Recommendations for the Screening, Monitoring & Treatment of Interstitial Lung Disease Under Final Development
Dr. Sindhu Johnson
Image Credit: Gajus/shutterstock.com
SAN DIEGO—Many patients with interstitial lung disease (ILD) have concurrent systemic autoimmune rheumatic diseases (SARDs), such as systemic sclerosis, rheumatoid arthritis, Sjögren’s syndrome, mixed connective tissue disease or idiopathic inflammatory myopathies. During a Sunday, Nov.12, scientific session at ACR Convergence, Sindhu Johnson, MD, PhD, professor of medicine at the University of Toronto, Canada, highlighted some key considerations and clinical pearls related to ACR’s new guideline on SARDs and ILD.1,2
Dinesh Khanna, MD, MSc, professor of medicine and director of the University of Michigan Scleroderma Program, Ann Arbor, illustrated some of the recommendations via case studies from his practice.
Example Case Presentation: Early Diffuse Systemic Sclerosis
Dr. Dinesh Khanna
Dr. Khanna described a 51-year-old woman with a new referral for early diffuse systemic sclerosis. Her first non-Raynauds phenomenon symptoms were joint swelling, followed by puffy fingers and other symptoms such as pruritus and gastroesophageal reflux disease; she now had significant disability.
The patient’s modified Rodnan skin score was 23/51, suggesting significant skin fibrosis. Her platelet count was elevated at 474,000 platelets/mcL (normal, less than 200,000) and her inflammatory markers were also elevated (e.g., a C-reactive protein of 2 mg/dL; normal, less than 0.6 mg/dL). She was also positive for antibodies against topoisomerase (anti-SCL-70 antibodies).
However, she did not report cough or dyspnea on exertion, and her chest was clear to auscultation.
Clinical Questions: Early ILD is often asymptomatic. Does this patient need screening for ILD? If so, which tests? What if she had a different SARD, clinical features or risk factors?
In her talk, Dr. Johnson pointed out that although all the SARDs impart an increased risk of ILD compared with the general population, some SARDs carry a higher risk than others. Additionally, patients with the same disease may have a greater likelihood of developing an ILD based on known risk factors.
For example, systemic sclerosis imparts the highest risk of ILD among the SARDs, and Dr. Johnson said the vast majority of such patients should be screened. In contrast, not all patients with rheumatoid arthritis or other SARDs need screening. However, if one or more risk factors are present, the patient and physician should at least discuss the need for screening.
Examples of risk factors include anti-SCL-70 antibody and elevated acute phase reactants in systemic sclerosis; high titer RF or anti-CCP in rheumatoid arthritis; anti Jo-1 or ulcerating lesions in idiopathic inflammatory myopathies; or dysphagia or Raynaud’s phenomenon in mixed connective tissue disease. (A more complete list of risk factors will be included in the full manuscript.)
Because this patient had both systemic sclerosis and factors increasing her risk, Dr. Khanna explained that she definitely needed screening, even though she did not have signs or symptoms of ILD, such as cough.
The guideline conditionally suggests that patients who have a relevant SARD but no other factors increasing their risk of ILD may not need such screening unless they have potential signs or symptoms; however, clinicians should still bring up the option with their patients.
Per the guideline, Dr. Khanna noted that screening for higher risk patients should consist of both pulmonary function testing—including spirometry, lung volumes and diffusion capacity—and high-resolution chest CT. Pulmonary function testing alone is not sufficient, as it can miss 15–20% of patients with early ILD, explained Dr. Khanna.
Dr. Johnson noted that CT angiogram, which may be administered to a patient with acute shortness of breath in an emergency setting, is often inadequate to screen for ILD.
The guideline also includes conditional recommendations against screening with the six-minute-walk test, chest radiography, ambulatory desaturation testing or bronchoscopy, with a strong recommendation against screening with surgical lung biopsy. However, using these tests may be helpful in specific circumstances.
Short-term glucocorticoids are conditionally recommended as part of treatment for other types of SARDs, but for systemic sclerosis, the strong recommendation is against their use. This is due to risks of triggering renal crisis in this condition & lack of data demonstrating their efficacy in treating systemic sclerosis-related ILD.
Clinical Case Continued
The patient’s pulmonary function tests showed a mild restriction in forced vital capacity confirmed with a decreased total lung capacity and a proportional decline in diffusion capacity, a finding that would be uncommon in lung disease of other etiology, such as pulmonary vascular disease. The high-resolution chest CT showed ground glass opacities and a few interstitial markings, with very early but definite ILD.
Clinical Question: Should this patient be treated? What is the best approach?
Dr. Khanna shared that this patient should definitely be treated, given these findings and her other high-risk factors. However, he added the guideline doesn’t imply that every patient with ILD necessarily needs immediate treatment. For example, a rheumatologist may use a different approach in a patient with a forced vital capacity of 100%.
The guideline presents initial treatment options, with mycophenolate, tocilizumab and rituximab in terms of first-line ILD therapy expected to be the most prescribed for systemic sclerosis, but with cyclophosphamide, nintedanib or azathioprine as additional options that may make sense in specific situations. Some slight differences exist in the recommendations for therapeutic treatments for different subtypes.
Dr. Johnson pointed out the evidence used to recommend one treatment over another was of very low certainty. Comorbidities, extra-pulmonary disease activity, patient preferences or other factors may lead clinicians to make different choices.
Dr. Khanna highlighted one key difference in treatment approaches among different SARDs: Short-term glucocorticoids are conditionally recommended as part of treatment for other types of SARDs, but for systemic sclerosis, the strong recommendation is against their use. This is due to risks of triggering renal crisis in this condition and lack of data demonstrating their efficacy in treating systemic sclerosis-related ILD.
Clinical Question: How often should this patient be rescreened?
Per the guideline, the conditional recommendation is that this patient should be screened again with pulmonary function testing within another three to six months, with less frequent screenings once the disease is stable, and with ambulatory desaturation testing every three to 12 months. High resolution CT can also be used if needed, e.g., to distinguish worsening symptoms from other possible etiologies.
Dr. Johnson underscored that ambulatory desaturation testing is not synonymous with the 6-minute-walk test. Rheumatologists may not be comfortable with the former test themselves, but they can collaborate with pulmonologists, who should become contributors to patient care if someone is diagnosed with an ILD.
Clinical Case Continued
The patient was prescribed mycophenolate mofetil at 500 mg twice a day, increasing to 3,000 mg/day over six weeks. The patient’s fatigue and pleuritis had improved at six-month follow-up, with a minimal improvement in her Rodnan skin score. She had developed minimal dyspnea on exertion and mild cough. Her pulmonary function tests had all dropped slightly.
By the time of another follow-up three months later, her pulmonary function tests had dropped more (e.g., forced vital capacity had fallen to 2.34 L from 2.62 L at pre-treatment; diffusion capacity had dropped to 65% from 73% pretreatment). She continued to display high inflammatory markers.
Clinical Question: Is a treatment change indicated? What approach should be used?
Dr. Khanna emphasized how important it is to follow these patients closely. He explained that this patient was clearly displaying a progression in her ILD, which in this case he confirmed via high-resolution chest CT, and she needed further treatment.
Treatment after progression on a first therapy may involve adding or switching treatments. The guideline provides a list of preferred therapies, but decisions will vary based on the clinical situation, extra-pulmonary manifestations and patient preference.
In this case, Dr. Khanna and the patient chose to add rituximab, the treatment listed right after mycophenolate (if it has not already been employed) for all five subtypes.
The guideline also contains recommendations for management of rapidly progressive ILD, although this was not relevant in the clinical case study because rapidly progressive disease is rare in systemic sclerosis.
A guideline summary with additional details on screening and monitoring is currently available online, as well as a summary on treatment. The full guideline manuscripts are under peer review, with publication anticipated in the spring of 2024.
Ruth Jessen Hickman, MD, is a graduate of the Indiana University School of Medicine. She is a freelance medical and science writer living in Bloomington, Ind.
References
- Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR) Guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis & Rheumatology. 2023; In preparation 2023.
- Johnson SR, Bernstein EJ, Bolster MB, et al. 2023 American College of Rheumatology (ACR) Guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis & Rheumatology. 2023; In preparation 2023.
- 2023 American College of Rheumatology (ACR) guideline for the screening and monitoring of interstitial lung disease in people with systemic autoimmune rheumatic disease: Guideline summary.
- 2023 American College of Rheumatology (ACR) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic disease: Guideline summary.
