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Scleroderma
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<h2 id="signs-and-symptoms">Signs and symptoms</h2> <p>Potential signs and symptoms include:<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a><a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a><a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a><a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> </p> <ul><li>Cardiovascular: <a href="/facts/Raynaud%27s_phenomenon/VorWr74H">Raynaud's phenomenon</a> (is the presenting symptom in 30% of affected persons, occurs in 95% of affected individuals at some time during their illness); healed pitting <a href="/facts/Ulcers/EpyxNx6b">ulcers</a> on the fingertips; skin and mucosal <a href="/facts/Telangiectasis/72MBl6oP">telangiectasis</a>; <a href="/facts/Palpitations/2wACMY49">palpitations</a>, irregular heart rate and <a href="/facts/Syncope_(medicine)/AqU1whYh">fainting</a> due to <a href="/facts/Electrical_conduction_system_of_the_heart/AouErvDx">conduction</a> abnormalities, <a href="/facts/Hypertension/wlAvBfcf">hypertension</a>, and <a href="/facts/Congestive_heart_failure/7fckX3Jm">congestive heart failure</a></li> <li>Digestive: <a href="/facts/Gastroesophageal_reflux_disease/8YhncnDz">gastroesophageal reflux disease</a>, bloating, <a href="/facts/Dyspepsia/axnCu0gn">indigestion</a>, loss of appetite, <a href="/facts/Diarrhoea/6TBHaRdA">diarrhoea</a> alternating with <a href="/facts/Constipation/l4DHHM6L">constipation</a>, <a href="/facts/Sicca_syndrome/U1p9IbFU">sicca syndrome</a> and its complications, <a href="/facts/Gastric_antral_vascular_ectasia/9GeeYWXh">gastric antral vascular ectasia</a>, loosening of teeth, and hoarseness (due to acid reflux).</li> <li>Pulmonary: progressive worsening of shortness of breath, chest pain (due to <a href="/facts/Pulmonary_artery_hypertension/4848aBJl">pulmonary artery hypertension</a>) and dry, persistent cough due to <a href="/facts/Interstitial_lung_disease/0LQEwsGc">interstitial lung disease</a></li> <li>Musculoskeletal: <a href="/facts/Arthralgia/jEHMRWX7">joint</a>, <a href="/facts/Myalgia/AbVybHB8">muscle aches</a>, loss of joint range of motion, <a href="/facts/Carpal_tunnel_syndrome/kkfl7ghv">carpal tunnel syndrome</a>, and <a href="/facts/Asthenia/U9wAgeLn">muscle weakness</a></li> <li>Genitourinary: <a href="/facts/Erectile_dysfunction/7HDetsos">erectile dysfunction</a>, <a href="/facts/Dyspareunia/qcoh8ltE">dyspareunia</a>, kidney problems, or <a href="/facts/Kidney_failure/gsqb5nos">kidney failure</a></li> <li>Other: facial pain due to <a href="/facts/Trigeminal_neuralgia/uu6XcP7J">trigeminal neuralgia</a>, hand <a href="/facts/Paresthesias/hRBAxluk">paresthesias</a>, headache, <a href="/facts/Stroke/DwpjdzY0">stroke</a>, fatigue, <a href="/facts/Calcinosis/g7y2BhIS">calcinosis</a>, and weight loss</li></ul> <h2 id="cause">Cause</h2> <p>Scleroderma is caused by genetic and environmental factors.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a><a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a><a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a><a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> Mutations in <a href="/facts/Human_leukocyte_antigen/6QRXe5QI">HLA</a> genes seem to play a crucial role in the <a href="/facts/Pathogenesis/o9kHHK0U">pathogenesis</a> of some cases; likewise <a href="/facts/Silica/A3WILp6J">silica</a>, <a href="/facts/Aromatic_hydrocarbon/3EXq8Tgf">aromatic</a> and <a href="/facts/Chlorinated_hydrocarbon/IbblBkcB">chlorinated</a> solvents, <a href="/facts/Ketones/BqQXpLo4">ketones</a>, <a href="/facts/Trichloroethylene/VrhHehsC">trichloroethylene</a>, <a href="/facts/Welding/6EJ62mYV">welding</a> fumes, and <a href="/facts/Mineral_spirits/qDgcURve">white spirits</a> exposure seems to contribute to the condition in a small proportion of affected persons.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a><a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a><a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a><a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a><a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> </p> <h2 id="pathophysiology">Pathophysiology</h2> <p>Scleroderma is characterised by increased <a href="/facts/Biosynthesis/aFk7Tk7f">synthesis</a> of <a href="/facts/Collagen/KsyAb72K">collagen</a> (leading to the <a href="/facts/Sclerosis_(medicine)/KPhDDorL">sclerosis</a>), damage to small blood vessels, activation of <a href="/facts/T_lymphocytes/5z6PQ9UN">T lymphocytes</a>, and production of altered <a href="/facts/Connective_tissue/mal3fc7k">connective tissue</a>.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> Its proposed pathogenesis is the following:<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a><a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a><a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a><a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> </p> <ul><li>It begins with an inciting event at the level of the <a href="/facts/Vasculature/WXwudzzc">vasculature</a>, probably the <a href="/facts/Endothelium/L4ENFVnw">endothelium</a>. The inciting event is yet to be elucidated, but may be a viral agent, <a href="/facts/Oxidative_stress/HX7dfUUb">oxidative stress</a>, or autoimmune. <a href="/facts/Endothelial_cell/L4ENFVnw">Endothelial cell</a> damage and <a href="/facts/Apoptosis/8dVzSm4y">apoptosis</a> ensue, leading to the vascular leakiness that manifests in early clinical stages as tissue <a href="/facts/Oedema/Q6MI3KdH">oedema</a>. At this stage, it is predominantly a <a href="/facts/Th1_cell/nhwAYkDj">Th1</a>- and <a href="/facts/Th17/V3TmUNSX">Th17</a>-mediated disease.</li> <li>After this, the vasculature is further compromised by impaired <a href="/facts/Angiogenesis/h0HF9IUd">angiogenesis</a> and impaired <a href="/facts/Vasculogenesis/CCStKYHz">vasculogenesis</a> (fewer endothelial progenitor cells), likely related to the presence of antiendothelinal cell antibodies (AECA). Despite this impaired <a href="/facts/Angiogenesis/h0HF9IUd">angiogenesis</a>, elevated levels of pro-angiogenic growth factors such as <a href="/facts/Platelet_derived_growth_factor/fYpbl1qA">PDGF</a> and <a href="/facts/Vascular_endothelial_growth_factor/kNDc0Xj0">VEGF</a> is often seen in persons with the condition. The balance of <a href="/facts/Vasodilation/cjzrU8Ro">vasodilation</a> and vasoconstriction becomes askew, and the net result is vasoconstriction. The damaged endothelium then serves as a point of origin for blood-clot formation and further contributes to <a href="/facts/Ischaemia/ySL9xbCl">ischaemia</a>-<a href="/facts/Reperfusion_injury/3MWNux98">reperfusion injury</a> and the generation of <a href="/facts/Reactive_oxygen_species/GpwSRugH">reactive oxygen species</a>. These later stages are characterised by <a href="/facts/Th2/nhwAYkDj">Th2</a> polarity.</li> <li>The damaged endothelium upregulates <a href="/facts/Adhesion_molecules/84EkpbAb">adhesion molecules</a> and <a href="/facts/Chemokine/YrySj9eD">chemokines</a> to attract <a href="/facts/Leucocyte/vsDunUK0">leucocytes</a>, which enables the development of innate and adaptive immune responses, including loss of tolerance to various oxidised <a href="/facts/Antigens/9JlAernG">antigens</a>, which includes <a href="/facts/Topoisomerase_I/F18wnC0U">topoisomerase I</a>. <a href="/facts/B_cells/6Y1tgwwp">B cells</a> mature into <a href="/facts/Plasma_cells/1fY4bFHR">plasma cells</a>, which furthers the autoimmune component of the condition. T cells differentiate into subsets, including Th2 cells, which play a vital role in tissue <a href="/facts/Fibrosis/VVSmVgr3">fibrosis</a>. <a href="/facts/Topoisomerase_1/mzwQc70k">Anti–topoisomerase 1</a> <a href="/facts/Antibodies/MX8pdTdP">antibodies</a>, in turn, stimulate <a href="/facts/Type_I_interferon/jQhMAFA3">type I interferon</a> production.</li> <li><a href="/facts/Fibroblast/n08KsFll">Fibroblasts</a> are recruited and activated by multiple <a href="/facts/Cytokine/SdWpWABH">cytokines</a> and growth factors to generate <a href="/facts/Myofibroblasts/n7YgT95j">myofibroblasts</a>. Dysregulated <a href="/facts/Transforming_growth_factor_%CE%B2/6bD65SWQ">transforming growth factor β</a> (TGF-β) signalling in fibroblasts and myofibroblasts has been observed in multiple studies of scleroderma-affected individuals. Activation of fibroblasts and myofibroblasts leads to excessive deposition of collagen and other related proteins, leading to fibrosis. B cells are implicated in this stage, <a href="/facts/Interleukin_6/FVQeAWkt">IL-6</a> and TGF-β produced by the B cells decrease collagen degradation and increase <a href="/facts/Extracellular_matrix/kaHC5Ez8">extracellular matrix</a> production. <a href="/facts/Endothelin/V4pSN8x0">Endothelin signalling</a> is implicated in the pathophysiology of fibrosis.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a></li></ul> <p><a href="/facts/Vitamin_D/No0zQB2W">Vitamin D</a> is implicated in the pathophysiology of the disease. An inverse correlation between plasma levels of vitamin D and scleroderma severity has been noted, and vitamin D is known to play a crucial role in regulating (usually suppressing) the actions of the immune system.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> </p> <h2 id="diagnosis">Diagnosis</h2> <p>Typical scleroderma is classically defined as symmetrical skin thickening, with about 70% of cases also presenting with Raynaud's phenomenon, nail-fold capillary changes, and <a href="/facts/Anti-nuclear_antibody/rKxKt85z">antinuclear antibodies</a>. Affected individuals may experience systemic organ involvement. No single test for scleroderma works all of the time, hence diagnosis is often a matter of exclusion. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> </p><p>Laboratory testing can show <a href="/facts/Anti-topoisomerase_antibodies/xwjESvxj">antitopoisomerase antibodies</a>, like <a href="/facts/Anti-scl70/wRW4gQmT">anti-scl70</a> (causing a diffuse systemic form), or <a href="/facts/Anti-centromere_antibodies/StQUophp">anticentromere antibodies</a> (causing a limited systemic form and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> Antidouble-stranded DNA autoantibodies are likely to be present in serum. </p> <h3>Differential</h3> <p>Diseases that are often in the differential include:<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a> </p> <ul><li><a href="/facts/Eosinophilia/RkFrKK10">Eosinophilia</a> is a condition in which too many <a href="/facts/Eosinophils/yhIKA8bE">eosinophils</a> (a type of immune cell that attacks parasites and is involved in certain allergic reactions) are present in the blood.</li> <li><a href="/facts/Eosinophilia-myalgia_syndrome/Y5l4emjr">Eosinophilia-myalgia syndrome</a> is a form of eosinophilia caused by <a href="/facts/L-tryptophan/JcUxlxAh">L-tryptophan</a> supplements.</li> <li><a href="/facts/Eosinophilic_fasciitis/5TDjRz54">Eosinophilic fasciitis</a> affects the connective tissue surrounding skeletal muscles, bones, blood vessels, and nerves in the arms and legs.</li> <li><a href="/facts/Graft-versus-host_disease/UjspvMVa">Graft-versus-host disease</a> is an autoimmune condition that occurs as a result of bone-marrow transplants in which the immune cells from the transplanted bone marrow attack the host's body.</li> <li><a href="/facts/Mycosis_fungoides/c0qdfwDH">Mycosis fungoides</a> is a type of <a href="/facts/Cutaneous_T_cell_lymphoma/gVeNtJ9N">cutaneous T cell lymphoma</a>, a rare cancer that causes rashes all over the body.</li> <li><a href="/facts/Nephrogenic_systemic_fibrosis/tJvXoCp7">Nephrogenic systemic fibrosis</a> is a condition usually caused by <a href="/facts/Kidney_failure/gsqb5nos">kidney failure</a> that results in fibrosis (thickening) of the tissues.</li> <li><a href="/facts/Primary_biliary_cirrhosis/9X0f10mz">Primary biliary cirrhosis</a> is an autoimmune disease of the liver.</li> <li><a href="/facts/Primary_pulmonary_hypertension/4848aBJl">Primary pulmonary hypertension</a></li> <li><a href="/facts/Complex_regional_pain_syndrome/u28BUyNw">Complex regional pain syndrome</a></li></ul> <h3>Classification</h3> <p>Scleroderma is characterised by the appearance of circumscribed or diffuse, hard, smooth, ivory-colored areas that are immobile and which give the appearance of hidebound skin, a disease occurring in both localised and systemic forms:<a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a> </p> <ul><li><a href="/facts/Localised_scleroderma/NPFeNrcM">Localised scleroderma</a> <ul><li><a href="/facts/Localised_morphea/NPFeNrcM">Localised morphea</a></li> <li><a href="/facts/Morphea-lichen_sclerosus_et_atrophicus_overlap/NPFeNrcM">Morphea-lichen sclerosus et atrophicus overlap</a></li> <li><a href="/facts/Generalised_morphea/NPFeNrcM">Generalised morphea</a></li> <li><a href="/facts/Atrophoderma_of_Pasini_and_Pierini/NPFeNrcM">Atrophoderma of Pasini and Pierini</a></li> <li><a href="/facts/Pansclerotic_morphea/NPFeNrcM">Pansclerotic morphea</a></li> <li><a href="/facts/Morphea_profunda/NPFeNrcM">Morphea profunda</a></li> <li><a href="/facts/Linear_scleroderma/NPFeNrcM">Linear scleroderma</a></li></ul></li> <li><a href="/facts/Systemic_scleroderma/K4UQIlxk">Systemic scleroderma</a> <ul><li><a href="/facts/CREST_syndrome/jKCFJhbU">CREST syndrome</a></li> <li><a href="/facts/Progressive_systemic_sclerosis/K4UQIlxk">Progressive systemic sclerosis</a></li></ul></li></ul> <h2 id="treatment">Treatment</h2> <p>No cure for scleroderma is known, although relief of symptoms is often achieved; these include treatment of:<a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a><a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a> </p> <ul><li><a href="/facts/Raynaud%27s_phenomenon/VorWr74H">Raynaud's phenomenon</a> with vasodilators such as <a href="/facts/Calcium_channel_blockers/st91pD2K">calcium channel blockers</a>, <a href="/facts/Alpha_blocker/MqNLhfS9">alpha blockers</a>, <a href="/facts/Serotonin_receptor_antagonist/Fp9DX8oW">serotonin receptor antagonists</a>, <a href="/facts/Angiotensin_II_receptor/RBLpGszE">angiotensin II receptor</a> inhibitors, <a href="/facts/Statins/ba4mes9W">statins</a>, local nitrates or <a href="/facts/Iloprost/AU41rWHI">iloprost</a></li> <li>Digital ulcers with <a href="/facts/Phosphodiesterase_5/clN3rEPe">phosphodiesterase 5</a> inhibitors (e.g., <a href="/facts/Sildenafil/2NHe0pwM">sildenafil</a>) or <a href="/facts/Iloprost/AU41rWHI">iloprost</a></li> <li>Prevention of new digital ulcers with <a href="/facts/Bosentan/DzvUTbao">bosentan</a></li> <li>Malnutrition, secondary to intestinal flora overgrowth with <a href="/facts/Tetracycline_antibiotic/IQx9gYrE">tetracycline antibiotics</a> such as <a href="/facts/Tetracycline/DQ0exP62">tetracycline</a></li> <li><a href="/facts/Interstitial_lung_disease/0LQEwsGc">Interstitial lung disease</a> with <a href="/facts/Cyclophosphamide/eTXHmLFV">cyclophosphamide</a>, <a href="/facts/Azathioprine/CmeIK3ca">azathioprine</a> with or without corticosteroids</li> <li><a href="/facts/Pulmonary_arterial_hypertension/4848aBJl">Pulmonary arterial hypertension</a> with endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and prostanoids</li> <li>Gastrooesophageal reflux disease with antacids or prokinetics</li> <li>Kidney crises with <a href="/facts/Angiotensin_converting_enzyme_inhibitor/cHT1Yxub">angiotensin converting enzyme inhibitors</a> and <a href="/facts/Angiotensin_II_receptor_antagonist/152pCs2x">angiotensin II receptor antagonists</a></li></ul> <p>Systemic <a href="/facts/Disease-modifying_treatment/h3hDQPCX">disease-modifying treatment</a> with immunosuppressants is often used.<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a><a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a><a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a><a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a><a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a><a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> Immunosuppressants used in its treatment include <a href="/facts/Azathioprine/CmeIK3ca">azathioprine</a>, <a href="/facts/Methotrexate/LoDvhRKX">methotrexate</a>, <a href="/facts/Cyclophosphamide/eTXHmLFV">cyclophosphamide</a>, <a href="/facts/Mycophenolate/kHpk0USt">mycophenolate</a>, intravenous <a href="/facts/Immunoglobulin/MX8pdTdP">immunoglobulin</a>, <a href="/facts/Rituximab/q6BLRsS6">rituximab</a>, <a href="/facts/Sirolimus/9hdLP135">sirolimus</a>, <a href="/facts/Alefacept/vxctjau5">alefacept</a>, and the tyrosine kinase inhibitors, <a href="/facts/Imatinib/PSpRplHy">imatinib</a>, <a href="/facts/Nilotinib/5dvWNTAb">nilotinib</a>, and <a href="/facts/Dasatinib/UyTuqLea">dasatinib</a>.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a><a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a><a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a><a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a><a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a><a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a><a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a><a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a> </p><p>Experimental therapies under investigation include endothelin receptor antagonists, tyrosine kinase inhibitors, beta-glycan peptides, <a href="/facts/Halofuginone/WPpBbXtr">halofuginone</a>, <a href="/facts/Basiliximab/6BLvotys">basiliximab</a>, <a href="/facts/Alemtuzumab/2qNI9kRc">alemtuzumab</a>, <a href="/facts/Abatacept/oM6Dpy1E">abatacept</a>, and <a href="/facts/Haematopoietic_stem_cell_transplantation/rGYRsATD">haematopoietic stem cell transplantation</a>.<a class="footnote-ref" id="fnref:67" href="#fn:67"><sup>67</sup></a><a class="footnote-ref" id="fnref:68" href="#fn:68"><sup>68</sup></a> </p> <table><tbody><tr><th colspan="5">Immunomodulatory agents in the treatment of scleroderma</th></tr><tr><th><a href="/facts/International_Nonproprietary_Name/wYL655x6">INN</a></th><th>Mechanism of action<a class="footnote-ref" id="fnref:69" href="#fn:69"><sup>69</sup></a><a class="footnote-ref" id="fnref:70" href="#fn:70"><sup>70</sup></a></th><th>Route of administration<a class="footnote-ref" id="fnref:71" href="#fn:71"><sup>71</sup></a></th><th>Pregnancy category<a class="footnote-ref" id="fnref:72" href="#fn:72"><sup>72</sup></a><a class="footnote-ref" id="fnref:73" href="#fn:73"><sup>73</sup></a></th><th>Major toxicities<a class="footnote-ref" id="fnref:74" href="#fn:74"><sup>74</sup></a></th></tr><tr><td><a href="/facts/Alefacept/vxctjau5">Alefacept</a></td><td>Monoclonal antibody to inhibit T lymphocyte activation by binding to CD2 portion of <a href="/facts/Human_leukocyte_antigen/6QRXe5QI">human leukocyte function antigen-3</a>.</td><td>IM</td><td>B (US)</td><td>Malignancies, injection site reactions, blood clots, <a href="/facts/Lymphopenia/sGQwg8ez">lymphopenia</a>, hepatotoxicity and infections.</td></tr><tr><td><a href="/facts/Azathioprine/CmeIK3ca">Azathioprine</a></td><td>Purine analogue that inhibits lymphocyte proliferation via conversion to <a href="/facts/Mercaptopurine/YeXPlXhI">mercaptopurine</a></td><td>PO, IV</td><td>D (Au)</td><td><a href="/facts/Myelosuppression/NEdoL9nj">Myelosuppression</a> and <i>rarely</i> malignancy, hepatitis, infection, <a href="/facts/Hepatic_sinusoidal_obstruction_syndrome/5l0gkjjV">hepatic sinusoidal obstruction syndrome</a> and hypersensitivity reactions.</td></tr><tr><td><a href="/facts/Cyclophosphamide/eTXHmLFV">Cyclophosphamide</a></td><td>Nitrogen mustard that cross-links DNA base pairs, leading to breakages and triggering apoptosis in haematopoietic cells.</td><td>PO, IV</td><td>D (Au)</td><td>Vomiting, myelosuppression, <a href="/facts/Haemorrhagic_cystitis/G19n5N4U">haemorrhagic cystitis</a> and <i>rarely</i> heart failure, pulmonary fibrosis, <a href="/facts/Hepatic_sinusoidal_obstruction_syndrome/5l0gkjjV">hepatic sinusoidal obstruction syndrome</a>, malignancy and <a href="/facts/Syndrome_of_inappropriate_secretion_of_antidiuretic_hormone/4sb69yBM">SIADH</a></td></tr><tr><td><a href="/facts/Dasatinib/UyTuqLea">Dasatinib</a></td><td><a href="/facts/Tyrosine_kinase/26Ln0qJ4">Tyrosine kinase</a> inhibitor against various proangiogenic growth factors (including PDGF and VEGF).</td><td>PO</td><td>D (Au)</td><td>Fluid retention, myelosuppression, haemorrhage, infections, pulmonary hypertension, electrolyte anomalies and <i>uncommonly</i> hepatotoxicity, heart dysfunction/failure, myocardial infarction, QT interval prolongation, renal failure and hypersensitivity.</td></tr><tr><td><a href="/facts/Imatinib/PSpRplHy">Imatinib</a></td><td>As above</td><td>PO</td><td>D (Au)</td><td>As above and <i>rarely:</i> GI perforation, avascular necrosis and <a href="/facts/Rhabdomyolysis/Cs08YHfR">rhabdomyolysis</a></td></tr><tr><td><a href="/facts/Immunoglobulin/MX8pdTdP">Immunoglobulin</a></td><td>Immunoglobulin, modulates the immune system.</td><td>IV</td><td>N/A</td><td>Varies</td></tr><tr><td><a href="/facts/Methotrexate/LoDvhRKX">Methotrexate</a></td><td>Antifolate; inhibits <a href="/facts/Dihydrofolate_reductase/sAEk55jF">dihydrofolate reductase</a>.</td><td>PO, IV, IM, SC, IT</td><td>D (Au)</td><td>Myeosuppression, pulmonary toxicity, hepatotoxicity, neurotoxicity and <i>rarely</i> kidney failure, hypersensitivity reactions, skin and bone necrosis, and osteoporosis</td></tr><tr><td><a href="/facts/Mycophenolate/kHpk0USt">Mycophenolate</a></td><td><a href="/facts/Inosine_monophosphate_dehydrogenase/9EsKAu1x">Inosine monophosphate dehydrogenase</a> inhibitor, leading to reduced purine biosynthesis in lymphocytes.</td><td>PO, IV</td><td>D (Au)</td><td>Myelosuppression, blood clots, <i>less commonly</i> GI perforation/haemorrhage and <i>rarely</i> <a href="/facts/Pancreatitis/gmbNTcCG">pancreatitis</a>, <a href="/facts/Hepatitis/FIN87T5e">hepatitis</a>, <a href="/facts/Aplastic_anaemia/8VMHLI6J">aplastic anaemia</a> and <a href="/facts/Pure_red_cell_aplasia/9em253bM">pure red cell aplasia</a>.</td></tr><tr><td><a href="/facts/Nilotinib/5dvWNTAb">Nilotinib</a></td><td>As per dasatinib</td><td>PO</td><td>D (Au)</td><td>As per imatinib</td></tr><tr><td><a href="/facts/Rituximab/q6BLRsS6">Rituximab</a></td><td>Monoclonal antibody against <a href="/facts/CD20/jaVQpvfy">CD20</a>, which is expressed on B lymphocytes</td><td>IV</td><td>C (Au)</td><td>Infusion-related reactions, infection, <a href="/facts/Neutropenia/qasEurVu">neutropenia</a>, reduced immunoglobulin levels, arrhythmias, <i>less commonly</i> anaemia, thrombocytopenia, angina, myocardial infarction, heart failure, and <i>rarely</i> <a href="/facts/Haemolytic_anaemia/qNz6wDct">haemolytic anaemia</a>, <a href="/facts/Aplastic_anaemia/8VMHLI6J">aplastic anaemia</a>, serum sickness, severe skin conditions, pulmonary infiltrates, <a href="/facts/Pneumonitis/Ls2TBRA7">pneumonitis</a>, cranial neuropathy (vision or hearing loss) and <a href="/facts/Progressive_multifocal_leucoencephalopathy/wl3Kbcsl">progressive multifocal leucoencephalopathy</a>.</td></tr><tr><td><a href="/facts/Sirolimus/9hdLP135">Sirolimus</a></td><td><a href="/facts/Mammalian_target_of_rapamycin/5l2dVa1p">mTOR</a> inhibitor, thereby reducing cytokine-induced lymphocyte proliferation.</td><td>PO</td><td>C (Au)</td><td><a href="/facts/Neutropenia/qasEurVu">Neutropenia</a>, <a href="/facts/Hypokalaemia/XvS1S7s6">hypokalaemia</a>, interstitial lung disease, <a href="/facts/Pericardial_effusion/JHybCM7I">pericardial effusion</a>, <a href="/facts/Pleural_effusion/34Y7pyFv">pleural effusion</a>, <i>less commonly</i> pulmonary haemorrhage, nephrotic syndrome, and <i>rarely</i> hepatotoxicity and <a href="/facts/Lymphoedema/BLCUBCvY">lymphoedema</a>.</td></tr><tr><td colspan="5">PO = Oral. IV = Intravenous. IM = Intramuscular. SC = Subcutaneous. IT = Intrathecal.<p>The preferred pregnancy category, above, is Australian, if available. If unavailable, an American one is substituted.</p></td></tr></tbody></table> <h2 id="prognosis">Prognosis</h2> <p>As of 2012<a href="https://en.wikipedia.org/w/index.php?title=Scleroderma&action=edit">[update]</a>, the five-year survival rate for systemic scleroderma was about 85%, whereas the 10-year survival rate was just under 70%.<a class="footnote-ref" id="fnref:75" href="#fn:75"><sup>75</sup></a> This varies according to the subtype; while localized scleroderma rarely results in death, the systemic form can, and the diffuse systemic form carries a worse prognosis than the limited form. The major scleroderma-related causes of death are: <a href="/facts/Pulmonary_hypertension/4848aBJl">pulmonary hypertension</a>, <a href="/facts/Pulmonary_fibrosis/9RVcVylE">pulmonary fibrosis</a>, and scleroderma renal crisis.<a class="footnote-ref" id="fnref:76" href="#fn:76"><sup>76</sup></a> People with scleroderma are also at a heightened risk for developing osteoporosis and for contracting cancer (especially liver, lung, haematologic, and bladder cancers).<a class="footnote-ref" id="fnref:77" href="#fn:77"><sup>77</sup></a> Scleroderma is also associated with an increased risk of cardiovascular disease.<a class="footnote-ref" id="fnref:78" href="#fn:78"><sup>78</sup></a> </p><p>According to a study of an Australian cohort, between 1985 and 2015, the average life expectancy of a person with scleroderma increased from 66 years to 74 years (the average Australian life expectancy increased from 76 to 82 years in the same period).<a class="footnote-ref" id="fnref:79" href="#fn:79"><sup>79</sup></a> </p> <h2 id="epidemiology">Epidemiology</h2> <p>Scleroderma most commonly first presents between the ages of 20 and 50 years, although any age group can be affected.<a class="footnote-ref" id="fnref:80" href="#fn:80"><sup>80</sup></a><a class="footnote-ref" id="fnref:81" href="#fn:81"><sup>81</sup></a> Women are four to nine times more likely to develop scleroderma than men.<a class="footnote-ref" id="fnref:82" href="#fn:82"><sup>82</sup></a> </p><p>This disease is found worldwide.<a class="footnote-ref" id="fnref:83" href="#fn:83"><sup>83</sup></a> In the United States, prevalence is estimated at 240 per million and the annual incidence of scleroderma is 19 per million people.<a class="footnote-ref" id="fnref:84" href="#fn:84"><sup>84</sup></a> Likewise in the United States, it is slightly more common in <a href="/facts/African_American/pTgcAdo8">African Americans</a> than in their white counterparts. Choctaw Native Americans are more likely than Americans of European descent to develop the type of scleroderma that affects internal organs.<a class="footnote-ref" id="fnref:85" href="#fn:85"><sup>85</sup></a> In <a href="/facts/Germany/paluuWBX">Germany</a>, the prevalence is between 10 and 150 per million people, and the annual incidence is between three and 28 per million people.<a class="footnote-ref" id="fnref:86" href="#fn:86"><sup>86</sup></a> In <a href="/facts/South_Australia/R7UdxV97">South Australia</a>, the annual incidence is 23 per million people, and the prevalence 233 per million people.<a class="footnote-ref" id="fnref:87" href="#fn:87"><sup>87</sup></a> </p> <h2 id="pregnancy">Pregnancy</h2> <p>Scleroderma in pregnancy is a complex situation; it increases the risk to both mother and child.<a class="footnote-ref" id="fnref:88" href="#fn:88"><sup>88</sup></a> Overall, scleroderma is associated with reduced fetal weight for gestational age.<a class="footnote-ref" id="fnref:89" href="#fn:89"><sup>89</sup></a> The treatment for scleroderma often includes known teratogens such as cyclophosphamide, methotrexate, <a href="/facts/Mycophenolate/kHpk0USt">mycophenolate</a>, etc., so careful avoidance of such drugs during pregnancy is advised.<a class="footnote-ref" id="fnref:90" href="#fn:90"><sup>90</sup></a> In these cases <a href="/facts/Hydroxychloroquine/cQkRhGIs">hydroxychloroquine</a> and low-dose <a href="/facts/Corticosteroid/jeL2QeIL">corticosteroids</a> might be used for disease control.<a class="footnote-ref" id="fnref:91" href="#fn:91"><sup>91</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Congenital_fascial_dystrophy/Esld4hs3">Congenital fascial dystrophy</a></li> <li><a href="/facts/Chi_Chi_DeVayne/RHKoRQQT">Chi Chi DeVayne</a>, (developed scleroderma in the years leading up to her death)</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="http://niams.nih.gov/Health_Info/Scleroderma/default.asp">Handout on Health: Scleroderma</a> – US National Institute of Arthritis and Musculoskeletal and Skin Diseases</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"Scleroderma". 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