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  • Review Article
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Acute exacerbation of interstitial lung disease associated with rheumatic disease

Nature Reviews Rheumatology volume 18, pages 85–96 (2022)Cite this article

Subjects

Abstract

Interstitial lung disease (ILD) is a cause of morbidity and mortality in patients with rheumatic diseases, such as connective-tissue diseases, rheumatoid arthritis and systemic vasculitis. Some patients with ILD secondary to rheumatic disease (RD–ILD) experience acute exacerbations, with sudden ILD progression and high mortality during or immediately after the exacerbation, and a very low 1-year survival rate. In the ILD subtype idiopathic pulmonary fibrosis (IPF), an acute exacerbation is defined as acute worsening or development of dyspnoea associated with new bilateral ground-glass opacities and/or consolidations at high-resolution CT, superimposed on a background pattern consistent with fibrosing ILD. However, acute exacerbation in RD–ILD (AE–RD–ILD) currently has no specific definition. The aetiology and pathogenesis of AE–RD–ILD remain unclear, but distinct triggers might include infection, mechanical stress, microaspiration and DMARD treatment. At this time, no effective evidence-based therapeutic strategies for AE–RD–ILD are available. In clinical practice, AE–RD–ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. In this Review, we summarize the clinical features, diagnosis, management and prognosis of AE–RD–ILD, enabling the similarities and differences with acute exacerbation in IPF to be critically assessed.

Key points

  • In patients with rheumatic diseases, interstitial lung disease (ILD) is a major cause of morbidity and mortality.

  • Some patients with rheumatic disease experience acute exacerbation of ILD (AE–ILD), a sudden worsening that is associated with high short-term mortality and a very low 1-year survival rate.

  • Diagnosis of AE–ILD relies on clinical suspicion, symptom worsening and identification of potential triggers combined with imaging and exclusion of other diseases.

  • Management strategies for AE–ILD are based on recommendations for idiopathic pulmonary fibrosis, including systemic steroids and broad-spectrum antibiotics.

  • Randomized controlled trials of the management of acute exacerbation are lacking.

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Fig. 1: Pathogenesis of acute exacerbation of interstitial lung disease in rheumatic disease.
Fig. 2: High-resolution chest CT in stable state and acute exacerbation of interstitial lung disease in rheumatic disease.
Fig. 3: Pathological examination of patients with acute exacerbation of interstitial lung disease in rheumatic disease.
Fig. 4: Diagnosis and treatment of acute exacerbation in interstitial lung disease in rheumatic disease.

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Acknowledgements

The work of F.L. was partially supported by the Italian Ministry of University and Research — Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinic).

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Authors and Affiliations

  1. Respiratory Diseases Unit, University of Milano-Bicocca, S. Gerardo Hospital, ASST Monza, Monza, Italy

    Fabrizio Luppi

  2. Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy

    Marco Sebastiani, Carlo Salvarani & Andreina Manfredi

  3. Rheumatology Unit, Dipartimento Medicina Interna e Specialità Mediche, Azienda Unità Sanitaria Locale di Reggio Emilia-Istituto di Ricerca e Cura a Carattere Scientifico, Reggio Emilia, Italy

    Carlo Salvarani

  4. Center for Rare Lung Disease, Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Aarhus, Denmark

    Elisabeth Bendstrup

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  1. Fabrizio Luppi
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  2. Marco Sebastiani
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  3. Carlo Salvarani
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  4. Elisabeth Bendstrup
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  5. Andreina Manfredi
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All authors contributed equally to all aspects of the article.

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Correspondence to Fabrizio Luppi.

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Nature Reviews Rheumatology thanks F. Bonella, A. Wells and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Dyspnoea

Difficult or laboured breathing.

Pneumothorax

Presence of air between the pleura and the lungs, causing the collapse of the lung.

Pleural effusion

Accumulation of fluid between the pleural layers.

Tachypnoea

Abnormally rapid breathing.

Cyanosis

A physical sign causing bluish discolouration of the skin and mucous membranes, caused by deoxygenated or reduced haemoglobin in the blood.

Ground-glass opacities

An area of increased attenuation in the lung on CT, with preserved bronchial and vascular markings, which is a non-specific sign with a wide aetiology, including infection, chronic interstitial disease and acute alveolar disease.

Hyaline membrane

Eosinophilic and proteinaceous material (derived from fibrin degradation) covering alveoli.

GAP

A clinical prediction model using commonly measured clinical (gender and age) and physiological (lung function) variables to predict mortality in patients with idiopathic pulmonary fibrosis.

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Luppi, F., Sebastiani, M., Salvarani, C. et al. Acute exacerbation of interstitial lung disease associated with rheumatic disease. Nat Rev Rheumatol 18, 85–96 (2022). https://doi.org/10.1038/s41584-021-00721-z

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