Photographic Negative Pulmonary Oedema Secondary to Aspergillus Flavus

Sharad Joshi¹, Ankit Bhatia^1*, Nitesh Tayal¹, Saloni Sehgal²

¹Department of Pulmonary Medicine, Max Super Speciality Hospital, Vaishali, Ghaziabad
²Department of Microbiology, Max Super Speciality Hospital, Vaishali, Ghaziabad

Abstract
Background: This article reports a unique case of severe pulmonary aspergillosis triggered by Aspergillus flavus infection, culminating in organising pneumonia with alveolar leaks and severe respiratory distress in a previously healthy individual. The patient, a 48-year-old man, presented with symptoms of fever, dry cough, and hypoxia, with imaging revealing bilateral ground-glass consolidations reminiscent of photographic negative pulmonary oedema. Bronchoalveolar lavage confirmed the presence of Aspergillus flavus hyphae, establishing the diagnosis of aspergillosis-induced organising pneumonia. Initial treatment with Initial treatment with voriconazole and methylprednisolone yielded partial improvement. However, the patient experienced subsequent deterioration, necessitating amphotericin therapy.

This case underscores the potential association between Aspergillus flavus infection and the pathogenesis of organising pneumonia, particularly in immunocompetent individuals. The presentation of severe respiratory compromise in the absence of predisposing factors highlights the diagnostic and therapeutic challenges posed by such cases.

This case serves as a compelling reminder of the diverse clinical manifestations of Aspergillus infections and underscores the importance of considering fungal aetiologies in the differential diagnosis of organising pneumonia, particularly in the absence of overt immunodeficiency.

Key words: Organising Pneumonia; Cryptogenic; Aspergillus

Introduction

Organising pneumonia (OP) represents a clinical, radiological, and histological condition indicative of lung tissue repair. It may arise as a consequence of a pulmonary lesion (such as infection, toxicity, or radiotherapy) or be linked with a primary pulmonary disorder (including vasculitis, neoplasia, or pulmonary infarction). In exceptional instances, it is deemed idiopathic and is categorized as cryptogenic organising pneumonia.¹

Aspergillus flavus is a ubiquitous fungus, having a propensity to affect immunocompromised patients. It can be an inciting agent for a secondary organising pneumonia as well.

In this article, we report the first case of severe pulmonary aspergillosis resulting from Aspergillus flavus infection, leading to an organising pneumonia with alveolar leaks and severe respiratory failure due to severe inflammation in the lungs.

Case report

A 48-year-old man, with no comorbidities presented to the emergency room (ER) with a one-week history of fever with chills, dry cough and shortness of breath. On evaluation in the ER, he was found to be hypoxic, with an oxygen saturation of 84% on room air. On physical examination, chest auscultation showed diffuse scattered crepitations. His chest X-ray showed bilateral peripheral parenchymal infiltrates (Figure 1).

A bronchoscopic lung biopsy was planned but was not consented to by the patient. A bronchoalveolar lavage (BAL) was done, which showed revealed septate and branching fungal hyphae consistent with the morphological features of Aspergillus flavus (Figure 3).

Figure 1 Chest X-ray showing peripheral consolidation

Initial investigations showed total leucocyte counts of 9 × 10³/mm³ and C-reactive protein level of 102mg/dL. His chest computed tomography (CT) scan showed bilateral peripheral ground-glass consolidation, consistent with a photographic negative of a pulmonary oedema (Figure 2).

Figure 2: CT Thorax: Bilateral peripheral ground-glass consolidation

Figure 3: Bronchoalveolar lavage (BAL) fungal stain showing septate and branching fungal hyphae consistent with the morphological features of Aspergillus flavus

He had a history of recent visit to his ancestral village house which had been closed for many years. Aspergillosis with OP was diagnosed, and the patient was started on voriconazole therapy along with methylprednisolone 16mg once a day. He improved subsequently, the oxygen requirement was reduced, and the patient was shifted to a ward. However, he deteriorated again, his oxygen requirement increased, and he was shifted back to the intensive care unit (ICU). A repeat CT Thorax was done which showed mediastinal emphysema, and alveolar leak. The patient was started on treatment with liposomal amphotericin B, while sputum cultures were sent which revealed Klebsiella spp. His antibiotics were also escalated. He improved slowly and was subsequently discharged in stable condition.

Discussion

Organising pneumonia can manifest unexpectedly, often without a discernible cause, referred to as cryptogenic organising pneumonia (COP). Alternatively, it can develop in conjunction with conditions known to trigger this pathological pattern, termed secondary cryptogenic organising pneumonia (SOP).¹

Histopathologically, OP is characterized by the filling of alveolar ducts and airspaces with granulation tissue, accompanied by chronic inflammation surrounding the alveoli. Its manifestation often lacks specificity, typically presenting symptoms such as persistent cough lasting from weeks to months, accompanied by fever, shortness of breath, and occasional fatigue. Radiological changes observed include lung opacities, which can be unilateral or bilateral on chest radiographs, with corresponding ground glass consolidations on CT scans. Unusual radiological features may include crazy-paving patterns, linear and band-like opacities, infiltrative opacities, and multiple nodular opacities

Organising pneumonias are usually treated with corticosteroids, with more than 50% of cases showing good initial improvement. In some cases refractory to corticosteroids, alternate management with pulse steroids, adjunctive immunosuppression therapy, macrolides, and cytotoxic agents have been reported.²

Aspergillus induces a range of ailments in humans, broadly categorized as saprophytic, allergic, or invasive, contingent upon the interplay between the host's immune response and the virulence of the fungus. Pulmonary aspergillosis typically necessitates predisposing host factors for infection, such as prior infections, chronic obstructive pulmonary disease (COPD), other obstructive lung diseases, or structural lung abnormalities. In the case of organising pneumonia

Cases of invasive pulmonary aspergillosis (IPA) have been reported in immunocompetent patients after extensive environmental exposure to Aspergillus spores. Organising pneumonia linked with IPA has been sporadically documented.

In 2014, a patient succumbed to the simultaneous occurrence of invasive pulmonary aspergillosis and OP.³ In 2017, a man experienced chronic pulmonary aspergillosis, resulting in the onset of OP, which responded well to corticosteroid treatment and surgical intervention.⁴ Subsequently, in 2018, a patient undergoing mechanistic Target of Rapamycin (mTOR) inhibitor

therapy developed invasive pulmonary aspergillosis, and presented with symptoms resembling OP.¹ These clinical cases, alongside our own observations, suggest a potential association between pulmonary aspergillosis and the pathogenesis of OP. However, this seems to be the first case of Aspergillus flavus causing this disorder in an immunocompetent patient. The previous two patients reported were immunocompromised.⁵

IPA continues to contribute substantially to both morbidity and mortality rates. The range of illnesses linked to Aspergillus species in the lungs varies. However, the precise relationship between Aspergillus species and the development or progression of OP remains largely uninvestigated.

In the case of OP secondary to IPA, management usually depends completely on the identified cause. Currently, there are no specific recommendations on the management, particularly regarding the value of prescribing corticosteroids in combination with antifungals

Clinicians need to be vigilant for invasive pulmonary aspergillosis alongside OP to prevent delays in diagnosis and potential treatment complications.

Source(s) of support: None
Presentation at a meeting: None
Conflicting Interest (If present, give more details): None

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