Pulmonary Fibrosis

Author: Shelley Ensz. Scleroderma is highly variable. See Types of Scleroderma. Read Disclaimer
Disease Correlations
Living with PF
Patient Stories


Pulmonary (lung) fibrosis, is a scarring of the lungs, and is the consequence of untreated pulmonary inflammation (alveolitis). It is often also referred to as interstitial lung disease.

Pulmonary fibrosis (PF) can occur by itself or as secondary to some autoimmune diseases, including systemic sclerosis (SSc, scleroderma).

What is pulmonary fibrosis? Pulmonary fibrosis is scarring throughout the lungs. Pulmonary fibrosis can be caused by many conditions such as sarcoidosis, hypersensitivity pneumonitis, asbestosis, certain medications, etc. MedicineNet

About 70% of patients with diffuse scleroderma develop some degree of pulmonary fibrosis, which is the most common cause of death directly related to scleroderma. Therefore, prompt diagnosis and aggressive treatment of pulmonary fibrosis is very important.

Pulmonary fibrosis is also one of the three minor criteria (1) for the classification of limited systemic scleroderma. (See Types of Scleroderma.)

Mortality and Prognosis

Pneumoproteins KL-6 and CCL-18 Predict Progression of Interstitial Lung Disease in Systemic Sclerosis (SSc-ILD). In a rigorously-conducted clinical trial for SSc-ILD, KL-6 and CCL-18 levels correlated with ILD severity and declined with immunosuppression. PubMed, Arthritis Rheumatol, 06/24/2019.

Short–term progression of interstitial lung disease (ILD) in systemic sclerosis (SSc) predicts long–term survival in two independent clinical trial cohorts. These findings suggest that short–term changes in surrogate measures of SSc–ILD progression may have important effects on long–term outcomes. PubMed, Ann Rheum Dis, 11/08/2018.

CCL2 in the Circulation Predicts Long-Term Progression of Interstitial Lung Disease (ILD) in Patients With Early Systemic Sclerosis (SSc). Higher CCL2 levels in the circulation were predictive of ILD progression and poorer survival in patients with early SSc, which support the notion that CCL2 has a role as a biomarker and potential therapeutic target. PubMed, Arthritis Rheumatol, 2017 Sep;69(9):1871-1878.

Pulmonary Artery (PA) Dimensions as a Prognosticator of Transplant–Free Survival in Scleroderma Interstitial Lung Disease (SSc–ILD). In SSc–ILD patients, a PA:ascending aorta (Ao) ratio ≥1.1 is associated with higher risk of lung transplant or death. PubMed, Lung, 04/29/2017.

Esophageal dilatation and interstitial lung disease in systemic sclerosis (SSc): A cross-sectional study. Increasing esophageal diameter on high–resolution computed tomography in patients with SSc is associated with more severe radiographic interstitial lung disease, lower lung volumes, and lower DLCO % predicted. PubMed, Semin Arthritis Rheum, 2016 Aug;46(1):109-14. (Also see Esophageal (Throat) Involvement)

Good outcome of interstitial lung disease in patients with scleroderma associated to anti-PM/Scl antibody. Several features and prognosis of ILD in SSc may be modified depending on the identified immunological profile. Seminars in Arthritis and Rheumatism. (Also see Antibodies in Systemic Scleroderma)


Symptoms of pulmonary fibrosis include shortness of breath (dyspnea) on exertion. In treating scleroderma, its best to identify pulmonary fibrosis before it is so advanced that it shows up on x-ray. That is why your doctor may order an echocardiogram, or other tests. ISN.

Correlation of Pulmonary Fibrosis with Other Complications

Pulmonary fibrosis complications iconPulmonary Fibrosis Correlations and Complications. Pulmonary fibrosis can be correlated or complicated with the following conditions, such as esophageal issues, cancer, connective tissue diseases, heart problems, infections, pulmonary hypertension and thyroid diseases. ISN.

Lung and Esophageal
Pulmonary Fibrosis and:
—Connective Tissue Disease
—Pulmonary Hypertension
—Thyroid Disease
Patient Stories


Diagnosis of Pulmonary Fibrosis. All systemic sclerosis patients should have regular screening for both pulmonary fibrosis and pulmonary hypertension. ISN.

High Resolution Computed Tomography
Induced Sputum and Bronchoalveolar Lavage
Lung Biopsy
Pulmonary Function Tests
Walking and Stress Tests
Pulmonary Fibrosis Antibodies

Living with Pulmonary Fibrosis

Living with Pulmonary Fibrosis requires a constant awareness of your symptoms, your breathing, your surroundings, and your overall well-being. Work closely with your doctors on treatments, diet and exercise. If you require oxygen therapy, use it. It protects your heart as well as improves the quality of your life. ISN.

Air Quality
Oxygen Therapy
Dangers of Oxygen
Support Groups


Treatments for Pulmonary Fibrosis include oxygen therapy, oral and IV cyclophosphamide, biologic agents, Mycophenolate Mofetil (cellcept), and lung transplants. There are current clinical trials that are studying the effectiveness of various treatments for scleroderma. Some of these trials are using the treatment's effect on the patient's pulmonary fibrosis as a measurement criterion. ISN.

Antihistamine Warning
Biologic Agents
CellCept® (Mycophenolate Mofetil)
Cyclosporine (CYC)
Esbriet® (Pirfenidone)
Lung Transplant
Lung Transplant Media Stories
Ofev® (Nintedanib)
Therapeutic Plasma Exchange
Velcade® (Bortezomib)
PF Clinical Trials
PF Research

Pulmonary Fibrosis Research

Short or long sleep associated with Idiopathic Pulmonary Fibrosis. The study reveals that targeting the body clock reduces fibrosis in vitro, revealing a potential target for this incurable disease. University of Manchester, 12/30/2019.

Interferon Lambda (IFNL3) genotype is associated with pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc). IFNL3 serum levels and the genetic variant known to be associated with liver fibrosis are similarly linked to PF, but not to worsening of skin fibrosis in SSc. PubMed, Sci Rep, 2019 Oct 16;9(1):14834.

Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis. CCL24 plays an important role in pathological processes of skin and lung inflammation and fibrosis. PubMed, Ann Rheum Dis, 05/25/2019.

Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study. Further investigation into the mechanistic role of monocytes in fibrosis might lead to insights that assist the development of new therapies. PubMed, Lancet Respir Med, 03/29/2019.

Anti-C1q autoantibodies (autoAbs) are frequently detected in patients with systemic sclerosis (SSc) associated with pulmonary fibrosis. Anti-C1q autoAbs were frequently detected in patients with SSc, and their high levels predict the co–occurrence of pulmonary fibrosis or pulmonary arterial hypertension. PubMed, Br J Dermatol, 03/15/2019.

Recent progress in systemic sclerosis–interstitial lung disease (SSc–ILD). The implications of much of this ongoing work is our ability to identify those patients at risk for progression, and to offer novel therapies that can limit the progression of inflammatory and fibrotic lung disease. PubMed, Curr Opin Rheumatol, 2018 Nov;30(6):570-575.

TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung. The results suggest that systemic scleroderma patients with high TLR4 activity might show optimal therapeutic response to selective inhibitors of MD2/TLR4 complex formation. PubMed, JCI Insight, 2018 Jul 12;3(13). (Also see Fibroblasts and Skin Fibrosis)

The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms. The analysis revealed that gene variation in four genes – IRF5, STAT4, CTGF and IRAK1 – was linked to lung fibrosis in scleroderma. PubMed, Rheumatol Int, 04/22/2017.

Th–17 cytokines and interstitial lung involvement in systemic sclerosis (SSc). In diffuse SSc patients our results show a clear link between Th–17 cytokines measured both in exhaled breath condensate and in serum with interstitial lung involvement. PubMed, J Breath Re, 2016 Nov 21;10(4):046013. (Also see Cytokines)

Netrin–1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin–Induced Pulmonary Fibrosis. Netrin–1 regulates bleomycin–induced pulmonary fibrosis in mice and it might be a novel therapeutic target in scleroderma–related interstitial lung disease. PubMed, Arthritis Rheumatol, 2016 May;68(5):1251-61.

Frequency of circulating topoisomerase–I–specific CD4 T cells predicts presence and progression of interstitial lung disease (ILD) in scleroderma. Topo–I–specific T cells can be reliably quantified in the peripheral blood of patients with scleroderma, exhibit a pro–inflammatory Th17 phenotype, and predict progression of ILD. BioMed Central, Arthritis Research & Therapy, 05/04/2016. (Also see Causes of Scleroderma: B Cells and T Cells)

M10, a caspase cleavage product of the hepatocyte growth factor receptor, interacts with Smad2 and demonstrates antifibrotic properties in vitro and in vivo. M10 peptide interacts with Smad2 and demonstrates strong antifibrotic effects in vitro and in vivo in an animal model of lung fibrosis and should be considered as a potential therapeutic agent for systemic sclerosis and other fibrosing diseases. PubMed, Transl Res, 2016 Apr;170:99-111. (Also see Skin Fibrosis)

Research of Lung Fibrosis in Scleroderma (SSc) Reveals High Levels of Antibodies That Correlate with Disease Progression. Circulating antibodies against specific chemokine receptors exist in higher levels in patients with SSc and these antibodies correlate with disease progression and clinical manifestations of the disease. Scleroderma News, 02/25/2016.

Scleroderma–related Interstitial Lung Disease (SSc–ILD) Not Linked to Idiopathic Interstitial Pneumonia. The study confirmed that SSc–ILD and idiopathic interstitial pneumonia are different diseases, not sharing a genetic basis. Scleroderma News, 02/02/2016. (Also see Lung Involvement)


(1) Reference: Subcommittee for Scleroderma criteria of the American Rheumatism Association diagnostic and therapeutic criteria committee. 1980. Preliminary criteria for the classification of systemic sclerosis (Scleroderma). Arthritis Rheum. 23,581:590.

Go to Pulmonary Fibrosis: Correlations

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