Evidence-Based European Consensus Statements for the Management of Interstitial Lung Disease in Systemic Sclerosis

Interstitial pulmonary fibrosis (IPF). Computed tomography (CT) scan of lungs affected by IPF. The two dark structures are the lungs. The white space in the upper center is the heart. The left lung is the most severely affected, with diseased tissue appearing white. IPF is characterized by progressive thickening and stiffening of the lining of the air sacs in the lungs, causing breathlessness and pain. The cause is often unknown but in some cases the disease is thought to result from an autoimmune disorder. Without treatment IPF can lead to heart failure or bronchopneumonia. Treatment depends on the suspected underlying cause.
Researchers developed the first expert consensus for the identification and management of interstitial lung disease in systemic sclerosis.

Based on emerging evidence and expert consensus, a panel of 27 pulmonologists, rheumatologists, and internists from Europe released recommendations for the identification and management of interstitial lung disease (ILD) in systemic sclerosis (SSc) and defined a management algorithm for clinical practice. This report was published in Lancet Rheumatology.

Investigators performed a systematic review of literature focused on treatment strategies for SSc-ILD published between July 2018 and August 2019. Recommendations for 6 domains (risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) of medical management were developed using a modified Delphi method, in which the panel participated in 3 rounds of online surveys, face-to-face discussions, and established consensus. Consensus was considered achieved if at least 80% of panelists indicated agreement or disagreement.

Recommendations for Risk Factors

According to the panelists, risk factors that might increase the likelihood of a patient with SSc having or developing ILD include respiratory symptoms, smoking history, ethnicity (black, Native American), being men, and prior or coexisting medical conditions. In addition, the presence of diffuse cutaneous SSc and SSc sine scleroderma may be risk factors for developing ILD.

The panel further suggested that certain laboratory parameters are associated with ILD risk for patients with SSc. Specifically, the presence of anti-topoisomerase I antibodies increases the likelihood of developing ILD while anticentromere antibodies decrease the likelihood.

Other biomarkers associated with SSc-ILD. reported in literature butnot commonly used in clinical practice, include Krebs von den Lungen-6, serum surfactant protein D, micro RNA-200, neutrophil to lymphocyte ratio, arachidonate 5-lipoxygenase activating protein polymorphisms, chemokine ligand 1, chemokine ligand 18, chemokine ligand 4, monocyte chemoattractant protein 1, chemokine receptor 3, chemokine receptor 4, interleukin 10, and plasma plasmin-α2-plasmin inhibitor complex.

Recommendations for Screening

The panel recommended that all patients with SSc be screened at baseline for ILD to establish baseline parameters for diagnosis. Screening is recommended using high-resolution computed tomography (CT) scans with lung function testing (forced vital capacity and diffusing capacity of carbon monoxide) and auscultation.

All patients with SSc should be repeatedly screened for ILD; however, no screening intervals are recommended and should be determined by the treating clinician.

Abnormalities on x-ray or in lung function testing, along with presence of respiratory symptoms, such as frequent cough or dyspnea, warrant the use of high-resolution CT examination to screen for SSc-ILD.

Recommendations for Diagnosis and Severity Assessment

High-resolution CT with pulmonary function testing (forced vital capacity and diffusing capacity of carbon monoxide) is the primary tool recommended for diagnosing ILD in patients with SSc. Diagnosis should be further supported by clinical assessment of respiratory symptoms.

The panel recommended that SSc-ILD severity be assessed using more than 1 measure, including high-resolution CT fibrosis score, lung function (forced vital capacity and diffusing capacity of carbon monoxide), respiratory symptoms, exercise-induced blood oxygen saturation, and quality of life.

Recommendations for Treatment Initiation and Options

The panel suggested that multiple factors drive treatment initiation and assessment of appropriate options for patients with SSc-ILD. These factors include current clinical guidelines, clinical experience, patient survival rate, prolongation of time to progression, symptom improvement, efficacy, safety, and tolerability, and quality of life.

Mycophenolate mofetil and cyclophosphamide were recommended by the panel as effective pharmacologic treatments for patients with SSc-ILD. For some patients with SSc-ILD, no treatment is an option; patients with severe ILD, however, should be offered treatment.

Decisions to initiate, change, or stop treatment should consider the current disease state and speed of progression. The panel recommended following up with patients diagnosed with early, stable, or mild SSc-ILD closely — every 3 to 6 months — in which treatment should be initiated in case of progression.

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Recommendations for Disease Progression

Disease progression in patients with SSc-ILD can be measured in a number of ways: changes in lung function (absolute values of forced vital capacity and diffusing capacity of carbon monoxide or decline in forced vital capacity), changes in the extent of fibrosis on high-resolution CT, changes in exercise-induced oxygen desaturation, or worsening of clinical symptoms.

The panel suggested that testing lung function is an appropriate and effective long-term follow-up measure for assessing SSc-ILD progression, and the decision to use high-resolution CT should be based on disease severity and speed of progression.

Recommendations for Treatment Escalation

Recommendations to escalate treatment are driven by disease severity and speed of progression; the panel suggested that all patients with severe or progressive SSc-ILD be offered pharmacologic treatment.

In subsets of patients with SSc-ILD, autologous hemopoietic stem cell transplantation or lung transplantation are effective treatments; patients diagnosed with advanced stages of the disease should be evaluated early for lung transplant suitability.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Hoffmann-Vold A-M, Maher TM, Philpot EE, et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements [published online January 14, 2020]. Lancet Rheumatol. doi:10.1016/S2665-9913(19)30144-4