SYSTEMIC SCLEROSIS (SCLERODERMA) Flashcards
What is systemic sclerosis?
Hardening or thickening of the skin owing to abnormal dermal collagen.
What is the difference between limited scleroderma and diffuse scleroderma?
Limited scleroderma involves cutaneous manifestations that mainly affect the hands, arms and face. (Also CREST syndrome)
Diffuse scleroderma is rapidly progressing and affects a large area of the skin and one or more internal organs, frequently the kidneys, esophagus, heart and/or lungs. This form of scleroderma can be quite disabling.
Are males or females more affected by systemic sclerosis and what is the ratio?
Females 3:1
What is the peak incidence in terms of age?
30 to 50 years
What are the components of CREST in systemic sclerosis?
Calcinosis Raynaud's phenomenon Esophageal dysmotility Sclerodactyly Telangiectasia
What is the difference between limited cutaneous scleroderma and diffuse cutaneous scleroderma?
Limited cutaneous scleroderma involves cutaneous manifestations that mainly affect the hands, arms and face. (Also CREST syndrome)
Diffuse cutaneous scleroderma is rapidly progressing and affects a large area of the skin and one or more internal organs, frequently the kidneys, esophagus, heart and/or lungs. This form of scleroderma can be quite disabling.
What are the components of CREST in systemic sclerosis?
Calcinosis Raynaud's phenomenon Esophageal dysmotility Sclerodactyly Telangiectasia
What does the C of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Calcinosis - thickening and tightening of the skin with deposition of calcific nodules
What does the R of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Raynaud’s phenomenon is frequently the first manifestation of CREST/lcSSc, preceding other symptoms by years. Stress and cold temperature induces an exaggerated vasoconstriction of the small arteries, arterioles, and thermoregulatory vessels of the skin of the digits. Clinically this manifests as a white-blue-red transitions in skin color. Underlying this transition is pallor and cyanosis of the digits, followed by a reactive hyperemia as they rewarm. In contrast to uncomplicated primary Raynaud phenomenon, this occurrence is often painful.[2] Frequently this phenomenon leads to digital ulcerations, gangrene, or amputation. Ulceration can predispose to chronic infections of the involved site
What does the R of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Raynaud’s phenomenon is frequently the first manifestation of CREST, preceding other symptoms by years. Stress and cold temperature induces an exaggerated vasoconstriction of the small arteries, arterioles, and thermoregulatory vessels of the skin of the digits. Clinically this manifests as a white-blue-red transitions in skin color. Underlying this transition is pallor and cyanosis of the digits, followed by a reactive hyperemia as they rewarm. In contrast to uncomplicated primary Raynaud phenomenon, this occurrence is often painful. Frequently this phenomenon leads to digital ulcerations, gangrene, or amputation.
What does the R of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Raynaud’s phenomenon is frequently the first manifestation of CREST, preceding other symptoms by years. Stress and cold temperature induces an exaggerated vasoconstriction of the small arteries, arterioles, and thermoregulatory vessels of the skin of the digits. Clinically this manifests as a white-blue-red transitions in skin color. Underlying this transition is pallor and cyanosis of the digits, followed by a reactive hyperemia as they rewarm. In contrast to uncomplicated primary Raynaud phenomenon, this occurrence is often painful. Frequently this phenomenon leads to digital ulcerations, gangrene, or amputation.
What does the E of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Esophageal dysmotility - Presents as a sensation of food getting stuck (dysphagia) in the mid or lower esophagus, atypical chest pain, or cough. Patients often state they must drink liquids to swallow solid food. This motility problem results from atrophy of the gastrointestinal tract wall smooth muscle. This change may occur with or without pathologic evidence of significant tissue fibrosis.
What does the E of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Esophageal dysmotility - Presents as a sensation of food getting stuck (dysphagia) in the mid or lower esophagus, atypical chest pain, or cough. Patients often state they must drink liquids to swallow solid food. This motility problem results from atrophy of the gastrointestinal tract wall smooth muscle. This change may occur with or without pathologic evidence of significant tissue fibrosis.
What does the S of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Though it is the most easily recognizable manifestation, it is not prominent in all patients. Thickening often only involves the skin of the fingers distal to the metacarpophalangeal joints. Early in the course of the disease, the skin may appear edematous and inflamed. Eventually, dermal fibroblasts overproduce extracellular matrix leading to increased tissue collagen deposition in the skin. Collagen cross-linking then causes a progressive skin tightening. Digital ischemic ulcers commonly form on the distal fingers in 30-50% of patients.
What does the S of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Though it is the most easily recognizable manifestation, it is not prominent in all patients. Thickening often only involves the skin of the fingers distal to the metacarpophalangeal joints. Early in the course of the disease, the skin may appear edematous and inflamed. Eventually, dermal fibroblasts overproduce extracellular matrix leading to increased tissue collagen deposition in the skin. Collagen cross-linking then causes a progressive skin tightening. Digital ischemic ulcers form in 30-50% of patients.
What does the S of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Sclerodactyly - Though it is the most easily recognizable manifestation, it is not prominent in all patients. Thickening often only involves the skin of the fingers distal to the metacarpophalangeal joints. Early in the course of the disease, the skin may appear edematous and inflamed. Eventually, dermal fibroblasts overproduce extracellular matrix leading to increased tissue collagen deposition in the skin. Collagen cross-linking then causes a progressive skin tightening. Digital ischemic ulcers form in 30-50% of patients.
What does the T of CREST in systemic sclerosis refer to? Describe the feature in more detail.
Telangiectasis - dilated capillaries occur in the skin of the face, the palmar surface of the hands, and the mucous membranes. Telangiectasias tend to be more numerous in those patients with other scleroderma related vascular disease (i.e. pulmonary arterial hypertension). The number of telangiectasias and the sites involved tend to increase over time.
What are the complication of organ involvement in patients with diffuse cutaneous systemic sclerosis?
Lethargy Anorexia Weight loss Heartburn, reflux or dysphagia Anal incontinence Malabsorption - related to bacterial overgrowth due to dilatation and atony of small bowel Pseudobstruction of bowel Acute hypertensive renal crisis Chronic kidney disease Fibrosis of the lungs Pulmonary hypertension Myocardial fibrosis - leading to arrythmias and conduction defects
What are the complication of organ involvement in patients with diffuse cutaneous systemic sclerosis?
Lethargy Anorexia Weight loss Heartburn, reflux or dysphagia Anal incontinence Malabsorption - related to bacterial overgrowth due to dilatation and atony of small bowel Pseudobstruction of bowel Acute hypertensive renal crisis Chronic kidney disease Fibrosis of the lungs Pulmonary hypertension Myocardial fibrosis - leading to arrythmias and conduction defects
What investigations would you order to further assess someone with suspected systemic sclerosis?
FBC U&E's Autoantibodies Urine dipstick Imaging of chest, hands and GI
What might you expect to see in the FBC of someone with systemic sclerosis?
Normochromic, normocytic anaemia
Microangiopathic haemolytic anaemia is seen in some people with renal disease
What might you expect to see in the U&E’s of someone with systemic sclerosis with renal involvement?
Rise in urea
Rise in creatinine
Both signs of AKI
What are the complication of organ involvement in patients with diffuse cutaneous systemic sclerosis?
Systemic:
Lethargy
Anorexia
Weight loss
GI: GORD Dysphagia Anal incontinence Malabsorption - related to bacterial overgrowth due to dilatation and atony of small bowel Pseudobstruction of bowel
Genitourinary:
Acute hypertensive renal crisis
Chronic kidney disease
Erectile dysfunction
Pulmonary:
Fibrosis of the lungs
Pulmonary hypertension
Cardiovascular:
Myocardial fibrosis - leading to arrythmias and conduction defects
Hypertension
Musculoskeletal:
Joint aches
Carpal tunnel syndrome
What investigations would you order to further assess someone with suspected systemic sclerosis?
FBC U&E's Autoantibodies Urine microscopy Imaging of chest, hands and GI
What might you expect to see in the U&E’s of someone with systemic sclerosis with renal involvement?
Rise in urea
Rise in creatinine
Both signs of AKI
What autoantibodies would you expect to find in someone with limited systemic sclerosis?
Anti-centromere antibodies (ACA) occur in 70% of cases Rheumatoid factor (RF) occur in 30% Anti-nuclear antibodies (ANA) occur in 95%
What autoantibodies would you expect to find in someone with diffuse systemic sclerosis?
Anti-topoisomerase-1 (anti-Scl-70) - highly specific for DcSSc but occur in only about 30% of cases
Anti-RNA polymerase (I, II and III) - occurs in 20-25% of cases
Rheumatoid factor
Anti-nuclear antibodies
What complication of diffuse systemic sclerosis is the presence of Anti-RNA antibodies associated with?
Pulmonary fibrosis
What complication of diffuse systemic sclerosis is the presence of Anti-RNA antibodies associated with?
Pulmonary fibrosis
What might you expect to find when imaging the hands of someone with systemic sclerosis?
Deposits of calcium around fingers
In severe cases you might see erosion and absorption of the tufts of distal phalanges (acroosteolysis)
What might you expect to find when imaging the hands of someone with systemic sclerosis?
Deposits of calcium around fingers
In severe cases you might see erosion and absorption of the tufts of distal phalanges (acroosteolysis)
What is the pathophysiology of systemic sclerosis?
Initial vascular damage involving small arteries, arterioles and capillaries. Endothelial cell are damaged with release of cytokines including endothelin-1 which causes vasoconstriction.
Damage causes widespread obliterative arterial lesions and subsequent chronic ischemia.
Damaged endothelium upregulates adhesion molecules and chemokines to attract leukocytes, which enables loss of tolerance to structures such as topoisomerase 1 (development of anti-topoisomerase 1). Th2 play vital role in fibrosis.
Fibroblast recruited by several cytokines.
Fibroblasts synthesize increased quantities of collagen types I and III, as well as fibronectin and glycosaminoglycans.
What environmental risk have been identified for systemic sclerosis?
Exposure to vinyl chloride (making plastic tubing)
Silica dust
Adulterated rapeseed oil
Trichloroethylene (solvent used in industry)
What environmental risk have been identified for systemic sclerosis?
Exposure to vinyl chloride (making plastic tubing)
Silica dust
Adulterated rapeseed oil
Trichloroethylene (solvent used in industry)
Disease severity is inversely related to vitamin D levels in the serum.
What environmental risk have been identified for systemic sclerosis?
Exposure to vinyl chloride (making plastic tubing)
Silica dust
Adulterated rapeseed oil
Trichloroethylene (solvent used in industry)
Disease severity is inversely related to vitamin D levels in the serum.
What are the treatment options for someone diagnosed with systemic sclerosis?
Treatment must be organ based as their is currently no cure.
Unlike other autoimmune rheumatic diseases, corticosteroid and immunosuppressants are rarely used in SSc, with the exemption of SSc related pulmonary fibrosis.
What are the treatment options for someone diagnosed with systemic sclerosis?
Treatment must be organ based as their is currently no cure.
Unlike other autoimmune rheumatic diseases, corticosteroid and immunosuppressants are rarely used in SSc, with the exemption of SSc related pulmonary fibrosis.
What is the treatment for pulmonary fibrosis related to systemic sclerosis?
Immunosuppression using cyclophosphamide or azathioprine combined with lose-dose oral prednisolone.
What can be done for someone experiencing recurring bouts of Raynaud’s phenomenon?
Hand warmers
Calcium-channel blockers
ACE inhibitors
Angiotensin receptor blockers
What can be done for someone experiencing recurring bouts of Raynaud’s phenomenon?
Hand warmers
Calcium-channel blockers
ACE inhibitors
Angiotensin receptor blockers
What is the 10 year prognosis of someone diagnosed with limited cutaneous systemic sclerosis?
70%
What is the 10 year prognosis of someone diagnosed with diffuse cutaneous systemic sclerosis?
20%
What are the major causes of death in people with systemic sclerosis?
Pulmonary fibrosis
Pulmonary hypertension
What is the incidence of systemic sclerosis?
1 per 100,000
What is the incidence of systemic sclerosis?
1 per 100,000 per year
