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This article is about the disease. For the mushroom, see Scleroderma (genus). Scleroderma is a genus of 25 species of Fungi, commonly known as earth balls, now known to belong to the Boletales.
Systemic sclerosis
Classification and external resources
ICD-10 M34.
ICD-9 710.1
OMIM 181750
DiseasesDB 12845
MedlinePlus 000429
eMedicine med/2076  med/3132 derm/677 ped/2197
MeSH D012595

Scleroderma is a chronic disease characterized by excessive deposits of collagen in the skin or other organs. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings M00-M99 - Diseases of the Musculoskeletal system and Connective tissue (M00-M25 Arthropathies (M00-M03 Infectious arthropathies The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books In Medicine, a chronic disease is a Disease that is long-lasting or recurrent Collagen is the main Protein of Connective tissue in Animals and the most abundant protein in Mammals making up about 50% of the whole-body protein The skin is the outer covering of living tissue of an animal (or plant The localized type of the disease, while disabling, tends not to be fatal. The systemic type or systemic sclerosis, the generalized type of the disease, can be fatal as a result of heart, kidney, lung or intestinal damage autoimmune disease. The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic The kidneys are complicated organs that have numerous biological roles lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive In Anatomy, the intestine is the segment of the alimentary canal extending from the Stomach to the Anus and in humans and other mammals consists Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body [1]

Contents

Signs and symptoms

Skin symptoms

Scleroderma affects the skin, and in more serious cases it can affect the blood vessels and internal organs. The skin is the outer covering of living tissue of an animal (or plant The blood vessels are part of the Circulatory system and function to transport Blood throughout the body The most evident symptom is usually the hardening of the skin and associated scarring. The skin may appear tight, reddish or scaly. Blood vessels may also be more visible. Where large areas are affected, fat and muscle wastage may weaken limbs and affect appearance.

The seriousness of the disease varies hugely between cases. The two most important factors to consider are the level of internal involvement (beneath the skin) and the total area covered by the disease. In general, the more skin that is involved, the more severe the case of scleroderma.

For the systemic form of the disease, almost all patients (over 80%) have vascular symptoms and Raynaud's phenomenon. Raynaud's phenomenon (reɪˈnoʊz (rāy-NŌZ in Medicine, is a vasospastic disorder causing discoloration of the Fingers Toes and occasionally During an attack, there is discoloration of the hands and feet in response to cold. Raynaud's normally affects the fingers and toes. A finger is a type of digit, an organ of manipulation and sensation found in the Hands of Humans and other Primates Normally humans have five digits

Systemic scleroderma and Raynaud's can cause painful ulcers on the fingers or toes which are known as digital ulcers.

Calcinosis is also common in systemic scleroderma, and is often seen near the elbows, knees or other joints. Calcinosis is the formation of Calcium deposits in any Soft tissue. A joint is the location at which two or more Bones make contact

Other organs

Diffuse scleroderma can cause musculoskeletal, pulmonary, gastrointestinal, renal and other complications. The musculoskeletal system (also known as the locomotor system is an organ system that gives Animals the ability to physically move using the Muscles and lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive The kidneys are complicated organs that have numerous biological roles [1]Patients with larger amounts of cutaneous involvement are more likely to have involvement of the internal tissues and organs.

Musculoskeletal

The first joint symptoms that patients with scleroderma have are typically non specific joint pains, which can lead to arthritis, or cause discomfort in tendons or muscles. Arthralgia (from Greek arthro-, joint + -algos, pain literally means joint pain; it is a symptom of injury infection illnesses -- in particular Arthritis (from Greek arthro-, joint + -itis, inflammation plural arthritides is a group of conditions involving damage to the Joints of the body Tenosynovitis is the Inflammation of the Fluid -filled sheath (called the Synovium) that surrounds a Tendon. Myalgia means " Muscle Pain " and is a symptom of many diseases and disorders [1] Joint mobility, especially of the small joints of the hand, may be restricted by calcinosis or skin thickening. Calcinosis is the formation of Calcium deposits in any Soft tissue. [2] Patients may develop muscle weakness, or myopathy, either from the disease, or its treatments. In Medicine, a myopathy is a neuromuscular Disease in which the Muscle fibers do not function for any one of many reasons resulting in Muscular weakness [3]

Lungs

Some impairment in lung function is almost universally seen in patients with diffuse scleroderma on pulmonary function testing;[4] however, it does not necessarily cause symptoms, such as shortness of breath. Spirometry (meaning the measuring of breath) is the most common of the Pulmonary Function Tests (PFTs measuring Lung function specifically the measurement Some patients can develop pulmonary hypertension, or elevation in the pressures of the pulmonary arteries. In Medicine, pulmonary hypertension (PH is an increase in blood pressure in the Pulmonary artery, Pulmonary vein, or pulmonary capillaries together known The pulmonary arteries carry Blood from the Heart to the Lungs. This can be progressive, and lead to right sided heart failure. Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply The earliest manifestation of this may be a decreased diffusion capacity on pulmonary function testing. In Biology, diffusion capacity is a measurement of the Lung 's ability to transfer gases

Other pulmonary complications in more advanced disease include aspiration pneumonia, pulmonary hemorrhage and pneumothorax. Aspiration pneumonia is Bronchopneumonia that develops due to the entrance of foreign materials that enter the bronchial tree usually oral or gastric contents (including food Pulmonary hemorrhage (or "pulmonary haemorrhage" refers to Bleeding from the Lung. [1]

Digestive tract
Endoscopic image of peptic stricture, or narrowing of the esophagus near the junction with the stomach due to chronic gastroesophageal reflux. This is the most common cause of dysphagia, or difficulty swallowing, in scleroderma.
Endoscopic image of peptic stricture, or narrowing of the esophagus near the junction with the stomach due to chronic gastroesophageal reflux. The esophagus or oesophagus (see American and British English spelling differences) sometimes known as the gullet, is an organ in In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following Gastroesophageal reflux disease ( American English and Canadian English) or Gastro-oesophageal reflux disease ( British English, Hiberno-English This is the most common cause of dysphagia, or difficulty swallowing, in scleroderma. Dysphagia should not be confused with the similarly pronounced Dysphasia, a language disorder

Diffuse scleroderma can affect any part of the gastrointestinal tract. [5] The most common manifestation in the esophagus is reflux esophagitis, which may be complicated by peptic stricturing, or benign narrowing of the esophagus. The esophagus or oesophagus (see American and British English spelling differences) sometimes known as the gullet, is an organ in Esophagitis (or Oesophagitis) is Inflammation of the Esophagus. [6] This is best initially treated with proton pump inhibitors for acid suppression,[7] but may require bougie dilatation in the case of stricture. Proton pump inhibitors (or "PPI"s are a group of drugs whose main action is pronounced and long-lasting reduction of Gastric acid production Esophageal dilatation is a therapeutic endoscopic procedure that enlarges the lumen of the Esophagus. [5]

Scleroderma can decrease motility anywhere in the gastrointestinal tract. Motility is a biological term which refers to the ability to move spontaneously and actively consuming energy in the process [5] The most common source of decreased motility involvement is the esophagus and the lower esophageal sphincter, leading to dysphagia and chest pain. Dysphagia should not be confused with the similarly pronounced Dysphasia, a language disorder As Scleroderma progresses, esophageal involvement from abnormalities in decreased motility may worsen due to progressive fibrosis (scarring). If this is left untreated, acid from the stomach can back up into the esophagus causing esophagitis, and GERD. Esophagitis (or Oesophagitis) is Inflammation of the Esophagus. Gastroesophageal reflux disease ( American English and Canadian English) or Gastro-oesophageal reflux disease ( British English, Hiberno-English Further scarring from acid damage to the lower esophagus many times leads to the development of fibrotic narrowing, also known as strictures which can be treated by dilitation, and Barrett's esophagus. Barrett's esophagus (UK Oesophagus (sometimes called Barrett's syndrome, CELLO, columnar epithelium lined lower oesophagus or colloquially as Barrett's The small intestine can also become involved, leading to bacterial overgrowth and malabsorption, of bile salts, fats, carbohydrates, proteins, and vitamins. In Biology the small Intestine is the part of the Gastrointestinal tract (gut between the Stomach and the Large intestine, and comprises Small bowel bacterial overgrowth syndrome ( SBBOS) or small intestinal bacterial overgrowth ( SIBO) also termed bacterial overgrowth; is Malabsorption is a state arising from abnormality in Digestion or Absorption of food nutrients across the gastrointestinal(GI tract. Bile acids (also known as bile salts are Steroid Acids found predominantly in the Bile of Mammals. Fats consist of a wide group of compounds that are generally soluble in organic solvents and largely insoluble in water Carbohydrates (from ' Hydrates of Carbon ' or saccharides ( Greek σάκχαρον meaning " Sugar " are the most Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl A vitamin is an Organic compound required as a Nutrient in tiny amounts by an Organism. The colon can be involved, and can cause pseudo-obstruction or ischemic colitis. The colon is a storage tube for solid wastes The main function of the colon appears to be extraction of Water and salts from Feces. Ogilvie syndrome is the acute pseudoobstruction and dilation of the colon in the absence of any mechanical obstruction in severely ill patients This article concerns ischemia of the large bowel See Mesenteric ischemia for ischemia of small bowel Ischemic colitis (Ischaemic Colitis [1]

Rarer complications include pneumatosis cystoides intestinalis, or gas pockets in the bowel wall, wide mouthed diverticula in the colon and esophagus, and liver fibrosis. Diverticulosis, otherwise known as " diverticular disease " is the condition of having diverticula in the colon which are outpocketings of the The esophagus or oesophagus (see American and British English spelling differences) sometimes known as the gullet, is an organ in Cirrhosis is a consequence of chronic Liver Disease characterized by replacement of liver tissue by fibrous Scar tissue as well as regenerative Patients with severe gastrointestinal involvement can become profoundly malnourished. Malnutrition is a general term for a medical condition caused by an improper or insufficient diet. [6]

Scleroderma may also be associated with gastric antral vascular ectasia (GAVE), also known as watermelon stomach. Gastric antral vascular ectasia ( GAVE) is an uncommon cause of chronic Gastrointestinal bleeding or Iron deficiency anemia. This is a condition where atypical blood vessels proliferate usually in a radially symmetric pattern around the pylorus of the stomach. The pylorus (from Greek πυλωρος = "gate guard" is the region of the Stomach that connects to the Duodenum. GAVE can be a cause of upper gastrointestinal bleeding or iron deficiency anemia in patients with scleroderma. }} Upper gastrointestinal (GI bleeding refers to Hemorrhage in the Upper gastrointestinal tract. For a discussion of iron deficiency more broadly see the Wikipedia article iron deficiency. [6]

Kidneys

Renal involvement, in scleroderma, is considered a poor prognostic factor and not infrequently a cause of death in patients with scleroderma. [8]

The most important clinical complication of scleroderma involving the kidney is scleroderma renal crisis. Symptoms of scleroderma renal crisis are malignant hypertension (high blood pressure with evidence of acute organ damage), hyperreninemia (high renin levels), azotemia (kidney failure with accumulation of waste products in the blood) and microangiopathic hemolytic anemia (destruction of red blood cells). Malignant hypertension is a complication of hypertension characterized by very elevated blood pressure and organ damage in the Eyes Brain, Lung and/or Renin (pronounced "Ree-nin" or "Rē-nin" (ˈriːnɨn also known as Angiotensinogenase, is a circulating Enzyme that participates in the body's Azotemia is a medical condition characterized by abnormal levels of Nitrogen -containing compounds such as Urea, Creatinine, various body waste compounds In Medicine ( Hematology) microangiopathic hemolytic anemia (MAHA is a microangiopathic subgroup of Hemolytic anemia ( Anemia, loss [9] Apart from the high blood pressure, hematuria (blood in the urine) and proteinuria (protein loss in the urine) may be indicative. In Medicine, hematuria (or "haematuria" is the presence of Red blood cells (erythrocytes in the Urine. Proteinuria (from protein and urine) means the presence of anexcess of serum Proteins in the Urine. [10]

In the past scleroderma renal crisis was almost uniformily fatal. [11] While outcomes have improved significantly with the use of ACE inhibitors[12][13] the prognosis is often guarded, as a significant number of patients are refractory to treatment and develop renal failure. ACE inhibitors, or inhibitors of '''A'''ngiotensin-'''C'''onverting '''E'''nzyme, are a group of Pharmaceuticals that are used primarily in treatment of Hypertension Renal failure or kidney Approximately 5-10% of all scleroderma patients develop renal crisis at some point in the course of their disease. [14] Patients that have rapid skin involvement have the highest risk of renal complications. [14] It is most common in diffuse cutaneous scleroderma, and is often associated with antibodies against RNA polymerase (in 59% of cases). RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA. Many proceed to dialysis, although this can be stopped within three years in about a third of cases. Higher age and (paradoxically) a lower blood pressure at presentation make it more likely that dialysis is needed. [15]

Treatments for scleroderma renal crisis include ACE inhibitors, which are also used for prophylaxis,[14][13] and renal transplantation. ACE inhibitors, or inhibitors of '''A'''ngiotensin-'''C'''onverting '''E'''nzyme, are a group of Pharmaceuticals that are used primarily in treatment of Hypertension Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose Kidney transplantation or renal transplantation is the Organ transplant of a Kidney in a patient with End-stage renal disease. Transplanted kidneys are known to be affected by scleroderma and patients with early onset renal disease (within one year of the scleroderma diagnosis) are thought to have the highest risk for recurrence. [16]

Diagnosis

Diagnosis is by clinical suspicion, presence of autoantibodies (specifically anti-centromere and anti-scl70/anti-topoisomerase antibodies) and occasionally by biopsy. Anti- Centromere antibodies (ACA occur in CREST syndrome and occasionally in systemic Scleroderma. Anti-topoisomerase antibodies (ATA are Autoantibodies directed against Topoisomerase and found in several diseases most importantly Scleroderma. Of the antibodies, 90% have a detectable anti-nuclear antibody. Anti-nuclear antibodies ( ANA s also known as anti-nuclear factor or ANF) are antibodies directed against contents of the cell nucleus Anti-centromere antibody is more common in the limited form (80-90%) than in the systemic form (10%), and anti-scl70 is more common in the diffuse form (30-40%) and in African-American patients (who are more susceptible to the systemic form). African Americans or Black Americans are citizens or residents of the United States who have origins in any of the black populations of Africa [17]

In 1980 the American College of Rheumatology agreed upon diagnostic criteria for scleroderma. Year 1980 ( MCMLXXX) was a Leap year starting on Tuesday (link displays the 1980 Gregorian calendar) The American College of Rheumatology is an organization of and for physicians health professionals and scientists that advances Rheumatology through programs of education [18]

Types

There are three major forms of scleroderma: diffuse, limited (CREST syndrome) and morphea/linear. Diffuse and limited scleroderma are both a systemic disease, whereas the linear/morphea form is localized to the skin. (Some physicians consider CREST and limited scleroderma one and the same, others treat them as two separate forms of scleroderma. ) There is also a subset of the systemic form known as "systemic scleroderma sine scleroderma", meaning the usual skin involvement is not present.

Diffuse scleroderma

Diffuse scleroderma (progressive systemic sclerosis) is the most severe form - it has a rapid onset, involves more widespread skin hardening, will generally cause much internal organ damage (specifically the lungs and gastrointestinal tract), and is generally more life threatening. lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive

Limited scleroderma/CREST syndrome

The limited form is much milder: it has a slow onset and progression, skin hardening is usually confined to the hands and face, internal organ involvement is less severe, and a much better prognosis is expected.

In typical cases of limited scleroderma, Raynaud's phenomenon may precede scleroderma by several years. Raynaud's phenomenon is due to vasoconstriction of the small arteries of exposed peripheries - particularly the hands and feet - in the cold. It is classically characterised by a triphasic colour change - first white, then blue and finally red on rewarming. The scleroderma may be limited to the fingers - known as sclerodactyly.

The limited form is often referred to as CREST syndrome. In Medicine and Psychology, the term syndrome refers to the association of several clinically recognizable features signs (observed by a physician [19] "CREST" is an acronym for the five main features:

CREST is a limited form associated with antibodies against centromeres and usually spares the lungs and kidneys. Calcinosis is the formation of Calcium deposits in any Soft tissue. Raynaud's phenomenon (reɪˈnoʊz (rāy-NŌZ in Medicine, is a vasospastic disorder causing discoloration of the Fingers Toes and occasionally The esophagus or oesophagus (see American and British English spelling differences) sometimes known as the gullet, is an organ in Sclerodactyly is a localized thickening and tightness of the skin of the Fingers or Toes Sclerodactyly is commonly accompanied by Atrophy of the underlying Telangiectasias are small dilated Blood vessels near the surface of the skin or Mucous membranes measuring between 0

Morphea/linear scleroderma

Morphea/linear scleroderma involves isolated patches of hardened skin - there generally is no internal organ involvement. Morphea is a medical term for localized Scleroderma. The disease involves isolated patches of hardened skin - there generally is no internal organ involvement [20]

Causes

There is no clear obvious cause for scleroderma and systemic sclerosis. Genetic predisposition appears to be limited: genetic concordance is small; still, there often is a familial predisposition for autoimmune disease. Polymorphisms in COL1A2 and TGF-β1 may influence severity and development of the disease. Collagen type I alpha 2, also known as COL1A2, is a human Gene. Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the Transforming growth factor beta superfamily of Cytokines It is a secreted protein There is limited evidence implicating cytomegalovirus (CMV) as the original epitope of the immune reaction, and organic solvents and other chemical agents have been linked with scleroderma. Cytomegalovirus (CMV (from the Greek cyto-, "cell" and -megalo-, "large" is a viral A solvent is a liquid or gas that dissolves a solid liquid or gaseous Solute, resulting in a Solution. [17]

One of the suspected mechanisms behind the autoimmune phenomenon is the existence of microchimerism, i. In Zoology, a chimera is an animal that has two or more different populations of genetically distinct cells that originated in different Zygotes if the e. fetal cells circulating in maternal blood, triggering an immune reaction to what is perceived as "foreign" material. [21][17]

A distinct form of scleroderma and systemic sclerosis may develop in patients with chronic renal failure. Chronic kidney disease (CKD also known as chronic renal disease, is a progressive loss of renal function over a period of months or years This entity, nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis,[22] has been linked to the exposure to gadolinium-containing radiocontrast. Nephrogenic systemic fibrosis ( NSF) or Nephrogenic fibrosing dermopathy is a rare and serious Syndrome that involves Fibrosis of skin joints Gadolinium (ˌgædəˈlɪniəm is a Chemical element that has the symbol Gd and Atomic number 64 Contrast medium Radiocontrast agents (also simply contrast agents or contrast materials) are compounds used to improve the visibility of internal bodily structures [23]

Bleomycin[24] (a chemotherapeutic agent) and possibly taxane chemotherapy[25] may cause scleroderma, and occupational exposure to solvents has been linked with an increased risk of systemic sclerosis. Bleomycin is a Glycopeptide antibiotic produced by the Bacterium Streptomyces verticillus. The taxanes are Diterpenes produced by the plants of the genus Taxus (yews A solvent is a liquid or gas that dissolves a solid liquid or gaseous Solute, resulting in a Solution. [26]

Pathophysiology

The overproduction of collagen is thought to result from an autoimmune dysfunction, in which the immune system would start to attack the kinetochore of the chromosomes. Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which results in an immune response against its own cells and tissues The kinetochore (pronounced kin et' o core is the protein structure on Chromosomes where the Spindle fibers attach during division to pull the chromosomes apart This would lead to genetic malfunction of nearby genes. T cells accumulate in the skin; these are thought to secrete cytokines and other proteins that stimulate collagen deposition. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Stimulation of the fibroblast, in particular, seems to be crucial to the disease process, and studies have converged on the potential factors that produce this effect. A fibroblast is a type of cell that synthesizes and maintains the Extracellular matrix of many Animal tissues [17]

A significant player in the process is transforming growth factor (TGFβ). Transforming growth factor (sometimes referred to as Tumor growth factor, or TGF) is used to describe two classes of Polypeptide Growth factors This protein appears to be overproduced, and the fibroblast (possibly in response to other stimuli) also overexpresses the receptor for this mediator. An intracellular pathway (consisting of SMAD2/SMAD3, SMAD4 and the inhibitor SMAD7) is responsible for the secondary messenger system that induces transcription of the proteins and enzymes responsible for collagen deposition. SMAD2 is a human Gene. The Protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila SMAD7 or Mothers against decapentaplegic homolog 7 is a polypeptide that as its name describes is a homolog of the Drosophila gene " Mothers against decapentaplegic Transcription is the synthesis of RNA under the direction of DNA Sp1 is a transcription factor most closely studied in this context. In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences Apart from TGFβ, connective tissue growth factor (CTGF) has a possible role. CTGF (connective tissue Growth factor) is a Cysteine -rich matrix -associated Heparin -binding Protein. [17] Indeed, a common CTGF gene polymorphism is present at an increased rate in systemic sclerosis. [27]

Damage to endothelium is an early abnormality in the development of scleroderma, and this too seems to be due to collagen accumulation by fibroblasts, although direct alterations by cytokines, platelet adhesion and a type II hypersensitivity reaction have similarly been implicated. The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Increased endothelin and decreased vasodilation has been documented. Endothelins are proteins that constrict blood vessels and raise blood pressure [17]

Jimenez & Derk[17] describe three theories about the development of scleroderma:

Therapy

There is no cure for every patient with scleroderma, though there is treatment for some of the symptoms, including drugs that soften the skin and reduce inflammation. Some patients may benefit from exposure to heat. [28]

Topical/symptomatic

Topical treatment for the skin changes of scleroderma do not alter the disease course, but may improve pain and ulceration. A range of NSAIDs (nonsteroidal anti-inflammatory drugs) can be used to ease painful symptoms, such as naproxen. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher Naproxen ( INN) (nəˈprɒksən is a Non-steroidal anti-inflammatory drug (NSAID commonly used for the reduction of moderate to severe Pain, Fever There is limited benefit from steroids such as prednisone. Glucocorticoids (GC are a class of Steroid hormones characterised by an ability to bind with the glucocorticoid receptor ( GR) and trigger similar effects Episodes of Raynaud's phenomenon sometimes respond to nifedipine or other calcium channel blockers; severe digital ulceration may respond to prostacyclin analogue iloprost, and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. Nifedipine (brand name Adalat, Nifedical, and Procardia) is a Dihydropyridine Calcium channel blocker. Prostacyclin (or PGI2) is a member of the family of Lipid Molecules known as Eicosanoids. Iloprost is a drug used to treat pulmonary arterial hypertension (PAH Scleroderma, Raynaud's phenomenon and Ischaemia. Bosentan (BOZENTAN is a dual Endothelin receptor antagonist important in the treatment of Pulmonary artery hypertension (PAH [29] The skin tightness may be treated systemically with methotrexate and cyclosporin. Ciclosporin (ˌsaɪkləˈspɔrən cyclosporine ( USAN) or cyclosporin (former BAN) is an Immunosuppressant drug widely [29]

Kidney disease

Scleroderma renal crisis, the occurrence of acute renal failure and malignant hypertension (very high blood pressure with evidence of organ damage) in people with scleroderma, is effectively treated with drugs from the class of the ACE inhibitors. Acute renal failure ( ARF) also known as acute kidney failure or acute kidney injury, is a rapid loss of Renal function due to damage to the Malignant hypertension is a complication of hypertension characterized by very elevated blood pressure and organ damage in the Eyes Brain, Lung and/or ACE inhibitors, or inhibitors of '''A'''ngiotensin-'''C'''onverting '''E'''nzyme, are a group of Pharmaceuticals that are used primarily in treatment of Hypertension The benefit of ACE inhibitors extends even to those who have to commence dialysis to treat their kidney disease, and may give sufficient benefit to allow the discontinuation of renal replacement therapy. In Medicine, hemodialysis (also haemodialysis) is a method for removing waste products such as Potassium and Urea, as well as free water [29]

Lung disease and pulmonary hypertension

Active alveolitis is often treated with pulses of cyclophosphamide, often together with a small dose of steroids. Cyclophosphamide (the generic name for Cytoxan Neosar Revimmune also known as cytophosphane is a Nitrogen mustard alkylating agent, from the oxazophorines group The benefit of this intervention is modest. [30][31]

Pulmonary hypertension may be treated with epoprostenol, bosentan and possibly aerolized iloprost. Epoprostenol is a synthetic form of Prostacyclin, and is used to treat Pulmonary hypertension. Bosentan (BOZENTAN is a dual Endothelin receptor antagonist important in the treatment of Pulmonary artery hypertension (PAH [29]

Experimental treatments

Given the difficulty in treating scleroderma, treatments with a smaller evidence base are often tried to control the disease. Evidence-based medicine (EBM aims to apply Evidence gained from the Scientific method to certain parts of medical practice These include antithymocyte globulin and mycophenolate mofetil; some reports have reported improvements in the skin symptoms as well as delaying the progress of systemic disease, but neither of them have been subjected to large clinical trials. Anti-thymocyte globulin (ATG is an infusion of horse or rabbit-derived antibodies against human T cells which is used in the prevention and treatment of acute rejection Mycophenolic acid ( INN) (ˌmaɪkoʊˈfɛnɒlɪk or mycophenolate is an immunosuppressant drug used to prevent rejection in Organ transplantation [29]

While still experimental (given its high rate of complications), hematopoietic stem cell transplantation is being studied in patients with severe systemic sclerosis; improvement in life expectancy and severity of skin changes has been noted. [32]

Epidemiology

Scleroderma affects approximately 300,000 people in the United States. It is four times as common in women than in men. Incidence rates are estimated at 2-20 per million per year in the United States.

Juvenile scleroderma affects approximately 7000 children in the United States. The most common form of juvenile scleroderma is localized scleroderma, morphea and/or linear.

Advocacy

The Juvenile Scleroderma Network is an organization dedicated to provide emotional support and educational information to parents and their children living with juvenile scleroderma, to support pediatric research to identify the cause of and the cure for juvenile sscleroderma, and to enhance public awareness. [33]

In the US, the Scleroderma Foundation is a leading organization dedicated to raising awareness of the disease and assisting those who are affected. [34] The Scleroderma Research Foundation sponsors research into the condition. [35] Comedian and television presenter Bob Saget, a board member of the SRF, directed the 1996 ABC TV movie For Hope, starring Dana Delany, which depicts a young woman fatally affected by scleroderma; the film was based on the experiences of Saget's sister Gay. Robert "Bob" Lane Saget (born May 17 1956) is an American Stand-up comedian, Television host, actor and Filmmaker For Hope is a 1996 ABC TV movie starring Dana Delany and directed by Bob Saget. Dana Welles Delany (born March 13, 1956) is an American Film, stage, and Television Actress [36]

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External links

Dictionary

scleroderma

-noun

  1. (medicine) A chronic disease characterized by excessive deposits of collagen in the skin or other organs.
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