Systemic Sclerosis PDF

Systemic sclerosis DR.HEMN MAHMOOD AGHA FIBMS RHEUMATOLOGY MRCP UK RHEUMATOLOGY  Systemic sclerosis Systemic sclerosis (SScl) is an autoimmune disorder of connective tissue, which results in fibrosis affecting the skin, internal organs and vasculature. It is chara...

Systemic sclerosis DR.HEMN MAHMOOD AGHA FIBMS RHEUMATOLOGY MRCP UK RHEUMATOLOGY  Systemic sclerosis Systemic sclerosis (SScl) is an autoimmune disorder of connective tissue, which results in fibrosis affecting the skin, internal organs and vasculature. It is characterized typically by Raynaud’s phenomenon, digital ischemia , sclerodactyly, and cardiac, lung, gut and renal involvement. 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-to-male. Tow types of systemic sclerosis: It is subdivided into diffuse cutaneous systemic sclerosis (dcSScl: 30% of cases) and limited cutaneous systemic sclerosis (lcSScl: 70% of cases). Skin involvement restricted to sites distal to the elbow or knee (apart from the face) is thus classified as “limited disease” lcSScl. Involvement proximal to the knee and elbow and on the trunk is classified as ‘diffuse disease’ (dcSScl). The prognosis in dcSScl is poor. Features that associate with a poor prognosis include older age, diffuse skin disease, proteinuria, high ESR, a low gas transfer factor for carbon monoxide (TLCO) and pulmonary hypertension. Pathophysiology The cause of SScl is not completely understood. There is evidence for a genetic component and associations with alleles at the HLA locus have been found. The disease occurs in all ethnic groups and race may influence severity. Isolated cases have been reported in which an SScl-like disease has been triggered by exposure to silica dust, vinyl chloride, epoxy resins and trichloroethylene. There is clear evidence of immunological dysfunction: T lymphocytes, infiltrate the skin and there is abnormal fibroblast activation, leading to increased production of extracellular matrix in the dermis, primarily type I collagen. This results in symmetrical thickening, tightening and induration of the skin. Arterial and arteriolar narrowing occurs due to intimal proliferation and vessel wall inflammation. Endothelial injury causes release of vasoconstrictors and platelet activation, resulting in further ischaemia, which is thought to exacerbate the fibrotic process. Clinical features  Clinical features: Skin: Initially, there is non-pitting oedema of fingers and flexor tendon sheaths. Subsequently, the skin becomes shiny and taut, and distal skin creases disappear. There can be capillary loss. The face and neck are often involved, with thinning of the lips and radial furrowing. In some patients, skin thickening stops at this stage. Raynaud’s phenomenon :This is a universal feature and can precede other features by many years. Involvement of small blood vessels in the extremities may cause critical tissue ischaemia, leading to localised distal skin infarction and necrosis. Musculoskeletal features: Arthralgia and flexor tenosynovitis are common. Restricted hand function is due to skin rather than joint disease and erosive arthropathy is uncommon. Skin manifestation : Skin manifestation : Gastrointestinal involvement: Smooth muscle atrophy and fibrosis in the lower two-thirds of the oesophagus lead to reflux with erosive oesophagitis. Dysphagia and odynophagia may also occur. Recurrent occult upper gastrointestinal bleeding may indicate a ‘watermelon’ stomach (antral vascular ectasia). Small intestine involvement may lead to malabsorption due to bacterial overgrowth and intermittent bloating, pain or constipation. Pulmonary involvement: Pulmonary hypertension complicates long-standing disease and is six times more prevalent in lcSScl than in dcSScl. It usually presents with insidiously evolving exertional dyspnoea and signs of right heart failure. Interstitial lung disease is common in patients with dcSScl who have topoisomerase 1 antibodies (Scl70). Dyspnoea can evolve slowly over time or rapidly in occasional cases. Renal involvement: One of the main causes of death is hypertensive renal crisis, characterised by rapidly developing accelerated phase hypertension and renal failure. Hypertensive renal crisis is much more likely to occur in dcSScl than in lcSScl, and in patients with topoisomerase 1 and RNP antibodies. Investigations As SScl can affect multiple organs, routine haematology, renal, liver and bone function tests and urinalysis are essential. ANA is positive in about 70%. About 30% of patients with dcSScl have antibodies to topoisomerase 1 (Scl70). About 60% of patients with lcSScl syndrome have anticentromere antibodies. Chest X-ray, echocardiography and PFT are recommended to assess for ILD and PAH). High-resolution lung CT is recommended if interstitial lung disease suspected. If PAH is suspected, right heart catheter measurements should be arranged. A barium swallow can assess esophageal involvement. A hydrogen breath test can indicate bacterial overgrowth Management No treatments are available that halt or reverse the fibrotic changes that underlie the disease. The focus of management, therefore, is to slow the effects of the disease on target organs. Raynaud’s phenomenon and digital ulcers. Avoidance of cold exposure, use of thermal insulating gloves/socks and maintenance of a high core temperature all help. If symptoms are persistent, calcium channel blockers, losartan, fluoxetine and sildenafil have efficacy. Gastrointestinal complications. Oesophageal reflux should be treated with proton pump inhibitors and anti-reflux agents. Rotating courses of antibiotics may be required for bacterial overgrowth while metoclopramide or domperidone may help patients with symptoms of dysmotility/ pseudo- obstruction. Management Hypertension. Aggressive treatment with ACE inhibitors is needed, even if renal impairment is present. Joint involvement. This may be treated with analgesics and/or NSAIDs OR low-dose methotrexate can be of value. Progressive pulmonary hypertension. Early treatment with bosentan is required. In severe or progressive disease, heart–lung transplant may be considered. Interstitial lung disease. Glucocorticoids and (pulse intravenous) cyclophosphamide are the mainstays of treatment in patients who have progressive interstitial lung disease.