| SKIN INVOLVEMENT: MAIN MENU |
| |
| 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 (SD) affects everyone differently. See Disclaimer. |
| |
| 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. |
| Chemokines and Chemokine Receptors in Scleroderma. Studies have shown that an increase in proinflammatory chemokines has been associated with initiation or development of skin fibrosis/sclerosis, suggesting that chemokines and their receptors may be important mediators of inflammation and fibrosis in scleroderma. PubMed. Int Arch Allergy Immunol. 2006 Jun 27;140(4):345-356. (Also see: Causes of Scleroderma: Cytokines) |
| Diagnosis |
| Hallmark of scleroderma, the skin fibrosis is responsible for its name. The diagnosis is clinical, and requires no laboratory or special testing. |
| Occasionally, your doctor may consider it necessary to perform a skin biopsy. This is usually the case where infrequent patterns or areas of skin become tight and firm. (Also see Types of Scleroderma) |
| Quantification of hardness, elasticity and viscosity of the skin of patients with systemic sclerosis(SSc) using a novel sensing device (Vesmeter): a proposal for a new outcome measurement procedure. The sensing device (Vesmeter) proved to be able to assess skin abnormalities of SSc with high reliability. Y. Kuwahara. Rheumatology Access Online. April 25, 2008. |
| Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: Application of a latent linear trajectory model. Although mortality was highest among patients with the worst skin-related outcomes, no simple relationship between burden of disease and change in skin score was observed. Arthritis and Rheumatism. Volume 56, Issue 7, Pages 2422 - 2431. |
| Skin involvement in scleroderma--where histological and clinical scores meet. The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT (haematopoietic stem cell transplantation). The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease. PubMed. Rheumatology (Oxford). 2007 Jan 25. (Also see: Causes of Scleroderma: Molecular Defect ) |
| Cutaneous gene expression by DNA microarray in murine sclerodermatous graft-versus-host disease, a model for human scleroderma. These constellations of immunologic changes provide a "fingerprint" for fibrosing autoimmune disease. They are useful to understand the pathogenesis of Scl GVHD, to identify markers for early diagnosis of disease, and to devise more effective strategies for intervention in early scleroderma and Scl GVHD. PubMed. J Invest Dermatol. 2007 Feb;127(2):281-92. (Also see: Graft-versus-Host-Disease ) |
| German researchers develop first non-invasive test to measure skin aging. This new laser-based technique images the fabric of the deeper layers of the skin, combining methods for imaging collagen and elastin, whose degeneration causes the appearance of wrinkles and the progressive loss of skin smoothness. The authors hope it could be useful in studying skin diseases that affect the collagen structure. EurekAlert! 10/03/06. |
| Ultrasonography of Hand Fingers Skin in Patients with Systemic Sclerosis. Analyzed skin of patients with SSc had considerably higher thickness than in healthy persons. Neither Raynaud’s phenomenon duration, nor major organ involvement, had a significant influence on the dimensions of examined skin. S. Z. Prodanovic. SAT0229 EULAR 2006. |
| Ultrasound Evaluation of Skin Involvement in Systemic Sclerosis. Correlations of ultrasound pictures with histological aspects are good and could serve to point-out areas of involvement which clinically seemed to be unaffected. S. Rednic. FRI0130 EULAR 2005. |
| Ultrasound Measurement of Skin Thickness Correlates With Skin Hardness and Clinical Skin Score in Systemic Sclerosis. In subjects with systemic sclerosis, skin thickness as measured by ultrasound is highly correlated to skin hardness and clinical skin score. Our data also suggest that disease duration correlates with skin thinning but not skin softening. Eugene Y. Kissin. 1046/426. ACR 2004. |
| Validity, Reliability, and Feasibility of Durometer Measurements of Scleroderma Skin Disease in a Multicenter Treatment Trial. DUR (Durometer) measurements of skin hardness in SSc are reliable, simple, accurate, and demonstrate good sensitivity to change compared to traditional skin scoring. Durometry may offer an increased range of values for skin assessment in SSc compared to semi-quantitative MRSS (modified Rodnan skin scoring). Peter A. Merkel. 1044/424. ACR 2004. |
| A new tactile skin sensor for measuring skin hardness in patients with systemic sclerosis and autoimmune Raynaud's phenomenon. We conclude that this new tactile sensor is useful for quantitatively measuring skin sclerosis and may help determine the efficacy of therapeutic treatments. PubMed. J Int Med Res. 2004 Mar-Apr;32(2):222-31. |
| Longitudinal development of skin involvement and reliability of high frequency ultrasound in systemic sclerosis. Separate measurements of skin thickness and echogenicity by high frequency ultrasound add a new dimension to the assessment of skin involvement in SSc, and this seems to be an objective non-invasive tool for use in the study of disease development and in clinical trials. PubMed. Ann Rheum Dis. 2004 Jul;63(7):791-6. |
| 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). |
| Skin Thickness Progression Rate (STPR) in Systemic Sclerosis with Diffuse Cutaneous Involvement: A Predictor of Outcome. Rapid STPR at first evaluation in early dcSSc patients is a predictor of both internal organ involvement at one year after onset of skin thickening and 5 year mortality. Assessment of individual risk in dcSSc patients and planning of clinical trials involving these patients should include evaluation of STPR. (Also see: Mortality and Prognosis and Diffuse SSc ). |
| Predicting 24 Month Pulmonary Function Test, Modified Rodnan Skin Score (mRSS) and Functional Results from Baseline Measurements in the Cyclophosphamide versus Placebo Trial of Systemic Sclerosis (SSc) Alveolitis. This study suggests that 12 months of cyclophosphamide results in continued benefit at 24 months. Daniel E. Furst. 1130/389. ACR 2006. (Also see: Pulmonary Fibrosis, and Clinical Trials: Cyclophosphamide and Scleroderma Lung Disease ) |
| Clinical Characteristics of Juvenile Systemic Sclerosis in Japanese. Our study suggests that Japanese patients with juvenile SSc have more severe skin sclerosis than adults with SSc, although the frequency of internal organ involvement and the mortality rate is lower than with adult SSc. J Rheumatol 2005 September;32:1850. (Also see: Juvenile Scleroderma) |
| 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. |
| Oral Hygiene |
| Oral hygiene may become difficult in cases where facial skin becomes tight. You must make frequent appointments with your dentist, who should be aware of your disease and maintain communication with your doctor. (Also see Dental Involvement) |
| Treatments |
| When the skin tightening progresses quickly, or involves the chest and abdomen, your doctor may choose among the medications currently used for this condition. |
| The effect of imatinib (Gleevec) on scleroderma and normal dermal fibroblasts: a preclinical study. This study suggests that imatinib can serve as therapy to limit dermal fibroblast proliferation in scleroderma. (PubMed) Dermatology. 2008; 216(2):109-17. (Also see: Clinical Trials ) |
| The Effect Of Cyclophosphamide Treatment On Skin Changes In Patients With Scleroderma Interstitial Lung Disease. Although the lot was small – only 28 patients- because they were treated with Cyclophosphamide according to their lung involvement, the Cyclophosphamide treatment seemed to ameliorate the skin thickening in Systemic Sclerosis. The effect is greater in those patients with higher mRodnanss. I. C. Oprisan. AB0518 EULAR 2007. (Also see: Pulmonary Fibrosis, and Cyclophosphamide ) |
| Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis. Considering its favorable pharmacokinetics and clinical experience with its use in other diseases, imatinib mesylate is a promising candidate for the treatment of fibrotic diseases such as SSc. PubMed. Arthritis Rheum. 2007 Jan;56(1):9-12. (Also see: Scleroderma Treatments ) |
| Photodynamic therapy: other uses. The ability of this treatment to hone in on dysplastic epithelial and endothelial cells while retaining viability of surrounding tissue is its key feature because this leads to specific tumor destruction with cosmesis and function of the target organ intact. PubMed. Dermatol Clin. 2007 Jan;25(1):101-9. (Also see: Morphea Treatments, and Clinical Trials: Positive Results: Phototherapy ) |
| High Dose Cyclophosphamide (CYC) Without Stem Cell Transplantation in Systemic Sclerosis. High dose CYC without stem cell transplantation leads to rapid improvement of the modified Rodnan skin, HAQ, and PGA scores in the severe early diffuse SSc. Christopher V. Tehlirian. 689 ACR 2006. (Also see: Cytoxan, SCOT Clinical Trial,and ASTIS Clinical Trial ) |
| Phototherapy: a promising treatment option for skin sclerosis in scleroderma? Phototherapy is able to stop or inhibit the fibrotic processes and to induce softening of sclerotic skin, especially in limited SSc. Rheumatology (Oxford). 2006 Oct;45 Suppl 3:iii52-iii54. (Also see: Clinical Trials: Phototherapy ) |
| Mechanisms and consequences of fibrosis in systemic sclerosis. Overall, this is an exciting time for new therapies in SSc and advances are being made in synchrony with an improved understanding of the molecular and biochemical basis of the disease. PubMed. Nat Clin Pract Rheumatol. 2006 Mar;2(3):134-44. (Also see: What is Scleroderma? ) |
| Twelve Weeks Therapy with Fluvastatin Improves Brachial Arterial Endothelium-Dependent Vasodilation in Patients with Systemic Sclerosis. In our study, flow-mediated dilation change is not accompanied by a significant decrease in cholesterol levels, indicating that the beneficial effect of fluvastatin on endothelial function of SSc patients is indeed pleiotropic. L. Beretta. FRI0324 EULAR 2006. (Also see: Medications ) |
| Off-Label Dermatologic Uses of Anti-TNF-a Therapies. Reports suggest that anti-TNF-a therapies may be effective in the treatment of numerous inflammatory skin diseases outside their currently approved indications. PubMed. J Cutan Med Surg. 2006 May 25. (Also see: Causes of Scleroderma: Interleukins, Medications,and Antibodies) |
| Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin. The pleiotropic protective effects of statins on various endothelial and immune cell functions in conjunction with their potent inhibitory effects on type I collagen gene expression suggest that statins may be effective therapeutic agents in systemic sclerosis. PubMed. Arthritis Rheum. 2006 Mar 30;54(4):1298-1308. |
| Bosentan for Systemic Scleroderma Skin Fibrosis. Bosentan is proving useful for a variety of scleroderma symptoms, including digital ulcers, pulmonary fibrosis, pulmonary hypertension, Raynaud's, and skin fibrosis. Therefore, scleroderma researchers suggest that an early use of this drug should be considered for systemic scleroderma patients. ISN. 2005. |
| Inhibition of collagen gene expression in systemic sclerosis dermal fibroblasts by mithramycin. Mithramycin causes potent inhibition of collagen production and gene expression in systemic sclerosis dermal fibroblasts in vitro in the absence of cytotoxic effects. These results suggest that this drug may be an effective treatment for the fibrotic process which is the hallmark of systemic sclerosis. PubMed. Ann Rheum Dis. 2005 May 18. |
| Treatment of early diffuse cutaneous systemic sclerosis patients in Japan by low-dose corticosteroids for skin involvement. We confirmed the usefulness of oral corticosteroid treatment for early dSSc in Japanese patients. PubMed. Clin Exp Rheumatol. 2004 Jan-Feb;22(3 Suppl 33):S87-9. (Also see: Medications) |
| Fibrosis regression induced by intravenous gammaglobulin treatment.I IVIg may enhance resorption of fibrosis and promote healing in patients with fibrotic associated disorders. PubMed. Ann Rheum Dis 2003 Feb;62(2):175-177 (Also see: Pulmonary Fibrosis) |
| Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma. As a first step toward future treatment of internal organ involvement, an oral administration study was performed in which halofuginone was well tolerated and plasma levels surpassed the predicted therapeutic exposure. PubMed. Biol Blood Marrow Transplant. 2003 Jul;9(7):417-25. (Also see: Treatments and Diseases Similar to Scleroderma) |
| Penicillamine |
 A 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. | A retrospective randomly selected cohort study of D-penicillamine treatment in rapidly progressive diffuse cutaneous systemic sclerosis of recent onset. In a population of patients with diffuse cutaneous systemic sclerosis, with progressive disease of recent onset, D-penicillamine treatment at a median dose of 750 mg per day caused a statistically significant reduction in skin involvement and improvement of renal, cardiac and pulmonary involvement. (PubMed) Br J Dermatol. 2008 Feb 16. (Also see: Scleroderma Treatments, and Clinical Trials ) | |
| 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) |
| 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 |
| Collagen Degradation Products And Elastin In Systemic (SSc) And Localized Scleroderma (lSSc) . Increased markers of collagen and elastin turnover in SSc and LSc reflect the active fibrotic process in the diseases and are accordance with the published data. High elastin levels in psoriasis vulgaris group are rather difficult to explain. R. Becvar FRI0245 EULAR 2008. (Also see: Localized Scleroderma, and Systemic Scleroderma ) |
| Rice University breakthrough could prevent multiple fibrotic diseases. A protein, which is called serum amyloid P (or SAP), has proven effective at preventing fibrotic disease from developing in the hearts and lungs of lab animals, and researchers hope it will eventually save thousands of lives once it is developed for human use. EurekAlert! 01/18/07. (Also see: Pulmonary Fibrosis ) |
| Collagen Degradation Products And Inflammatory Activity In Systemic (SSc) And Localized Scleroderma (LSc). In patients with SSc our data have shown the most intensive collagen degradation and simultanously an active inflammation which reflects the pathological processes in the skin and visceral organs, compared with psoriasis vulgaris patients and healthy inviduals. In LSc group collagen degradation was similar to that in control groups but a certain inflammatory activity was observed. R. Becvar THU0242 EULAR 2007. (Also see: Systemic Scleroderma and Localized Scleroderma ) |
| Urticarial vasculitis appearing in the progression of systemic sclerosis (SSc). We demonstrate that, in the present case, mast cells might be involved in both courses of urticarial vasculitis and SSc as a common factor. PubMed. J Dermatol. 2006 Nov;33(11):792-7. (Also see: Vasculitis, Causes of Scleroderma: Molecular Defect, and Limited Scleroderma ) |
| B-Lymphocyte Depletion Reduces Skin Fibrosis and Autoimmunity in the Tight-Skin Mouse Model for Systemic Sclerosis. B-cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance. American Journal of Pathology. 2006;169:954-966. (Also see: Causes of Scleroderma: B Cells and Autoimmunity ) |
| Scleroderma-like remodeling induced by type V collagen. It has been discovered that New Zealand rabbits immunized with human type V collagen plus Freund's adjuvant present fibrosis and vasculitis of organs usually affected by systemic sclerosis. In this way, the fibrillogenesis process was studied to identify possible factors involved in altered remodeling observed in this scleroderma-like model. PubMed. Arch Dermatol Res. 2006 May 3. |
| Serum xylosyltransferase I activity, the new biochemical fibrosis marker, is not affected by renal insufficiency. Serum xylosyltransferase I (XT-I) is a marker for the determination of tissue remodeling in systemic sclerosis. Serum XT-I activity is applicable as a fibrosis marker independent from renal function. PubMed. Clin Biochem. 2005 May;38(5):486-488. (Also see: Kidney Involvement) |
| Anti-lipoprotein lipase antibody in systemic sclerosis: association with elevated serum triglyceride concentrations. Our results suggest that anti-LPL autoantibody contributes to elevated serum triglyceride levels by inhibiting LPL enzyme activity in patients with SSc. J Rheumatol. 2005 Apr;32(4):629-36. (Also see: Antibodies, Pulmonary Fibrosis, and Cardiac Involvement) |
| Genetic factors predisposing to fibrosis in systemic sclerosis. Identification of genetic factors involved in the susceptibility to fibrosis of systemic sclerosis would lead to a better understanding of physiopathological mechanisms of this disease and to therapeutic targets using immunomodulation with drugs, such as already performed in rheumatoid arthritis. PubMed. Rev Med Interne. 2005 Apr;26(4):294-303. (Also see: Causes of Scleroderma: Genetics) |
| Animal models in scleroderma. A hallmark feature of scleroderma is the excess synthesis and deposition of collagen resulting in a fibrotic state. In an effort to better understand the pathophysiology of this disease, researchers have developed a variety of animal models that display features of the human condition. PubMed. Curr Rheumatol Rep. 2005 Apr;7(2):150-5. |
| Personal Stories of Skin Fibrosis |
| 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... |
| 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... |
