Bahtiyar Toz

Primary Burkitt's Lymphoma Presenting as a Rapidly Growing Thyroid Mass.

A 31-year-old male patient presented with a rapidly growing neck mass with normal thyroid function tests. Ultrasonography showed thyroidal expansion, a hypoechoic nodule that completely filled the right lobe, and 2 hypoechoic lymphadenopathies in the right jugulodigastric chain. The patient underwent right total and left subtotal thyroidectomy, following the diagnosis of nodular goiter; however, postoperative histopathological evaluation demonstrated primary Burkitt’s lymphoma of the thyroid gland. The tumor was staged as stage 1, and R-hyper-CVAD protocol (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) was administered. The protocol was changed to R-CHOP after 4 cycles due to recurrent grade III/IV cytopenias and febrile neutropenia. The PET-CT scans performed after chemotherapy and at the 6-month follow-up were normal. In summary, we reported a case with a diagnosis of Burkitt’s lymphoma, which is a rare type of primary thyroid lymphoma.

Cystatin C is better than albuminuria as a predictor of pulse wave velocity in hypertensive patients

Abstract Introduction: Arterial stiffness is important in the evaluation of the cardiovascular risk in both general population and hypertensive patients. In this study, we aimed to investigate the associations of both serum cystatin C levels and albuminuria with arterial stiffness in healthy controls and hypertensive patients. Patients and methods: Seventy-six healthy controls (male/female = 44/32) and 76 hypertensive patients (male/female = 43/33) were enrolled. Arterial stiffness parameters such as augmentation index (AIx) and pulse wave velocity (PWV) were non-invasively measured with the Arteriograph (Tensiomed Ltd., Budapest, Hungary). Results: AIx (31.92 ± 14.31 vs. 27.95 ± 11.03, p = 0.03) and PWV (9.84 ± 1.62 vs. 8.87 ± 2.04, p < 0.001) were significantly higher in hypertensive patients compared to healthy controls. Patients with microalbuminuria had significantly higher AIx (43.47 ± 9.91 vs. 30.37 ± 14.13, p = 0.002) and higher serum cystatin C levels [0.76 (0.67–0.95) vs. 0.68 (0.62–0.78) mg/L, p = 0.03]. In the hypertensive group, AIx was significantly correlated with PWV (r = 0.519, p < 0.001), glomerular filtration rate (cystatin C) (r = –0.438, p = 0.003), mean arterial pressure (MAP) (r = 0.288, p = 0.015) and urinary albumin–creatinine ratio (ACR) (r = 0.386, p = 0.004). PWV was associated with serum cystatin C (r = 0.442, p = 0.003) and MAP (r = 0.377, p = 0.001). In the linear regression analysis (model r = 0.577, p = 0.006) for the prediction of PWV in hypertensive patients, MAP, urinary ACR, age and serum cystatin C levels were included as independent variables. Cystatin C was found to be the significant determinant of PWV in hypertensive patients. Conclusion: Multivariate analysis revealed that serum cystatin C but not albuminuria was significantly associated with PWV in hypertensive patients. Serum cystatin C may be better than albuminuria as a predictor of arterial stiffness in hypertensive patients.

There is an increased risk of atherosclerosis in hereditary angioedema.

BACKGROUND Hereditary angioedema is associated either with a deficiency in the amount or in the function of the C1 inhibitor (C1 INH). OBJECTIVE In this study the endothelial function of HAE patients was investigated to evaluate the impact of hereditary C1-INH deficiency on atherosclerosis, which has not yet been established before. METHODS A total of 26 patients (14 female, 12 male. Mean age: 38±13) diagnosed with HAE and 30 healthy controls were enrolled in the study. Measurement of coronary flow reserve (CFR) in the left anterior descending coronary artery was performed using transthoracic doppler harmonic echocardiography at baseline and following dipyridamol infusion. The intima-media thickness (IMT) in the carotid artery was measured using an echocardiographic system equipped with 10 MHz linear transducer (Vingmed System Five). RESULTS The mean CFR value for the HAE patient group was significantly lower than that of the control group (p<0.001). The mean IMT was not found to be significantly different between the two groups, although it was slightly higher in the HAE patient group. No correlation was found between the CFR and the disease severity scores, nor was it shown between the CFR values and the duration of danazol treatment. CONCLUSION Our results indicate that there is a microvascular endothelial dysfunction in HAE patients. Although carotid intima media thickness of these patients was not significantly increased, the presence of microvascular endothelial dysfunction might be regarded as an early indicator of a premature atherosclerosis.

Factors affecting progression-free survival in non-HIV-related Kaposi sarcoma

Abstract Background: Non-HIV related Kaposi sarcoma (NHKS) is a rare indolent neoplasm which is more common around Mediterranean origin. Data concerning factors that influence progression-free survival (PFS) for NHKS are insufficient. The purpose of present retrospective analysis was to distinguish the factors affecting PFS in patients with NHKS. Methods: A hundred and twenty-eight consecutive patients with NHKS who were treated or observed between 1997 and 2014 at Istanbul University Institute of Oncology were included into the study. Treatment response and progression definitions were determined according to different treatment modalities administered at first line. Results: Majority of patients were male (n = 97, 75.8%). Median age of the whole group was 66 years (28–85). Of the patients, 15 patients were immunosuppressant, whereas 113 patients had no disease that caused immunosuppression. Patients were treated with local excision (n = 57, 44.5%), chemotherapy (n = 32, 25.0%) and/or radiotherapy (n = 13, 10.2%) or observed without treatment (n = 26, 20.3%). At a median follow-up of 28 months, 71 (55.5%) patients had progression, while 3 patients (2.3%) died of NHKS. On univariate analysis, patients who had hypertension (HT) had poorer PFS compared with others (19 ± 12 versus 41 ± 22 months; p = 0.03), whereas plaque formation was associated with better outcome (25 ± 9 versus 54 ± 12 months; p = 0.03). In addition, heavy smoking (≥40 pack-years) had a borderline significance regarding better PFS time (23 ± 24 versus 45 ± 38 months, p = 0.06). On multivariate analysis, none of factors evaluated had any impact on PFS. Conclusions: HT was correlated with poorer outcome among NHKS patients. Patients with plaque formation and ≥40 pack-years of smoking had better PFS than others.

Multicentric reticulohistiocytosis: Rheumatology perspective

Multicentric reticulohistiocytosis (MRH) is a rare, multisystemic non-Langerhans cell histiocytosis characterized by skin and articular involvement, and rarely involves various other organs. There are no specific laboratory findings for MRH. Diagnosis is based on clinical findings and skin or synovial biopsy results. There is currently no consensus for the treatment of MRH. Here, we review the differential diagnosis and treatment options of MRH from the rheumatologists perspective. We also report an index case of MRH associated with Sjögrens syndrome and pulmonary embolism.

Serologic features of cohorts with variable genetic risk for systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease with genetic, hormonal, and environmental influences. In Western Europe and North America, individuals of West African descent have a 3–4 fold greater incidence of SLE than Caucasians. Paradoxically, West Africans in sub-Saharan Africa appear to have a low incidence of SLE, and some studies suggest a milder disease with less nephritis. In this study, we analyzed sera from African American female SLE patients and four other cohorts, one with SLE and others with varying degrees of risk for SLE in order to identify serologic factors that might correlate with risk of or protection against SLE.MethodsOur cohorts included West African women with previous malaria infection assumed to be protected from development of SLE, clinically unaffected sisters of SLE patients with high risk of developing SLE, healthy African American women with intermediate risk, healthy Caucasian women with low risk of developing SLE, and women with a diagnosis of SLE. We developed a lupus risk index (LRI) based on titers of IgM and IgG anti-double stranded DNA antibodies and levels of C1q.ResultsThe risk index was highest in SLE patients; second highest in unaffected sisters of SLE patients; third highest in healthy African-American women and lowest in healthy Caucasian women and malaria-exposed West African women.ConclusionThis risk index may be useful in early interventions to prevent SLE. In addition, it suggests new therapeutic approaches for the treatment of SLE.

Biologic therapy in familial Mediterranean fever: Comment on the study by Koga et al

We read with great interest the article by Koga et al. entitled ‘‘Biologic therapy in familial Mediterranean fever (FMF)’’ [1]. The authors reported that IL-1, TNF and IL-6 inhibitors were effective in colchicine-resistant or intolerant patients with FMF. However, it is not clearly stated in this review when to use each of these agents according to the clinical picture of the patient. We would like to point out that different clinical pictures indicate activation of different pathways of the immune system in FMF. First, in FMF patients, mutated pyrin which is encoded by MEFV may activate inflammasome, thereby caspase-1-related induction of IL-1b activation from cells occurs and causes increased inflammatory response in FMF. Thus, IL-1 blocking agents such as anakinra is generally favored as an initial approach in colchicine resistant patients [2]. Response to anti-TNF treatments have been reported especially in FMF patients with chronic arthritis. Furthermore, anti-TNF has not been generally found beneficial in other inflammatory findings of FMF such as peritonitis and pleuritis [3]. Second, the authors stated that tocilizumab treatment could be used in colchicine resistant patients to prevent development of amyloidosis, based on the findings of Yilmaz et al. [4]. However, in this study, 11 patients with FMF and AA amyloidosis were reported to undergo a stable course under tocilizumab treatment for 3–16 months, which is too short for prediction of amyloidosis. Risk of amyloidosis is not directly related to the number of attacks and it is still too early for reporting a favorable effect on amyloidosis for both IL-1 and IL-6 blocking treatments. Actually, prevention of amyloidosis by means of controlling FMF attacks may be possible with anti-IL-1 treatment. Lastly, there is no widely accepted definition for colchicine resistance. However, patients with FMF who continue to experience six or more typical attacks over a year or three attacks over 4–6 months under colchicine therapy at optimal dose is commonly defined as colchicine resistant FMF in the literature [5]. In colchicine resistant patients, biological therapy should be chosen in an individual basis according to the clinical picture and safety profile. At the moment, anti-IL1 treatment is an effective and safe way to control inflammatory activity, and we need to see results of randomized controlled trial documentary its long-term safety and efficacy. Anti-TNF agents may be an option in selected patients with chronic arthritis. Although, there is a room for IL-6 blockade.

Rheumatologic manifestations of primary immunodeficiency diseases: comment on the study by Dimitriades et al.

We read with interest the review entitled BRheumatologic manifestations of primary immunodeficiency diseases^ by Dimitriades et al. [1]. This is a well-written review providing guidance for rheumatologists regarding when they should consider primary immunodeficiency diseases and also explores how these immunodeficiency states may be underlying their rheumatologic disorder. We would like to comment on this review regarding other associations between rheumatologic disorders and primary immunodeficiency diseases. In addition to inflammasome-related disorders, interferonopathies such as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature and STINGassociated vasculopathy with onset in infancy may be seen in the setting of autoinflammatory disorders. Furthermore, PLCγ2associated antibody deficiency and immune dysregulation, autoinflammation and PLCγ2-associated antibody deficiency and immune dysregulation, HOIL-1, and NF-kB disorders including Blau syndrome and early onset enterocolitis, familial psoriasis may be seen in association with autoinflammatory disorders [2]. Secondly, adenosine deaminase 2 protein (encoded by CECR1 gene) deficiency has recently been defined and may be associated with recurrent fever and early onset vasculopathy mimicking classical polyarteritis nodosa characterized by stroke and microaneurysms, inflammation, and mild immunodeficiency [3]. Thus, this entity may also be included in the list. Lastly, hyper-immunoglobulin E syndrome is a rare primary immune deficiency disease characterized by skin and lung infections and dermatitis. Vasculitis leading to stenosis, occlusion, and aneurysm formation has been reported in this syndrome [4]. We suggest the inclusion of these entities in this extensive review which provides guidance in the setting of rheumatologic presentations in association with primary immunodeficiency diseases.

FRI0502 Biologic Agents in Refractory Adult Still's Disease: Better Response Rates and Acceptable Safety with Anakinra and Tocilizumab

Background There is no randomized controlled trial data to guide us for the management of Adult Stills Disease (AOSD) patients refractory to conventional treatments. Objectives We herein aimed to analyze retrospectively the treatment results of a series of refractory AOSD patients, who received different biologics. Methods We screened our database for patients diagnosed with AOSD between 1987–2015, and reviewed charts of those patients refractory to corticosteroid and DMARD combination and received biologics including TNF, IL-1 and IL-6 inhibitors. Patients were grouped according to their first biologics as TNF-inhibitors (TNF-i) or others [anakinra (ANK) or tocilizumab (TCZ)]. We also analyzed the patient responses according to their disease course characteristics as polycyclic or chronic patients. Time to remission were analysed by Kaplan-Meier method, and the association of response with first biological treatment was analysed by regression analysis Results Twenty-four patients with refractory AOSD (chronic=9 and polycyclic=15),who received biologic treatments with a mean duration of 41±27 months. The first biological treatment was TNF-i in 14 and other agents in 10 (ANK in 7 and TCZ in 3).Of the patients,50% were switched from TNF-i to ANK or TCZ. Comparison of the patients according to their first biologic therapy is given in Table 1. The patients who received other biologics were associated with a better response as the first treatment and tended to achieve remission earlier compared with those who received TNF-i as their first biological treatment (median time to remission 4 vs, 8 months, log-rank p=0.44). Joint involvement was more common and skin involvement tended to be more common in the chronic course group (100% vs 50%,78% vs 36%, respectively). While the duration of biologic treatment tended to be longer in the chronic course group (51 mo vs 28 mo,p=0.04), duration of remission was similar between the groups (26 mo vs 20 mo, p=0.4). The remission rate tended to be higher in the polycyclic group, whereas CRP and ESH tended to be lower in the chronic group. Complete remission rates under biologics course were as follows: 63% with TCZ 8mg/kg (7/11), 61% with ANK 100–200mg (11/18), 27% with etanercept (3/11), and 9% with infliximab (1/11) treatments. Regression analysis showed that selection of TCZ or ANK biologics as the first biologic was associated with a better response independent of the disease course type (estimate 2.5, 95% CI 0.3–4.7, p=0.026).No serious infection was observed in patients treated with biologics. In two patients severe skin reactions occurred with ANK and infliximab and, in one patient an immune thrombocytopenia developed under TCZ treatment. TNF inhibitors (n=14) Anakinra ( n=7) or Tocilizumab (n=3) Current age (years) 37±13 35±10 Age at diagnosis (years) 26 (20–59) 26 (5–46) Follow up (months) 72 (18–252) 54 (26–288) Gender (% males) 31 46 Sore throat (%) 54 73 Skin involvement (%) 54 46 Joint involvement (%) 85 55 Hepatotoxicity (%) 31 46 CRP (mg/L) 115±88 131±78 ESR (mm/h) 101±30 102±32 Ferritin (ng/ml) 1000 (281–29979) 1280 (424–5181) Conclusions This case series of AOSD patients suggest that ANK and TCZ seem to be better treatment choices in terms of remission rate and time to remission in patients refractory to conventional treatments Disclosure of Interest None declared

SAT0343 Utility of Vascular Findings by PET/CT Scan in The Diagnosis and Activity Assessment of Takayasu Arteritis

Background Takayasu arteritis (TA) is a large-vessel vasculitis predominantly affecting the aorta and its main branches. Assessing disease activity is difficult and mainly based on the clinical findings, levels of acute phase reactants and angiography, but these items generally do not correlate well Objectives The aim of the this study was to investigate the role of PET/CT in the diagnosis of the disease and assessing disease activity in TA Methods Thirty TA patients fulfilling ACR criteria underwent FDG-PET/CT were retrospectively assessed. Disease activity was defined according to NIH criteria. A nuclear physician who was blinded to clinical and laboratory data examined all PET/CT scans. PET/CT scans were considered negative if vascular FDG uptake was lower than liver uptake, if there was moderate (equivalent to that of liver) or marked (more than liver) FDG uptake in at least one vessel area, the scan was considered positive for vasculitis. The levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured concomitantly. The correlation between CRP and ESR with SUVmax values of vessels was investigated. Disease activity with the NIH cirteria, CRP levels and ESRs were compared in subjects with or without positive PET/CT scans. ROC curve analyses were performed to assess the sensitivity and specificity of CRP and ESR according to PET/CT positivity Results PET/CT was performed for diagnostic purposes early in the disease course in 9 subjects and to assess disease flare in 21 subjects on follow-up. The rate of a positive PET/CT examination tended to be higher in diagnostic/early use (88.9% positive) compared with use for flare-assessment (61.9% positive), although the difference was not significant (Fisher=0.2). Median CRP and ESR tended to be higher in PET/CT positive patients compared with PET/CT negative subjects (median CRP 19 vs. 14, p=0.16; mean ESR 59.8±36.5 vs. 35.2±19.7, p=0.07). ROC curve analysis showed an ESR of 38 mm/h or higher was 68.4% sensitivity and 66.7% specificity to predict a positive PET/CT examination (positive and negative predictive values 81.6% and 50%). A CRP of 14.5 mg/L or higher was 66.7% and 55.6% specific to predict a positive PET/CT examination (positive and negative predictive values 77.8% and 41.7%). While CRP was significantly correlated with mean SUVmax value of aorta (r=0.41, p=0.02), ESR was weakly correlated with SUVmax value of aorta (r=0.3, p=0.13). There was moderate agreement between PET-CT and NIH criteria (kappa 0.462, p=0.01, sensitivity 81%, spesificity 67%). Conclusions These results suggested that clinical benefit of PET/CT might be higher in diagnostic use (early in the disease course) compared with use for flare assessment (after treatment) in TA. There was a moderate association between NIH activity criteria and PET/CT activity. The predictive value of increased ESR and CRP was similar for a positive PET/CT scan with lower negative predictive values. CRP levels had a better correlation with SUVmax levels of aorta compared to ESR. PET/CT is a promising tool in the diagnosis and activity assessment of TA but discrepancies with other activity parameters do exist. Disclosure of Interest None declared