Nicola Ambrose

Photoprotective behaviour and sunscreen use: impact on vitamin D levels in cutaneous lupus erythematosus

Background: Sun exposure of the skin, independent of dietary sources, may provide sufficient vitamin D in healthy individuals. A recent study of patients with cutaneous lupus erythematosus concluded that over 70% of them restrict their sun exposure.

Heme Induces Heme Oxygenase 1 via Nrf2 Role in the Homeostatic Macrophage Response to Intraplaque Hemorrhage

Objective—Intraplaque hemorrhage (IPH) is an important progression event in advanced atherosclerosis, in large part because of the delivery of prooxidant hemoglobin in erythrocytes. We have previously defined a novel macrophage phenotype (hemorrhage-associated-mac) in human advanced plaques with IPH. These may be atheroprotective in view of raised heme oxygenase 1 (HO-1), CD163, and interleukin-10 expression and suppressed oxidative stress. Methods and Results—We have used a combination of small interfering RNA and pharmacological reagents, protein analysis, and oxidative stress measurements to dissect the pathway leading to the development of this phenotype. We found that erythrocytes, hemoglobin, or purified heme similarly induced CD163 and suppressed human leukocyte antigen and reactive oxygen species. HO-1 was required for the development of each of these features. Challenge of macrophages with purified heme provoked nuclear translocation of Nrf2, and Nrf2 small interfering RNA resulted in significant inhibition of the ability of heme to induce HO-1 protein. Furthermore, tert-butyl-hydroquinone, which activates Nrf2, upregulated CD163, suppressed human leukocyte antigen, and induced interleukin-10, further supporting a role for Nrf2-mediated signaling. However, an inducible protein transactivator is also probably necessary, as heme-induced HO-1 mRNA expression was fully inhibited by the protein synthesis inhibitor cycloheximide. Conclusion—Our experiments define an Nrf2-mediated pathway by which heme induces a homeostatic macrophage response following IPH.

Differential diagnosis and management of Behçet syndrome

Behçet syndrome (also known as Behçet disease) is a rare condition that is associated with considerable morbidity. Cases of Behçet syndrome have been reported worldwide, but the highest prevalence occurs in countries that border the ancient Silk Route, such as Turkey and Iran. Although oral ulceration, genital ulceration and eye disease are the classic triad of manifestations, the cardiovascular, gastrointestinal, musculoskeletal and central nervous systems can also be affected. The syndrome is chronic and relapsing with some patients having benign episodes whereas others have more serious complications, including blindness or the rupture of a pulmonary arterial aneurysm. Diagnosing Behçet syndrome, particularly outside of endemic regions, often incurs a considerable delay owing to the rarity of this condition. Furthermore, a paucity exists of data from randomized controlled trials on the optimal therapeutic approaches to use in patients, as well as a lack of informative laboratory surrogate markers to monitor disease progression. This Review discusses the issues surrounding the diagnosis and differential diagnosis of Behçet syndrome and presents the current approaches to managing patients with this complex group of disorders.

Etanercept Treatment in Sweet's Syndrome with Inflammatory Arthritis

To the Editor: A 55-year-old Caucasian man initially presented 6 years earlier to an outside facility with a photosensitive rash, arthritis, fatigue, and mild neutrophilia. He had a history of liver cirrhosis, felt to be secondary to previous alcohol consumption. He had several inflammatory papules and plaques on his trunk and forearms that clinically were suggestive of Sweet’s syndrome. A skin biopsy showed a dense, perivascular, neutrophilic infiltrate, which confirmed the diagnosis1. He was prescribed prednisolone and a calcium-vitamin D3 preparation. Standard investigations for an underlying malignancy were undertaken2, with results that were normal. Both his arthritis and his skin disease improved dramatically under steroid treatment, but both flared again once the steroid dose was tapered below 20 mg per day. Over the next 5 years he was followed up by a dermatology service and was maintained on 20–40 mg prednisolone. Concomitant treatment with colchicine, hydroxychloroquine, and chloroquine was ineffective, nonsteroidal antiinflammatory drugs were not tolerated because of gastrointestinal side effects, and liver … Address reprint requests to Dr. Ambrose; E-mail: nambrose2001{at}yahoo.co.uk

Diffusion-weighted imaging is a sensitive biomarker of response to biologic therapy in enthesitis-related arthritis.

Objective. The aim was to evaluate diffusion-weighted imaging (DWI) as a tool for measuring treatment response in adolescents with enthesitis-related arthropathy (ERA). Methods. Twenty-two adolescents with ERA underwent routine MRI and DWI before and after TNF inhibitor therapy. Each patient’s images were visually scored by two radiologists using the Spondyloarthritis Research Consortium of Canada system, and sacroiliac joint apparent diffusion coefficient (ADC) and normalized ADC (nADC) were measured for each patient. Therapeutic clinical response was defined as an improvement of ⩾ 30% physician global assessment and radiological response defined as ⩾ 2.5-point reduction in Spondyloarthritis Research Consortium of Canada score. We compared ADC and nADC changes in responders and non-responders using the Mann–Whitney–Wilcoxon test. Results. For both radiological and clinical definitions of response, reductions in ADC and nADC after treatment were greater in responders than in non-responders (for radiological response: ADC: P < 0.01; nADC: P = 0.055; for clinical response: ADC: P = 0.33; nADC: P = 0.089). ADC and nADC could predict radiological response with a high level of sensitivity and specificity and were moderately sensitive and specific predictors of clinical response (the area under the receiver operating characteristic curves were as follows: ADC: 0.97, nADC: 0.82 for radiological response; and ADC: 0.67, nADC: 0.78 for clinical response). Conclusion. DWI measurements reflect the response to TNF inhibitor treatment in ERA patients with sacroiliitis as defined using radiological criteria and may also reflect clinical response. DWI is more objective than visual scoring and has the potential to be automated. ADC/nADC could be used as biomarkers of sacroiliitis in the clinic and in clinical trials.

The exaggerated inflammatory response in Behçet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-γ/CXCL10 IP-10 pathway

The mechanisms underlying the exaggerated inflammatory response in Behçets syndrome (BS) remain poorly understood. We investigated the response of CD14+ blood monocytes to interferon (IFN)‐γ, focusing on the chemokine CXCL10. Chemokine synthesis and release were analysed at a protein and mRNA level following stimulation with IFN‐γ. Findings in BS patients were compared with 25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus erythematosus (SLE) disease control patients. BS monocytes produced significantly more CXCL10 protein than HC monocytes from 2 h following IFN‐γ stimulation, despite equivalent quantities of mRNA, suggesting more efficient translation. This was significantly more pronounced in BS with high disease activity and in those with ocular and neurological clinical manifestations. The imbalance between CXCL10 protein and mRNA expression was not observed in either RA or SLE patients, and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2). Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not show abnormal tumour necrosis factor (TNF)‐α release. Sucrose density gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome‐associated RNA showed equal proportions in BS and HC samples, suggesting that the difference between BS and HC may be due to reduced negative control of CXCL10 translation in BS at a post‐initiation level. We conclude that BS monocytes have dysfunctional post‐transcriptional regulation of CXCL10 mRNA, resulting in over‐expression of CXCL10 protein upon IFN‐γ stimulation. As CXCL10 is a chemokine that recruits mononuclear cells, this abnormality may contribute to the exaggerated inflammatory responses that characterizes BS.

Obesity and disability in the symptomatic Irish knee osteoarthritis population

BackgroundOsteoarthritis (OA) of the knee is a common disorder with significant social and financial implications. Obesity is the strongest modifiable risk factor of knee OA. There is little data on obesity in Irish knee OA populations and its relationship to other measures of disease severity.AimsIn Beaumont Hospital, we have been collecting data on patients presenting with knee OA as part of a screening process for potential candidates for therapeutic exercise intervention studies. Here, we present data on the first 96 candidates screened during this process.ResultsThe mean body mass index (BMI) of the group fell within the obese range (31); indeed, only 21% had a normal BMI. The vast majority of our patients had severe self-reported disability. In contrast, the distribution of radiographic severity of knee OA was more even. There was no significant relationship between radiographic severity and disability. BMI did predict disability but had a weak correlation. Radiographic severity did not correlate with BMI.ConclusionIrish patients with knee OA referred for physiotherapy were very disabled, significantly obese and represent a challenging cohort of patients to treat.

The importance of diagnosing neck pain

Diffuse idiopathic skeletal hyperostosis is a common but poorly recognised condition that may have important and occasionally life-threatening clinical outcomes. We report the case of a 71-year-old man with giant osteophytes in his cervical spine which caused dysphagia and silent aspiration, leading to pneumonia, septicaemia, aortic wall infection and septic arthritis. Early recognition of the cause of his neck pain may have averted the subsequent clinical course.

Male lupus: a diagnosis often delayed—a case series and review of the literature

IntroductionSystemic lupus erythematosus (SLE) is an auto-immune disease that is characterised by autoantibody production. Male lupus is rare, apart from at either end of the age spectrum.AimIn this series, we review the histories of six male lupus patients attending our service.ResultsOur patients presented in middle age and tended to develop haematological abnormalities, renal involvement and neurological manifestations which preceded the onset of their skin and joint complaints. Our patients accrued damage rapidly and overall did badly. They tended to respond sub-optimally to standard treatments. These cases highlight the need an increased awareness that male SLE patients present with a wide variety of symptoms, and that they accrue damage quickly. There is a need for timely diagnosis and appropriate initiation of treatment. This may help avoid preventable organ damage and increase the survival of men with SLE.

Limiting cardiovascular risk in Irish rheumatoid arthritis patients

BackgroundPatients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease and premature death.ObjectivesOur aims were: (1) to assess how thoroughly RA patients were being screened for cardiovascular risk factors in our outpatient population and (2) to evaluate the benefit of introducing a shared care cardiovascular booklet.MethodsWe assessed 80 patients who attend our service with RA. Our initial audit revealed that 80% of patients had not been thoroughly assessed for basic cardiovascular risk. Based on these findings, we created a shared care booklet.ResultsOn re-auditing our service, we found a significant improvement in the assessment of cardiovascular risks.ConclusionThere is currently a low level of screening for cardiovascular risks in busy outpatient clinics. We felt the introduction of a shared care booklet allowed an increased level of screening in our clinics and also acted as a tool for doctor and patient education.