Page 776 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 55 Scleroderma–Systemic Sclerosis 747

KEY CONCEPtS Although classification of SSc as diffuse and limited cutaneous
Clinical Patterns of Systemic Sclerosis has utility, disease expression is far more complex, and several
distinct phenotypes are recognized within each of the two subsets.
Limited Cutaneous Scleroderma For example, 10–15% of patients with lcSSc develop severe
• Distal skin sclerosis (sclerodactyly) pulmonary arterial hypertension without significant lung fibrosis.
• Severe Raynaud phenomenon with digital ischemia Other patients develop systemic features of SSc without appre-
• Numerous telangiectasia ciable skin involvement, a phenotype that is termed systemic
• Isolated pulmonary arterial hypertension sclerosis sine scleroderma. Unique clinical phenotypes of SSc are
associated with specific autoantibodies (Table 55.4). For example,
Diffuse Cutaneous Scleroderma anticentromere antibodies are associated with lcSSc, whereas
• Rapidly progressing widespread skin involvement antitopoisomerase-I antibodies are associated with the presence
• Scleroderma renal crisis of interstitial lung disease. The presence of anti-RNA polymerase
• Interstitial lung disease
• Severe gastrointestinal dysmotility antibodies is associated with rapid and widespread skin disease
• Cardiomyopathy and an increased risk of an SRC. In some patients with SSc who
have “overlap” features, SSc coexists with clinical and laboratory
evidence of another autoimmune disease, such as polymyositis,
autoimmune thyroid disease, Sjögren syndrome, polyarthritis,
autoimmune liver disease, or SLE (see Table 55.4).
TABLE 55.3 Classification of Systemic Instead of SSc, the term “ localized scleroderma” is now
Sclerosis (SSc) properly used to describe a group of patients with disease generally
limited to fibrosing skin disorders that occurs with similar
Diffuse cutaneous scleroderma—skin thickening on the trunk in
addition to the face, proximal and distal extremities frequency in both children and adults (Table 55.5). Localized
Limited cutaneous scleroderma—skin thickening limited distal to scleroderma is infrequently associated with significant systemic
the elbow and knee; may also involve the face and neck involvement. Morphea, a form of localized scleroderma, can
CrESt syndrome—subcutaneous calcinosis; Raynaud phenomenon; occur as solitary or multiple lesions (generalized morphea) of
esophageal dysmotility; sclerodactyly; telangiectasia expanding circular patches of thickened skin. The most common
Sine scleroderma—no apparent skin thickening but characteristic form of localized scleroderma in children is linear scleroderma.
visceral organ involvement, vascular and serological features
Overlap syndrome—criteria for SSc, coexisting with features of It presents as a streak of thickened skin, generally in one or both
systemic lupus erythematosus, rheumatoid arthritis, or inflammatory lower extremities. Linear scleroderma often involves the subcu-
muscle disease taneous tissues with fibrosis and atrophy of supporting structures,
Mixed connective tissue disease—overlap syndrome with anti-U1 muscle, and bone, and radiographs may show melorheostosis
ribonucleoprotein (RNP) antibodies of long bones. In children with linear scleroderma, the growth
Early disease—Raynaud phenomenon (RP) with clinical and/or of affected tissues, muscles, and long bones can be retarded.
laboratory features of SSc; specific autoantibodies, abnormal nailfold
capillaroscopy, finger edema, and ischemic injury When the lesions cross joints, significant contractures of the
affected joint can develop. Linear scleroderma can occur on the

TABLE 55.4 Frequency and Clinical Correlations of Systemic Sclerosis (SSc) autoantibodies
% Frequency in SSc Disease Subtype Clinical associations Prognosis
Anticentromere 20–38 lcSSc Pulmonary arterial hypertension Better prognosis
Antitopoisomerase I 15–42 dcSSc Pulmonary fibrosis Worse prognosis
Heart involvement
Anti-RNA polymerase III 5–31 dcSSc Renal crisis Increased mortality
Tendon friction rubs, synovitis,
myositis, Joint contractures.
Increased risk of malignancy
Anti-U3 RNP (fibrillarin) 4–10 dcSSc Renal crisis and cardiac involvement Poor prognosis especially
in African Americans
Anti-Th/To 1–13 lcSSc Pulmonary fibrosis and renal crisis Poor prognosis
Anti-U11/U12 RNP 3.2 — RP Increased mortality
Gastrointestinal involvement
Lung fibrosis
Anti-U1 RNP 2–14 lcSSc RP, puffy fingers, arthritis, myositis, Better prognosis
overlap syndrome (i.e., MCTD)
Anti-PM-Scl 4–11 Overlap with polymyositis RP, arthritis, myositis pulmonary Better prognosis
lcSSc involvement, calcinosis, and sicca
symptoms
Anti-Ku 2–4 — Myositis, arthritis, and joint —
contractures
Anti-hUBF (NOR 90) <5 lcSSc Mild internal organ involvement Better prognosis
Anti-Ro52/TRIM21 15–20 Association with other Older age onset, pulmonary fibrosis —
autoimmune diseases
dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc; MCTD, mixed connective tissue disease; RNP; ribonucleoprotein; RP, Raynaud phenomenon; TRIM, tripartite motif.
From Kayser C, Fritzler MJ. Autoantibodies in systemic sclerosis: unanswered questions. Frontiers Immunol 2015;6:167.