Systemic sclerosis
*definition
Systemic sclerosis (previously called 'scleroderma') is a generalized disorder of connective tissue affecting the skin, internal organs and vasculature. The clinical hallmark is the presence of sclerodactyly in combination with Raynaud's phenomenon or digital ischemia. The peak age of onset is in the fourth and fifth decades, and overall prevalence is 10-20 per 100 000 with a 4:1 female: male ratio*
Scleroderma –, Raynaud’s phenomenon , esophageal dysmotility , sclerodactyly and telangiectasia
Etiological factors
Environmental factors:- increased frequency in coal & gold minors. induced scleroderma like syndrome ; exposure to polyvinyl chloride, bleomycine therapy & silicone breast implants. scleroderma like lesions in GVHD. Genetic factors: .High risk in 1st degree relative.*
pathology
Early in the disease there is skin infiltration by T lymphocytes and abnormal fibroblast activation that leads to increased production of extracellular matrix in the dermis, primarily type I collagen. This results in symmetrical thickening, tightening and induration of the skin (sclerodactyly). There is arteriolar narrowing due to intimal proliferation and vessel wall inflammation. Endothelial injury causes release of vasoconstrictors and platelet .activation, resulting in ischemia*
The initial phase of skin disease is characterised by non-pitting oedema of the fingers and flexor tendon sheaths. Subsequently, the skin becomes shiny and taut, and distal skin creases disappear. There is usually erythema and tortuous dilatation of capillary loops in the nail-fold bed, readily visible with an ophthalmoscope set to +20. The face and neck are usually involved next, with thinning of the lips and radial furrowing.
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Scleroderma: edematous changes, hands
Systemic sclerosis Fibrotic contractures . Acrolysis of the distal phalanges . Pigmentation . Spots of depigmentation .
Skin involvement restricted to sites distal to the elbow or knee (apart from the face) is classified as 'limited cutaneous disease' or CREST syndrome … Involvement proximal to the knee and elbow and on the trunk is classified as 'diffuse cutaneous disease'. fingertips. *
Scleroderma
Head and Neck Manifestations tight skin, thin lips, vertical perioral furrows dermal and subcutaneous inflammatory process edema preceeds epidermal atrophy, loss of appendagesScleroderma
Head and Neck Manifestations decreased mouth opening Peaked nose Tight neck bandsScleroderma: facial changes marked telangiectasia
Scleroderma: Raynaud’s phenomenon, blanching of handsMusculoskeletal features
Arthralgia, morning stiffness and flexor tenosynovitis are common. Restricted hand function is due to skin rather than joint disease and erosive arthropathy is uncommon. Muscle weakness and wasting are usually due to myositis.*
Gastrointestinal features
Gut involvement is common. Smooth muscle atrophy and fibrosis in the lower two-thirds of the oesophagus lead to acid reflux with erosive oesophagitis. Since this may progress to further fibrosis, adequate treatment of reflux (usually with proton pump inhibitors) is important. Dysphagia and odynophagia (painful dysphagia) may also occur
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Cardiorespiratory features
Pulmonary involvement is a major cause of morbidity and mortality. Fibrosing alveolitis mainly affects patients with diffuse disease, particularly those with antibodies to topoisomerase 1. Pulmonary hypertension is a complication of long-standing disease and is six times more prevalent in limited than in diffuse disease.*
Renal features
One of the main causes of death is hypertensive renal crisis characterized by rapidly developing malignant hypertension and renal failure. Treatment is by angiotensin-converting enzyme (ACE) inhibition even if renal impairment is present. Hypertensive renal crisis is much more likely to occur in patients with diffuse rather than limited disease*
Scleroderma: acrosclerosis
CREST syndrome: calcinosis cutis, fingersScleroderma: calcinosis and acrolysis (radiograph)
Laboratory findings -1-
Raised inflammatory markers. Anemia: of chronic illness. Microangiopathic hemolytic anemia (hemolysis is caused by factors in the small blood vessels) . malabsorption. Complication related e.g. renal failure findings and restrictive lung function tests.
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Laboratory findings -2-
Autoantibodies Anticentromere Abs:40-80% of cases with limited SSc or CREST. Rare (2-5%) in diffuse SSc & in other connective tissue disorders. Antitopoisomerase 1 Abs: about 40% of cases of diffuse SSc specially with visceral involvement. Rare in other disorders. Antinucleolar Abs :near 20-30% of SSc. High speceficity. ANA in up to 90% of patients (poor specificity) .*
prognosis
5-years survival is about 70%. Bad prognostic features include: -diffuse cutaneous form. -onset at an older age. -male gender. -renal involvement. -pulmonary hypertension.*
Management
Infection of ulcerated skin should be treated with prompt antibiotic therapy. Antibiotics penetrate poorly into the skin lesions of systemic sclerosis and therefore need to be given at higher dose for longer periods (e.g. flucloxacillin 500 mg 6-hourly for 14 days).*
Calcium antagonists (e.g. nifedipine, amlodipine) or angiotensin II receptor antagonists (e.g. valsartan) may be effective for Raynaud's symptoms. For severe digital ischaemia, intermittent infusions of epoprostenol may be helpful. Corticosteroids and cytotoxic drugs are indicated in patients with myositis or alveolitis. No agent has been shown to arrest or improve skin changes.
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Management
2- Special drug groups Antifibroitic agents :D-penicillamine , colchicine ,corticosteroids. Corticosteroids : edematous phase / inflammatory myositis / pericarditis / active alveolitis. Note: renal crisis may follow cessation. Immunosuppressive agents: azathioprine , MTX , cyclophosphamide . Antiplatelet drugs: low dose aspirin / dipyridamol 200-400mg/d (divided doses).*
Mixed connective tissue disorders (MCTD)
An overlap syndrome showing variable combinations of features of SLE ,SSc & dermatomyositis. Overlap features accumulate over months to years.
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