Types of Scleroderma

Types of Scleroderma: Overview

This page was written by Shelley Ensz and has not yet been medically edited. See disclaimer.

Two Main Types
Brochures about Scleroderma
Books About Scleroderma
Determining the Type of Scleroderma
Juvenile Scleroderma
Localized Scleroderma
Nodular Scleroderma

Systemic Sclerosis
Systemic: Prognosis & Mortality
CREST Syndrome
Limited Scleroderma
Diffuse Scleroderma
Overlap Syndrome
Juvenile Scleroderma

Two Main Types

There are many methods used to categorize the various forms of scleroderma, which has brought about a confusing abundance of terms. The following categories are often found in patient literature, but use and interpretation of these categories varies quite a bit.

There are two main types of scleroderma: Localized and Systemic.

Systemic sclerosis. Systemic sclerosis and its subtypes differ significantly from other diseases in rheumatology and clinical immunology, as the aberrant activation of the immune system does not result in an inflammation-driven destruction but in a progressive matrix synthesis, especially of the skin. (PubMed) Muller-Ladner U. Internist(Berl). 2008 Mar;49(3):278-285. (Also see: Prof. Ulf Müller-Ladner, MD: ISN Medical Advisory Board )

Classification criteria of scleroderma. Those patients with systemic scleroderma involving the trunk are classified as "Cutaneous diffuse systemic scleroderma"; the association of Raynaud's phenomenon, capillaroscopic abnormalities and specific autoantibodies defines "limited systemic scleroderma"; among the latter patients, those with distal skin involvement are classified "Cutaneous limited systemic sclerosis". The old term "CREST" tends to be abandoned due to its lack of specificity. PubMed. Presse Med. 2006 Dec;35(12 Pt 2):1916-22.

Classification in Systemic Sclerosis. Accurate classification of systemic sclerosis (SSc) has been an evolving issue in both pediatric and adult rheumatology literature. The need for classification criteria has been long recognized as a necessity for scientific inquiry, and prognosis is dependent on disease severity and target organ involvement. J Rheumatol 2006 May;33:840 Editorial. (Also see: Juvenile Scleroderma)

Nodular Scleroderma: A Report of 2 Cases. Nodular scleroderma, also known as keloidal scleroderma, is a rare form of scleroderma that may occur with either systemic sclerosis or localized scleroderma. American Journal of Dermatopathology. 30(4):385-388, August 2008.

Brochures About Scleroderma

These brochures are in PDF format. The files will open automatically in Adobe Reader, which is a free program which is already installed on most computers. If you click on the file link and it doesn't open, download Adobe Reader here.

What in the world is Scleroderma? (PDF Brochure) Scleroderma (sklare-oh-derma) means "hard skin." This complex disease involves tightening and thickening of the skin, blood vessel damage, inflammation and immune system changes. Brochure includes a systemic scleroderma symptom checklist ! International Scleroderma Network.

(Español/Spanish) ¿Que es Escleroderma? (PDF) Escleroderma o Esclerodermia significa ‘piel dura.’ La forma sistemica de esta complicada enfermedad involucra la rigidez y el endurecimiento de la piel, daño a los vasos sanguineos, inflamacion y cambios en el sistema inmunologico. International Scleroderma Network.

Books About Scleroderma

But what is scleroderma really like?! To answer that, we strongly recommend the ISN's Voices of Scleroderma book series for top quality medical and support information.

This book series receives rave reviews from patients, caregivers and doctors alike! Articles by highly esteemed scleroderma experts are combined with true stories from patients and caregivers explaining their illness and sharing their ideas for coping with all types of scleroderma symptoms.

Determining the Type of Scleroderma

Dartmouth researchers discover gene signatures for scleroderma. Distinct genetic profiles can discern different groups of patients with scleroderma. This discovery of distinguishing molecular subtypes within the disease offers new insight into the complexity of a poorly understood and hard to treat illness and opens a window for better diagnosis and targeted therapies.Genetic Engineering & Biotechnology News. July 15, 2008. (Also see: Causes of Scleroderma )

The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. In this nationwide register, a descriptive classification of patients with disease manifestations characteristic of SSc in five groups allows to include a broader spectrum of patients with features of SSc. Rheumatology 2008 47(8):1185-1192.

Systemic sclerosis - diagnosis and classification. Early diagnosis and classification may be difficult if disease expression is oligosymptomatic (undifferentiated), presenting with only Raynaud's phenomenon or limited scleroderma. PubMed. Z Rheumatol. 2006 Jun 28. (Also see: Difficult Diagnosis)

Studies of scleroderma at The Alfred Hospital, Melbourne. All types have a high incidence of autoantibodies, but these are generally not related to the severity of the disease and do not occur in relatives or spouses. PubMed. Intern Med J. 2006 Aug;36(8):513-8. (Also see: Antibodies )

Juvenile Scleroderma

When scleroderma of any type (either localized or systemic) afflicts children, it is called Juvenile Scleroderma. The localized forms of scleroderma (such as Linear and Morphea) are most common in children.

Unilateral generalized morphea (UGM) is a rare variant of localized scleroderma. As the onset of UGM usually occurs in pediatric patients, pediatricians should be cognizant of the presentation of this uncommon condition. PubMed. Eur J Med Res. 2006 Apr 28;11(4):152-6. (Also see: Localized Scleroderma: Morphea and Linear)

Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome. PubMed. Rheumatology (Oxford). 2005 Dec 20.

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: Skin Fibrosis)

Juvenile Systemic Sclerosis: A Follow-up Study of Eight Patients. Our results suggest that in Juvenile Systemic Sclerosis (jSSc), Raynaud's phenomenon is more severe, whereas internal organ manifestations and the frequency of autoantibodies are far less pronounced than in adult-onset SSc. Also, the survival rate and final outcome of patients with jSSc appear to be better than those in patients with adult-onset SSc. PubMed. Ann N Y Acad Sci. 2005 Jun;1051:229-34.

Localized

There are two types of Localized Scleroderma: Linear and Morphea. Localized scleroderma affects the skin. It may also affect the underlying muscles and bones, but it does not affect internal organs.

In general, Localized Scleroderma is relatively mild, and may be related to Systemic Scleroderma only in terms of similar superficial symptoms, such as the appearance of skin biopsy under the microscope.

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: Systemic Scleroderma, and Skin Involvement )

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 Skin Involvement )

Localized Fibrosing Disorders: Linear Scleroderma, Morphea, Regional Fibrosis. Localized fibrosing disorders include several clinical and histopathological conditions that are similar to the skin involvement of systemic sclerosis, but the systemic features are absent. Localized fibrosing disorders can be classified into several subtypes that include morphea, generalized morphea, and linear scleroderma, in which facial involvement is termed en coup de sabre. eMedicine.com. 11/07/06. (Also see: Morphea)

Muscle Cramps Associated with Localized Scleroderma Skin Lesions: Focal Dystonia, Neuromyotonia, or Nerve Entrapment? Based on the temporal and spatial correlation of skin lesions and muscle cramps in our patients, we propose that localized scleroderma may precipitate muscle cramps, possibly caused by local nerve injury. J Rheumatol 2006 December;33:2549. Letter.

Chronic venous insufficiency (CVI) - a potential trigger for localized scleroderma. It may be that CVI is a potential trigger factor for LS, which may only develop if a certain amount of trigger factors are present and resolves if one or more of the contributing factors (such as CVI) can be treated. PubMed. J Eur Acad Dermatol Venereol. 2006 Jan;20(1):96-9.

Localized scleroderma in childhood is not just a skin disease. Extracutaneous manifestations of juvenile localized scleroderma developed in almost one-fourth of the children in this study. These extracutaneous manifestations often were unrelated to the site of the skin lesions and sometimes were associated with multiple organ involvement. The risk of developing SSc was very low. PubMed. Arthritis Rheum. 2005 Sep 2;52(9):2873-2881.

Localized scleroderma is an autoimmune disorder. Many previous studies conclude that localized scleroderma involves autoimmune abnormalities and is one of the organ-specific autoimmune disorders targeting mainly skin, although the types of autoimmune abnormality are different from systemic sclerosis. PubMed. Rheumatology (Oxford). 2004 Nov 23. (Also see: Morphea, Linear, and Dr. Shinichi Sato)

Antinucleosome antibody is a major autoantibody in localized scleroderma. Although antinucleosome antibody was not specific to localized scleroderma, its high prevalence in localized scleroderma indicates that antinucleosome antibody is a major autoantibody in this disease. PubMed. Br J Dermatol. 2004 Dec;151(6):1182-8. (Also see: Antibodies)

Novel Autoantibody to Cu/Zn Superoxide Dismutase in Patients with Localized Scleroderma. IgG or IgM anti-Cu/Zn SOD antibody was detected in the serum of 89% of localized scleroderma patients, especially 100% of patients with generalized morphea. Minoru Hasegawa. 1687/510. ACR 2004. (Also see: Generalized Morphea and Antibodies)

Localized Scleroderma There is a wide spectrum of localized scleroderma, with types ranging from mild to disabling. eMedicine Dermatology.

Nodular Systemic Scleroderma

Nodular Scleroderma: Case Report and Literature Review. Nodular Systemic Sclerosis is a rare variant that presents with lesions that clinically resemble keloids. Most patients had symptoms of systemic sclerosis. J Rheumatol. Volume 30: No. 11 November 2003;30:2500-2. (Also see: Diseases Similar to Scleroderma)

Systemic Sclerosis (Systemic Scleroderma)

There are several types of Systemic Scleroderma: CREST, Limited and Diffuse. Systemic scleroderma is also known as systemic sclerosis (SSc). It may also be referred to as Progressive Systemic Sclerosis (PSSc), or Familial Progressive Systemic Sclerosis (FPSSc).

Systemic scleroderma may affect the skin, blood vessels, and/or internal organs. When it affects the skin, it can cause the skin —most commonly on the hands and/or face —to harden. With the blood vessels, it can cause Raynaud's. When it affects the internal organs, it may cause disability or even death. (Also see Systemic Scleroderma Symptoms )

The Cutoff Points of Antinuclear Antibody (ANA) with High Negative and Positive Predictive Values. Analysis of 5655 Cases. The cutoff point of ANA titer 160 is appropriate to exclude SLE (Lupus), MCTD (Mixed Connective Tissue Disease), SSc (Systemic Scleroderma) in most of the clinical setting. ANA 640 or higher deserves further investigation such as disease specific autoantibodies even without characteristic clinical findings, especially after proper exams for chronic liver and thyroid diseases and RA (Rheumatoid Arthritis). Hisanori Shimizu. 1515/129. ACR 2007. (Also see: Antibodies, Lupus, MCTD, and RA )

Risk Factors For Mortality In Patients With Systemic Sclerosis (SSc) And Interstitial lung disease (ILD). Mortality in patients with SSc and ILD is increased in those with an early and severe impairment of pulmonary function, concomitant cardiac involvement and elevated ESR (Sed rate), but not in Scl-70 positive patients. Beatriz E. Joven. 6/6. ACR 2007. (Also see: Pulmonary Fibrosis)

Scleroderma patients nailfold videocapillaroscopic patterns are associated with disease subset and disease severity. Nailfold videocapillaroscopy, a simple, non-invasive and non-expensive investigation, is useful in staging scleroderma patients and also provides prognostic information. Rheumatology 2007 46(10):1566-1569. (Also see: Nailfold Capillaroscopy )

Update on pathophysiology of scleroderma with special reference to immunoinflammatory events. Scleroderma or systemic sclerosis (SSc) is a complex disease in which the vasculopathy and the activation of the immune system with production of inflammatory mediators lead to dysregulated fibroblast activation. The resulting excessive deposition of collagens and other extracellular matrix proteins ends in fibrosis and organ dysfunction. The cause is unknown, but environmental factors are thought to play a role by triggering abnormal responses in genetically susceptible hosts. PubMed. Ann Med. 2007;39(1):42-53. (Also see: Causes of Scleroderma: Genetics, and Environmental )

Clinical risk assessment of organ manifestations in systemic sclerosis - a report from the EULAR Scleroderma Trials And Research (EUSTAR) group data base. Diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subsets are associated with particular organ manifestations, but in this analysis the clinical distinction appeared superseded by an antibody based classification in predicting some scleroderma complications. PubMed. Ann Rheum Dis. 2007 Feb 1. (Also see: Antibodies )

Clinical and Immunological Features in Patients with Systemic Sclerosis. There are differences in clinical and immunological findings between diffuse scleroderma (dSSc) and limited scleroderma (lSSc): severe capillary damage, arthralgia, muscle weakness, tendon friction rubs, joint contractures, esophageal, pulmonary, cardiac and renal involvement are more common in patients with dSSc. S. Arsik. AB0194 EULAR 2005. (Also see: Diffuse Scleroderma, and Limited Scleroderma)

Classification of systemic sclerosis. There is no convincing evidence of any advantage for distinguishing the limited, intermediate and diffuse forms of SSc rather than only the limited and diffuse forms. PubMed. Rheumatology (Oxford). 2005 May 3.

Systemic Sclerosis: Prognosis and Mortality

Years ago, only the worst cases of systemic scleroderma were diagnosed, thus leading to the widespread belief that systemic scleroderma was always progressive and fatal. Now that the full range of types and severity of scleroderma are being recognized and diagnosed, there is increasing awareness that many people have a milder type of illness with a much rosier longterm prognosis.

Fear Of Progression: Forms Of Fear-Expressions In Patients With Rheumatic Diseases. Fear of Progression is a high relevant problem for patients with rheumatic diseases, can differentiated in a variety of fear-expressions in intensity, forms, contents and can be reduced by individual learned coping-strategies. U. Engst-Hastreiter SAT0493-AHP EULAR 2008.

Cardiac Involvement in Systemic Sclerosis: The Strongest Predictive Factor of Prognosis in Patients with Scleroderma. The results disclosed that most frequent cardiac manifestation at the initial evaluation of scleroderma is subclinical arrhythmia. More importantly, cardiac involvement at early stage of the disease is the strongest predictive factor for death. Sumiaki Tanaka. 13/13. ACR 2007. (Also see: Cardiac Involvement )

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: Diffuse SSc, and Skin Fibrosis ).

Systemic Sclerosis Patients Have Activating Antibodies Targeting Both Endothelin Receptor Type A And Angiotensin Ii Type 1 Receptor Predicting Worse Prognosis. Anti-AT1R and anti-ETAR antibodies are a biomarker for severe disease and worse prognosis and could explain pathogenic features found in systemic sclerosis. The detection of these antibodies could identify SSc patients that might benefit from a receptor blockade or from a specific modulation of the antibody-receptor interaction. G. Riemekasten OP0162 EULAR 2007. (Also see: Causes of Scleroderma: Endothelin and Antibodies )

Mortality And Histological Characteristics Of SSc - A Retrospective Study Of 12 Autopsy Patients. SSc is a progressive multifocal process characterized by histological (vascular and interstitial) changes co-existing in different stages of their progression. In the course of the disease new foci develop, which increase in size and number, may become confluent, ultimately leading to diffuse, systemic interstitial sclerosis. Á. Apáthy THU0235 EULAR 2007.

Impairment of the antifibrotic effect of hepatocyte growth factor (HGF) in lung fibroblasts from African Americans: Possible role in systemic sclerosis. Reduced levels of HGF as well as a deficiency in c-Met receptor function appear to be present in African American patients with SSc. These findings may explain in part the greater disease severity and worse prognosis observed in African Americans with SSc. Arthritis and Rheumatism. Volume 56, Issue 7, Pages 2432 - 2442. (Also see: Pulmonary Fibrosis )

Scleroderma Outlook Improves as Survival Increases. Professor Virginia Steen, M.D., studied 2,000 patients with scleroderma (also known as systemic sclerosis) treated between 1972 and 2001 at the University of Pittsburgh and found that 10-year survival steadily improved over those years by 12 percent-- from 54 percent to 66 percent. Georgetown University Medical Center. 07/10/07.

Changes in causes of death in systemic sclerosis, 1972- 2002. Survival of scleroderma has changed since the treatment of renal crisis became possible. The change in pattern of scleroderma- related mortality over the past 30 years implicates the lung (both pulmonary hypertension and pulmonary fibrosis) as the primary causes of scleroderma related deaths today. PubMed. Ann Rheum Dis. 2007 Feb 28. (Also see: Pulmonary Involvement and Renal Involvement )

Prognostic markers for systemic sclerosis. The prognosis of systemic sclerosis depends chiefly on the extent of the skin lesions, which correlates with the severity of the cardiovascular, pulmonary, and renal manifestations. PubMed. Joint Bone Spine. 2006 Oct;73(5):490-4.

Morbidity and mortality of patients diagnosed with systemic sclerosis after the age of 75: a nested case-control study. We conclude that a diagnosis of SSc at an older age appears to be a poor prognostic indicator related to both disease severity and comorbidities. A higher clinical suspicion will lead to an earlier diagnosis and a potential decrease in morbidity and mortality. PubMed. Clin Rheumatol. 2006 Nov;25(6):831-4.

Outcome of patients with scleroderma admitted to intensive care unit. A report of nine cases. The outcome of scleroderma patients admitted to the ICU was extremely poor. Infectious complication was the most common cause of death in our patients. PubMed. Clin Exp Rheumatol. 2006 Jul-Aug;24(4):380-6. (Also see: Pulmonary Fibrosis )

Gender Differences in Systemic Sclerosis Clinical Expression and Survival. Male systemic sclerosis patients present more renal failure, conduction disturbances and inflammatory myopathy, and less anti-centromere antibodies than female patients. B. Joven. FRI0361 EULAR 2006. (Also see: Causes of Scleroderma: Hormones and Chromosomes )

Predictive markers for development of severe organ involvement in patients with systemic sclerosis (SSc). Prognosis of SSc is associated with the extent of skin involvement and the presence of lung, heart, kidney, and/or digestive tract damage. Tto avoid irreversible tissue injury, early detection of visceral involvement is crucial for prompt initiation of therapy. PubMed. Ann N Y Acad Sci. 2005 Jun;1051:455-64.

Predictors of Severe Internal Organ Involvement in Early Systemic Sclerosis. Rapidly progressive SSc may be predictable on clinical and lab grounds at the time of disease onset that allow to identify patients who require more careful follow-up and aggressive treatment. N. G. Guseva. FRI0100 EULAR 2005.

Changes in Causes of Death in Systemic Sclerosis Over the Past 30 Years. Throughout the past 30 years, the frequency of deaths from RC (renal crisis) has dramatically decreased and at the same time the frequency of PF (pulmonary fibrosis) increased. However, only 10% of SSc patients surviving RC have died of PF, which may be because patients with the highest frequency of RC have a low frequency of PF. Over the past 10 years, SSc patients have had improved survival, longer disease duration at the time they die and are less likely to die from scleroderma related complications. Pulmonary hypertension and pulmonary fibrosis now account for 50% of SSc related deaths and 25% of all causes of death in SSc patients. Virginia Steen. 1052/432. ACR 2004. (Also see: Renal Involvement, Pulmonary Fibrosis, and Pulmonary Hypertension.)

The Outcome of Systemic Sclerosis Patients who Present in the First Year of Their Illness. Systemic sclerosis (SSc) has a variable onset and course. Patients who have diffuse skin thickening very early in their disease have the highest risk for severe organ involvement, but those patients with diffuse scleroderma who do not develop severe organ involvement within the first 3 years of disease have an excellent long term survival. Virginia Steen. 1051/431. ACR 2004. (Also see Diffuse Scleroderma )

CREST Syndrome

CREST Syndrome, by itself, does not have any skin tightening at all. CREST stands for Calcinosis, Raynaud's, Esophagus, Sclerodactyly, and Telangiectasia. CREST may occur alone, or in combination with any other form of Scleroderma (or even other autoimmune diseases) such as CREST with Limited Scleroderma, or CREST with Lupus. See CREST Syndrome.

Limited Scleroderma

Limited Scleroderma is when skin involvement is limited to the hands (although the face and neck may also be involved.) See Limited Scleroderma.

Diffuse Scleroderma

Diffuse Scleroderma is when skin tightening also occurs above the wrists (or elbows, see below). There are several subcategories of Diffuse, such as Scleroderma sans Scleroderma where there is internal organ fibrosis, but no skin tightening; and Familial Progressive Systemic Sclerosis, a rare form which runs in families. See Diffuse Scleroderma.

Overlap Syndrome

Overlap Syndrome. If a scleroderma patient also has any other autoimmune disease (such as lupus, rheumatoid arthritis, etc.) it is referred to as overlap ; as in "Diffuse scleroderma in overlap with lupus." Scleroderma symptoms can also be a part of mixed connective tissue disease (MCTD), or undifferentiated connective tissue disease (UCTD). See Overlap Syndrome.