A case of segmental stiff skin syndrome treated with systemic losartan

Maillet-Lebel, Nicole; Kokta, Victor; Coulombe, Jérôme; Powell, Julie

doi:10.1111/pde.13330

Cited by 14 publications

(26 citation statements)

References 5 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent publication, a distinct segmental variant was proposed with a unilateral predominance, later age of onset, reduced morbidity and lack of evolution into a generalised cutaneous disease. 1,6 This variant comprises up to one third of all SSS-reported cases and exhibit similar histopathologic features as the widespread SSS. 7 Both are characterised by thickened collagen bundles in the deep reticular dermis, increased connective tissue mucin, lack of inflammation, preservation of the adnexa and adipocyte entrapmentwhich is considered the histopathologic hallmark of the disease.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Segmental stiff skin syndrome (SSS): Clinical case and a brief review

et al. 2021

View full text Add to dashboard Cite

Stiff skin syndrome (SSS) is a rare, scleroderma-like condition that is commonly characterised by stony hard skin and limited joint mobility, in the absence of visceral involvement or immunologic abnormalities. Depending on the distribution of the disease, this disorder can be further categorised into classic (widespread) SSS or its newly described segmental variant. Additional features of this syndrome may include hypertrichosis, lipodystrophy, dysmetria and scoliosis. In this report, we present the case of a patient with segmental SSS and we briefly review the current literature about the topic.

show abstract

Section: Discussionmentioning

confidence: 99%

“…9 Mycophenolate mofetil, losartan and more recently secukinumab have all been used with variable degree of success. 6,7,9,12 However, the mainstay of treatment remains supportive and rehabilitative care at an early stage. 1,8…”

Section: Discussionmentioning

confidence: 99%

Segmental stiff skin syndrome (SSS): Clinical case and a brief review

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In a further work, secukinumab, a humanized IL-17A antibody, was used to treat a patient with segmental SSS and carrying a variant in IL-17C [ 15 ]. A third paper empirically proposed the assumption of losartan in a single pediatric patient with segmental SSS [ 16 ]. In this case, a 2-year treatment was reported as effective in attenuating disease manifestations.…”

Section: Discussionmentioning

confidence: 99%

“…As a consequence, SSS is without a cure. Single case reports suggest improvement with an oral intake of mycophenolate mofetil [ 14 ], secukinumab [ 15 ] , and losartan [ 16 ], the latter already known as a treatment resource for other disorders related to transforming growth factor-β (TGF-β) signaling dysregulation, such as Marfan syndrome [ 17 ]. All these reports are preliminary observations without any experimental proof of the presumed biological rationale.…”

Section: Introductionmentioning

confidence: 99%

Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation

Fusco

Nardella

Augello

et al. 2020

IJMS

View full text Add to dashboard Cite

Transforming growth factor β (TGF-β) superfamily signaling pathways are ubiquitous and essential for several cellular and physiological processes. The overexpression of TGF-β results in excessive fibrosis in multiple human disorders. Among them, stiff skin syndrome (SSS) is an ultrarare and untreatable condition characterized by the progressive thickening and hardening of the dermis, and acquired joint limitations. SSS is distinct in a widespread form, caused by recurrent germline variants of FBN1 encoding a key molecule of the TGF-β signaling, and a segmental form with unknown molecular basis. Here, we report a 12-year-old female with segmental SSS, affecting the right upper limb with acquired thickening of the dermis evident at the magnetic resonance imaging, and progressive limitation of the elbow and shoulder. To better explore the molecular and cellular mechanisms that drive segmental SSS, several functional studies on patient’s fibroblasts were employed. We hypothesized an impairment of TGF-β signaling and, consequently, a dysregulation of the associated downstream signaling. Lesional fibroblast studies showed a higher phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), increased levels of nuclear factor-kB (NFkB), and a nuclear accumulation of phosphorylated Smad2 via Western blot and microscopy analyses. Quantitative PCR expression analysis of genes encoding key extracellular matrix proteins revealed increased levels of COL1A1, COL3A1, AGT, LTBP and ITGB1, while zymography assay reported a reduced metalloproteinase 2 enzymatic activity. In vitro exposure of patient’s fibroblasts to losartan led to the partial restoration of normal transforming growth factor β (TGF-β) marker protein levels. Taken together, these data demonstrate that in our patient, segmental SSS is characterized by the overactivation of multiple TGF-β signaling pathways, which likely results in altered extracellular matrix composition and fibroblast homeostasis. Our results for the first time reported that aberrant TGF-β signaling may drive the pathogenesis of segmental SSS and might open the way to novel therapeutic approaches.

show abstract

“…It is characterized by progressive, noninflammatory fibrosis of the skin that may result in limitation of joint mobility 3 . Segmental SSS (SSSS) has been described as a distinct clinical variant, possibly resulting from a mosaic mutation in FBN1 2 . Unlike the widespread SSS phenotype, SSSS has a later onset and a better prognosis 3 .…”

mentioning

confidence: 99%

Clinical presentation, sonographic features and treatment options of segmental stiff skin syndrome

Quintana‐Castanedo¹,

Bandera²,

Rodríguez³

et al. 2020

Clin Experimental Derm

View full text Add to dashboard Cite

Segmental stiff skin syndrome is a rare genetic connective tissue disease, which is often misdiagnosed. High-frequency ultrasonography can represent a useful clinical adjunct in the differential diagnosis of this condition, in conjunction with the clinical and histopathological findings. Treatment options are limited and evidence is scarce. We present the clinical, sonographic and histological features of five paediatric patients diagnosed at our institution and discuss their response to treatment.

show abstract

A case of segmental stiff skin syndrome treated with systemic losartan

Cited by 14 publications

References 5 publications

Segmental stiff skin syndrome (SSS): Clinical case and a brief review

Segmental stiff skin syndrome (SSS): Clinical case and a brief review

Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation

Clinical presentation, sonographic features and treatment options of segmental stiff skin syndrome

Contact Info

Product

Resources

About