A.U. Unal

Sequencing of 16S rRNA reveals a distinct salivary microbiome signature in Behçet's disease

Behçets disease (BD) is characterized by recurrent oro-genital ulcers, mucocutaneous lesions, and serious organ involvement. We investigated the salivary microbiome in BD using high-throughput sequencing of the 16S rRNA V4 region. Stimulated saliva samples were collected from 31 BD patients and 15 healthy controls, and in 9 BD patients, a second saliva sample was collected following dental and periodontal treatment. Sequence analysis identified a total of 908 operational taxonomic units (OTUs) present across all samples. Patients had a microbial community structure that is significantly less diverse than healthy controls. The most overabundant species in BD was Haemophilus parainfluenzae, while the most depleted included Alloprevotella rava and species in the genus Leptotrichia. Periodontal treatment improved oral health indices in BD but had no short-term effect on bacterial community structure. Neither the BD-associated genetic risk locus within the HLA-B/MICA region nor being on immunosuppressive medications explained the differences between patients and controls.

Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices.

To determine the frequency of subclinical atherosclerosis in patients with systemic sclerosis (SSc; scleroderma) compared to healthy subjects (HS) and rheumatoid arthritis (RA) patients and to determine the ability of cardiovascular (CV) risk indices in detecting SSc patients with subclinical atherosclerosis.

Association of , and Polymorphisms with Radiographic Severity of Ankylosing Spondylitis

Background: Radiographic severity of ankylosing spondylitis (AS) shows such great variance that some patients never develop syndesmophytes throughout the entire disease span, whereas some develop bamboo spine relatively early. Objective: To study the association between ERAP1, IL23R and PTGER4 single nucleotide polymorphisms (SNPs) and radiographic severity in AS patients. Methods: rs27044 and rs30187 (ERAP1), rs11209032 (IL23R) and rs10440635 (PTGER4) SNPs were genotyped in 235 AS patients fulfilling the modified New York criteria. Patients were classified as mild- and severe-AS according to modified Stoke AS spinal score (mSASSS). Mild-AS is defined as having mSASSS of “0” following at least 10 years of disease duration. Severe-AS is defined as having mSASSS of >20 (patients with mild vertebral changes (i.e. squaring or erosions) were omitted for clear stratification) regardless of disease duration. Results: The genotype distributions and allele frequencies of ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs were similar in mild- (n=171, mSASSS=0, 55.6% HLA-B27 positive) and severe-AS patients (n=64, mSASSS=48.5±17.8, 73.4% HLA-B27 positive). After adjustment for clinical differences between groups (gender, disease duration, HLA-B27 and smoking status) by logistic regression analysis, none of the alleles in the investigated SNPs were found to be associated with radiographic severity of AS. Conclusion: In radiographically well-categorized AS patients, ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs are not found to be associated with radiographic severity of AS.

A Nationwide Experience With The Off‐label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

Approximately 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine‐unresponsive or colchicine‐intolerant FMF patients are limited; the most promising alternatives seem to be anti–interleukin‐1 (anti–IL‐1) agents. Here we report our experience with the off‐label use of anti–IL‐1 agents in a large group of FMF patients.

Th17-Inducing Conditions Lead to in vitro Activation of Both Th17 and Th1 Responses in Behcet’s Disease

ABSTRACT Objectives: Interleukin-17 (IL-17) has been associated with the pathogenesis of various autoimmune/inflammatory diseases. The aim of this study was to investigate the expression of Th17-related immunity in an innate immunity-dominated vasculitis, namely Behcet’s disease (BD). Methods: Peripheral blood mononuclear cells from 37 patients (age: 38.5 ± 9.8 years) with BD, and 25 healthy controls (HC) (age: 39.1 ± 9.3 years), were cultured in Th17-inducing conditions (IL-6, Phytohemagglutinin (PHA), IL-1β, and IL-23) for 6 days. Cultured cells were stained with CD4, CD8, CD3, TCR gamma/delta, CD19, interferon-γ (IFN-γ), and IL-17 antibodies to determine the intracellular cytokine secretion by flow cytometry. Results: IL-17 expression by CD8+ and γδ+ T cells was higher in BD compared to HC (p = 0.004, p = 0.003, respectively). No differences were observed between the groups in the IL-17 production by B cells. Under Th17-inducing conditions, production of IFN-γ by CD4+, CD8+, and γδ+ T cells was also higher in BD compared to HC (p < 0.05 in all). Conclusion: Our results suggest that under Th17-stimulating conditions, T cells express both IL-17 and IFN-γ in BD. More prominent IL-17 and IFN-γ production by all lymphocyte subsets in BD might be associated with the increased innate responses, early tissue neutrophil infiltrations and late adaptive immunity in BD.

Infliximab-induced cutaneous eruption resembling pityriasis rubra pilaris in a patient with Takayasu's arteritis

Dear Editor, Infliximab is a widely used chimeric, monoclonal antibody for the treatment of various chronic, inflammatory, immune-mediated diseases. It has been associated with several cutaneous toxicities (Hawryluk, Linskey, Duncan, & Nazarian, 2012). Herein, we report a patient with Takayasu’s arteritis in whom a cutaneous eruption clinically mimicking pityriasis rubra pilaris (PRP) developed soon after starting infliximab treatment. A 53-year-old woman presented with a 4-week-history of generalized eruption. Her medical history was unremarkable except for Takayasu’s arteritis for 18 years. She was on treatment with infliximab and isoniazid for 6 weeks along with methylprednisolone, acetylsalicyclic acid, pantoprazole, calcium, and vitamin D for the last 4 years. Shortly after the second cycle of infliximab, a mild, erythematous, scaly rash developed on the scalp which rapidly spreaded to the trunk and extremities. No personal or family history of papulosquamous diseases was present. Dermatological examination revealed orange-tosalmon-colored, scaly patches with islands of sparing and follicular, erythematous papules on the trunk and extremities reminiscent of PRP (Figure 1a–c). Erythema with fine scales on the scalp and face was also evident. Two punch biopsies were obtained from erythematous patches and follicular papules. Histopathological examination showed hyperkeratosis and focal parakeratosis, necrotic keratinocytes, vacuolar degeneration and mild acanthosis in the epidermis and extravasated erythrocytes and superficial perivascular mononuclear infiltration in dermis (Figure 2). Laboratory tests including complete blood count, hepatic transaminases, renal function tests, and anti-HIV showed no abnormalities. The eruption gradually resolved spontaneously without any intervention, probably due to decreasing serum levels of infliximab inbetween infusions (Figure 1d–f). Based on the clinicopathological findings and the temporal relationship between the eruption and infliximab treatment, a diagnosis of infliximab-induced cutaneous eruption resembling PRP was made. Considering the severity of initial eruption and ethical concerns, no rechallenge was planned and infliximab was discontinued which led to further improvement of her skin reaction. The patient is currently being treated with leflunomide. Infliximab, a TNF-alpha inhibitor, is an effective treatment alternative in numerous disorders including rheumatoid arthritis, Crohn’s disease and psoriasis. In addition to infusion reactions, a wide variety of cutaneous side effects including non-specific maculopapular rash and paradoxical onset or exacerbation of psoriasis, sarcoidosis or hidradenitis suppurativa have been reported during infliximab treatment (Hawryluk et al., 2012; Mocci, Marzo, Papa, Armuzzi, & Guidi, 2013). Cutaneous eruption resembling PRP has been reported in association with other drugs including sorafenib, imatinib, ponatinib and telaprevir (Jack, Mauro, & Ehst, 2013; Paz, Querfeld, & Shea, 2011; Plana, Carrascosa, Vilavella, & Ferrandiz, 2013; Stalling, Vu, & English, 2012). However, to our knowledge, infliximab-induced cutaneous eruption suggestive of PRP or paradoxical development of PRP have not been reported before. Besides, off-label and efficacious use of infliximab has been repeatedly reported in treatment-resistant, severe PRP (Garcovich, Di Giampetruzzi, Antonelli, Garcovich, & Didona, 2010; Petrof, Almaani, Archer, Griffiths, & Smith, 2013; Wollina, 2012). In the present case, clinical differential diagnosis encompassed infliximab-induced cutaneous eruption resembling PRP and infliximabinduced paradoxical PRP. Clinical characteristics suggestive of PRP in our patient were orange-to-red-colored erythematous patches with fine scale and areas of sparing, and follicular papular lesions. However, the presence of necrotic keratinocytes and prominent vacuolar degeneration on the histopathological examination supported a diagnosis of drug-induced cutaneous eruption over PRP. Switching to another anti-TNF agent was not attempted in our patient due to a possible class effect. In conclusion, although infliximab holds a promising potential in treatment of recalcitrant PRP, it may induce cutaneous eruptions clinically simulating PRP as well. Thus, all patients presenting with PRP-like clinical features should be asked for the use of infliximab in addition to other drugs causing PRP-like drug eruptions.

Assessment of the frequency of cardiovascular risk factors in patients with Takayasu’s arteritis

Objectives The prevalence of atherosclerotic risk factors and disease in Takayasus arteritis (TAK) has not been well defined. We aimed to assess the frequency of cardiovascular (CV) risk factors and the incidence of CV events (CVEs) in patients with TAK from two ethnically different populations. Methods Patients with TAK followed at Mayo Clinic, Rochester, MN, USA and Marmara University, Istanbul, Turkey were included in this retrospective study. Patients with TAK were compared with age-, sex- and calendar year-matched controls from the same geographical region without TAK. The 2008 Framingham 10-year general CV risk score (FRS) was used for the evaluation of CV risk at the time of TAK incidence/index date. Results In total, 191 patients with TAK and 191 non-TAK controls were included. Hypertension and the prevalence of lipid-lowering treatments were significantly more frequent in TAK. Prior to the incidence/index date, occurrence of CVE was significantly higher in TAK. The FRS was significantly higher in TAK compared with non-TAK at incidence/index date. The cumulative incidence of CVE was 15.4% at 10 years in TAK vs 5.8% in non-TAK; the risk of CVE was increased among patients with TAK (hazard ratio = 4.36; 95% CI: 1.25, 15.13). Conclusion CV risk factors are more common in patients with TAK, particularly hypertension. The FRS is higher in patients with TAK at the time of diagnosis. The cumulative incidence of CVE was also significantly higher during follow-up in TAK. Our results suggest that patients with TAK should undergo careful assessment of CV risk factors, and an aggressive risk modification approach is warranted.

SAT0526 Is relapse rate of giant cell arteritis in real-life experience lower than in the controlled trials? results of a retrospective, multi-centre cohort study

Objectives Corticosteroids (CS) are accepted as the standard first-line treatment for giant cell arteritis (GCA). However, controlled trials of tocilizumab and abatacept demonstrated relapse rates of up to 70%–80% in patients on CS-only protocols in 12–24 months. Though level of evidence is low and not suggested by guidelines (except for methotrexate), conventional immunosuppressives (ISs) are also commonly used. We aimed to assess the relapse rates in patients with GCA in routine practice, retrospectively. Methods We assembled a retrospective cohort of patients with GCA from Turkey. All data was abstracted from records. Relapse was defined as any new manifestation or increased acute-phase response leading to the change of the CS dose or use of a new therapeutic agent by the treating physician. Results The study included 156 (F/M: 95/61) patients with GCA (table 1). The mean age at disease onset was 67.8±9.1 years. Polimyalgia Rheumatica was also present in 48 (30,8%) patients. Diagnosis was proven histopathologically in 99 patients.All patients received 1 mg/kg/day CS for remission induction, additional CS pulses were given to 36 (23.1%) patients. Conventional ISs including methotrexate and azathioprine were used in 89 (56.1%) and 26 (16.6%) patients respectively, while 10 (6.4%) patients received biologic treatments (8 tocilizumab,2 etanercept). Fourty-four (28.2%) patients used only CS during follow-up. Follow-up of at least 6 months was available for 132 patients, and median follow-up duration was 35 (6–268) months. Relapses occurred in 27 (20.5%) patients during follow-up. Mortality rate was 7.5% (n=10) during follow-up. VDI score was 2.4±1.7. Main causes of damage were related to CS treatments such as cataract, osteoporosis and diabetes mellitus. Conclusions In this first multi-centre series of GCA from Turkey, we observed that only one fifth of patients had relapses during a mean follow-up of 35 months. This lower relapse frequency suggests a different clinical spectrum in routine practice compared to patients included in controlled trials. Our results also suggest that there is a clear need for a steroid sparing agent in patients with GCA, that is a older aged population prone to CS side effects. Disclosure of Interest None declared

THU0372 Ultrasonographic scoring of the major salivary glands: is there a relationship with disease activity and functional status of the glands ?

Background Ultrasonography (USG) of major salivary glands (SG-USG)is a non-invasive tool that has been used to evaluate salivary glands in primary and secondary Sjogren’s syndrome (SjS). Objectives We aimed to investigate relation between the ultrasonographic scoring of major salivary glands and systemic disease activity or salivary secretion in patients with primary SjS. Methods Seventy-five SjS patients (F/M:73/2) with the mean age of 52±12 and duration of follow-up period of 58±54 months fulfilling ACR-EULAR classification criteria (2002) were included. Disease activity indexes (Sjögren’s Syndrome Patients Reported Index (ESSPRI), Visual Analogue Scale (VAS), EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI)] were recorded. Simultaneously, sialometric evaluation of the salivary glands was performed. Major salivary glands (bilateral parotis and submandibular glands) were scored according to two different scoring systems [Hocevar A.(0–48) and Milic VD. (0–12)] and elastography was recorded as well. Results Demographics, clinical characteristics, disease activity indexes and SG-USG scores were summarised in table 1 and table 2. Forty-one (55%) and 45 (60%) patients had the cut-off values of ≥17 (Hocevar) and ≥6 (Milic USG). The patients with the scores of ≥17 (Hocevar) were found to have higher scores of ESSPRI-total (16±6 vs 13±7, p=0,045) and lower sialometry (4,6±4,7 vs 8,4±4,6 ml, p=0,002). Scores of Hocevar and Milic-USG were negatively correlated with sialometry (r=-,430, p=0001 and r=-,430, p=0,001). Hocevar, Milic and elastography-USG scores were shown to be higher in patients with sialometry of ≤1,5 ml (n=7)(28±3 vs 17±10, p=0,010, 8±1 vs 5±3, p=0006 and 9±1 vs 5±2, p=0,028) and anti-Ro positivity(n=24) (24±10 vs 13±8 7±3 vs 4±2, p<0001 and 7±2 vs 3±2, p=0,003). The patients with severe parotid involvement (inhomogeneity/hypoechogenic areals≥2) had more frequent anti-Ro and anti-La positivity (80 vs 42%, p=0004 and 48 vs 17%, p=0,011)Abstract THU0372 – Table 1 Demographics and Clinical Characteristics of SjS patients.Abstract THU0372 – Table 2 Disease Activity Indexes and SG-USG Scores of SjS Patients Conclusions Hocevar scoring system of major salivary glands was found to be related to patient reported activity in SjS. USG scores were associated with reduced saliva secretion and anti-Ro positivity. Severe parotid involvement was shown to be related to anti-RO and La positivity. Evaluation of SG-USG including different scoring systems and elastography might reflect function of the salivary glands. Disclosure of Interest None declared

THU0329 Budd-chiari syndrome in behÇet's disease: a retrospective multicenter study

Background The aim of this study was to determine the demographic, clinical, laboratory and management characteristics along with the clinical course of Budd-Chiari syndrome (BCS) associated with Behçets disease (BD). Methods Sixty patients with BD with BCS (40 male, 20 female) were identified in 23 rheumatology centers (Group I). A total of 169 consecutive patients (100 male, 69 female) with BD who did not have clinically apparent BCS during the follow-up were evaluated as the control group (Group II). Results Comparison of the demographic and clinical findings between the Group I and the Group II were as follows: The mean age of disease onset was 23.1 +/- 6.7 years vs. 26.8±0.6 years (p=0.013), mean age at diagnosis was 27.2±0.9 vs. 30.4±0.6 years (p=0.008), arthritis was 10% vs. 28.4% (p=0.002), papulopustular skin lesion was 48.3% vs 69.2% (p=0.003), central nervous system (CNS) involvement 10% vs. 3% (p=0.03), cardiac involvement was 16.7% vs. 2.4% (p<0.001), superficial thrombophlebitis was 23.3% vs. 4.7% (p<0.001), and deep vein thrombosis was 58.3% vs. 15.4% (p<0.01). On diagnosis 50% of BD patients with BCS were classified as Child-Pugh A. Inferior vena cava obstruction was observed in 38.3% and portal vein thrombosis was seen in 3.3% of the patients with BCS. Mortality in BCS patients with BD was 18.3%. BCS related treatment after diagnosis in patients with BD were as follows: 71.7% of patients were treated with monthly cyclophosphamide intravenous pulses, 53.3% received intravenous pulse corticosteroids, 55.9% used azathioprine, 54.2% had warfarine treatment, and 50.8% were treated with low molecular weight heparin. Conclusions This study shows a higher frequency of cardiac and CNS involvement, superficial thrombophlebitis, papulopustular skin lesion, deep vein thrombosis in BD patients with BCS. Arthritis was observed less common in BD patients with BCS. The mean age onset was lower in patients with BCS. Medical treatment with immunosuppressive agents and anticoagulation appears to be the treatment of choice in BD patients with BCS. The majority of the patients with BCS were Child–Pugh class A on diagnosis. The inferior vena cava is frequently involved and, often associated with deep vein thrombosis and cardiac involvement. Disclosure of Interest None declared