INTERLEUKIN-17INHIBITION WITH SECUKINUMAB IMPROVES SUDOMOTOR DYSFUNCTION IN PSORIATIC ARTHRITIS

Psoriatic arthritis (PsA) is a relapsing inflammatory disease, most commonly a seronegative oligoarthritis found in patients with psoriasis, characterized by the absence of rheumatoid factor in serum, with differentiating features of distal joint involvement and in extreme cases of arthritis mutilans (which is a destructive form of PsA). Cardiovascular autonomic and peripheral sympathetic neuropathy occurs in PsA. However, there is no specific treatment recommendation for autonomic neuropathy (AN) in psoriatic diseases. Secukinumab, a recently approved therapeutic advancement for psoriasis and psoriatic arthritis, is an immunoglobulin G (IgG) 1k fully monoclonal antibody that selectively inhibits the effector function of interleukin (IL)-17A. Its effect on sudomotor dysfunction in PsA has not yet been reported. This is the first reported observation of improvement in peripheral sympathetic autonomic neuropathy with secukinumab in PsA. We report a case of a 52-year-old male with PsA on methotrexate 15 mg/week with severe disease activity treated with the addition of subcutaneous secukinumab 150 mg once a week for 5 w followed by once a month dose. We found significant improvement in sudomotor dysfunction after 4 and 8 w of treatment

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Atherosclerosis in Psoriatic Arthritis: A Multiparametric Analysis Using Imaging Technique and Laboratory Markers of Inflammation and Vascular Function

Die Reflexionsphase ist beim Forschen und beim Forschenden Lernen gleichermaßen bedeutsam. Dieser Beitrag untersucht die Reflexionen im Forschenden Lernen bei Studierenden der Erziehungswissenschaft. Die Reflexionen wurden anonym erhoben und inhaltsanalytisch nach ihrer Breite (Themen) und Tiefe (Komplexität) ausgewertet. Die meisten Reflexionsaussagen beziehen sich auf methodisches Wissen und Können sowie kooperatives Arbeiten, aber bleiben grösstenteils beschreibend. Die Ergebnisse deuten darauf hin, dass sowohl Forschen als auch Reflektieren erlernt werden müssen. Die empirische Untersuchung der Reflexionen ermöglicht einen vielfältigen und vertieften Einblick in den Lern- und Forschungsprozess der Studierenden, was für eine adaptive und konstruktive Begleitung und Betreuung seitens der Dozierenden wesentlich ist.The reflexion phase is equally meaningful in research and research-based learning. This article analyses reflections within research-based learning of students in educational science. Reflections were collected anonymously and evaluated using content analysis in terms of breadth (topics) and depth (complexity). Most reflections refer to methodical knowledge and skills as well as to collaborative working but are mostly rather descriptive. The results indicate that both research and reflection must be learned. Empirically examining students' reflections enables a diverse and deepened insight into students' learning and research process, which is important to adaptively and constructively mentor and coach students

Predictors of endothelial dysfunction and atherosclerosis in rheumatoid arthritis in Indian population

Objective: Cardiovascular (CV) disease is leading cause of mortality in rheumatoid arthritis (RA). Dysfunction of the vascular endothelium is a hallmark of most conditions that are associated with atherosclerosis and is therefore an early feature in atherogenesis. Biomarkers for rapid evolution of CV complications would be highly desirable for risk stratification. Finally, predictive biomarkers for cardiovascular risk would allow tailoring therapy to the individual. We assessed endothelial function and atherosclerosis utilizing carotid intima-media thickness (CIMT) in RA in context of clinical and laboratory markers in Indian RA population. Methods: We performed a prospective study of 35 consecutive RA patients and 25 age- and sex matched healthy controls. Patients with traditional CV risk factors were excluded. Flow mediated dilatation (FMD) as measures of endothelial function and CIMT as measures of atherosclerosis were assessed. Disease-specific measures, inflammatory measures, serum cytokines, serum nitrite, lipids and endothelial progenitor cells (EPCs) were estimated. Results: FMD was significantly lower in RA (6.53% ± 1.81%) compared to controls (10.77% ± 0.53%; p < 0.001). CIMT (mm) was significantly increased in RA (0.62 ± 0.17) vs. controls (0.043 ± 0.07; p = 0.003). In RA patients, FMD% inversely correlated with CIMT, CRP, DAS-28, TNF-α, serum nitrite and positively correlated with EPC. CIMT correlated with age, DAS-28, IL-6, HDL, LDL, and inversely correlated with EPC. Conclusions: In the present study, FMD and CIMT were impaired in RA, indicating endothelial dysfunction and accelerated atherosclerosis respectively. CRP, TNF-α, serum nitrite, DAS-28 and depleted EPC population predicted endothelial dysfunction. Age, IL-6, HDL, LDL and depleted EPC population predicted accelerated atherosclerosis