Table 1 The final set of 14 recommendations based on both evidence from the literature and expert opinion
NoRecommendationStrength of recommendationReferences
ISSc-related digital vasculopathy (RP, digital ulcers)
1A meta-analysis on dihydropiridine-type calcium antagonists and one meta-analysis on prostanoids indicate that nifedipine and intravenous iloprost reduce the frequency and severity of SSc-RP attacksA 14 24
Dihydropiridine-type calcium antagonists, usually oral nifedipine, should be considered for first-line therapy for SSc-RP, and intravenous iloprost, or other available intravenous prostanoids for severe SSc-RP
2Two RCT indicate that intravenous prostanoids (particularly intravenous iloprost) are efficacious in healing digital ulcers in patients with SSc. Intravenous prostanoids (in particular iloprost) should be considered in the treatment of active digital ulcers in patients with SScA 21 22
3Bosentan has no confirmed efficacy in the treatment of active digital ulcers in SSc patients. Bosentan has confirmed efficacy in two high-quality RCT to prevent digital ulcers in diffuse SSc patients, in particular in those with multiple digital ulcersA 30 32
Bosentan should be considered in diffuse SSc with multiple digital ulcers after failure of calcium antagonists and, usually, prostanoid therapy
IISSc-PAH
4Two high-quality RCT indicate that bosentan improves exercise capacity, functional class and some haemodynamic measures in PAH. Bosentan should be strongly considered to treat SSc-PAHA/B 36 37
5Two high-quality RCT indicate that sitaxentan improves exercise capacity, functional class and some haemodynamic measures in PAH. At present, sitaxentan may also be considered to treat SSc-PAHA/B 39 47 48
6One high-quality RCT indicates that sildenafil improves exercise capacity, functional class and some haemodynamic measures in PAHA/B 52
Sildenafil may be considered to treat SSc-PAH
7One high-quality RCT indicates that continuous intravenous epoprostenol improves exercise capacity, functional class and haemodynamic measures in SSc-PAH. Sudden drug withdrawal may be life threateningA 29
Intravenous epoprostenol should be considered for the treatment of patients with severe SSc-PAH
IIISSc-related skin involvement
8Two RCT have shown that methotrexate improves skin score in early diffuse SSc. Positive effects on other organ manifestations have not been establishedA 60 61
Methotrexate may be considered for treatment of skin manifestations of early diffuse SSc
IVSSc-ILD
9In view of the results from two high-quality RCT and despite its known toxicity, cyclophosphamide should be considered for treatment of SSc-ILDA 62 63
VSRC
10Despite the lack of RCT, experts believe that ACE inhibitors should be used in the treatment of SRCC 64 66
11Four retrospective studies suggest that steroids are associated with a higher risk of SRC. Patients on steroids should be carefully monitored for blood pressure and renal functionC 67 70
VISSc-related gastrointestinal disease
12Despite the lack of specific RCT, experts believe that PPI should be used for the prevention of SSc-related gastro-oesophageal reflux, oesophageal ulcers and stricturesB 71 72
13Despite the lack of specific RCT, experts believe that prokinetic drugs should be used for the management of SSc-related symptomatic motility disturbances (dysphagia, GORD, early satiety, bloating, pseudo-obstruction, etc)C 73 80
14Despite the lack of specific RCT, experts believe that, when malabsorption is caused by bacterial overgrowth, rotating antibiotics may be useful in SSc patientsD
  • ACE, angiotensin-converting enzyme; GORD, gastro-oesophageal reflux disease; PAH, pulmonary arterial hypertension; PPI, proton pump inhibitor; RCT, randomised controlled trial; RP, Raynaud’s phenomenon; SRC, scleroderma renal crisis; SSc, systemic sclerosis; SSc-ILD, SSc-related interstitial lung disease; SSc-PAH, SSc-related pulmonary arterial hypertension; SSc-RP, SSC-related Raynaud’s phenomenon.