{"orpha":90291,"name":"Systemic sclerosis","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Systemic scleroderma"],"definition":"Systemic sclerosis (SSc) is a generalized disorder of small arteries, microvessels and connective tissue, characterized by fibrosis and vascular obliteration in the skin and organs, particularly the lungs, heart, and digestive tract. There are two main subsets of SSc: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). A third subset of SSc has also been observed, called limited Systemic Sclerosis (lSSc) or systemic sclerosis sine scleroderma.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-90291/","orphanet_url":"https://www.orpha.net/en/disease/detail/90291","names":{"fr":{"name":"Sclérodermie systémique","definition":"La sclérodermie systémique (ScS) est une affection généralisée des artérioles, des microvaisseaux et du tissu conjonctif, caractérisée par une fibrose et une oblitération vasculaire dans la peau et d'autres organes, en particulier les poumons, le coeur et l'appareil digestif. Il existe deux formes principales de ScS : la forme cutanée diffuse (ScScd) et la forme cutanée limitée (ScScl). Une troisième forme appelée sclérose systémique limitée (ScSl ou sclérodermie systémique sans sclérose cutanée) a aussi été observée."},"de":{"name":"Systemische Sklerodermie","synonyms":["Sklerose, systemische"],"definition":"Die Systemische Sklerodermie (SSc) ist eine generalisierte Erkrankung der kleinen Arterien, der Mikrogefäße und des Bindegewebes und gekennzeichnet durch Fibrose und Gefäßobliterationen in der Haut und anderen Organen, besonders in Lunge, Herz und Verdauungstrakt. Zwei hauptsächliche Untergruppen der SSc sind die diffuse kutane SSc (dcSSc) und die limitierte kutane SSc (lcSSc) (s. diese Termini). Als dritte Untergruppe wurde die limitierte Systemische Sklerodermie (lSSc) oder Scleroderma sine scleroderma (s. diese Termini) beschrieben."},"es":{"name":"Esclerosis sistémica","synonyms":["Esclerodermia sistémica"],"definition":"La esclerosis sistémica (SSc) es un trastorno generalizado de las arterias pequeñas, microvasos y tejido conectivo, caracterizado por fibrosis y obliteración vascular en piel y órganos, particularmente en los pulmones, el corazón y el tracto digestivo. Existen dos formas principales: SSc cutánea difusa (dcSSc) y SSc cutánea limitada (lcSSc). Se ha observado también una tercera forma de SSc llamada esclerosis sistémica limitada (lSSc) o esclerosis sistémica sin esclerodermia."},"it":{"name":"Sclerosi sistemica","definition":"La sclerosi sistemica (SSc) è una malattia generalizzata delle piccole arterie, dei microvasi e del tessuto connettivo, caratterizzata da fibrosi e obliterazione vascolare della cute e di altri organi, in particolare i polmoni, il cuore e il tubo digerente. Si conoscono due sottotipi di SSc: la SSc cutanea diffusa (dcSSc) e la SSc cutanea limitata (lcSSc) (si vedano questi termini). È stato descritto un terso sottoitpo di SSc, noto come sclerosi sistemica limitata (lSSc) o sclerosi sistemica sine sclerodermia (si vedano questi termini)."},"nl":{"name":"Systemische sclerose","synonyms":["Systemische sclerodermie"],"definition":"Systemische sclerose (SSc) is een gegeneraliseerde aandoening van kleine slagaders, microvaten en bindweefsel, gekenmerkt door fibrose en vasculaire obliteratie in huid en organen, voornamelijk long, hart en spijsverteringsstelsel. Er zijn twee grote subtypes van SSc: diffuse cutane SSc (dcSSc) en gelimiteerde cutane SSc (lcSSc). Er werd ook een derde subtype van SSc waargenomen, genaamd gelimiteerde systemische sclerose (lSSc) of systemische sclerose zonder sclerodermie."},"pt":{"name":"Esclerose sistémica","synonyms":["Esclerodermia sistémica"],"definition":"A esclerose sistémica (ES) é um distúrbio generalizado das pequenas artérias, microvasos e do tecido conjuntivo caracterizada por fibrose e obliteração vascular na pele e órgãos, especialmente pulmões, coração e aparelho digestivo. Há dois subtipos principais de SSc: a SSc cutânea difusa (dcSSc) e a SSc cutânea limitada (lcSSc) (ver estes termos). Um terceiro subtipo de SSc foi também descrito, chamada esclerose sistémica limitada (lSSc) ou esclerodermia sine escleroderma (ver estes termos)."},"pl":{"name":"Twardzina układowa","synonyms":["Systemic scleroderma"],"definition":"Twardzina układowa jest uogólnioną chorobą małych tętnic, mikronaczyń i tkanki łącznej, charakteryzuje się zwłóknieniem i obliteracją naczyniową w skórze i narządach, szczególnie płuc, serca i układu pokarmowego. Wyróżnia się dwa główne podtypy twardziny układowej: rozsianą skórną i ograniczoną do skóry (zobacz te terminy). Obserwuje się również trzeci podtyp, nazywany ograniczoną twardziną układową albo układową twardziną bez sklerodermii"},"cs":{"name":"Systémová skleróza","synonyms":["Systémová sklerodermie"]},"uk":{"name":"Системний склероз","synonyms":["Системна склеродермія"],"definition":"Systemic sclerosis (SSc) is a generalized disorder of small arteries, microvessels and connective tissue, characterized by fibrosis and vascular obliteration in the skin and organs, particularly the lungs, heart, and digestive tract. There are two main subsets of SSc: diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) (see these terms). A third subset of SSc has also been observed, called limited Systemic Sclerosis (lSSc) or systemic sclerosis sine scleroderma (see these terms)."},"zh":{"name":"系统性硬化症","synonyms":["系统性硬皮病"]},"tr":{"name":"Sistemik skleroz","synonyms":["Sistemik skleroderma"]}},"xrefs":[{"source":"OMIM","code":"181750","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"M34.0","qualifier":"BTNT","icd_relation":"specific","validated":true},{"source":"ICD-10","code":"M34.1","qualifier":"BTNT","icd_relation":"specific","validated":true},{"source":"ICD-10","code":"M34.2","qualifier":"BTNT","icd_relation":"specific","validated":true},{"source":"ICD-10","code":"M34.8","qualifier":"BTNT","icd_relation":"specific","validated":true},{"source":"ICD-10","code":"M34.9","qualifier":"BTNT","icd_relation":"specific","validated":true},{"source":"ICD-11","code":"4A42","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"1084365812"},{"source":"MONDO","code":"0005100","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D012595","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0036421","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"9748","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10042953","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Referred to","orpha":93567,"name":"OBSOLETE: Pediatric systemic sclerosis","status":"inactive"}],"preferential_parent":{"orpha":98023,"name":"Rare systemic or rheumatologic disease"},"parents":[{"orpha":217720,"name":"Non-familial restrictive cardiomyopathy","classifications":[146]},{"orpha":567558,"name":"Non-genetic systemic disease with glomerulopathy as a major feature","classifications":[188,233]},{"orpha":280373,"name":"Rare pediatric systemic disease","classifications":[231]},{"orpha":101944,"name":"Rare pulmonary disease","classifications":[184]},{"orpha":801,"name":"Scleroderma","classifications":[187]},{"orpha":182228,"name":"Systemic autoimmune disease","classifications":[196]}],"children":[{"orpha":220393,"name":"Diffuse cutaneous systemic sclerosis","type":"Clinical subtype"},{"orpha":220402,"name":"Limited cutaneous systemic sclerosis","type":"Clinical subtype"},{"orpha":220407,"name":"Limited systemic sclerosis","type":"Clinical subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"CAV1","name":"caveolin 1","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Assessed","source":"22402147[PMID]","hgnc":"1527","ensembl":"ENSG00000105974","omim":"601047","loci":["7q31.2"],"via":{"orpha":220393,"name":"Diffuse cutaneous systemic sclerosis"}},{"symbol":"CAV1","name":"caveolin 1","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Assessed","source":"22402147[PMID]","hgnc":"1527","ensembl":"ENSG00000105974","omim":"601047","loci":["7q31.2"],"via":{"orpha":220402,"name":"Limited cutaneous systemic sclerosis"}},{"symbol":"CCN2","name":"cellular communication network factor 2","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Not yet assessed","source":null,"hgnc":"2500","ensembl":"ENSG00000118523","omim":"121009","loci":["6q23.2"],"via":{"orpha":220393,"name":"Diffuse cutaneous systemic sclerosis"}},{"symbol":"CCN2","name":"cellular communication network factor 2","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Not yet assessed","source":null,"hgnc":"2500","ensembl":"ENSG00000118523","omim":"121009","loci":["6q23.2"],"via":{"orpha":220402,"name":"Limited cutaneous systemic sclerosis"}},{"symbol":"CCR6","name":"C-C motif chemokine receptor 6","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Assessed","source":"23983073[PMID]","hgnc":"1607","ensembl":"ENSG00000112486","omim":"601835","loci":["6q27"],"via":{"orpha":220393,"name":"Diffuse cutaneous systemic sclerosis"}},{"symbol":"CCR6","name":"C-C motif chemokine receptor 6","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Assessed","source":"23983073[PMID]","hgnc":"1607","ensembl":"ENSG00000112486","omim":"601835","loci":["6q27"],"via":{"orpha":220402,"name":"Limited cutaneous systemic sclerosis"}},{"symbol":"HLA-DRB1","name":"major histocompatibility complex, class II, DR beta 1","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Not yet assessed","source":null,"hgnc":"4948","ensembl":"ENSG00000196126","omim":"142857","loci":["6p21.32"],"via":{"orpha":220393,"name":"Diffuse cutaneous systemic sclerosis"}},{"symbol":"HLA-DRB1","name":"major histocompatibility complex, class II, DR beta 1","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Not yet assessed","source":null,"hgnc":"4948","ensembl":"ENSG00000196126","omim":"142857","loci":["6p21.32"],"via":{"orpha":220402,"name":"Limited cutaneous systemic sclerosis"}},{"symbol":"HLA-DRB1","name":"major histocompatibility complex, class II, DR beta 1","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Not yet assessed","source":null,"hgnc":"4948","ensembl":"ENSG00000196126","omim":"142857","loci":["6p21.32"],"via":{"orpha":220407,"name":"Limited systemic sclerosis"}},{"symbol":"IRF5","name":"interferon regulatory factor 5","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Assessed","source":"23372721[PMID]","hgnc":"6120","ensembl":"ENSG00000128604","omim":"607218","loci":["7q32.1"],"via":{"orpha":220393,"name":"Diffuse cutaneous systemic sclerosis"}},{"symbol":"IRF5","name":"interferon regulatory factor 5","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Assessed","source":"23372721[PMID]","hgnc":"6120","ensembl":"ENSG00000128604","omim":"607218","loci":["7q32.1"],"via":{"orpha":220402,"name":"Limited cutaneous systemic sclerosis"}},{"symbol":"KIAA0319L","name":"KIAA0319 like","gene_type":"gene with protein product","association":"Major susceptibility factor in","status":"Not yet assessed","source":"23740937[PMID]","hgnc":"30071","ensembl":"ENSG00000142687","omim":"613535","loci":["1p34.3"],"via":{"orpha":220402,"name":"Limited cutaneous systemic sclerosis"}}],"inheritance":["Multigenic/multifactorial","Not applicable"],"onset":["Adult"],"prevalence":[{"type":"Point prevalence","qualification":"Value and class","class":"1-5 / 10 000","value":15.4,"area":"Europe","status":"Validated","source":"[EXPERT]"},{"type":"Annual incidence","qualification":"Value and class","class":">1 / 1000","value":230.0,"area":"Spain","status":"Validated","source":"18794710[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-5 / 10 000","value":27.7,"area":"Spain","status":"Validated","source":"18794710[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":8.8,"area":"United Kingdom","status":"Validated","source":"14872101[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-5 / 10 000","value":17.3,"area":"France","status":"Validated","source":"ORPHANET_15213329[PMID]_23290691[PMID]_26816302[PMID]"},{"type":"Annual incidence","qualification":"Value and class","class":">1 / 1000","value":110.0,"area":"Greece","status":"Validated","source":"15846586[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-5 / 10 000","value":15.4,"area":"Greece","status":"Validated","source":"15846586[PMID]"},{"type":"Annual incidence","qualification":"Value and class","class":"6-9 / 10 000","value":72.0,"area":"Japan","status":"Validated","source":"1796818[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":4.6,"area":"Japan","status":"Not yet validated","source":"1796818[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-5 / 10 000","value":30.0,"area":"United States","status":"Validated","source":"18430269[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-5 / 10 000","value":44.3,"area":"Canada","status":"Validated","source":"19248123[PMID]"},{"type":"Annual incidence","qualification":"Value and class","class":">1 / 1000","value":204.0,"area":"Australia","status":"Validated","source":"11456035[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-5 / 10 000","value":23.3,"area":"Australia","status":"Validated","source":"11456035[PMID]"},{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 100 000","value":1.09,"area":"Taiwan, Province of China","status":"Validated","source":"21388247[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":5.63,"area":"Taiwan, Province of China","status":"Validated","source":"21388247[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-5 / 10 000","value":22.2,"area":"Italy","status":"Validated","source":"33596949[PMID]"},{"type":"Annual incidence","qualification":"Value and class","class":"1-9 / 100 000","value":1.7,"area":"Italy","status":"Validated","source":"33596949[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-12-11","source":"28792092[PMID]_31498665[PMID]_26577237[PMID]","terms":[{"hpo":"HP:0011024","label":"Abnormality of the gastrointestinal tract","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003493","label":"Antinuclear antibody positivity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002829","label":"Arthralgia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0031359","label":"Cutaneous sclerotic plaque","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003326","label":"Myalgia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030880","label":"Raynaud phenomenon","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001072","label":"Thickened skin","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002031","label":"Abnormal esophagus morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006261","label":"Abnormal phalangeal joint morphology of the hand","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006530","label":"Abnormal pulmonary interstitial morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000077","label":"Abnormality of the kidney","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006121","label":"Acral ulceration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034089","label":"Anti-B23 antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034088","label":"Anti-Ku antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0033560","label":"Anti-PM-Scl antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034085","label":"Anti-PM-Scl100 antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034086","label":"Anti-PM-Scl75 antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0033038","label":"Anti-RNA-polymerase-III-autoantibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034093","label":"Anti-Ro52/TRIM21 antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034090","label":"Anti-RuvBL1/2 antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034081","label":"Anti-Th/To antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034087","label":"Anti-U11/U12 RNP antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034080","label":"Anti-U3 RNP antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034094","label":"Anti-angiotensin receptor type-1 antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034117","label":"Anti-angiotensin-converting enzyme 2 antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034082","label":"Anti-bicaudal D2 antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0033394","label":"Anti-carbonic anhydrase II antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034078","label":"Anti-centromere protein A antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034079","label":"Anti-centromere protein B antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034095","label":"Anti-endothelin-1 type A receptor antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034083","label":"Anti-nucleolus-organizing region antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:4000170","label":"Anti-platelet antigen antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034091","label":"Anti-platelet derived growth factor receptor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030859","label":"Anti-topoisomerase I antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:4000171","label":"Anti-voltage-gated potassium channel antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030873","label":"Anticentromere antibody positivity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025520","label":"Calcinosis cutis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031293","label":"Digital pitting scar","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031917","label":"Digital ulcer","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025131","label":"Finger swelling","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007400","label":"Irregular hyperpigmentation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001386","label":"Joint swelling","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001232","label":"Nail bed telangiectasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000160","label":"Narrow mouth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012531","label":"Pain","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002206","label":"Pulmonary fibrosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011838","label":"Sclerodactyly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005590","label":"Spotty hypopigmentation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001009","label":"Telangiectasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002250","label":"Abnormal large intestine morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002577","label":"Abnormal stomach morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011799","label":"Abnormality of facial soft tissue","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002244","label":"Abnormality of the small intestine","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001919","label":"Acute kidney injury","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012592","label":"Albuminuria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001596","label":"Alopecia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001369","label":"Arthritis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100580","label":"Barrett esophagus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002607","label":"Bowel incontinence","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012622","label":"Chronic kidney disease","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012185","label":"Constrictive median neuropathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002617","label":"Dilatation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002094","label":"Dyspnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001371","label":"Flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002604","label":"Gastrointestinal telangiectasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002578","label":"Gastroparesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000099","label":"Glomerulonephritis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000966","label":"Hypohidrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031329","label":"Interstitial cardiac fibrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002584","label":"Intestinal bleeding","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012819","label":"Myocarditis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009771","label":"Osteolytic defects of the phalanges of the hand","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002754","label":"Osteomyelitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001701","label":"Pericarditis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000093","label":"Proteinuria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000989","label":"Pruritus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002092","label":"Pulmonary arterial hypertension","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001581","label":"Recurrent skin infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000083","label":"Renal insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001708","label":"Right ventricular failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001279","label":"Syncope","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100758","label":"Gangrene","frequency":"Very rare (<4-1%)","criteria":null}]}}