Ozkan Varan

Predictive value of neutrophil/lymphocyte ratio in renal prognosis of patients with granulomatosis with polyangiitis

Abstract Introduction: Granulomatosis with polyangiitis (GPA) is a rare necrotizing vasculitis, which usually involves the upper and lower respiratory systems and kidneys and often have a relapsing course. Neutrophil/lymphocyte ratio (NLR) has been shown to be a useful marker predicting not only progressive disease, but also mortality in various inflammatory diseases. We aimed to investigate the roles of NLR in predicting the extend of clinical involvement and prognosis of patients with GPA. Materials and methods: Consecutive newly diagnosed GPA patients who had follow-up for at least 6 months between 2010 and 2016 at Gazi University Internal Medicine-Rheumatology clinic were retrospectively analyzed. Results: Fifty-three newly diagnosed GPA patients were studied. NLR was significantly higher in the GPA group compared with the control group (4.50 [min–max: 0.07–34.81] vs 1.77 [min–max: 1.04–2.90], respectively, p < .001). NLR significantly correlated with ESR and CRP levels (r = .40 and r = .48, respectively, p < .001 for both). Discussion: GPA is a vasculitis with a significant morbidity and mortality (REF). Renal involvement usually presents with crescentric glomerulonephritis, resulting in significant and permanent loss of renal functions and end-stage kidney disease. Higher NLR at baseline is associated with worse renal outcome. Our findings suggest that baseline NLR could have a predictive value for renal prognosis. We have also demonstrated a significant correlation between NLR and BVAS activity scores. Our data suggest that GPA patients with a significantly high NLR at baseline might need closer follow-up for persistent disease activity.

Anakinra for the treatment of familial Mediterranean fever-associated spondyloarthritis

aorta and its branches. TA may be complicated by life-threatening pulmonary arterial hypertension (PAH) (2). Treatment with glucocorticoids and disease-modified anti-rheumatic drugs (DMARDs) appears to be partially effective (3). Strong expression of IL-6 in the aorta and elevated serum IL-6 levels have been reported in patients with TA and correlated with disease activity (4). Accumulating evidence also shows, in animal models, that lung-specific overexpression of IL-6 resulted in increased pulmonary vascular resistance (PVR) and pathological lesions similar to that seen in patients with PAH, including distal arteriolar muscularization, plexogenic arteriopathy, and periarteriolar infiltration of T cells (5). Altogether, these findings seem to indicate that IL-6 directly or indirectly promotes proliferation of both smooth muscle cells and endothelial cells, and that the IL-6 blocking could represent an ideal therapeutic target in TA patients with PAH (5–8). The rapidity of effectiveness of tocilizumab appears surprising in this case and could be related to an initial effect on vascular inflammation, as indicated by the fast clinical and biological effects observed in our and other studies (9, 10).

Efficacy and safety of interleukin-1 inhibitors in familial mediterranean fever patients complicated with amyloidosis

Abstract Background: Colchicine is the mainstay of the treatment of familial Mediterranean fever (FMF). However, 10% of FMF patients do not respond well to colchicine. Efficacy of interleukin (IL)-1 inhibitors in reducing attacks have been demonstrated in colchicine-resistant FMF (crFMF) patients recently. Colchicine is still the only approved drug for the prevention of amyloidosis in FMF and utility of IL-1 inhibitors in crFMF cases who already has amyloidosis remain to be elucidated. Herein, we evaluated efficacy and safety of IL-1 inhibitors in patients with crFMF-associated AA amyloidosis in a relatively large single center study. Methods: Medical records of FMF patients complicated with AA amyloidosis in our dedicated FMF center were retrospectively reviewed and those patients who ever treated with IL-1 inhibitors were enrolled into the study. Patient global, physician global assessments (on 0–10 cm visual analog scale), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatinine and 24-h urinary protein excretion values for each visit were recruited from computer-based hospital records. Treatment response of patients were assessed with clinical symptoms, serum albumin, CRP and ESR values. Renal outcome parameters were analyzed on those not receiving renal replacement therapy. Results: Seventeen patients were identified with crFMF-amyloidosis that ever treated with IL-1 inhibitors. Background colchicine therapy was continued in all patients in maximal-tolerated dose along with IL-1 inhibitors. All patients benefit from IL-1 antagonists assessed by patient and physician global assessments. Inflammatory markers, CRP and ESR, were significantly reduced in all and normalized in 12 out of 17 patients. More importantly, the amount of proteinuria was remarkably improved following IL-1 inhibitor therapy (1606 mg/day to 519 mg/day, p = .008). Both anakinra and canakinumab were well-tolerated without severe side effects. All patients were initially treated with anakinra but switched to canakinumab in seven patients (one leukopenia, four injection site reaction, two inefficacy). Conclusion: We evaluated the clinical and laboratory responses to IL-1 inhibitors in crFMF-associated amyloidosis patients. We found significant decreases in CRP, ESR and proteinuria after IL-1 inhibitor therapy. This study confirmed that IL-1 inhibitors are effective for controlling attacks and inflammatory activity in FMF patients complicated with AA amyloidosis. Moreover, they reduce or stabilize amount of proteinuria and preserve renal function in short-term follow-up. Prolonged prospective clinical trials are warranted to assess their long-term efficacy in this particular patient group.

Serum ferritin as an activity marker for granulamotosis with polyangiitis

Abstract Background: Serum ferritin correlates well with the activities of systemic lupus erythematosus (SLE) and dermatomyositis, but it has not been previously studied in patients with vasculitis. Methods: Medical records of granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis) patients with at least six months of regular follow-up were evaluated. The activity of GPA was assessed with Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (BVAS/WG). Serum ferritin and other acute phase markers were measured at initial presentation. Results: Serum ferritin levels were found to be the highest in GPA patients with alveolar hemorrhage, median (IQR) 1041 (1281) μg/L. Patients with renal disease also had high levels of ferritin and it was correlated with concurrent glomerular filtration rate (r = −0.65, p < .001). Serum ferritin is also correlated well with the BVAS/WG scores (r = 0.79, p < .001). Conclusions: Measurement of serum ferritin might help in assessing disease activity of GPA.

Associations between Depressive Disorders and Inflammatory Rheumatic Diseases

Depressive disorders, are not only common but also among the leading causes of disability worldwide. They are associated with increased incidences of various other diseases. It has been shown that in patients with autoimmune diseases, when depression coexists, the quality of life is worse and medical treatment and management is compromised. Depression-like symptoms, such as fatigue and disinterest are also common in inflammatory rheumatic diseases and often associated with poor quality of life. Medical therapy targeting inflammation results in alleviation of these symptoms in many patients. Interestingly, there is cumulating evidence suggesting potential roles of inflammatory cytokines in the pathogenesis of major depression. Effects of some of the biological agents used in rheumatic diseases have been studied on depressive disorders. Results have been controversial and further studies are needed in this area. These findings suggest associations between depression and inflammatory rheumatic diseases and raise the possibility that treatment of one of them might influence the outcome of the other. We have reviewed the current literature on associations between depression and inflammatory rheumatologic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögrens syndrome and ankylosing spondylitis.

SAT0611 Canakinumab use in adult familial mediterranean fever patients: a large single centre experience

Background IL-1 blocking agents have been shown to be effective in the prevention of attacks in colchicine resistant FMF (crFMF) patients. Canakinumab is FDA approved long acting recombinant IL-1 receptor antagonist for use in crFMF patients which is available for off label use in Turkey. Herein, we aimed to share our real life single centre experience for use of canakinumab in adult crFMF patients. Methods Data was derived from Gazi FMF cohort which was established in year 2010. From that date patients with FMF who were diagnosed according to the Tel Hashomer criteria were registered. Co-morbidities, detailed attack characteristics, type, duration, severity, treatments, laboratory parameters and impact of FMF on their life in terms of quality of life and work productivity were recorded either by FMF diary or a mobile phone application (FMF AIDD free to download from AppStore and android market). A retrospective cohort analysis was made from records of patients who were treated with canakinumab. Results Eighteen adult crFMF patients (%61 female) treated with canakinumab were enrolled in this study. The median age was 3124–58 years and the median disease duration was 2816–40 years. All patients harbour homozygous or compound heretozygos exon 10 MEFV mutations. Treatment reasons for canakinumab were colchicine resistance (n=14) and amyloidosis (n=4). In three patients canakinumab was initiated directly, while in 15 it was switched from anakinra (seven was allergic to anakinra, one patient had significant leukopenia, in six fail to control attacks). The median duration of canakinumab use was 8 (min 1- max 22) months. In two patients canakinumab was used as 300 mg/monthly, and in remaining as 150 mg/monthly. Pre- and post-canakinumab periods of patients were compared (Table). Patient reported attack severity (p≤0.01), duration (p≤0.01), frequency (p≤0.01), C-reactive protein (CRP) (p≤0.01) and erythrocyte sedimentation rates (p≤0.01) were significantly improved while serum creatinine and alanine aminotransferase (ALT) levels remained same (p=0.2, p=0.35, respectively). Canakinumab achieved complete disease remission in 5 patients. Side effects requiring discontinuation of canakinumab were observed in none of patients. Table. Comparison of attack characteristics of 18 Adult crFMF patients before and after canakinumab Colchisine Colchicine+canakinumab P Attack severity, VAS 8,5 (5–10) 3,5 (0–10) <0,01 Attack duration, hours 108 (48–144) 24 (0–96) <0,01 Attack frequency* 6 (1–10) 1 (0–3) <0,01 CRP, mg/L 35,8 (3,8–85,0) 4,2 (2,45–55) <0,01 ESR, mm/h 38 (11–67) 12 (3–44) <0,01 Serum creatinine 0,66 (0,40–3,00) 0,70 (0,43–3,00) 0,20 ALT 20 (10–55) 19 (9–70) 0,35 Treatment duration, months 204 (48–456) 8 (1–22) *Attack frequencies adjusted for 3 months intervals. VAS: visual analogue scale, CRP: C-reactive protein, ALT: alanine aminotranspherase, ESR: erythrocyte sedimentation rate Conclusions Canakinumab is effective in the prevention of attacks with a favourable safety profile. Disclosure of Interest None declared

Nailfold Capillaroscopy Findings Mimicking Systemic Sclerosis in a Patient With Port-Wine Stain

E xamination of nailfold capillaries by video capillaroscopy is a valued diagnostic tool for evaluation of connective tissue disorders, particularly in systemic sclerosis and in differentiating primary and secondary Raynaud phenomenon. Nailfold capillary changes, such as giant capillaries, dilated capillaries, hemorrhages, and capillary loss, are also helpful in determining early, active, and late stages of disease in systemic sclerosis. However, pathologic capillary changes may also be observed in conditions other than connective tissue diseases. Herein, we present nailfold capillary changes of a patient with isolated port-wine stain (nevus flammeus) who presented outpatient clinic with arthralgia. Physical examination of the patient is nonremarkable, except for a large facial port-wine stain (Figure, A). He had had normal C-reactive protein levels, and his autoantibody profile was negative for antinuclear antibodies. Video capillaroscopic examination revealed multiple hemorrhages

Acute lupus choroidopathy: multimodal imaging and differential diagnosis from central serous chorioretinopathy

ImportanceSystemic lupus erythematosus (SLE) is a thoroughly examined multi-organ disease whose common ocular complications are also well documented. However, SLE choroidopathy, being a rare ocular complication, is needed to be better understood, in order to make the differential diagnosis from clinical conditions such as central serous chorioretinopathy and provide adequate prompt treatment.ObjectiveTo provide a clear understanding for the clinical course of SLE choroidopathy by the help of enhanced depth imaging optical coherence tomography, fluorescein angiography, and indocyanine angiography.DesignThe study is designed as a case presentation, consisting of the physical examination results and the data gathered by the relevant screening methods for each visit, applied by the same ophthalmologists and technicians.SettingThe visits were organized as same day examinations as needed, in a university hospital which works as a referral center.

AB0472 Impact of disease on family and social life in women with systemic lupus erythematosus (SLE)

Background Systemic lupus erythematosus (SLE) is a chronic connective tissue disease with involvement of various organ systems and characteristically has a higher incidence in women than men1. The disease, as well as its treatment, could have significant effects on the quality of life of lupus patients. Objectives Here, we aimed to investigate the impact of SLE on quality of the social and family life of women. Methods One hundred and twenty women diagnosed with SLE were included in the study. A questionnaire including questions about family and social relations were applied and demographic information, educational status, marital status, organ involvement and treatment data were obtained. The results of this study are preliminary and the study is still ongoing. Results One hundred and twenty patients were studied. The average age was 37 (± 10). 77 patients were married, 29 patients were single, 12 patients were divorced and 2 patients were widows. 29% of the patients were employed. 10,8% of the patients declared having difficulty in accepting their illnesses. 94,8% of the married patients had nuclear families. Relationship with partners and family members detoriated in 15,5% of the married patients after the diagnosis of SLE. 10,7% of single patients ended their serious relationships and 28,6% developed negative thoughts about marriage after the diagnosis of SLE. 17,6% of the married patients were exposed to verbal or physical violence by their partners. 33% of the patients declared having worse social life compared to prior to diagnosis and 20,7% declared having poor relations with their friends due to their disease. 34.5% of the patients stated that they received psychological counseling after their diagnosis. No significant relationship was found between family problems, social activities, age and educational level. Conclusions Systemic lupus erythematosus is a connective tissue disease affecting various organ systems and leading to various comorbidities. Our results suggest that family and social relations detoriate in lupus patients due to their illness independent of their age and educational level. Over one third of the patients received psychological counseling after diagnosis. Moreover, results of this study suggest that having a diagnosis of lupus has substantial impact on the marital considerations. References Hochberg, Marc C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis & Rheumatology 40.9 (1997): 1725–1725. Disclosure of Interest None declared

FRI0320 Predictive value of platelet to lymphocyte ratio in renal involvement in patients with granulomatosis with polyangiitis

Background Granulomatosis with polyangiitis (GPA) is a granulomatous necrotizing vasculitis with high morbidity and mortality. Anti-neutrophil cytoplasmic antibody (ANCA) is a rvaluable diagnostic marker, however its titer lacks predictive value for the severity of organ involvement. Platelet to lymphocyte ratio (PLR) and mean platelet volume has been regarded as a potential marker in assessing systemic inflammation. Objectives We aimed to investigate PLR and MPV as inflammatory marker in patients with GPA. Methods GPA patients and age-sex matched healthy controls were included. Demographic, clinical and laboratory information were extracted from medical records. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell (WBC), platelets (PLT), lymphocyte and neutrophils counts and glomerular filtration rate (GFR) were recorded. PLR was calculated. Disease activity was assessed with Birmingham Vasculitis Activity Score for WG vasculitis (BVAS/WG). Results 56 patients with GPA and 53 healty controls were included. Clinical characteristics and laboratory findings of the study population are shown in Table 1. ESR, CRP, MPV and PLR were significantly higher in patients with GPA than controls. PLR positively correlated with ESR and CRP (r:0.389, p:0.005 and r:0.512 p<0.001, respectively). In contrast, MPV negatively correlated with ESR and CRP (r:-0.308, p:0.028 and r:-0.337 p:0.014, respectively). There were no significant correlation between PLR, MPV and BVAS/WG. Patients with renal involvement had statistically significantly higher PLR than patients without renal involvement (303.01±287.33 vs177.98 + 75.43, p: 0.020 respectively). Moreover PLR negatively correlated with glomerlar filtration rate (r:-0.266 and p:0.009). Receiver operating characteristic curve of PLR, ESR and CRP for differentiating renal involvement is presented in Figure 1. Area Under Curves (AUCs) for PLR, CRP and ESR were 0.703 (95% confidence interval [CI], 0.558–0.849, p=0.016), 0.577 (95% CI: 0.416–0.738, p=0.362), 0.508 (95% CI: 0.337–0.678, p=0.929), respectively. The cutoff level of PLR was 204 (sensitive 65.6%, specifity 62.5%, positive predictive value 70%, negative predictive value 57.7%). Patients with alveolar hemorrhage tended to have higher PLR but this difference did not reach statistically significance (266.60 + 182.90 vs 240.61 + 252.43 p=0.382, respectively). Conclusions Results suggest that PLR exhibit favorable diagnostic performance in predicting renal involvement in patients with GPA. Disclosure of Interest None declared