الفهرس 
Definition of Systemic Sclerosis
EPIDEMIOLOGYOnly 14 pages are availabe for public view
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Abstract
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by micro vascular damage and excessive fibrosis of the skin and various internal organs.Estimates of incidence and prevalence of systemic sclerosis have varied widely by the period of observation, disease definition, and population.Systemic sclerosis (SSc) is an idiopathic systemic autoimmune disease, characterized by three pathological processes:
1-Severe and often progressive cutaneous and visceral fibrosis;
2-Fibroproliferative vasculopathy;
3-Pronounced cellular and humoral immunity abnormalities
Skindisease is a cardinal feature of systemic sclerosis, almost all patients have skin involvement. As such, skin manifestations are critical in the initial diagnosis of SSc and in the subsequent sub-classification into the different subsets of disease. The two principal subsets are, Limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc). The main difference between these two subsets is the speed of disease progression and the extent and severity of skin and visceral involvement.
The gastrointestinal (GI) tract is primarily responsible for the processes of digestion and excretion, and is frequently affected by manifestations of SSc. Lung involvement is a frequent complication and a leading cause of morbidity and mortality in this syndrome. Two major pulmonary syndromes are associated with scleroderma; a pulmonary vascular disorder evolving over time into relatively isolated pulmonary arterial hypertension (PAH), and interstitial lung disease (ILD).Renal manifestations occur frequently in scleroderma (SSc). Commonest is a reduction in renal function due to chronic disease but most clinically important is the scleroderma renal crisis (SRC). This life-threatening complication occurs in up to 15% of the cases of dcSSc.
Like any presentation of cardiac disease. the symptoms of patients with cardiac involvement in SSc is varied. In patients presenting with signs of left heart failure, pulmonary congestion, and elevated left heart filling pressures, the most common complaints are dyspnea with exertion, paroxysms of nocturnal dyspnea and/or orthopnea and, if chronic in nature, may present with ascites and pedal edema.
SSc is characterized by a complex array of clinical features involving internal organs and the skin. A common pathogenetic leitmotif to all these features is not only fibrosis due to excessive collagen production, but is also the overall microvascular involvement, in the early phases of the disease.
Raynaud’s phenomenon (RP) is often the very first manifestation of SSc, frequently preceding the onset of all the other signs and symptoms of the disease, and subcutaneous edema is also an early feature as well.
Digital ulcers were defined as a loss of surface epithelialization without including fissures or cracks in the skin or areas of calcinosis. Digital ulcers(DUs) are a major clinical problem in SSc, occurring in _30% of the patients each year. DUs may occur on the fingers or toes and can manifest on the tips, the finger creases, over the extensor surfaces of the joints or in association with calcinosis . DUs cause local pain and functional impairment (e.g. eating and dressing), and have a major negative impact on quality of life.
Several methods have been developed to assess microvascular structural and functional abnormalities in patients with SSc in order to study the mechanisms of RP attacks, for differential diagnosis between primary RP and secondary RP, and for measuring responsiveness to treatment, these methods include:
8- Biomarkers in Vascular Disease in SSc
9- Nailfold Capillaroscopy
10- fingertip lacticemy
11- laser Doppler imaging (LDI)
12- magnetic resonance angiography (MRA)
13- Thermography
14- Functional Vascular Studies.
In scleroderma, vascular biomarkers could be used in several different ways. They may aid identifying patients with high risk for future vascular complications. They may help define patients as early responders or non responders to vascular therapies. Importantly, they may also be utilized as a probe to understand the pathobiology of the vascular insult. Ideally one biomarker may fulfill all of these roles at least in regard to a specific vascular complication such as PH.
Nailfold capillaroscopy has great diagnostic value in the early stages of the disease. It is the technique of choice for the identification of patients with Raynaud’s phenomenon who are at risk for developing SSc. Lactate analysis is a common procedure in exercise physiology laboratories to measure endurance performance [251,252]. Determination of the lactic acid concentration in blood obtained from fingertips (fingertip lacticemy (FTL)) before and after a cold stimulus (CS) for assessment of the biochemical component of peripheral perfusion, and has been shown to provide accurate information on the degree of local anerobiosis in patients with RP and SSc.
The relatively new technique of laser Doppler imaging (LDI) allows an objective measurement of superficial cutaneous microvascular blood flow, and constitutes a promising approach in the assessment of the digital microvascular vasoreactivity in response to CS in SSc. LDI has the advantages of being non-invasive and of mapping tissue perfusion over a wide area of the skin, thus providing more reproducible values [258]. The principle of the LDI technique is based on the Doppler effect, where changes in wavelength due to movement between red blood cells and the observer (the scanner) are used to determine the speed of blood flow.
Magnetic resonance angiography (MRA) has been used with and without contrast material as a safe, reliable, and accurate technique for evaluation of vascular pathology of the hand. MRA allows accurate evaluation of arterioles and is also well suited for evaluating the extent of venous lesions.
Infrared thermography images surface temperature and is therefore an indirect measure of blood flow. Dynamic imaging, examining response to a cold challenge, helps to differentiate between patients with primary RP and SSc.
Numerous methods are used to investigate vascular function in SSc. Most of the reported techniques are not standardized, validated, or uniformly adapted by all investigators. The reported noninvasive vascular studies include:
1. Ultrasound-based techniques for the assessment of blood flow including color laser Doppler ultrasound measurements of blood flow, flow velocity, pulse waveform, wall–lumen ratio, and digital pressure.
2. Provocative tests that examine vasospasm or defective vascular dilatory potential in SSc
3. Digital blood pressure
4. Skin temperature
The care of a patient with systemic sclerosis (scleroderma) is particularly challenging because of the multiple potential complications of scleroderma, the variable clinical course, and imperfect treatment options. Management, currently, is based on early diagnosis of systemic sclerosis, regular screening and prompt detection of organ based complications. In the management of digital ulcers, the objective is to alleviate pain and disability, to preserve tissue integrity and reduce the impact on quality of life, key issues are good skin care, management of infection, tissue debridement when necessary and techniques such as digital sympathectomy for severe and refractory cases.
Pharmaceutical Approaches to Vascular Protection in SSc:
1-Calcium Channel Blockers
2- Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Receptor Antagonists
3- Prostacyclin Analogues
4- Endothelin Receptor Antagonists
5- Phosphodiesterase Inhibitors
6-Statins(3-Hydroxy-3-Methylglutaryl-CoenzymeA(HMG-CoA) reductase Inhibitors)
7- Antioxidants
Sympathectomy, which can be performed by a variety of techniques, is an option for persistent RP or digital ischemia. The rationale for this surgical intervention is to interrupt the sympathetic tone that is responsible for the exaggerated vasoconstriction in response to cold. A temporary chemical sympathectomy can beachieved when local anesthetic, such as lidocaine or bupivacaine, is injected near the appropriate sympatheticganglia.
Localinjection of botulinum toxin A has also been reported incase series as beneficial in improving color, warmth, and decreasing pain associated with RP. A more invasive and potentially longer lasting procedure is a cervical or thoracic sympathectomy.
Therapeutic angiogenesis by autologous transplantation of bone-marrow-derived cells in patients with intractable ulcers of ischemic limbs associated with SSc. Prompt pain reduction and ulcer healing were found in all patients. Rehabilitation therapies, such as occupational and physical therapy, are indicated for the person with SSc to improve joint motion, hand function, strength and general conditioning, and participation in daily activities such as self care, home management, leisure, and work. Referral to therapy should be made early in the course of the disease especially in patients with early diffuse SSc. Rehabilitation therapies include: 1-Range-of-Motion Exercises 2-Strengthening and General Exercise and Conditioning 3-Self-Management Programs 4-Paraffin wax 5-Ultrasound 6-Splints.