Pearls of Wisdom from an Expert: Challenging ILD Cases with a Pulmonologist-Rheumatologist

ORLANDO—Interstitial lung disease (ILD) affects many patients with rheumatic disease. And close collaboration with your local pulmonologist is vital to achieving the best outcomes for our patients. But what if you’re a pulmonologist and a rheumatologist at the same time?

At the 2022 ACR Education Exchange, April 28–May 1, Erin Wilfong, MD, PhD, clinical instructor of rheumatology and pulmonary critical care, Vanderbilt University Medical Center, Nashville, shared her niche expertise in connective tissue disease ILD (CTD-ILD) via case-based learning.

Case 1

A 38-year-old woman presented for consideration of a lung transplant. She worked as an aluminum smelter and was not always compliant with personal protective equipment. On further questioning, she described Raynaud’s phenomenon of eight years’ duration that had been worsening in the past year, one year of progressive dyspnea requiring oxygen therapy and six months of new-onset acid reflux. On examination, she was found to have abnormal nailfold capillaries and digital pits. Her modified Rodnan skin score was 0. Chest computed tomography (CT) revealed groundglass opacities, but no traction bronchiectasis or honeycombing. Laboratory studies were notable for a strongly positive anti-ribonucleic acid polymerase III (anti-RNA pol III) antibody. She met ACR classification criteria for a diagnosis of systemic sclerosis sine scleroderma (ssSSc).

“I was asked to consider whether this patient should be evaluated for lung transplant or if she could receive a trial of immunosuppression,” Dr. Wilfong said. “The groundglass changes told me this was inflammatory, and in the absence of traction bronchiectasis or honeycombing to suggest fibrosis, there was a good chance she’d get better or at least stabilize with immunosuppression. This is especially relevant [because] average lung transplant survival is only five to seven years.”

The patient was treated with mycophenolate mofetil (MMF) with substantial improvement in six months. Her six-minute walk test nearly doubled, and her oxygen requirements decreased to only 2 L per minute with exertion, and none at rest.

For patients with SSc or myositis with high-risk autoantibodies for ILD, Dr. Wilfong recommends baseline complete pulmonary function tests (PFTs) and high-resolution CT (HRCT) of the chest.

“After that, I try to be judicious with radiation,” she said. “I’ll follow PFTs every three months at first, and space them out if they’re improving. I’ll re-image patients for a distinct clinical change [that’s much better or much worse]. If somebody gets way better, it’s helpful to have a new baseline scan for comparison in case they get worse again one day. I don’t routinely rescan stable patients.”

Case 2

A 51-year-old woman with a five-year history of recurrent pneumonia and heavy tobacco use was referred for evaluation of CTD-ILD after surgical lung biopsy showed usual interstitial pneumonia (UIP) vs. diffuse interstitial pneumonia. She was initially diagnosed with idiopathic pulmonary fibrosis (IPF) but couldn’t tolerate treatment with pirfenidone. Two years ago, the patient developed joint pain and stiffness. Dyspnea worsened to the point she required supplemental oxygen.

An examination revealed active inflammatory arthritis. Laboratory tests were notable for positive anti-cyclic citrullinated peptide (anti-CCP) antibodies. CT chest imaging showed UIP. Radiographs revealed erosive disease of the small joints of the hands and feet. Her clinical picture was most consistent with seropositive rheumatoid arthritis (RA).

“Remember, lung disease precedes articular symptoms in about 10 to 15% of ILD, so it’s important to check serologies,” Dr. Wilfong said.

A consensus guideline on which serologies should be checked has yet to be established, but she recommended immunofluorescent anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), rheumatoid factor (RF), anti-CCP antibody and an extended myositis antibody panel.^1,2

When it comes to the treatment of RA-ILD, there are no specific therapeutic recommendations. “If there is articular disease, it’s really just important to treat it with something. Options [may] include a tumor necrosis factor inhibitor, tocilizumab, abatacept or rituximab,” she said. “Of note, methotrexate is not absolutely contraindicated in mild ILD. I use a maximum dose of 20 mg of methotrexate weekly and watch closely for signs and symptoms of methotrexate toxicity.”

This patient had marked improvement of articular symptoms with etanercept until suffering a secondary loss of efficacy, at which time she was switched to adalimumab. She declined alternative agents, such as disease-modifying anti-rheumatic drugs or nintedanib, due to concerns about side effects. Unfortunately, the patient’s pulmonary function continued to decline, and she wasn’t a transplant candidate. She was transitioned to hospice.

‘ILD imaging is all about learning by doing. Talk to your radiologists & review interesting scans together.’—Dr. Wilfong

Case 3

A 46-year-old woman with a diagnosis of seronegative RA organizing pneumonia was referred for a second opinion. She had been treated with prednisone at doses greater than or equal to 20 mg daily for the past year, without prophylaxis against Pneumocystis jiroveci pneumonia. She now had a worsening cough and intermittent fevers. The examination was notable for Gottron’s papules, inflammatory arthritis and mechanic’s hands. Laboratory studies showed an elevated creatinine kinase level.

Prior CT imaging showed migratory consolidative infiltrates. Recent CT imaging showed dense consolidation in the right middle lobe with air bronchograms.

“I performed bronchoscopy [because] I was worried about infection given lobar consolidation and high-dose steroids,” Dr. Wilfong said. “However, bronchoalveolar lavage revealed lipid-laden macrophages consistent with recurrent aspiration.”

The patient was found to have normal esophageal motility and, ultimately, underwent Nissen fundoplication with resolution of her CT findings. Surgical management of gastroesophageal reflux disease is associated with improved survival in IPF.³

“There are only so many ways the lung can repair itself, so you don’t need to be dumping stomach acid on it every night,” Dr. Wilfong said. “The challenge in our patient population is that Nissen fundoplication is contraindicated if there is significantly impaired esophageal motility.”

Thus, it may not be an option for all patients with SSc or myositis.

“This case underlines another critical point: An RA-ILD diagnosis should always be anti-CCP positive,” she said. “We know that RA likely starts in the lungs or the mouth, not the joints. So if an anti-CCP negative patient is diagnosed with RA-ILD, rethink that diagnosis.”⁴

For dermatomyositis—the true etiology of her inflammatory arthritis and rashes—the patient was treated with MMF, abatacept and hydroxychloroquine. Her PFTs have nearly normalized, and prednisone has been tapered to 5 mg daily.

Summary

To conclude, Dr. Wilfong stressed take-home points. Groundglass changes are likely to be inflammatory and potentially reversible, whereas fibrotic changes are currently irreversible. RA-ILD should always be anti-CCP positive. And don’t forget to rule out mimics, such as aspiration and infection, as a cause of worsening pulmonary function in your ILD patients.

She also encouraged the audience to start looking at the images we order. “ILD imaging is all about learning by doing,” she said. “Talk to your radiologists and review interesting scans together. For practice, find out if your institution has an ILD conference. That’s where all the weird CT scans go.”

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Samantha C. Shapiro, MD, is an academic rheumatologist and an affiliate faculty member of the Dell Medical School at the University of Texas at Austin. She received her training in internal medicine and rheumatology at Johns Hopkins University, Baltimore. She is also a member of the ACR Insurance Subcommittee.

References

1. Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44–e68.
2. Wilfong EM, Young-Glazer JJ, Sohn BK, et al. Anti-tRNA synthetase syndrome interstitial lung disease: A single center experience. Respir Med. 2022 Jan;191:106432.
3. Lee JS, Ryu JH, Elicker BM, et al. Gastroesophageal reflux therapy is associated with longer survival in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 Dec 15;184(12):1390–1394.
4. Pruijn GJM. Citrullination and carbamylation in the pathophysiology of rheumatoid arthritis. Front Immunol. 2015 Apr 27;6:192.