: The most prominent feature of systemic sclerosis (SSc), besides vasculopathy and autoimmune disorders, is excessive fibrosis. Serotonin affects hemostasis and can induce vasoconstriction, which is ...presumed to be one of the pathophysiological patterns in SSc that leads to fibrosis. Our aim was to explore the possible association of serotonin with some of the clinical features of SSc in our cohort of patients.
: We measured serotonin levels in sera of 29 female SSc patients. Patients were 41-79 years old, their average disease duration was 9 years. Serotonin values were analyzed in correlation with clinical and laboratory parameters, such as modified Rodnan skin score (mRSS), digital ulcers (DU), and spirometry parameters-forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and lung diffusion capacity of carbon monoxide (DLCO). Statistical analyses were performed using statistical software Statistica.
: We found correlation of serotonin level with mRSS (r = 0.388,
= 0.038). The highest values of serotonin were documented in patients with refractory DU, but this was not statistically significant. We also found a negative correlation between serotonin and FVC (r = -0.397), although it did not reach the level of significance (
= 0.114).
: Our study suggests that levels of serum serotonin could affect the course of skin fibrosis and partially restrictive pulmonary dysfunction in patients with SSc. We assume that serotonin might have influence on several features of SSc, but more studies are needed to reveal those relations.
The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature ...review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD.
COVID-19 presentations range from cold-like symptoms to severe symptoms with the development of acute respiratory distress syndrome (ARDS). We report on a severe COVID-19 patient who was mechanically ...ventilated and who developed ARDS and bacterial infection. Because of rapid clinical deterioration and the exhaustion of other treatment options, the family and attending physicians requested a compassionate use of adult allogeneic bone marrow-derived mesenchymal stem cells (MSC) in addition to commonly used immunosuppressive, antiviral, and supportive therapy. The clinical course is discussed thoroughly, with a special emphasis on the safety and effect of MSC therapy. Compassionate MSC treatment, given in three rounds, affected ARDS regression. The patient was discharged from the intensive care unit after 31 days and from hospital after 49 days in a good general condition. MSC treatment was not associated with any side effects and was well tolerated in a three-week period; therefore, it should be studied in larger trials and considered for compassionate use.
Based on the hypothesis that there is a substantial rate of adults with prediabetes and undiagnosed diabetes mellitus (DM), our aim was to perform haemoglobin A1c (HbA
)-based screening in a cohort ...of Croatian adults and estimate the prevalence of prediabetes and undiagnosed DM according to American Diabetes Association criteria.
This multi-center, cross-sectional study performed in six Croatian hospitals included 5527 patients aged 40 to 70 years admitted to the Emergency Department or undergoing a primary care check-up. Haemoglobin A1c was measured from leftover whole blood samples using the enzymatic method on either Alinity c or Architect c-series analyser (Abbott Laboratories, Chicago, USA). Haemoglobin A1c between 39-47 mmol/mol was classified as prediabetes, while ≥ 48 mmol/mol as undiagnosed DM.
After exclusion of 435 patients with known DM, the final cohort included 5092 patients (median age 57; 56% males). A total of 882 (17.3%) patients had HbA
values between 39 and 47 mmol/mol. There were 214 (4.2%) patients with HbA
≥ 48 mmol/mol. Prediabetes prevalence ranged from 14.2% to 20.5%, while undiagnosed DM from 3.3% to 7.3%, with statistically significant differences among settings (P < 0.001). Age-stratified analysis showed that prediabetes and undiagnosed DM prevalence increase with age (P < 0.001), being 25.4% and 5.8%, respectively, in patients aged 60 to 70 years.
Underlying impairment of glucose metabolism was identified in about one in five adults, with significant number of patients with already overt DM. These results should serve as a starting point for further steps directed towards promotion of preventive measures for DM in Croatia.
ObjectiveThe aim of this pilot-study was to examine serum calprotectin levels (sCAL) in patients with SLE and determine possible association with disease activity and history of vascular ...events.Methods27 consecutive SLE patients from daily hospital and outpatient rheumatology clinic and 13 healthy volunteers underwent demographic data collection, sCAL assessment (ELISA Buhlmann sCAL diagnostic test), and disease activity assessment by SLEDAI-2K for SLE patients. Patients were divided into two groups, active disease and remission, taking SLEDAI-2K value of 6 as a cut-off, and defined patients who had recent vascular incidents associated with SLE.Results13 patients in active group (38.5% women, median age 50 (35–58), SLE duration 8.85±6.26 years, SLEDAI-2K 14 (7–21)) were compared to 14 patients in remission group (85,7% women, median age 39 (35–53), disease duration 5.21±2.78 years, SLEDAK-2K 3.5 (2–4)) and to 13 control subjects (76,9% women, median age 25 (24–26)). Significantly higher occurrence of neuropsychiatric disease (53.8% vs. 14.3%, P=0.032) and vascular manifestations (76.9% vs. 14.3%, P=0.001) was observed in active patients compared to those in remission. We haven’t observed the difference in occurrence of APS, serositis, dermatologic, constitutional, renal, or hematologic manifestations of SLE between groups. sCAL levels were higher in all patients compared to the control group (1.1 (0.53–1.8) μg/ml vs. 0.7 (0.38–1.1) μg/ml, P=0.02). Moreover, sCAL was higher in the active group compared to remission patients (1.6 (1.1–3.0) μg/ml vs. 0.8 (0.2–1.4) μg/ml, P= 0.02). Patients with a history of recent vascular events had greater sCAL respect other SLE patients (1.7 (1.15–3) μg/ml vs. 1.0 (0.225–1.375) μg/ml, P=0.015). There was a positive correlation between SLEDAI and sCAL in all patients (ρ=0.532, P=0.0043), particularly in active ones (ρ=0.673, P=0.0017). There was no correlation between SLEDAI and sCAL within inactive patients (ρ=0.0678, P=0.818).ConclusionsSLE patients, especially those with active disease, had higher sCAL compared to healthy subjects. We established a positive correlation between vascular manifestations of SLE and sCAL, but also between SLEDAI-2K and sCAL in patients with active disease. Our study was limited due to the small sample size. Further research should confirm these hypotheses on a larger number of subjects.AcknowledgementThe authors declare no conflict of interest. This research was funded by the University of Split, School of Medicine.
Background: We aimed to investigate possible association between the HLA-B*35 allele and peripheral arthritis, tenosynovitis and enthesitis. Methods: Ultrasound of peripheral joints and tendons was ...performed in 72 HLA-B*35 positive patients with preliminary diagnosis of undifferentiated axial form of spondyloarthitis and joint and tendon pain. Patients with other known types of axial and peripheral spondyloarthritis were excluded as well as patients with other known types of arthritis. Results: Pathological changes were found in the joints of 33 (46%) patients and on the tendons in 13 (18%) patients. The most common ultrasound findings were joint effusion and synovial proliferation with positive power Doppler signal grade 1. The most common ultrasound finding in patients with painful tendons was tenosynovitis. A higher disease activity and an increased incidence of elevated CRP (≥5 mg/L) were more often observed in the group with positive ultrasound findings. Conclusion: In this study, we showed that the HLA-B*35 allele could be a potential risk factor for developing peripheral arthritis, but not for tenosynovits and enthesitis in patients with the undifferentiated axial form of spondyloarthritis. This result may influence the follow up of these patients, especially since it gives us an opportunity to consider the use of different types of DMARDs in the treatment of these patients.
Biologic disease-modifying antirheumatic drugs (DMARDs) are very effective in treating rheumatic diseases with a good patient tolerance. However, high cost and individualistic approach requires ...dedication of the physician. Therefore, the aim of this study was to determine how the COVID-19 pandemic has affected the prescription of biologic DMARDs in rheumatology at the University Hospital of Split. The data collection was conducted through an archive search in the Outpatient Clinic for Rheumatology in the University Hospital of Split, Split, Croatia. The search included the period before and after the start of the COVID-19 pandemic in Croatia (31 March 2020). Collected data included age, sex, ICD-10 code of diagnosis, generic and brand name of the prescribed drug, date of therapy initiation, and medication administration route. In the pre-COVID-19 period, 209 patients were processed, while in the COVID-19 period, 185 patients were processed (11.5% fewer). During pre-COVID-19, 231 biologic medications were prescribed, while during COVID-19, 204. During COVID-19, IL-6 inhibitors were less prescribed (48 (21%) vs. 21 (10%) prescriptions, p = 0.003), while IL-17A inhibitors were more prescribed (39 (17%) vs. 61 (30%) prescriptions, p = 0.001). In ankylosing spondylitis (AS), adalimumab was prescribed more during pre-COVID-19 (25 vs. 15 patients, p = 0.010), while ixekizumab was prescribed less (1 vs. 10 patients, p = 0.009). In rheumatoid arthritis, tocilizumab was prescribed more in the pre-COVID-19 period (34 vs. 10 patients, p = 0.012). Overall, the prescription trends of biologic DMARDs for rheumatologic diseases did not vary significantly in the University Hospital of Split, Croatia. Tocilizumab was prescribed less during COVID-19 due to shortages, while ixekizumab was more prescribed during COVID-19 due to an increase in psoriatic arthritis patients processed and due to being approved for treating AS.
Summary
Objective
The aim of this study was to investigate the distribution of HLA-DRB1 alleles in patients with rheumatoid arthritis (RA) in the Sinj Region (SR) and the rest of the Split-Dalmatia ...County (SDC) in Croatia and to determine their relationship with disease severity.
Methods
A total of 74 RA patients and 80 healthy controls from the SR, and 74 RA patients and 80 healthy controls from the rest of the SDC were genotyped using sequence-specific oligonucleotide primed PCR. High-resolution typing of HLA-DRB1*04 alleles was performed using the single specific primed polymerase chain reaction (PCR-SSP) method. Serum anti-CCP, rheumatoid factor, C‑reactive protein, and erythrocyte sedimentation rate were measured in all RA patients, whereas disease activity was assessed by DAS-28 and functional status by the Health Assessment Questionnaire Disability Index.
Results
The HLA-DRB1*04 allele was more frequent in patients with RA from the SR than that in patients from the rest of the SDC (18.2% vs. 9.5%;
P
= 0.014), whereas the HLA-DRB1*15 allele was more frequent in patients with RA from the rest of the SDC than in patients from the SR (16.2% vs. 7.4%;
P
= 0.010). Shared epitope (SE) positive patients from the SR had significantly higher serum anti-CCP and RF antibody levels (
P
= 0.014 and
P
= 0.004, respectively), higher disease activity (
P
= 0.043), and worse functional status (
P
< 0.001), than SE-positive patients from the rest of the SDC.
Conclusion
The observed higher incidence of more severe forms of RA in the SR in comparison to the rest of the SDC might be associated with the higher incidence of HLA-DRB1*04 allele in the SR.
Objective
To investigate possible association between sacroiliitis and HLA-B*35 positivity.
Method
After excluding patients with axial spondyloarthritis and HLA-B*27 positivity, psoriasis ...inflammatory bowel disease, preceding infections, or juvenile type of spondyloarthritis, 110 patients were recruited with a diagnosis of undifferentiated axial spondyloarthritis. All of them had inflammatory back pain of short duration (3 months to 2 years) and 72 were HLA-B*35 positive. In order to determine if there is a possible association of sacroiliitis and HLA-B*35 positivity, all patients underwent MRI of sacroiliac joints.
Results
A statistically significant association between the detection of bone marrow edema at sacroiliac joints on MRI and HLA-B*35 positivity (χ2 = 6.25;
p
= 0.022) was found. A logistic regression analysis revealed that the presence of HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI (OR 6, 95% CI 1.3–27,
p
= 0.021). HLA-B*35 positivity was also associated with a 4.7 times greater chance of finding elevated CRP (OR 4.7, 95% CI 1–11.9,
p
= 0.047) and a 5 times greater chance of finding peripheral joint synovitis (OR 5, 95% CI 1.75–14.3,
p
= 0.003). HLA-B*35-positive patients had high disease activity (mean ± SD of Bath Ankylosing Spondylitis Disease Activity Index 6.1 ± 1.72 and Ankylosing Spondylitis Disease Activity Score C-reactive protein Index 3 ± 0.64) with a high degree of functional limitations (mean ± SD of Bath Ankylosing Spondylitis Functional Index 5.3 ± 2.16).
Conclusion
The data clearly show the association between bone marrow edema on MRI at sacroiliac joints and HLA-B*35 allele in patients with undifferentiated spondyloarthritis. Further work is needed to understand how much this result may influence follow-up of these patients.
Key Points
• HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI in un-axSpa patients.
• HLA-B*35 allele was also associated with a 4.7 times greater chance of finding elevated CRP and a 5 times greater chance of finding peripheral joint synovitis in un-axSpa patients.
• HLA-B*35 allele could be a potential risk factor for developing sacroiliitis and axSpA.
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