Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD) Guidelines

Updated: Aug 06, 2020
  • Author: Aniruddh Kapoor, MBBS; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Guidelines Summary

Idiopathic Pulmonary Fibrosis (IPF)

In 2018, the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society released their clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis, as outlined below. [97, 98]

Obtain a detailed history for possible environmental exposures or medication use to exclude potential causes of interstitial lung disease (ILD).

Perform serologic testing to exclude connective-tissue disease.

With newly diagnosed ILD, perform high-resolution CT (HRCT) scanning of the chest; determine if findings indicate a pattern of (1) usual interstitial pneumonia (UIP), (2) probable UIP, (3) indeterminate of UIP, or (4) alternate diagnosis.

For probable UIP, indeterminate findings, or alternate diagnosis, bronchoalveolar lavage and surgical lung biopsy are recommended; evidence is insufficient to recommend for or against transbronchial lung biopsy or lung cryobiopsy.

For a UIP pattern, bronchoalveolar lavage (cellular analysis) and surgical lung biopsy are not recommended (risks outweigh benefits); guidelines strongly recommend against transbronchial lung biopsy or lung cryobiopsy in this situation.

Multidisciplinary discussions (MDDs) should include interactions between pulmonologists, possibly rheumatologists (on a case-by-case basis), pathologists, and radiologists. MDDs are recommended with newly detected ILD of an unknown cause in patients whose findings clinically suggest idiopathic pulmonary fibrosis. MDDs likely provide the greatest benefit in situations in which HRCT patterns indicate probable UIP, indeterminate findings, or alternative diagnoses, or when clinical, histologic, or radiologic data are incongruous.

For serum biomarker measurements, measuring serum matrix metalloproteinase 7, chemokine ligand 18, Krebs von den Lungen-6, or surfactant protein D is not recommended solely to distinguish idiopathic pulmonary fibrosis from other ILDs, owing to high false-positive and false-negative results.

Interstitial pneumonia with autoimmune features (IPAF)

In 2015, the European Respiratory Society and American Thoracic Society released a joint consensus statement proposing the term interstitial pneumonia with autoimmune features (IPAF) be used for idiopathic interstitial pneumonia (IIP) with clinical features that suggest an underlying autoimmune process. Proposed classification criteria include the presence of interstitial pneumonia (by HRCT or surgical lung biopsy); alternative etiologies are excluded and the patient does not meet the criteria for a connective tissue disease; and at least one feature from two domains (clinical, serologic, morphologic) is present. [10]

The clinical domain includes specific features suggestive of an underlying CTD. While they are specific findings, their presence alone does not meet the criteria for the diagnosis of a defined CTD. These features include distal digital fissuring (ie, “mechanic hands”), distal digital tip ulceration, inflammatory arthritis or polyarticular morning joint stiffness ≥60 min, palmar telangiectasia, Raynaud's phenomenon, unexplained digital edema, unexplained fixed rash on the digital extensor surfaces (Gottron sign). [10]

The serologic domain includes circulating autoantibodies known to be associated with CTDs. (See Table 2 in Workup) Less specific serologic markers, such as a low-titer antinuclear antibody (ANA), low-titer rheumatoid factor (RF), erythrocyte sedimentation rate, C-reactive protein or creatine phosphokinase, are not included. [10]

The morphology domain is divided into three sections: interstitial pneumonia patterns suggested by HRCT imaging, histopathologic features identified by surgical lung biopsy, or evidence of additional thoracic compartment involvement as determined by diagnostic imaging, histopathologic findings, right heart catheterization (RHC) or pulmonary function testing. [10]

When these proposed criteria were applied to 422 patients previously diagnosed with idiopathic interstitial pneumonia (IIP) or undifferentiated CTD-ILD (UCTD), 144 (34%) met IPAF criteria. The mean age was 63.2 years with a slight female predominance. IPAF cohort survival was marginally better than patients with idiopathic pulmonary fibrosis but worse than CTD-ILD. A non-usual interstitial pneumonia pattern was associated with improved survival, as was the presence of the clinical domain. A modified IPAF cohort of those meeting the clinical domain and a radiographic or histological feature within the morphological domain displayed survival similar to those with CTD-ILD. [9]