Table 2.

Supportive treatment and perioperative significance. SIADH, syndrome of inappropriate antidiuretic hormone secretion; ACEi, angiotensin-converting enzyme inhibitors; TGF β, transforming growth factor beta; PDGF, platelet derived growth factor; TNF α, tumour necrosis factor alpha; cGMP, cyclic guanosine monophosphate; cAMP, cyclic adenosine monophosphate.

Drug and mechanism of action	Adverse effects
Skin and musculoskeletal
Skin thickening/restriction of joints
Methotrexate Mechanism Immunomodulator; inhibits dihydropholic acid reductase leading to impaired DNA synthesis and immune cells replication impairment.	Hepatic fibrosis (rare), bone marrow suppression (rare), acute pneumonitis (rare).
Mycophenolate mofetil Mechanism Immunomodulator; antimetabolite with antifibrotic role via lymphocytes (T and B) activation suppression and antibody production impairment.	Myelosuppression, pancytopenia, hepatotoxicity, increased risk infection.
Cyclophosphamide Mechanism Immunomodulator; cytotoxic effect on both resting and active lymphocytes (particularly T-helper and B cells).	Drug-induced cardiomyopathy, immunosuppression, haemorrhagic cystitis, pneumonitis, SIADH.
Steroids (e.g. prednisolone) Mechanism Immunomodulator; supresses lymphocytes, fibroblasts and antibody production.	Hypertension, diabetes, electrolyte imbalances, peptic ulcer disease, skin frailty, adrenal suppression.
Rituximab Mechanism Immunomodulator; induces killing of the CD20+ cells (lymphocytes B depletion).	Progressive multi-focal leucoencephalopathy, increased risk of infection including serious infections.
Finger ulcers
Phosphodiesterase 5 inhibitor (PDEI) (e.g. sildenafil) Mechanism Vasodilator; increases intracellular cGMP leading to vasodilatation.	Ischaemic optic neuropathy, ventricular function reduction, cerebral venous thrombosis. Risk of severe hypotension with gram-negative sepsis. Unpredictable effects when nitrates are co-administered.
Endothelin-1 receptor antagonists (ERAs) (e.g. bosentan) Mechanism Vasodilator and (?) antifibrotic role via competitive inhibition of endothelin-1 receptors; endothelin also plays a role in cell proliferation, fibrosis and inflammation.	May increase blood loss (vasoconstriction inhibition), negative lusitropic effect.
Reynaud's phenomenon
Calcium channel blockers	Reduces cardiac morbidity in non-cardiac surgery.
Fluoxetine Mechanism Vasodilator; selective serotonin uptake inhibitor; serotonin causes direct vasodilation through 5HT7 and 5HT2B receptors.	Bradycardia, coronary vasospasm, SIADH, platelet inhibition, prolonged bleeding times, cytochrome P450 inhibition
Angiotensin receptor blockers Mechanism Vasodilator; displacement of angiotensin II via competitive antagonism of the angiotensin II receptors.	Hyperkalaemia (dysrhythmias), renal impairment
Prostacyclin receptors analogues (e.g. epoprostenol) Mechanism Vasodilator and platelet aggregation/adhesion inhibitor; increases intracellular cAMP via action on the prostacyclin IP receptor.	May increase blood loss through vasodilation.
Interstitial lung disease
Mycophenolate mofetil	See above.
Cyclophosphamide	See above.
Azathioprine Mechanism Immunomodulator; purine synthesis inhibition leading to DNA/RNA synthesise inhibition affecting B and T cells.	Reduces the effect of atracurium, vecuronium and pancuronium.
Nintedanib Mechanism Antifibrotic and anti-inflammatory; reduces fibroblasts activity via inhibition of profibrotic mediators (PDGF, fibroblast growth factor, TGF-β and vascular endothelia growth factor).	Vomiting, gastrointestinal perforation, weight loss, arterial thromboembolism, myocardial infarction, bleeding, hypothyroidism, increased liver enzymes.
Pirfenidone Mechanism Antifibrotic and anti-inflammatory; reduces fibroblasts proliferation, collagen production and reduces the production of mediators such as TGF-β, TNF-α and IL-1β.	Gastroesophageal reflux disease, vomiting, photosensitivity, increase hepatic enzyme concentrations (high risk if a CYP1A2 inhibitor is being used concomitantly).
Rituximab	See above.
Tocilizumab Mechanism Immunomodulator; monoclonal antibody that inhibits competitively the IL-6 receptor leading to failure of inflammatory recruitment of B and T cells.	Mouth ulcers, gastrointestinal perforation, hypertension, increased risk of infections, malignancy, liver dysfunction.
Calcineurin inhibitors (e.g. cyclosporine, tacrolimus) Mechanism Immunomodulator; inhibits calcineurin enzyme leading to decreased T cell activation and signalling.	Used post lung transplant in some SSc patients. Associated with renal vasoconstriction and SRC.
Cardiac disease
Systolic dysfunction: ACEi	Hyperkalaemia (dysrhythmias), renal impairment.
Diastolic dysfunction: diuretics	Hypovolemia, electrolyte losses, dysrhythmias.
Cardiac resynchronisation therapy/pacemakers	May require preoperative reprogramming to avoid interference from diathermy.
Pulmonary arterial hypertension
ERAs, PDE5i, Prostacyclin analogues	See above.
Prostacyclin receptor agonists (e.g. selexipag) Mechanism Vasodilator and platelet aggregation/adhesion inhibitor; prostacyclin IP receptor agonism leading to vasodilatation, decreased cell proliferation and platelet aggregation inhibition.	Myalgia, anaemia, nasopharyngitis.
Anticoagulation	Ensure timely discontinuation or reversal.
Oesophageal disease
Proton pomp inhibitors	Hypomagnesaemia, hypocalcaemia.
H2 blockers	Confusion, pancreatitis, hepatitis, seizures.
Antiacids	Hypermagnesemia, milk-alkali syndrome, hypophosphataemia.
Gastric disease
Prokinetics	Risk of aspiration in patients who missed prokinetics or are not on them.
Scleroderma renal crisis
ACEi	See above.