A Rare Case of Rapidly Progressive Diffuse Parenchymal Lung Disease

Introduction

Diffuse parenchymal lung disease (DPLD), also known as interstitial lung disease (ILD), is classified on the basis of shared clinical, radiographic, physiological, or pathological features. The complexity in comprehending this category of diseases arises from the intricate terminology used. In reality, the pathogenic progression entails a sequence of inflammation and fibrosis that extends beyond merely affecting the interstitial bed, as suggested by the name ILD. In DPLD, the pathology alters the lung parenchyma, encompassing the alveoli, alveolar ducts, and bronchioles.1

One condition in which ILD occurs is anti-synthetase syndrome (ASS). It is an autoimmune disease characterised by antibodies directed against an aminoacyl transfer t-RNA synthetase, along with clinical features that can include ILD, myositis, Raynaud’s phenomenon, and arthritis.2 ASS is categorised as an idiopathic inflammatory myopathy (IIM), and is more likely to be associated with ILD than other IIMs, such as dermatomyositis (DM) and polymyositis (PM), with which it shares similar features. The ILD observed in individuals with ASS is frequently intense and progresses rapidly, thus contributing significantly to the elevated morbidity and mortality linked to this syndrome.3

Case Report

A 56-year-old male presented to the emergency department with complaints of shortness of breath and dry cough for one month. The patient had no history of fever, weight loss, or haemoptysis, and was admitted to the ward. He denied any other symptoms, and reported no relevant family history. The patient had previously been treated elsewhere as a case of community-acquired pneumonia based on clinical and radiological findings (Figure 1A).

On examination, the patient was dyspnoeic; the heart rate was 92/min, blood pressure was 110/70 mmHg, and room-air oxygen saturation was 90%, with bilateral crepitations on auscultation. He was initially managed with intravenous (IV) antibiotics, oxygen supplementation, and other supportive measures.

IDespite treatment, his respiratory distress worsened, with new onset haemoptysis and increasing oxygen requirements. The patient was intubated and started on invasive mechanical ventilation. Investigations were sent (enlisted in Tables 1 and 2), and a repeat computed tomography (CT) scan of the chest was performed (Figure 1B) on Day 5 that showed increase in ground-glass opacities indicating worsening of condition.

Upon investigation, the patient tested positive for elevated C-reative protein (CRP), myositis panel (anti-PL-12), and SSA/Ro52 antibodies, and therefore met the diagnostic criteria (Table 3) for ASS. As the patient was not responding to the initial line of treatment involving antibiotics and steroids, on Day 5 he was subsequently treated with IV methylprednisolone 500 mg/day for three doses and 1 gm rituximab for two doses, two weeks apart. Following this, the patient showed significant improvement and was extubated on Day 10. A CT scan was repeated post extubation to assess for sequelae (Figure 1C).

Table 1: Blood and basic investigation.

Abbreviations: AFB Stain: Acid-Fast Bacilli Stain; BUN: Blood Urea Nitrogen; CMV Titre: Cytomegalovirus Antibody Titre; CRP: C-Reactive Protein; DVT: Deep Vein Thrombosis; HIV: Human Immunodeficiency Virus; NT-proBNP: N-terminal pro–B-type natriuretic peptide; PCR: Polymerase Chain Reaction; PJP: Pneumocystis jirovecii pneumonia. PLT: Platelet; SGOT: Serum Glutamic-Oxaloacetic Transaminase; SGPT: Serum Glutamic Pyruvic Transaminase; TLC: Total Leucocyte Count.

Table 2: Specific investigations done for the patient.

Abbreviations: ANA: Anti-Nuclear Antibody; EMG: Electromyography; IF: Indirect Immunofluorescence; NCV: Nerve Conduction Velocity.

Abbreviations: ARS: Aminoacyl t-RNA Synthetase. Conduction Velocity.

Figure 1: Computed tomography (CT) of the chest: A. A small focal area of patchy ground-glass opacity in the subpleural area of the lateral segment of the right middle lobe. Curvilinear ground-glass opacities with stranding in subpleural areas of the superior segment of bilateral lower lobes, B. Day 5: In comparison to prior high-resolution computed tomography (HRCT), an increase in size and attenuation of the ground-glass opacities in the subpleural areas of the superior segments of bilateral lower lobes. Focal ground-glass opacity in the lateral segment of the right middle lobe also shows an increase in attenuation, C. Day 10: Scan shows near complete resolution of the ground-glass opacities in both lower lobes with increased reticulations and strandings representing chronic fibrotic changes post pulse therapy

Discussion

ASS is a rare, multisystemic autoimmune disease with variable symptoms ranging from myositis, ILD, and non-erosive arthritis. The diagnosis of ASS can be facilitated by employing the precise criteria outlined by Solomon et al., and Connors et al. (Table 3).2,4

Six anti-aminoacyl transfer RNA (t-RNA) synthetase autoantibodies have been associated with ASS: anti-histidyl-tRNA synthetase (anti-Jo-1), anti-isoleucyl-tRNA (anti-OJ), anti-threonyl-tRNA (anti-PL7), anti-alanyl-tRNA (anti-PL12), anti-glycyl-tRNA (anti-EJ), and anti-asparaginyl-tRNA (anti-KS). Amongst these, the most common and well-recognised antibody is anti-Jo-1, detected in approximately 20%–30% of such patients.5

Essential components of the diagnostic process include high-resolution computed tomography (HRCT) imaging, which may show nodules, micronodules, linear opacities, irregular interfaces, ground-glass opacities, fibrosis with or without honeycombing, consolidation, traction bronchiectasis, and bronchiectasis.6 Among the observed patterns, nonspecific interstitial pneumonitis (NSIP) is the most common, followed by organising pneumonia.7 Bronchoscopic or muscle biopsy may seldom be required; however, if the patient’s condition permits, a bronchoscopic lavage prior to initiating immunosuppression may be performed to rule out secondary infection.

Currently, there are no established treatment protocols or guidelines for individuals affected by this condition. The first-line of treatment is corticosteroids. Other immunosuppressants such as azathioprine, mycophenolate mofetil, tacrolimus, rituximab, and cyclophosphamide may be used in conjunction with steroids as augmentative therapy for pulmonary and muscular movement. Due to the rarity of the disease, no large-scale treatment trials have been conducted. The available medical literature primarily consists of individual case reports and small case series, with no head-to-head trials. Some reports comparing cyclophosphamide with rituximab have found rituximab to be associated with better progression-free survival at two years, leading some authors to consider it a firstline option.8,9 The use of pulse steroids as a last resort in refractory autoimmune conditions is well-established and may be a viable option in this setting, even though the evidence for its use in ASS remains scarce.10

Contribution

All the authors were involved in the literature search, planning, conducting, writing the original manuscript draft, and editing. All the authors have agreed with the submitted manuscript. Dr. Nikhil Raj is the corresponding author and guarantor for all.

Acknowledgments

The authors would like to thank the residents and interventional pulmonology staff for their support in patient care and data collection.

Conflicts of interest

The authors declare no conflicts of interest regarding the current study.

Funding

The current research received no external funding.

Availability of data and material

The clinical data and the study materials are available from the corresponding author upon reasonable request.

Patient consent

Written informed consent has been obtained from the patient or their legally authorised representative.