Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. It results from autoimmune dysfunction leading to accumulation of T cells and cytokines in the skin that stimulate collagen deposition by fibroblasts. There are two main types: limited cutaneous SSc affects only the hands and forearms, while diffuse cutaneous SSc affects the skin over much of the body. SSc most commonly affects women ages 30-50 and can involve serious complications like scleroderma renal crisis resulting in high blood pressure, kidney damage, and other symptoms. Diagnosis involves clinical signs and presence of autoantibodies, and treatment depends on complications but may include ACE inhibitors for renal problems. Mixed connect

1. Systemic sclerosis (SSc)
Systemic sclerosis (SSc)
Limited cutaneous SSc
Diffuse cutaneous SSc
Overlap syndromes
Mixed connective tissue disease

2. 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

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

5. 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.

21. S

39. 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.

41. 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%)

46. MCTD
MIXED 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.

47. • MCTD commonly causes:
• joint pain/swelling,
• malaise,
• Raynaud phenomenon,
• muscle inflammation, and
• sclerodactyly (thickening of the skin of the pads of the fingers)

48. 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).