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{{Scleroderma}}
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==Overview==
==Overview==
The mainstay of treatment for scleroderma is medical therapy. Pharmacologic medical therapies for scleroderma include [[topical]] [[tacrolimus]] for [[morphea]], [[methotrexate]] for diffuse [[sclerosis]] of the [[skin]], [[minocycline]] for [[calcinosis cutis]], [[nifedipine]] for [[Raynaud's phenomenon]], [[captopril]] for scleroderma [[renal]] crisis, treatment of [[gastroesophageal reflux disease]] and [[pulmonary hypertension]]. Localized [[phototherapy]] with [[ultraviolet light]] is preferred for the treatment of [[morphea]].


==Medical Therapy==
==Medical Therapy==
Pharmacologic medical therapies for scleroderma include [[topical]] [[tacrolimus]] for [[morphea]], [[methotrexate]] for diffuse [[sclerosis]] of the [[skin]], [[minocycline]] for [[calcinosis cutis]], [[nifedipine]] for [[Raynaud's phenomenon]], [[captopril]] for scleroderma [[renal]] crisis, treatment of [[gastroesophageal reflux disease]] and [[pulmonary hypertension]]. Localized [[phototherapy]] with [[ultraviolet light]] is preferred for the treatment of [[morphea]].


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.<ref>{{cite journal |author=Oliver GF, Winkelmann RK |title=The current treatment of scleroderma |journal=Drugs |volume=37 |issue=1 |pages=87-96 |year=1989 |pmid=2651089 |doi=}}</ref>
===Scleroderma===


Digital ulcerations and pulmonary hypertension can be helped by [[prostacyclin]] (iloprost) infusion. Iloprost being a drug which increases blood flow by relaxing the arterial wall.<ref>{{cite journal |author=Zandman-Goddard G, Tweezer-Zaks N, Shoenfeld Y |title=New therapeutic strategies for systemic sclerosis--a critical analysis of the literature |journal=Clin. Dev. Immunol. |volume=12 |issue=3 |pages=165-73 |year=2005 |pmid=16295521 |doi=}}</ref>
* '''1 Treatment of skin manifestations'''
** 1.1  '''Limited cutaneous scleroderma-morphea'''
*** 1.1.1 '''Adult'''
**** Preferred regimen (1): localized [[phototherapy]] with [[ultraviolet light]] for 15 to 20 treatments<ref name="pmid21645943">{{cite journal |vauthors=Zwischenberger BA, Jacobe HT |title=A systematic review of morphea treatments and therapeutic algorithm |journal=J. Am. Acad. Dermatol. |volume=65 |issue=5 |pages=925–41 |date=November 2011 |pmid=21645943 |doi=10.1016/j.jaad.2010.09.006 |url=}}</ref>   
**** Preferred regimen (2): [[topical]] [[tacrolimus]] 0.1% [[ointment]] twice daily<ref name="pmid19120765">{{cite journal |vauthors=Stefanaki C, Stefanaki K, Kontochristopoulos G, Antoniou C, Stratigos A, Nicolaidou E, Gregoriou S, Katsambas A |title=Topical tacrolimus 0.1% ointment in the treatment of localized scleroderma. An open label clinical and histological study |journal=J. Dermatol. |volume=35 |issue=11 |pages=712–8 |date=November 2008 |pmid=19120765 |doi=10.1111/j.1346-8138.2008.00552.x |url=}}</ref>
**** Preferred regimen (3): [[methotrexate]] 15 mg PO once weekly, maximum dose is 25 mg per week<ref name="pmid11407694">{{cite journal |vauthors=Pope JE, Bellamy N, Seibold JR, Baron M, Ellman M, Carette S, Smith CD, Chalmers IM, Hong P, O'Hanlon D, Kaminska E, Markland J, Sibley J, Catoggio L, Furst DE |title=A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma |journal=Arthritis Rheum. |volume=44 |issue=6 |pages=1351–8 |date=June 2001 |pmid=11407694 |doi=10.1002/1529-0131(200106)44:6<1351::AID-ART227>3.0.CO;2-I |url=}}</ref>
**** Alternative regimen (1): [[topical]] [[calcipotriene]] 0.005% [[ointment]] twice daily 
**** Alternative regimen (2): [[mycophenolate]] mofetil 500 mg PO q12h for 7-14 days, then increase to maintenance dose of 500 mg to 1500 mg PO q12h as tolerated<ref name="pmid28188239" />
** 1.2 '''Diffuse sclerosis of the skin'''
*** 1.2.1 '''Adult'''
**** Preferred regimen (1): [[methotrexate]] 15 mg PO once weekly, maximum dose is 25 mg per week<ref name="pmid8624641">{{cite journal |vauthors=van den Hoogen FH, Boerbooms AM, Swaak AJ, Rasker JJ, van Lier HJ, van de Putte LB |title=Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial |journal=Br. J. Rheumatol. |volume=35 |issue=4 |pages=364–72 |date=April 1996 |pmid=8624641 |doi= |url=}}</ref> 
**** Alternative regimen (1): [[mycophenolate]] mofetil 500 mg PO q12h for 7-14 days, then increase to maintenance dose of 500 mg to 1500 mg PO q12h as tolerated<ref name="pmid28188239">{{cite journal |vauthors=Herrick AL, Pan X, Peytrignet S, Lunt M, Hesselstrand R, Mouthon L, Silman A, Brown E, Czirják L, Distler JHW, Distler O, Fligelstone K, Gregory WJ, Ochiel R, Vonk M, Ancuţa C, Ong VH, Farge D, Hudson M, Matucci-Cerinic M, Balbir-Gurman A, Midtvedt Ø, Jordan AC, Jobanputra P, Stevens W, Moinzadeh P, Hall FC, Agard C, Anderson ME, Diot E, Madhok R, Akil M, Buch MH, Chung L, Damjanov N, Gunawardena H, Lanyon P, Ahmad Y, Chakravarty K, Jacobsen S, MacGregor AJ, McHugh N, Müller-Ladner U, Riemekasten G, Becker M, Roddy J, Carreira PE, Fauchais AL, Hachulla E, Hamilton J, İnanç M, McLaren JS, van Laar JM, Pathare S, Proudman S, Rudin A, Sahhar J, Coppere B, Serratrice C, Sheeran T, Veale DJ, Grange C, Trad GS, Denton CP |title=Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS) |journal=Ann. Rheum. Dis. |volume=76 |issue=7 |pages=1207–1218 |date=July 2017 |pmid=28188239 |pmc=5530354 |doi=10.1136/annrheumdis-2016-210503 |url=}}</ref>
**** Alternative regimen (2): [[cyclophosphamide]] ≤ 2 mg/kg PO daily<ref name="pmid16790698">{{cite journal |vauthors=Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M |title=Cyclophosphamide versus placebo in scleroderma lung disease |journal=N. Engl. J. Med. |volume=354 |issue=25 |pages=2655–66 |date=June 2006 |pmid=16790698 |doi=10.1056/NEJMoa055120 |url=}}</ref>
** 1.3 '''Calcinosis'''
*** 1.3.1 '''Adult'''
**** Preferred regimen (1): [[minocycline]] 50-100 mg PO q12h for 6-12 weeks<ref name="pmid12594118">{{cite journal |vauthors=Robertson LP, Marshall RW, Hickling P |title=Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline |journal=Ann. Rheum. Dis. |volume=62 |issue=3 |pages=267–9 |date=March 2003 |pmid=12594118 |pmc=1754479 |doi= |url=}}</ref>
**** Alternative regimen (1): [[infliximab]]<ref name="pmid24255162">{{cite journal |vauthors=Tosounidou S, MacDonald H, Situnayake D |title=Successful treatment of calcinosis with infliximab in a patient with systemic sclerosis/myositis overlap syndrome |journal=Rheumatology (Oxford) |volume=53 |issue=5 |pages=960–1 |date=May 2014 |pmid=24255162 |doi=10.1093/rheumatology/ket365 |url=}}</ref>
**** Alternative regimen (2): [[rituximab]]<ref name="pmid23179007">{{cite journal |vauthors=de Paula DR, Klem FB, Lorencetti PG, Muller C, Azevedo VF |title=Rituximab-induced regression of CREST-related calcinosis |journal=Clin. Rheumatol. |volume=32 |issue=2 |pages=281–3 |date=February 2013 |pmid=23179007 |doi=10.1007/s10067-012-2124-z |url=}}</ref>
** 1.4 '''Raynaud's phenomenon'''
*** 1.4.1 '''Adult'''
**** Oral regimen
***** Preferred regimen (1): [[nifedipine]] 30-120 mg (extended release) PO once daily<ref name="pmid26914257">{{cite journal |vauthors=Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL |title=Calcium channel blockers for primary Raynaud's phenomenon |journal=Cochrane Database Syst Rev |volume=2 |issue= |pages=CD002069 |date=February 2016 |pmid=26914257 |doi=10.1002/14651858.CD002069.pub5 |url=}}</ref>
***** Preferred regimen (2): [[amlodipine]] 5-20 mg PO once daily<ref name="pmid8508292">{{cite journal |vauthors=La Civita L, Pitaro N, Rossi M, Gambini I, Giuggioli D, Cini G, Ferri C |title=Amlodipine in the treatment of Raynaud's phenomenon |journal=Br. J. Rheumatol. |volume=32 |issue=6 |pages=524–5 |date=June 1993 |pmid=8508292 |doi= |url=}}</ref>
***** Alternative regimen (1): [[sildenafil]] 20 mg PO once daily, then increase to a maximum dose of 20 mg PO q8h<ref name="pmid23426043">{{cite journal |vauthors=Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL |title=Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials |journal=Ann. Rheum. Dis. |volume=72 |issue=10 |pages=1696–9 |date=October 2013 |pmid=23426043 |doi=10.1136/annrheumdis-2012-202836 |url=}}</ref>
***** Alternative regimen (2): [[losartan]] 50 mg PO once daily<ref name="pmid10616013">{{cite journal |vauthors=Dziadzio M, Denton CP, Smith R, Howell K, Blann A, Bowers E, Black CM |title=Losartan therapy for Raynaud's phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial |journal=Arthritis Rheum. |volume=42 |issue=12 |pages=2646–55 |date=December 1999 |pmid=10616013 |doi=10.1002/1529-0131(199912)42:12<2646::AID-ANR21>3.0.CO;2-T |url=}}</ref>
**** Topical regimen
***** Alternative regimen (3): Topical [[nitroglycerin]] applied to affected digits<ref name="pmid19248104">{{cite journal |vauthors=Chung L, Shapiro L, Fiorentino D, Baron M, Shanahan J, Sule S, Hsu V, Rothfield N, Steen V, Martin RW, Smith E, Mayes M, Simms R, Pope J, Kahaleh B, Csuka ME, Gruber B, Collier D, Sweiss N, Gilbert A, Dechow FJ, Gregory J, Wigley FM |title=MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: a randomized, controlled trial |journal=Arthritis Rheum. |volume=60 |issue=3 |pages=870–7 |date=March 2009 |pmid=19248104 |doi=10.1002/art.24351 |url=}}</ref>  
* 2 '''Treatment of gastrointestinal manifestations'''
** 2.1 '''Gastroesophageal reflux symptoms'''
:::To review the treatment for gastroesophageal reflux symptoms [[Gastroesophageal reflux disease medical therapy |click here.]]


===Pharmacotherapy===
* 3 '''Treatment of pulmonary manifestations'''
** 3.1 '''Pulmonary arterial hypertension'''
:::To review the treatment for pulmonary arterial hypertension [[Pulmonary hypertension medical therapy |click here.]]


====Topical/symptomatic====
* 4 '''Treatment of renal manifestations'''
** 4.1 '''Scleroderma renal crisis'''
*** 4.1.1 '''Adult'''
**** Oral regimen
***** Preferred regimen (1): [[captopril]] 12.5-25 mg PO q12h<ref name="pmid17601770">{{cite journal |vauthors=Penn H, Howie AJ, Kingdon EJ, Bunn CC, Stratton RJ, Black CM, Burns A, Denton CP |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=}}</ref>
***** Alternative regimen (1): [[enalapril]] 5mg PO once daily
***** Alternative regimen (2): [[ramipril]] 2.5 mg PO once daily


Topical treatment for the skin changes of scleroderma do not alter the disease course, but may improve pain and ulceration. A range of [[NSAID]]s (nonsteroidal anti-inflammatory drugs) can be used to ease painful symptoms, such as [[naproxen]]. There is limited benefit from [[glucocorticoid|steroids]] such as prednisone. 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.<ref name=Zandberg>{{cite journal |author=Zandman-Goddard G, Tweezer-Zaks N, Shoenfeld Y |title=New therapeutic strategies for systemic sclerosis--a critical analysis of the literature |journal=Clin. Dev. Immunol. |volume=12 |issue=3 |pages=165–73 |year=2005 |pmid=16295521 |doi=}} {{PMC|2275417}}</ref> The skin tightness may be treated systemically with [[methotrexate]] and [[cyclosporin]].<ref name=Zandberg/> If there is esophageal dysmotility (in CREST or systemic sclerosis), care must be taken with NSAIDs as they are gastric irritants, and so a [[proton pump inhibitor]] (PPI) such as [[omeprazole]] can be given in conjunction.
==References==
{{Reflist|2}}


====Kidney disease====
{{WH}}
{{WS}}


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 inhibitor]]s. The benefit of ACE inhibitors extends even to those who have to commence [[hemodialysis|dialysis]] to treat their kidney disease, and may give sufficient benefit to allow the discontinuation of renal replacement therapy.<ref name=Zandberg/> [[ACE inhibitors]] are also used for [[prophylaxis]],<ref name=jimenez/><ref name=steen11033587/> and [[renal transplantation]]. 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>Pham PT, Pham PC, Danovitch GM, Gritsch HA, Singer J, Wallace WD, Hayashi R, Wilkinson AH. Predictors and risk factors for recurrent scleroderma renal crisis in the kidney allograft: case report and review of the literature. Am J Transplant. 2005 Oct;5(10):2565-9. PMID 16162209.</ref>
[[Category:Up-To-Date]]
 
[[Category:Medicine]]
====Lung disease and pulmonary hypertension====
[[Category:Dermatology]]
 
[[Category:Rheumatology]]
Active alveolitis is often treated with pulses of [[cyclophosphamide]], often together with a small dose of steroids. The benefit of this intervention is modest.<ref>{{cite journal |author=Tashkin DP, Elashoff R, Clements PJ, ''et al'' |title=Cyclophosphamide versus placebo in scleroderma lung disease |journal=N. Engl. J. Med. |volume=354 |issue=25 |pages=2655–66 |year=2006 |month=June |pmid=16790698 |doi=10.1056/NEJMoa055120 |url=http://content.nejm.org/cgi/content/full/354/25/2655}}</ref><ref>{{cite journal |author=Hoyles RK, Ellis RW, Wellsbury J, ''et al'' |title=A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma |journal=Arthritis Rheum. |volume=54 |issue=12 |pages=3962–70 |year=2006 |month=December |pmid=17133610 |doi=10.1002/art.22204 | url=http://www3.interscience.wiley.com/cgi-bin/fulltext/113490260/HTMLSTART}}</ref>
 
Pulmonary hypertension may be treated with [[epoprostenol]], [[bosentan]] and possibly aerolized iloprost.<ref name=Zandberg/>
 
==References==
{{Reflist|2}}

Latest revision as of 00:06, 30 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: M. Khurram Afzal, MD [2]

Overview

The mainstay of treatment for scleroderma is medical therapy. Pharmacologic medical therapies for scleroderma include topical tacrolimus for morphea, methotrexate for diffuse sclerosis of the skin, minocycline for calcinosis cutis, nifedipine for Raynaud's phenomenon, captopril for scleroderma renal crisis, treatment of gastroesophageal reflux disease and pulmonary hypertension. Localized phototherapy with ultraviolet light is preferred for the treatment of morphea.

Medical Therapy

Pharmacologic medical therapies for scleroderma include topical tacrolimus for morphea, methotrexate for diffuse sclerosis of the skin, minocycline for calcinosis cutis, nifedipine for Raynaud's phenomenon, captopril for scleroderma renal crisis, treatment of gastroesophageal reflux disease and pulmonary hypertension. Localized phototherapy with ultraviolet light is preferred for the treatment of morphea.

Scleroderma

  • 1 Treatment of skin manifestations
    • 1.1 Limited cutaneous scleroderma-morphea
    • 1.2 Diffuse sclerosis of the skin
      • 1.2.1 Adult
        • Preferred regimen (1): methotrexate 15 mg PO once weekly, maximum dose is 25 mg per week[5]
        • Alternative regimen (1): mycophenolate mofetil 500 mg PO q12h for 7-14 days, then increase to maintenance dose of 500 mg to 1500 mg PO q12h as tolerated[4]
        • Alternative regimen (2): cyclophosphamide ≤ 2 mg/kg PO daily[6]
    • 1.3 Calcinosis
    • 1.4 Raynaud's phenomenon
      • 1.4.1 Adult
        • Oral regimen
          • Preferred regimen (1): nifedipine 30-120 mg (extended release) PO once daily[10]
          • Preferred regimen (2): amlodipine 5-20 mg PO once daily[11]
          • Alternative regimen (1): sildenafil 20 mg PO once daily, then increase to a maximum dose of 20 mg PO q8h[12]
          • Alternative regimen (2): losartan 50 mg PO once daily[13]
        • Topical regimen
  • 2 Treatment of gastrointestinal manifestations
    • 2.1 Gastroesophageal reflux symptoms
To review the treatment for gastroesophageal reflux symptoms click here.
  • 3 Treatment of pulmonary manifestations
    • 3.1 Pulmonary arterial hypertension
To review the treatment for pulmonary arterial hypertension click here.
  • 4 Treatment of renal manifestations
    • 4.1 Scleroderma renal crisis
      • 4.1.1 Adult
        • Oral regimen
          • Preferred regimen (1): captopril 12.5-25 mg PO q12h[15]
          • Alternative regimen (1): enalapril 5mg PO once daily
          • Alternative regimen (2): ramipril 2.5 mg PO once daily

References

  1. ↑ Zwischenberger BA, Jacobe HT (November 2011). "A systematic review of morphea treatments and therapeutic algorithm". J. Am. Acad. Dermatol. 65 (5): 925–41. doi:10.1016/j.jaad.2010.09.006. PMID 21645943.
  2. ↑ Stefanaki C, Stefanaki K, Kontochristopoulos G, Antoniou C, Stratigos A, Nicolaidou E, Gregoriou S, Katsambas A (November 2008). "Topical tacrolimus 0.1% ointment in the treatment of localized scleroderma. An open label clinical and histological study". J. Dermatol. 35 (11): 712–8. doi:10.1111/j.1346-8138.2008.00552.x. PMID 19120765.
  3. ↑ Pope JE, Bellamy N, Seibold JR, Baron M, Ellman M, Carette S, Smith CD, Chalmers IM, Hong P, O'Hanlon D, Kaminska E, Markland J, Sibley J, Catoggio L, Furst DE (June 2001). "A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma". Arthritis Rheum. 44 (6): 1351–8. doi:10.1002/1529-0131(200106)44:6<1351::AID-ART227>3.0.CO;2-I. PMID 11407694.
  4. ↑ 4.0 4.1 Herrick AL, Pan X, Peytrignet S, Lunt M, Hesselstrand R, Mouthon L, Silman A, Brown E, Czirják L, Distler J, Distler O, Fligelstone K, Gregory WJ, Ochiel R, Vonk M, Ancuţa C, Ong VH, Farge D, Hudson M, Matucci-Cerinic M, Balbir-Gurman A, Midtvedt Ø, Jordan AC, Jobanputra P, Stevens W, Moinzadeh P, Hall FC, Agard C, Anderson ME, Diot E, Madhok R, Akil M, Buch MH, Chung L, Damjanov N, Gunawardena H, Lanyon P, Ahmad Y, Chakravarty K, Jacobsen S, MacGregor AJ, McHugh N, Müller-Ladner U, Riemekasten G, Becker M, Roddy J, Carreira PE, Fauchais AL, Hachulla E, Hamilton J, İnanç M, McLaren JS, van Laar JM, Pathare S, Proudman S, Rudin A, Sahhar J, Coppere B, Serratrice C, Sheeran T, Veale DJ, Grange C, Trad GS, Denton CP (July 2017). "Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)". Ann. Rheum. Dis. 76 (7): 1207–1218. doi:10.1136/annrheumdis-2016-210503. PMC 5530354. PMID 28188239. Vancouver style error: initials (help)
  5. ↑ van den Hoogen FH, Boerbooms AM, Swaak AJ, Rasker JJ, van Lier HJ, van de Putte LB (April 1996). "Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial". Br. J. Rheumatol. 35 (4): 364–72. PMID 8624641.
  6. ↑ Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M (June 2006). "Cyclophosphamide versus placebo in scleroderma lung disease". N. Engl. J. Med. 354 (25): 2655–66. doi:10.1056/NEJMoa055120. PMID 16790698.
  7. ↑ Robertson LP, Marshall RW, Hickling P (March 2003). "Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline". Ann. Rheum. Dis. 62 (3): 267–9. PMC 1754479. PMID 12594118.
  8. ↑ Tosounidou S, MacDonald H, Situnayake D (May 2014). "Successful treatment of calcinosis with infliximab in a patient with systemic sclerosis/myositis overlap syndrome". Rheumatology (Oxford). 53 (5): 960–1. doi:10.1093/rheumatology/ket365. PMID 24255162.
  9. ↑ de Paula DR, Klem FB, Lorencetti PG, Muller C, Azevedo VF (February 2013). "Rituximab-induced regression of CREST-related calcinosis". Clin. Rheumatol. 32 (2): 281–3. doi:10.1007/s10067-012-2124-z. PMID 23179007.
  10. ↑ Ennis H, Hughes M, Anderson ME, Wilkinson J, Herrick AL (February 2016). "Calcium channel blockers for primary Raynaud's phenomenon". Cochrane Database Syst Rev. 2: CD002069. doi:10.1002/14651858.CD002069.pub5. PMID 26914257.
  11. ↑ La Civita L, Pitaro N, Rossi M, Gambini I, Giuggioli D, Cini G, Ferri C (June 1993). "Amlodipine in the treatment of Raynaud's phenomenon". Br. J. Rheumatol. 32 (6): 524–5. PMID 8508292.
  12. ↑ Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL (October 2013). "Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials". Ann. Rheum. Dis. 72 (10): 1696–9. doi:10.1136/annrheumdis-2012-202836. PMID 23426043.
  13. ↑ Dziadzio M, Denton CP, Smith R, Howell K, Blann A, Bowers E, Black CM (December 1999). "Losartan therapy for Raynaud's phenomenon and scleroderma: clinical and biochemical findings in a fifteen-week, randomized, parallel-group, controlled trial". Arthritis Rheum. 42 (12): 2646–55. doi:10.1002/1529-0131(199912)42:12<2646::AID-ANR21>3.0.CO;2-T. PMID 10616013.
  14. ↑ Chung L, Shapiro L, Fiorentino D, Baron M, Shanahan J, Sule S, Hsu V, Rothfield N, Steen V, Martin RW, Smith E, Mayes M, Simms R, Pope J, Kahaleh B, Csuka ME, Gruber B, Collier D, Sweiss N, Gilbert A, Dechow FJ, Gregory J, Wigley FM (March 2009). "MQX-503, a novel formulation of nitroglycerin, improves the severity of Raynaud's phenomenon: a randomized, controlled trial". Arthritis Rheum. 60 (3): 870–7. doi:10.1002/art.24351. PMID 19248104.
  15. ↑ Penn H, Howie AJ, Kingdon EJ, Bunn CC, Stratton RJ, Black CM, Burns A, Denton CP (August 2007). "Scleroderma renal crisis: patient characteristics and long-term outcomes". QJM. 100 (8): 485–94. doi:10.1093/qjmed/hcm052. PMID 17601770.

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