Ponatinib Inducing a Panuveitis with Choroidal Effusions and Neurosensory Retinal Detachment in a Patient with Chronic Myeloid Leukaemia.

CASE SUMMARY: We present the case of a 50 year old male patient being treated for chronic myeloid leukemia by the tyrosine kinase inhibitor, Ponatinib. After 3 months of treatment, he developed a sight-threatening granulomatous panuveitis in both eyes, with choroidal effusions and neurosensory retinal detachments. Except for a positive interferon-gamma release assay suggesting previous Tuberculosis exposure, all uveitis investigations were normal. Discontinuation of the suspected causative drug led to resolution of signs and a consequent improvement in visual acuity. CONCLUSION: Ponatinib use may be associated with with a uveitic phenotype that is reminiscent of Harada's disease. We compare and contrast this rare ocular phenomenon with Vogt-Koyanagi-Harada syndrome and discuss a possible immunological basis.

Assessment of two screening tools to identify psoriatic arthritis in patients with psoriasis.

BACKGROUND: Many patients with psoriasis have undiagnosed psoriatic arthritis. Low specificity is found with many PsA screening tools. A new instrument, the CONTEST questionnaire, was developed utilizing the most discriminative items from existing instruments. OBJECTIVE: The aim of this study was to compare the CONTEST and PEST screening tools. METHODS: People attending secondary care clinics with psoriasis, but not PsA, completed the questionnaires, were assessed for function and quality of life, and had a physical examination. Patients thought to have PsA were compared to those without. The performance of CONTEST and PEST was compared using area under the receiver operating curve (AUC), and sensitivity and specificity at the previously published cut-offs. RESULTS: A total of 451 dermatology patients were approached, 35% were reviewed and 27 (17%, 95% CI 12.3-21.7) had unidentified psoriatic arthritis. The sensitivity and specificity (95% CI) of PEST were 0.60 (0.42-0.78)/0.76 (0.69-0.83) and for CONTEST 0.53 (0.34-0.72)/0.71 (0.63-0.79). The confidence limits for the AUC overlapped (AUC for PEST 0.72 (0.61-0.84), for CONTEST 0.66 (0.54-0.77). CONCLUSIONS: PEST and CONTEST questionnaires performed equally well, with no superiority of the new CONTEST tool.

Use of optical coherence tomography for the diagnosis of preclinical lesions of circumscribed palmar hypokeratosis.

Circumscribed hypokeratosis of palms and soles is a rare dermatosis, usually affecting women. Diagnosis is mainly based on the clinical characteristics, including the clinical appearance and anatomical site of the skin lesions and on the demographic features of the affected patients, usually middle-aged to elderly women. Skin biopsy may be performed to confirm clinical diagnosis. Optical coherence tomography (OCT) is a technique that has been undergone substantial development in dermatology in recent years, and its use in clinical practice has been growing progressively. Several dermatological conditions have been studied with this tool, but to our knowledge, it has not been used to investigate this form of hypokeratosis. We report a case of circumscribed palmar hypokeratosis for which diagnosis was confirmed by OCT, which was performed as the patient was reluctant to undergo skin biopsy because of its invasiveness. We highlight the potential use of OCT in obtaining a virtual skin biopsy to confirm clinical diagnosis and identify preclinical skin lesions amenable to early treatment.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Differential expression of antimicrobial peptides in psoriasis and psoriatic arthritis as a novel contributory mechanism for skin and joint disease heterogeneity.

OBJECTIVES: This study tested the hypothesis that a differential innate immune antimicrobial peptide (AMP) profile was evident between the skin and joints in psoriasis and psoriatic arthritis (PsA) and that PsA synovitis may have a distinct AMP pattern compared to other arthropathies. METHOD: Twenty-two cases had knee biopsies [10 PsA, eight rheumatoid arthritis (RA), and four osteoarthritis (OA)]. Lesional and non-lesional skin biopsies in psoriasis and control tissue were also obtained (n = 4 each). Immunohistochemistry with semi-quantitative scoring of both synovium and skin was performed using the following panel of AMPs: S100 A8, S100 A9, human neutrophil peptides 1-3 (HNP1-3), human ß-defensins 2 and 3 (hBD-2 and hBD-3), cathelicidin LL-37, psoriasin (S100 A7), and ribonuclease 7 (RNase 7). RESULTS: Similar expression of S100 A8, S100 A9, and HNP1-3 was detectable in PsA and RA synovium but only in the synovium sublining layer (SSL). No expression of psoriasin, RNase 7, hBD-2, and hBD-3 could be detected in the synovial tissue of PsA, RA, or OA. All psoriasis skin samples exhibited broad expression of all investigated AMPs, with strong keratinocyte expression. CONCLUSIONS: Given that some AMPs, especially hBD-2, are genetically linked to psoriasis and are only expressed in the skin, these findings show how differential AMP expression in innate immune responses may contribute to disease heterogeneity between PsA and psoriasis and provides a genetic basis for the non-progression of psoriasis subgroups to PsA.

Role of vascular channels as a novel mechanism for subchondral bone damage at cruciate ligament entheses in osteoarthritis and inflammatory arthritis.

OBJECTIVES: The purpose of this work was to test whether normal peri-entheseal vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was associated with distribution of peri-entheseal bone erosion/bone marrow lesions (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA). METHODS: Normal microanatomy was defined histologically in mice and by 3 T MRI and histology in 21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27 patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced arthritis (AIA) in mice was evaluated to ascertain whether putative peri-entheseal vascular regions influenced osteitis and bone erosion. RESULTS: Vascular channels penetrating cortical bone were identified in knees of non-arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers, vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were observed. Histology of 10 macroscopically normal cadaveric specimens confirmed the location of vascular channels and associated subclinical changes including subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA model, vascular channels clearly provided a site for inflammatory tissue entry and osteoclast activation. MRI showed BMLs in the same topographic locations in both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%). CONCLUSION: The findings show that normal ACL and PCL entheses have immediately adjacent vascular channels which are common sites of subtle bone marrow pathology in non-arthritic joints. These channels appear to be key determinants in bone damage in inflammatory and degenerative arthritis.

Mesenchymal stem cells, autoimmunity and rheumatoid arthritis.

The vast majority of literature pertaining to mesenchymal stem cells (MSC) immunomodulation has focussed on bone marrow-derived MSC that are systemically infused to alleviate inflammatory conditions. Rheumatoid arthritis (RA) is the commonest autoimmune joint disease that has witnessed significant therapeutic advances in the past decade, but remains stubbornly difficult to treat in a subset of cases. Pre-clinical research has demonstrated that bone marrow, adipose, synovial and umbilical cord-derived MSC all suppress the functions of different immune cells thus raising the possibility of new therapies for autoimmune diseases including RA. Indeed, preliminary evidence for MSC efficacy has been reported in some cases of RA and systemic lupus erythromatosis. The potential use of bone marrow-MSC (BM-MSC) for RA therapy is emerging but the use of synovial MSC (S-MSC) to suppress the exaggerated immune response within the inflamed joints remains rudimentary. Synovial fibroblasts that are likely derived from S-MSCs, also give rise to a cell-cultured progeny termed fibroblast-like synoviocytes (FLS), which are key players in the perpetuation of joint inflammation and destruction. A better understanding of the link between these cells and their biology could be a key to developing novel MSC-based strategies for therapy. The review briefly focuses on BM-MSC and gives particular attention to joint niche synovial MSC and FLS with respect to immunoregulatory potential therapy roles.

European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies.

BACKGROUND: Psoriatic arthritis (PsA) is a clinically heterogeneous disease. Clear consensual treatment guidance focused on the musculoskeletal manifestations of PsA would be advantageous. The authors present European League Against Rheumatism (EULAR) recommendations for the treatment of PsA with systemic or local (non-topical) symptomatic and disease-modifying antirheumatic drugs (DMARD). METHODS: The recommendations are based on evidence from systematic literature reviews performed for non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, synthetic DMARD and biological DMARD. This evidence was discussed, summarised and recommendations were formulated by a task force comprising 35 representatives, and providing levels of evidence, strength of recommendations and levels of agreement. RESULTS: Ten recommendations were developed for treatment from NSAID through synthetic DMARD to biological agents, accounting for articular and extra-articular manifestations of PsA. Five overarching principles and a research agenda were defined. CONCLUSION: These recommendations are intended to provide rheumatologists, patients and other stakeholders with a consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes, based on combining evidence and expert opinion. The research agenda informs directions within EULAR and other communities interested in PsA.

The use of the reamer-irrigator-aspirator to harvest mesenchymal stem cells.

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a 'waste' bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA. The solid fraction from the filtrate was digested for 60 minutes at 37° C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105). MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 µl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114,983 (16,500 to 477,750), RIA-solid = 12,785 (7210 to 28 475). The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.

Large-scale extraction and characterization of CD271+ multipotential stromal cells from trabecular bone in health and osteoarthritis: implications for bone regeneration strategies based on uncultured or minimally cultured multipotential stromal cells.

OBJECTIVE: To test the hypothesis that CD45(low)CD271+ bone marrow multipotential stromal cells (MSCs) are abundant in the trabecular bone niche and to explore their functional "fitness" in health and osteoarthritis (OA). METHODS: Following enzymatic extraction, MSC release was evaluated using colony-forming unit-fibroblast (CFU-F) and colony-forming unit-osteoblast assays, flow cytometry, and confocal microscopy. CD45(low)CD271+ cells isolated by fluorescence-activated cell sorting were enumerated and expanded under standard and clonal conditions. Their proliferative and osteogenic potencies were assessed in relation to donor age and compared with those of aspirated CD45(low)CD271+ cells. In vitro and in vivo MSC "aging" was measured using quantitative polymerase chain reaction-based telomere length analysis, and standard differentiation assays were utilized to demonstrate multipotentiality. RESULTS: Cellular isolates from trabecular bone cavities contained approximately 65-fold more CD45(low)CD271+ cells compared with aspirates (P < 0.0001) (median 1.89% [n = 39] and 0.029% [n = 46], respectively), concordant with increased CFU-F release. Aspirated and enzymatically released CD45(low)CD271+ cells had identical MSC phenotypes (approximately 100% CD73+CD105+CD13+, approximately 50-60% CD146+CD106+CD166+) and contained large proportions of highly clonogenic multipotential cells. In vitro osteogenic potency of freshly isolated CD45(low)CD271+ cells was comparable with, and often above, that of early-passage MSCs (8-14%). Their frequency and in vivo telomere status in OA bone were similar to those in bone from age-matched controls. CONCLUSION: Our findings show that CD45(low)CD271+ MSCs are abundant in the trabecular bone cavity and indistinguishable from aspirated CD45(low)CD271+ MSCs. In OA they display aging-related loss of proliferation but no gross osteogenic abnormality. These findings offer new opportunities for direct study of MSCs in musculoskeletal diseases without the requirement for culture expansion. They are also relevant for direct therapeutic exploitation of prospectively isolated, minimally cultured MSCs in trauma and OA.

The fatty Romanus lesion: a non-inflammatory spinal MRI lesion specific for axial spondyloarthropathy.

BACKGROUND: Fatty changes at vertebral corners have been reported on MRI in ankylosing spondylitis but the distribution or specificity of these lesions to early axial spondyloarthropathy (axial-SpA) has not been determined. OBJECTIVE: To assess the diagnostic utility of fatty Romanus lesions (FRLs) for axial-SpA in a population with chronic back pain. METHODS: Axial-skeleton TI SE and fat-suppressed MRI were performed on 174 patients with back pain and 11 controls. MRI lesions including FRLs were scored blind. An imaging diagnosis was given on MRI findings alone and compared with the 'gold standard' treating doctor's diagnosis. RESULTS: Twenty-nine patients had FRLs: 31% (20/64) of patients with spondyloarthropathy, 13% (6/45) with degenerative arthritis, 4% (2/45) with spinal malignancy, 5% (1/20) with 'other' diagnoses; none of 11 normal subjects had FRLs. The majority of the FRLs in SpA 60% (135/226) were present in the thoracic spine. The diagnostic utility of FRLs for SpA (likelihood ratio (LR) = 4.7) was significantly (p<0.05) greater than for other diagnoses and increased further (LR = 12.6, p<0.05) when more than five FRLs were present. Of note 5/20 (25%) patients with SpA with FRLs had no diagnostic bone-oedema lesions on fat-suppressed MRI, suggesting that FRLs may be useful diagnostically in axial-SpA. CONCLUSION: This study defines the FRL as a diagnostic imaging feature of axial-SpA, which may be useful where inflammatory changes are absent on fat-suppression MRI and where radiography is normal.

Mesenchymal stem cells in rheumatoid synovium: enumeration and functional assessment in relation to synovial inflammation level.

OBJECTIVE: Achieving joint regeneration in rheumatoid arthritis (RA) represents a future challenge. Autologous synovial mesenchymal stem cells (MSCs) could be therapeutically exploited. However, the inflammatory milieu in the RA synovium could adversely affect endogenous MSC function. To test this hypothesis, the frequency and multipotency of RA synovial MSCs was evaluated in relation to existing synovial inflammation. METHODS: Synovial inflammation was measured using the arthroscopic visual analogue score (VAS) and further validated using immunohistochemistry and flow cytometry. Highly proliferative clonogenic in vivo MSCs were enumerated following fluorescence-activated cell sorting and expansion for 20 population doublings. MSC multipotency was quantified following standard in vitro culture expansion and trilineage differentiation assays. Real-time PCR, flow cytometry and ELISA were used to evaluate pro- and anti-chondrogenic molecules in standard polyclonal synovial MSCs. RESULTS: The arthroscopic VAS significantly correlated with synovial macrophage infiltration. In RA, synovial MSC chondrogenesis was inhibited in direct relation to VAS (r = -0.777, p<0.05) and reduced compared with control osteoarthritis (OA)-MSCs (p<0.05). In vivo, MSCs resided in the synovial fibroblastic/stromal fraction (CD45(-)CD31(-)) and were reduced in frequency in relation to VAS (r = -0.695, p<0.05). In RA-MSCs, CD44 levels correlated negatively with inflammation and positively with chondrogenesis (r = -0.830 and r = 0.865, respectively). Cytokine production and Sox9 expression was similar in RA-MSCs and OA-MSCs. CONCLUSIONS: There is a negative relationship between synovial MSC chondrogenic and clonogenic capacities and the magnitude of synovitis in RA. Effective suppression of joint inflammation is therefore necessary for the development of autologous MSC treatments aimed at cartilage regeneration in RA.

Enthesitis: an autoinflammatory lesion linking nail and joint involvement in psoriatic disease.

The traditional model for psoriasis and psoriatic arthritis (PsA) is that autoimmunity directed against a common skin and joint autoantigen leads to chronic autoreactive T cell driven inflammation. However, recent imaging, histological and genetic studies have challenged this view, especially with respect to joint and nail disease, and provide a broader insight into the pathogenesis of PsA and associated nail involvement. Clinically unrecognized enthesitis (inflammation at tendon and ligament attachments) is commonly seen in early PsA at all sites of the disease. Specifically, enthesitis is associated with adjacent osteitis or bone and synovial inflammation. Even in normal joints, normal insertions are associated with microdamage and inflammatory change, strongly suggesting that local tissue specific, or what has been described as autoinflammatory factors, may dictate disease expression. Distal interphalangeal (DIP) joint disease in PsA is associated with diffuse inflammation that envelops the nail root and adjacent bone. In fact, the nail is intimately linked to entheses, with the extension tendon of the DIP joint sending fibres from bone that envelop the nail root in an interdigitating fashion. Furthermore, the joint collateral ligament enthesis has fibres that merge with the lateral borders of the nail. Other anchorage mechanisms include fibres that directly tether the nail plate to the underlying periosteum, which itself is closely anchored to the extension tendon. The frequent microdamage and tissue repair at normal enthesis attachment sites in healthy joints has resulted in a proposed new model of PsA pathogenesis embracing the concept of autoinflammation, whereby tissue specific factors, including microtrauma, lead to regional innate immune activation and persistent inflammation, as an alternative to primary immunopathology driven by T and B cell abnormalities. Unlike the classical autoimmune diseases, which may attack a completely normal organ, autoimmunity in psoriatic disease is likely to involve tissues where there is intrinsic dysregulation of the target tissues. These tissue specific factors related to the enthesis appear to be key to the phenotypic expression of diseases hitherto regarded as autoimmune. The pathogenesis of PsA, nail disease and to a lesser extent psoriasis therefore appear to have an autoinflammatory (innate immune driven) rather than autoimmune basis. Taken together, these findings are important for better understanding PsA, nail disease and psoriasis, and for conceptualizing the immunopathogenic basis of these diseases and further exploring the role of enthesitis in their pathophysiology.

Evaluation of the diagnostic utility of spinal magnetic resonance imaging in axial spondylarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI) is increasingly used for the diagnosis of axial spondylarthritis (SpA), but it is unknown whether characteristic lesions are actually specific for SpA. This study was undertaken to compare MRI patterns of disease in active SpA, degenerative arthritis (DA), and malignancy. METHODS: Fat-suppressed MRI of the axial skeleton was performed on 174 patients with back pain and 11 control subjects. Lesions detected by MRI, including Romanus lesions (RLs) and end-plate, diffuse vertebral body, posterior element, and spinous process bone marrow edema (BME) lesions, were scored in a blinded manner. An imaging diagnosis was given based on MRI findings alone, and this was compared with the gold-standard treating physician's diagnosis. RESULTS: The physician diagnosis was SpA in 64 subjects, DA in 45 subjects, malignancy in 45 subjects, other diagnoses in 20 subjects, and normal in 11 subjects. There was 72% agreement between the imaging diagnosis and physician diagnosis. End-plate edema, degenerative discs, and RLs were frequently observed in patients with any of the 3 major diagnoses. Single RLs were of low diagnostic utility for SpA, but >or=3 RLs (likelihood ratio [LR] 12.4) and severe RLs (LR infinite) in younger subjects were highly diagnostic of SpA. Posterior element BME lesions of mild or moderate grade were also highly diagnostic of SpA (LR 14.5). The most common diagnostic confusion was between SpA and DA, since both had RLs present and the presence/absence of degenerative discs did not change the diagnostic assessment. CONCLUSION: This study confirms the high diagnostic utility of MRI in axial SpA, with severe or multiple RLs evident on MRI being characteristic in younger patients and mild/moderate posterior element lesions being specific for SpA. However, MRI lesions previously considered to be characteristic of SpA could also be found frequently in patients with DA and patients with malignancy, and therefore such lesions should be interpreted with caution, particularly in older patients.

Magnetic resonance imaging in the assessment of metacarpophalangeal joint disease in early psoriatic and rheumatoid arthritis.

OBJECTIVES: The aim of this study was to determine whether magnetic resonance imaging (MRI)-related entheseal changes including osteitis and extracapsular oedema could be used to differentiate between metacarpophalangeal (MCP) joint involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: Twenty patients (10 each with early RA and PsA) had dynamic contrast-enhanced MRI (DCE-MRI) of swollen MCP joints. Synovitis and tenosynovitis was calculated using quantitative analysis including the degree and kinetics of enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Periarticular bone erosion and bone oedema were scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) proposals. Entheseal-related features including extracapsular soft tissue enhancement or regions of diffuse bone oedema were also evaluated. RESULTS: MRI was not able to differentiate at the group level between both cohorts on the basis of entheseal-related disease but a subgroup of PsA patients had diffuse extracapsular enhancement (30%) or diffuse bone oedema (20%). The RA patient group had a greater degree of MCP synovitis (p<0.0001) and tenosynovitis than PsA patients (p<0.0001). There were no significant differences in either the total number of erosions (p = 0.315) or the presence of periarticular bone oedema (p = 0.105) between the groups. CONCLUSION: Although conventional MRI shows evidence of an enthesitis-associated pathology in the MCP joints in PsA, this is not sufficiently common to be of diagnostic utility.

Evidence for a distinctive pattern of bone formation in enthesophytes.

OBJECTIVES: The mechanism of new bone formation at entheses in spondyloarthritis (SpA) is poorly understood, but it is a key factor contributing to disability in disease. As bony spur development is also an age-related phenomenon, spurs in elderly dissecting room cadavers were studied in order to establish general principles relating to their development. METHODS: Spurs of different sizes were studied by routine histology at 26 different entheses (a total of 76 specimens) from the upper limb, lower limb and spine. The percentage of bone:marrow was compared in the posterior part of the calcaneus in cadavers with and without Achilles spurs to ascertain the relationship between spurs and immediately adjacent trabecular bone. RESULTS: Bony spur formation was a common age related phenomena and typically occurred in the most fibrous part of an enthesis. Paradoxically, it was often heralded by the initial appearance of a thick zone of calcified fibrocartilage that subsequently developed bony nodules within it. Uncalcified fibrocartilage was more prominent around large spurs. Endochondral, intramembranous and chondroidal ossification all contributed to spur formation and growth, but cell hypertrophy and florid vascular invasion of a cellular calcified cartilage, typical of endochondral ossification, were not conspicuous features. CONCLUSION: Entheseal new bone formation occurs by a combination of three methods of ossification. However, endochondral ossification was atypical and differed from that seen in the normal development of cartilage bones or during fracture healing. How the inflammatory process modulates these processes could lead to a better understanding of entheseal new bone formation in SpA.

MRI and clinical findings in patients with ankylosing spondylitis eligible for anti-tumour necrosis factor therapy after a short course of etoricoxib.

OBJECTIVE: To describe and assess the response to short-term etoricoxib as shown by MRI and clinical variables in patients with ankylosing spondylitis (AS) selected for eligibility for anti-tumour necrosis factor therapy. METHODS: In a 6-week open-label study, 22 patients with AS and eligible for biological therapy were treated with 90 mg of etoricoxib daily. Clinical and laboratory parameters were obtained and MRI of the sacroiliac joints and the lower thoracic and lumbar spine performed at baseline and at week 6. The primary end point was the proportion of patients fulfilling the SpondyloArthritis international Society (ASAS) response criteria for biological therapies (ASASBIO) while secondary end points included the change in MRI-determined bone lesions. RESULTS: Eight of 20 completers improved enough to meet the ASASBIO response criteria and most clinical variables improved significantly. Fifteen patients had a total of 63 MRI-detectable lesions; overall, 13/60 lesions with paired scans either resolved completely or improved, while five lesions worsened or appeared during treatment. CONCLUSION: Etoricoxib is an effective symptomatic treatment for patients with AS; however, its effect on MRI-detected lesions is small. Further studies are needed to determine the effect of etoricoxib on MRI-determined bone oedema.