Page 781 - Clinical Immunology_ Principles and Practice ( PDFDrive )

752 Part SIX Systemic Immune Diseases

of detection. Clinical criteria are insensitive, but modern sensitive process, which leads to glomerular hypoperfusion and a high
tools, such as echocardiography, tissue Doppler imaging, speckle- renin state.
tracking echocardiography, cardiac magnetic resonance imaging, Patients with SRC who present with a creatinine >3 mg/dL have
or thallium scanning, can detect disease early and suggest that a poor outcome, with increased likelihood of permanent hemo-
40–60% of patients have heart disease. When heart disease is dialysis, need for renal transplantation, and/or high mortality.
symptomatic, the prognosis is poor. SSc can affect virtually any Prompt and aggressive intervention with angiotensin-converting
cardiac structure, including the myocardium with fibrosis or enzyme (ACE) inhibitors to achieve blood pressure control before
inflammatory myocarditis, the myocardial microvasculature, or evidence of renal dysfunction is seen significantly improves the
the pericardium with asymptomatic small effusions or large prognosis. Introduction of ACE inhibitors dramatically improved
effusions leading to cardiac tamponade. As a consequence of survival from a 1-year survival rate of 10% to a 5-year survival
cardiac tissue injury, left ventricular (LV) systolic dysfunction rate of 60%. All patients with SRC should be treated with an
and/or LV diastolic dysfunction and/or right ventricular (RV) ACE inhibitor, but other vasodilators, including calcium channel
failure and/or conduction abnormalities with complex arrhyth- blockers, endothelin receptor inhibitors, and prostaglandins,
mias can occur, but valvular heart disease is unusual. Cardiac can be helpful. About 45% of patients whose blood pressure is
dysfunction can be primary to the disease process or secondary normalized do not require dialysis. Reasonable kidney function
to other organ diseases, including PAH, ILD, or SRC. Cardiac can resume months after renal failure and the need for dialysis
disease occurs in both the limited and the diffuse subtypes but support. Despite ideal therapy, approximately 40% of patients
is more common in the patients with rapidly progressive diffuse still need long-term kidney support or have a poor survival.
skin disease, in those with anti-U3 RNP antibodies, and in Overall survival on chronic dialysis is worse in patients with SSc
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association with peripheral muscle disease. Heart disease is compared with those without SSc, but renal transplantation is
reported to be a cause of death in 20–30% of patients and is an still an option with a long-term outcome similar to that of other
independent risk factor for death. Optimal screening for heart causes of renal failure.
disease is not well defined, but periodic clinical assessment coupled
with echocardiography and blood levels of BNP is recommended.
Modern techniques for detecting occult heart disease provide CLINICaL PEarLS
opportunities for early intervention and should be used for Recommended Approach to Systemic Sclerosis
thorough evaluation of the patient when cardiac involvement
is suspected. The ideal therapy is defined by the underlying situ- • Determine scleroderma skin score to define clinical subtype
• Frequent clinical reassessment to define disease activity
ation (e.g., vasodilator therapy to improve heart perfusion or • Careful clinical history to evaluate for gastrointestinal dysmotility
antiarrhythmia therapy for a complex arrhythmia). A disease- • Monitor for new onset hypertension: prevent renal crisis
modifying drug that specifically targets scleroderma heart disease • Pulmonary function test: early detection of interstitial lung disease
has not yet been discovered. • Doppler echocardiography: screen for pulmonary arterial hypertension
• Obtain serology profile to help predict clinical outcome
Renal Involvement
Renal disease is an important clinical problem with both direct
involvement and kidney compromise secondary to other organ Musculoskeletal Complications
dysfunction. The most dreaded renal complication is an SRC, Musculoskeletal impairment is a leading cause of disability and
which is defined as the new onset of accelerated arterial hyper- poor quality of life among patients with SSc. It is seen in the
tension and/or rapidly progressive oliguric renal failure during majority of patients, occurs early in the disease, and commonly
the course of the disease. It is recognized that other causes of has a dominant effect on hand function. There is a variety of
renal disease, including interstitial nephritis, glomerulonephritis, associated clinical symptoms, including arthralgias, myalgias,
and antineutrophil cytoplasmic antibody (ANCA)–associated stiffness, pain and loss of function as a result of joint contractures,
vasculitis, can occur. SRC develops in 10–15% of patients with inflammatory arthritis, myopathy, nerve entrapment (e.g., carpal
dcSSc, but in less than 5% of patients with lcSSc. It is gener- tunnel syndrome), fibrosis of tendons, and deconditioning from
ally a relatively early (<3–4 years) complication of the disease disuse. Loss of joint function is less likely to be secondary to
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and is more likely to occur in males. The presence of rapid synovitis but is usually caused by fibrosis of the overlying skin,
progression of diffuse skin disease; tendon friction rubs; cardiac the supporting joint structures, and the joint capsule itself. Flexion
disease with clinically silent pericardial effusion, arrhythmias, contractures associated with “friction rubs” most prominently
or congestive heart failure; new unexplained anemia; or the felt over the ankles, knees, shoulders, and wrist are typical of
use of corticosteroids are all associated with an increased risk advanced dcSSc. Muscle weakness is a common comorbid condi-
of SRC. The autoantibody status is also helpful in identifying tion caused by deconditioning, muscle disuse, or malnutrition
patients at risk for SRC. In approximately 30% of patients with associated with weight loss. A scleroderma-related myopathy
anti-RNA polymerase III, seen almost exclusively in dcSSc, SRC defined by weakness with elevated serum creatine kinase (CK)
develops; however, SRC occurs in only 10% of patients with level; myopathic features on electromyography (EMG); and/or
antitopoisomerase antibodies and only rarely in patients with muscle biopsy is reported to occur in about 20% of patients. Most
anticentromere antibody. SRC characteristically presents as sudden patients with skeletal myopathy have proximal muscle weakness
onset of malignant hypertension with rapidly progressive oliguric on examination, and about 40% have one of the scleroderma/
renal failure. Proteinuria, microhematuria, and evidence of a myopathy–associated autoantibodies (i.e., anti-PM/Scl-75,
microangiopathic hemolytic process with thrombocytopenia anti-PM/Scl-100, or anti-CD1). The histopathological findings
are present. The exact mechanism triggering acute SRC is are highly variable, with fibrosis alone seen only in a small subset.
not known, but an autoimmune insult to the underlying SSc When inflammation and/or necrosis are seen, immunosuppressive
microvascular disease is thought to initiate a self-perpetuating therapy has the potential to control the muscle disease.