Familial scleroderma: nature, nurture or both?

Englert, H.; Roberts‐Thomson, Peter; Byth, Kate; Manolios, Nicholas

doi:10.1111/j.1445-5994.2007.01525.x

Cited by 3 publications

(5 citation statements)

References 26 publications

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“…Among the SASR, 1.2% of probands had another immediate family member with scleroderma, and the λ sibship was 17 3 . Familial scleroderma showed a female predominance; Raynaud's onset was relatively late, and the diffuse : limited ratio was similar with idiopathic scleroderma 4 . It is likely that familial scleroderma is under‐ascertained, particularly because the milder forms of scleroderma may not have been recognised among older relatives.…”

Section: Epidemiological Analysis Of Risk Factors In Sclerodermamentioning

confidence: 99%

Stochastic processes in the aetiopathogenesis of scleroderma

Roberts‐Thomson

Walker

2012

Internal Medicine Journal

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We review the aetiology of scleroderma from an epidemiological perspective examining genetic, environmental and stochastic risk factors. The presence of familial clustering (but with low twin concordance) suggests a genetic contribution, and this has been confirmed with recent candidate gene and genome‐wide association screening demonstrating both major histocompatibility complex and non‐major histocompatibility complex genetic linkage. In contrast, environmental associations are weak or inconsistent. An examination of the age‐adjusted incidence curve of scleroderma is consistent with a stochastic process involving five to eight random events. In pathogenesis, scleroderma is best considered as an autoimmune disorder where genetic and environmental factors are both important variables, but random events are also likely to play a pivotal role. We suggest that these random events might result in acquired somatic mutations or epigenetic alterations involving genes coding for immune receptors, tolerogenic gates or proteins involved in immune regulation, inflammation and/or repair that, over time, might summate to form a requisite cassette (of genetic changes), which allows the initiation and progression of the autoimmune process.

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Section: Epidemiological Analysis Of Risk Factors In Sclerodermamentioning

confidence: 99%

Stochastic processes in the aetiopathogenesis of scleroderma

Roberts‐Thomson

Walker

2012

Internal Medicine Journal

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“…1). The first – Phase 1 – represents the genetic load and intrauterine environment 1–4 . Phase 2, of variable duration, represents the extrauterine phase predating environmental exposure.…”

Section: Discussionmentioning

confidence: 99%

“…The first -Phase 1 -represents the genetic load and intrauterine environment. [1][2][3][4] Phase 2, of variable duration, represents the extrauterine phase predating environmental exposure. In silica-induced scleroderma, this phase often lasts into early to mid-adulthood because this is classically when intense silica exposure often first occurs in an occupational capacity.…”

Section: Discussionmentioning

confidence: 99%

“…Scleroderma is a connective tissue disease of poorly defined, probably multifactorial aetiology 1 with peak onset around the fifth to sixth decades 2 . Its clinical onset is often heralded by the development of Raynaud's phenomenon which, in the limited cutaneous disease subtype may predate the second disease symptom by two decades 3 . At the time of clinical presentation, antinuclear antibody is usually present in high titre and nailfold capillaroscopy is classically abnormal.…”

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confidence: 99%

“…2 Its clinical onset is often heralded by the development of Raynaud's phenomenon which, in the limited cutaneous disease subtype may predate the second disease symptom by two decades. 3 At the time of clinical presentation, antinuclear antibody is usually present in high titre and nailfold capillaroscopy is classically abnormal. Indeed, the presence of high titre antinuclear antibody and abnormal nailfold capillaroscopy, both of which are independent antecedents for scleroderma, is often used to delineate primary Raynaud's from Raynaud's secondary to an evolving connective tissue disorder, including scleroderma.…”

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confidence: 99%

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Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of ‘prescleroderma’

Englert

Champion

Wu³

et al. 2011

Internal Medicine Journal

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In a patient with early topoisomerase antibody-positive scleroderma, antinuclear antibody positivity was fortuitously observed to predate nailfold capillaroscopy changes. Using this case as a template, the prediagnostic phase of the presumed multifactorial disease may be divided into 5 temporal phases--phase 1 representing conception and intrauterine environment, phase 2 representing the extrauterine environment predating environmental exposure; phase 3 representing the early post-environmental exposure interval with no detectable perturbed body status; phase 4 representing the post-environmental exposure interval characterized by autoantibody production and microvascular changes, and phase 5, the symptomatic clinical prediagnostic interval (Raynaud's, skin, musculoskeletal, gastrointestinal, cardiorespiratory) prompting scleroderma diagnosis. Temporal classification of prescleroderma aids in both the understanding and definition of scleroderma 'onset'. If altered nailfold capillaries and autoantibodies develop at comparable rates, and if the findings from this case--that autoantibody changes precede microvascular changes--are truly representative of the preclinical disease phase, then these findings argue that the evolution of the disease is from within the vessel outwards, rather than vice versa.

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Progressive Hemifacial Atrophy and Linear Scleroderma En Coup de Sabre: A Spectrum of the Same Disease?

Хамаганова

2018

Front. Med.

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Similar clinical and histhopathological features in progressive hemifacial atrophy and linear scleroderma en coup de sabre are well known. Trauma may predispose to the development of both diseases. The lack of association with anti-Borrelia antibodies was shown in both cases as well. The otolaryngological and endocrine disorders may be associated findings in both diseases. However, there are certain differences in neurological and ophthalmological changes in the diseases.

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Familial scleroderma: nature, nurture or both?

Cited by 3 publications

References 26 publications

Stochastic processes in the aetiopathogenesis of scleroderma

Stochastic processes in the aetiopathogenesis of scleroderma

Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of ‘prescleroderma’

Progressive Hemifacial Atrophy and Linear Scleroderma En Coup de Sabre: A Spectrum of the Same Disease?

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