Anti-inflammatory effect of biologic therapy in patients with psoriatic disease: A prospective cohort FDG PET study.

AIM: The aim of the study was to evaluate the changes in central vascular inflammation measured by FDG PET and myocardial blood flow reserve (MFR) determined by 82Rb PET following therapy with biologic agents for 6 months in patients with psoriatic arthritis (PsA) and/or cutaneous psoriasis (PsO) (group 1) and compare with PsO subjects receiving non-biologic therapy (group 2) and controls (group 3). METHODS AND RESULTS: Target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta (TBRmax) was measured to assess vascular inflammation. 82Rb PET studies were used to assess changes in left ventricular MFR. A total of 34 participants were enrolled in the study (11 in group 1, 13 in group 2, and 10 controls). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (ΔTBRmax: - .46 ± .55) compared to the PsO group treated with non-biologic therapy (ΔTBRmax: .23 ± .67). Those showing response to biologic agents maintained MFR compared to who showed no response. CONCLUSION: In a cohort of psoriasis patients treated with biologics, FDG uptake in the thoracic aorta decreased over the study period. Patients who demonstrated a significant anti-inflammatory response on FDG PET imaging maintained their MFR compared to non-responders.

Evidence that systemic therapies for psoriasis may reduce psoriatic arthritis occurrence.

OBJECTIVES: Contemporary biologic therapies for psoriasis are independently licensed for psoriatic arthritis (PsA). Since skin disease generally predates PsA and PsA has a subclinical phase, we investigated the pattern of PsA evolution in psoriasis treated with biologic agents compared to other medications including oral therapy, topical agents or no treatments. METHODS: A retrospective chart review was performed in psoriasis patients with musculoskeletal symptoms referred for rheumatological assessment. Patients who had a final diagnosis of PsA were identified. The frequency and clinical features of PsA were compared for biologics versus the other strategies. RESULTS: Between 2015-18, 203 psoriasis patients were referred for musculoskeletal symptoms with 25 on biologics, 31 on non-biologic systemic therapies and 147 on topical/no therapies. A final diagnosis of PsA was similar in all groups (biologics: 36%; non-biologic systemic treatments: 35.4%; none/local treatments: 37.4%). Most patients had musculoskeletal symptoms before systemic therapy initiation but new onset PsA was evident in 12% (3/25) biologics treated patients, 9.6% (3/31) in non-biologic systemic therapy patients and was significantly higher in patients on topical/no therapy (55/147; 37.4%, p<0.001). Among patients with PsA, none of the patients on biologics exhibited dactylitis compared to 28.6% of other systemic treatments and 48.6% of none/local treatments (p=0.046). CONCLUSIONS: New symptoms and signs leading to PsA diagnosis appear to decrease with systemic treatments. The characteristic PsA dactylitis lesion was not evident in the biologic therapy group.

Rheumatologists lack confidence in their knowledge of cannabinoids pertaining to the management of rheumatic complaints.

BACKGROUND: Arthritis pain is reported as one of the most common reasons for persons using medical herbal cannabis in North America. "Severe arthritis" is the condition justifying legal use of cannabis in over half of all authorizations in Canada, where cannabis remains a controlled substance. As champions for the care of persons with arthritis, rheumatologists must be knowledgeable of treatment modalities both traditional and non-traditional, used by their patients. As study of cannabinoid molecules in medicine is recent, we have examined the confidence in the knowledge of cannabinoids expressed by Canadian rheumatologists. METHODS: The confidence of rheumatologists in their knowledge of cannabinoid molecules and mechanisms relevant to rheumatology, and their ability to advise patients about cannabinoid treatments was recorded by an online questionnaire circulated via email to the entire Canadian Rheumatology Association membership. RESULTS: Over three quarters of the 128 respondents lacked confidence in their knowledge of cannabinoid molecules. While 45% of respondents believed there was no current role for cannabinoids in rheumatology patient care, only 25% supported any use of herbal cannabis. With 70% never having previously prescribed or recommended any cannabinoid treatment, uncertainty regarding good prescribing practices was prevalent. Concerns about risks of cannabis use were in line with the current literature. CONCLUSIONS: Rheumatologists lacked confidence in their knowledge of cannabinoid molecules in general and in their competence to prescribe any cannabinoid for rheumatic complaints. In line with this uncertainty, there is reticence to prescribe cannabinoid preparations for rheumatology patients. Guidance is required to inform rheumatologists on the evidence regarding cannabinoids.

Disease-specific definitions of new bone formation on spine radiographs: a systematic literature review.

Objectives: We aimed to explore the radiographic definitions of types of New Bone formation (NBF) by focusing on the terminology, description and location of the findings. Methods: Three systematic literature reviews were conducted in parallel to identify the radiographic spinal NBF definitions for spondyloarthritis (SpA), Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Osteorathritis (OA). Study characteristics and definitions were extracted independently by two reviewers. Definitions were analysed and collated based on whether they were unique, modified or established from previous research. Results: We identified 33 studies that indicated a definition for the NBF in SpA, 10 for DISH and 7 for spinal OA. In SpA, the variations in syndesmophytes included the description as well as the subtypes and locations. The differentiation of syndesmophytes from osteophytes were included in 12 articles, based on the origin and the angle of the NBF and associated findings. The definitions of DISH varied in the number of vertebrae, level and laterality. For OA, five articles indicated that osteophytes arose from the anterior or lateral aspects of the vertebral bodies, and two studies required a size cut-off. Discussion: Our ultimate aim is to create formal NBF definitions for SpA, DISH and OA guided by an atlas, through a Delphi exercise with international experts. The improved ability to differentiate these conditions radiographically will not only allow the clinicians to accurately approach patients but also will help the researchers to better classify patient phenotypes and focus on accurate radiographic outcomes.

Celecoxib modifies glomerular basement membrane, mesangium and podocytes in OVE26 mice, but ibuprofen is more detrimental.

The role of COXs/PGs (cyclo-oxygenases/prostaglandins) in diabetic kidneys remains unclear. NSAIDs (non-steroidal anti-inflammatory drugs) that inhibit COXs/PGs are known for their renal toxicity, and COX-2 inhibitors worsen cardiovascular outcomes in susceptible individuals. Given the renal controversies concerning COX-2 inhibitors, we compared the effect of chronic NSAIDs (non-selective, ibuprofen; COX-2-selective, celecoxib) on diabetic kidneys in OVE26 mice from 8 weeks of age. Systolic BPs (blood pressures) were increased by NSAIDs in diabetic mice at 20 weeks, but were unchanged at 32 weeks. Although NSAIDs further increased diabetic kidney/body weight ratios, they did not affect albuminuria. Mesangial matrix was increased 2-fold by celecoxib but not ibuprofen. Electron microscopy revealed that NSAIDs reduced GBM (glomerular basement membrane) thickness and slit pore diameters. Although diabetics had increased glomerular diameters and reduced foot process densities, these were unaltered by NSAIDs. Celecoxib does not exacerbate the diabetic state, but PG inhibition may contribute to disease progression by modifying the GBM, mesangial area and podocyte structure in OVE26 mice. Despite these findings, celecoxib remains safer than a similar dose of ibuprofen. The present study substantiates the need to more closely consider selective COX-2 inhibitors such as celecoxib as alternatives to non-selective NSAIDs for therapeutic management in a setting of chronic kidney disease.

Celiac disease arthropathy and autoimmunity study.

BACKGROUND AND AIM: To evaluate presence of sero-negative spondyloarthritis (SpA) in celiac disease (CD) patients, and whether compliance with a gluten free diet (GFD) improved arthritis manifestations in these patients. METHODS: We undertook a prospective, questionnaire based, cross-sectional cohort study to evaluate the presence or absence of SpA simultaneously in both CD and non-CD cohorts. RESULTS: 356/590 (60.3%) patients with CD participated in this study. 99% had diagnosis confirmed by a diagnostic test (79% small bowel biopsy, 19.8% blood test, 3.9% stool test). Approximately 131 (37%) cases of arthritis were reported in CD patients. Of the 6/356 CD patients with seronegative spondyloarthritides, four had sacroiliitis, two ankylosing spondylitis, and one psoriatic arthritis, compared to one ankylosing spondylitis and five psoriatic arthritis in non-CD. Osteoarthritis (89 vs 59, P = 0.93) was the most common diagnosis reported by respondents. More CD patients with diarrhea (94%) and anemia (81%) improved on GFD, compared to arthritis symptoms (30%). Autoimmune thyroiditis (10.6% vs 0.4%), insulin dependent diabetes mellitus (IDDM) (2.2% vs 1.7%), systemic Lupus erythematosus (SLE) (1.1% vs 0), and psoriasis (12.9% vs 5.5%) occurred more frequently in CD patients. The prevalence of Crohn's disease, ulcerative colitis, Sjogren's syndrome, primary biliary cirrhosis, and primary sclerosing cholangitis was around 1% each. Univariate Logistic regression analysis showed ≤ high school education (odds ratio [OR] 2.01, P < 0.003), age ≥ 60 years (OR 4.13, P < 0.001), and osteoporosis (OR 2.78, P < 0.001) to be significantly associated with report of arthritis in CD patients. CONCLUSION: We did not find a high rate of SpA in CD patients. In contrast, increased rates of autoimmune thyroiditis, SLE, IDDM, and psoriasis were seen in CD.

Amplification of Inflammation by Lubricin Deficiency Implicated in Incident, Erosive Gout Independent of Hyperuricemia.

OBJECTIVE: In gout, hyperuricemia promotes urate crystal deposition, which stimulates the NLRP3 inflammasome and interleukin-1ß (IL-1ß)-mediated arthritis. Incident gout without background hyperuricemia is rarely reported. To identify hyperuricemia-independent mechanisms driving gout incidence and progression, we characterized erosive urate crystalline inflammatory arthritis in a young female patient with normouricemia diagnosed as having sufficient and weighted classification criteria for gout according to the American College of Rheumatology (ACR)/EULAR gout classification criteria (the proband). METHODS: We conducted whole-genome sequencing, quantitative proteomics, whole-blood RNA-sequencing analysis using serum samples from the proband. We used a mouse model of IL-1ß-induced knee synovitis to characterize proband candidate genes, biomarkers, and pathogenic mechanisms of gout. RESULTS: Lubricin level was attenuated in human proband serum and associated with elevated acute-phase reactants and inflammatory whole-blood transcripts and transcriptional pathways. The proband had predicted damaging gene variants of NLRP3 and of inter-α trypsin inhibitor heavy chain 3, an inhibitor of lubricin-degrading cathepsin G. Changes in the proband's serum protein interactome network supported enhanced lubricin degradation, with cathepsin G activity increased relative to its inhibitors, SERPINB6 and thrombospondin 1. Activation of Toll-like receptor 2 (TLR-2) suppressed levels of lubricin mRNA and lubricin release in cultured human synovial fibroblasts (P < 0.01). Lubricin blunted urate crystal precipitation and IL-1ß induction of xanthine oxidase and urate in cultured macrophages (P < 0.001). In lubricin-deficient mice, injection of IL-1ß in knees increased xanthine oxidase-positive synovial resident M1 macrophages (P < 0.05). CONCLUSION: Our findings linked normouricemic erosive gout to attenuated lubricin, with impaired control of cathepsin G activity, compounded by deleterious NLRP3 variants. Lubricin suppressed monosodium urate crystallization and blunted IL-1ß-induced increases in xanthine oxidase and urate in macrophages. The collective activities of articular lubricin that could limit incident and erosive gouty arthritis independently of hyperuricemia are subject to disruption by inflammation, activated cathepsin G, and synovial fibroblast TLR-2 signaling.

Assessment of thiopurine S-methyltransferase activity in patients prescribed thiopurines: a systematic review.

BACKGROUND: The evidence for testing thiopurine S-methyltransferase (TPMT) enzymatic activity or genotype before starting therapy with thiopurine-based drugs is unclear. PURPOSE: To examine the sensitivity and specificity of TPMT genotyping for TPMT enzymatic activity, reducing harm from thiopurine by pretesting, and the association of thiopurine toxicity with TPMT status in adults and children with chronic inflammatory diseases. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library, and Ovid HealthSTAR (from inception to December 2010) and BIOSIS and Genetics Abstracts (to May 2009). STUDY SELECTION: Two reviewers screened records and identified relevant studies in English. DATA EXTRACTION: Data on patient characteristics, outcomes, and risk for bias were extracted by one reviewer and independently identified by another. DATA SYNTHESIS: 54 observational studies and 1 randomized, controlled trial were included. Insufficient evidence addressed the effectiveness of pretesting. Genotyping sensitivity to identify patients with low and intermediate TPMT enzymatic activity ranged from 70.33% to 86.15% (lower-bound 95% CI, 54.52% to 70.88%; upper-bound CI, 78.50% to 96.33%). Sparse data precluded estimation of genotype sensitivity to identify patients with low to absent enzymatic activity. Genotyping specificity approached 100%. Compared with noncarriers, heterozygous and homozygous genotypes were both associated with leukopenia (odds ratios, 4.29 [CI, 2.67 to 6.89] and 20.84 [CI, 3.42 to 126.89], respectively). Compared with intermediate or normal activity, low TPMT enzymatic activity was significantly associated with myelotoxicity and leukopenia. LIMITATION: Available evidence was not rigorous and was underpowered to detect a difference in outcomes. CONCLUSION: Insufficient evidence addresses the effectiveness of TPMT pretesting in patients with chronic inflammatory diseases. Estimates of the sensitivity of genotyping are imprecise. Evidence confirms the known associations of leukopenia or myelotoxicity with reduced TPMT activity or variant genotype. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Limited added value of whole spine MRI in spondyloarthritis for disease activity assessment.

OBJECTIVE: To evaluate the added value of whole spine magnetic resonance imaging (MRI) for disease activity assessment in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHOD: Spine and sacroiliac joint (SIJ) MRI scans requested by rheumatologists between 2012 and 2018 were screened retrospectively, and patients who had known diagnosis of AS or PsA were included, if the MRI was done for disease activity assessment. All MRI scans were reviewed by two experienced musculoskeletal radiologists independently, blinded to patients' diagnosis and to the other MRI. Comparisons were done for the presence of active and structural lesions. In addition, radiologists were asked to rate for "confidence level for active inflammation related to SpA." Analysis was done using the consensus scores. RESULTS: Ninety patients with known diagnosis of AS (n = 55) or PsA (n = 35) were included. The frequency of active and structural lesions was not significantly different both in AS vs PsA, neither in the cervical/thoracic/lumbar spine or the SIJ. The percentage of people only with any inflammatory changes on the spine MRI without any inflammation in the SIJ MRI was 24% in AS and 23% in PsA. However, considering the confidence level of the radiologists on active inflammation, only one patient's spine MRI was scored as active, while SIJ MRI being negative for inflammation. CONCLUSIONS: The spinal MRI had limited added value to the SIJ MRI in SpA, when performed to assess disease activity, limiting its value in routine practice unless clinically indicated. Key Points • Spine MRI adds limited value to SIJs in SpA, when performed for disease activity assessment. • SpA disease activity assessment may be restricted to sacroiliac joint MRI, unless clinically indicated.

Canadian Rheumatologists' Perspectives on Moderate Psoriatic Arthritis and Oligoarticular Psoriatic Arthritis.

OBJECTIVE: Psoriatic arthritis (PsA) substantially impairs quality of life. Clinical trials generally focus on polyarticular PsA, but less is known about the assessment and management of oligoarticular and moderate PsA. An online survey was conducted to determine Canadian rheumatologists' perspectives on the definition and treatment of oligoarticular and moderate PsA. METHODS: Regional and national experts treating patients with PsA were asked to complete an online survey to assess their approach to identifying and managing patients with PsA. Survey questions were developed based on guidance from a committee of Canadian rheumatologists. RESULTS: Sixty-four of 78 rheumatologists responded, representing 6 major Canadian provinces. Nearly half of respondents were in practice > 20 years. The majority of rheumatologists reported using swollen joint count (SJC) to describe moderate PsA (86.4%) and oligoarticular PsA (96.7%), and considered location of inflammation in PsA assessments. SJC cutoff scores for reporting moderate PsA varied among rheumatologists, suggesting lack of an agreed-upon definition for moderate PsA. Sixty-eight percent of rheumatologists identified access to treatment as the greatest challenge with oligoarticular PsA. CONCLUSION: According to the surveyed rheumatologists, SJC remains a key assessment variable when defining oligoarticular and moderate PsA. Although the number of joints is considered when determining the effect of PsA on patients, joint location and functional impairment are also considered when describing the disease as moderate. Access to treatment for patients with < 5 affected joints is challenging.

Successful prevention of thrombotic thrombocytopenic purpura (TTP) relapse using monthly prophylactic plasma exchanges throughout pregnancy in a patient with systemic lupus erythematosus and a prior history of refractory TTP and recurrent fetal loss.

BACKGROUND: The occurrence of thrombotic thrombocytopenic purpura (TTP) in the setting systemic lupus erythematosus (SLE) is rare. In women of childbearing age, TTP is associated with high rates of recurrence in pregnancy. Furthermore, both TTP and SLE are associated with a significant risk of adverse pregnancy outcomes. CASE PRESENTATION: We describe the case of a 36 year old female in her first trimester of pregnancy with a prior history of SLE-associated severe refractory TTP who was treated with a combination of corticosteroids and prophylactic plasma exchanges (PLEX) throughout pregnancy to prevent TTP recurrence. She delivered a healthy infant at 33 weeks of gestation after the onset of preterm labor. There was no evidence of TTP recurrence in the antepartum or postpartum period in this high risk patient. CONCLUSION: Prophylactic PLEX should be considered as a therapeutic option to prevent recurrent TTP during pregnancy in high risk patients, including patients with previous SLE-associated TTP.

Accuracy of Physical Examination to Detect Synovial and Extra-Synovial Pathologies in Psoriatic Arthritis in Comparison to Ultrasonography.

We aimed to explore the accuracy of physical examination (PE) to detect the synovial and extra-synovial pathologies in psoriatic arthritis (PsA) in comparison to ultrasonography (US). Twenty-nine PsA patients with hand pain were included in the study. A detailed PE of the hands was performed and US scans were performed for the joints, extensor and flexor tendons, and entheses of the second to fifth fingers of both hands. The agreement between PE and US findings was calculated. The strongest agreement for the joints was between "swollen joints" and power Doppler (PD) signals in the metacarpophalangeal (MCP) joints and grey scale synovitis in the proximal interphalangeal (PIP) joints. The agreement of tender entheses on PE and inflammation on US (hypoechogenicity, thickening, and/or PD signals) was poor for both extensor (Kappa = -0.027, Prevalence Adjusted and Bias Adjusted Kappa (PABAK) = 0.344) and flexor compartments (Kappa = 0.039, PABAK = 0.569). Similar to enthesitis, comparison of any PE and US findings showed a poor agreement at the extensor and flexor tendon regions (extensor: Kappa = 0.123, PABAK = 0.448, and flexor: Kappa = 0.171, PABAK = 0.431). Our study showed that there was a poor to fair agreement of PE and US findings of hands. US can add value when determining the source of pain in PsA in the small joints.

Psoriasis is an independent risk factor for entheseal damage in axial spondyloarthritis.

OBJECTIVES: To understand whether psoriasis has disease modifying effects on disease features and/or severity of enthesitis and spine disease in axial SpA (axSpA). METHODS: Patients with a diagnosis axSpA were included. Demographics, patient and physician reported outcomes were collected. Radiographic damage in the spine was assessed using modified Ankylosing Spondylitis Spine Score (mSASSS). Twelve entheses of the upper and lower extremity were assessed using ultrasound, focusing on inflammation and damage separately. The association between mSASSS, enthesitis scores and extra-articular manifestations such as psoriasis was analyzed using linear regression analysis. RESULTS: Among 120 axSpA patients 114 (95%) had axSpA according to The Assessment of SpondyloArthritis international Society (ASAS) criteria. Sixty-two were classified as ankylosing spondylitis (AS), fulfilling the modified New York criteria. Thirty-one patients had psoriasis. For spinal damage, entheseal damage was an independent and the strongest predictor (B = 0.52, p = 0.025), in addition to longer disease duration (B = 0.22, p = 0.045) and male gender (B = 6.1, p = 0.041) but not psoriasis. For enthesitis, psoriasis was found as an independent risk factor to increase the entheseal damage (B = 4.38, p = 0.009), in addition to age (B = 0.17, p = 0.007), male gender (B = 2.8, p = 0.032), mSASSS (B = 0.11, p = 0.035) and body mass index (B = 0.57, p < 0.001), but not entheseal inflammation (B = 2.0, p > 0.05) when corrected for HLA-B27. CONCLUSIONS: Psoriasis is an independent risk factor to increase the severity of entheseal damage, but not spinal damage. Peripheral enthesitis predicts spinal damage, regardless of the subtypes of SpA.

Comparison of Female Sexual Function Index in patients with psoriatic and rheumatoid arthritis and healthy controls.

OBJECTIVE: The aim of the recent study was to identify and compare the Female Sexual Function Index (FSFI) of three female populations: those with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and healthy individuals. METHODS: In this descriptive correlational study, convenience sampling was used to recruit 50 female RA patients, 36 female PsA patients and 50 healthy women between June and September 2018. RESULTS: The mean ages of the RA patients, PsA patients and healthy controls were, respectively, 53.1 ± 11.8 years, 51.6 ± 13.7 years and 37.4 ± 10.4 years. Controls were significantly younger than RA (p < 0.001) and PsA (p = 0.002) patients. Data including all participants: Based on the total sexual functioning cut-off score of 26.55, 68% of RA patients (34/50), 67% of PsA patients (22/33) and 44% of healthy controls (11/25) met the criteria for sexual dysfunction. Data excluding participants who reported not having had sex in the previous month: Controls had significantly higher FSFI scores than the RA patients across all six domains (p ≤ 0.001) and the overall score (p < 0.001). Controls had significantly higher FSFI scores than the PsA patients across four of the six domains (p ≤ 0.026) and the overall score (p = 0.008). There were no statistically significant differences between the RA and PsA groups. Patient pain, patient global status and Health Assessment Questionnaire scores were not significantly correlated with the total FSFI score in either PsA or RA. CONCLUSIONS: These findings demonstrate that decreased sexual functioning is more common in women with RA and PsA when compared with controls. All female patients with RA and PsA should be screened for sexual dysfunction.

What does evidence-based medicine tell us about treatments for different subtypes of psoriatic arthritis? A systematic literature review on randomized controlled trials.

OBJECTIVE: PsA is a heterogeneous disease with various subtypes of joint manifestations, which can affect the homogeneity of randomized controlled trials (RCTs). The aim of this systematic literature review was to evaluate the inclusion criteria, demographics and outcomes of RCTs to see whether the whole spectrum of PsA was represented. METHODS: Medline, EMBASE and Cochrane databases were screened for RCTs on the efficacy of any treatment for PsA up to 4 October 2016 to investigate the inclusion criteria, demographics, outcomes and efficacy. RESULTS: Two thousand and sixty-eight abstracts were identified at screening; 76 articles and 52 conference proceedings were included in the final analysis. The main inclusion criteria always included the number of active joints and never axial symptoms, enthesitis nor dactylitis. Only 10 studies provided information about subtypes, of which symmetrical polyarthritis was the main subtype. Mean (s.d.) tender and swollen joints were between 7.8 and 35.8 (1.8-22.1) and between 5.2 and 25.2 (1.5-16.2), respectively. All studies had responses in joint counts as their primary outcome. Responses in enthesitis and dactylitis were usually secondary or tertiary outcomes. Response in BASDAI was among the outcomes in four studies. The comparison of efficacy in polyarticular vs oligoarticular disease was given in three studies, whereas no information was available for DIP joint disease or arthritis mutilans. CONCLUSION: There is evidence in the literature to guide clinicians on how to treat PsA patients with polyarticular disease, but there is a gap in knowledge about the other subtypes. PROTOCOL REGISTRATION: The study protocol is registered at PROSPERO (CRD42017053907).