AB0566 NAILFOLD EXTENT OF REDUCED CAPILLARY DENSITY IS ASSOCIATED WITH DIGITAL ULCERS AND WITH AN INCREASED RISK OF DIGITAL ULCERS IN SYSTEMIC SCLEROSIS

Background:A growing evidence supports the role of microvasculopathy as a primary pathogenic event in systemic sclerosis (SSc). The most commonly used imaging technique to identify microangiopathy in SSc is high magnification videocapillaroscopy (NVC), and reduced capillary density and/or capillary loss, which is a typical feature of “scleroderma microangiopathy”, easily identified by NVC, has been associated with digital ulcers (DUs). Different approaches have been proposed to measure capillary density or capillary loss. Some of these were qualitative methods, others semi-quantitative, others only concerned a limited nailfold area, without ever evaluating the overall density, which is more suitable for quantitative estimate.Objectives:To assess the association between the extent of different values of nailfold capillary density and the presence of DUs and to identify the risk of developing DUs, based on quantitative parameters.Methods:The study involved 54 SSc selected patients (47 women and 7 men, mean age 59.5 years, 50 with limited and 4 with diffuse). The study population came from an ongoing database, that includes clinical and laboratory data of patients with definite SSc. A videocapillaroscope (VideoCap® 3.0, DS Medica, Milan, Italy) with a 200x optical probe was used. During examination, eight fingers (fingers 2–5 of each hand), 4 fields per finger, according to the standard literature were assessed. For each patient, a total of 32 images were collected, then classified as having either “normal”, “non-specific” or the “scleroderma pattern” (SP). Capillary density was defined as the number of capillaries/mm in the distal row, regardless of its shape and morphology. Avascular areas were defined by the absence of loops within a width/area extending over more than 500 microns. For each patient, the SP images were further graded with no/slight reduction of the capillary density (7-9 loops/mm) (NOR), with a well-defined reduction of capillary density (6-4 loops/mm) (RED) and with loss of capillaries (<4) plus avascular areas (AA). Then, the overall percentages were calculated (the number with SP, the number with NOR, with RED and with AA, respect to 32), thus obtaining the quantitative measures. All data were analysed using the MedCalc® version 18.6; 64-bit (MedCalc Software, Mariakerke, Belgium).Results:A total of 1728 images were analyzed. Patients with DUs were 16/54 (29.6%). All patients had a SP, but only five patients showed a SP along the entire nailfold. A comparison between patients with or without DUs showed a significant difference both for the overall extent of AA (p=0.032), and particularly for the overall extent of RED (p<0.001). No significant difference was found regarding the overall extent of the SP (p=0.085). Factor significantly associated with DUs in multivariate analysis was the overall extent of RED (p=0.0286). The ROC curve was very effective at discriminating the capillary feature able to distinguish patients with DUs from patients without DUs. The discriminatory power of the overall extent of RED was very good, with an AUC of 0.948 (95 % CI 0.852 ± 0.990). Then, we calculated the cut-off values of the overall extent of RED for presence/absence of DUs with the highest combination of sensitivity and specificity. The resulting cut-off value (Yourden index of 0.825) was >68.7 (sensitivity 92.31 %; specificity 90.24 %) with a LR+ of 9.46.Conclusion:Our data strongly support that the capillary density between 4 and 6 loops/mm is the best capillaroscopic quantitative measure associated with DUs and able to discriminate the probability of having DUs. If all SSc-specific antibodies and/or other laboratory/clinical parameters are not yet available, the overall capillary density can allow physicians to assess SSc patients easily, regarding DUs and risk for developing DUs.Disclosure of Interests:None declared

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Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

Disease Markers ◽

10.1155/2016/6064830 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Andréa Tavares Dantas ◽

Sayonara Maria Calado Gonçalves ◽

Anderson Rodrigues de Almeida ◽

Rafaela Silva Guimarães Gonçalves ◽

Maria Clara Pinheiro Duarte Sampaio ◽

...

Keyword(s):

Systemic Sclerosis ◽

Clinical Manifestations ◽

Serum Levels ◽

Vascular Involvement ◽

Digital Ulcers ◽

Serum Samples ◽

Peripheral Blood Mononuclear ◽

Pbmc Culture ◽

Significant Difference ◽

Skin Biopsies

Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

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AB1076 COLOR DOPPLER HIGH- FREQUENCY ULTRASOUND OF DIGITAL ARTERIES IN PATIENTS WITH SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5395 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1827.3-1827

Author(s):

O. Alekseeva ◽

N. Yudkina ◽

A. Demina ◽

A. Volkov ◽

E. Nasonov

Keyword(s):

Blood Flow ◽

Systemic Sclerosis ◽

Color Doppler ◽

Laboratory Data ◽

Clinical Signs ◽

Vascular Complications ◽

Nailfold Capillaroscopy ◽

Exclusion Criterion ◽

Digital Ulcers ◽

Linear Probe

Background:Systemic sclerosis (SSc) can lead to vascular complications such as digital ulcers or pitting scars (DU/PS). These changes develop in most patients with SSc and exacerbate their condition. However, there are no methods for dynamic assessment of the vascular involvement. The dynamics of capillaroscopic changes is very slow.Objectives:The aim of the study was to compare blood flow parameters of digital arteries in SSc patients and healthy individuals and to compare with nailfold capillaroscopy and clinical signs of ischemia (DU/PS).Methods:32 SSc patients, mean age 49,5 [42,0; 59,0] yrs and 26 ‘healthy’, mean age 43,5 [33,0; 57,0], were included. Groups of patients differed by gender and age. The exclusion criterion was the presence of obliterating vascular disease of the upper extremities. An Esaote MyLab Twice US system with 22 MHz linear probe was used. A total of SSc patients and controls underwent Color Doppler ultrasonography (CDUS) of 376 (256 + 208) digital arteries to compare blood flow velocity, resistive indices (RIs) and presence of occlusion. Nailfold capillaroscopy, clinical and laboratory data were also evaluated.Results:In digital arteries, pulsatility index (PI), peak systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly lower and RI higher in SSc patients compared with controls (PSV: 13,28 [9,88; 16,7] vs17,45 [12,65; 22,5] cm/s, p=0,008; EDV: 2,68 [1,78, 4,05] vs 6,37 [4,75; 8,5] cm/s, p=0,000; RI: 0,78 [0,69; 0,81] vs 0,68 [0,59; 0,74], p=0,005; PI: 1,73 [1,32; 2,19] vs 1,22 [0,99; 1,55], p=0,002).We did not find any correlation between two methods. Also, we did not reveal any correlation between DU/PS, clinical, laboratory data and CDUS, but we found relationship between DU/PS and avascular areas or capillaroscopic findings (r= 0,37, p=0,045 and r= 0,40, p=0,03 correspondingly).Conclusion:Blood flow is significantly decreased in digital arteries in SSc, but clinical features of vasculopathy depend on microcirculatory disorders. It is important to continue research to find methods for dynamic evaluation of microcirculatory changes.References:noDisclosure of Interests:None declared

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Evaluating the Incidence of Leukopenia and Neutropenia with Valproate, Quetiapine, or the Combination in Children and Adolescents

Annals of Pharmacotherapy ◽

10.1345/aph.1l617 ◽

2009 ◽

Vol 43 (5) ◽

pp. 822-830 ◽

Cited By ~ 28

Author(s):

Aminur Rahman ◽

Lisa M Mican ◽

Charles Fischer ◽

Angela H Campbell

Keyword(s):

Children And Adolescents ◽

State Hospital ◽

Laboratory Data ◽

Child And Adolescent ◽

Severe Neutropenia ◽

Combination Group ◽

Hematologic Toxicity ◽

Monotherapy Group ◽

Increased Risk ◽

Significant Difference

Background At the Austin State Hospital, Austin, TX, a number of cases of neutropenia and leukopenia have been observed in children and adolescents who were treated with the combination of valproate and quetiapine. Use of this combination has raised concerns regarding an increased risk of hematologic toxicity. Objective To evaluate the incidence of leukopenia and neutropenia associated with the use of valproate, quetiapine, or the combination in the child and adolescent population. Methods This study was a retrospective evaluation of patients from the child and adolescent psychiatric service of the Austin State Hospital who were treated with valproate, quetiapine, or the combination. Subjects were selected from patients discharged between August 1, 2004, and August 31, 2007. Laboratory data were evaluated to determine the incidence and severity of leukopenia and neutropenia associated with valproate, quetiapine, and a combination of the 2. Results A total of 131 patients were included in the study. Analysis of the laboratory data revealed a combined incidence of neutropenia and/or leukopenia of 44%, 26%, and 6% in the combination group, valproate monotherapy group, and quetiapine monotherapy group, respectively. Differences in the incidence of neutropenia and/or leukopenia between the quetiapine monotherapy group and valproate monotherapy group, as well as the quetiapine monotherapy group and the combination group reached statistical significance. A significant difference was found among groups based on absolute neutrophil count Common Toxicity Criteria severity (p < 0.001). The combination group differed significantly in incidence of moderate-to-severe neutropenia (14 cases) from both the valproate (5 cases) and quetiapine (0 cases) monotherapy groups, A significantly greater number (44%) of African American patients experienced neutropenia and/or leukopenia than white (not Hispanic or Latino; 29%) or Hispanic or Latino (11%) patients. Conclusions Patients treated with valproate or the combination of valproate and quetiapine should be monitored for the occurrence of leukopenia and neutropenia. Controlled studies are warranted to examine possible pharmacokinetic and pharmacodynamic interactions with the combination of valproate and quetiapine to further evaluate the hematologic findings of this study.

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SAT0326 SYSTEMIC SCLEROSIS WITHOUT ANTINUCLEAR ANTIBODIES: A MULTI-CENTER STUDY OF EUSTAR COHORT IN CHINA

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3168 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1108.1-1109

Author(s):

M. Hui ◽

J. Zhou ◽

L. Zhang ◽

X. Duan ◽

M. Li ◽

...

Keyword(s):

Systemic Sclerosis ◽

Clinical Features ◽

Topoisomerase I ◽

Antinuclear Antibody ◽

Antinuclear Antibodies ◽

Rna Polymerase Iii ◽

Laboratory Data ◽

Positive Group ◽

Significant Difference ◽

Chi Square Analysis

Background:The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation and malfunction in patients with systemic sclerosis (SSc)[1]. A variety of ANAs[2], including anti-centromere antibody, anti-topoisomerase I antibody, and anti-RNA polymerase III antibody, are associated with unique sets of disease manifestations and widely used in routine clinical practice for diagnosis, clinical subgrouping, risk stratification and prediction of future organ involvements and prognosis in SSc patients[3,4].Objectives:This study aimed to investigate the clinical features of SSc patients with negative ANAs in a European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) and Chinese Rheumatism Data Center (CRDC) multi-center cohort in China.Methods:Patients were prospectively recruited between April 2008 and June 2019 based on the EUSTAR database and CRDC multi-center cohort from 154 clinical centers nationwide, all of whom fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Antinuclear antibody testing result was intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those with negative ANAs. T-test and chi-square analysis were performed in the comparisons.Results:Antinuclear antibodies were detected in 2129 out of 2809 systemic sclerosis patients enrolled in the multi-center cohort and 4.2% of them were negative. There was significant difference between patients with negative and positive ANAs based on gender (29/60 vs 294/1746, p<0.001). The presence of Raynaud’s phenomenon is less common (71.8% vs 99.8%, p<0.001) in the ANA-negative patients. In addition, compared with ANA-positive patients, the incidence of certain critical organ involvements, including gastroesophageal reflux (5.6% vs 18.5%, p=0.002), interstitial lung disease (65.2% vs 77.9%, p=0.015) and pulmonary arterial hypertension (11.5% vs 29.0%, p=0.006) were significantly lower in ANA-negative patients than in the positive group. The proportion of IgG elevation, an indicator of disease activity and severity of inflammation, was significantly lower in the ANA-negative patients than that in the positive group (14.3% vs 41.2%, p<0.001), while no significant differences were found in other inflammatory indicators and skin scores.Conclusion:This study describes the clinical features of SSc patients with negative ANAs, which have been rarely mentioned or focused in existing studies. Antinuclear antibody is proved to be strongly associated with the clinical manifestations of systemic sclerosis patients and ANA-negative SSc patients tend to be in relatively milder conditions, including a less common involvement of critical organs and a more temperate inflammatory severity.References:[1]Seri, Jeong, Dahae, et al. Diagnostic value of screening enzyme immunoassays compared to indirect immunofluorescence for anti-nuclear antibodies in patients with systemic rheumatic diseases: A systematic review and meta-analysis. [J]. Seminars in arthritis and rheumatism, 2018.[2]Hesselstrand, R. The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis[J]. Rheumatology, 2003, 42(4):534-540.[3]Behmanesh F, Amin R, Khajedaluee M, et al. Autoantibody Profile in Systemic Sclerosis[J]. Acta Medica Iranica, 2010, 48(1):12-20.[4]Hachulla E, Dubucquoi S. Nuclear auto-antibodies: a useful tool for the diagnosis, the classification and the prognosis of systemic sclerosis. [J]. La Revue de Médecine Interne, 2004, 25(6):442-447.Disclosure of Interests:None declared

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Systemic Sclerosis Patients With Negative Antinuclear Antibodies Have Distinctive Clinical Manifestations: a Multicenter CRDC Cohort in China

10.21203/rs.3.rs-147806/v1 ◽

2021 ◽

Author(s):

Min Hui ◽

Jiaxin Zhou ◽

Liyun Zhang ◽

Xinwang Duan ◽

Mengtao Li ◽

...

Keyword(s):

Systemic Sclerosis ◽

Data Center ◽

Antinuclear Antibodies ◽

Laboratory Data ◽

Clinical Manifestations ◽

Organ Involvement ◽

Multicenter Cohort ◽

Significant Difference ◽

Critical Organ ◽

Pulmonary Arterial

Abstract Objective: The presence of circulating antinuclear antibodies (ANAs) is a hallmark of immune dysregulation in patients with systemic sclerosis (SSc). A variety of ANAs are associated with unique sets of disease manifestations and are widely used in clinical practice for diagnosis, clinical subgrouping, and prediction of future organ involvement and prognosis in SSc. This study aimed to investigate the clinical features of SSc patients negative for ANAs in a Chinese Rheumatism Data Center (CRDC) multicenter cohort in China.Methods: Based on the CRDC database, patients were prospectively recruited between April 2008 and June 2019 from 154 clinical centers nationwide, and all cases fulfilled the 2013 ACR/EULAR classification criteria for systemic sclerosis. Results for antinuclear antibodies were intensively collected. Demographic, clinical, and laboratory data were compared between ANA-positive SSc patients and those negative for ANAs.Results: Antinuclear antibodies were detected in 2129 of 2809 patients enrolled in the study; 4.2% patients were negative. There was a significant difference between patients negative and positive for ANAs based on sex (29/60 vs 294/1746, p＜0.001). The presence of Raynaud’s phenomenon was less common (71.8% vs 91.8%, p＜0.001) in the ANA-negative patients. In addition, the incidence of certain critical organ involvement, including gastroesophageal reflux (5.6% vs 18.5%, p=0.002), interstitial lung disease (65.2% vs 77.9%, p=0.015) and pulmonary arterial hypertension (11.5% vs 29.0%, p=0.006), was significantly lower in ANA-negative patients than in ANA-positive patients. The proportion of abnormal ESR (32.4% vs 47.6%, p=0.013) and IgG elevation (14.3% vs 37.0%, p=0.003), an indicator of disease activity, was significantly lower in ANA-negative patients than in ANA-positive patients.Conclusion: Antinuclear antibodies are strongly associated with the clinical manifestations of systemic sclerosis, with ANA-negative SSc patients tending to exhibit relatively milder disease.

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Effect of bosentan in pulmonary hypertension development in systemic sclerosis patients with digital ulcers

PLoS ONE ◽

10.1371/journal.pone.0243651 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243651

Author(s):

Ivan Castellví ◽

Carmen Pilar Simeón ◽

Monica Sarmiento ◽

Jordi Casademont ◽

Hèctor Corominas ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Statistical Significance ◽

Vascular Complications ◽

Digital Ulcers ◽

Entire Cohort ◽

Increased Risk ◽

Pulmonary Arterial ◽

Hypertension Development

Systemic sclerosis is a disease where microcirculation damage is critical in their beginning and vascular complications have similar pathogenic findings. Digital ulcers are a frequent complication in systemic sclerosis patients and pulmonary hypertension is one of the leading causes of death. The use of bosentan has been shown to be useful for the treatment of pulmonary arterial hypertension and to prevent new digital ulcers. However, is unknown if bosentan can prevent pulmonary hypertension. Our objective was to determine if bosentan is useful to prevent pulmonary hypertension in SSc patients. A retrospective study in 237 systemic sclerosis patients with digital ulcers history treated or not with bosentan to prevent it was made. We analyzed the occurrence of pulmonary hypertension defined by an echocardiogram pulmonary arterial pressure > 40 mmHg in the entire cohort. Demographic, clinical, and treatment variables were recorded for all patients. Statistical significance was denoted by p values < 0.05. Fifty-nine patients were treated with bosentan a median of 34 months. 13.8% of treated patients had pulmonary hypertension vs 23.7% of untreated patients (p 0.13) during the follow up. In multivariate analysis patients not treated with bosentan had 3.9fold-increased risk of pulmonary hypertension compared with patients under bosentan treatment (p < 0.02). Moreover the percentage carbon monoxide diffusing capacity (DLCO) in bosentan treated patients did not decrease from baseline to the end of follow-up (61.8±14% vs 57±20.1%, p = 0.89). We concluded that Systemic sclerosis patients with digital ulcers treated with bosentan seems to have less risk to develop pulmonary hypertension and to stabilize DLCO

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Breed related odds ratio and anatomic distribution of canine mast cell tumours in Austria

Tierärztliche Praxis Ausgabe K Kleintiere / Heimtiere ◽

10.15654/tpk-140165 ◽

2014 ◽

Vol 42 (06) ◽

pp. 367-373 ◽

Cited By ~ 6

Author(s):

K. Freeman ◽

G. Kirtz ◽

E. H. Hooijberg ◽

K. Sick ◽

E. F. Leidinger

Keyword(s):

Mast Cell ◽

Disease Risk ◽

Laboratory Data ◽

Age Distribution ◽

Odds Ratios ◽

Skin Tumours ◽

Increased Risk ◽

Mixed Breed ◽

Significant Difference ◽

Anatomic Distribution

SummaryObjective: An increased risk of mast cell tumours (MCT) in certain breeds has been described repeatedly in the literature. The incidence of MCTs for registered breeds in Austria, an estimate of the risk by means of the odds ratios based on breed as well as the anatomic localisation of MCTs were examined. Material and methods: In the first part of the study, the ranking of breeds in Austria based on 147,802 dogs with known breed (including mixed breed) was determined, based on those dogs included in the laboratory data base from 2000 to 2010. In the second part of the study, 476 dogs were identified with MCTs and analysed by age, sex, Patnaik grade of MCT and breed distribution. The odds ratios with confidence intervals were calculated for all breeds with skin tumours. Results: The age distribution showed a peak in the age group from 6.1 to 8.0 years; 70% of MCTs were localised to the head and trunk. No significant difference was found based on gender. The evaluation of the odds ratios showed that only four of the 20 of the most popular in Austria breeds (Boxer, Bernese Mountain Dog, Golden Retriever, Spaniel) had an increased risk; on the other hand, some breeds which have not been previously identified in the literature were indicated to have a significantly increased risk for MCT (e.g., Dogo Argentino, Tibetan Spaniel, Pyrenean Mountain Dog, Beauceron, and Austrian Smooth-haired Hound). Conclusion and clinical relevance: Because disease risk may influence the popularity of some currently rare breeds, consultation with breeders and owners regarding the identification of the breeds newly identified in this study as an increased risk for development of mast cell tumours is indicated.

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OP0270 LONG-TERM EFFICACY AND SAFETY OF BOSENTAN IN PATIENTS WITH DIGITAL ULCERS RELATED TO SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1916 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 164-164

Author(s):

N. Cristina ◽

L. Groseanu ◽

F. Berghea ◽

A. Balanescu ◽

V. Bojinca ◽

...

Keyword(s):

Systemic Sclerosis ◽

Control Group ◽

Digital Ulcers ◽

Efficacy And Safety ◽

Term Efficacy ◽

Elevated Liver Enzymes ◽

Significant Difference ◽

The Mean

Background:Two pivotal studies, RAPIDS-1 and RAPIDS-2 revealed that bosentan reduces the development of new digital ulcers (DUs) in patients with systemic sclerosis (SSc). However data regarding the long-term use of this dual endothelin antagonist receptor in the treatment of DUs is scarce.Objectives:The aim of the present study was to evaluate long term efficacy and safety profile of bosentan in patients with DUs related to SSc.Methods:A prospective observational case-control study, conducted between 2014 and 2020 enrolled 65 SSc patients with ≥1 active DUs at baseline, who received bosentan therapy. Demographic and clinical features, including DUs incidence and patients subjective perception of DU pain and/or Raynaud’s Phenomenon, were collected. Nailfold videocapillaroscopy was performed in all patients.Results:The study included 51 females and 14 males, with a mean age of 52.6 years, 30 with diffuse subset, most of them with late scleroderma pattern (46/65). Number of DUs at baseline was 4.55 (±2.8), median duration of treatment was 25.95 (±19.4) months. Microangiopathy evolution score (MES) was 5.1 (2.19), visual analog scale (VAS) for DU was 77.9, VAS for Raynaud was 73.4.Patients receiving bosentan had clinically significant reduction in the mean number of DU (p<0.001). The effect was most powerful for the first 6 months of treatment, but the improvement was sustained until 24 months’ follow-up, when the mean DU number reached a plateau that was kept until end of study. 6 month and 24 month evaluations also revealed significant decrease in the VAS for DU (p<0.05) and in the VAS for Raynaud (p<0.01). Statistically significant difference was noted between bosentan-treated and the control group with respect to the decrease in the mean number of digital ulcers. (p=0.005).There was a clear trend towards an improvement in MES score, between baseline and the next follow-up assessments (p=0.003). The difference was statistically significant when compared to control group, but only for the first 18 months of treatment (p<0.001).14 patients (28.75%) discontinued bosentan therapy for administrative reasons. The median time among patients who interrupted the treatment was 6.9 months. An accelerated development of new DU was described 6 months after (p=0.02). Following recommencement of bosentan, the mean number of DU has rapidly decreased (p=0.008). There was no significant difference between patients who temporarily discontinued bosentan for 6 or 12 months.Bosentan was stopped due to lack of efficacy in 2 cases and due to side effects in 7 cases: 4 elevated liver enzymes, 1 severe trombocytopenia, 1 dyspneea agravation and low blood pressure.Conclusion:The present data suggest that treatment with endothelin receptor antagonist bosentan was associated with a significant reduction in the mean number of DU in patients with SSc. The beneficial effect of bosentan persisted throughout the study but was most evident in the first 6 months of treatment. Statistical analysis showed a significant improvement of the microangiopathy evolution score from baseline to end of therapy. 14 patients had a high relapse rate due to potential rebound effect, 6 months after bosentan withdrawal.The drug was reintroduced succesfully for 10 (70%) patients with a significant decrease in the number of DU.References:[1]UK Scleroderma Study Group: digital vasculopathy in systemic sclerosis, Rheumatology, Volume 54, Issue 11, November 2015, Pages 2015[2]Groseanu L, Berghea F, Bojinca V, et al AB0779 Long term follow-up of a systemic sclerosis group treated with bosentan, Annals of the Rheumatic Diseases 2018;77:1523-1524.Disclosure of Interests:None declared

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Clinical Characteristics of COVID-19 Patients with Gastrointestinal Symptoms

Archives of Iranian Medicine ◽

10.34172/aim.2021.21 ◽

2021 ◽

Vol 24 (2) ◽

pp. 131-138

Author(s):

Mahnaz Montazeri ◽

Nastaran Maghbouli ◽

Raika Jamali ◽

Alireza Sharifi ◽

Marzieh Pazoki ◽

...

Keyword(s):

Disease Severity ◽

Clinical Characteristics ◽

Laboratory Data ◽

Gastrointestinal Symptoms ◽

Chi Square ◽

Increased Risk ◽

Gi Symptoms ◽

Significant Difference ◽

Treatment Data ◽

Risk Of Disease

Background: We aimed to assess the gastrointestinal (GI) manifestations of patients with severe acute respiratory syndrome coronavirus 2 infection and determine factors predicting disease prognosis and severity among patients with GI symptoms. Methods: In this retrospective study, we evaluated laboratory confirmed (by real-time polymerase chain reaction) inpatient cases of coronavirus-associated disease 2019 (COVID-19), referred to Sina hospital, a tertiary educational hospital of Tehran University of Medical Sciences, from March 10 to May 20, 2020. Demographic and clinical characteristics, laboratory data, outcomes and treatment data were extracted and analyzed using SPSS version 20. Results: A total of 611 patients (234 women and 377 men) were included with 155 patients having GI symptoms. The most prevalent reported GI symptom was nausea/vomiting in 115 (18.8%) of patients. A total of 20 patients (3.2%) only had GI symptoms (without respiratory symptoms). There was no statistically significant difference in the clinical outcomes, disease severity, intensive care unit (ICU) admission and mortality between patients with and without GI symptoms. Aspartate Aminotransferase level was associated with 446% increased risk of disease severity (adjusted odds ratio: 5.46, 95% CI: 2.01 to 14.81) (P=0.040) among patients with GI symptoms. Additionally, we found that treatment with antibiotics in addition to mechanical ventilation was associated with increased survival among patients with GI symptoms (Pearson Chi square: 6.22; P value: 0.013). Conclusion: More attention should be paid to patients with only GI symptoms for early patient detection and isolation. Moreover, patients with GI manifestations are not exposed to higher rates of disease severity or mortality.

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Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound

Rheumatology International ◽

10.1007/s00296-021-04956-7 ◽

2021 ◽

Author(s):

Rositsa Valerieva Karalilova ◽

Zguro Anastasov Batalov ◽

Tanya Lyubomirova Sapundzhieva ◽

Marco Matucci-Cerinic ◽

Anastas Zgurov Batalov

Keyword(s):

Systemic Sclerosis ◽

Treatment Options ◽

Unmet Need ◽

Skin Thickness ◽

Digital Ulcers ◽

Internal Organs ◽

Percent Improvement ◽

Significant Difference ◽

Modified Rodnan Skin Score ◽

Musculoskeletal Involvement

AbstractSystemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (p < 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (p < 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (p = 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile.

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