Sie sind auf Seite 1von 16

Overview of the clinical manifestations of systemic sclerosis (scleroderma) in adults

Author
John Varga, MD
Section Editor
John S Axford, DSc, MD, FRCP, FRCPCH
Deputy Editor
Monica Ramirez Curtis, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2016. | This topic last updated: Jun 03, 2016.
INTRODUCTION The term scleroderma is used to describe the presence of thickened, hardened
skin (from the Greek scleros) [1]. Scleroderma is the hallmark feature of a heterogeneous group of
conditions, the classification of which is discussed in more detail separately. (See "Overview and
classification of scleroderma disorders".)
Scleroderma may be a clinical feature of limited anatomic extent affecting only the skin and subjacent
tissues, or it may be associated with systemic involvement. When the characteristic skin disorder is
associated with internal organ involvement, the disease is termed systemic sclerosis (SSc). SSc is
subcategorized further into diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) on the
basis of the extent and distribution of skin involvement. lcSSc is commonly associated with the
CREST syndrome [2]. (See 'Limited cutaneous SSc' below.)
Other disorders that may either have typical scleroderma skin changes or those that have
scleroderma-like cutaneous involvement are considerations in the differential diagnosis of SSc.
(See "Diagnosis and differential diagnosis of systemic sclerosis (scleroderma) in adults".)
The systemic manifestations of SSc are diverse. Most prominent are abnormalities of the circulation
(most notably Raynaud phenomenon) and involvement of multiple organ systems, including the
musculoskeletal, renal, pulmonary, cardiac, and gastrointestinal systems, with fibrotic and/or vascular
complications.
The prevalence rates of scleroderma-like conditions range from 4 to 489 cases per million individuals
[3,4]. Incidence figures for SSc are 0.6 to 122 per million persons per year; the actual prevalence is
probably at the high end of the range noted above [4]. There are regional differences in incidence. For
example, higher rates are seen in the United States and Australia than in Japan or Europe, and in
blacks than whites [4].
A brief overview of the clinical features of SSc in adults is presented here. The pathogenesis,
diagnosis, and treatment of SSc are discussed separately. (See "Pathogenesis of systemic sclerosis
(scleroderma)" and "Diagnosis and differential diagnosis of systemic sclerosis (scleroderma) in
adults" and "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults".)
Localized forms of scleroderma and scleroderma in childhood are discussed separately.
(See "Localized scleroderma in childhood".)
GENERAL MANIFESTATIONS Fatigue, arthralgias, and myalgias are common symptoms in
patients with systemic sclerosis (SSc). The frequency of these symptoms is uncertain.
One of the few estimates of the type and frequency of general symptoms among those with SSc was
reported in a study of 107 patients with established disease (median 10 years, range 1 to 37 years)
[5]. The following were the most frequent symptoms:
Fatigue (76 percent)
Stiff joints (74 percent)
Loss of strength (68 percent)

Pain (67 percent)


Sleep difficulties (66 percent)
Skin discoloration (47 percent)
Less commonly noted symptoms were breathlessness, upset stomach, depression, nausea, and
weight loss.
The level of fatigue in SSc is comparable to that in rheumatoid arthritis, systemic lupus, or cancer
patients in active treatment [6]. The presence of fatigue was associated with poorer physical function
and greater pain [5]. Causes of pain include skin-related discomfort, joint pain, Raynaud
phenomenon, and ischemic digital ulcers.
SKIN INVOLVEMENT Skin involvement is a nearly universal feature of systemic sclerosis (SSc). It
is characterized by variable extent and severity of skin thickening and hardening. The fingers, hands,
and face are generally the earliest areas of the body involved. Edematous swelling and erythema may
precede skin induration (figure 1).
Other prominent skin manifestations include:
Pruritus in the early stages
Edema in the early stages
Skin hyperpigmentation or depigmentation (salt-and-pepper)
Loss of appendicular hair
Sclerodactyly
Digital ulcers
Pitting at the fingertips
Telangiectasia
Calcinosis cutis
The assessment of skin involvement includes semiquantitative estimation of skin thickness, pliability
(hardness), and fixation to underlying structures (tethering). The modified Rodnan skin score is
commonly used as an outcome measure in clinical trials (figure 2A-B). This semi-quantitative score
rates the severity of these features from 0 (normal) to 3 (most severe) in 17 distinct areas of the body.
Objective approaches to measuring scleroderma skin involvement, such as ultrasonography [7,8] and
use of a durometer, are under investigation.
The distribution of skin lesions forms the basis for the current classification system of SSc into limited
and diffuse forms of the disease (table 1). (See "Overview and classification of scleroderma
disorders".)
Radiographs of the hands may reveal soft tissue calcifications (calcinosis cutis) (image 1) and
resorption of the distal phalangeal tufts (acro-osteolysis). Articular erosions, joint space narrowing,
and demineralization are less common radiographic findings [9].
A small percentage of patients with SSc have no skin induration (termed SSc sine scleroderma) [10].
Although there is no clinically evident skin sclerosis, these patients have characteristic
vascular and/or fibrotic features of systemic disease, including Raynaud phenomenon, gastrointestinal
involvement, renal crisis, pulmonary hypertension, and/or interstitial lung disease.
Limited cutaneous SSc In patients with limited cutaneous SSc (lcSSc), skin sclerosis is restricted
to the hands, the distal forearm, and, to a lesser extent, the face and neck. These patients generally
have prominent vascular manifestations, including severe Raynaud phenomenon and cutaneous

telangiectasia. Many patients with lcSSc have manifestations of the CREST syndrome (Calcinosis
cutis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia).
Diffuse cutaneous SSc Sclerotic skin on the chest, abdomen, or upper arms and shoulders is
indicative of diffuse cutaneous SSc (dcSSc). Patients with dcSSc are more likely to have, or to
develop, significant internal organ damage due to ischemic injury or fibrosis than those with limited
cutaneous SSc.
VASCULAR DISEASE Vascular dysfunction is a significant component of the pathogenesis of
systemic sclerosis (SSc). The most characteristic clinical manifestation of vascular dysfunction of SSc
is Raynaud phenomenon, defined as sequential color changes in the digits precipitated by cold,
stress, or even change in temperatures. Raynaud phenomenon is due to arterial vasoconstriction in
the digits. The color changes of pallor ("white"), acrocyanosis ("blue"), and reperfusion hyperemia
("red") are characteristic. (See "Clinical manifestations and diagnosis of the Raynaud phenomenon".)
Vascular injury and consequent chronic tissue damage underlie other serious systemic complications
of SSc, including gastric antral vascular ectasia, digital ischemic ulcers, pulmonary artery
hypertension, scleroderma renal crisis, and myocardial infarction.
Raynaud phenomenon Raynaud phenomenon is classically viewed as reversible vasospasm due
to functional changes in the digital arteries of the hands and feet. However, in many patients with SSc,
progressive structural changes develop in the small blood vessels, with permanently impaired flow. In
such patients, episodes of Raynaud phenomenon may be prolonged and can result in ischemic digital
ulceration or infarction.
It is important to realize that persons presenting with Raynaud phenomenon may have primary (no
definable underlying disease) or secondary Raynaud phenomenon. Whereas Raynaud phenomenon
is seen in SSc and other connective tissue diseases, as well as a number of disorders which result in
abnormal blood flow (table 2), primary Raynaud phenomenon is common in the general population,
occurs in otherwise healthy individuals, and almost always follows a benign course. In patients with
lcSSc, Raynaud phenomenon generally precedes other disease manifestations, sometimes by years
or even decades. In contrast, in patients with dcSSc, the onset of Raynaud phenomenon generally
coincides with, and in some cases may even follow, the appearance of characteristic skin or
musculoskeletal manifestations.
Thromboembolic disease An increased risk of venous thromboembolism (VTE) has been
reported among patients with SSc [11,12]. A large population-based study observed a threefold
increased risk of pulmonary embolism, deep vein thrombosis, and VTE among 1245 patients with
incident SSc, compared with matched non-SSc controls, after adjusting for relevant risk factors such
as age, sex, and recent hospitalizations [11]. The increased risk of VTE was highest during the first
year after SSc diagnosis.
EXTRACUTANEOUS ORGAN INVOLVEMENT Extracutaneous organ involvement is virtually
universal in systemic sclerosis (SSc). Along with musculoskeletal involvement, the lungs, kidneys,
gastrointestinal tract, and heart are commonly affected (table 3).
Gastrointestinal involvement Nearly 90 percent of patients with either subtype of SSc (diffuse
cutaneous SSc [dcSSc] or limited cutaneous SSc [lcSSc]) have evidence of gastrointestinal
involvement [13,14]. Nearly half of these patients may have no symptoms. These issues are
discussed in detail separately but will be briefly reviewed here. (See "Gastrointestinal manifestations
of systemic sclerosis (scleroderma)".)

Esophageal hypomotility and incompetence of the lower esophageal sphincter disease were the
earliest described visceral manifestations of SSc. Symptoms principally result from chronic
gastroesophageal reflux, with subsequent chronic esophagitis and stricture formation, Barrett's
esophagus, and pulmonary microaspiration.
Any part of the gastrointestinal tract from mouth to anus may be affected in SSc. Common symptoms
of gastrointestinal involvement include dysphagia and choking, heartburn, hoarseness, cough after
swallowing, bloating, alternating constipation and diarrhea, pseudo-obstruction and bacterial small
bowel overgrowth with malabsorption, and fecal incontinence. Chronic gastroesophageal reflux and
recurrent episodes of microaspiration may contribute to the development or progression of interstitial
lung disease [15]. Vascular ectasia (angiodysplasia) in the antrum of the stomach ("watermelon
stomach") is frequent and may be a cause of chronic gastrointestinal bleeding and anemia.
Pulmonary involvement Pulmonary involvement is seen in more than 70 percent of patients with
SSc. The two principal clinical manifestations are interstitial lung disease (also called fibrosing
alveolitis or pulmonary fibrosis) and pulmonary vascular disease, leading to pulmonary arterial
hypertension (PAH) (table 4). These issues are discussed in detail separately but will be briefly
reviewed here. (See "Clinical manifestations, evaluation, and diagnosis of interstitial lung disease in
systemic sclerosis (scleroderma)".)
Interstitial lung disease Some degree of interstitial lung disease occurs in more than threequarters of patients with SSc. The most common symptoms are breathlessness on exertion (which
may progress to dyspnea at rest) and a nonproductive cough. However, patients may have alveolitis
and early pulmonary fibrosis in the absence of respiratory symptoms or physical findings. Chest pain
is infrequent and hemoptysis is rare. In advanced disease, auscultation over the lungs reveals
"Velcro" rales most prominent at the lung bases.
Pulmonary vascular disease Pulmonary vascular disease, primarily pulmonary arterial
hypertension, occurs in 10 to 40 percent of patients with SSc and is more common in patients with
limited cutaneous disease. Vascular disease may occur with or without concurrent interstitial lung
disease. Dyspnea with exertion and diminished exercise tolerance are the most common initial
symptoms, but these may be absent until the disease is fairly advanced.
Pulmonary arterial hypertension is generally a late complication of SSc. It is typically progressive and,
if severe, can lead to cor pulmonale and right-sided heart failure. Thrombosis of the pulmonary
vessels is a common late-stage complication and is a frequent cause of death. (See "Cor pulmonale".)
Lung cancer The risk of lung cancer is increased in patients with both lcSSc and dcSSc. The
incidence rate of malignant lung neoplasms is approximately fivefold higher than that for an age and
gender matched subset of the general population. (See 'Cancer risk' below.)
Renal disease Autopsy studies suggest that 60 to 80 percent of patients with dcSSc have
pathologic evidence of kidney damage [16,17]. Impaired renal reserve may be present in the absence
of clinical renal disease [18]. Microalbuminuria, a mild elevation in the plasma creatinine
concentration, and/or hypertension is observed in as many as 50 percent of patients, but most do not
progress to chronic kidney failure [19-21].
Scleroderma renal crisis Severe and life-threatening renal involvement develops in approximately
10 to 15 percent of patients. It is far more frequent in patients with dcSSc than lcSSc and almost
invariably occurs in the early stages of the disease. This form of renal involvement is characterized
by:
Acute onset of oliguric renal failure

Urinalysis that reveals only mild proteinuria with few cells or casts
Abrupt onset of moderate to marked or malignant hypertension (although some patients remain
normotensive)
Microangiopathic hemolysis and thrombocytopenia
Other features of scleroderma renal crisis may be due to severe hypertension or vasculopathy and
include microangiopathic hemolytic anemia and thrombocytopenia, pulmonary edema, headache,
blurred vision, and hypertensive encephalopathy, often complicated by generalized seizures.
Scleroderma renal crisis is discussed in more detail separately. (See "Renal disease in systemic
sclerosis (scleroderma), including scleroderma renal crisis".)
Cardiac disease Patients with SSc and symptomatic cardiac involvement have a poor prognosis,
with two- and five-year mortality rates of approximately 60 and 75 percent, respectively [22]. Cardiac
involvement appears to be more severe in men compared with women [23]. Most commonly, cardiac
complications are secondary to pulmonary arterial hypertension, but primary cardiac involvement has
been increasingly recognized. The manifestations of primary cardiac involvement in SSc include
pericarditis, pericardial effusion, myocardial fibrosis, heart failure, myocarditis, microvascular disease,
myocardial infarction (MI), conduction disturbances, and arrhythmias [22,24].
Pericardial disease Symptomatic pericarditis occurs in 7 to 20 percent of patients with SSc, but
pathologic evidence of pericardial involvement is observed in 70 to 80 percent at autopsy. Pericardial
effusions may be small or large and can develop rapidly.
There is an association between pericardial effusion and the development of acute renal failure. Two
potential explanations for this association have been suggested. First, pericardial effusion may simply
be a marker of activeand/or severe SSc. Second, the presence of a large pericardial effusion could
compromise cardiac output, resulting in renal hypoperfusion and triggering a cascade of events
culminating in scleroderma renal crisis. (See "Renal disease in systemic sclerosis (scleroderma),
including scleroderma renal crisis".)
Myocardial disease
Myocardial fibrosis Patchy myocardial fibrosis is a pathological hallmark of cardiac
involvement in SSc [25]. It is distinguishable from the fibrosis associated with coronary
atherosclerotic disease and is independent of the secondary cardiac involvement that may result
from pulmonary hypertension. Myocardial fibrosis is thought to result from recurrent vasospasm
of small vessels and is often associated with contraction band necrosis, a histological lesion
indicative of myocardial ischemia (MI) followed by reperfusion. The degree of myocardial fibrosis
may be increased in SSc patients with a long history of Raynaud phenomenon [25].
Myocardial involvement can lead to systolic or more often diastolic ventricular dysfunction. This
was illustrated in a Doppler echocardiography study of 570 patients with SSc in which left
ventricular systolic and diastolic dysfunction were present in 1 and 18 percent, respectively [26].
Higher rates of myocardial dysfunction have been reported with tissue Doppler studies in which
the abnormalities were independent of pulmonary artery hypertension or interstitial lung disease
[27]. (See "Tissue Doppler echocardiography".)
Myocardial ischemia Patients with SSc have an increased risk of acute MI [28,29]. The
largest study to evaluate the risk of acute MI in SSc patients included 1344 Scc patients and
13,440 matched controls from a Taiwanese national insurance database during the period from
1997 to 2006 [28]. After adjusting for age, sex, and comorbidities, SSc was found to be an

independent risk factor for acute MI (HR 2.45, CI 1.60-3.75). There also appeared to be no effect
of immunosuppressive therapy on the risk of MI.
Arrhythmias Conduction system disease and arrhythmias are common. They are likely to result
from fibrosis of the myocardium and conduction system. Many deaths among SSc patients are
sudden, and some may result from a ventricular arrhythmia.
Musculoskeletal disease The earliest manifestations of diffuse SSc are swelling of the hands,
arthralgia, myalgia, and fatigue.
Joint pain, immobility and contractures develop as the result of fibrosis around tendons and other
periarticular structures. Contractures of the fingers from this process are most common, but large joint
contractures involving the wrists, elbows, and ankles may also occur. The process is sometimes
associated with palpable and/or audible deep tendon friction rubs. Tendon friction rubs occur
predominantly in patients with dcSSc. The most common sites of involvement are the extensor and
flexor tendons of the fingers and wrist, tendons over the elbow (triceps), knee (patellar), and ankle
(anterior and posterior tibial, peroneal and Achilles).
Frank inflammatory arthritis is uncommon in SSc. When present, it is usually accompanied by joint
contractures and tendon friction rubs and is more likely to occur in patients with diffuse cutaneous
SSc [30]. The pattern of arthritis is most commonly polyarticular, but oligoarticular and monoarticular
patterns can also be observed. In some patients, an erosive polyarticular arthritis of the small joints,
particularly the metacarpophalangeal joints and wrists, can be seen. The distal interphalangeal joints
are generally not affected. The pattern of articular involvement in the hands is similar to that in
rheumatoid arthritis, and it can be difficult to distinguish an overlap syndrome from an SSc-related
primary arthropathy in such cases.
Several studies suggest that the presence of tendon friction rubs in patients with SSc is a marker for
aggressive disease and increased risk of internal organ involvement [31-33]. Destructive joint disease
in a patient with SSc may suggest an overlap syndrome with rheumatoid arthritis.
(See "Undifferentiated systemic rheumatic (connective tissue) diseases and overlap syndromes".)
Neuromuscular involvement Neuromuscular involvement in SSc is discussed in more detail
elsewhere. (See "Neuromuscular manifestations of systemic sclerosis (scleroderma)".) The following
is a brief summary of the types of neurologic and muscle disorders that have been noted in case
reports and series:
Cranial, entrapment, peripheral, cutaneous, and autonomic neuropathies
Myopathy and inflammatory myositis
Less commonly, central nervous system involvement including headache, seizures, stroke,
radiculopathy, and myelopathy
Genitourinary SSc in men is very commonly associated with erectile dysfunction, which can be an
early and even initial manifestation of disease [34]. This was illustrated in a survey that compared 43
SSc patients to 23 patients with rheumatoid arthritis (RA) [35]. Among the SSc patients, 81 percent
had self-reported erectile dysfunction versus 48 percent of those with RA. While Raynaud
phenomenon was more prevalent in SSc than in RA (86 versus 19 percent), it was not an independent
predictor of erectile dysfunction.
Women with SSc may also have sexual dysfunction. This is related to decreased vaginal lubrication or
constriction of the vaginal introitus. In one study, dyspareunia was present in 56 percent of 60 women
with SSc [36].

PREGNANCY A detailed discussion of issues related to pregnancy in SSc is presented separately.


(See "Systemic sclerosis (scleroderma) and pregnancy".)
CANCER RISK There have been several reports demonstrating an increased risk of malignancy in
patients with systemic sclerosis (SSc) [37-44]. The most significant association appears to be with
lung cancer, which accounts for approximately one-third of the cancers seen in SSc patients [39];
however, a significantly increased incidence was not noted in a population with a high background
rate of lung cancer [42]. In a study of 632 Australian patients with SSc, 19 developed lung cancer [45].
Those who smoked were seven times as likely to develop cancer as those who did not. Pulmonary
fibrosis and antitopoisomerase antibodies were not risk factors for lung cancer.
The issue of malignancy in SSc was assessed in a nationwide population-based, retrospective cohort
analysis from Denmark performed between 1977 and 2006; 2046 patients with systemic sclerosis
were evaluated [43]. Patient records were compared with a cohort from the Danish Cancer Registry.
The ratio of cancers in SSc patients to expected cancers (the standardized incidence ratio, SIR) was
1.5 overall. The most frequent cancers were lung (SIR 1.6), hematologic (SIR 2.5), and immunerelated (SIR 1.4).
A similar, modest increase in the overall risk of malignant disease (SIR 1.55) was also seen in a
cohort of 769 patients seen from 1987 to 2002 [44]. There was, however, a marked increase in the
risk of esophageal carcinoma (SIR 15.9 [95% CI 4.2-27.6]) and oropharyngeal carcinoma (SIR 9.63
[95% CI 2.97-16.3]).
The cause of an increased cancer risk in SSc is not well understood. The association with lung and
skin cancers suggests that sites of disease activity may be prone to malignant transformation.
A close temporal relationship between the onset of cancer and of SSc has been observed among
patients with autoantibodies to RNA polymerase I/III [46,47]. One study demonstrated that tumors with
somatic mutations in the POLR3A gene, which encodes for RNA polymerase III, may induce the
development of autoantibodies to RNA polymerase III and thereby trigger the development of SSc
[48]. In a series of 16 patients with SSc who also had cancer, somatic mutations in the POLR3A gene
were present in the tumors from six of eight patients with anti-RNA polymerase III antibodies; by
contrast, the POLR3A gene was not mutated in the eight patients without such antibodies [48]. Among
the eight patients with antibodies to RNA polymerase III, the cancers were diagnosed between five
months prior to their SSc diagnosis and 2.5 years afterward. However, additional studies are needed
to determine whether or not somatic mutations in tumors, with subsequent development of
autoantibodies, represent a potential mechanistic link between cancer and SSc.
There are conflicting data regarding whether the presence of antibodies to topoisomerase-I (Scl-70)
identifies a population of SSc patients who are more likely to have, or to develop, cancer [49,50].
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The
Basics and Beyond the Basics. The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10 th to 12th grade reading level
and are best for patients who want in-depth information and are comfortable with some medical
jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on patient info and the keyword(s) of interest.)

Basics topics (see "Patient education: Raynaud disease (The Basics)" and "Patient education:
Systemic scleroderma (The Basics)")
Beyond the Basics topic (see "Patient education: Raynaud phenomenon (Beyond the Basics)")
SUMMARY
Systemic sclerosis (SSc) is categorized into diffuse cutaneous SSc (dcSSc) and limited
cutaneous SSc (lcSSc) subsets on the basis of the extent and distribution of skin involvement.
lcSSc is commonly associated with the CREST syndrome. (See 'Introduction' above.)
Skin involvement is a nearly universal feature of SSc and is characterized by variable
thickening and hardening of the skin. The fingers, hands, and face are generally the earliest
areas of the body involved. Edematous swelling and erythema of the skin generally precedes
skin induration (figure 1). Other skin manifestations can occur. Malaise, fatigue, arthralgias, and
myalgias are common. (See 'Skin involvement' above and 'General manifestations' above.)
The most obvious clinical manifestation of vascular dysfunction of SSc is Raynaud
phenomenon, which is due to arterial vasoconstriction in the digits. Characteristic sequential
color changes in the digits of pallor ("white"), acrocyanosis ("blue"), and reperfusion hyperemia
("red") are precipitated by cold, stress, or even change in temperatures. (See 'Vascular
disease' above.)
Vascular injury and subsequent chronic damage underlie other serious complications of SSc,
including pulmonary artery hypertension, scleroderma renal crisis, and gastric antral vascular
ectasia, and also contribute to the pathogenesis of cardiac and gastrointestinal complications.
(See 'Vascular disease' above and 'Extracutaneous organ involvement' above.)
Gastrointestinal involvement is present in most patients and can involve any part of the
gastrointestinal tract. Symptoms are present in more than half of patients and most commonly
result from chronic gastroesophageal reflux, with subsequent chronic esophagitis and stricture
formation, Barretts esophagus, and abnormal motility. (See 'Gastrointestinal
involvement' above.)
Pulmonary involvement is seen in more than 70 percent of patients. The principal pulmonary
manifestations are interstitial lung disease and pulmonary vascular disease. The latter leads to
pulmonary arterial hypertension and is more common in patients with limited cutaneous disease.
(See 'Pulmonary vascular disease' above.)
Clinical renal disease is observed in up to half of patients. Findings may include albuminuria, a
mild elevation in the plasma creatinine concentration, and/or hypertension. Pathologic vascular
changes are present in the kidneys in 60 to 80 percent of patients with dcSSc. Scleroderma
renal crisis, the most serious renal complication, occurs in up to 10 to 15 percent of patients,
generally among those with early-stage dcSSc, and is associated with a poor prognosis.
(See 'Renal disease' above.)
Cardiac disease in SSc may be primary or secondary and is associated with a poor prognosis.
Musculoskeletal disease, neuromuscular involvement, and genitourinary involvement may also
occur, and the risk of malignancy may be increased. (See 'Cardiac disease' above
and 'Musculoskeletal disease' above and 'Neuromuscular involvement' above
and 'Genitourinary' above and 'Cancer risk' above.)
The risk of cancer is increased. (See 'Cancer risk' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
1.
2.

REFERENCES
Black CM. Scleroderma--clinical aspects. J Intern Med 1993; 234:115.
LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification,
subsets and pathogenesis. J Rheumatol 1988; 15:202.

3.
4.
5.
6.

7.

8.

9.
10.

11.

12.

13.
14.

15.
16.
17.
18.
19.

20.
21.

22.
23.
24.
25.

Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and
selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 41:778.
Chifflot H, Fautrel B, Sordet C, et al. Incidence and prevalence of systemic sclerosis: a
systematic literature review. Semin Arthritis Rheum 2008; 37:223.
Sandusky SB, McGuire L, Smith MT, et al. Fatigue: an overlooked determinant of physical
function in scleroderma. Rheumatology (Oxford) 2009; 48:165.
Thombs BD, Bassel M, McGuire L, et al. A systematic comparison of fatigue levels in
systemic sclerosis with general population, cancer and rheumatic disease samples. Rheumatology
(Oxford) 2008; 47:1559.
Scheja A, Akesson A. Comparison of high frequency (20 MHz) ultrasound and palpation for
the assessment of skin involvement in systemic sclerosis (scleroderma). Clin Exp Rheumatol 1997;
15:283.
Hesselstrand R, Scheja A, Wildt M, Akesson A. High-frequency ultrasound of skin involvement
in systemic sclerosis reflects oedema, extension and severity in early disease. Rheumatology
(Oxford) 2008; 47:84.
Avouac J, Guerini H, Wipff J, et al. Radiological hand involvement in systemic sclerosis. Ann
Rheum Dis 2006; 65:1088.
Poormoghim H, Lucas M, Fertig N, Medsger TA Jr. Systemic sclerosis sine scleroderma:
demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis Rheum 2000;
43:444.
Schoenfeld SR, Choi HK, Sayre EC, Avia-Zubieta JA. Risk of Pulmonary Embolism and
Deep Venous Thrombosis in Systemic Sclerosis: A General Population-Based Study. Arthritis Care
Res (Hoboken) 2016; 68:246.
Chung WS, Lin CL, Sung FC, et al. Systemic sclerosis increases the risks of deep vein
thrombosis and pulmonary thromboembolism: a nationwide cohort study. Rheumatology (Oxford)
2014; 53:1639.
Turner R, Lipshutz W, Miller W, et al. Esophageal dysfunction in collagen disease. Am J Med
Sci 1973; 265:191.
Akesson A, Wollheim FA. Organ manifestations in 100 patients with progressive systemic
sclerosis: a comparison between the CREST syndrome and diffuse scleroderma. Br J Rheumatol
1989; 28:281.
Marie I, Dominique S, Levesque H, et al. Esophageal involvement and pulmonary
manifestations in systemic sclerosis. Arthritis Rheum 2001; 45:346.
Medsger TA Jr, Masi AT, Rodnan GP, et al. Survival with systemic sclerosis (scleroderma). A
life-table analysis of clinical and demographic factors in 309 patients. Ann Intern Med 1971; 75:369.
Medsger TA Jr, Masi AT. Survival with scleroderma. II. A life-table analysis of clinical and
demographic factors in 358 male U.S. veteran patients. J Chronic Dis 1973; 26:647.
Livi R, Teghini L, Pignone A, et al. Renal functional reserve is impaired in patients with
systemic sclerosis without clinical signs of kidney involvement. Ann Rheum Dis 2002; 61:682.
Traub YM, Shapiro AP, Rodnan GP, et al. Hypertension and renal failure (scleroderma renal
crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases. Medicine
(Baltimore) 1983; 62:335.
TUFFANELLI DL, WINKELMANN RK. Systemic scleroderma, A clinical study of 727 cases.
Arch Dermatol 1961; 84:359.
Nikpour M, Hissaria P, Byron J, et al. Prevalence, correlates and clinical usefulness of
antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an
Australian cohort. Arthritis Res Ther 2011; 13:R211.
Janosik DL, Osborn TG, Moore TL, et al. Heart disease in systemic sclerosis. Semin Arthritis
Rheum 1989; 19:191.
Elhai M, Avouac J, Walker UA, et al. A gender gap in primary and secondary heart
dysfunctions in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis 2016; 75:163.
Byers RJ, Marshall DA, Freemont AJ. Pericardial involvement in systemic sclerosis. Ann
Rheum Dis 1997; 56:393.
Tzelepis GE, Kelekis NL, Plastiras SC, et al. Pattern and distribution of myocardial fibrosis in
systemic sclerosis: a delayed enhanced magnetic resonance imaging study. Arthritis Rheum 2007;
56:3827.

26.

27.

28.
29.

30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.

de Groote P, Gressin V, Hachulla E, et al. Evaluation of cardiac abnormalities by Doppler


echocardiography in a large nationwide multicentric cohort of patients with systemic sclerosis. Ann
Rheum Dis 2008; 67:31.
Meune C, Avouac J, Wahbi K, et al. Cardiac involvement in systemic sclerosis assessed by
tissue-doppler echocardiography during routine care: A controlled study of 100 consecutive patients.
Arthritis Rheum 2008; 58:1803.
Chu SY, Chen YJ, Liu CJ, et al. Increased risk of acute myocardial infarction in systemic
sclerosis: a nationwide population-based study. Am J Med 2013; 126:982.
Nordin A, Jensen-Urstad K, Bjrndal L, et al. Ischemic arterial events and atherosclerosis in
patients with systemic sclerosis: a population-based case-control study. Arthritis Res Ther 2013;
15:R87.
Morrisroe KB, Nikpour M, Proudman SM. Musculoskeletal Manifestations of Systemic
Sclerosis. Rheum Dis Clin North Am 2015; 41:507.
Steen VD, Medsger TA Jr. The palpable tendon friction rub: an important physical examination
finding in patients with systemic sclerosis. Arthritis Rheum 1997; 40:1146.
Dor A, Lucas M, Ivanco D, et al. Significance of palpable tendon friction rubs in early diffuse
cutaneous systemic sclerosis. Arthritis Care Res (Hoboken) 2013; 65:1385.
Avouac J, Walker UA, Hachulla E, et al. Joint and tendon involvement predict disease
progression in systemic sclerosis: a EUSTAR prospective study. Ann Rheum Dis 2016; 75:103.
Walker UA, Tyndall A, Ruszat R. Erectile dysfunction in systemic sclerosis. Ann Rheum Dis
2009; 68:1083.
Hong P, Pope JE, Ouimet JM, et al. Erectile dysfunction associated with scleroderma: a casecontrol study of men with scleroderma and rheumatoid arthritis. J Rheumatol 2004; 31:508.
Bhadauria S, Moser DK, Clements PJ, et al. Genital tract abnormalities and female sexual
function impairment in systemic sclerosis. Am J Obstet Gynecol 1995; 172:580.
Rosenthal AK, McLaughlin JK, Gridley G, Nyrn O. Incidence of cancer among patients with
systemic sclerosis. Cancer 1995; 76:910.
Kyndt X, Hebbar M, Queyrel V, et al. [Systemic scleroderma and cancer. Search for predictive
factors of cancer in 123 patients with scleroderma]. Rev Med Interne 1997; 18:528.
Bielefeld P, Meyer P, Caillot D, et al. [Systemic scleroderma and cancers: 21 cases and
review of the literature]. Rev Med Interne 1996; 17:810.
Hill CL, Nguyen AM, Roder D, Roberts-Thomson P. Risk of cancer in patients with
scleroderma: a population based cohort study. Ann Rheum Dis 2003; 62:728.
Derk CT, Rasheed M, Spiegel JR, Jimenez SA. Increased incidence of carcinoma of the
tongue in patients with systemic sclerosis. J Rheumatol 2005; 32:637.
Chatterjee S, Dombi GW, Severson RK, Mayes MD. Risk of malignancy in scleroderma: a
population-based cohort study. Arthritis Rheum 2005; 52:2415.
Olesen AB, Svaerke C, Farkas DK, Srensen HT. Systemic sclerosis and the risk of cancer: a
nationwide population-based cohort study. Br J Dermatol 2010; 163:800.
Derk CT, Rasheed M, Artlett CM, Jimenez SA. A cohort study of cancer incidence in systemic
sclerosis. J Rheumatol 2006; 33:1113.
Pontifex EK, Hill CL, Roberts-Thomson P. Risk factors for lung cancer in patients with
scleroderma: a nested case-control study. Ann Rheum Dis 2007; 66:551.
Shah AA, Rosen A, Hummers L, et al. Close temporal relationship between onset of cancer
and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis Rheum 2010; 62:2787.
Moinzadeh P, Fonseca C, Hellmich M, et al. Association of anti-RNA polymerase III
autoantibodies and cancer in scleroderma. Arthritis Res Ther 2014; 16:R53.
Joseph CG, Darrah E, Shah AA, et al. Association of the autoimmune disease scleroderma
with an immunologic response to cancer. Science 2014; 343:152.
Rothfield N, Kurtzman S, Vazques-Abad D, et al. Association of anti-topoisomerase I with
cancer. Arthritis Rheum 1992; 35:724.
Derk CT, Sakkas LI, Rasheed M, et al. Autoantibodies in patients with systemic sclerosis and
cancer: a case-control study. J Rheumatol 2003; 30:1994.
Topic 7551 Version 22.0

GRAPHICS
Puffy hands and shiny skin in early systemic sclerosis

(A) Diffusely puffy hands are a common initial presentation.


(B) Shiny skin suggests impending skin thickening.
Reprinted with permission from Systemic Sclerosis/Scleroderma: A Treatable Multisystem Disease,
October 15, 2008, Vol 78, No 8, American Family Physician. Copyright 2008 American Academy
of Family Physicians. All Rights Reserved.
Graphic 96749 Version 1.0

Modified Rodnan skin score for systemic sclerosis

Method used to semi-quantify skin thickness in scleroderma. The modified Rodnan skin score
is obtained by clinical palpation of 17 different body areas (fingers, hands, forearms, upper
arms, face, chest, abdomen, thighs, lower legs, and feet) and subjective averaging of the
thickness of each specific site: 0 = normal (A); 1 = mild (B); 2 = moderate (C); and 3 =
severe (D). The maximum total score is 51.
Reproduced from: Firestein GS, Budd RC, Gabriel SE, et al. Kelley's Textbook of Rheumatology,
9th ed, Saunders, Philadelphia 2012. Illustration used with the permission of Elsevier Inc. All
rights reserved.
Graphic 96747 Version 2.0

Clinical assessment of skin thickening

The modified Rodnan skin score. Semiquantitative estimates by clinical palpation of the
extent and severity of scleroderma skin change. The total skin surface is divided into 17
different areas, and in each of these areas the skin score is estimated by manual palpation.
The total skin score is the sum of the skin scores of the individual areas.
Original figure modified for this publication. Bolster MB, Silver RM. Clinical features of systemic
sclerosis. In: Hochberg MC, Silman AJ, Smolen JS, et al. Rheumatology, 5th ed, Mosby (Elsevier),
Philadelphia 2010. Illustration used with the permission of Elsevier Inc. All rights reserved.
Graphic 97759 Version 1.0

Classification of systemic sclerosis

ally decades

eet, and forearms (acral distribution)

derma predominantly nailfold capillary loops with capillary dropout

nce of pulmonary hypertension, with or without skin calcification, gastrointestinal disease, telangiectasias (CREST syndrome), or interstitial lung disease

60 percent, but other patterns also occurring in 5 to 10 percent (especially anti-PM/Scl and anti-Scl-70)

ne year, by puffy or hidebound skin changes

n friction rubs

derma with dilatation (early), dilatation and dropout (active), and tortuosity with dropout (late)

nterstitial lung, diffuse gastrointestinal, and myocardial disease

lymerase-I, II, or III (12 to 15 percent) antibodies

nal, cardiac, or gastrointestinal disease

ti-Scl-70, ACA, or anti-RNA polymerase-I, II, or III)

ma

rosis and a history of exposure to an environmental agent suspected of causing scleroderma

with those of another autoimmune rheumatic disease, such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, vasculitis, or Sjgren's syndrome

pattern typical) and evidence of digital ischemia

opoisomerase-I (Scl-70), anticentromere (ACA), or anti-RNA polymerase-I, II, or III or other hallmark scleroderma reactivity
CREST syndrome: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and
telangiectasia syndrome, also called limited scleroderma or limited cutaneous form of systemic
sclerosis; anti-PM/Scl: anti-polymyositis/scleroderma antinuclear antibodies, also called antiexosome antibodies; anti-Scl-70: antinuclear autoantibody to the scleroderma 70 kD antigen
fragment, also called the anti-topoisomerase I antibody; RNA: ribonucleic acid; ACA:
anticentromere antibody.
Graphic 80559 Version 6.0

Calcinosis cutis in scleroderma on radiograph

A-P view of the hands in a patient with scleroderma shows extensive calcification involving
the soft tissues of the distal phalanges of both hands.
A-P: anteroposterior.
Graphic 97989 Version 1.0

Disorders and factors associated with Raynaud phenomenon

POEMS: polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin


changes.
Adapted with permission from: Block JA, Sequiera W. Lancet 2001; 357:2042. Copyright 2001
The Lancet, Ltd.
Graphic 77253 Version 6.0

Clinical features of the major systemic Sclerosis subsets

ly (<3 years after onset)

Late (>3 years after onset)

loss

Minimal, weight gain typical

atively mild

Raynaud's more severe, more telangiectasia

nvolving arms, trunk, face

Stable or regression

a, stiffness, myalgia, muscle weakness,

Flexion contractures and deformities, joint/muscle symptoms less prominent

More pronounced symptoms, midgut and anorectal complications more common

myocarditis, pericardial effusion, intersitital

Reduced risk of new involvement but progression of existing established visceral fibrosis

od for scleroderma after 5 years

Renal crisis less frequent, uncommon after 5 years

y (<10 years after onset)

Late (>10 years after onset)


Only secondary to visceral complications

severe and longstanding telangiectasia

Raynaud's persists, often causing digital ulceration or gangrene

little progression on trunk, face

Stable, calcinosis more prominent

fness

Mild flexion contractures

More pronounced symptoms, midgut and anorectal complications more common

ment

Lung fibrosis may develop, but often progresses slowly, Anti-SCL-70 predicts increased risk of severe fibrosis. Maxi
hypertension and secondary right ventricular failure.
Rarely involved, anti-RNA polymerase predicts increased risk of renal involvement.
Graphic 67889 Version 1.0

Clinical manifestations of lung disease in scleroderma


Disease

Symptoms
Dyspnea

Chest expansion

Dry cough

Basal crepitations (rales

Clubbing (late, very un


Dyspnea

Loud P2

Ankle edema

Right ventricular heave

Pleuritic chest pain

Pleural rub

Dyspnea

Pleural effusion (rare)

Cough with purulent sputum

Basal crepitations

Dyspnea
Chest pain

Resonant percussion

ll

nvolvement

Dyspnea

Reduced breath sounds

Cough

Possible signs of collap

Hemoptysis
Dyspnea
Reduced chest expansion

Hypoventilation

Das könnte Ihnen auch gefallen