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Overarching principles for management of systemic sclerosis) /E (Figure 1. 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Classification and initial risk assessment of each potential complication guides future treatment including overlap features and frequency of review. All cases should have baseline assessment of relevant organ systems, and in adults, high-risk cases require screening for concurrent cancer. Regular review with proactive detection and treatment of organ-based disease is central to long term management. Appreciation of the differences between clinical problems common to early and established disease is important. 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0 R /K [18] >> endobj 98 0 obj << /Type /StructElem /S /H5 /T (Neurological complications of SSc require multi-speciality management with careful exclusion of other relevant causes 1C Peripheral Sensory neuropathy of the feet is common 2C ) /E (Neurological complications of SSc require multi-speciality management with careful exclusion of other relevant causes 1C Peripheral Sensory neuropathy of the feet is common 2C ) /Pg 8 0 R /K [4] >> endobj 99 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 100 0 obj << /Type /StructElem /S /H3 /T (ILD) /E (ILD) /Pg 8 0 R /K [19] >> endobj 101 0 obj << /Type /StructElem /S /H5 /T (MMF is recommended as first line treatment with rituximab or cyclophosphamide i.v. as alternative 1B Consider adding rituximab or tocilizumab to MMF for progressive disease 2C Nintedanib recommended for progressive pulmonary fibrosis 1B) /E (MMF is recommended as first line treatment with rituximab or cyclophosphamide i.v. as alternative 1B Consider adding rituximab or tocilizumab to MMF for progressive disease 2C Nintedanib recommended for progressive pulmonary fibrosis 1B) /Pg 8 0 R /K [11] >> endobj 102 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 103 0 obj << /Type /StructElem /S /H3 /T (PAH) /E (PAH) /Pg 8 0 R /K [20] >> endobj 104 0 obj << /Type /StructElem /S /H5 /T (PAH diagnosis by right heart catheter and treatment 1A initiated by a designated Pulmonary Hypertension Centres 1B Anticoagulation is not recommended in PAH-SSc 1B) /E (PAH diagnosis by right heart catheter and treatment 1A initiated by a designated Pulmonary Hypertension Centres 1B Anticoagulation is not recommended in PAH-SSc 1B) /Pg 8 0 R /K [12] >> endobj 105 0 obj << /Type /StructElem /S /H4 /T (Renal) /E (Renal) /Pg 8 0 R /K [21] >> endobj 106 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 107 0 obj << /Type /StructElem /S /H5 /T (ACEi should be used in all cases of diagnosed SRC 1A Glucocorticoid treatment avoided in adult SSc due increased SRC risk 1A Renal biopsy should be considered when diagnosis uncertain 1C Referral for renal transplantation in cases without significant renal recovery 1B) /E (ACEi should be used in all cases of diagnosed SRC 1A Glucocorticoid treatment avoided in adult SSc due increased SRC risk 1A Renal biopsy should be considered when diagnosis uncertain 1C Referral for renal transplantation in cases without significant renal recovery 1B) /Pg 8 0 R /K [13] >> endobj 108 0 obj << /Type /StructElem /S /H4 /T (Skin) /E (Skin) /Pg 8 0 R /K [22] >> endobj 109 0 obj << /Type /StructElem /S /H5 /T (MMF is first line treatment for skin fibrosis in dcSSc 1C Antihistamines are often used for itch 2C Options for telangiectasia include skin camouflage, pulsed dye laser or intense pulsed light therapy 2C) /E (MMF is first line treatment for skin fibrosis in dcSSc 1C Antihistamines are often used for itch 2C Options for telangiectasia include skin camouflage, pulsed dye laser or intense pulsed light therapy 2C) /Pg 8 0 R /K [6] >> endobj 110 0 obj << /Type /StructElem /S /H4 /T (Musculoskeletal) /E (Musculoskeletal) /Pg 8 0 R /K [23] >> endobj 111 0 obj << /Type /StructElem /S /H5 /T (Musculoskeletal manifestations of SSc may benefit from immunomodulatory treatments given for other complications 1C) /E (Musculoskeletal manifestations of SSc may benefit from immunomodulatory treatments given for other complications 1C) /Pg 8 0 R /K [7] >> endobj 112 0 obj << /Type /StructElem /S /H4 /T (Digital ulcers) /E (Digital ulcers) /Pg 8 0 R /K [17] >> endobj 113 0 obj << /Type /StructElem /S /H5 /T (Severe digital vasculopathy with new tissue necrosis or critical ischaemia requires urgent clinical assessment 1C Sildenafil \(or tadalafil\) as 1st line agent in DU healing and secondary prevention and bosentan as second line treatment 1C Expert opinion supports use of IV prostanoids in promoting DU healing 1C ) /E (Severe digital vasculopathy with new tissue necrosis or critical ischaemia requires urgent clinical assessment 1C Sildenafil \(or tadalafil\) as 1st line agent in DU healing and secondary prevention and bosentan as second line treatment 1C Expert opinion supports use of IV prostanoids in promoting DU healing 1C ) /Pg 8 0 R /K [28] >> endobj 114 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 115 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 116 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 117 0 obj << /Type /StructElem /S /H4 /T (Fatigue and Health related Quality of Life) /E (Fatigue and Health related Quality of Life) /Pg 8 0 R /K [3] >> endobj 118 0 obj << /Type /StructElem /S /H5 /T (Physical and occupational therapy may improve quality of life, pain, and fatigue 2C) /E (Physical and occupational therapy may improve quality of life, pain, and fatigue 2C) /Pg 8 0 R /K [8 9] >> endobj 119 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 120 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 121 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 122 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 123 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 124 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 125 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 126 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R /K [1] >> endobj 127 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 128 0 obj << /Type /StructElem /S /H4 /T (Cardiac) /E (Cardiac) /Pg 8 0 R /K [29] >> endobj 129 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 130 0 obj << /Type /StructElem /S /H5 /T (Immunosuppression with MMF for SSc- pHI when investigation suggests myocardial inflammation 2C Glucocorticoids and other bDMARDs may be added if appropriate and/or cyclophosphamide 2C) /E (Immunosuppression with MMF for SSc- pHI when investigation suggests myocardial inflammation 2C Glucocorticoids and other bDMARDs may be added if appropriate and/or cyclophosphamide 2C) /Pg 8 0 R /K [10] >> endobj 131 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 132 0 obj << /Type /StructElem /S /H4 /T (Gastrointestinal) /E (Gastrointestinal) /Pg 8 0 R /K [30] >> endobj 133 0 obj << /Type /StructElem /S /H5 /T (PPI and/or H2 receptor antagonists for reflux 1C Parenteral nutrition for severe malnutrition 1B Intermittent or rotational antibiotics SIBO 2B Anti-diarrhoeal agents or laxatives 2B Surgical intervention should be avoided 1C) /E (PPI and/or H2 receptor antagonists for reflux 1C Parenteral nutrition for severe malnutrition 1B Intermittent or rotational antibiotics SIBO 2B Anti-diarrhoeal agents or laxatives 2B Surgical intervention should be avoided 1C) /Pg 8 0 R /K [5] >> endobj 134 0 obj << /Type /StructElem /S /H4 /T (Reproductive health) /E (Reproductive health) /Pg 8 0 R /K [14] >> endobj 135 0 obj << /Type /StructElem /S /H5 /T (Sexual dysfunction needs engagement of gynaecology, urology, and sexual health clinical services 1C For planned pregnancy in SSc identify significant organ dysfunction and discontinue harmful medication 1C Pregnancy management requires integrated multi-disciplinary care 2C) /E (Sexual dysfunction needs engagement of gynaecology, urology, and sexual health clinical services 1C For planned pregnancy in SSc identify significant organ dysfunction and discontinue harmful medication 1C Pregnancy management requires integrated multi-disciplinary care 2C) /Pg 8 0 R /K [2] >> endobj 136 0 obj << /Type /StructElem /S /H4 /T <5261796E6175649073207068656E6F6D656E6F6E> /E <5261796E6175649073207068656E6F6D656E6F6E> /Pg 8 0 R /K [15] >> endobj 137 0 obj << /Type /StructElem /S /H5 /T (Calcium channel blockers and other vasodilators may be considered in management of SSc-RP 1B Expert opinion suggests that PDE5i are effective as 2nd line agent for refractory SSc-RP 1B For rescue therapy in severe SSc-RP IV prostanoids may be considered 1C) /E (Calcium channel blockers and other vasodilators may be considered in management of SSc-RP 1B Expert opinion suggests that PDE5i are effective as 2nd line agent for refractory SSc-RP 1B For rescue therapy in severe SSc-RP IV prostanoids may be considered 1C) /Pg 8 0 R /K [16] >> endobj 138 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 139 0 obj << /Type /StructElem /S /H5 /T (Life-threatening complications ) /E (Life-threatening complications ) /Pg 8 0 R /K [25] >> endobj 140 0 obj << /Type /StructElem /S /Figure /P 37 0 R /Pg 8 0 R >> endobj 141 0 obj << /Type /StructElem /S /H2 /T (KEY:) /E (KEY:) /Pg 8 0 R /K [24] >> endobj 142 0 obj << /Type /StructElem /S /H5 /T (Non-lethal morbidity that has major impact on people with SSc) /E (Non-lethal morbidity that has major impact on people with SSc) /Pg 8 0 R /K [26] >> endobj 143 0 obj << /Type /StructElem /S /P /ActualText (Systemic sclerosis organ-based complications each require specific treatment. Key recommendations based upon evidence review and expert opinion are summarised in this schematic. See full guideline text and supplementary material for more detail. Strength of recommendation \(1 or 2\), quality of supporting evidence/level of evidence \(A, B, C\) is indicated for each statement. See full guideline for more detail.) /Pg 8 0 R /K [31] >> endobj 144 0 obj << /Type /StructElem /S /P /ActualText (dcSSc = diffuse cutaneous Systemic Sclerosis; SSc-pHI = primary systemic sclerosis cardiac involvement; ACEi = Angiotensin Converting Enzyme inhibitor; HRQoL = Health Related Quality of Life; sGS = soluble Guanylate Cyclase; SRC = Scleroderma Renal Crisis; PPI - Proton Pump Inhibitor; SIBO = Small Intestinal Bacterial Overgrowth, PAH = Pulmonary Arterial Hypertension.) /Pg 8 0 R /K [32] >> endobj 145 0 obj << /ca 1 /BM /Normal >> endobj 146 0 obj << /ca .2 /BM /Normal >> endobj 147 0 obj << /ca .48 /BM /Normal >> endobj 148 0 obj << /ca .15 /BM /Normal >> endobj 149 0 obj << /Length 293 /N 3 /Filter /FlateDecode >> stream x}JԂ(28hiRpi"VSAOHStspu+.c(#ARx@?F[V[G@`*dK$O.K o@6`O,f'˘O asx0A6vf 8{c7%opZ:u Q 0Q٣F *Ԑ(SDGACAajgrx]s PxM cvhO> stream x]ү;9c GTPL`Vs#F1!3b@A@ D@Q9# }avz'03EQDEQDEQDEQDEQDEQDEQDEQDEQDEQDEQDEQDEQDA4UQDR4$;DovѽrZ#:IQ=sMd#"(T vԤ21aXe WPAL (Q7вtCȏc"Gt#0n!}ՃHAJA݉y=&pD*NRz4ܘ'^cH$ „ ZDAËy&v_U@̕ŃEfqqzbӽ2_YlXYI4У%z%2|+c ˥USNQ5-j1{~HzDϯ0XZD"ސƓ58 b>+ħSr|c~}} c148{dpd ,-mC\*L.J^&hݕ¤w'-+GItP7rO~Lj혰,ILq󈈕y\x*P}+3S8XzB{3 c8X[tU(fAu6Ji0 "dc4x q]O;ׅm >btX18eČ?#:ᐺFo5ub'QEف&9xi&W soO?2roB)dUF<t< qJSQ!1!1K>λ@MoDOy\z,ฝ0]_泪h Jx :e"R&t]E 'A$FhEp*wE'U e56(M^=h P%S}[#1ȹ>E p 6{kp+ƑS 4 ۥ%܁ , 582n<0 X-W@~4ئdrvIc\Qn, }YDzE!?mY rw; pؽd352F G0fHXH8H jRĩpi ^`Ҹ#]7Ѝ5v~:РW KŇD;FgNϲM sU 땅-< (M|!G>_'Χ3)3tc]uo"ɞ5cgaha34P_O"j $pK zoմ>FA+4S!Y&Q/JFmuϳf4ZٷpwA@ML4&;&h1M) ܁`g+3j 5y¨W|(` L,8~${;ntǠ!;11FOzCϽ)WI8^ :󓄽_2  {e)+ڳ4B' M@SWgHm̳~1-D2$MYQ# 18޸ϡhX0c= SRqq>.lnX 4`ЧҐȣ V1>50dٚ<2bCriT&F"S[Drv5,Ap9'ir ImjJr3U%0gC1~Eq/-Н`.mM\= glfdLEL>SMM5;/oMvwCiIݳ;RB_sm9Pho8648 OVɬbp}9bލO$q*C!h1x,Nt\Su[6?ʞvYvF e*p^6*olh5&_bydr=rvÚԯA 7,S&+znɭݸa0ɋJJP!Jh&Fq7fħ| x6@aJ Nxz9+7 0:1ݏoHZMzP&B'|StLfL*?fCP{1 i 0N6cO]fy\rh.ЫUb]vc qBC|o52]d}[#`du<~ٮ-򁣜 Uh.ߒm5{vaɪ ~m]ڻw O& Buƍ5>\I6~ĜM{vyC?YP83>-n5)PC>  y=(0k%p g0ǻ/c\TXS @:oAv+P7ײCl4jPe1rD1~v?W.tpL}g.|Ku52|U-u5lɏT. u͡ tݲ,srrKeg"ϰ^5/KM|958 0ڋyzGzƓ|Ƶ0H$jȆa?<]#B)&2ǃۼm7s~N~"@Yҫdˏ )$y-`Td=u=_,i4ݝ TJ2rA)ؘbA͡ވ2tHfˆS|=rTL IHt/BҠ(\).ؚ0 {x|.$1 z #nWsmMYNq-=5D a;=ܠWT xAm6&i1YdWGePEI..@YF*@̛W u=?n'(Kv7qf\z=\+,,\ݸq~}1 v9ŠVmW~@$/̓ Ӵp7qK$p0TU%0ni99wRnmtBtNO6Up?h>S 5프YWK ;oLݱw֧?%iO%fpf 䞿51vxVb2{ָ 'tկغُjX O(A;92^p*Xtԇc {*kI߲KQ`>VLT6 N׵òR z\A*tnk:d'$lUKusN'Por!aOôq  7'lଲ5 ^S"W: ALyIj?'Uz2u`;k' KD v {zV [P-;nɕ׻15"g=׼޳IۼzM*a}-nمB̰t;YNqܱ?>k{`lj##=W[y $.\Ҡ;M%`Vi}B(1UUIg~5GI(yQgBEly-iII.$T~C,Z\Ըq4kg⪲_-ׯlgoN3<u{y >˿IXΎ-)ސ dZlɕ$vNڠٹvsXÙ}q9*SL҉fnqPR!`L?{˟${dhL% @Ik\7LOȆ1ޚ3q ,%)gְ.өEs;2SƏ% LJm%' wʮMvVwmгq=eL PltQ(>;H\27(v)Í/RKjtesz::Ja ;ɝ Sm͂vBшԤRg[f&nBP_kp`nf3ORzYŒ :s[BO9[ıiOCd) xNKk蔚$A3擜>,Z1=x6+Rx_ B:mszop|013CCU輐i@e00j DI;tM^c Rא+'pڵ{>f|xK3 =jԯgSflnڴM$Rd5xC,AqPH>vHbεBaBϣԇZuLOGtNj'1pa#EK {YAQ@;{qC,6jAoGvzd.J'9LO#{Z~{:B/N"/;6j ,6󵔠WXؖ󜫘C0ʖbp 7xؒIza`V%UDhQ]ɏ mC!wTW_7yw*ho|Lw x z֞GvPYΡ>(\`nqXB xC.⟘R̋~dgZ?OԆu n]EƪIzf7@d@)Z!HOOC_PfK=gp8)_<YPz'ěBi:3Y$@e+ A^âR>ypP-!mYX*T:69@P*p*IVy^t}LXb/"! : 7/whFQ@ϴ'ޑ >A^g *.fHt<c! onf=( P7ʇ? 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