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Skin Fibrosis

This initial page was excerpted with permission from "Understanding Scleroderma" by Dolores Vazquez-Abad, M.D. Copyright © 1997. Items have been added to this page since then, as noted by dates. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer
Overview
Diagnosis
Progression
Physical Therapy
Oral Hygiene
Treatments
d-Penicillamine
Spontaneous Remission
Myositis (Muscle Inflammation)
Research
Personal Storie

Overview: What is Fibrosis?

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.

Diagnosis

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)

Self–assessment of skin tightness severity by scleroderma patients. The respective modified Rodnan skin score assessment by patient versus the physician was highly correlated with a high level of agreement. PubMed, Int J Rheum Dis, 04/29/2016.

High frequency ultrasound of skin involvement in systemic sclerosis — a follow-up study. Ultrasound examination of the skin allows for objective assessment of one facet of the complex process of skin fibrosis in early SSc. PubMed, Arthritis Res Ther, 2015 Nov 19;17(1):329.

A Longitudinal Biomarker for the Extent of Skin Disease in Patients with Diffuse Cutaneous Systemic Sclerosis (SSc). Skin gene expression can be used effectively to monitor SSc skin disease change over time. PubMed, Arthritis Rheumatol, 08/03/2015. (Also see Diffuse Scleroderma)

A preliminary study of acoustic radiation force impulse (ARFI) quantification for the assessment of skin in diffuse cutaneous systemic sclerosis (dSSc). ARFI quantification is feasible and reliable for assessing the skin involvement in dcSSc and may be a valuable adjunct to skin evaluation in patients with SSc. PubMed, J Rheumatol, 2015 Mar;42(3):449-55. (Also see Diffuse Scleroderma)

Novel Ideas: The Increased Skin Viscoelasticity - A Possible New Fifth Sign for the Very Early Diagnosis of Systemic Sclerosis. In combination with nailfold videocapillaroscopy, the increased skin viscoelasticity parameter could be proposed as the possible new fifth sign for the very early diagnosis of SSc. Current Rheumatology Reviews, 08/06/2014. (Also see Skin Viscoelasticity)

Assessment of skin microcirculation by laser Doppler flowmetry (LDF) in systemic sclerosis patients (SSc). LDF is suitable for the assessment of the microangiopathy degree in SSc patients. Ter Media, Postep Derm Alergol, 03/05/2014.

Progression

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).

Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis. Patients with advanced skin fibrosis at baseline and absence of tendon friction rubs are more likely to regress in the next year than patients with milder skin fibrosis. PubMed, Ann Rheum Dis, 03/25/2016.

The Tumor Necrosis Factor Superfamily Molecule LIGHT Promotes Keratinocyte Activity and Skin Fibrosis. LIGHT, a TNF superfamily molecule, may be an important mediator of skin inflammation and fibrosis in diseases such as scleroderma or atopic dermatitis. PubMed, J Invest Dermatol, 03/19/2015.

Effect of menopause on the modified Rodnan skin score (mRSS) in systemic sclerosis (SSc). Results suggest that menopause has a substantial effect on skin thickening in diffuse SSc, with postmenopausal status being associated with a lower mean mRSS compared to premenopausal status. PubMed, Arthritis Res Ther, 2014 Jun 23;16(3):R130.

Physical Therapy

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.

A personalized physical therapy program or usual care for patients with systemic sclerosis (SSc): A randomized controlled trial. A personalized physical therapy program did not reduce disability at 12 months but had short–term benefits for patients with SSc. PubMed, Arthritis Care Res (Hoboken), 10/12/2016.

Oral Hygiene

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)

Treatments of Skin Fibrosis

Low dose UVA1 phototherapy has been found especially effective for morphea and also, in some cases, for systemic sclerosis.

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 scleroderma expert to see if it they will recommend it for you. 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.

Pan peroxisome proliferator–activated receptors (PPAR) agonist IVA337 is effective in prevention and treatment of experimental skin fibrosis. These findings indicate that simultaneous activation of all three PPAR isoforms exerts a dampening effect on inflammation and fibrosis, making IVA337 a potentially effective therapeutic candidate in the treatment of fibrotic diseases including SSc. PubMed, Ann Rheum Dis, 2016 Dec;75(12):2175-2183. (Also see Molecular Defect)

Targeting microRNA (miR)–155 to Treat Experimental Scleroderma. Our data suggest the potential of miR–155 silencing as a promising treatment for dermal fibrosis, especially in topical applications. PubMed, Sci Rep, 2016 Feb 1;6:20314.

Topical Paste May Prevent Skin Hardening in Scleroderma Patients. This treatment also has therapeutic potential for other collagen–related diseases, including scleroderma and interstitial pulmonary fibrosis. Scleroderma News, 01/12/2016.

Ultraviolet A1 phototherapy beyond morphea: experience in 83 patients. UVA1 phototherapy is effective and safe in the treatment of graft–versus–host disease, nephrogenic systemic fibrosis, systemic sclerosis, and mast cell disorders. PubMed, Photodermatol Photoimmunol Photomed, 2015 Nov;31(6):289-95. (Also see Morphea Treatments and Graft-versus-Host Disease)

Penicillamine

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)

Cat by Lisa Volz, ISN ArtistA word of caution regarding single-center, retrospective studies. Patients frequently improve on placebo. Patients who are improving usually attribute it to their therapy and thus stay with it. Thus uncontrolled cohorts become enriched for "responders" while failures seek other paths. This dynamic underlies virtually all therapeutic "breakthroughs" which is why large scale double-blinded clinical trials are crucial for determining valid scleroderma treatments.

Methotrexate

At present a similar study is being conducted to evaluate the role of Methotrexate. (1) (Also see Clinical Trial: Open Enrollments)

Spontaneous Remission

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)

Myositis (Muscle Inflammation)

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)

Research

Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04755) As a Potential Topical Treatment for Scleroderma A new topical medicine, called SM04755, significantly decreased and even reversed fibrosis and inflammation in in vitro and in vivo mouse studies of scleroderma. American College of Rheumatology, 11/08/2016.

An Autotaxin–LPA–IL–6 Amplification Loop Drives Scleroderma (SSc) Fibrosis. Results suggest that concurrent inhibition of two pathways, LPA and IL–6, may be an effective therapeutic strategy for SSc fibrosis. PubMed, Arthritis Rheumatol, 07/07/2016.

Scleroderma Mouse Study Suggests Estrogen Therapy Might Slow Skin Fibrosis. The study confirmed that estrogens play a role in protecting against skin fibrosis in experimental models representative of systemic sclerosis and the next step will be to begin investigating the potential role of hormone therapies as a treatment. Scleroderma News, 06/13/2016.

M10, a caspase cleavage product of the hepatocyte growth factor receptor, interacts with Smad2 and demonstrates antifibrotic properties in vitro and in vivo. M10 peptide interacts with Smad2 and demonstrates strong antifibrotic effects in vitro and in vivo in an animal model of lung fibrosis and should be considered as a potential therapeutic agent for systemic sclerosis and other fibrosing diseases. PubMed, Transl Res, 2016 Apr;170:99-111. (Also see Pulmonary Fibrosis)

Effect of endothelin–1 receptor antagonists (ETRAs) on skin fibrosis in scleroderma (SSc) patients from the EUSTAR database. ETRAs have well–proven clinical effects in the prevention of digital ulcers and in the treatment of pulmonary hypertension, but there is no evidence from clinical studies to support its use as an anti–fibrotic therapy. Journal of Scleroderma and Related Disorders, 03/30/2016. (Also see Endothelin and Systemic Scleroderma)

Origin of fibrosing cells in systemic sclerosis. In this review, recent evidence arguing in favor of and against proposed origins of fibrosing cells in diverse models of fibrosis are discussed. PubMed, Curr Opin Rheumatol, 2015 Nov;27(6):555-62.

Novel Mechanism Contributing To Skin Fibrosis in Systemic Sclerosis Identified. The TGF–beta signaling pathway is strongly involved with systemic sclerosis pathogenesis. Scleroderma News, 07/31/2015.

Study Shows Treatment with Fresolimumab Able to Reduce Skin Scarring in Systemic Scleroderma patients. Fresolimumab, sponsored by Genzyme, a drug agent that targets a chemical mediator in the body called TGF-beta, is able to block scarring which could mean a major treatment advance for scarring-mediated organ dysfunction. Scleroderma News, 06/23/2015. (Also see Causes of Scleroderma: Molecular Defect and Scleroderma Clinical Trials)

Fat Tissue May Be Key to Scleroderma’s Progression. This is the first study to associate fat cells with fibrosis which has implications for understanding and treating scleroderma, as well as more common forms of fibrosis. Northwestern Medicine, 02/09/2015.

Emerging roles of innate immune signaling and toll-like receptors (TLRs) in fibrosis and systemic sclerosis (SSc). Recent advances and emerging paradigms are highlighted for understanding the regulation, complex functional roles, and therapeutic potential of TLRs in SSc pathogenesis. PubMed, Curr Rheumatol Rep, 2015 Jan;17(1):474.

Myofibroblasts in cutaneous fibrosis originate from adiponectin-positive intradermal progenitors. There is a novel link between intradermal adipose loss and dermal fibrosis, and we demonstrate that adiponectin–positive intradermal progenitors give rise to dermal myofibroblasts. PubMed, Arthritis Rheumatol, 12/10/2014.

Lipoic acid (LA) plays a role in scleroderma: insights obtained from scleroderma (SSc) dermal fibroblasts. Dihydrolipoic acid (DHLA) not only acts as an antioxidant but also an antifibrotic since it has the ability to reverse the profibrotic phenotype of SSc dermal fibroblasts. Also thiol antioxidants, including N-acetylcysteine and LA/DHLA, could be beneficial for patients with SSc. PubMed, Arthritis Res Ther, 2014 Aug 15;16(5):411. (Also see Lipoic Acid)

The expression profile of the toll-like receptor (TLR) family in scleroderma (SSc) dermal fibroblasts. TLR5 and TLR10 expression is increased in SSc fibroblasts. TLR5 itself may have suppressive effects on collagen expression, and its overexpression in SSc fibroblasts may be the negative feedback against tissue fibrosis. Clinical and Experimental Rheumatology, 14 June 2014.

Scientists identify agent that can block fibrosis of skin, lungs. Researchers at the University of Pittsburgh School of Medicine have identified an agent, E4 (which is a piece of protein or peptide derived from endostatin) that in lab tests protected the skin and lungs from fibrosis. MedicalXpress. (Also see Pulmonary Fibrosis Treatments)

Personal Stories of Skin Fibrosis

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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