BSR Guidelines for Systemic Sclerosis Management Save

The British Society for Rheumatology (BSR) has updated its 2015 guidelines for the management of patients with sytemic sclerosis (SSc) based on published evidence, systematic literature review and expert opinion. 

The guideline addresses general management, treatment of organ-based complications, including cardiopulmonary, renal and gastrointestinal tract manifestations. This guideline does not address localized scleroderma (morphea) and of ‘scleroderma-like’ conditions (e.g. scleredema, scleromyxedema, fasciitis, nephrogenic systemic fibrosis).  Selected recommendations from this article include:

Diagnosis and classification 

• Clinical diagnosis of SSc should be guided by validated classification criteria 
• Skin subset and SSc associated autoantibody subset should be used to stratify for risk of specific organ-based complications 
• Assessment of nailfold microcirculation (capillaroscopy) should be performed as part of initial SSc assessment 

Treatment of Early Diffuse SSc

• Early dcSSc is defined by disease duration from first non-RP manifestation of <3 years, although cases may show improvement in skin from 18 months, and some have clinical features of skin worsening and progression over >5 years
• All early dcSSc cases should be considered for immunosuppression with MMF as treatment for skin fibrosis. Alternatively, MTX may be used for skin fibrosis 
• Multi-disciplinary and multi-speciality care should be available. All early dcSSc cases should be assessed in a specialist centre for consideration of clinical trials and specialized treatments including biological agents such as rituximab or tocilizumab and autologous haematopoietic stem cell transplant (AHSCT) 
• All paediatric SSc should be managed in a tertiary paediatric rheumatology service with multi-disciplinary and multi-speciality input 

Treatment of organ-based complications of SSc

Interstitial Lung Disease in SSc (SSc-ILD):

• All SSc cases should be screened for ILD with baseline chest high-resolution CT (HRCT) and pulmonary function tests (PFTs) 
• PFTs should be repeated every 3–6 months in recently diagnosed SSc (first 3–5 years) and considered every 6–12 months thereafter 
• Chest HRCT should be repeated to evaluate ILD progression if symptoms worsen 
• MMF is recommended as first-line treatment. Rituximab and/or CYC by i.v. infusion may be used as an alternative 
• Consider tocilizumab as first-line treatment in early dcSSc with raised inflammatory markers and ATA positivity, independent of the extent of ILD on CT 
• Consider adding rituximab or tocilizumab to background treatment with MMF or other immunosuppressant, as rescue immunomodulatory therapy 
• Nintedanib is recommended in progressive pulmonary fibrosis despite immunosuppressant treatment, dependent on tolerability, and may be considered as first-line treatment in combination with MMF in extensive fibrosis 
• Referral for lung transplantation is appropriate in some cases although comorbidity, particularly oesophageal involvement, may limit eligibility 

Pulmonary Hypertension in SSc

• Screening for PAH should be undertaken in all people with SSc on an annual basis (PFTs, echocardiography, NTproBNP and use DETECT tool)
• The threshold for initiation of PAH drug therapy - precapillary PAH with mean pulmonary artery pressure ≥25 mmHg 
• PAH therapies should be initiated and monitored by a designated PH centre.
• PAH-SSc treatments: phosphodiesterase type 5 inhibitors (PDE5i) (tadalafil, sildenafil), endothelin receptor antagonists (ambrisentan, macitentan, bosentan), prostaglandins (e.g. inhaled iloprost, i.v. epoprostenol, s.c. or inhaled treprostinil), prostacyclin receptor agonist (selexipag) and riociguat (sGC stimulator)
• Combining riociguat and any PDE5i is contraindicated due to risk of hypotension 
• Counseling on vaccination against SARS-CoV-2, influenza and S. pneumoniae, contraception and pregnancy counselling for women of child-bearing age, and psychosocial support 
• Anticoagulation with warfarin is not recommended in SSc-PAH 

SSc Cardiac 

• Screening may include ECG, echocardiography and serum troponin (ideally, I or T) and NTproBNP (or BNP in renal disease)
• Endomyocardial biopsy should only be considered in selected cases 
• Cardiovascular magnetic resonance (CMR) screening should be considered in high-risk individuals (male gender, diffuse cutaneous skin subset, anti-topoisomerase I, early disease, ILD, peripheral myositis and other inflammatory manifestations) 
• Immunosuppression with MMF should be considered in with myocardial inflammation. Glucocorticoid may also be added to MMF [although risk of scleroderma renal crisis should warrant caution] 
• Other biological DMARDs (rituximab, tocilizumab) may be added to MMF therapy if appropriate, and/or CYC 
• Robust studies ae lacking regading treatment of myocardial fibrosis

AHSCT - autologous haematopoietic stem cell transplant 

• AHSCT may be considered in selected dcSSc where benefit is likely to be greater than treatment-related risk. Severe internal organ disease may preclude AHSCT 
• AHSCT should be delivered within an experienced specialized centre 
• Use of AHSCT in adults with later-stage dcSSc and in lcSSc is not recommended 
• AHSCT may be considered in children and young people with SSc who have severe or refractory disease, regardless of disease subset 

Gastrointestinal Complications of SSc

• Proton pump inhibitors and/or histamine H2 receptor antagonists are recommended for treatment of symptomatic gastro-oesophageal reflux and dysphagia 
• Promotility agents including prokinetic dopamine antagonists may be used for dysphagia and reflux 
• Parenteral nutrition should be considered for those with severe weight loss and/or malnutrition (including high risk), which is refractory to enteral supplementation 
• Intermittent broad-spectrum oral antibiotics (e.g. ciprofloxacin) are recommended for symptomatic small intestinal bacterial overgrowth, with rotational regimes. Rifaximin may be an effective alternative in refractory cases 
• Anti-diarrhoeal agents (e.g. loperamide) or laxatives may be used for symptomatic management of diarrhoea or constipation - non-SSc causes should be excluded 

Serious Renal Complication of SSc 

• The most serious renal complication (SRC) of SSc is thrombotic microangiopathy with acute kidney injury, generally associated with significant new-onset hypertension 
• Angiotensin-converting enzyme inhibitor should be initiated or continued in all cases of diagnosed SRC to maximum therapeutic dose 
• Glucocorticoid treatment should be minimized in SSc 
• Renal replacement therapy - use the least haemodynamically demanding approach (e.g. haemofiltration or peritoneal dialysis) 
• Renal biopsy should be considered when diagnosis is uncertain (especially if substantial proteinuria, ANCA+, overlap serology SLE, etc.) 
• Referral for renal transplantation may be considered after 12 months in cases without features suggesting significant renal recovery 

Non-fibrotic Skin Manifestations in SSc

• Moisturized skin is essential. Avoid frequent bathing with harsh deodorant soaps, and emollients should be used as soap substitutes 
• Anti-pruritic moisturizers and antihistamines are often used for itch. Expert opinion suggests low-dose opioid antagonists, e.g. naloxone and naltrexone, and other options including gabapentin and pregabalin, and low-dose antidepressants such as mirtazapine, may be considered 

Calcinosis in SSc

• There is a very limited evidence base to guide clinicians on the management of calcinosis in patients with SSc
• Be aware of secondary infection of calcinosis and need for appropriate antibiotic therapy 
• Surgical intervention should be considered in severe, refractory calcinosis 

Cancer Screening in Adults with SSc

• Cases over 65 years or with a clinical phenotype of paraneoplastic SSc [overlap DM; anti-RNA polymerase III (ARA), palmar fibrosis; red flag symptoms of malignancy] should have baseline screening with breast examination, lymphoreticular assessment, fecal immunochemical testing (FIT) and endoscopy if indicated 
• In addition, chest, abdomen and pelvis (CAP) CT scan with contrast, and/or ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT scanning should be considered on an individual basis 
• Follow-up screening should be guided by clinical suspicion and in high-risk cases with history of Barrett’s oesophagus or previous treatment with high cumulative dose of CYC