Editing Systemic scleroderma (section)

===Other organs===
Diffuse scleroderma can cause [[musculoskeletal system|musculoskeletal]], pulmonary, gastrointestinal, renal, and other complications.<ref name=Primer>{{cite book |author=Klippel, John H. |title=Primer On the Rheumatic Diseases 11ED |year=2020 |publisher=Arthritis Foundation |location=Atlanta, GA |isbn=978-1-912423-16-3}}</ref> Patients with greater cutaneous involvement are more likely to have involvement of the internal tissues and organs. Most patients (over 80%) have vascular symptoms and Raynaud's phenomenon, which leads to attacks of discoloration of the hands and feet in response to cold. Raynaud's normally affects the fingers and toes. Systemic scleroderma and Raynaud's can cause painful ulcers on the fingers or toes, which are known as digital ulcers. Calcinosis (deposition of calcium in lumps under the skin) is also common in systemic scleroderma, and is often seen near the elbows, knees, or other [[joints]].<ref>{{cite web |title=Limited Scleroderma |url=https://www.mayoclinic.org/diseases-conditions/crest-syndrome/symptoms-causes/syc-20355535 |website=www.mayoclinic.org |publisher=Mayo Clinic |access-date=6 June 2019}}</ref>

;Musculoskeletal
The first joint symptoms that patients with scleroderma have are typically nonspecific [[arthralgia|joint pains]], which can lead to [[arthritis]], or cause discomfort in [[tenosynovitis|tendons]] or [[myalgia|muscles]].<ref name=Primer/>  Joint mobility, especially of the small joints of the hand, may be restricted by calcinosis or skin thickening.<ref>{{cite journal |vauthors=Valentini G, Black C |title=Systemic sclerosis |journal=Best Practice & Research. Clinical Rheumatology |volume=16 |issue=5 |pages=807–16 |year=2002 |pmid=12473275| doi = 10.1053/berh.2002.0258}}</ref>  Patients may develop muscle weakness, or [[myopathy]], either from the disease or its treatments.<ref>{{cite journal |vauthors=Olsen NJ, King LE, Park JH |title=Muscle abnormalities in scleroderma |journal=Rheum. Dis. Clin. North Am. |volume=22 |issue=4 |pages=783–96 |year=1996 |pmid=8923596| doi = 10.1016/S0889-857X(05)70301-X}}</ref>

;Lungs
Some impairment in lung function is almost universally seen in patients with diffuse scleroderma on [[pulmonary function test]]ing,<ref>{{cite journal |author=Steen VD |title=The lung in systemic sclerosis |journal=Journal of Clinical Rheumatology |volume=11 |issue=1 |pages=40–6 |year=2005 |pmid=16357695 |doi=10.1097/01.rhu.0000152147.38706.db}}</ref> but it does not necessarily cause symptoms, such as shortness of breath.  Some patients can develop [[pulmonary hypertension]], or elevation in the pressures of the [[pulmonary arteries]]. This can be progressive, and can lead to right-sided [[heart failure]]. The earliest manifestation of this may be a decreased [[diffusion capacity]] on pulmonary function testing.{{citation needed|date=October 2020}} Other pulmonary complications in more advanced disease include [[aspiration pneumonia]], [[pulmonary hemorrhage]] and [[pneumothorax]].<ref name=Primer/>

;Digestive tract
[[Image:Peptic stricture.png|right|thumb|200px|[[Gastroscopy|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.]]
Diffuse scleroderma can affect any part of the gastrointestinal tract.<ref name=Sallam>{{cite journal |vauthors=Sallam H, McNearney TA, Chen JD |title=Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma) |journal=Aliment. Pharmacol. Ther. |volume=23 |issue=6 |pages=691–712 |year=2006 |pmid=16556171 |doi=10.1111/j.1365-2036.2006.02804.x|s2cid=46188776 |doi-access=free }}</ref>  The most common manifestation in the esophagus is reflux [[esophagitis]], which may be complicated by [[esophageal stricture]]s or benign narrowing of the esophagus.<ref name=Rose>{{cite journal |vauthors=Rose S, Young MA, Reynolds JC |title=Gastrointestinal manifestations of scleroderma |journal=Gastroenterol. Clin. North Am. |volume=27 |issue=3 |pages=563–94 |year=1998 |pmid=9891698 | doi = 10.1016/S0889-8553(05)70021-2}}</ref>  This is best initially treated with [[proton pump inhibitor]]s for acid suppression,<ref>{{cite journal |vauthors=Hendel L, Hage E, Hendel J, Stentoft P |title=Omeprazole in the long-term treatment of severe gastro-oesophageal reflux disease in patients with systemic sclerosis |journal=Aliment. Pharmacol. Ther. |volume=6 |issue=5 |pages=565–77 |year=1992 |pmid=1420748 |doi=10.1111/j.1365-2036.1992.tb00571.x|s2cid=31418099 }}</ref> but may require [[esophageal dilatation|bougie dilatation]] in the case of stricture.<ref name=Sallam/>

Scleroderma can decrease [[motility]] anywhere in the gastrointestinal tract.<ref name=Sallam/> The most common source of decreased motility is the esophagus and the lower esophageal sphincter, leading to dysphagia and chest pain. 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 [[gastroesophageal reflux disease]]. 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 dilatation{{citation needed|date=December 2020}}.

In patients with neuromuscular disorders, particularly progressive systemic sclerosis and visceral myopathy, the [[duodenum]] is frequently involved.<ref>{{Cite journal |last=Tandaipan |first=Jose Luis |last2=Castellví |first2=Ivan |date=April 2020 |title=Systemic sclerosis and gastrointestinal involvement |url=https://linkinghub.elsevier.com/retrieve/pii/S2444440520300017 |journal=Revista Colombiana de Reumatología (English Edition) |language=en |volume=27 |pages=44–54 |doi=10.1016/j.rcreue.2019.12.003|url-access=subscription }}</ref> Dilatation may occur, which is often more pronounced in the second, third, and fourth parts. The dilated duodenum may be slow to empty, and the grossly dilated, atonic organ may produce a sump effect.{{citation needed|date=December 2020}}

The [[small intestine]] can also become involved, leading to [[bacterial overgrowth]] and [[malabsorption]] of [[bile salts]], [[fat]]s, [[carbohydrate]]s, [[protein]]s, and [[vitamin]]s. The [[colon (anatomy)|colon]] can be involved, and can cause [[Ogilvie's syndrome|pseudo-obstruction]] or [[ischemic colitis]].<ref name=Primer/>

Rarer complications include [[pneumatosis cystoides intestinalis]], or gas pockets in the bowel wall, [[diverticulosis|wide-mouthed diverticula]] in the colon and esophagus, and [[cirrhosis|liver fibrosis]].  Patients with severe gastrointestinal involvement can become profoundly [[malnutrition|malnourished]].<ref name=Rose/>

Scleroderma may also be associated with [[gastric antral vascular ectasia]], also known as "watermelon stomach". This is a condition in which atypical blood vessels proliferate, usually in a radially symmetric pattern around the [[pylorus]] of the stomach. It can be a cause of [[upper gastrointestinal bleeding]] or [[iron deficiency anemia|iron-deficiency anemia]] in patients with scleroderma.<ref name=Rose/>

;Kidneys
[[Image:Thrombotic microangiopathy - very high mag.jpg|thumb|[[Micrograph]] showing [[thrombotic microangiopathy]], the [[histomorphology|histomorphologic]] finding seen in scleroderma renal crisis, [[kidney biopsy]], [[PAS stain]]]]
Kidney involvement, in scleroderma, is considered a poor prognostic factor and frequently a cause of death.<ref>{{cite journal |vauthors=Ruangjutipopan S, Kasitanon N, Louthrenoo W, Sukitawut W, Wichainun R |title=Causes of death and poor survival prognostic factors in thai patients with systemic sclerosis |journal=Journal of the Medical Association of Thailand |volume=85 |issue=11 |pages=1204–9 |year=2002 |pmid=12546318 }}</ref>

The most important clinical complication of scleroderma involving the kidney is scleroderma renal crisis (SRC), the  symptoms of which are [[malignant hypertension]] (high blood pressure with evidence of acute organ damage), [[Renin|hyperreninemia]] (high renin levels), [[azotemia]] (kidney failure with accumulation of waste products in the blood), and [[microangiopathic hemolytic anemia]] (destruction of red blood cells).<ref>{{cite journal |vauthors=Steen VD, Mayes MD, Merkel PA |title=Assessment of kidney involvement |journal=Clin. Exp. Rheumatol. |volume=21 |issue=3 Suppl 29 |pages=S29–31 |year=2003 |pmid=12889219 }}</ref> Apart from the high blood pressure, [[hematuria]] (blood in the urine) and [[proteinuria]] (protein loss in the urine) may be indicative of SRC.<ref>{{cite journal |author=Steen VD |title=Renal involvement in systemic sclerosis |journal=Clin. Dermatol. |volume=12 |issue=2 |pages=253–8 |year=1994 |pmid=8076263 | doi = 10.1016/S0738-081X(94)90329-8|s2cid=906790 }}</ref>

In the past, SRC was almost uniformly fatal.<ref name=steen>{{cite journal |author=Steen VD |title=Scleroderma renal crisis |journal=Rheum. Dis. Clin. North Am. |volume=29 |issue=2 |pages=315–33 |year=2003 |pmid=12841297| doi = 10.1016/S0889-857X(03)00016-4}}</ref> While outcomes have improved significantly with the use of [[ACE inhibitors]],<ref>{{cite journal |vauthors=Rhew EY, Barr WG |title=Scleroderma renal crisis: new insights and developments |journal=Current Rheumatology Reports |volume=6 |issue=2 |pages=129–36 |year=2004 |pmid=15016343| doi = 10.1007/s11926-004-0057-5|s2cid=37453739 }}</ref><ref name="steen11033587">{{cite journal|year=2000|title=Long-term outcomes of scleroderma renal crisis|url=http://aramis.stanford.edu/downloads/2000SteenAIM600.pdf|journal=Ann. Intern. Med.|volume=133|issue=8|pages=600–3|doi=10.7326/0003-4819-133-8-200010170-00010|pmid=11033587|archive-url=https://web.archive.org/web/20150619184802/http://aramis.stanford.edu/downloads/2000SteenAIM600.pdf|archive-date=19 June 2015|vauthors=Steen VD, Medsger TA|citeseerx=10.1.1.494.6389|s2cid=29564540}}</ref> the prognosis is often guarded, as a significant number of patients are refractory to treatment and develop [[kidney failure]]. About 7–9% of all diffuse cutaneous scleroderma patients develop renal crisis at some point in the course of their disease.<ref>{{Cite journal|last1=Turk|first1=Matthew|last2=Pope|first2=Janet E.|date=July 2016|title=The Frequency of Scleroderma Renal Crisis over Time: A Metaanalysis|journal=The Journal of Rheumatology|volume=43|issue=7|pages=1350–1355|doi=10.3899/jrheum.151353|issn=0315-162X|pmid=27134252|s2cid=23093684}}</ref><ref name="Denton">{{cite journal |vauthors=Denton C, Lapadula G, Mouthon L, Müller-Ladner U | year = 2009 | title = Renal complications and scleroderma renal crisis | journal = Rheumatology | volume = 48 | pages = 32–35 | doi = 10.1093/rheumatology/ken483 | pmid = 19487221 | doi-access = free }}</ref> Patients who have rapid skin involvement have the highest risk of renal complications.<ref name=jimenez>Jimenez S, Koenig AS. [http://www.emedicine.com/MED/topic2076.htm Scleroderma]. eMedicine.com. Accessed: May 22, 2006.</ref> It is most common in diffuse cutaneous scleroderma, and is often associated with antibodies against [[RNA polymerase]] (in 59% of cases). 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  dialysis more likely to be needed.<ref>{{cite journal  |vauthors=Penn H, Howie AJ, Kingdon EJ, etal |title=Scleroderma renal crisis: patient characteristics and long-term outcomes |journal=QJM |volume=100 |issue=8 |pages=485–94 |date=August 2007 |pmid=17601770 |doi=10.1093/qjmed/hcm052 |url=http://qjmed.oxfordjournals.org/cgi/content/full/100/8/485|doi-access=free }}</ref>

Treatments for SRC include ACE inhibitors. Prophylactic use of ACE inhibitors is currently not recommended, as recent data suggest a poorer prognosis in patient treated with these drugs prior to the development of renal crisis.<ref>{{cite journal|last1=Hudson|first1=M|last2=Baron|first2=M|last3=Tatibouet|first3=S|last4=Furst|first4=DE|last5=Khanna|first5=D|last6=International Scleroderma Renal Crisis Study|first6=Investigators|title=Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis-results from the International Scleroderma Renal Crisis Survey|journal=Seminars in Arthritis and Rheumatism|date=April 2014|volume=43|issue=5|pages=666–72|doi=10.1016/j.semarthrit.2013.09.008|pmid=24176729}}</ref>{{MEDRS|date=November 2014}} 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.<ref>{{cite journal  |vauthors=Pham PT, Pham PC, Danovitch GM, etal |title=Predictors and risk factors for recurrent scleroderma renal crisis in the kidney allograft: case report and review of the literature |journal=Am. J. Transplant. |volume=5 |issue=10 |pages=2565–9 |date=October 2005 |pmid=16162209 |doi=10.1111/j.1600-6143.2005.01035.x |s2cid=36783555 |doi-access=free }}</ref>