The predictors of paradoxical reactions, especially psoriasis, to biologic therapy-findings from the TReasure database: a 5-year follow-up study.

OBJECTIVES: The objectives of this study were to assess the clinical characteristics, predictive factors, and practical algorithms of paradoxical reactions (PRs), specifically paradoxical psoriasis (PP). METHODS: The TReasure database is a web-based prospective observational cohort comprised of patients with RA and SpA from 17 centres around Turkey since 2017. A cohort study and a case-control study nestled within the cohort were identified. RESULTS: In total, 2867 RA and 5316 SpA patients were evaluated. The first biologic agent was found to have caused PRs in 60% of the 136 patients (1.66%) who developed the PRs. The median time interval between the PRs and biological onset was 12 months (range 1-132 months, mean 21 months). The most common types of PP, constituting 92.6% of PRs, were pustular (60.3%) and palmoplantar (30.9%). Adalimumab (30.9%), infliximab (19%) and etanercept (17.4%) were the most common agents causing the PP. In the treatment of most PP patients (73.2%), switching biologic agents was favoured, with TNF inhibitor (TNFi) chosen in 46.03% and non-TNFi in 26.9% of cases. The three most frequently selected drugs were etanercept (24.6%), secukinumab (9.5%) and adalimumab (8.7%). Only 5.17% of patients who switched to another TNFi showed progression. The odds ratios (s) for SSZ, HCQ, and LEF use were significantly higher in RA controls than in PP patients (P = 0.033, OR = 0.15; P = 0.012, OR = 0.15; and P = 0.015, OR = 0.13, respectively). In the PP group with SpA, the number of smokers was significantly higher (P = 0.003, OR: 2.0, 95% CI: 1.05, 3.81). CONCLUSION: Contrary to expectations based on earlier research suggesting that paradoxical reactions develop with the class effect of biological agents, the response of patients who were shifted to another TNFi was favourable.

Mortality in psoriatic arthritis patients, changes over time, and the impact of COVID-19: results from a multicenter Psoriatic Arthritis Registry (PsART-ID).

BACKGROUND: This study aimed to assess the mortality of PsA before and during the COVID-19 pandemic. METHODS: From the prospective, multicenter PsART-ID (Psoriatic Arthritis Registry-International Database), patients from Turkey were analyzed by linking the registry to the Turkish Cause of Death Registry. The outcome of interest was death from any cause, pre-pandemic (since the onset of registry-March 2014-March 2020), and during the pandemic (March 2020-May 2021). The crude mortality rate and standardized mortality ratio (SMR) were determined. RESULTS: There were 1216 PsA patients with a follow-up of 7500 patient-years. Overall, 46 deaths (26 males) were observed. In the pre-pandemic period, SMR for PsA vs the general population was 0.95 (0.61-1.49), being higher in males [1.56 (0.92-2.63)] than females [0.62 (0.33-1.17)]. The crude mortality rate in PsA doubled during the pandemic (pre-pandemic crude mortality rate: 5.07 vs 10.76 during the pandemic) with a higher increase in females (2.9 vs 8.72) than males (9.07 vs 14.73). CONCLUSION: The mortality in PsA was found similar to the general population in the pre-pandemic era. The mortality rates in PsA doubled during the pandemic. Whether PsA patients have more risk of mortality than the general population due to COVID-19 needs further studies. Key Points • Decrease in mortality in PsA might be expected with the more effective treatment options and better disease control. • A crude mortality rate is comparable to the general population and not increased until the pandemic. • Currently, there is a 2-fold increase in crude mortality rate possibly due to the COVID-19.

Clinical and laboratory factors associated with bamboo spine in patients with axial spondyloarthritis: are there clues for bamboo spine?

OBJECTIVES: To analyse the clinical and laboratory factors associated with bamboo spine. METHODS: Data of patients fulfilling the 2009 ASAS classification criteria for axial spondyloarthritis, registered in the national, multicentre, longitudinal, and observational database of TReasure was analysed. Radiographs were assessed using the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Data of patients with a bamboo spine (Group 1) was compared to data derived from patients with a longstanding disease of at least 15 years but no syndesmophytes (Group 2). RESULTS: Out of the 5060 patients, 1246 had eligible radiographs. There were 111 patients (8.9%) with a bamboo spine. Male sex was more common among patients with bamboo spine. The median BMI of 27.7 (25.8-31.1) in Group1 was higher than the BMI of 25.9 (22.9-29.2) in Group 2 (p<0.001). Hip arthritis, present or documented by a physician, was more common in Group 1 [(58/108 (53.7%) vs. 35/103 (34%), p=0.004]. There was a tendency towards a more prevalent enthesitis in these patients [29.1% (25/86) vs. 15.9%(11/69), p=0.054]. HLA-B27 status did not differ between groups. Smoking was more prevalent in Group 1. Multivariate logistic regression analysis revealed that male sex, body mass index, hip arthritis, and enthesitis are associated with bamboo spine in axSpA. CONCLUSIONS: Bamboo spine was more common in the male sex and associated with a delay in diagnosis, high BMI, hip involvement, and enthesitis. The constellation of increased body weight, hip arthritis, and enthesitis may imply that mechanical stress contributes to radiographic damage in the presence of chronic inflammation.

Case of MOG-IgG-associated disease with ankylosing spondylitis: A rare coexistence.

Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is an inflammatory neurological disease. It progresses with attacks by affecting the optic nerves and spinal cord. Bilateral or recurrent optic neuritis are the most common findings in adult patients. Its association with systemic autoimmune disorders such as Sjögren syndrome, antiphospholipid syndrome, autoimmune thyroiditis, and celiac disease is rare. The first and only case of MOGAD in a patient with ankylosing spondylitis with a history of anti-tumor necrosis factor-alpha (anti-TNF-α) use was reported. Herein, we present the coexistence of MOGAD in a patient with AS who did not have a history of anti-TNF-α therapy.

Evaluation of the frequency and intensity of COVID-19 in patients with ankylosing spondylitis under anti-TNF therapy.

BACKGROUND: Dear Editor, After the coronavirus disease 2019 (COVID-19) pandemic affected the whole world, rheumatologists began to think about how COVID-19 will progress in patients with inflammatory conditions. High cytokine levels play a role in the pathophysiology of COVID-19 infection. Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine known to have a key role in the pathogenesis of chronic immune-mediated diseases. AntiTNF therapy may cause an increase in active tuberculosis, other granulomatous diseases, and serious infections [1]. According to many studies, rheumatological diseases have not been identified as a risk factor for severe COVID-19 infection [2]. Should significantly increased cytokine levels during COVID-19 infection make us consider anticytokine therapies that may be used in the treatment of patients with COVID-19 a risk? We aimed to explore whether the frequency of COVID-19 infection increased, the effect of comorbidities on the frequency of infection, and whether the severity of the disease and need for intensive care support increased in patients who used anti-TNF agents. We performed a retrospective case-control study between March and December 2020 in Sakarya University Training and Research Hospital. Retrospectively, we evaluated whether there was a difference in the frequency and severity of COVID-19 in our patients diagnosed with ankylosing spondylitis (AS), 77 of whom were using anti-TNF and 49 of whom didn't use anti-TNF. Hospitalization and intensive care unit (ICU) requirements were evaluated as endpoints. In the anti-TNF group, patients used adalimumab, etanercept, certolizumab, infliximab, and golimumab. Patients were questioned at an outpatient clinic in person or by phone. Seventy-seven patients with AS using anti-TNF agents (58 males, 19 females) and 49 patients with AS (38 males, 11 females) not using anti-TNF agents were included in the study (p = 0.943). Mean age of patients using antiTNF agents was 41.53 ± 10.38, and mean age of patients not using anti-TNF agents was 42.94 ± 10.86 (p = 0.468). Thirty-three (42.9%) patients were smokers in the antiTNF group, while 23 (46.9%) patients were smokers in the group not using TNFi (p = 0.791). There was 12 pack-year smoking in the anti-TNF group, and 14 pack-year smoking in not using TNFi (p = 0.623). The frequency of diabetes mellitus (DM), hypertension (HT), amiloidosis, familial mediterranean fever (FMF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD) was similar in both groups (p = 0.403, p = 0.999, p = 0.521, p = 0.999, p = 0.999, respectively). Six patients using TNFi and 3 patients not using TNFi recovered from COVID-19 infection. However, this result was not statistically significant (p = 0.999). One patient using anti-TNF was hospitalized but with no need for admission to the ICU (p = 0.999). All 9 patients recovering from COVID-19 were male (p = 0.113). There were 2 (22.2%) smokers in the SARS-CoV-2 positive group and 54 (46.2%) smokers in SARS-CoV-2 negative group (p = 0.297). There was 37.5 pack-year smoking in SARS-CoV-2 positive group, and 12 pack-year smoking in SARS-CoV-2 negative group (p = 0.151). Nobody has comorbidities (DM, HT, amiloidosis, FMF, CAD, COPD) in SARS-CoV-2 positive group. There were patients with DM (5.1%), HT (15.4%), amiloidosis (1.7%), FMF (1.7%), CAD (0.9%) and COPD (0.9%) in SARS-CoV-2 negative group (p = 0.999, p = 0.356, p = 0.999, p = 0.999, p = 0.999, p = 0.999, respectively). Having comorbidities was not detected to be associated with frequency of COVID-19. 31 (40.3%) patients were using adalimumab, 25 (32.5%) patients were using etanercept, 13 patients were using (16.9%) certolizumab, 6 (7.8%) patients were using golimumab, and 2 patients (2.6%) were using infliximab in TNF group. Six patients using anti-TNF (2 adalimumab, 1 etanercept, 1 golimumab,2 infliximab) and 3 nonuser patients recovered from COVID-19 (p = 0.999). No statistically significant difference was found between SARS-CoV-2 positive and negative patients in terms of the types of anti TNF they used. Patients were called in March 2020, and they were advised to terminate their anti-TNF therapy, when the COVID-19 pandemic began. Among those who used antiTNF, 2 (33.3%) people who had COVID-19 and 38 (53.5%) people who did not have COVID-19 interrupted treatment (p = 0.419). Anti-TNF users who did not have COVID-19 stopped taking the treatment for an average of 3 months (min 2-max 4 months) starting from March 2020, and the patients who had COVID-19 (p = 0.102) stopped taking the treatment for 1.5 months (min 1-max 2 months). Duration of interrupting TNFi was not significant for the risk of COVID-19. Comorbidities, older age, and the presence of active disease have been associated with worse outcomes in previous studies [3]. In our study, the anti-TNF using and the nonuser groups were similar according to age, sex, and comorbidities. Although comorbidities in COVID-19 are associated with severe disease in the literature, we did not find a significant difference in our study. This result is probably related to our insufficient number of patients. As a result, we found that the use of anti-TNF did not increase the frequency and severity of COVID-19. In a recently published multicenter study, it was stated that the use of biological DMARDs in patients with inflammatory rheumatic diseases was not significantly associated with a worse outcome of COVID-19. But unlike our study, having no comorbidities was associated with a decreased risk of a worse outcome [4]. There are currently studies investigating the therapeutic utility of infliximab and adalimumab in hospitalized COVID-19 patients [5]. The results of these studies are very important. The usability of TNFi in treatment and at which stage of the disease anti-TNF agents can be used are wondered. We will see the course of the disease all over the world after the administration of the COVID-19 vaccines, but we still need more information about effective and safe treatment. RESULTS: The authors declare that there is no conflict of interest. DISCUSSION: The authors did not receive support from any organization for this work.

Tuberculin skin test before biologic and targeted therapies: does the same rule apply for all?

This study aimed to compare Tuberculin Skin Test (TST) and QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients scheduled for biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) in a Bacillus Calmette-Guérin-vaccinated population. Adult RA (n = 206) and SpA (n = 392) patients from the TReasure database who had both TST and QFT-GIT prior to initiation of biological and targeted synthetic DMARDs were included in the study. Demographic and disease characteristics along with pre-biologic DMARD and steroid use were recorded. The distribution of TST and performance with respect to QFT-GIT were compared between RA and SpA groups. Pre-biologic conventional DMARD and steroid use was higher in the RA group. TST positivity rates were 44.2% in RA and 69.1% in SpA for a 5 mm cutoff (p < 0.001). Only 8.9% and 15% of the patients with RA and SpA, respectively, tested positive by QFT-GIT. The two tests poorly agreed in both groups at a TST cutoff of 5 mm and increasing the TST cutoff only slightly increased the agreement. Among age, sex, education and smoking status, pre-biologic steroid and conventional DMARD use, disease group, and QFT-GIT positivity, which were associated with a 5 mm or higher TST, only disease group (SpA) and QFT-GIT positivity remained significant in multiple logistic regression. TST positivity was more pronounced in SpA compared to that in RA and this was not explainable by pre-biologic DMARD and steroid use. The agreement of TST with QFT-GIT was poor in both groups. Using a 5 mm TST cutoff for both diseases could result in overestimating LTBI in SpA.

Uveitis-related Factors in Patients With Spondyloarthritis: TReasure Real-Life Results.

PURPOSE: Spondyloarthritis (SpA) is a group of diseases with overlapping skeletal and extra-articular features. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. The relation between AAU and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients. DESIGN: Retrospective cohort study. METHODS: The data were obtained from the TReasure database, which compiles data from records of the web-based Rheumatoid Arthritis (RA) and SpA patients treated with biological disease-modifying anti-rheumatismal drugs from different regions of Turkey. The clinical characteristics of SpA and uveitis are recorded. RESULTS: Data of the 4,297 SpA patients were included in the study. Overall, 475 of 4,297 patients (11.0%) had experienced 1 or more episodes of uveitis. SpA patients with older age (P < .001), a smoking history (P = .004), delayed diagnosis (P = .001), longer disease duration (P < .001), arthritis (P < .001), positive HLA-B27 (P < .001), a family history of SpA (P < .001), and radiographic damage (presence of sacroiliitis, syndesmophytes, bamboo spine, hip involvement) (P < .001 for all) more commonly had uveitis. On the other hand, uveitis was less prevalent in patients with psoriasis and psoriatic arthritis (P < .001 for both). CONCLUSION: Uveitis may be the key feature leading to SpA diagnosis. Patients with radiographic damage and long disease duration have an increased risk for uveitis in both male and female SpA patients. Patients with uveitis should be referred to a rheumatologist for a thorough evaluation of SpA.

Disease characteristics of psoriatic arthritis patients may differ according to age at psoriasis onset: cross-sectional data from the Psoriatic Arthritis-International Database.

OBJECTIVES: To explore the impact of early versus late-onset psoriasis (PsO) on the disease characteristics of psoriatic arthritis (PsA) in a large-multicentre cohort. METHODS: The data from a multicentre psoriatic arthritis database was analysed. Patients were grouped according to age at psoriasis onset (early onset; <40 years of age, late-onset; >40 years of age) and disease characteristics of the groups were compared by adjusting for BMI and PsA duration, where necessary. RESULTS: At the time of analyses, 1634 patients were recruited [62.8% females; early onset 1108 (67.8%); late-onset, 526 (32.2%)]. The late-onset group was more over-weight [66.8% vs. 86.8%, p<0.001; adjusted for age - aOR 1.55 (1.11-2.20; 95% CI)]. The early onset group had more scalp psoriasis at onset (56.7% vs. 43.0%, p<0.001), whereas extremity lesions were more common in the late-onset group (63.8% vs. 74.2%, p<0.001). Axial disease in males and psoriatic disease family history in females were significantly higher in the early onset group [38.0% vs. 25.4%; p=0.005; adjusted for PsA duration - aOR 1.76 (1.19-2.62; 95% CI) / 39.5% vs. 30.1%; p=0.003; OR 1.51 (1.15-1.99; 95% CI), respectively]. Psoriatic disease activity parameters, patient-physician reported outcomes and HAQ-DI scores were similar in both groups. CONCLUSIONS: Clinical features of PsA may be affected by the age at onset of PsO. Different genetic backgrounds in early and late-onset PsO may be driving the differences in psoriasis and PsA phenotypes.

Biological and targeted-synthetic disease-modifying anti-rheumatic drugs with concomitant methotrexate or leflunomide in rheumatoid arthritis: real-life TReasure prospective data.

OBJECTIVES: To determine the real-life efficacy, safety, and drug-retention rates of leflunomide (LEF) or methotrexate (MTX) as a synthetic DMARD used in combination with biological DMARDs for rheumatoid arthritis (RA). METHODS: The TReasure database is a web-based, prospective, observational cohort of RA and spondyloarthritis patients from 17 centres in different regions of Turkey and data entry was enabled since December 2017. Until May 2019, 2556 RA patients on biologic treatment were recorded. Demographic and RA-related data of 1526 patient either received LEF or MTX were compared, efficacy of both drugs compared by RA-disease activity composite indices. Reasons fordrug discontinuation also recorded. Drug retention rates were compared with Kaplan-Meier curves (log-rank test). RESULTS: Of 2556 RA patients 1526 (59.7%) were receiving concomitant LEF (n=646, 42.3%; median follow up 35 months) or concomitant MTX (n=880, 57.3%; median follow-up 32 months) at the time of initiation to their first bDMARDs. The LEF group were older and had longer disease duration, proportion of females and seropositive patients was higher in this group. In the LEF group, non-anti-TNF agents were used in higher rate. Remission rates, changes in composite indices and rate of comorbidities and adverse events were similar in both groups. The retention rate of LEF + non-anti-TNF b/tsDMARDs was higher compared to MTX + anti-TNF bDMARDs (p=0.002, log-rank). Rates of adverse events were similar in both groups. CONCLUSIONS: LEF in combination with either anti-TNF or non-anti-TNF drugs appears as an effective and safe therapeutic option at least as MTX.

PsART-ID inception cohort: clinical characteristics, treatment choices and outcomes of patients with psoriatic arthritis.

OBJECTIVES: Our aim is to understand clinical characteristics, real-life treatment strategies, outcomes of early PsA patients and determine the differences between the inception and established PsA cohorts. METHODS: PsArt-ID (Psoriatic Arthritis- International Database) is a multicentre registry. From that registry, patients with a diagnosis of PsA up to 6 months were classified as the inception cohort (n==388). Two periods were identified for the established cohort: Patients with PsA diagnosis within 5-10 years (n = 328), ≥10 years (n = 326). Demographic, clinical characteristics, treatment strategies, outcomes were determined for the inception cohort and compared with the established cohorts. RESULTS: The mean (s.d.) age of the inception cohort was 44.7 (13.3) and 167/388 (43.0%) of the patients were male. Polyarticular and mono-oligoarticular presentations were comparable in the inception and established cohorts. Axial involvement rate was higher in the cohort of patients with PsA ≥10 years compared with the inception cohort (34.8% vs 27.7%). As well as dactylitis and nail involvement (P = 0.004, P = 0.001 respectively). Both enthesitis, deformity rates were lower in the inception cohort. Overall, 13% of patients in the inception group had a deformity. MTX was the most commonly prescribed treatment for all cohorts with 10.7% of the early PsA patients were given anti-TNF agents after 16 months. CONCLUSION: The real-life experience in PsA patients showed no significant differences in the disease pattern rates except for the axial involvement. The dactylitis, nail involvement rates had increased significantly after 10 years from the diagnosis and the enthesitis, deformity had an increasing trend over time.

Impact of Having Family History of Psoriasis or Psoriatic Arthritis on Psoriatic Disease.

OBJECTIVE: Psoriatic arthritis (PsA) has a genetic background. Approximately 40% of patients with psoriasis or PsA have a family history of psoriasis or PsA, which may affect disease features. The aim of this study was to assess the effects of family history of psoriasis and PsA on disease phenotypes. METHODS: Data from 1,393 patients recruited in the longitudinal, multicenter Psoriatic Arthritis International Database were analyzed. The effects of family history of psoriasis and/or PsA on characteristics of psoriasis and PsA were investigated using logistic regression. RESULTS: A total of 444 patients (31.9%) had a family history of psoriasis and/or PsA. These patients were more frequently women, had earlier onset of psoriasis, more frequent nail disease, enthesitis, and deformities, and less frequently achieved minimal disease activity. Among 444 patients, 335 only had psoriasis in their family, 74 had PsA, and 35 patients were not certain about having PsA and psoriasis in their family, so they were excluded from further analysis. In the multivariate analysis, family history of psoriasis was associated with younger age at onset of psoriasis (odds ratio [OR] 0.976) and presence of enthesitis (OR 1.931), whereas family history of PsA was associated with lower risk of plaque psoriasis (OR 0.417) and higher risk of deformities (OR 2.557). Family history of PsA versus psoriasis showed increased risk of deformities (OR 2.143) and lower risk of plaque psoriasis (OR 0.324). CONCLUSION: Family history of psoriasis and PsA impacts skin phenotypes, musculoskeletal features, and disease severity. The link between family history of psoriasis/PsA and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets.

Exon 2: Is it the good police in familial mediterranean fever?

OBJECTIVE: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. Most of the identified disease-causing mutations are located on exon 10. As the number of studies about the effect of the exonal location of the mutation and its phenotypic expression is limited, we aimed to investigate whether the exonic location of the Mediterranean fever (MEFV) mutation has an effect on the clinical manifestation in patients with FMF. METHODS: Study population was derived from the main FMF registry that included 2246 patients from 15 different rheumatology clinics. We categorized the mutations according to their exon locations and retrieved the clinical and demographic information from the database. RESULTS: Patients having the MEFV mutations on exon 2 or 10 (n:1526) were divided into three subgroups according to the location of the MEFV mutations: Group 1 (exon 2 mutations), Group 2 (exon 10 mutations), and Group 3 (both exon 2 and exon 10 mutations). Group 2 patients were of a significantly younger age at onset, and erysipel-like erythema, arthritis, amyloidosis, and a family history of FMF were more common in this group. CONCLUSION: Patients with FMF and exon 10 mutations show more severe clinical symptoms and outcome. Exon 2 mutations tend to have a better outcome.

Comparison of early versus late onset familial Mediterranean fever.

AIM: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. One of the common characteristics of this disease is its young age predominance. Nearly 90% of patients experience disease flares during early adult age periods. Currently there are limited data for the comparison of early versus late onset FMF and therefore the primary aim of this study was to investigate these two subsets with regard to their certain demographic, clinical and genetic differences. METHODS: Early (≤ 20 years, Group 1) and late (> 20 years, Group 2) onset FMF patients were identified from the national FMF registry that involves 2246 patients from 15 adult rheumatology clinics located in different geographical areas of Turkey. RESULTS: Of the 2246 patients, 1633 (72.7%) were aged ≤ 20 years old (Group 1) and the remaining 613 were older than 20 years (Group 2). Delay in diagnosis was longer in Group 1 and fever, peritonitis, pleuritis, erysipelas-like erythema (ELE), arthritis, family history of FMF and amyloidosis were more common in Group 1. On the other hand, sex distribution, rates of amyloidosis, vasculitis and kidney failure were not different between the groups. Among patients with available genotypes, homozygous and heterozygous M694V mutations were significantly higher and heterozygous E148Q mutation was significantly lower in Group 1 compared to Group 2. CONCLUSION: Patients with FMF whose symptoms start before 20 years of age seem to have severe symptoms and M694V mutation may be responsible for the early expression of the disease.

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study.

OBJECTIVE: The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS: Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS: There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION: In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

The association between gene polymorphisms and leukocytosis with thrombotic complications in patients with essential thrombocythemia and polycythemia vera.

OBJECTIVE: Vascular events are a common complication in patients with polycythemia vera (PV) and essential thrombocythemia (ET). This study aimed to analyze the association between PAI-1 4G/5G and ACE I/D gene polymorphisms, and leukocytosis with thrombosis in patients with PV and ET. MATERIAL AND METHODS: In total, 64 patients with ET and PV were evaluated. Arterial or venous thrombosis, such as cerebral transient ischemic attack, ischemic stroke, myocardial infarction, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary embolism, were defined as a vascular event. DNA samples were screened for mutations via reverse hybridization strip assay. RESULTS: In terms of PAI-1 gene polymorphism, the frequency of the 4G and 5G allele was 48.5% and 51.5%, respectively. The ACE allele frequency was 51.2% and 48.8% for D and I, respectively. There wasn't an association between occurrence of vascular events and the frequency of any allele. In terms of occurrence of vascular events, there weren't any significance differences between the patients that were carrying the ACE D/D homozygous allele to ACE I/D and those that carried the I/I allele (P = 0.93). There wasn't a significant difference in occurrence of vascular events between the PAI-1 5G/5G homozygote allele carriers, and the 4G/5G and 4G/4G allele carriers (P = 0.97). Vascular events were significantly more common in the patients with leukocytosis (leukocyte count >10 × 109 L-1) than in those without leukocytosis (leukocyte count ≤10 × 109 L-1) (P = 0.00). Age >60 years was also a significant risk factor for occurrence of vascular events(P = 0.008). CONCLUSION: PAI-1 and ACE gene polymorphisms were not considered new risk factors for thrombosis in PV and ET patients. On the other hand, leukocytosis at diagnosis was associated with the occurrence of vascular events in the patients with ET and PV.

Effect of heat shock protein-90 (HSP90) and vascular endothelial growth factor (VEGF) on survival in acute lymphoblastic leukemia: an immunohistochemical study.

BACKGROUND: The significance of vascular endothelial growth factor (VEGF) and heat shock protein-90 (HSP90) has received only limited attention especially in acute lymphoblastic leukemia (ALL). In this study, we assessed expressions of HSP90 and VEGF in bone marrow samples of patients with ALL and effect of these expression quantities on the mean overall survival. PATIENTS AND METHODS: Using immunohistochemical methods, we assessed expression of HSP90 and VEGF in 22 cases of ALL. RESULTS: Expression of HSP90 was detected in 19/22 (86.4%) and 3/22 (13.6%) of patients with ALL, for strongly positive and moderate-weakly positive, respectively. Negative HSP90 expression was not detected in patients with ALL. Expression of HSP90 in patients with ALL and in control group were statistically significant (P<0.001), however, did not reflect the mean overall survival (P=0.910). Mean OS was evaluated 992±181 and 724.8±88.2 days for moderate-weak and high HSP90 expression, respectively. VEGF expressions were not significantly different between ALL and control groups (P<0.087). We did not find any relationship between HSP90 and VEGF expressions in bone marrow specimens of patients with ALL. CONCLUSION: This study demonstrated that HSP90 expression grades in patients with ALL were significantly higher than that in controls and presence of strong HSP90 expression was associated with worse overall survival. VEGF expression in patients with ALL was not different from that in control samples. Determination HSP90 with immunohistochemical method in bone marrow can provide information about prognosis.

Are cup-like blasts specific to AML patients with FLT3 ITD and a normal karyotype? An ALL case report and review of the literature.

Cup-like morphology is defined as cup-like nuclear invagination spanning ≥25% of the nuclear diameter in >10% of blasts. Studies have shown that FLT3 ITD and normal cytology are strongly associated with cup-like morphology in acute myeloid leukemia (AML) patients. Herein we describe a patient with cup-like blasts that was diagnosed and treated for common acute lymphoblastic leukemia (ALL). In contrast to the literature, the presented case was Philadelphia chromosome positive and FLT3 ITD negative.

Acute severe cardiac failure in a myeloma patient due to proteasome inhibitor bortezomib.

We present here a case of severe congestive cardiac failure, in a 47-year-old patient with myeloma who had no prior cardiac history, after receiving bortezomib. Bortezomib is a boron-containing molecule, which reversibly inhibits the proteasome, an intracellular organelle, which is central to the breakdown of ubiquitinated proteins and consequently crucial for normal cellular homeostasis. Phase II clinical trials demonstrate that it is effective for the treatment of relapsed refractory myeloma. Acute development of congestive cardiac failure associated with bortezomib therapy occurs very rarely or may be underestimated. Inhibition of proteasome activity may impair cardiac function due to accumulation of unfolded, damaged and undegraded proteins in myocytes. Patients with or without cardiac disease or previously received anthracycline-containing regimes should be closely monitored when being subjected to treatment with bortezomib.

Lymphomas of Waldeyer's ring: Clinical features, management and prognosis of eleven adult patients.

Lymphoma is the second most common neoplasm of the head and neck after squamous carcinoma. The majority of lym¬phomas involving the head and neck are non-hodgkin's lymphomas. Hodgkin's lymphoma is rare in Waldeyer's ring. Between 1999 and 2006, the medical records and pathology data of all newly diagnosed, previously untreated adult patients with Waldeyer's ring lymphomas were retrospectively reviewed. Pathologic specimens were adopted according to WHO his¬tologic classification. All patients were clinically staged with history and physical examination, routine hematologic and bio¬chemical profiles, chest X-ray, and computerized tomography of the head and neck, chest, abdomen and pelvis. All patients were treated with chemotherapy. Approximately one month after the end of the scheduled initial management, patients were restaged for evidence of residual disease with physical examination, laboratory profiles and relevant radiologic studies. Total patient number was 11 in our institution. Complete remission was achieved in 6 patients and partial remission in 3 patients; 1 patient did not achieve remission and 1 patient with anaplastic large cell lymphoma died. Patients who are alive are still being followed in our institution. The progression of patients with lymphoma is closely associated with the diagnosis, stage and histologic grade of the disease. This series characterized the clinicopathologic features and outcomes of adult patients. Our data have shown that there is relatively good survival in these diseases but more patients must be evaluated for mean¬ingful results.