Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5 mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.

Poor obstetric outcomes in women with takayasu arteritis: a retrospective cohort study.

The objective of this study was to assess the pregnancy outcomes in a cohort of patients who experienced pregnancies before and/or after being diagnosed with Takayasu's arteritis (TA). The present investigation encompassed a total of 88 pregnancies seen in a cohort of 35 patients who met the criteria outlined by the American College of Rheumatology in 1990 for the classification of Takayasu arteritis (TA). Pregnancies were classified into two categories. 1. Pregnancies that occurred before the diagnosis (pre-d or pre-TA) 2. Pregnancies that happened following a diagnosis (post-d or post-TA). Fifty-nine pregnancies (67.0%) occurred in 21 TA patients before the diagnosis with and a complication rate of 15.2%, and twenty-nine pregnancies (33.0%) occurred in 14 patients concomitant with or after TA diagnosis and complication rate 100%. Although the hypertension rate was higher in the pre-d group than in the post-d group, it was not significant (32.2% vs. 10.3%, p = 0.160). However, preeclampsia (20.6% vs. 0%, p = 0.001), low birth weight (27.5% vs. 1.6%, p = 0.001), and prematurity (24.1% vs. 1.6%, p = 0.035) were observed more frequently in the post-d group compared to the pre-d group. The frequency of abortions and in-utero deaths were similar in both groups (p > 0.05). Patients with hypertension had significantly higher rates of preeclampsia (p = 0.003), preterm birth (p = 0.036), low birth weight (p = 0.250), abortion (p = 0.018), in utero death (p = 0.128), and cesarean section (p = 0.005) than those without hypertension. Renal artery involvement was detected in 15 (42.8%) patients. All patients with renal artery involvement had hypertension, and they had significantly more pregnancy complications than the other group (p = 0.001). TA negatively affects pregnancy outcomes. A good control of arterial hypertension before conception and during pregnancy is critical to improve both maternal and fetal outcomes. In addition, detecting renal artery stenosis before pregnancy is important in reducing possible negative pregnancy outcomes.

Evaluation of the frequency and risk factors of spontaneous intramuscular hemorrhage associated with dermatomyositis.

Dermatomyositis (DM) is an idiopathic inflammatory myositis (IIM) characterized by skin manifestations and muscle involvement. Spontaneous intramuscular hemorrhage (SIH) is a fatal complication that is very rare in the course of DM, but not well known to rheumatologists. Our aim was to determine the frequency and possible risk factors of DM-related SIH. A retrospective analysis was conducted on a cohort of DM patients who were observed in the rheumatology department of the university hospital between 1998 and January 2024. The clinical, laboratory, radiological data of the patients and the treatments they received during the follow-up were analyzed. To determine possible risk factors for the development of SIH in the course of DM, our patients with DM were analyzed together with other rare SIH cases in the literature. The study included 42 of our DM patients. 32 of the patients (76.2%) were female. The median age of the patients was 53 (24-82) years, the median age of DM diagnosis of the patients was 47 (18-75) years, and the median duration of DM of the patients was 36 (2-276) months. 7.1% of patients had dysphagia, and 16.7% had intertitial lung disease (ILD). 5 (11.9%) patients were diagnosed with malignancy. The incidence rate of SIH development in our DM cohort was 0.238/100 patient years (95% CI 0.006-1.256). We tried to identify independent risk factors for SIH development by comparing our 41 DM patients without SIH with the data of patients with 23 DM-related SIH collected from the literature by adding our 1 patient (24 pts). Male sex (OR 4.97, 95% CI 1.66-14.92, p = 0.003), ILD presence (OR 9.71, 95% CI 2.99-31.47, p < 0.001), anti-MDA5 positivity (OR 16.0, 95% CI 1.60-159.3, p = 0.006), anti-Ro52 positivity (OR 11.6, 95% CI 2.93-46.34, p < 0.001), heparin use (OR 4.42, 95% CI 2.68-7.24, p < 0.001), intravenous immunoglobulin (IVIG) use (OR 11.7, 95% CI 2.26-60.54, p < 0.001), and steroid dose (OR 1.03, 95% CI 1.00-1.05, p = 0.005) were identified as risk factors for the development of SIH in the univariate analysis. The death rate due to hemorrhage was 50%. No single risk factor was found to be associated with death. As a result, SIH may occasionally arise in patients with DM. Rheumatologists should be aware that patients with dysphagia and/or ILD, who are on heparin, getting high doses of steroids, and test positive for anti-MDA5 and/or anti-Ro52 antibodies may develop SIH in the early stages of DM.

COVID-19 severity and vaccine breakthrough infections in idiopathic inflammatory myopathies, other systemic autoimmune and inflammatory diseases, and healthy controls: a multicenter cross-sectional study from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) survey.

OBJECTIVES: We aimed to compare the spectrum and severity of COVID-19 and vaccine breakthrough infections (BIs) among patients with IIMs, other systemic autoimmune and inflammatory diseases (SAIDs), and healthy controls (HCs). METHODS: This is a cross-sectional study with data from the COVAD study, a self-reported online global survey that collected demographics, COVID-19 history, and vaccination details from April to September 2021. Adult patients with at least one COVID-19 vaccine dose were included. BIs were defined as infections occurring > 2 weeks after any dose of vaccine. Characteristics associated with BI were analyzed with a multivariate regression analysis. RESULTS: Among 10,900 respondents [42 (30-55) years, 74%-females, 45%-Caucasians] HCs were (47%), SAIDs (42%) and IIMs (11%). Patients with IIMs reported fewer COVID-19 cases before vaccination (6.2%-IIM vs 10.5%-SAIDs vs 14.6%-HC; OR = 0.6, 95% CI 0.4-0.8, and OR = 0.3, 95% CI 0.2-0.5, respectively). BIs were uncommon (1.4%-IIM; 1.9%-SAIDs; 3.2%-HC) and occurred in 17 IIM patients, 13 of whom were on immunosuppressants, and 3(18%) required hospitalization. All-cause hospitalization was higher in patients with IIM compared to HCs [23 (30%) vs 59 (8%), OR = 2.5, 95% CI 1.2-5.1 before vaccination, and 3 (18%) vs 9 (5%), OR = 2.6, 95% CI 1.3-5.3 in BI]. In a multivariate regression analysis, age 30-60 years was associated with a lower odds of BI (OR = 0.7, 95% CI 0.5-1.0), while the use of immunosuppressants had a higher odds of BI (OR = 1.6, 95% CI 1.1-2.7). CONCLUSIONS: Patients with IIMs reported fewer COVID-19 cases than HCs and other SAIDs, but had higher odds of all-cause hospitalization from COVID-19 than HCs. BIs were associated with the use of immunosuppressants and were uncommon in IIMs.

Investigation of the relationship of CO-RADS and CT patterns with laboratory parameters in COVID-19 patients and a new perspective on the total CT scoring system.

BACKGROUND: It is important to determine the correlation of the CO-RADS classification and computed tomography (CT) patterns of the lung with laboratory data. To investigate the relationship of CO-RADS categories and CT patterns with laboratory data in patients with a positive RT-PCR test. We also developed a structured total CT scoring system and investigated its correlation with the total CT scoring system. METHOD: The CT examinations of the patients were evaluated in terms of the CO-RADS classification, pattern groups and total CT score. Structured total CT score values were obtained by including the total CT score values and pattern values in a regression analysis. The CT data were compared according to the laboratory data. RESULTS: A total of 198 patients were evaluated. There were significant differences between the CO-RADS groups in terms of age, ICU transfer, oxygen saturation, creatinine, LDH, D-dimer, high-sensitivity cardiac troponin-T (hs-TnT), CRP, structured total CT score values, and total CT score values. A significant difference was also observed between the CT pattern groups and oxygen saturation, creatinine and CRP values. When the structured total CT score values and total CT score values were compared they were observed to be correlated. CONCLUSIONS: Creatinine can be considered as an important marker for the CO-RADS and pattern classifications in lung involvement. LDH can be considered as an important marker of parenchymal involvement, especially bilateral and diffuse involvement. The structured total CT scoring system is a new system that can be used as an alternative.

Menorrhagia due to uterine amyloidosis in familial Mediterranean fever: case-based review.

Amyloidosis is described by the deposition of misfolded proteins in the tissues. Amyloidoses are classified into two as systemic and localized. Out of the systemic forms, AL (light chain) amyloidosis is the most prevalent type; however, amyloid A (AA) amyloidosis is more frequently encountered in the rheumatology practice. AA amyloidosis stands out as a major complication of familial Mediterranean fever (FMF). Splenic and renal involvement is more likely in FMF-associated systemic amyloidosis. The involvement of thyroid and adrenal glands has also been described, although infrequently. Amyloidoses have a heterogeneous plethora of clinical manifestations, with certain phenotypes associated with specific amyloid forms. Gynecological amyloidosis is a rare condition. Uterine involvement may occur in a localized fashion or may also arise as a part of systemic involvement, albeit at a lesser ratio. Several cases of uterine AL amyloidosis have been documented so far as an organ involvement in systemic AL amyloidosis. On the other hand, uterine amyloidosis associated with AA amyloidosis has been described merely in one case with rheumatoid arthritis (RA). Here, we presented a 40-year-old female patient with FMF known for 38 years who underwent splenectomy and hysterectomy due to massive splenomegaly, deep anemia, and persistent menometrorrhagia. Histological examinations of materials revealed uterine and splenic AA amyloidosis. This case report is first-of-its-kind to describe FMF-associated uterine AA amyloidosis and also provides a discussion of possible mechanisms of amyloidosis-induced uterine bleeding.

Aseptic meningitis in rheumatoid arthritis after anti-TNF administration: a case-based literature review.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular and extra-articular manifestations. Among extra-articular involvement, rheumatoid meningitis (RM) is a rare condition, which may exhibit variable symptoms including headache, focal and/or generalized neurologic deficits. It may develop as the preceding manifestation of RA or occur at any time of the disease course. Some drugs used for the treatment of RA may give rise to aseptic meningitis or create a tendency to infectious meningitis due to their immunosuppressive effect. All these possibilities may lead to difficulties in the differential diagnosis. Achieving a diagnosis in a short time is crucial in terms of prognosis. Here, we would like to report a case with longstanding RA manifested by left-sided weakness and seizure shortly after initiating etanercept (ETA) therapy. ETA-induced meningitis was confirmed with appropriate diagnostic tools. Our aim with this case-based review is to attract the attention of this rare condition and discuss diagnostic challenges.

Damage assessment in adult IgA vasculitis. Cross-sectional results of a multicentre cohort.

OBJECTIVES: Immunoglobulin (Ig) A vasculitis affects children more commonly than adults and previous literature lacks any formal damage assessment. Our aim in this study is to investigate the disease course, relapse rates and prognostic factors in adult patients with IgA vasculitis and to evaluate the disease-related damage. METHODS: We assembled a retrospective cohort of adult IgA vasculitis from six tertiary Rheumatology Centres in Turkey. The demographics, clinical characteristics, treatment and outcomes of patients were abstracted from medical records. RESULTS: The study included 130 (male/female: 85/45) patients and the mean age was 42.2±17 years. Cutaneous manifestations and arthritis/arthralgia were the most common clinical manifestations. One hundred thirteen patients (86.9%) were treated with oral glucocorticoids (GC). As additional immunosuppressive (IS) agents, azathioprine was given to 44 (34.9%) and pulse cyclophosphamide to 18 (12.6%) patients. Seventy-nine patients (60%) had follow-up of median 15 (IQR 7-40) months. Twelve (15%) patients relapsed during follow-up. The mean VDI score was 0.4 in the last visit. Nineteen (24.7%) patients had at least one damage item at the end of follow-up. Most frequent damage items were renal 11 (42%), ocular 4 (15%) and cardiovascular 4 (15%). CONCLUSIONS: In this cohort the most frequent damage item was renal and was related to the disease itself. Damage score was higher in patients with more severe disease and treated more aggressively. Our results suggest that more effective treatment options are needed in a subgroup of patients with IgA vasculitis to prevent the damage related with the vasculitis, especially with more severe disease.

The influence of genotype on disease severity and concomitant diseases in familial Mediterranean fever patients.

OBJECTIVES: To evaluate differences between the patients with familial Mediterranean fever (FMF) with homozygous (Hom), heterozygous (Het) and compound heterozygous (cHet) MEFV mutations in terms of clinical features and severity of the disease, as well as frequency of concomitant disorders, without focusing on Exon 10 mutations. METHODS: The patients with FMF were diagnosed using the Tel-Hashomer diagnostic criteria. The presence of MEFV mutations was investigated in exons 2,3,5 and 10 by multiplex-PCR reverse hybridisation method. All the patients were questioned for the presence of concurrent disorders, and the medical records of these patients were revised retrospectively. RESULTS: 259 unrelated patients (female: 143, male: 116; mean age: 33.5±12 years) were included in this study. Hom and Het mutations were found in 79 (31.9%) and 88 (35.6%) patients with FMF, respectively. cHet mutations were found in 68 (27.5%) FMF patients. Early onset and early diagnosis of FMF were found in Hom group compared to Het and compound Het groups. The number of the patients with a higher severity score was significantly higher in Hom group (n=40, 50.6%) than Het (n=12, 13.6%) and cHet groups (n=10, 14.7%), (p<0.0001). No significant differences were found between the groups in terms of clinical features, except for erysipelas like erythema (ELE) (Hom group: 69.6% vs. Het group 37.5%, p<0.0001). Amyloidosis and concomitant disorders were found in 22 FMF patients with Hom MEFV mutations, 16 FMF patients with heterozygous mutations, 7 FMF patients with cHet mutations. CONCLUSIONS: While the presence of homozygous mutations creates tendency for a severe disease phenotype, the development of concomitant disorders seems to be independent of homozygous mutations.

Indications for bone marrow examinations in rheumatology.

Hematologic involvement or hematologic malignancies are frequently encountered during the course of rheumatic diseases. Bone marrow (BM) aspiration and/or biopsy examinations may have a diagnostic role in explaining hematologic findings detected in rheumatology clinical practice. Our aim was to describe the indications for BM examinations and to share our BM aspiration/biopsy results. We analyzed 140 BM aspiration/biopsy results of patients conducted at the Department of Rheumatology from 2010 to 2018. Demographics, complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) values, serum biochemistry test results including lactate dehydrogenase (LDH), organomegaly, indications for BM examinations and BM examination results for each patient, and mortality rates were recorded. Out of the 140 patients, 63.6% were female, and the median (Q1-Q3) age was 53 (39.5-65) years. One hundred fifteen (82.1%) patients were diagnosed as having primary rheumatic disease, and 25 (17.8%) were admitted due to musculoskeletal symptoms. Rheumatoid arthritis (RA) (n = 34, [29.5%]), and systemic lupus erythematosus (SLE) (n = 21, [18.2%]) were the most common rheumatic diseases. Cytopenia was the most common indication for BM aspiration/biopsy (n = 83, [59.3%]). Thirty-nine (47%) of 83 patients had drug-induced cytopenia. A pathology was detected in 40 (28.5%) of the 140 BM examinations. Patients with pathologic BM results had either a hematologic malignancy (n = 38, [95%]) or metastasis to a solid organ (n = 2, [5%]). The group of patients with pathologic BM biopsy results had significantly higher rates of lymphadenopathy, splenomegaly, and monoclonal gammopathy compared with the group with non-pathologic results (p = 0.001, p = 0.011, and p = 0.023, respectively). Likewise, LDH concentrations of those with pathologic results were higher than in patients with non-pathologic results [737 (range 577-1420) IU/L vs. 541 (range 306-840) IU/L, p = 0.019]. In this study, cytopenia or CBC abnormalities accompanied by elevated LDH values or anemia along with increased ESR were the most common indications for BM aspiration/biopsy. Further prospective studies are needed to determine the indications of BM aspiration/biopsy and establish the parameters that predict abnormal BM results in rheumatology practice.

Why are male patients with Behçet's disease prone to thrombosis? A rotational thromboelastographic analysis.

OBJECTIVES: To investigate whether there is a difference between male and female patients with Behçet's disease (BD) in terms of hypercoagulability by using modified rotational thromboelastograhic (ROTEM) analysis. METHODS: 126 BD patients (71 male, 55 female; mean age: 41±9 yrs) who met ISSG criteria for BD were included into the study. 23 patients with vasculitis (16 female, 7 male; mean age 49±16 yrs), and 25 healthy individuals (11 female, 14 male; mean age: 37±10 yrs) were included to the study as disease and healthy control (HC) group, respectively. Clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) were determined by INTEM and EXTEM analyses. As a marker of vascular endothelial injury, along with inflammatory markers, vWFag levels were investigated in patients and HC group. RESULTS: Extem-CFT was shorter in only vasculitic group compared to HC group. Intem-CFT was found to be shorter in BD patients and vasculitis group compared to HC. Intem-MCF was significantly longer in male BD patients than female BD patients. Extem-CFT was found to be shorter in male BD patients compared to female BD patients. Extem-MCF was statistically longer in male BD patients. In inactive male BD patients, while Intem-CFT was shorter than HC individuals, Intem-MCF and Extem-MCF were statistically longer than HC (p<0.02, p<0.03), respectively. However, no significant differences were found between inactive female BD patients and HC in terms of all ROTEM parameters. CONCLUSIONS: These results support that male BD patients have a hypercoagulable state compared to female BD patients, which may explain why male patients are prone to thrombotic complications.

Do pulmonary findings of granulomatosis with polyangiitis respond to anti-tuberculosis treatment?

Granulomatosis with polyangiitis (GPA) involves upper and lower respiratory tracts and kidneys. Lung involvement is among the most important organ involvements in GPA. GPA's lung involvement might be confused with other granulomatous conditions with lung involvement. In this report, we presented clinical features of two cases with GPA who had been diagnosed as tuberculosis (TBC) and well treated with anti-tuberculosis (anti-TBC) drugs. However, one of two cases had ear-nose-throat (ENT) manifestations before the diagnosis of TBC and her extrapulmonary findings related with GPA have added to clinical features in the following years. In the second case, the manifestations of GPA appeared after 13 months of anti-TBC treatment. We speculated that lung involvement in these cases may be due to GPA rather than TBC. Our aim was to highlight difficulties in the differential diagnosis between GPA and TBC and suggest the possible beneficial effect of anti-TBC drugs on the lung involvement due to GPA in light of the literature data.

Atrium Advanta V12 Large Diameter Stent-Graft Applications for Infrarenal Abdominal Aortic Pseudoaneurysms (due to Behcet Disease): Safety and Efficacy.

BACKGROUND: The aim of the study was to determine the safety and effectiveness of Atrium Advanta V12 large diameter stent-graft applications for infrarenal abdominal aortic pseudoaneurysms (due to Behcet disease [BD]). METHODS: Data of Advanta V12™ (Atrium Europe B.V, Mijdrecht, the Netherlands) applied 12 female patients (mean age 30.5 ± 6.3, range 26-44) with infrarenal abdominal aortic pseudoaneurysms were analyzed retrospectively. All Advanta V12 large diameter stent grafts were implemented from right or left sided 12F femoral sheaths. Stent grafts with 12-16 mm in size and 29-61 mm in length were utilized. Technical success rate, procedure-related mortality and morbidity, and primary patency rate at 4 years were evaluated. RESULTS: Technical success rate was 100%. Neither procedure-related mortality nor morbidity was determined. The mean aortic diameter was 14.0 ± 0.8 mm for pseudoaneurysmatic abdominal aortas. The mean follow-up period was 46.5 ± 40.3 months (range 18-75). During follow-ups, only one recurrent aneurysm has evolved at the stenting site due to patients' withdrawal of immunosuppressive treatment. The advent of a new aneurysm proximal or distal to the stent-graft region or at the femoral access localization was not observed. There were no stent occlusions. Primary patency rate at 4 years was 100%. Complete aneurysm exclusion was achieved 100% at 48 months. CONCLUSIONS: The use of Advanta V12 large diameter stent grafts for infrarenal abdominal aortic pseudoaneurysms (due to BD), especially in female patients with small aortic diameter, is safe and efficient. Primary patency rate of the stent grafts at 4 years is excellent.

Etanercept-induced leukemia: could increased mean corpuscular volume be a predictor of hematologic malignancy?

In rheumatology practice, anti-tumor necrosis factor (TNF) alpha agents are frequently used medications, more so in ankylosing spondylitis (AS). There are case reports, besides their adverse effects, such as infection and injection site reaction, suggesting these agents may cause solid or hematologic malignancies. Acute leukemia secondary to anti-TNF alpha agents has been rarely reported in patients with AS. In this case report, based on a patient who developed acute leukemia while on the treatment with etanercept, we will discuss whether it is possible to predict acute leukemia by monitoring the mean corpuscular volume in light of the literature.

Urolithiasis as an extraarticular manifestation of ankylosing spondylitis.

Ankylosing spondylitis (AS) affects sacroiliac and axial joints as well as extraarticular organs, such as the eye, lung, bowel, and heart. Although examples of renal involvement in AS, such as IgA nephropathy, amyloidosis, and glomerulonephritis, have been reported, it has not been emphasized that urolithiasis is frequently formed in the clinical course of AS. Growing evidence indicates that urolithiasis may be observed in AS patients and is more frequent than other extraarticular features. In this review, we will discuss frequency and predictors of AS-related urolithiasis and summarize the possible underlying genetic and biochemical mechanisms. We believe an increased awareness of urolithiasis as a complication of AS will encourage future studies that will shed light on disease mechanisms and preventative therapies.

Butrylcholinesterase activity in chronic liver disease patients and correlation with Child-Pugh classification and MELD scoring system.

BACKGROUND: After 40 years since establishment of Child-Pugh staging, 14 years since establishment of MELD scoring system, and 25 years since establishment of King's College Criteria, there is still a search for more accurate systems for determination of prognosis in patients with acute liver failure--cirrhosis and prioritization for receipt of a liver transplant--prediction of post transplant mortality. Butrylcholinesterase is an enzyme which is synthesized in the liver. The aim of the study was to evaluate the clinical utility of butrylcholinesterase as a discriminatory and prognostic factor in chronic liver disease patients. METHODS: Intergroup diversity for butrylcholinesterase activity was investigated in sixty cirrhotic, 20 chronic hepatitis patients, and 20 healthy subjects. Correlations between butrylcholinesterase activity and Child-Pugh classification and MELD scoring systems were examined. RESULTS: In addition to the statistically significant decrease in butrylcholinesterase activity among Child-Pugh A/B/C stages, the decrease in butrylcholinesterase activity was also statistically significant in control vs. Child-Pugh stage A and chronic hepatitis vs. Child Pugh stage A groups. A statistically significant correlation was determined between butrylcholinesterase activity and Child Pugh/MELD scores. CONCLUSIONS: Serum butrylcholinesterase activity might be helpful for discrimination of chronic hepatitis from cirrhosis after determination of reliable cut-off levels and dependent on the reductions of serum levels in acute liver failure and cirrhosis. It might be a useful tool for prioritization of liver transplantation.

Regulatory T cells in Behçet's disease: is there a correlation with disease activity? Does regulatory T cell type matter?

The aim of this study was to investigate the percentage of regulatory T cells and the correlation with clinical activity in Behçet's disease. Forty Behçet's disease (BD) patients, 18 males and 22 females, were included in the study. The patients were diagnosed according to the published BD criteria. Twenty age- and sex-matched volunteer healthy donors were also included. At the time of sampling, clinical activity was assessed for activity signs and symptoms according to the BD Current Activity Form. We considered active those patients with a clinical activity index equal to and/or above 2. Eleven patients had active disease and the remaining were considered as clinically inactive. We have studied the percentages of CD4+CD25+FOXP3+, CD4+CD25+ and CD4+FOXP3+regulatory T cells by flow cytometry and investigated the correlation with disease activity. Percentage of CD4+CD25+FOXP3+Treg in active patients was lower than clinically inactive patients and healthy controls. Percentage of CD4+CD25+Treg was not different between active and inactive patients and healthy controls. Percentage of CD4+FOXP3+Treg was lower than healthy controls in clinically active patients but was not different for inactive group and healthy controls. Patients were active when CD4+CD25+FOXP3+Treg was ≤1.19 %, CD4+CD25+Treg was ≤2.68 %, and CD4+FOXP3+Treg was ≤2.60. CD4+CD25+FOXP3+Treg and CD4+FOXP3+Treg were found negatively correlated with disease activity. Peripheral blood regulatory T cells are decreased in clinically active Behçet's disease patients. The advances in our understanding of the interactions between distinct subsets of Treg and clinical activity might help in modulating BD treatment.

Pulmonary hypertension in connective tissue diseases: epidemiology, pathogenesis, and treatment.

Pulmonary hypertension (PH) is a clinical condition characterized by increased pulmonary arterial pressure arising from a heterogeneous range of diseases that has a deteriorating effect on the quality of life and may cause early mortality if left untreated. Connective tissue disorders (CTD)-associated PH is the second most common cause of pulmonary arterial hypertension (PAH), after the idiopathic form, categorized as group I. Systemic scleroderma (SSc) accounts for 75% of CTD-associated PH cases. Although SSc ranks first place for CTD-associated PH, SSc is followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD), having a lesser frequency of PH occurrence, while it occurs as a rare complication in cases with rheumatoid arthritis (RA) and inflammatory myositis. PH may also occur during non-SSc CTDs and even other rheumatic diseases, including Behcet's disease and adult-onset Still's disease, albeit to a lesser extent. The prognosis of CTD-associated PH is worse than the other forms of PH. Although, as in idiopathic pulmonary arterial hypertension (IPAH), the mechanism of CTD-related PH is associated with an increase in vasoconstrictors like endothelin-1 and a decrease in vasodilators like prostacyclin and nitric oxide production, inflammation, and autoimmune mechanisms also play a role in the development and progression of PH. This may lead to the involvement of more than one mechanism in CTD-associated PH. Knowing which mechanism is dominant is very important in determining the treatment option. This review will primarily focus on the epidemiology, risk factors, and prognosis of PH that develops during rheumatic diseases; the pathogenesis and treatment will be briefly mentioned in light of the newly published guidelines. Key Points • Pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) in Western countries is the second most common type of PAH after idiopathic PAH (IPAH). • CTD-PH can be seen most often in systemic scleroderma (SSc), less in systemic lupus erythematosus (SLE), mixed CTD (MCTD), and rarely in other CTDs. • While current guidelines recommend annual transthoracic echocardiography as a screening test for asymptomatic SSc patients, screening for PH is not advised in the absence of symptoms suggestive of PH in other CTDs. • CTD-PH treatment can be divided into specific vasodilator PH treatments and immunosuppressive therapy. Current treatment guidelines recommend the same treatment algorithm for patients with CTD-associated PH as for patients with IPAH. Several case series have shown the beneficial effect of immunosuppressive agents in patients with SLE-PH and MCTD-PH.

A Hypothesis Regarding Neurosecretory Inhibition of Stress Mediators by Colchicine in Preventing Stress-Induced Familial Mediterranean Fever Attacks.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease characterized by recurrent episodes of fever and serositis. Colchicine (Col) has a crucial role in the prevention of amyloidosis and FMF attacks. The effect of Col on innate immune cells is based on the inhibition of the microtubule system. The microtubule system is also very important for neurosecretory functions. The inhibitory effect of Col on neurosecretory functions is an overlooked issue. Considering that the neuroimmune cross-talk process plays a role in the development of inflammatory diseases, the effect of Col on the neuronal system becomes important. FMF attacks are related to emotional stress. Therefore, the effect of Col on stress mediators is taken into consideration. In this hypothetical review, we discuss the possible effects of Col on the central nervous systems (CNS) and peripheral nervous systems (PNS) in light of mostly experimental study findings using animal models. Studies to be carried out on this subject will shed light on the pathogenesis of FMF attacks and the other possible mechanisms of action of Col apart from the anti-inflammatory features.