Candida pulmonary infection mimicking steroid-refractory radiation pneumonitis during corticosteroid taper: a case report

Introduction

Radiation pneumonitis (RP) is a common early manifestation of radiation-induced lung injury, typically occurring within 0–12 months after thoracic radiotherapy and characterized by inflammatory damage to alveolar epithelium and capillary endothelium; reported incidences range up to ~30% depending on dose, volume irradiated, and concurrent treatments (1,2). Corticosteroids remain the cornerstone of symptomatic RP management, but their prolonged or high-dose use can suppress host immunity and disrupt pulmonary microbiota, predisposing patients to opportunistic fungal infections (3). Despite this biologically plausible risk, the literature has focused predominantly on bacterial superinfections in severe RP. In a large cohort of non-small cell lung cancer (NSCLC) patients with severe RP, 44.5% developed secondary lung infections, yet the majority were bacterial, and the study only inferred a potential benefit of empirical antifungal therapy without detailing individual fungal cases (4,5). Consequently, the true incidence of proven fungal pneumonia during steroid treatment for RP remains uncertain and likely underrecognized.

Current practice recommendations for RP focus primarily on indications for initiating corticosteroids, suggested dosing, and tapering schedules, but they provide limited guidance on the systematic evaluation and management of opportunistic infection during treatment, particularly fungal disease. Most available data on infections complicating RP describe bacterial pathogens, and only sporadic reports mention fungal superinfections, usually without detailing the diagnostic pathway, interpretation of fungal biomarkers, or strategies for adjusting immunosuppression. As a result, clinicians lack practical algorithms for distinguishing RP flare from fungal pneumonia in patients who deteriorate while receiving steroids, especially during the tapering phase.

This case is unique in several respects. First, it describes Candida pulmonary infection occurring during the tapering phase of corticosteroid therapy for RP, a period in which clinical deterioration is easily misinterpreted as steroid-refractory RP or ‘RP rebound’. Second, it details a stepwise diagnostic workup that integrates evolving chest computed tomography (CT) findings, bronchoscopy with bronchoalveolar lavage (BAL), and (1,3)-β-D-glucan (BDG) to distinguish inflammatory progression from opportunistic infection. Third, it illustrates a practical diagnostic-therapeutic pathway in which timely bronchoscopy, initiation of targeted antifungal therapy, and deliberate tapering rather than escalation of steroids led to rapid clinical and radiologic improvement. By presenting this pathway, we aim to provide concrete guidance for clinicians on when to suspect fungal superinfection and how to adjust immunosuppression when RP worsens under steroid therapy. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-211/rc).

Case presentation

A 55-year-old man presented in 2022 with intermittent hemoptysis (Table 1). Contrast-enhanced chest CT performed at a local hospital in December 2023 revealed thickening of the bronchial wall in the left upper lobe, suspicious for malignancy. Bronchoscopic biopsy confirmed squamous cell carcinoma in situ of the left upper lobe and left main bronchus, with focal areas of invasion. Staging investigations—including brain magnetic resonance imaging (MRI), abdominal CT, and bone scintigraphy—showed no evidence of distant metastasis. The patient subsequently received two cycles of neoadjuvant therapy consisting of tislelizumab 200 mg, albumin-bound paclitaxel 200 mg, and carboplatin 500 mg. In February 2024, he underwent left upper lobectomy combined with tracheoplasty, pulmonary artery reconstruction, and lymph node dissection. Postoperative pathology demonstrated moderately differentiated squamous cell carcinoma with invasion of the bronchial adventitia; among 10 lymph node groups sampled, one of six nodes was positive. The final pathological stage was ypT1aN2bM0. One additional cycle of adjuvant chemotherapy was administered. The patient had no relevant family history, psychosocial conditions, lifestyle exposures, or genetic predisposition.

Given the pathological findings and clinical indications, volumetric modulated arc therapy (VMAT) using 6 megavolts (MV) X-rays [95% planning target volume (PTV); 45 Gy/1.8 Gy/25 fractions] was delivered in July 2024. The course was uneventful, and the patient was discharged. Two weeks after completing radiotherapy, he developed fever (maximum temperature 39.2 °C), productive cough, anorexia, and approximately 3 kg weight loss. On August 13, 2024, outpatient chest CT demonstrated bilateral interstitial changes, more prominent on the left, and he was admitted with a working diagnosis of RP (Figure 1).

Figure 1 CT of initial RP. CT, computed tomography; RP, radiation pneumonitis.

Physical examination revealed decreased breath sounds over the left lung without audible rales. Laboratory data showed leukopenia (white blood cell count 3.18×10⁹/L), neutrophilia (85.6%), C-reactive protein 121.5 mg/L, and procalcitonin 0.260 ng/mL. Chest CT changes overlapped the irradiated field (Figure 2). He was started on intravenous methylprednisolone 80 mg every 12 hours, ceftazidime, omeprazole, and supportive care. Symptoms initially improved, allowing steroid tapering to 40 mg every 12 hours. Thereafter, the dose was reduced in a stepwise manner over approximately 6 weeks in parallel with antifungal therapy until complete discontinuation. This regimen lasted only 2 weeks before the patient’s condition showed progression.

Figure 2 Radiotherapy target field.

On August 30, he experienced recurrent fever and worsening dyspnea. Repeat chest CT revealed extensive bilateral ground-glass opacities and reticular changes extending beyond the original radiation field, indicating disease progression (Figure 3). Given the new radiologic pattern and clinical relapse under steroid therapy, an opportunistic infection was strongly suspected, although an RP flare could not be excluded. Bronchoscopy showed congested, edematous mucosa in the left lower lobe bronchus with abundant yellow-white secretions. Microscopy of BAL fluid identified fungal spores, and Candida species grew in culture. Serum BDG exceeded 600 pg/mL, and serial galactomannan (GM) measurements ranged from 0.098 to 1.07 ng/mL, with a single modest elevation above the diagnostic cut-off. In the absence of CT features typical of invasive aspergillosis and without isolation of Aspergillus species from BAL, the multidisciplinary team considered invasive mold disease less likely and diagnosed RP complicated by Candida pulmonary infection. Based on this integrated assessment, the treatment plan was modified to address both ongoing inflammation and superimposed fungal infection.

Figure 3 RP combined with PM. PM, pulmonary mycosis; RP, radiation pneumonitis.

Therapy was adjusted to include oral fluconazole 200 mg once daily and trimethoprim-sulfamethoxazole (TMP-SMX) (600 mg/1,200 mg every 6 hours), together with ongoing hepatogastric protection and supportive care. Fluconazole was selected because Candida species had been repeatedly isolated from BAL culture, and there were no radiologic or microbiologic features strongly suggestive of invasive mold disease, despite only a single modest GM elevation around the diagnostic cut-off. TMP-SMX at therapeutic dosing was administered as empirical treatment for Pneumocystis jirovecii pneumonia in view of the patient’s prolonged high-dose corticosteroid exposure, markedly elevated BDG, and progressive hypoxemic respiratory failure, and was subsequently continued as prophylaxis during a planned 6-week course. Systemic corticosteroids, which had already been reduced from intravenous methylprednisolone 80 mg every 12 hours to 40 mg every 12 hours after the initial improvement in RP, were then tapered in a stepwise manner, decreasing the dose by 5 mg every 5 days in parallel with antifungal therapy, until discontinuation over approximately 6 weeks. Medication adherence was confirmed through telephone follow-ups, and the regimen was well-tolerated without treatment-limiting side effects. No adverse or unanticipated events, including hepatic enzyme elevation, QT prolongation, rash, cytopenia, or electrolyte imbalance, were observed during follow-up. After 2 weeks, the patient’s symptoms markedly improved; he reported only occasional mild cough without fever or dyspnea, and laboratory markers showed improvement [serum BDG decreased from >600 to 55.479 pg/mL; GM 0.066 (negative); white blood cell count 6.60×10⁹/L with neutrophils 78.90%; C-reactive protein 1.59 mg/L]. He was discharged on continued oral antifungal therapy. Six weeks later, follow-up CT demonstrated substantial absorption of the previous ground-glass opacities, and his condition remained stable (Figure 4).

Figure 4 After 2 months of antifungal treatment.

Patient perspective

I first noticed intermittent coughing of blood, which made me anxious about whether the cancer had returned. After surgery, chemotherapy, and radiotherapy, I hoped the worst was behind me. When my breathing worsened while I was already taking steroids and antibiotics, I felt confused and worried that the treatment was failing. The medical team explained that infection can mimic radiation injury and advised further tests.

The bronchoscopy was uncomfortable but brief, and I was relieved to receive a clear explanation of the results. Once antifungal treatment was added, and the steroids were tapered, my fever resolved, and breathing improved within days. I could sleep better and gradually return to daily activities. Regular follow-up and repeat scans reassured me that I was recovering. I am grateful for the coordinated care and agreed to share my experience so that other patients in a similar situation might be diagnosed and treated sooner.

Ethical consideration

The contents and purpose of this report were explained to the patient. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

This report underscores that the steroid tapering phase in RP management is a high-risk window for fungal infection and cautions clinicians against mislabeling symptom exacerbation as mere “RP rebound”. In the presented case of a stage IIIA locally advanced NSCLC patient, dyspnea and radiographic changes emerged 1 month after postoperative radiotherapy. According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria, these findings met grade II RP (6). Standard care—intravenous dexamethasone or methylprednisolone at 1–4 mg/(kg·d)—was initiated, typically continued for 1–2 weeks until respiratory symptoms stabilize. However, in this patient, clinical deterioration occurred after 2 weeks of combined steroid and antibiotic therapy. Chest CT and bronchoscopy then suggested a concomitant pulmonary mycosis (PM). Antifungal therapy led to symptom reduction and radiographic improvement.

Radiotherapy can suppress immune function, and patients with lung cancer often have underlying chronic pulmonary conditions that increase infection susceptibility. Prolonged, high-dose steroids and antibiotics exacerbate immunosuppression and alter microbial flora, facilitating opportunistic infections. While sputum cultures can help identify pathogens, they frequently yield negative results and do not exclude PM. Recurrence or worsening of RP manifestations is often misinterpreted as disease rebound, yet clinical worsening during steroid tapering may instead signal superimposed infection. Differentiating RP flare from infection is therefore crucial to guide therapy (7,8).

The choice of fluconazole and TMP-SMX in this case reflects both the most likely pathogen spectrum and the diagnostic uncertainty in non-neutropenic hosts. Fluconazole was selected because Candida spp. were repeatedly isolated from BAL fluid, and there was no compelling radiologic or microbiologic evidence of invasive mold disease, even though GM values fluctuated around the diagnostic threshold, which is consistent with recent global candidiasis guidelines recommending fluconazole as targeted therapy in clinically stable patients with susceptible Candida isolates and low suspicion for mold infection (9-13). We recognize that fluconazole has no activity against Aspergillus, and this constitutes a limitation of our management; however, the rapid clinical and radiologic response in the absence of mold-active therapy makes clinically significant invasive aspergillosis unlikely. TMP-SMX was used as empirical therapy for possible Pneumocystis jirovecii pneumonia in the context of prolonged high-dose corticosteroid treatment and markedly elevated BDG and was then continued as prophylaxis while steroids were tapered, in line with current recommendations for Pneumocystis jirovecii pneumonia prevention in immunocompromised adults (14).

The clinical spectrum of PM includes fever, dry cough, chest tightness, and dyspnea; physical examination may be unremarkable or reveal scattered crackles. Radiologically, chest X-rays can show bilateral decreased translucency or central ground-glass opacities, while CT may reveal miliary nodules, patchy or diffuse ground-glass opacities, and even interstitial fibrosis. Notably, PM changes may extend beyond the radiation field, heightening suspicion. Diagnostic confirmation typically requires sputum analysis, BAL, or lung biopsy to detect causative organisms (15). In this case, RP with PM necessitated adding antifungal agents, and drug selection should be tailored to microbial sensitivity to ensure therapeutic efficacy.

In this case, the diagnosis of RP complicated by PM was established by integrating the clinical course, imaging evolution, bronchoscopic findings, microbiology, and fungal biomarkers, in line with current practice for invasive fungal disease in high-risk non-neutropenic hosts. Candida isolated from respiratory specimens, including BAL, is often regarded as colonization, and serum BDG is not perfectly specific; GM values around the diagnostic cut-off can also be difficult to interpret. These limitations must be considered in context. Our patient had malignancy, recent thoracic radiotherapy, and high-dose glucocorticoids with broad-spectrum antibiotics; he progressed from field-congruent opacities to diffuse bilateral ground-glass changes beyond the radiation volume, showed abundant exudate with BAL microscopy and culture repeatedly positive for Candida spp., and had markedly elevated BDG levels that fell sharply after initiation of fluconazole, in parallel with rapid clinical and radiologic improvement. GM measurements fluctuated between 0.098 and 1.07 ng/mL, with only a single modest elevation above the cut-off and no CT features typical of invasive aspergillosis, such as discrete nodules with halo sign or cavitation, and Aspergillus species were not isolated from BAL (16,17). Taken together, these findings led the multidisciplinary team to consider clinically significant invasive aspergillosis unlikely and to interpret the GM signal as probably false-positive or non-specific. Lung biopsy was not pursued because of respiratory compromise, so histopathological proof of tissue invasion is lacking, as in many real-world cases; nevertheless, the overall constellation is most consistent with a Candida pulmonary infection superimposed on RP.

For patients requiring long-term steroids, periodic imaging is recommended to promptly detect infectious changes. In refractory or recurrent cases, bronchoscopy allows direct visualization of airway pathology and targeted sampling through BAL for culture and biomarkers. In our patient, bronchoscopy with BAL was performed when clinical deterioration occurred despite 2 weeks of steroid and antibiotic therapy, chest CT showed new bilateral ground-glass opacities extending beyond the radiation field, and inflammatory markers remained abnormal. More generally, recurrent fever or dyspnea during steroid taper, radiologic progression beyond the irradiated volume, and unexplained elevation of inflammatory markers should prompt early bronchoscopy with BAL in RP patients receiving corticosteroids. Because RP and PM overlap clinically and radiographically, misdiagnosis is common; clinicians must integrate history, imaging, and laboratory tests—especially during steroid taper—to consider concurrent infection. The key to recovery was timely antifungal therapy combined with deliberate steroid tapering once PM was recognized, rather than simple continuation of antibacterial agents or escalation of immunosuppression.

Conclusions

This case highlights that opportunistic fungal infection, particularly Candida pulmonary infection, can closely mimic steroid-refractory RP during corticosteroid tapering. In patients with RP who deteriorate under steroid therapy—especially when radiologic abnormalities extend beyond the radiation field—clinicians should maintain a high index of suspicion for superimposed infection rather than reflexively escalating immunosuppression. Early bronchoscopy with BAL, combined with careful interpretation of fungal biomarkers, is crucial for timely diagnosis. Prompt initiation of targeted antifungal therapy together with judicious tapering of corticosteroids may reverse clinical deterioration and improve short-term outcomes. This case underscores the importance of reassessing the etiology of apparent RP relapse and adopting an integrated diagnostic–therapeutic approach during steroid treatment.

Acknowledgments

We gratefully acknowledge the Department of Radiation Oncology, Inner Mongolia People’s Hospital, for providing the clinical case materials and invaluable support in patient management and data collection.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-211/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-211/prf

Funding: This work was supported by the Hohhot Health Science and Technology Plan Fund (No. 2024-Huweike-012).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-211/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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