Systemic sclerosis (SSc; scleroderma) is a chronic autoimmune connective tissue disease characterized by microvascular obliteration and sclerosis of the skin and internal organs. Although the clinical hallmark of the disease is the appearance of taut tethering of the skin, one of the earliest manifestations of SSc is a painful symmetrical arthropathy ranging from minimal arthralgia to overt polyarthritis. Musculoskeletal (MSK) involvement in SSc occurs more frequently than expected. Arthralgia is the most commonly reported manifestation. Some of the existing composite and organ-specific indices of disease activity and/or disease severity in SSc include MSK manifestations.
Key points
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Musculoskeletal (MSK) involvement in systemic sclerosis (SSc) occurs more frequently than expected, with a prevalence of 24% to 97%, and is associated with significant disability and psychosocial and economic burden.
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There is no formal classification system for MSK manifestations in SSc. MSK involvement presents as one or more of stiffness, arthritis, tendon sheath involvement, joint contractures, and proximal muscle weakness.
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Rheumatologic examinations should include searching for tendon friction rubs (TFRs), especially in patients with recent-onset Raynaud phenomenon and swollen fingers, as their presence is important in terms of disease classification, severity, progression, and prognostication.
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Autoantibodies in SSc frequently characterize distinct phenotypic subsets of disease. Anticyclic citrullinated peptide antibody (ACPA) can predict patients SSc who will develop arthritis and identify patients with scleroderma-rheumatoid arthritis (SSc-RA) overlap syndrome. Anti-polymyositis scleroderma (PM-Scl) antibody is often indicative of an overlap syndrome with an inflammatory myositis and is associated with a more favorable disease course.
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Large controlled randomized trials with adequate follow-up are required to establish treatment guidelines for patients with SSc.
Articular involvement in systemic sclerosis
Definition
Articular and tendon involvement in SSc is defined by the occurrence of synovitis, arthralgia, and joint contractures, often accompanied by TFRs. These manifestations are more likely to occur together in the same patient and are associated with the diffuse cutaneous disease subtype and a more severe disease phenotype.
Prevalence
Articular involvement is common is SSc, eventually affecting 46% to 95% of patients. Data from the European League Against Rheumatism Scleroderma Trial and Research Group (European Scleroderma and Trials and Research group) database indicate point prevalences of 16% for synovitis, 11% for TFRs, and 31% for joint contractures. Hands (particularly the metacarpophalangeal [MCP] and proximal interphalangeal [PIP] joints) and wrists are the most commonly affected joints. Impaired hand function with reduced hand grip due to pain, arthritis, and joint contractures has a significant psychosocial and economic impact on patients by reducing the ability to perform activities of daily living and to participate in work. Articular involvement, disability, pain, and unemployment are all independent risk factors for depression in patients with SSc, which occurs with a prevalence of 36% to 65% and is associated with social isolation, worse perception of quality of life, and decreased adherence to medications.
Clinical Features
Generalized arthralgias and stiffness are the most common presentations of joint involvement. Clinically evident arthritis occurs in 12% to 65% of patients with SSc. It may be the first manifestations of SSc, preceding even the onset of Raynaud phenomenon, and can cause diagnostic confusion. Hence, it is important to examine for clinical signs of early SSc, such as puffy fingers and nail fold capillary changes in anyone presenting with inflammatory arthritis.
The onset of joint involvement in SSc may be acute or insidious, with an intermittent or chronic course. The pattern of distribution is most commonly polyarticular but can be oligoarticular or monoarticular. Effusions, if present, are usually small and occur predominantly in the knee joint. With disease progression, joint contractures due to joint destruction, ankylosis, and dermal fibrotic changes occur in 31% of patients resulting in functional disability. Joint contractures are most apparent at the MCP and interphalangeal joints.
Recent EUSTAR registry data indicate that the frequency of synovitis is significantly higher in patients with diffuse cutaneous disease and that synovitis occurring within 5 years of the first non-Raynaud symptom is predictive of the diffuse disease subset. The presence of synovitis was associated with severe vascular (pulmonary hypertension defined as systolic pulmonary arterial pressure on echocardiogram >40 mm Hg) and muscular (defined as muscle weakness) involvement. Synovitis was also associated with elevated acute phase reactants, indicating more severe systemic inflammation and disease course. Similarly, the prevalence of joint contractures was higher in the diffuse subset and was associated with severe vascular, muscular, and pulmonary interstitial involvement.
Investigations
Laboratory findings
Although rheumatoid factor is present in 30% of patients with SSc, this is nonspecific and does not predict MSK involvement. ACPAs on the other hand, are helpful in identifying those patients with SSc who will develop arthralgia and inflammatory arthritis. In particular, ACPA has a sensitivity of 50% to 100% and specificity of 95% in identifying patients with SSc-RA overlap syndrome. SSc-RA overlap is a distinct genetic, clinical, and serologic entity and is uncommon in SSc, with a prevalence of 1% to 5%. However, these patients are more likely to develop bone erosions and joint deformities.
Synovial fluid from SSc arthritis reveals normal or modestly increased leukocyte concentrations (<2000 cells/mm 3 ) with a predominantly mononuclear infiltrate. Synovial biopsies show evidence of inflammation, with lymphocytic and plasma cell infiltration, associated with focal microvascular obliteration and superficial fibrin deposits. Pannus is rarely present. The lack of synovial proliferation and pannus formation in SSc suggests a benign synovitis in comparison with RA.
Imaging
Radiographic findings vary widely in SSc. Distinctive abnormalities include juxta-articular osteopenia, joint space narrowing, and erosions. A distinct pattern of distribution of erosions occurs in SSc, primarily affecting the MCP joints and the distal interphalangeal joints. Erosions also occur in the wrist, PIP joints, and the first carpometacarpal joint. Erosions are small, discrete, and less invasive than those of RA. Erosions on baseline imaging predict further progression of erosive changes. No independent predictor of erosion progression has yet been identified.
Power Doppler ultrasonography is a useful tool for detecting inflammation, synovial proliferation, synovitis, erosions, calcinosis, and subclinical TFRs in SSc. Ultrasonography preformed on 52 consecutive patients with SSc identified more patients with synovitis and tenosynovitis than clinical examination alone. Given the aforementioned predictive value for the presence of synovitis, ultrasound imaging may have a role in detecting patients at a higher risk of a severe progressive disease phenotype.
MRI demonstrates a high prevalence of inflammatory findings in SSc. In one study, MRI detected synovitis in 47%, tenosynovitis in 47%, erosions in 41%, and bone edema in 53% of patients. None of these inflammatory findings correlated consistently with clinical findings.
Given the burden of MSK manifestations in SSc, their associated morbidity, and lack of evidence-based therapeutic options, randomized trials are required to determine effective treatment regimes. Ultrasonography and MRI could be integrated into these trials to enable adequate patient selection and response to therapy.
Articular involvement in systemic sclerosis
Definition
Articular and tendon involvement in SSc is defined by the occurrence of synovitis, arthralgia, and joint contractures, often accompanied by TFRs. These manifestations are more likely to occur together in the same patient and are associated with the diffuse cutaneous disease subtype and a more severe disease phenotype.
Prevalence
Articular involvement is common is SSc, eventually affecting 46% to 95% of patients. Data from the European League Against Rheumatism Scleroderma Trial and Research Group (European Scleroderma and Trials and Research group) database indicate point prevalences of 16% for synovitis, 11% for TFRs, and 31% for joint contractures. Hands (particularly the metacarpophalangeal [MCP] and proximal interphalangeal [PIP] joints) and wrists are the most commonly affected joints. Impaired hand function with reduced hand grip due to pain, arthritis, and joint contractures has a significant psychosocial and economic impact on patients by reducing the ability to perform activities of daily living and to participate in work. Articular involvement, disability, pain, and unemployment are all independent risk factors for depression in patients with SSc, which occurs with a prevalence of 36% to 65% and is associated with social isolation, worse perception of quality of life, and decreased adherence to medications.
Clinical Features
Generalized arthralgias and stiffness are the most common presentations of joint involvement. Clinically evident arthritis occurs in 12% to 65% of patients with SSc. It may be the first manifestations of SSc, preceding even the onset of Raynaud phenomenon, and can cause diagnostic confusion. Hence, it is important to examine for clinical signs of early SSc, such as puffy fingers and nail fold capillary changes in anyone presenting with inflammatory arthritis.
The onset of joint involvement in SSc may be acute or insidious, with an intermittent or chronic course. The pattern of distribution is most commonly polyarticular but can be oligoarticular or monoarticular. Effusions, if present, are usually small and occur predominantly in the knee joint. With disease progression, joint contractures due to joint destruction, ankylosis, and dermal fibrotic changes occur in 31% of patients resulting in functional disability. Joint contractures are most apparent at the MCP and interphalangeal joints.
Recent EUSTAR registry data indicate that the frequency of synovitis is significantly higher in patients with diffuse cutaneous disease and that synovitis occurring within 5 years of the first non-Raynaud symptom is predictive of the diffuse disease subset. The presence of synovitis was associated with severe vascular (pulmonary hypertension defined as systolic pulmonary arterial pressure on echocardiogram >40 mm Hg) and muscular (defined as muscle weakness) involvement. Synovitis was also associated with elevated acute phase reactants, indicating more severe systemic inflammation and disease course. Similarly, the prevalence of joint contractures was higher in the diffuse subset and was associated with severe vascular, muscular, and pulmonary interstitial involvement.
Investigations
Laboratory findings
Although rheumatoid factor is present in 30% of patients with SSc, this is nonspecific and does not predict MSK involvement. ACPAs on the other hand, are helpful in identifying those patients with SSc who will develop arthralgia and inflammatory arthritis. In particular, ACPA has a sensitivity of 50% to 100% and specificity of 95% in identifying patients with SSc-RA overlap syndrome. SSc-RA overlap is a distinct genetic, clinical, and serologic entity and is uncommon in SSc, with a prevalence of 1% to 5%. However, these patients are more likely to develop bone erosions and joint deformities.
Synovial fluid from SSc arthritis reveals normal or modestly increased leukocyte concentrations (<2000 cells/mm 3 ) with a predominantly mononuclear infiltrate. Synovial biopsies show evidence of inflammation, with lymphocytic and plasma cell infiltration, associated with focal microvascular obliteration and superficial fibrin deposits. Pannus is rarely present. The lack of synovial proliferation and pannus formation in SSc suggests a benign synovitis in comparison with RA.
Imaging
Radiographic findings vary widely in SSc. Distinctive abnormalities include juxta-articular osteopenia, joint space narrowing, and erosions. A distinct pattern of distribution of erosions occurs in SSc, primarily affecting the MCP joints and the distal interphalangeal joints. Erosions also occur in the wrist, PIP joints, and the first carpometacarpal joint. Erosions are small, discrete, and less invasive than those of RA. Erosions on baseline imaging predict further progression of erosive changes. No independent predictor of erosion progression has yet been identified.
Power Doppler ultrasonography is a useful tool for detecting inflammation, synovial proliferation, synovitis, erosions, calcinosis, and subclinical TFRs in SSc. Ultrasonography preformed on 52 consecutive patients with SSc identified more patients with synovitis and tenosynovitis than clinical examination alone. Given the aforementioned predictive value for the presence of synovitis, ultrasound imaging may have a role in detecting patients at a higher risk of a severe progressive disease phenotype.
MRI demonstrates a high prevalence of inflammatory findings in SSc. In one study, MRI detected synovitis in 47%, tenosynovitis in 47%, erosions in 41%, and bone edema in 53% of patients. None of these inflammatory findings correlated consistently with clinical findings.
Given the burden of MSK manifestations in SSc, their associated morbidity, and lack of evidence-based therapeutic options, randomized trials are required to determine effective treatment regimes. Ultrasonography and MRI could be integrated into these trials to enable adequate patient selection and response to therapy.
Tendon involvement in systemic sclerosis
Tendon abnormalities are a common finding in SSc, including inflammatory proliferative tenosynovitis, tendon rupture, and TFRs. TFRs are defined by a leathery, rubbing, squeaking sensation detected as the tendon is moved actively or passively through its range of action. TFRs occur at a prevalence of 20% in patients with established diffuse disease and in 36% of early diffuse disease. The etiology is unknown but is thought to be secondary to fibrin deposition within tendon synovial sheaths and overlying fascia. Pathologic examination demonstrates thickening and fibrinous deposits on the surface of the affected sheaths with little inflammatory reaction. Over time, fibrous deposits develop, leading to audible tendon rubs and flexion contractures.
TFRs occur throughout the body. In the legs, TFRs can be detected over the tendons of tibialis anterior and peroneus muscles and the Achilles tendon. In the forearm, the rub is usually felt over the flexor and extensor muscles proximal to the wrist. Median nerve compression leading to carpal tunnel syndrome can also occur as a consequence of tendon involvement beneath the transverse carpal ligament.
The presence of palpable TFRs is associated with active disease and is a significant predictor of severe diffuse cutaneous involvement; internal organ involvement, including renal, muscular, and cardiac manifestations; and increased mortality. The presence of TFRs is independently associated with digital ulceration, muscle weakness, pulmonary fibrosis, proteinuria, and active disease. The occurrence of TFRs in early disease is associated with more severe disease regardless of the disease subtype. Therefore, searching for TFRs should be part of every rheumatologic examination, especially in patients with recent onset of Raynaud phenomenon and swollen fingers, as the presence of TFRs is important in terms of disease classification, severity, progression, and prognostication.
Clinical examination often underestimates the presence of tenosynovitis, which can be further characterized by ultrasonography or MRI, although the place of these modalities in the assessment of tendon involvement in SSc is yet to be defined.
Calcinosis in systemic sclerosis
Involvement of digits by the vascular abnormalities and fibrosis that characterize SSc results in digital ischemia and sclerodactyly, often with contractures and ulceration over the extensor aspects of the interphalangeal joints ( Figs. 1–4 ). It is a major contributor to morbidity, disability, and pain. In addition, a significant proportion of patients develop subcutaneous calcinosis, which can ulcerate through the skin, causing pain, disability, and infection (see Figs. 2 and 3 ).
