# Pathogenesis of systemic sclerosis associated interstitial lung disease

## TL;DR

This paper reviews the causes and mechanisms behind lung fibrosis in systemic sclerosis, highlighting key factors like inflammation and immune responses.

## Contribution

The paper proposes a new model for the pathogenesis of systemic sclerosis–interstitial lung disease based on current literature.

## Key findings

- Non-specific interstitial pneumonia is the most common histological pattern in systemic sclerosis–interstitial lung disease.
- IL6, CCL2, and transforming growth factor beta are key mediators in the disease's pathogenesis.
- Epithelial injury markers like surfactant proteins and KL-6 are associated with systemic sclerosis–interstitial lung disease.

## Abstract

Systemic sclerosis is an autoimmune disease leading to vasculopathy and fibrosis
of skin and internal organs. Despite likely shared pathogenic mechanisms, the
patterns of skin and lung fibrosis differ. Pathogenesis of interstitial lung
disease, a major cause of death in systemic sclerosis, reflects the intrinsic
disease pathobiology and is associated with distinct clinical phenotypes and
laboratory characteristics. The commonest histological pattern of systemic
sclerosis–interstitial lung disease is non-specific interstitial pneumonia.
Systemic sclerosis–interstitial lung disease pathogenesis involves multiple
components, including susceptibility and triggering factors, which could be
genetic or environmental. The process is amplified likely through ongoing
inflammation and the link between inflammatory activity and fibrosis with IL6
emerging as a key mediator. The disease is driven by epithelial injury,
reflected by markers in the serum, such as surfactant proteins and KL-6. In
addition, mediators that are produced by epithelial cells and that regulate
inflammatory cell trafficking may be important, especially CCL2. Other factors,
such as CXCL4 and CCL18, point towards immune-mediated damage or injury
response. Monocytes and alternatively activated macrophages appear to be
important. Transforming growth factor beta appears central to pathogenesis and
regulates epithelial repair and fibroblast activation. Understanding
pathogenesis may help to unravel the stages of systemic sclerosis–interstitial
lung disease, risks of progression and determinants of outcome. With this
article, we set out to review the multiple factors, including genetic,
environmental, cellular and molecular, that may be involved in the pathogenesis
of systemic sclerosis–interstitial lung disease and the mechanisms leading to
sustained fibrosis. We propose a model for the pathogenesis of systemic
sclerosis–interstitial lung disease, based on the available literature.