Jacques P.,Ghent University |
McGonagle D.,Chapel Allerton Hospital
Best Practice and Research: Clinical Rheumatology | Year: 2014
Given that entheses are sites of high mechanical stress that concentrate the forces of large contracting muscles down onto a small footprint of bone contact, it was recognized nearly 60 decades ago that stress and injury at such sites may play a role in the pathogenesis of mechanically related enthesopathy. In recent years, the role of mechanical stress and its related consequences on inflammatory enthesitis have also been recognized. Clinical imaging studies and experimental animal models of spondyloarthropathy including tumor necrosis factor (TNF) transgenic models and interleukin (IL)-23 overexpression systems are associated with a primary enthesitis with disease subsequently spreading to adjacent joint structures including the synovium and bone. Joint mechanical stress, without discernible microdamage or injury, leads to spondyloarthritis (SpA) in a TNF transgenic model. Normal-aged human entheses often demonstrate microdamage, but it is unclear whether an abnormal response to mechanical stress alone or the need for stress-induced microdamage is involved in human disease initiation. Clinically, the contribution of mechanical stress to SpA including psoriatic arthritis (PsA) helps conceptualize the disease in a new way and provides obvious mechanistic links to skin and nail Koebner responses. It also offers novel epidemiological explanations for why PsA develops in subjects with high body mass indices most typically in the fourth and fifth decades. Molecularly, the monogenic forms of SpA including caspase recruitment domain-containing protein 14 (CARD14) and IL36RN mutations have site-specific expression of mutated proteins in the skin, thus offering a direct molecular link between local inflammation-related pathway dysregulation and local stress or injury in disease causation. Given that many of the pathways that govern both immunity and mechanical stress including extracellular-signal-regulated kinase (ERK) and mitogen-activated protein kinase (MAPK) are shared, it may be difficult to develop strategies that selectively target mechanical stress-related pathways. However, occupational- and obesity-related factors may be potentially modifiable in susceptible individuals to prevent or ameliorate disease. © 2014 Elsevier Ltd. All rights reserved.
Din O.S.,Weston Park Hospital |
Dodwell D.,University of Leeds |
Wakefield R.J.,Chapel Allerton Hospital |
Coleman R.E.,Weston Park Hospital
Breast Cancer Research and Treatment | Year: 2010
Aromatase inhibitors (Als) are a standard of care for the adjuvant treatment of hormone responsive early carcinoma of the breast as demonstrated in a number of large international phase III randomised trials. Arthralgia was a somewhat unexpected side effect of this class of agents and has proven to be potentially problematic in clinical practice. Although rates of up 35% have been reported in the randomised trials, the figure has been much higher in subsequent case series. There is concern that these symptoms are significant and may affect compliance and thus the overall efficacy of treatment. It is therefore extremely important that we evaluate this syndrome with a view to gaining more information regarding its clinical features and possible aetiological mechanism. The potential aetiological mechanisms and evidence for aromatase inhibitor-induced arthralgia (AIA) are reviewed in this article. Looking forward, it is now important that prospective clinical trials are well designed to evaluate this syndrome and potential therapeutic strategies to circumvent it. Radiological imaging and biochemical analyses may help our understanding of AIA and these are discussed.
Hafiji J.,Skin Cancer Institute |
Salmon P.,Skin Cancer Institute |
Hussain W.,Chapel Allerton Hospital
Journal of the American Academy of Dermatology | Year: 2012
Background: Defects of the distal nose and nasal tip are inherently challenging to reconstruct. Although the bilobed flap has a pivotal role for the closure of such defects to achieve a satisfactory outcome, it demands meticulous planning and execution. Objective: We sought to present our experience of the advancement and inferior rotation of the nasal sidewall (AIRNS) flap as a possible alternative to the bilobed flap for reconstruction of the distal nose. Methods: All patients who underwent AIRNS repair after Mohs tumor extirpation of the nose at 2 regional skin cancer units since April 2011 were reviewed. Results: In all, 45 patients underwent the AIRNS flap repair. There were 25 men and 20 women, with a mean age of 70 years (range 41-88). The average defect size was 1.2 × 1.2 cm. The majority of cases involved the nasal tip. A single case of postoperative infection occurred in a smoker, which resolved without any long-term sequelae. No cases of flap necrosis or nasal airflow obstruction were seen. All cases produced good or excellent cosmetic results. Limitations: Because of blunting of the superior alar crease, which may be avoided in a bilobed repair, the AIRNS flap is best avoided in laterally based defects of the nasal alar. Conclusions: The AIRNS flap is a reliable, single-stage closure option that, in our opinion, is simpler in design and execution compared with the bilobed flap and thus adds to the reconstructive surgeon's armamentarium when faced with centrally located defects of the distal nose.
Nam J.,Chapel Allerton Hospital
Modern rheumatology / the Japan Rheumatism Association | Year: 2010
Treatment outcomes in rheumatoid arthritis (RA) have improved considerably with the use of biological therapies. Since the discovery of the role of tumor necrosis factor (TNF) alpha in the pathogenesis of the disease, three TNF inhibitors, infliximab, etanercept and adalimumab, have become widely used for the treatment of RA. More recently, two newer TNF inhibitors-certolizumab pegol and golimumab-have become available, increasing the armamentarium of therapy. With improved therapies, treatment strategies have also changed, with the aims now being to achieve and maintain remission. This article addresses some of these aspects of treating RA, reviewing the studies on these two newer TNF inhibitors, certolizumab pegol and golimumab, and those addressing the induction of remission or low disease activity with TNF inhibitors and maintenance with less intensive treatment.
Hodgson R.J.,Chapel Allerton Hospital
Orthopaedics and Trauma | Year: 2011
Magnetic resonance imaging is widely used in the investigation of disorders of the musculoskeletal system.When a patient is placed in a strong magnetic field a signal can be obtained, the frequency of which is related to the strength of the magnetic field. By changing the field strength so it depends on location, it is possible to create an image of the patient. The image intensity depends on several inherent properties of the tissues including hydrogen content, and T1 and T2 relaxation times. MRI is uniquely able to control the sensitivity of the image to these properties to generate different types of image contrast, including T1, T2 and proton density weighting, with and without fat suppression. The most appropriate image for a particular application is a compromise between the conflicting requirements of image resolution, time and image quality.A number of artefacts including chemical shift, metal and magic angle artefacts may degrade images of the musculoskeletal system; however these can be minimized by appropriate choice of imaging parameters.Newer techniques such as delayed gadolinium enhanced MRI of cartilage, dynamic contrast enhanced MRI and ultrashort echo time imaging are now becoming available and these further extend the capabilities of MRI. © 2010 Elsevier Ltd.
Rowbotham E.L.,Chapel Allerton Hospital |
Grainger A.J.,Chapel Allerton Hospital
American Journal of Roentgenology | Year: 2011
OBJECTIVE. Rheumatoid arthritis is a predominantly joint-based disease affecting approximately 1% of the world's population. This article will address the increasing use of both ultrasound and MRI in the diagnosis and monitoring of rheumatoid arthritis and will highlight both the strengths and weaknesses of these two imaging modalities, with particular reference to bone erosions and synovitis. CONCLUSION. Because they can detect early disease, both ultrasound and MRI will become increasingly important in the diagnosis and management of rheumatoid arthritis. Future studies with increased patient numbers will be necessary if one of these two modalities is to emerge as a clear winner as the imaging modality of choice. © American Roentgen Ray Society.
Latheef F.,Chapel Allerton Hospital |
Wilkinson S.M.,Chapel Allerton Hospital
Current Opinion in Allergy and Clinical Immunology | Year: 2015
Purpose of review The aim of this review was to examine the current outbreak of cases of contact allergy to methylisothiazolinone in Europe, a phenomenon that has also been observed worldwide, despite initial legislative control of the introduction of methylisothiazolinone into the market. Recent findings Reported allergic contact reactions are primarily eczematous, most commonly in women over 40 from cosmetic use, but there are reports of noneczematous eruptions such as lichen planus-like or lymphomatoid reactions. Methylisothiazolinone in cosmetic, personal care, for example, wet wipe, and household products are the most common exposure. Occupational exposure is represented by workplace use of hygiene (healthcare) and beauty products (hairdressers, beauticians) together with water-based paints and other aqueous solutions such as cutting fluid. Methylisothiazolinone should be patch tested at a concentration of 2000ppm (0.2% aqueous) to maximize sensitivity of the test. Notwithstanding the recommendation to discontinue the use of methylisothiazolinone in leave-on cosmetics, studies suggest safer use of concentrations should also be determined for rinse-off products. Legislation to improve labelling of industrial materials is also required. Going forward there is a need for collaboration between the cosmetic industry and interested physicians to break the recurrent cycle of sensitization to preservatives as one is replaced with another to maintain the risk of sensitization at an acceptably low level. Summary Methylisothiazolinone is particularly relevant at present as strategies to control the outbreak are yet to be enforced and there is no current evidence of the outbreak abating. © 2015 Wolters Kluwer Health, Inc.
Wittmann M.,Chapel Allerton Hospital |
Wittmann M.,University of Bradford |
Helliwell P.S.,Chapel Allerton Hospital
Dermatology and Therapy | Year: 2013
Agents which increase intracellular cyclic adenosine monophosphate (cAMP) may have an antagonistic effect on pro-inflammatory molecule production so that inhibitors of the cAMP degrading phosphodiesterases have been identified as promising drugs in chronic inflammatory disorders. Although many such inhibitors have been developed, their introduction in the clinic has been hampered by their narrow therapeutic window with side effects such as nausea and emesis occurring at sub-therapeutic levels. The latest generation of inhibitors selective for phosphodiesterase 4 (PDE4), such as apremilast and roflumilast, seems to have an improved therapeutic index. While roflumilast has been approved for the treatment of exacerbated chronic obstructive pulmonary disease (COPD), apremilast shows promising activity in dermatological and rheumatological conditions. Studies in psoriasis and psoriatic arthritis have demonstrated clinical activity of apremilast. Efficacy in psoriasis is probably equivalent to methotrexate but less than that of monoclonal antibody inhibitors of tumour necrosis factor (TNFi). Similarly, in psoriatic arthritis efficacy is less than that of TNF inhibitors. PDE4 inhibitors hold the promise to broaden the portfolio of anti-inflammatory therapeutic approaches in a range of chronic inflammatory diseases which may include granulomatous skin diseases, some subtypes of chronic eczema and probably cutaneous lupus erythematosus. In this review, the authors highlight the mode of action of PDE4 inhibitors on skin and joint inflammatory responses and discuss their future role in clinical practice. Current developments in the field including the development of topical applications and the development of PDE4 inhibitors which specifically target the subform PDE4B will be discussed. © The Author(s) 2013.
Hussain W.,Chapel Allerton Hospital
British Journal of Dermatology | Year: 2014
Background Due to the relative lack of a mobile tissue reservoir, the flap repair of large defects of the temple and lateral forehead is challenging. Objective To present our experience of the contralateral subgaleal sliding (CLASS) flap for the single-stage aesthetic repair of such defects. Methods Data were collated on all patients at one regional Mohs centre in whom the CLASS flap had been performed since 2011. Results The CLASS flap was performed on 16 patients (11 male, five female) with an average age of 63 years (range 42-90). The average defect size was 2·8 × 3·1 cm. A single case of postoperative infection occurred, which settled with appropriate therapy with no adverse sequelae. All patients rated their outcome as good or excellent. Conclusion The CLASS flap is a reliable, aesthetic, single-stage reconstructive technique for large defects of the lateral forehead and temple. What's already known about this topic? Due to the relative lack of a mobile tissue reservoir, the single-stage, aesthetic local flap repair of large defects of the temple and forehead is challenging. In an attempt to facilitate tissue movement at this relatively immobile facial site, the use of galeotomies, tissue expanders and imbrication sutures have previously been reported. What does this study add? We highlight a modified approach for the single-stage flap repair of large defects of the temple and forehead under local anaesthesia. The contralateral subgaleal sliding flap provides the reconstructive surgeon with a highly reliable flap with a robust vascular supply. Despite the extensive tissue dissection required, the flap is very well tolerated by patients under local anaesthesia and produces favourable aesthetic results. © 2013 British Association of Dermatologists.
Hackney R.G.,Chapel Allerton Hospital
Orthopaedics and Trauma | Year: 2012
Groin pain has a wide differential diagnosis, and its aetiology may be multifactorial. Common causes include hip joint pathology, sports hernia and snapping psoas, but rarer causes such as stress fracture, spinal pathology and intra-pelvic causes must be considered. Investigation is specific to the diagnosis postulated through a carefully taken history and examination. Femoroacetabular impingement is common and increasingly managed with hip arthroscopy, good short term results being reported. © 2012.