Scleroderma is a complex, autoimmune disease of the blood vessels and connective tissue. The localised form affects the skin alone, however systemic scleroderma, known as systemic sclerosis (SSc), also affects the internal organs including the heart, lungs, kidneys, gastrointestinal tract and musculoskeletal system.1,2

PAH is a well-recognised complication of SSc; it occurs in around 16% of patients3 and is the leading cause of death in these patients.4

PAH associated with SSc (PAH-SSc) has a worse prognosis than idiopathic PAH (IPAH).2

Compared with IPAH, the outcomes for patients with PAH-SSc are particularly poor. This may be due to delays in identifying the disease, the high prevalence of comorbidities affecting the heart and lungs, and the relatively poor response to treatment.2

Figure 1. Kaplan-Meier estimates of survival in patients with IPAH and PAH-SSc over 60 and 72 months, respectively.5 Adapted from Launay, Rheumatology 2010

Rationale for screening for PAH in SSc patients

Early recognition of PAH in SSc is difficult as symptoms at disease onset are mild and the complex nature of SSc makes interpretation of fatigue and breathlessness challenging.4

Screening SSc patients for PAH can lead to early diagnosis and improvements in long-term outcomes compared with diagnosis during routine care.6 It is therefore recommended that all asymptomatic patients with SSc are screened for PAH annually.7

Figure 2. Impact of screening on survival in patients with SSc.8 Adapted from Humbert, Arthritis Rheum 2011

Practicalities of screening for PAH in patients with SSc

Although the benefit of screening for PAH is clear, there is no consensus on the optimal screening approach. Several screening methods can identify patients who should undergo right heart catheterisation (RHC), for example assessment of pulmonary function tests, biomarkers and echocardiography (echo).7

Development of a screening algorithm

The DETECT study (funded by Actelion Pharmaceuticals Ltd) was an international study to develop the first evidence-based screening algorithm for PAH in SSc.

Over 450 adult SSc patients across North America, Europe and Asia underwent a broad panel of non-invasive assessments followed by RHC. Variables such as patient demographics, clinical parameters, serum tests, ECG, and echo were analysed to identify the best discriminatory variables for identifying PAH.6

Based on the results, a two-step algorithm was developed:6

> Step 1: six non-invasive assessments are used to determine the need for echo
> Step 2: variables from the echo are combined with the score from step 1 to determine whether referral for RHC is indicated

Click here to download a nomogram which can be used to calculate the risk scores of patients in your clinical practice.

This algorithm recommended that 62% of patients should have a RHC with a false negative rate of 4%. This compared favourably with the European Society of Cardiology and European Respiratory Society (ESC/ERS) joint guidelines, which when applied to the same patients, recommended that just 40% should be referred for RHC with a false negative rate of 29%.6

Although, no currently available screening method for PAH is perfect, screening offers the prospect of early diagnosis and improved outcomes for patients with SSc with PAH.

Figure 3. The DETECT 2-step screening approach for PAH in SSc.6 Adapted from Coghlan, Ann Rheum Dis 2014


Click here to read a Rheumatologist’s guide to screening strategies for PAH in connective tissue disease written in collaboration with Dr John Pauling, Consultant Rheumatologist at the Royal National Hospital for Rheumatic Diseases in Bath.


Download the free Detect PAH app (Actelion Pharmaceutical Ltd) Available on iOS here. Or use the online calculator


  1. Kowal-Bielecka O, et al. Ann Rheum Dis 2017;76:1327–39
  2. Chaisson NF, Hassoun PM. Chest 2013;144:1346–56
  3. McGoon M, et al. Chest 2004; 126:14S–34S
  4. Morrisroe et al. Arthritis Res Ther 2017;19:42
  5. Launay D, et al. Rheumatology 2010;49:490–500
  6. Coghlan JG, et al. Ann Rheum Dis 2014;73:1340–49
  7. Galiè N, et al. Eur Heart J 2016;37:67–119
  8. Humbert M, et al. Arthritis Rheum 2011;63:3522–30

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