Cytomegalovirus Pneumonia Requiring Intensive Care During Treatment for Rapidly Progressive Interstitial Lung Disease Associated With Anti‐Synthetase Syndrome: A Case Report

ABSTRACT

A 70‐year‐old man presented with fever and malaise and was diagnosed with anti‐synthetase syndrome based on chest computed tomography and laboratory findings. Steroid therapy was initiated because of progressive respiratory failure. However, despite steroid therapy, his respiratory status worsened, accompanied by expansion of ground‐glass opacities (GGOs) on imaging. On hospital day 26, the patient developed severe respiratory failure, requiring mechanical ventilation and prone positioning, at which time cytomegalovirus (CMV) antigenemia was detected. After clinically diagnosing CMV pneumonia superimposed on interstitial lung disease (ILD), ganciclovir was initiated while gradually tapering corticosteroid therapy. This approach led to significant clinical and radiological improvements. The patient was successfully weaned from ventilation on day 30 and discharged on day 70. In patients with rapidly progressive ILD who deteriorate despite high‐dose corticosteroids and develop new diffuse GGOs, superimposed CMV infection should be suspected and promptly evaluated. Early recognition and antiviral therapy are essential for improving outcomes.

We report a case of anti‐synthetase syndrome associated with rapidly progressive interstitial lung disease (RP‐ILD), complicated by early‐onset cytomegalovirus pneumonia that mimicked treatment‐resistant RP‐ILD on imaging. The patient survived intensive care and received antiviral therapy. Although interstitial pneumonia requiring invasive mechanical ventilation is generally associated with a poor prognosis, careful evaluation is essential to avoid overlooking treatable conditions.

1. Introduction

Interstitial lung disease (ILD) with anti‐synthetase syndrome (ASyS) frequently requires early steroid and immunosuppressive therapy because of its poor prognosis in acute and subacute cases [1]. However, such aggressive immunosuppression substantially increases the risk factor for cytomegalovirus (CMV) reactivation. Here, we report a case of anti‐EJ antibody‐positive rapidly progressive interstitial lung disease [2] (RP‐ILD) that deteriorated during corticosteroid therapy. Although the initial presentation suggested primary disease progression, CMV pneumonia was ultimately diagnosed based on serum antigenemia levels. The patient was successfully treated with combined antiviral therapy and intensive care.

2. Case Report

The patient was a 70‐year‐old man with diabetes and a 40‐pack‐year smoking history. One week before admission, he developed fatigue and fever. Initial treatment with oral antibiotics was ineffective, prompting transfer to the previous hospital.

On admission, he was febrile (37.8°C) with tachypnea (24 breaths/min) and oxygen saturation (SpO₂) of 94% on 3 L/min via nasal cannula. Chest computed tomography (CT) revealed infiltrative opacities and ground‐glass opacities (GGOs), predominantly in the dorsal regions of both lower lung fields (Figure 1a). Despite intravenous antibiotic therapy (piperacillin/tazobactam (PIPC/TAZ)), the patient's respiratory status worsened. High‐dose intravenous methylprednisolone (IVMP; 500 mg/day for 3 days) was initiated on hospital Day 3.

FIGURE 1.

Serial changes in chest computed tomography (CT) findings. Chest CT images on admission (a) demonstrate consolidation and ground‐glass opacities (GGOs) with subpleural sparing in the lower lobes, indicative of nonspecific interstitial pneumonia with organising pneumonia pattern. Despite steroid pulse therapy, the GGOs had expanded bilaterally by Days 7 (b) and 15 (c), accompanied by interlobular septal thickening and traction bronchiectasis. Following ganciclovir treatment and intensive care, the infiltrate significantly improved by Day 72 (d). Upper row: Axial sections at the tracheal carina level. Lower row: Axial sections at the lower lobe level.

By day 10, his oxygen requirement had increased to 6 L/min. Serological testing was positive for anti‐aminoacyl‐tRNA synthetase antibodies, prompting a second course of IVMP. Despite these interventions, follow‐up chest CT revealed expansion of GGOs (Figure 1b,c), and hypoxemia persisted. A third course of IVMP was administered on Day 17, and antibiotic therapy was continued (PIPC/TAZ from day 1 to day 15, followed by PIPC/TAZ plus vancomycin from Day 16 to 24); however, no clinical improvement was observed. Consequently, on Day 24 after the initial admission, the patient was transferred to our institution for intensive management.

On admission, his vital signs included a body temperature of 36.4°C and SpO₂ of 91% (High‐Flow Nasal Cannula (HFNC) 60 L/min, FiO₂ 90%). Physical examination revealed fine crackles in the bilateral dorsal lung fields, without cutaneous manifestations typical of dermatomyositis and muscle weakness. Laboratory findings were as follows: White blood cell count, 6900/μL; platelet count, 12.3 × 10⁴/μL; lactate dehydrogenase, 434 U/L; C‐reactive protein, 6.4 mg/dL; HbA1c, 8.5%; Krebs von den Lungen‐6, 3762 U/mL; surfactant protein‐D, 682.3 ng/mL; ferritin, 1377 ng/mL; and β‐D‐glucan, 7.8 pg/mL. Creatine kinase and transaminase levels were not elevated. The serum Aspergillus antigen test result was negative. Arterial blood gas analysis revealed a PaO₂/FiO₂ ratio of 82.4. Specific autoantibody testing confirmed anti‐EJ antibody.

Given the refractory ASyS diagnosis, intravenous cyclophosphamide 800 mg (500 mg/m²) was administered on Day 25. However, on Day 26, the CMV antigenemia assay (C7‐HRP) performed on Day 24 returned positive results (517 positive cells per slide). Although bronchoalveolar lavage could not be performed due to severe respiratory failure, CMV pneumonia superimposed on RP‐ILD was clinically suspected.

His respiratory status deteriorated on Day 26, necessitating invasive mechanical ventilation. Prone positioning therapy and lung‐protective ventilation using neuromuscular blockade were instituted promptly. Intravenous ganciclovir (GCV) was initiated, and the corticosteroid dose was tapered concurrently (Figure 2).

FIGURE 2.

Clinical course of the patient. The clinical timeline illustrates the treatments administered and changes in respiratory status, inflammatory markers, and platelet counts. Despite repeated high‐dose intravenous methylprednisolone therapy, the PaO₂/FiO₂ (P/F) ratio (solid line) deteriorated, and C‐reactive protein (CRP) levels (long‐dashed line) fluctuated. After initiating ganciclovir (GCV) for suspected cytomegalovirus pneumonia and mechanical ventilation with prone positioning, the P/F ratio dramatically improved. Additionally, platelet counts (short‐dashed line) showed a declining trend before treatment and subsequently increased after initiating GCV. CRP, C‐reactive protein; GCV, ganciclovir; IVCY, intravenous cyclophosphamide; mPSL, methylprednisolone; P/F, PaO₂/FiO₂ ratio; PIPC/TAZ, piperacillin/tazobactam; PSL, prednisolone; VCM, vancomycin. Black stars (★) on the horizontal axis indicate the timing of CT scans shown in Figure 1.

After initiating GCV, his oxygenation status and radiological findings improved rapidly. Neuromuscular blockade was discontinued on Day 28, and the patient was successfully extubated on Day 30, transitioning to HFNC therapy. Oxygen support was gradually weaned to the nasal cannula on Day 50. He was discharged on Day 70 and required supplemental oxygen at 3 L/min on exertion. A chest CT scan obtained on Day 72 (Figure 1d) revealed near‐complete resolution of the bilateral GGOs and infiltrates, along with increased lung volume. Based on the clinical course, we concluded that the patient had CMV pneumonia complicating RP‐ILD.

3. Discussion

Herein, we report a case of RP‐ILD complicated by CMV pneumonia and resulting in severe respiratory failure during the early stages of treatment for ASyS. Although temporary mechanical ventilation was required, the patient survived the antiviral therapy and intensive care. This case illustrates the diagnostic challenge of distinguishing RP‐ILD from CMV pneumonia and emphasises the need to recognise CMV pneumonia as a treatable condition.

The principal diagnostic challenge was differentiating “refractory RP‐ILD” from “CMV pneumonia” based solely on clinical and radiologic findings. CMV pneumonia in non‐AIDS immunocompromised patients can present with nonspecific imaging shadows, including GGOs and multiple nodular lesions [3]. Therefore, GGO expansion observed during RP‐ILD exacerbation and that caused by CMV pneumonia are essentially indistinguishable on imaging alone.

In this case, we longitudinally evaluated imaging findings from the initiation of immunosuppressive therapy to the development of CMV pneumonia. The patient fulfilled the diagnostic criteria for ASyS [1] and presented with a relatively acute ILD course, commonly observed in anti‐EJ antibody‐positive cases [4]. Initial CT findings (Figure 1a) were consistent with nonspecific interstitial pneumonia with an organising pneumonia pattern. Despite high‐dose steroid therapy, the bilateral GGOs enlarged and expanded ventrally from as early as Day 7, accompanied by interlobular septal thickening and traction bronchiectasis (Figure 1b,d), suggesting treatment‐resistant RP‐ILD. However, in retrospect, despite the expanding GGOs, the posterior basal infiltrates had partially regressed by Day 15. These findings may have indicated a new process rather than a simple progression of RP‐ILD. Additionally, laboratory findings revealed that platelet counts began to decline from Day 13 onward, providing another important clinical clue that raised suspicion of CMV involvement.

The second issue involves the risk assessment of CMV reactivation. The 2022 European Alliance of Associations for Rheumatology guidelines recommend prophylaxis for pneumocystis pneumonia but provide no clear guidance on CMV screening. Here, CMV pneumonia developed early, approximately 2 weeks after initiating treatment. Previous reports have indicated that 76% of CMV infections occur within the first 6 months of glucocorticoid or immunosuppressive therapy [5], with risk increasing alongside peak and cumulative steroid doses [6]. Additionally, in patients receiving methylprednisolone 500 mg/day for at least 1 day, older age (≧ 65 years) and a decreased baseline platelet count (< 30.20 × 10⁴/μL) have been reported as risk factors for developing CMV infection [7]. Furthermore, reports have suggested an association between acute exacerbation of ILD and CMV infection [8]. Therefore, clinicians should be aware that CMV reactivation may occur even early in treatment, particularly in high‐risk patients.

Finally, the appropriate treatment selection is crucial in severe cases. Prognosis is generally poor for patients with ILD requiring mechanical ventilation. Here, aggressive intensive care was justified because the respiratory failure was due to treatable CMV pneumonia, and the patient retained decision‐making capacity. Careful evaluation to identify treatable causes of severe respiratory failure is crucial for favourable outcomes.

In conclusion, CMV pneumonia may closely mimic the exacerbation of RP‐ILD observed on imaging studies. Therefore, early risk assessments and prompt initiation of antiviral therapy are crucial, as appropriate treatment can result in rapid clinical improvement.

Author Contributions

H.A. is the corresponding and principal author. K.F. substantially contributed to the conception of the work and revision of the manuscript drafts. S.M., Y.Y., M.S., S.O., H.K., S.N., and T.F. provided helpful advice to participants. All authors have approved the submitted version of the manuscript and agreed to be accountable for any part of this work.

Funding

The authors have nothing to report.

Consent

The authors declare that written informed consent was obtained for the publication of this manuscript and the accompanying images using the consent form provided by the journal.

Conflicts of Interest

The authors declare no conflicts of interest.

Aramaki H., Fukaguchi K., Miyashita S., et al., “Cytomegalovirus Pneumonia Requiring Intensive Care During Treatment for Rapidly Progressive Interstitial Lung Disease Associated With Anti‐Synthetase Syndrome: A Case Report,” Respirology Case Reports 14, no. 3 (2026): e70553, 10.1002/rcr2.70553.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.