Nailfold capillary density is associated with the presence and severity of pulmonary arterial hypertension in systemic sclerosis

Objective:The aim of this study was to investigate whether there are differences in capillary nailfold changes in patients with systemic sclerosis (SSc) with and without pulmonary arterial hypertension (PAH), and whether these changes are associated with PAH severity and disease specificity.Methods:Capillary density and loop dimensions were studied in 21 healthy controls, 20 patients with idiopathic PAH (IPAH) and 40 patients with SSc. Of the 40 patients with SSc, 19 had no PAH (SSc–nonPAH) and 21 had PAH (SSc–PAH), of whom eight had PAH during exercise.Results:Capillary density was lower in SSc–PAH compared with patients who had SSc–nonPAH (4.33/mm vs 6.56/mm respectively, p = 0.001), but loop dimensions were equal. In comparison with IPAH, patients with SSc–PAH had reduced capillary density (4.33/mm vs 7.86/mm, p<0.001) and larger loop dimensions (total width 101.05 µm vs 44.43 µm, p<0.001). Capillary density in healthy controls (9.87/mm) was significantly higher when compared with SSc–nonPAH (6.56/mm), SSc–PAH (4.33/mm) and with IPAH (7.86/mm). No differences in capillary dimensions were present between healthy controls and IPAH.Capillary density correlated with mean pulmonary arterial pressure (PAP) at rest in SSc–PAH at rest (r = −0.58, p = 0.039) and IPAH (r = −0.67, p = 0.001).Conclusions:Reduction of nailfold capillary density, but not capillary loop dimensions is associated with PAH, and correlates with the severity of PAH in both SSc and IPAH. This suggests that either systemic microvascular changes play a part in the development of PAH, or that PAH itself contributes to systemic microvascular changes.

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Nailfold Videocapillaroscopy in Systemic Sclerosis–related Pulmonary Arterial Hypertension: A Systematic Literature Review

The Journal of Rheumatology ◽

10.3899/jrheum.190296 ◽

2019 ◽

Vol 47 (6) ◽

pp. 888-895 ◽

Cited By ~ 3

Author(s):

Vanessa Smith ◽

Amber Vanhaecke ◽

Els Vandecasteele ◽

Miguel Guerra ◽

Sabrina Paolino ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Literature Review ◽

Arterial Hypertension ◽

Systematic Literature Review ◽

Capillary Density ◽

Nailfold Videocapillaroscopy ◽

Pulmonary Arterial ◽

Current Screening

Objective.Pulmonary arterial hypertension (PAH) is one of the leading causes of death in systemic sclerosis (SSc). Current screening algorithms are hampered by low positive predictive values. Outcome measures that could add to performance characteristics would be welcome. We aim to evaluate the role of nailfold videocapillaroscopy (NVC) using standardized definitions, in SSc-related PAH (SSc-PAH).Methods.A systematic review to identify original research papers documenting an association between NVC and right heart catheterization-defined SSc-PAH was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Subsequently, NVC characteristics were subdivided into quantitative (capillary density, dimension, morphology, and hemorrhages), semiquantitative, and qualitative assessment (NVC pattern), according to the definitions of the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases.Results.The systematic search identified 316 unique search results, of which 5 were included in the final qualitative analysis. The occurrence of incident SSc-PAH unequivocally associated in 2 longitudinal studies with progressive capillary loss (p = 0.04 and p = 0.033) and the progression to a severe (active/late) NVC pattern (p = 0.05/0.01 and HR = 5.12, 95% CI 1.23–21.27). In 3 cross-sectional studies, SSc-PAH was found to be unequivocally inversely associated with capillary density (p = 0.001 and p < 0.05) and associated with the presence of a severe NVC pattern (p = 0.03 and p < 0.05).Conclusion.This is the first systematic literature review investigating the role of NVC in SSc-PAH using standardized description, to our knowledge. Unequivocal associations were found between (incident) SSc-PAH and capillary density and NVC pattern. Integration of NVC into current screening algorithms to boost their performance may be a future step.

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Nailfold Capillaroscopy in Systemic Sclerosis Patients with and without Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10071528 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1528

Author(s):

Ioanna Minopoulou ◽

Marieta Theodorakopoulou ◽

Afroditi Boutou ◽

Alexandra Arvanitaki ◽

Georgia Pitsiou ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Meta Analysis ◽

Capillary Density ◽

Right Heart Catheterization ◽

Nailfold Capillaroscopy ◽

Cochrane Library ◽

Heart Catheterization ◽

Pulmonary Arterial

Systemic sclerosis (SSc)-related pulmonary arterial hypertension (SSc-PAH) is a leading cause of mortality in SSc. The extent of peripheral microvasculopathy assessed through nailfold capillaroscopy might correlate with the presence of PAH in SSc patients. We searched the PubMed, Cochrane Library, Scopus, and Web of Science databases and performed a random effects meta-analysis of observational studies comparing nailfold capillaroscopic alterations in SSc-PAH versus SSc-noPAH patients. Weighted mean differences (WMD) with the corresponding confidence intervals (CIs) were estimated. The quality of the included studies was evaluated using a modified Newcastle–Ottawa scale. Seven studies with 101 SSc-PAH and 277 SSc-noPAH participants were included. Capillary density was marginally reduced in the SSc-PAH group (WMD: −1.0, 95% CI: −2.0 to 0.0, I2 = 86%). This effect was strengthened once PAH diagnosis was confirmed by right heart catheterization (WMD: −1.2, 95% CI: −2.3 to −0.1, I2 = 85%). An increase in capillary loop width was observed in SSc-PAH compared to SSc-noPAH patients (WMD: 10.9, 95% CI: 2.5 to 19.4, I2 = 78%). Furthermore, SSc-PAH patients had a 7.3 times higher likelihood of active or late scleroderma pattern (95% CI: 3.0 to 18.0, I2 = 4%). SSc-PAH patients presented with worse nailfold capillaroscopic findings compared to SSc-noPAH patients.

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POS0335 THE POTENTIAL ROLE OF IL13 IN VASCULOPATHY IN SYSTEMIC SCLEROSIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3534 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 395.1-395

Author(s):

A. Schumann ◽

H. Grasshoff ◽

S. Comduehr ◽

G. Riemekasten

Keyword(s):

T Cells ◽

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Cd8 T Cells ◽

Receptor Type ◽

Type I ◽

Healthy Controls ◽

Pulmonary Arterial ◽

Acral Ulcers

Background:Systemic sclerosis (SSc) is a heterogeneous disease characterized by fibrosis, vasculopathy and autoimmunity. Dysfunctions causing disease pathology are characterized by the activation and recruitment of immune cells, as well as the formation of autoantibodies and cytokines. Profibrotic cytokines, such as interleukin-(IL)13, IL4 or IL6 play a crucial role in collagen production and fibrosis development [1]. Preliminary data reveal IL13 as a main driver for obliterative vasculopathy characterized by severe Raynaud phenomenon, acral ulcers and pulmonary arterial hypertension (PAH). Particularly acral ulcerations lead to a severe impairment in functional capacity in everyday life. In addition, pulmonary arterial hypertension is one of the main causes of the high mortality rate in SSc [2].Objectives:To prove the impact of IL13 in the pathogenesis of systemic sclerosis and thus provide the rationale for the identification of a potential new therapeutic target, we investigated IL13 expression in CD4 and CD8 T cells in patients suffering from systemic sclerosis compared to healthy controls.Methods:Peripheral blood mononuclear cells (PBMC) obtained from systemic sclerosis (SSc, n=31) patients and healthy controls (HC, n=13) were cultured without or in the presence of phorbol myristate acetate and ionomycin to activate T cells for cytokine production. Brefeldin A was used as an inhibitor of cytokine secretion. The intracellular IL13 and IL4 expression of CD4 and CD8 positive T cells were measured by flow cytometry and were compared between the investigated subgroups.To identify a disease phenotype mediated by IL13, the expression levels in the SSc group were correlated to clinical, laboratory and apparative parameters assessing organ dysfunction.Results:While there were no significant differences in IL4 expression between healthy and diseased individuals, analyses of IL13 positive CD4 and CD8 T cells showed significant differences compared to HC (CD8+IL13 p=0.048; CD4+IL13 p=0.0046) revealing the functional differences though high structural homology of the two interleukins. The increased expression of IL13 in T cells from patients with systemic sclerosis further supports the assumption of an interleukin mediated pathomechanism. Considering the IL13-mediated clinical phenotype, high levels were detected in patients showing signs for vasculopathy, correlation with sPAP (CD8+IL13 p=0.0392), NTproBNP (CD4+IL13 p=0.0461), creatinine (CD4+IL13 p=0.0227), angiotensin II receptor type I and endothelin receptor type A antibodies (CD4+IL13 p=0.0105, p=0.0042) was demonstrated. In addition, patients in the fourth quartile of CD4+IL13 expression showed a higher incidence of acral ulcers and pits than patients with low interleukin levels. Moreover, this group of patients had an increased cardiovascular comorbidity including atherosclerosis, coronary heart disease and arterial hypertension.Conclusion:Increased IL13 levels could be detected in patients with SSc, especially in patients with the phenotype of an obliterative vasculopathy. This indicates preliminary evidence for the use of IL13 blockers as a new therapeutic approach in systemic sclerosis.References:[1]Furue M, Mitoma C, Mitoma H, Tsuji G, Chiba T, Nakahara T, Uchi H, Kadono T. Pathogenesis of systemic sclerosis-current concept and emerging treatments. Immunol Res. 2017 Aug;65(4):790-797. doi: 10.1007/s12026-017-8926-y.[2]Tyndall AJ, Bannert B, Vonk M, et alCauses and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database Annals of the Rheumatic Diseases 2010;69:1809-1815. doi: 10.1136/ard.2009.114264Disclosure of Interests:None declared

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Successful Treatment of Pulmonary Arterial Hypertension in Systemic Sclerosis with Anticentriole Antibody

Case Reports in Rheumatology ◽

10.1155/2020/1926908 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Yusho Ishii ◽

Hiroshi Fujii ◽

Koichiro Sugimura ◽

Tsuyoshi Shirai ◽

Yosuke Hoshi ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Multiple Organ ◽

Exertional Dyspnea ◽

Mean Pulmonary Arterial Pressure ◽

Therapeutic Drugs ◽

Skin Sclerosis ◽

Pulmonary Arterial ◽

Minute Walk Distance

Systemic sclerosis (SSc) is characterized by skin sclerosis and multiple organ damages which may cause mortality and is usually accompanied with several specific autoantibodies, each of which is associated with characteristic complications. Among them, anticentriole antibody is recently reported to be highly associated with SSc-associated pulmonary arterial hypertension (SSc-PAH). In general, several vasodilators are used as therapeutic drugs for SSc-PAH, whereas immunosuppressive therapies are not. Here, we report the case of a 62-year-old female with anticentriole antibody-positive SSc-PAH treated with immunosuppressants and vasodilators. She presented with two-year exertional dyspnea and was diagnosed with PAH and SSc owing to the centriole staining pattern and other symptoms without digital sclerosis. Oral vasodilators were initially administered but were not sufficiently effective on dyspnea. Immunosuppressants such as prednisolone and cyclophosphamide were started. Both of them improved mean pulmonary arterial pressure and 6-minute walk distance, and the anticentriole antibody also disappeared. In this case, SSc-PAH with anticentriole antibody was properly diagnosed and immunosuppressants and vasodilators improved the hemodynamics of PAH with anticentriole antibody and stably maintained it and, in addition, reduced the titer of anticentriole antibody. This indicates that anticentriole antibody might represent a good responsive group to therapies among subgroups of patients with SSc-PAH.

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Bosentan Improves Skin Perfusion of Hands in Patients with Systemic Sclerosis with Pulmonary Arterial Hypertension

The Journal of Rheumatology ◽

10.3899/jrheum.100358 ◽

2010 ◽

Vol 37 (12) ◽

pp. 2531-2539 ◽

Cited By ~ 31

Author(s):

EDOARDO ROSATO ◽

ILENIA MOLINARO ◽

FEDERICA BORGHESE ◽

CARMELINA ROSSI ◽

SIMONETTA PISARRI ◽

...

Keyword(s):

Blood Flow ◽

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Skin Blood Flow ◽

Dorsal Surface ◽

Laser Doppler ◽

Healthy Controls ◽

Skin Perfusion ◽

Pulmonary Arterial

Objective.Our aim was to investigate effects of bosentan on hand perfusion in patients with systemic sclerosis (SSc) with pulmonary arterial hypertension (PAH), using laser Doppler perfusion imaging (LDPI).Methods.We enrolled 30 SSc patients with PAH, 30 SSc patients without PAH, and 30 healthy controls. In SSc patients and healthy controls at baseline, skin blood flow of the dorsum of the hands was determined with a Lisca laser Doppler perfusion imager. The dorsal surface of the hands was divided into 3 regions of interest (ROI). ROI 1 included 3 fingers of the hand from the second to the fourth distally to the proximal interphalangeal finger joint. ROI 2 included the area between the proximal interphalangeal and the metacarpophalangeal joint. ROI 3 included only the dorsal surface of the hand without the fingers. LDPI was repeated in SSc patients and controls after 4, 8, and 16 weeks of treatment. In SSc patients, nailfold videocapillaroscopy and Raynaud Condition Score (RCS) were performed at baseline and at 4, 8, and 16 weeks.Results.SSc patients with PAH enrolled in the study received treatment with bosentan as standard care for PAH. In these patients with PAH, after 8 and 16 weeks of treatment, bosentan improved minimum, mean, and maximum perfusion and the perfusion proximal-distal gradient. Bosentan seems to be most effective in patients with the early and active capillaroscopic pattern than in patients with the late pattern. Bosentan improved skin blood flow principally in the ROI 1 compared to the ROI 2 and ROI 3. Bosentan restored the perfusion proximal-distal gradient in 57% of SSc patients with the early capillaroscopic pattern. No significant differences from baseline were observed in the RCS in SSc patients with PAH.Conclusion.Bosentan improved skin perfusion in SSc patients with PAH, although it did not ameliorate symptoms of Raynaud’s phenomenon. Skin blood perfusion increased in SSc patients with PAH, particularly in the skin region distal to the proximal interphalangeal joint, and in patients with the early/active capillaroscopic pattern. Double-blind randomized clinical trials are needed to evaluate the effects of bosentan on skin perfusion of SSc patients without PAH and with active digital ulcers.

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