One year in review 2021: systemic sclerosis

Orlandi, Martina; Lepri, Gemma; Damiani, Arianna; Barsotti, Simone; Battista, Marco Di; Codullo, Veronica; Rossa, Alessandra Della; Guiducci, Serena; Allanore, Yannick

doi:10.55563/clinexprheumatol/izadb8

Cited by 53 publications

(69 citation statements)

References 38 publications

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“…In addition to the recruitment of inflammatory cells caused by activated endothelial cells, changes in both innate and adaptive immune responses are observed in the early stage of SSc, which result in altered function of inflammatory cells. From the perspective of cells, T cells (CD4+ T cells) (especially type 2 T helper (Th2) cells are more common in SSc than Th1), T regulatory (Treg) cells, T follicular helper (TFh)-like cells, Th17 and Th22 cells, plasmacytoid dendritic cells, myofibroblasts, mesenchymal stromal cells, monocyte-derived dendritic cells, monocytes, and macrophages play an important role in the pathogenesis of SSc [17,20,21]. After the change in immune responses, a prominent type I interferon (IFN) signature emerges and elevated IFN levels are detected in the blood and skin.…”

Section: Skin Involvement and Inflamm-aging In Sscmentioning

confidence: 99%

Inflamm-Aging: A Mechanism of Aging That Contributes to the Characteristics of Skin Involvement in Systemic Sclerosis

Gökçen

2022

AAEE

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Aging is associated with deterioration of the immune function. Two contributory mechanisms are inflamm-aging, which is a chronic, low-grade systemic inflammation, and immunosenescence, an impairment of adaptive immune function that may also contribute to the development of inflamm-aging. This age-related inflammatory event is associated with alteration to the balance of pro-inflammatory and anti-inflammatory cytokines. The effect of inflamm-aging on skin aging in healthy people is accepted; however, its effect on normal skin aging and/or skin characteristics in systemic sclerosis is unknown. The hypothesis presented herein suggests that inflamm-aging may contribute to the evolution of the skin phases in systemic sclerosis, which progress from edematous, fibrotic, and indurative phases to the atrophic phase.

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Section: Skin Involvement and Inflamm-aging In Sscmentioning

confidence: 99%

Inflamm-Aging: A Mechanism of Aging That Contributes to the Characteristics of Skin Involvement in Systemic Sclerosis

Gökçen

2022

AAEE

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“…Systemic sclerosis (SSc) is characterized by exuberant fibrosis of the skin, gastrointestinal tract, heart, lungs, and kidneys and complicated by extensive vasculopathy with severe vasospasm and progressive vascular obliteration. 1,2 The etiology of SSc is multifactorial with both environmental and genetic aspects driving the pathologic processes. 1 SSc manifestations in Hispanic/Latino (Hispanic) Caucasians relative to non-Hispanic Caucasians have been studied in Spain, Mexico, other Spanish-speaking countries, and in discrete areas of the United States with variable results, perhaps related to different environmental settings and the well-known genetic heterogeneity between regional Hispanic populations.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 The etiology of SSc is multifactorial with both environmental and genetic aspects driving the pathologic processes. 1 SSc manifestations in Hispanic/Latino (Hispanic) Caucasians relative to non-Hispanic Caucasians have been studied in Spain, Mexico, other Spanish-speaking countries, and in discrete areas of the United States with variable results, perhaps related to different environmental settings and the well-known genetic heterogeneity between regional Hispanic populations. 3 - 8 However, the manifestations, severity, and outcome of SSc in Hispanics in the American Southwest outside of Texas, California, and Arizona are less well described.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systemic sclerosis manifestations and clinical outcomes in Hispanics/Latinos of the American Southwest

Nunez

Ariza-Hutchinson

Fields

et al. 2022

Journal of Scleroderma and Related Disorders

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Objective: Certain Hispanic/Latino (Hispanic) populations have been reported to have higher rates and severity of systemic sclerosis; however, little is known of systemic sclerosis in the American Southwest. This study compared manifestations of systemic sclerosis in Hispanics with non-Hispanics of New Mexico. Methods: This cross-sectional longitudinal study included 109 systemic sclerosis patients followed over a mean of 12.6 ± 8.9 years. Subjects were repetitively evaluated including physical examination, echocardiography, chest imaging, and serologic testing and observed for complications. Disease characteristics and long-term outcomes were statistically compared between self-identified Hispanic and non-Hispanic subjects. Results: A total of 73 (67%) systemic sclerosis subjects were Hispanic and 36 (33%) were non-Hispanic. The cohorts were similar in mean age, age of systemic sclerosis onset, limited versus diffuse cutaneous systemic sclerosis, telangiectases, gastroesophageal reflux disease, Raynaud’s phenomenon, autoantibody profile, interstitial lung disease, pulmonary hypertension, scleroderma renal crisis, mortality, and comorbid malignancy (all p > 0.05). However, the standardized mortality ratio was increased in both cohorts relative to age-adjusted mortality: Hispanic: 2.08, confidence interval (1.94–2.24); non-Hispanic: 1.56, confidence interval (1.46–1.68). Furthermore, the standardized incidence ratio for malignancy was increased in both cohorts: Hispanic: 1.45, confidence interval (1.35–1.56); non-Hispanic: 1.24, confidence interval (1.16–1.34). The mean age of cancer diagnosis occurred at a significantly younger age in Hispanics (Hispanics: 53.1 ± 9.7 years; non-Hispanics 63.7 ± 7.9 years; 95% confidence interval: −19 ⩽ 10.6 ⩽ 2.2; p = 0.016). Conclusion: Systemic sclerosis phenotype, autoantibodies, complications, outcomes, malignancy rates, and mortality are generally similar between Hispanics and non-Hispanics with systemic sclerosis in the American Southwest. However, age-adjusted comorbid malignancy and mortality rates are significantly increased in both groups.

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A 24‐Week, Phase IIa, Randomized, Double‐Blind, Placebo‐Controlled Study of Ziritaxestat in Early Diffuse Cutaneous Systemic Sclerosis

Khanna

Denton

Fürst

et al. 2023

Arthritis & Rheumatology

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Objective We undertook this study to explore the efficacy, safety, and tolerability of ziritaxestat, a selective autotaxin inhibitor, in patients with early diffuse cutaneous systemic sclerosis (dcSSc). Methods NOVESA was a 24‐week, multicenter, phase IIa, double‐blind, placebo‐controlled study. Adults with dcSSc were randomized to oral ziritaxestat 600 mg once daily or matching placebo. The primary efficacy end point was change from baseline in modified Rodnan skin score (MRSS) at week 24. Secondary end points assessed safety and tolerability; other end points included assessment of skin and blood biomarkers. Patients in NOVESA could enter a 104‐week open‐label extension (OLE). Results Patients were randomized to ziritaxestat (n = 21) or placebo (n = 12). Reduction in MRSS was significantly greater in the ziritaxestat group versus the placebo group (–8.9 versus –6.0 units, respectively; P = 0.0411). Placebo patients switching to ziritaxestat in the OLE showed similar reductions in MRSS to those observed for ziritaxestat patients in the parent study. Ziritaxestat was well tolerated; the most frequent treatment‐related treatment‐emergent adverse events were headache and diarrhea. Circulating lysophosphatidic acid (LPA) C18:2 was significantly reduced, demonstrating ziritaxestat target engagement, and levels of fibrosis biomarkers were reduced in the blood. No differentially expressed genes were identified in skin biopsies. Significant changes in 109 genes were identified in blood samples. Conclusion Ziritaxestat resulted in significantly greater reduction in MRSS at week 24 than placebo; no new safety signals emerged. Biomarker analysis suggests ziritaxestat may reduce fibrosis. Modulation of the autotaxin/LPA pathway could improve skin involvement in patients with dcSSc. A plain language summary is provided in the Supplementary Material, available on the Arthritis & Rheumatology website at https://onlinelibrary.wiley.com/doi/10.1002/art.42477.

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One year in review 2021: systemic sclerosis

Cited by 53 publications

References 38 publications

Inflamm-Aging: A Mechanism of Aging That Contributes to the Characteristics of Skin Involvement in Systemic Sclerosis

Inflamm-Aging: A Mechanism of Aging That Contributes to the Characteristics of Skin Involvement in Systemic Sclerosis

Systemic sclerosis manifestations and clinical outcomes in Hispanics/Latinos of the American Southwest

A 24‐Week, Phase IIa, Randomized, Double‐Blind, Placebo‐Controlled Study of Ziritaxestat in Early Diffuse Cutaneous Systemic Sclerosis

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