Deepak Jadon

Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas

Objective  Reports suggest that up to 70% of patients with microprolactinomas treated with dopamine agonist therapy may achieve long‐term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration of therapy nor is therapeutic interruption universally practised. We have assessed remission rates in a large cohort of treatment‐naive subjects with microprolactinomas. Subjects received dopamine agonist (DA) therapy with either cabergoline or bromocriptine for a period of 2 to 3 years in the majority of cases, followed by a trial of treatment withdrawal.

Smoking and delay to diagnosis are associated with poorer functional outcome in psoriatic arthritis

Objective To identify predictors of poorer physical function in established psoriatic arthritis (PsA). Methods PsA patients with disease duration of ≥10 years were identified from the Bath longitudinal cohort. Physical function was assessed using the Stanford Health Assessment Questionnaire (HAQ). Sex, age at diagnosis, duration of symptoms prior to diagnosis, smoking, treatment and year of diagnosis were included in a multivariable regression analysis to identify associations with HAQ. Results 267 patients were identified for inclusion. The median age was 56 years (IQR 45–63), median disease duration was 13 years (IQR 10–18) and median HAQ score was 0.63 (IQR 0.13–1.25). The model predicted significant increases in HAQ related to smoking (0.23, 95% CI 0.04 to 0.42), age >50 years at diagnosis (0.27, 95% CI 0.03 to 0.51), symptom duration of ≥1 year before diagnosis (0.22, 95% CI 0.02 to 0.42), female sex (0.39, 95% CI 0.20 to 0.57) and history of treatment with an anti-TNF agent (0.63, 95% CI 0.32 to 0.93) at follow-up. Conclusions Smoking, delay to diagnosis, older age at diagnosis, female sex and a history of anti-TNF treatment are associated with worse physical function in established PsA.

The ClASsification for Psoriatic ARthritis (CASPAR) Criteria – A Retrospective Feasibility, Sensitivity, and Specificity Study

Objective. To evaluate the sensitivity, specificity, and feasibility of the ClASsification criteria for Psoriatic ARthritis (CASPAR) to retrospectively classify an existing research cohort. Methods. In total, 480 patient records were reviewed from the Royal National Hospital for Rheumatic Diseases Psoriatic Arthritis (PsA) cohort and for 100 consecutive controls with inflammatory arthritis from a general rheumatology clinic. The CASPAR score was modified for retrospective use; both “inflammation” and “current psoriasis” were recorded as present if they had ever been confirmed in the rheumatology clinic. Sensitivity and specificity of the CASPAR criteria were compared with expert clinical diagnosis. Results. A total of 480 database records were identified. Nine sets of records had been lost or destroyed. The diagnoses had changed in 15 cases, which were transferred to the control arm, leaving 456 patients with an expert diagnosis of PsA. Of 115 controls, 96 had rheumatoid arthritis, 5 osteoarthritis, 3 reactive arthritis, 3 seronegative arthritis, 3 undifferentiated arthralgia, 2 ankylosing spondylitis, 1 spondyloarthritis, and 2 systemic sclerosis. Sensitivity (99.7%) and specificity (99.1%) were both high and equivalent to previous reports. Sensitivity remained high even after inclusion of 7 PsA patients with insufficient data to complete the CASPAR assessment (sensitivity 98.2%, specificity 99.1%). The criteria were found to be easy and practical to apply to case records. Conclusion. Our study demonstrates that the feasibility, specificity, and sensitivity of the CASPAR are maintained when adapted for retrospective use to classify an established research cohort.

Exploring ankylosing spondylitis-associated ERAP1, IL23R and IL12B gene polymorphisms in subphenotypes of psoriatic arthritis

OBJECTIVE To ascertain whether AS-associated polymorphisms of ERAP1, IL23R and IL12B genes associate with subphenotypes of PsA, particularly axial radiographic disease once stratified by HLA-B27 and HLA-Cw*0602 status. METHODS rs30187 (ERAP1 gene), rs6887695 (IL12B gene), rs11209026 and rs7530511 (IL23R gene) single nucleotide polymorphisms were genotyped in 263 PsA cases from a prospective cohort and compared with data from healthy controls (n = 3266-5422). ERAP1 results were stratified according to HLA-B27 and HLA-Cw*0602 status. Investigation of association with age at onset of psoriasis/PsA, arthritic joint count, axial radiographic disease, peripheral radiographic erosions, Psoriasis Area Severity Index, nail score and HAQ was made. RESULTS There was a strong association between rs6887595 (IL12B) and PsA, with homozygosity for the major allele being more frequent in PsA than controls (odds ratio 1.70; 95% CI 1.3, 2.2; P < 0.001). A trend was demonstrated for the minor allele of rs11209026 (IL23R) to be less frequent in patients with erosive joint disease than in those without erosions or controls (7%, 14% and 12%, respectively). None of the polymorphisms associated with the presence of axial radiographic disease or other clinical parameters. CONCLUSION We have confirmed a strong association between rs6887595 (IL12B) and PsA. A trend has been demonstrated between an IL23R variant and peripheral erosive disease. ERAP1 was not associated with axial radiographic disease in PsA. Spinal involvement in PsA may be genetically different from that in AS, which is in keeping with previous observations that the clinical and radiographic pattern of axial disease also differs.

Serum Soluble Bone Turnover Biomarkers in Psoriatic Arthritis and Psoriatic Spondyloarthropathy

Because psoriatic arthritis (PsA) is an inflammatory disease of joints, serum soluble biomarkers specific for chronic joint and bone inflammation may predict future disease severity and response to therapy, thereby informing stratified medicine approaches. The objectives of our systematic review were to determine whether serum soluble bone and cartilage turnover biomarkers are (1) associated with PsA or psoriatic spondyloarthropathy; and (2) associated with disease activity, disease severity, or clinical phenotype. Ten studies met eligibility criteria. Matrix metalloproteinase (MMP)-3, Dickkopf (DKK)-1, macrophage colony-stimulating factor (M-CSF), crosslinked telopeptide of collagen-1, and tumor necrosis factor-related apoptosis-inducing ligand were associated with PsA, with equivocal results for osteoprotegerin (OPG) and bone alkaline phosphatase (ALP). MMP-3, DKK-1, M-CSF, CPII:C2C (ratio of cartilage degradation vs byproduct formation), and possibly OPG were associated with PsA independently of psoriasis. C1-2C (a neoepitope released when type 2 cartilage is degraded by collagenases) was associated with both tender and swollen joint counts, and bone morphogenetic protein-4 with patient global assessment of disease, pain score, and the Bath Ankylosing Spondylitis Disease Activity Index. Bone ALP was associated with disease activity. M-CSF and receptor activator of nuclear factor-κB ligand were associated with several plain radiographic features. No studies have investigated biomarker associations specifically with axial PsA.

Axial Disease in Psoriatic Arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis

Objectives To compare the prevalence, clinical and radiographic characteristics of psoriatic spondyloarthritis (PsSpA) in psoriatic arthritis (PsA), with ankylosing spondylitis (AS). Methods A prospective single-centre cross-sectional observational study recruited consecutive PsA and AS cases. Participants completed outcome measures, and underwent clinical examination, axial radiographic scoring and HLA-sequencing. Multivariable analyses are presented. Results The 402 enrolled cases (201 PsA, 201 AS; fulfilling classification criteria for respective conditions) were reclassified based upon radiographic axial disease and psoriasis, as: 118 PsSpA, 127 peripheral-only PsA (pPsA), and 157 AS without psoriasis (AS) cases. A significant proportion of patients with radiographic axial disease had PsSpA (118/275; 42.91%), and often had symptomatically silent axial disease (30/118; 25.42%). Modified New York criteria for AS were fulfilled by 48/201 (23.88%) PsA cases, and Classification of Psoriatic Arthritis criteria by 49/201 (24.38%) AS cases. pPsA compared with PsSpA cases had a lower frequency of HLA-B*27 (OR 0.12; 95% CI 0.05 to 0.25). Disease activity, metrology and disability were comparable in PsSpA and AS. A significant proportion of PsSpA cases had spondylitis without sacroiliitis (39/118; 33.05%); they less frequently carried HLA-B*27 (OR 0.11; 95% CI 0.04 to 0.33). Sacroiliac joint complete ankylosis (adjusted OR, ORadj 2.96; 95% CI 1.42 to 6.15) and bridging syndesmophytes (ORadj 2.78; 95% CI 1.49 to 5.18) were more likely in AS than PsSpA. Radiographic axial disease was more severe in AS than PsSpA (Psoriatic Arthritis Spondylitis Radiology Index Score: adjusted incidence risk ratio 1.13; 95% CI 1.09 to 1.19). Conclusions In a combined cohort of patients with either PsA or AS from a single centre, 24% fulfilled classification criteria for both conditions. The pattern of axial disease was influenced significantly by the presence of skin psoriasis and HLA-B*27.

Juvenile versus adult-onset ankylosing spondylitis -- clinical, radiographic, and social outcomes. a systematic review.

Ankylosing spondylitis (AS) has 2 main modes of onset: juvenile-onset AS (JoAS) and adult-onset AS (AoAS). It is not known whether JoAS is a subtype of AS, or AS modulated by early age of onset and longer disease duration. We performed a systematic review of the literature, identifying 12 articles and 1 abstract directly comparing JoAS and AoAS cohorts, with observational study design. Patients with JoAS appear to have more peripheral joint involvement both clinically and radiographically (especially knees and ankles) and more root joint involvement (hips and shoulders); they are more likely to proceed to hip arthroplasty and often initially present with peripheral rather than axial symptoms. Patients with AoAS appear to have more axial symptoms and radiographic disease, particularly in the lumbar spine, and worse axial metrology. In terms of other characteristics, more evidence is needed to confidently state whether JoAS and AoAS are different.

Clinical outcomes and progression to orthopedic surgery in juvenile versus adult-onset ankylosing spondylitis

Juvenile‐ and adult‐onset ankylosing spondylitis (AS) are subtypes of AS that may have different clinical outcomes. We compared cohorts of juvenile‐onset AS and adult‐onset AS in terms of clinical characteristics, clinical outcomes, proceeding to AS‐related orthopedic surgery, and type of orthopedic surgery.

Feasibility, reliability, and sensitivity to change of four radiographic scoring methods in patients with psoriatic arthritis

We set out to assess the feasibility, reliability, and sensitivity to change of 4 radiographic scoring methods in psoriatic arthritis (PsA).

Psoriatic Arthritis Mutilans: Characteristics and Natural Radiographic History

Objective. (1) To compare clinical characteristics of patients with psoriatic arthritis (PsA) with PsA mutilans (PAM) and without PAM, and (2) to determine the rate of PAM radiographic progression. Methods. A retrospective cohort study was conducted of all patients with PsA attending a teaching hospital. The most recent hand and feet radiographs were screened for PAM. Serial radiographs (earliest to most recent) were quantitatively scored for osteolysis, erosion, joint space narrowing, and osteoproliferation. Results. Out of the 610 cases, 36 PsA cases had PAM (5.9%). PAM cases were younger at diagnosis of PsA than non-PAM cases (p = 0.04), had more prevalent psoriatic nail dystrophy (OR 5.43, p < 0.001), and worse health assessment questionnaire score (1.25 vs 0.63, p < 0.04). Radiographic axial disease (OR 2.31, adjusted p = 0.03) and especially radiographic sacroiliitis (OR 2.99, adjusted p = 0.01) were more prevalent in PAM. PAM were more likely than non-PAM cases to have used a disease-modifying antirheumatic drug (DMARD; OR 16.36, p < 0.001). Out of 33 cases, 29 PAM cases had initiated a synthetic DMARD and 4/13 had initiated anti-tumor necrosis factor (anti-TNF) prior to first demonstration of PAM. A median 5 radiographs were scored for each PAM case (interquartile range 3–7). PAM progressed from monoarticular (60%) to polyarticular (80%) involvement. Osteolysis was initially rapid and progressive in the hands and feet, tapering later during disease course. Nail dystrophy predicted more severe osteolysis (p = 0.03). Conclusion. Compared with non-PAM cases, PAM cases have earlier age at PsA diagnosis, poorer function, more prevalent nail dystrophy, and more radiographic axial disease/sacroiliitis. The rate of osteolysis is higher in earlier disease, and more severe in those with nail dystrophy. DMARD and anti-TNF therapy appear not to prevent PAM occurrence.