatment in both nbDMARD-IR and bDMARD-IR PsA studies, which likely contributed to UPA effects on psoriasis improvement in a broad range of PsA patients.

Joint manifestation of quasi-phase-matching and resonance enhancement of harmonics in laser-induced plasmas

We compare two processes (resonance enhancement and quasi-phase-matching) allowing the enhancement of the high-order harmonics of ultrashort pulses during propagation through different laser-induced plasmas (vanadium, antimony, indium, and manganese). We show how the tuning of maximally enhanced harmonics during quasi-phase-matching in multi-jet plasmas can enhance the resonantly-enhanced harmonics. Theoretical calculations support experimentally observed quasi-phase-matching of a group of harmonics and single harmonic enhancement.

P253 Ultrasound demonstrates continued improvement in psoriatic arthritis synovitis and enthesitis with secukinumab: 52-week results from a Phase 3 study

Abstract Background/Aims Power Doppler ultrasound (PDUS) is a sensitive non-invasive imaging tool to visualize a wide range of articular and periarticular inflammation in psoriatic arthritis (PsA). ULTIMATE (NCT02662985) is the first large RCT that used ultrasound with Global OMERACT ultrasound synovitis score (GLOESS) as the primary endpoint, to demonstrate early benefits of secukinumab on synovitis in patients with PsA through 12 weeks. Here we report the responsiveness of ultrasound on synovitis and enthesitis, clinical efficacy, and safety of secukinumab up to 52 weeks. Methods This was a 52-week study with 12-week double-blind placebo-controlled treatment followed by 12-week open-label treatment and 6-month open-label extension treatment in all patients. Synovitis and ultrasound enthesitis response were measured by GLOESS and Global OMERACT enthesitis score (definitions 1 and 2) at patient level, respectively. Other assessments across key PsA manifestations of joints (ACR responses), enthesitis, (SPARCC), skin (PASI responses), dactylitis (LDI) and physical function (HAQ-DI) were also evaluated. Data are presented as observed. Results A total of 166 patients were enrolled, of which 90% (75/83) of secukinumab and 83% (69/83) of placebo-secukinumab participants completed 52 weeks. A continued improvement in GLOESS was observed in both secukinumab and placebo-secukinumab groups after switching to active therapy at Week 12 through Week 52 and a similar trend of improvement in Global OMERACT enthesitis score (definition 1 and 2) was observed up to 52 weeks in both groups (Table). At 52 weeks, sustained clinical response rates were observed in secukinumab (ACR20, 89%; ACR50, 68%; ACR70, 48%; PASI 90, 59%; PASI 100, 55%) and placebo-secukinumab groups (ACR20, 84%; ACR50, 72%; ACR70, 47%; PASI 90, 74%; PASI 100, 48%). Mean changes from baseline at Week 52 in HAQ-DI and SPARCC were -3.0 and -0.8 and -3.6 and -0.7 for secukinumab and placebo-secukinumab, respectively. There were no new or unexpected safety findings. Conclusion ULTIMATE demonstrated the responsiveness of ultrasound on both synovitis and enthesitis outcomes in PsA supporting its use in clinical trials, and confirmed the rapid and continued benefits of secukinumab through 52 weeks. Sustained efficacy was also observed across key clinical PsA manifestations with a safety profile consistent with previous reports. Disclosure P.G. Conaghan: Consultancies; AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer. M.A. D’Agostino: Consultancies; Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, Eli Lilly. Member of speakers’ bureau; Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, Eli Lilly. G. Schett: Member of speakers’ bureau; AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche, UCB. C. Guerrero: None. P. Hanova: None. T. Cazenave: None. M.S. Stoenoiu: Honoraria; Roche, AbbVie, BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; Roche, AbbVie, UCB. Grants/research support; Roche, AbbVie, UCB. M. Backhaus: Honoraria; Roche, AbbVie, BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; Roche, AbbVie, UCB. Grants/research support; Roche, AbbVie, UCB. G. Mouterde: Consultancies; AbbVie, Lilly. Honoraria; AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, Chugai, UCB. Grants/research support; Celgene, Pfizer. M. Boers: Consultancies; BMS, Novartis, Pfizer, GSK. A. Duggan: Other; Employee of Novartis. P. Goyanka: Other; Employee of Novartis MSD. C. Gaillez: Shareholder/stock ownership; Novartis, BMS. Other; Employee of Novartis.

A Narrative Literature Review Comparing the Key Features of Musculoskeletal Involvement in Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Although the clinical approach to the management of musculoskeletal manifestations in systemic lupus erythematosus (SLE) is often similar to that of rheumatoid arthritis (RA), there are distinct differences in immunopathogenesis, structural and imaging phenotypes and therapeutic evidence. Additionally, there are few published comparisons of these diseases. The objective of this narrative literature review is to compare the immunopathogenesis, structural features, magnetic resonance imaging (MRI) and musculoskeletal ultrasound (MSUS) studies and management of joint manifestations in RA and SLE. We highlight the key similarities and differences between the two diseases. Overall, the literature evaluated indicates that synovitis and radiographical progression are the key features in RA, while inflammation without swelling, tendinitis and tenosynovitis are more prominent features in SLE. In addition, the importance of defining patients with RA by the presence or absence of autoantibodies and categorizing patients with SLE by synovitis detected by musculoskeletal ultrasound and by structural phenotype (non-deforming, non-erosive arthritis, Jaccoud’s arthropathy and ‘Rhupus’) with respect to joint manifestations will also be discussed. An increased understanding of the joint manifestations in RA and SLE may inform evidence-based clinical decisions for both diseases.

Оценка агроэкологического состояния агроландшафтов для повышения их устойчивости

Introduction. Agricultural land use organized in the dry steppe Kulunda of Altai Krai, with an area of more than 1,8 million hectares, is unsustainable. This is due to many factors, but the main ones are agro-climatic conditions (temperature and precipitation), as well as anthropogenic elements of landscapes, as a result of the joint manifestation of which erosion processes develop. The purpose of the study: to conduct a multicomponent analysis of agricultural lands in the dry steppe Kulunda Altai Krai to optimize their agro- and geo-ecological state, as well as increase the sustainability of agricultural landscapes. Research methods: a systematic approach and a comparative geographical method used in the processing of materials characterizing the qualitative and quantitative indicators of agricultural landscapes and the analysis of zonal physical and geographical characteristics of the territory. Relationships and mutual influences within anthropogenic landscapes have been studied using the ecological-landscape approach. Research results. Over a thirty-year period of monitoring the heat and moisture supply of the territory, it was found that only 1-2 years per decade are optimal for growing crops (spring wheat), and agricultural land prevails in the structure of the land fund (seven municipal districts), and their share varies from 47 % to 96 % in Uglovsky and Tabunsky districts, respectively. Examining the structure of sown areas and crop rotations, it was found that arable land is the most common agricultural land, it accounts for more than 70 %, pastures – almost 20 %, hayfields and fallow lands – 8,5 %, perennial plantations – only 0,04%. It was determined that cultivated crop rotations lead to degradation of the soil cover, which occurs due to active dehumification – the loss of humus reserves in the process of deflation and active mineralization on fallows and fields with tilled crops. It was calculated that the rate of humus loss on an area of one hectare is 0,24 tons per year. Conclusion. The calculations made show that the coefficient of environmental stability is much lower than the threshold, and a relatively high indicator of environmental stability in the Mikhailovsky and Uglovsky districts was achieved due to the tape forest and salt lakes located on their territory, which do not have a positive impact on the sustainability of agricultural areas. Improving the sustainability of agricultural land use is possible with the organization of a grass field system by changing the structure of sown areas and crop rotations.

Infliximab therapy in refractory sarcoidosis: a multicenter real-world analysis

BackgroundInfliximab is a monoclonal antibody that binds and neutralizes circulating tumor necrosis factor-alpha, a key inflammatory cytokine in the pathophysiology of sarcoidosis. Despite the paucity of randomized clinical trials, infliximab is often considered a therapeutic option for refractory disease. Our study aimed to investigate the effectiveness of infliximab in patients with refractory sarcoidosis.MethodsSarcoidosis patients from three tertiary centres were retrospectively identified by pharmacy records based on treatment with infliximab. Treatment with Infliximab was initiated in patients who failed first and second line immunomodulators as determined by a multidisciplinary team of Respirologists, Dermatologists, ENT specialists, Rheumatologists, and Neurologists. Participants were characterized by the primary organ for which infliximab was initiated and the total number of organs involved. Clinical outcomes were categorized as treatment success versus failure. We defined treatment success as (A) improvement of cutaneous, upper airway, lymph node, gastrointestinal, eye, or joint manifestations; or (B) improvement or no change in central nervous system (CNS) or pulmonary manifestations.Results33 patients with refractory sarcoidosis were identified. The proportion of treatment success was 100% (95% CI 54.1–100) in CNS, 91.7% (95% CI 61.5–99.8) in cutaneous, 78.6% (95% CI 49.2–95.3) in pulmonary and 71.5% (95% CI 29.0–96.3) in upper airway disease. The use of infliximab was associated with a reduction prednisone dose by 50%.ConclusionInfliximab is possibly an effective therapy for refractory sarcoidosis, with the greatest value in neurologic and cutaneous manifestations. Across all disease presentations, infliximab facilitated a clinically relevant reduction in corticosteroid dose. Relapse is common after discontinuation of infliximab.