Temporal trends in COVID-19 outcomes in people with rheumatic diseases in Ireland: data from the COVID-19 Global Rheumatology Alliance registry.

OBJECTIVES: Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. METHODS: Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher's exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. RESULTS: Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13-96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. CONCLUSION: No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland.

Behçet syndrome.

Behçet syndrome is a systemic vasculitis with an unknown aetiology affecting the small and large vessels of the venous and arterial systems. The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest that multiple pathological pathways are involved in Behçet syndrome. These disease features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 as a genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bona fide disease, especially in non-endemic regions, suggests that other factors must also be operative in Behçet syndrome. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease, eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve. New treatment options and a better understanding of the underlying pathogenesis for various manifestations of this condition are required to further improve the management of the disease, which will improve patient quality of life.

Comparing the clinical profile of adults and children with Behçet's syndrome in the UK.

OBJECTIVES: Behçet's syndrome (BS) is a rare multi-system inflammatory disorder. Clinical phenotypic variance across geographical regions is recognised but UK BS patients' variance by age groups and gender has not been studied. This study compares the clinical features of adult and juvenile onset Behçet's Syndrome (JBS) in a UK population. METHODS: Two clinical databases of BS patients were compared. The JBS database was collected at the Great Ormond Street Hospital for Children, London (n=46). The adult database was collected at the Hammersmith Hospital, London (n=560). RESULTS: Oro-genital aphthosis had high prevalence in both the JBS and the adult cohort (oral: 97.8% vs. 96.6%, genital: 73.9% vs. 75.7%). The JBS cohort was more likely to have gastrointestinal involvement (21.7% vs. 4.5%, p<0.001) and arthritis (21.7% vs. 9.6%, p=0.021) compared to adults. The JBS cohort was less likely to have eye involvement (4.3% vs. 37%, p<0.001), skin (21.7% vs. 55.4%, p<0.001) and vascular involvement (6.5% vs. 17.5% p=0.063). JBS females had a higher rate of genital aphthosis than JBS males (87.5% vs. 59.1%, p=0.044). Adult females had higher rates of genital (85.2% vs. 64.5%, p<0.001) and oral (99.0% vs. 93.8%, p=0.001) aphthosis than adult males. Adult males were more likely to have ophthalmological (44.9% vs. 30.3%, p<0.001) and vascular (23.0% vs. 12.8%, p=0.002) manifestations than adult females. CONCLUSIONS: UK JBS patients displayed less ocular and skin manifestations compared to the adult BS patients. This information will aid clinicians in diagnosing BS in UK adult and paediatric populations.

Course of Neuropsychiatric Symptoms during Flares of Systemic Lupus Erythematosus (SLE).

We present the case of a seventeen-year-old girl who presents with an interesting course of neuropsychiatric symptoms during several flares of SLE. The patient was diagnosed at the age of thirteen and has had four flares in total. The latter two flares included cutaneous and neuropsychiatric symptoms. The most recent flare occurred when she was aged seventeen. She had cutaneous symptoms which coincided with an episode of hypomania. Her mental state further deteriorated following steroid treatment. She exhibited affective and psychotic symptoms. Treatment with cyclophosphamide and olanzapine was associated with an improvement in both cutaneous and neuropsychiatric symptoms. Previously aged sixteen the patient had presented with cutaneous symptoms and a moderate depressive episode which was also exacerbated by steroid treatment. The patient's mood improved when the dose of oral steroids was reduced to a daily dose of 15-20 mg prednisolone.

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.

Paediatric Behçet's disease: a UK tertiary centre experience.

There are currently limited data regarding paediatric Behçet's disease (BD), particularly in the UK. We describe the clinical spectrum, treatment and outcome of BD, and explore the relative sensitivities of the criteria for the diagnosis of BD in a UK paediatric cohort. Single retrospective case note review of children with a clinical diagnosis of BD presenting between 1987 and 2012. Demographics, clinical features, treatment and outcomes were recorded. The sensitivities of the International Study Group (ISG) and International Criteria for BD (ICBD) criteria were explored. BD disease activity was calculated using the Behçet's Disease Activity Index (BDAI). Forty-six patients (22 male) were identified. Median age of onset was 4.87 (0.04-15.71) years; median time to diagnosis was 3.74 (0.25-13.48) years. Clinical features were recurrent oral ulceration (97.8 %), recurrent genital ulceration (73.9 %), gastrointestinal (58.7 %), musculoskeletal (47.83 %), cutaneous (23.9 %) involvement and uveitis (2 %). Recurrent genital ulceration was more common in female patients (P = 0.044). Thirty-seven patients (80.4 %) fulfilled the ICBD criteria; only 12 patients (26.1 %) fulfilled the ISG criteria. BDAI score at diagnosis was 7/20 (0-10/20) and significantly decreased to 5/20 (0-9/20) (P < 0.0001) at latest follow-up. The commonest systemic treatment was colchicine (76.1 %); anti-TNFα treatment was reserved for severe cases (15.5 %). Paediatric BD in the UK may present very early in life, sometimes with a family history, and with a low incidence of ocular involvement. Diagnostic delay is common. The majority of our patients required systemic therapy; anti-TNFα was reserved for severe cases and has largely superseded the use of thalidomide.

Magnetic resonance imaging of vein wall thickness in patients with Behçet's syndrome.

OBJECTIVES: Vascular disease is a serious complication of Behçet's syndrome (BS), occurring in up to 20% of subjects. Superficial thrombophlebitis, deep vein thrombosis, and arterial aneurysm formation are the most common manifestations. Venous thrombosis is thought to result from vessel wall inflammation. This work investigated the potential usefulness of high resolution magnetic resonance imaging (MRI) to identify inflammation in the venous walls in BS subjects. METHODS: Seven healthy control (HC) subjects and five BS subjects were scanned with 3T MRI (Siemens Skyra). A standard MRI sequence was adapted for use in the venous system. Metronome guided breathing generated a regular respiratory variation of venous blood velocity. The vein wall imaging was triggered at an appropriate delay after the metronome. The popliteal vein was imaged. Vein wall images were ranked based on wall thickness and signal enhancement by two blinded, experienced observers. RESULTS: Popliteal vein rank scores were found to be significantly increased in BS versus HC subjects by the first observer (p(Observer 1)=0.025, p(Observer2)=0.07) and also averaging both observers (p=0.05). The repeated images of each subject gave a degree of variability in results, potentially from drifting response to metronome guidance over the 10 minute scan. CONCLUSIONS: MR imaging can detect increased vein wall thickness in BS subjects compared to healthy controls. Variable response to the metronome-guided breathing requires further development.

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.

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.

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. METHODS: We recruited 52 patients with biopsy-proven cutaneous lupus erythematosus to establish whether they are deficient in 25-hydroxyvitamin D [25(OH)D]. We measured their serum 25(OH)D levels during summer months, investigated the effects of several variables on 25(OH)D levels and assessed the role of vitamin D supplementation. RESULTS: An overall mean 25(OH)D level of 63.03 (+/-23.3) nmol/l was obtained. Significantly low values (<25 nmol/l) were recorded in two (3.8%) patients and concentrations below 75 nmol/l were found in 34 (65.4%) patients. 25(OH)D levels were significantly lower among sun avoiders and daily sunscreen users, while significantly higher values were found among those who took cholecalciferol (vitamin D3) supplements. Low values were recorded among those with renal disease despite supplementation with vitamin D3 in some cases. CONCLUSIONS: We suggest that patients with cutaneous lupus erythematous have suboptimal 25(OH)D levels, which are significantly raised by the addition of at least 400 IU/day of cholecalciferol. We recommend supplementation with an active vitamin D analogue in collaboration with a consultant nephrologist, for the subgroup of patients with renal disease.

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.