Scleroderma

Systemic sclerosis (SSc)

Systemic sclerosis (SSc)

Limited cutaneous SScDiffuse cutaneous SSc

Overlap syndromes

Mixed connective tissue disease

Pathophysiology• autoimmune dysfunction• T cells accumulate in the skin• secrete cytokines and other proteins that stimulate collagen

deposition.• Stimulation of the fibroblast • transforming growth factor (TGFβ)• connective tissue growth factor (CTGF) • Damage to endothelium is an early abnormality in the development

of scleroderma

• due to collagen accumulation by fibroblasts, although direct alterations by cytokines, platelet adhesion and a type II hypersensitivity reaction• Increased endothelin and decreased vasodilation

Epidemiology• SSc is an acquired sporadic disease • Like other connective tissue diseases, SSc shows a female

predominance • most pronounced in the childbearing years and declines after

menopause. • SSc can present at any age• the most common age of onset for both limited and diffuse cutaneous

forms is in the range of 30–50 years.

S

scleroderma renal crisis. • The most important clinical complication of scleroderma involving the kidney

• Symptoms• malignant hypertension• azotemia • microangiopathic hemolytic anemia • high blood pressure• hematuria • proteinuria

• Treatment for scleroderma renal crisis include ACE inhibitors.

Diagnosis• clinical suspicion• presence of autoantibodies (specifically anti-centromere and anti-

scl70/anti-topoisomerase antibodies) • Of the antibodies, 90% have a detectable ANA. • Anti-centromere antibody is more common in the limited form (80-

90%) than in the diffuse form (10%)• anti-scl70 is more common in the diffuse form (30-40%)

MCTDMIXED CONNECTIVE TISSUE DISORDERS• an autoimmune disease• Signs and symptoms• combines features of scleroderma, myositis, systemic lupus

erythematosus, and rheumatoid arthritis• thus considered an overlap syndrome.

• MCTD commonly causes:

• joint pain/swelling,• malaise,• Raynaud phenomenon,• muscle inflammation, and• sclerodactyly (thickening of the skin of the pads of the fingers)

Diagnosis• positive, speckled anti-nuclear antibody and an anti-U1-RNP antibody.

• Cause• It has been associated with HLA-DR4

• Prognosis• In spite of prednisone treatment, this disease is progressive

• Most deaths from MCTD are due to heart failure caused by Pulmonary Arterial Hypertension (PAH).