Myositis (Muscle Inflammation)
Fibrosis is a process that follows chronic inflammation. Fibrotic tissue is like a scar tissue, thick, and rigid, due to excess accumulation of protein below the skin.
Scleroderma is named after skin fibrosis, which is one of its most common and recognizable symptoms. Skin fibrosis eventually develops in most patients.
Sclero means "hard" and derma means "skin". The diagnosis of skin fibrosis is clinical and it requires no laboratory or special testing.
Doctors may request skin biopsies when there are unusual patterns or areas of skin that become tight and firm. (Also see Types of Scleroderma)
Comparative analysis of affected and unaffected areas of systemic sclerosis (SSc) skin biopsies by high-throughput proteomic approaches. We identified a number of proteins and pathways that might be involved in SSc progression and pathogenesis. PubMed, Arthritis Res Ther, 2020 May 7;22(1):107.
IL-16 expression is increased in the skin and sera of patients with systemic sclerosis. The regional up-regulation of IL-16 in the skin is not only associated with skin sclerosis, but also with systemic IL-16 activation. PubMed, Rheumatology (Oxford), 08/03/2019. (Also see Interleukins)
An extended high–frequency ultrasound protocol for assessing and quantifying of inflammation and fibrosis in localized scleroderma (LoS). High–frequency ultrasound allows an accurate assessment of the inflammatory and fibrotic skin lesions in LoS. PubMed, Skin Res Technol, 01/14/2019. (Also see Localized Scleroderma)
Impact of EUSTAR standardized training on accuracy of modified Rodnan skin score (mRSS) in patients with systemic sclerosis. New EUSTAR standardized mRSS training significantly enhanced mRSS accuracy, especially in participant with less previous experience in skin scoring. PubMed, Int J Rheum Dis, 11/05/2018.
High–frequency ultrasound (HFU) of the skin in systemic sclerosis (SSc): an exploratory study to examine correlation with disease activity and to define the minimally detectable difference. In the study, HFU was able to measure skin thickness, it correlated quantitatively with a valid measure of SSc activity, and a minimal detectable difference was identified. PubMed, Arthritis Res Ther, 2018 Aug 16;20(1):181.
An Ultrasound Surface Wave Technique (USWT) for Assessing Skin and Lung Diseases. USWE is a non-invasive and non-ionizing technique for measuring both skin and lung surface wave speed and may be useful for quantitative assessment of scleroderma and/or interstitial lung disease. PubMed, Ultrasound Med Biol, 2018 Feb;44(2):321-331. (Also see Common Tests and Skin Viscoelasticity)
The usual presentation is distal to proximal: finger tips first with progression to the fingers, hands, forearms, and arms. By the time the skin of the arms is tight, there may be stiffness of the legs, thighs, and in some cases, chest and abdomen. The pattern of skin stiffness is usually bilateral and symmetrical.
The skin of the face and neck may be involved in the mild, also called localized Scleroderma (with only finger tightness), or in proximal or diffuse Scleroderma (tight skin proximal to the hands).
Translational engagement of lysophosphatidic acid receptor 1 (LPA1) in skin fibrosis: from dermal fibroblasts of patients with scleroderma to tight skin 1 mouse. Our results support the therapeutic potential of LPA1 receptor antagonists in systemic sclerosis. PMC, Br J Pharmacol, 2020 Sep; 177(18): 4296–4309. (Also see Fibroblasts)
Early trajectories of skin thickening are associated with severity and mortality in systemic sclerosis (SSc). Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. PubMed, Arthritis Res Ther, 2020 Feb 18;22(1):30.
Skin improvement is a surrogate for favourable changes in other organ systems in early diffuse cutaneous systemic sclerosis (dcSSc). Changes in lung function in early dcSSc closely parallel skin changes and modified Rodnan skin score improvement reflects better prognosis for visceral disease. PubMed, Rheumatology (Oxford), 11/27/2019.
Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis (SSc). This data suggests that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes. PubMed, Exp Dermatol, 09/10/2019. (Also see Prognosis and Mortality)
Microbiome dysbiosis is associated with disease duration and increased inflammatory gene expression in systemic sclerosis (SSc) skin. These data provide a comprehensive portrait of the SSc skin microbiome and its association with local gene expression. PubMed, Arthritis Res Ther, 2019 Feb 6;21(1):49.
CCN proteins as potential actionable targets in scleroderma (SSc). We discuss the possible implication of CCN proteins in SSc pathogenesis, with a special focus on skin features, and identify the potential actionable CCN targets. PubMed, Exp Dermatol, 10/17/2018. (Also see Causes of Scleroderma)
Ubiquitination in Scleroderma (SSc) Fibrosis and Its Treatment. In this review, we will summarize the molecular mechanisms of ubiquitination in patients with SSc and explore the potential targets for treatment. PubMed, Front Immunol, 2018 Oct 17;9:2383.
Skin Gene Expression Is Prognostic for the Trajectory of Skin Disease in Patients With Diffuse Cutaneous Systemic Sclerosis. Skin gene expression of biomarkers may provide guidance in decision–making about which patients should be considered for aggressive therapies and/or for clinical trials. PubMed, Arthritis Rheumatol, 2018 Jun;70(6):912-919. (Also see Diffuse Scleroderma)
Do scleroderma patients look young?: Evaluation by using facial imaging system. The severity of wrinkles, texture and pores were significantly lower in SSc patients than control subjects and among them, wrinkles showed better correlation with skin thickness score. PubMed, Drug Discov Ther, 2017;11(6):342-345.
Quantitative Assessment of Skin Stiffness in Localized Scleroderma (LS) Using Ultrasound Shear–Wave Elastography. This non–invasive, real–time imaging technique is an ideal tool for assessing and monitoring LS disease severity and progression. PubMed, Ultrasound Med Biol, 04/27/2017. (Also see Localized Scleroderma)
At the first stages of skin tightening on the fingers, hands, and legs occupational and physical therapy are important in preventing, and ameliorating irreversible limiting contractures of the fingers.
Protection of the hand, and fingers by utilization of gloves when doing the dishes, gardening, and other physical activities prevents trauma that may break the skin, and produce slow healing ulcers with risk of infection.
Oral hygiene may become difficult in cases where facial skin becomes tight. When the skin around the mouth becomes tight, it is called microstomia. You must make frequent appointments with your dentist, who should be aware of your disease and maintain communication with your doctor. (Also see Scleroderma Dental Involvement)
When the skin tightening progresses quickly, or involves the chest and abdomen, your doctor may choose among the medications currently used for this condition.
For UVA1 treatment, first contact your doctor to see if it they will recommend it for you. It is not used for lichen sclerosus that is on the genital area. If they recommend and prescribe it for you, try to find UVA1 facilities near you. Some dermatology offices (usually large offices or with major health centers) have UVA1 equipment (not UVB). It may also be possible to buy UVA1 phototherapy equipment for home use. It is manufactured by Daavlin and distributed worldwide. Home users must be monitored by a physician, who will prescribe the necessary dosage and monitor for possible side-effects, such as skin cancer.
Evolving insights into the cellular and molecular pathogenesis of fibrosis in systemic sclerosis. This article looks to identify clinical applications where this new molecular knowledge may allow for targeted treatment and personalized medicine approaches. PubMed, Transl Res, 2019 Jul;209:77-89. (Also see Molecular Defect)
Association of serum homocysteine level and lung involvement in systemic sclerosis (SSc). It seems that the serum level of homocystein has a minor role in the lung involvement of SSc patients or its effects are modified by other factors. PubMed, Curr Rheumatol Rev, 06/28/2018.
Cell Therapy for Localized Scleroderma Can Reverse Fibrosis in Mice. A cell therapy based on injected genetically modified human skin cells and a pill that activates a protein has the capacity for breaking down fibrosis in localized scleroderma – at least in mice. Scleroderma News, 05/11/2017.
A multicenter double blinded study in 1997 showed that d-Penicillamine does not soften the skin, and that there was no improvement in internal organ involvement from d-Penicillamine. (Also see Clinical Trials: Ineffective or Unproven Treatments)
At present a similar study is being conducted to evaluate the role of Methotrexate. (1) (Also see Clinical Trial: Open Enrollments)
In addition, anecdotal reports of spontaneous remission are well known. Consequently, the initiation of specific therapy for this condition should be carefully evaluated and followed by your doctor. If started, all of these drugs require frequent laboratory monitoring for toxicity, and secondary effects. (1)
The skin tightening may occur rapidly, producing sudden increase in the pressure under the skin, and rubbing of the muscles and tendons below the skin. This may cause inflammatory muscle disease (Myositis), which frequently accompanies Scleroderma. In these cases, a blood test will show elevation of muscle enzymes.
Cessation of exercise, especially isotonic exercises that require repeated contraction of muscle groups, is mandatory. Isotonic exercises will increase the rubbing produced by the thickened skin, and augment the inflammation in the muscles. Your doctor may contemplate the use of steroids according to the degree of myositis. Repeated blood work for detection of muscles enzymes should be performed at your doctor's discretion. (Also see Skeletal Involvement)
Targeting the α7 nicotinic acetylcholine receptor - a novel road towards the future treatment of skin diseases. Emphasis on translational research targeting the α7nAChR in skin may lead to the development of new treatment and prevention modalities against fibrosclerotic skin diseases. PubMed, Exp Dermatol, 08/11/2020.
Estrogens counteract the profibrotic effects of TGF-β and their inhibition exacerbates experimental dermal fibrosis. These findings are consistent with the prominent development of scleroderma in postmenopausal women and the greater severity of the disease in men. PubMed, J Invest Dermatol, 08/30/2019.
CCL3, IL-7, IL-13 and IFNγ transcripts are increased in skin's biopsy of systemic sclerosis (SSc). These molecules are involved in the pathogenesis of SSc, and how their interactions occur should be the subject of further studies. PubMed, Exp Dermatol, 06/04/2019. (Also see Cytokines)
Interleukin-17 pathways in systemic sclerosis–associated fibrosis. There is multitude of evidence from across different tissues that interleukin-17 (IL-17) and its downstream pathways are strongly associated with the initiation and propagation of fibrosis. PubMed, Rheumatol Int, 05/09/2019. (Also see Interleukins)
Pharmacological Inhibition of Toll–Like Receptor-4 Signaling by TAK242 Prevents and Induces Regression of Experimental Organ Fibrosis. These findings identify TAK242 as an anti–fibrotic agent in preclinical models of organ fibrosis and might potentially represent a novel strategy for the treatment of scleroderma and other fibrotic diseases. PubMed, Front Immunol, 2018 Oct 23;9:2434.
TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung. The results suggest that systemic scleroderma patients with high TLR4 activity might show optimal therapeutic response to selective inhibitors of MD2/TLR4 complex formation. PubMed, JCI Insight, 2018 Jul 12;3(13). (Also see Fibroblasts and Pulmonary Fibrosis Research)
Methyl-CpG-binding protein 2 (MeCP2) mediates antifibrotic effects in scleroderma (SSc) fibroblasts. This study demonstrates a novel role for MeCP2 in skin fibrosis and identifies MeCP2-regulated genes, which can be potentially targeted for therapy in SSc. PubMed, Ann Rheum Dis, 05/14/2018. (Also see Fibroblasts)
Correlations between blood perfusion (BP) and dermal thickness (DT) in different skin areas of systemic sclerosis (SSc) patients. This study demonstrates for the first time in SSc patients a significant inverse relationship between skin BP, measured by laser speckle contrast analysis, and DT, evaluated by both ultrasound and modified Rodnan skin score (mRSS), at the level of dorsum of the middle phalanx of the third fingers. PubMed, Microvasc Res, 2018 Jan;115:28-33. (Also see Vascular Involvement)
The roles of dermal white adipose tissue (DWAT) loss in scleroderma skin fibrosis. The loss of skin–protective mechanisms with DWAT loss further contributes to skin fibrosis and injury. PubMed, Curr Opin Rheumatol, 08/10/2017.
Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned extracellular matrix (ECMs). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. PubMed, PLoS One, 2017 Jun 29;12(6):e0180751.
CD16-positive circulating monocytes and fibrotic manifestations of systemic sclerosis (SSc). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered. PubMed, Clin Rheumatol, 03/14/2017.
Alana: Scleroderma (Peru) I cannot open my mouth completely, I have lost strength in my hands, I have breathing problems, my face looks different, my skin is really tight and I have lost my appetite…
(Español/Spanish) Alana: Paciente Nuevo con Esclerodermia (Peru) Le dije que ya no podía abrir la boca completamente, he perdido la fuerza de las manos, tengo problemas respiratorios, mi rosto está diferente, mi piel está dura y he perdido casi el apetito…
Alexandra: Scleroderma My scleroderma symptoms arrived in great style: reflux, itchy swollen skin, joint and muscle pain and tiredness. Plus hundreds of little red spots (telangiectasia). My mouth was tight and getting smaller too…
Allen's Mom: Son has Scleroderma With his tightness of skin he has a very hard time bending, walking up the stairs and for the most part he cannot walk for more than a few minutes without his legs giving out…
Dawn M: Linear/Systemic Scleroderma My family and I were informed by the doctors, that the localized/linear form of scleroderma that I was diagnosed with, would never progress into the potentially fatal, systemic form…
Gioia: Systemic Progressive Sclerosis (Italy) I was unable to swallow food, and a few times I was at risk of suffocating, and I also had terrible ulcers in my hands…
(Italiano) Gioia: Sclerosi Sistemica Progressiva (Italia) Poi però mi sono resa conto a mie spese che non era così, non riuscivo più a deglutire il cibo, più di qualche volta ho rischiato di soffocarmi, per non parlare delle ulcere alle mani…
Heather A: Scleroderma (South Africa) My fingers started to curl up and I could not wear any rings on my fingers anymore as they were so swollen…
Kamlesh: Husband of Limited Scleroderma Patient (India) In a pulmonary function test, there was severe restriction and severe obstruction…
Karligash: Systemic Scleroderma (Republic of Kazakhstan) Young, beautiful, full of hope and expectations for my life, for happiness and love — that was me, nineteen years of age…
(Russian) Карлыгаш: системная склеродермия (Республика Казахстан) Молодая,красивая,полная ожидания от жизни счастья,любви такая я была в 19 лет…
Kristi U: Systemic Scleroderma We sold our motel business because it hurt me so bad to work each and every day…
Laira: MCTD, Scleroderma, SLE, Lupus, CREST, Lymphoma I was just seventeen when I was told I had rheumatoid arthritis…
Leslie R: Scleroderma, Vitiligo, Lupus, Anemia, Hypertension and Type 2 Diabetes He told me that I have scleroderma and explained what this disease is about. After suffering so long I finally got some answers…
Manu: Daughter of Patient with Systemic Scleroderma (Italy) I recently lost my father, and in his last moments he suffered very much. He was affected by systemic scleroderma that began with simple inflammation of his hand in November of 2006…
(Italiano) Manu: Figlia di Padre Malato di Sclerodermia Sistemica (Italia) Ho perso mio papà una settimana fa, dopo atroci sofferenze. Era affetto da sclerodermia sistemica iniziata con un banale gonfiore di una mano nel novembre 2006…
Matilda: Systemic Scleroderma (South Africa) I don't think there is a lot of support in South Africa and I would actually like to start a group where people with the same disease can meet and discuss how they cope with the illness…
Sheila Z: Scleroderma I would like to first say that this site has been a great help for me to understand what is happening to my body and my life…
Sibel: Scleroderma and Raynaud's (Turkey) Changes in my skin were making me look different in the mirror…
Sue D: Diffuse Scleroderma Pain developed in my hands, then I noticed pain in my knees, then my shoulders, down my back, elbows, hips, feet…
Susan L: Diffuse Scleroderma I first noticed the swelling in my hands and feet shortly after my daughter was born in 2005, and thought that it was post-pregnancy fluid…
Theon: Scleroderma and Pneumothorax This is very hard for me, because I was a very active woman, and then suddenly I am totally and completely disabled…
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