Allergic Bronchopulmonary Mycosis Caused by Nigroporus vinosus

Abstract

Allergic bronchopulmonary mycosis (ABPM) is a chronic respiratory disease in which saprophytic fungi grow in the airways of adults and induce types I and III allergic reactions. ABPM is often caused by Aspergillus spp.; however, data on non-Aspergillus ABPM are limited. The newly proposed diagnostic criteria for ABPM in Japan allow for the diagnosis without asthma or with non-Aspergillus ABPM. Nigroporus vinosus is a filamentous fungus present in mushrooms. We herein present the first case of ABPM caused by Nigroporus vinosus. The organism was identified in the sputum of a patient with clinically suspected ABPM, and the symptoms improved with corticosteroid treatment.

Introduction

Allergic bronchopulmonary mycosis (ABPM) is a chronic respiratory disease characterized by the growth of saprophytic fungi in the airways of adult patients with asthma or cystic fibrosis, which induces type I and III allergic reactions. The most common causative fungi of ABPM are Aspergillus spp., and there are limited data on non-Aspergillus ABPM causative fungi. The diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) are based on the criteria of Rosenberg et al. (1) and the International Society for Human and Animal Mycology (ISHAM) (2). However, it has been pointed out that these criteria have low sensitivity for the diagnosis of ABPM. New clinical diagnostic criteria for ABPM have been proposed in Japan, allowing for its diagnosis even in patients without asthma or with non-Aspergillus ABPM (3).

Nigroporus vinosus is a filamentous fungus found in the mushroom called “budoutake” in Japan. To date, there have been no reports of Nigroporus vinosus causing ABPM; however, we report this case. The fungus was identified by a genetic analysis, and the patient's condition improved with the administration of oral and inhaled corticosteroids (ICS).

Case Report

A 65-year-old man was diagnosed with bronchial asthma by a primary care physician two years prior and was prescribed ICS/long-acting beta 2-agonists (LABA). Three months before visiting our hospital, he had cleared undergrowth from the trees behind his house and had removed a flat, brownish-red mushroom growing at the base of a Japanese apricot tree with his bare hand (Fig. 1). Subsequently, his cough and dyspnea worsened. His symptoms did not improve despite an increase in the ICS dose. Chest radiography revealed multiple nodules and the patient was referred to our hospital for further examination and treatment. The patient's medical history included bronchial asthma. There was no history of malignancy or family history of autoimmune diseases. The patient regularly received montelukast sodium and inhaled dual therapy with budesonide and formoterol fumarate dihydrate. There were no abnormalities in vital signs, and wheezing was heard in both lung fields. Blood tests revealed an elevated absolute peripheral eosinophilic count (870/μL), C-reactive protein (0.73 mg/dL), and IgE (240 U/mL). β-D-glucan was within the normal range (＜5.0 pg/mL), and Aspergillus-specific IgE antibody was negative. Chest radiography revealed multiple bilateral nodular shadows predominantly in the lower lung fields (Fig. 2). High-resolution chest computed tomography (CT) revealed multiple mucus plugs in both lower lobes (Fig. 3a, b), which appeared as high-attenuation areas. Most of these plugs showed attenuation values ≥70 Hounsfield units, consistent with high-attenuation mucus (HAM). Respiratory function tests showed normal vital capacity (VC, 3.18 L; %VC, 84.1%). However, the forced expiratory volume in 1 second (FEV1) was reduced (FEV1, 1.73 L; %FEV1, 67.1%; FEV1%, 54.9%), and the fraction of exhaled nitric oxide was high (74 ppb). Although no mucus plugs were observed in the subsegmental bronchi during bronchoscopy, a large amount of thick sputum was collected from the periphery of the lower lobe (Fig. 4). Microscopic examination of the sputum collected via bronchoscopy did not reveal any filamentous fungi; however, culture testing detected filamentous fungi and giant colonies (Fig. 5a, b). Fungal culturing was initially performed on Sabouraud dextrose agar at 38°C for two days, followed by continued incubation at 25°C. Nigroporus vinosus was detected on day 10 of culture. Because it was difficult to identify the filamentous fungus at our hospital, we asked the Fungus Reference Center at Chiba University to identify it. The fungus was identified as Nigroporus vinosus through an internal transcribed spacer gene sequence analysis. We started treatment with prednisolone (0.5 mg/kg/day), considering it to be ABPM, and the patient's asthma symptoms improved. Antifungal agents were not administered. On chest CT three months after the initial examination, most of the mucus plugs had disappeared, but central bronchiectasis was apparent (Fig. 6). Subsequently, the patient's condition improved with oral corticosteroids and ICS/LABA. Six months after the initial examination, the patient reported that his asthma symptoms temporarily worsened after the removal of Nigroporus vinosus-like mushrooms from the forest behind his house with his bare hands without wearing a mask. Subsequently, we instructed the patient not to remove the mushrooms, and he did not experience any further asthma attacks.

Figure 1.

Photograph of a mushroom removed manually by the patient.

Figure 2.

Chest radiography findings on admission. Nodular shadows are seen in the lower lung fields on both sides.

Figure 3.

High-resolution chest computed tomography (CT) findings on admission. Chest CT shows a nodular shadow in the lower lobe bronchus in the lung window (a) and high-attenuation mucus in the mediastinal window (b).

Figure 4.

Bronchial lumen findings. The presence of a mucus plug is recognized.

Figure 5.

Fungal culture obtained from sputum collected during bronchoscopy (a) and a giant colony (b).

Figure 6.

Chest computed tomography 3 months after admission. The sputum in the bilateral lower lobe bronchi disappeared, and centripetal bronchiectasis persisted.

Discussion

ABPM develops as a result of type I and III hypersensitivity reactions to filamentous fungi (2). Aspergillus is the most common fungus known to induce ABPM. However, other organisms, including Schizophyllum commune, Alternaria, Bipolaris, Cladosporium, Curvularia, Fusarium, Penicillium, Pseudallescheria, Rhizopus, Saccharomyces, Stemphylium, and Trichosporon, can cause clinical manifestations similar to those of ABPM (3-7).

Nigroporus vinosus is a poroid fungus belonging to the family Steccherinaceae and is a type species of the genus Nigroporus. Nigroporus vinosus has a pantropical distribution. This species has been recorded in Africa, North America, Central America, South America, Asia and Oceania. Nigroporus vinosus is a white-rot fungus that grows on decaying hardwood trees (8). Although expert mycological identification was not performed in this case, the collected mushroom exhibited the following morphological characteristics: a cap diameter of approximately 15 cm, semicircular shape, and a reddish-brown color resembling that of grapes. These characteristics were considered consistent with the genus Nigroporus vinosus. To our knowledge, Nigroporus vinosus has not been previously reported as a causative agent of ABPM. Although no reports have directly linked Nigroporus vinosus to bronchial asthma, a study involving patients with bronchial asthma and chronic obstructive pulmonary disease (COPD) demonstrated that Nigroporus species were more frequently detected in the sputum of patients with eosinophilic COPD (9). In this case, we considered that the patient developed ABPM due to Nigroporus vinosus based on the following factors: exacerbation of asthma symptoms following unprotected exposure to the fungus, presence of HAM in the bronchi on chest CT, and detection of Nigroporus vinosus in the sputum collected from the bronchi during bronchoscopy.

The conventional criteria for the diagnosis of ABPA are specific to Aspergillus fumigatus (1,2,4,10); therefore, it is challenging to make a definitive diagnosis using the former ABPM criteria. Laboratory tests for specific IgE/IgG are not necessarily available for ABPM-causing fungi and clinical characteristics are often atypical. In addition, Ishiguro et al. reported 17 cases with biopsy-confirmed ABPM and found that seven cases lacked peripheral blood eosinophilia and three had total serum IgE of ＜1,000 IU/mL (11).

In our case, the patient met six of the ten criteria proposed by the Japanese Research Group for Allergic Bronchopulmonary Mycosis in 2019 (3): 1) current or previous history of asthma or asthmatic symptoms; 2) peripheral blood eosinophil count ＞500/mm³; 3) filamentous fungal growth in sputum cultures or bronchial lavage fluid; 4) central bronchiectasis on CT; 5) presence of mucus plugs in the central bronchi, based on CT/bronchoscopy or mucus plug expectoration history; and 6) HAM in the bronchi on CT. According to the revised diagnostic criteria for ABPM proposed by the ISHAM working group in 2024 (4), the presence of HAM on chest CT is considered a pathognomonic feature with high diagnostic specificity. Although our case did not meet the required criteria of fungus-specific IgE or IgG and the patient's total serum IgE level was not elevated, several other supporting findings were present. These included peripheral eosinophilia (＞500 cells/μL), detection of Nigroporus vinosus from a bronchoscopic specimen, and multiple mucus plugs demonstrating attenuation values of ≥70 Hounsfield units on CT. In the revised criteria, HAM is described as a highly specific radiologic finding for ABPM, and its presence alone may be sufficient to support the diagnosis, even in the absence of other major criteria.

Differentiating ABPM from severe eosinophilic asthma can be challenging, particularly in cases lacking full serological confirmation. However, our patient exhibited several features that favored the diagnosis of ABPM rather than severe asthma. These include the presence of HAM on chest CT, a hallmark finding not typically seen in asthma, and the isolation of filamentous fungus (Nigroporus vinosus) directly from bronchial specimens. Furthermore, the temporal relationship between symptom exacerbation and environmental fungal exposure supports a hypersensitivity mechanism. Although severe asthma may present with mucus hypersecretion and eosinophilia, the constellation of radiological, clinical, and microbiological findings in this case strongly supports ABPM over isolated eosinophilic asthma.

Contamination must be carefully considered when identifying new fungal species as the causative agents of ABPM. In the present case, bronchial asthma was diagnosed several years before the onset of ABPM, and the patient's asthma symptoms worsened after the mushrooms were manually removed without wearing a mask.

Furthermore, despite continued treatment with inhaled and oral corticosteroids (5 mg/day), the patient's symptoms worsened again after manually collecting mushrooms of the same type with his bare hands. Based on this temporal association, we concluded that the inhalation of Nigroporus vinosus spores contributed to the exacerbation of the patient's asthma symptoms.

Written informed consent was obtained from the patient for the publication of this case report.

The authors state that they have no Conflict of Interest (COI).