Selected Immune Disorders and Disability (2022) / Chapter Skim
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4 Scleroderma
4 Scleroderma
Pages 93-128
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From page 93... ...
The hallmark of SSc is its clinical heterogeneity, as the disease encompasses several distinct sub-phenotypes and autoantibody groups with a disease course, risk of complications, and response to therapy that are all highly variable. Medical providers must carefully characterize each patient to understand the specific manifestations, level of disease activity, and risk for organ specific complications, as this influences potential screening and therapeutic strategies (Shah and Wigley, 2013)
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From page 94... ...
There are numerous complications that can occur, usually in the first 5 years, including interstitial lung disease (ILD) , renal crisis, and myopathy; on the other hand, pulmonary hypertension occurs later in the disease.
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From page 95... ...
than those with secondary Raynaud's phenomenon, and there is no evidence of a secondary cause (e.g., peripheral vascular disease, digital ischemic injury, or abnormal nailfold capillaries) (Wigley and Flavahan, 2016)
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From page 96... ...
Diffuse cutaneous disease is seen in 30–40 percent of SSc patients in most international cohorts. Patients may present with inflammatory skin changes, often with puffy or swollen fingers.
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From page 97... ...
The mRSS is thought to be a good measure of disease severity, but it does not fully encompass the spectrum of disease activity. It may lag other measures of disease activity, such as patient-reported pruritis and cutaneous discomfort, skin thickening, and tendon friction rubs.
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From page 98... ...
Finger flexion contractures may develop, are typically irreversible, and can be quite severe, especially in patients who have had the diffuse cutaneous form of the disease. Joint contractures may also develop in other small and large joints as sequelae of the skin thickening and tendon friction rubs.
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From page 99... ...
The two most common complications are ILD and pulmonary arterial hypertension (PAH)
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From page 100... ...
, or diastolic dysfunction and subsequent heart failure with preserved ejection fraction. HFrEF may also develop in the setting of an acute scleroderma renal crisis with a high afterload; LV systolic function may recover in this setting once a renal crisis is adequately managed.
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From page 101... ...
Because there is no single diagnostic test to prove the presence or absence of SSc, multiple classification criteria have been proposed to standardize definitions for research studies and clinical trials. The 1980 preliminary ACR criteria for SSc included a major criterion (scleroderma skin thickening proximal to the digits)
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From page 102... ...
Fingertip pitting scars 3 Telangiectasia -- 2 Abnormal nailfold capillaries -- 2 Pulmonary arterial hypertension and/or Pulmonary arterial hypertension 2 interstitial lung disease (maximum score Interstitial lung disease 2 is 2) Raynaud's phenomenon -- 3 SSc-related autoantibodies Anticentromere 3 (anticentromere, anti–topoisomerase Anti–topoisomerase I I [anti–Scl-70]
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From page 103... ...
Those with more extensive limited skin involvement had intermediate risks of restrictive lung disease and mortality than those with mild limited skin thickening and those with diffuse disease (Cottrell et al., 2014)
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From page 104... ...
Diffuse > limited cutaneous disease ILD African-Americans RNA polymerase III Rapidly progressive diffuse cutaneous disease, contractures Contemporaneous cancer with disease onset Renal crisis (25–33%) Myopathy and cardiac disease GAVE
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From page 105... ...
ILD Ku* Limited cutaneous disease Myositis NOTES: CREST = calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia; GAVE = gastric antral vascular ectasia; ILD = interstitial lung disease; PAH = pulmonary arterial hypertension; RNP = ribonucleoprotein.
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From page 106... ...
Although anti-fibrillarin autoantibodies and anti-RNA-polymerase III autoantibodies occur less frequently, they are also predictive of diffuse skin involvement and systemic disease. Patients with anti-RNA polymerase III antibodies also have a higher risk of renal crisis and of having an underlying malignancy (Igusa et al., 2018)
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From page 107... ...
, survival remains poor. In a multicenter French study of 546 SSc patients undergoing routine pulmonary FIGURE 4-3 Patterns of disease course in systemic sclerosis–interstitial lung disease.
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From page 108... ...
The prognosis of SSc renal crisis has improved significantly over time due to the use of ACE inhibitors. Steen and colleagues examined the outcomes of SSc renal crisis before and after the a vailability of ACE inhibitors (Steen and Medsger, 2000)
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From page 109... ...
Importantly, more than 50 percent of patients who started dialysis were able to discontinue it 3–18 months later. Over a 30-year time period, the frequency of deaths due to renal crisis has decreased dramatically, from 42 percent of SSc-related deaths to 6 percent (Steen and Medsger, 2000)
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From page 110... ...
Additionally, there are now FDA-approved therapies for organ-specific complications of scleroderma, including ILD and PAH. While it is beyond the scope of this report to cover all potential therapies for the various manifestations of SSc, we present detailed information about therapies for the most common disabling manifestations of the disease, including Raynaud's phenomenon, active cutaneous disease, ILD, and PAH.
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From page 111... ...
Therapeutics for Active Cutaneous Disease A key aspect of scleroderma management is determining whether clinical features reflect disease activity or reflect damage. For patients with more extensive limited scleroderma or diffuse cutaneous disease, the signs of cutaneous disease activity include progressive skin thickening involving new body areas, worsening skin thickening in previously affected body areas, persistent and severe pruritis -- often with a neuropathic discomfort to the skin -- and tendon friction rubs.
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From page 112... ...
The choice of therapy is often influenced by whether there are other manifestations of disease activity. In an observational study of patients with refractory, active diffuse cutaneous scleroderma, the addition of IVIG resulted in significant improvements in mRSS over time, and tendon friction rubs resolved in most patients in whom they were present at baseline (Poelman et al., 2015)
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From page 113... ...
Interstitial Lung Disease Management The first-line therapy for scleroderma-ILD includes MMF, based on data from the SLS II trial. Patients were randomized to MMF versus cyclophosphamide as described above.
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From page 114... ...
These data suggested that tocilizumab could have a role in preserving lung function in patients with early SSc ILD and high acute phase reactants. This drug may be attractive for use in patients with concomitant inflammatory arthritis or tendon friction rubs.
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From page 115... ...
is sometimes used in patients with recurrent pulmonary thromboembolic disease secondary to pulmonary arterial hypertension Scleroderma renal crisis Dialysis Angiotensin-converting enzyme inhibitors SOURCE: Reprinted with permission from Hinchcliff and Varga, 2008.
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From page 116... ...
DISEASE-SPECIFIC FUNCTIONAL LIMITATIONS Patients with SSc may develop functional impairment due to skin thickening, small and large joint contractures, inflammatory a rthritis, tendon friction rubs, myositis, digital ulcers, GI d ysmotility, and dyspnea from cardiopulmonary complications. Skin thickening, joint contractures, synovitis, and digital ulcers in particular may contribute to hand disability.
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From page 117... ...
In another study of patients with diffuse SSc from the EUSTAR database, baseline severity of skin thickening as assessed by the mRSS was an important predictor of subsequent disability (Allanore et al., 2020)
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From page 118... ...
. In children, the most prominent feature of the systemic form is skin manifestations, followed by musculoskeletal and vascular involvement.
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From page 119... ...
The disease course was drawn from a retrospective analysis of patients' clinical features, treatment, and disease course and outcome at last evaluation. Disease activity and the severity of tissue damage were assessed using thermography and the Localized Scleroderma Cutaneous Assessment Tool.
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From page 120... ...
Skin thickening, joint contractures, synovitis, and digital ulcers in particular may contribute to hand disability. SSc has the highest case-specific mortality and major morbidity of any of the autoimmune rheumatic diseases.
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From page 121... ...
2010. Gastroesophageal reflux incites interstitial lung disease in systemic sclerosis: Clinical, radiologic, histopatho logic, and treatment evidence.
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From page 122... ...
2020. Underdetection of interstitial lung disease in juvenile systemic sclerosis.
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From page 123... ...
2018. Long-term outcomes in systemic sclerosis-associated pulmonary arterial hypertension from the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS)
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From page 124... ...
2018. Dis ease course and long-term outcome of juvenile localized scleroderma: Experience from a single pediatric rheumatology centre and literature review.
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From page 125... ...
2019. Changes in disability and their relationship with skin thickening, in dif fuse and limited cutaneous systemic sclerosis: A retrospective cohort study.
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From page 126... ...
2014. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: A randomized clinical trial.
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From page 127... ...
2005. Localized scleroderma in childhood is not just a skin disease.
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