Allergic bronchopulmonary mycosis caused by Schizophyllum commune in a patient with severe food allergy and asthma

Abstract

Schizophyllum commune is a basidiomycete. Allergic bronchopulmonary mycosis (ABPM) is mainly caused by Aspergillus species; however, that caused by S. commune is occasionally found, especially in Japan. The patient was a 46-year-old female with a history of severe food allergies, asthma, and anaphylaxis. Atelectasis and bronchiectasis were observed in the left lower lobes of the lungs. The patients showed high levels of IgG and IgE against Aspergillus; however, anti-Asp f 1 IgE, Aspergillus antigen in serum, and Aspergillus species in respiratory specimen cultures were not detected. S. commune was only slightly detected in the culture of bronchial lavage fluids, but not in mucus plugs, and was identified using MALDI-TOF mass spectrometry and the gene sequence of the internal transcribed spacer region. However, clamp connections of the hypha were not observed. Seven of the ten clinical diagnosis criteria of ABPM were met, thus we diagnosed with ABPM caused by S. commune. The patient was treated with 200 mg once daily of oral itraconazole for approximately 10 months and 30 mg (gradually reduced) once daily of oral prednisolone for approximately 7 and a half months.

Introduction

Allergic bronchopulmonary mycosis (ABPM) is caused by exposure of certain fungi into the lungs. ABPM is associated with allergy to mold, and it includes not only type I allergy via specific immunoglobulin E (IgE), but also type III allergy via specific immunoglobulin G (IgG) [1,2]. Recent IgE- and IL-5-targeted therapies using monoclonal antibodies have suggested that the eosinophilic component is a cardinal feature of the development of ABPM, whereas IgE responses are important factors modulating disease manifestation [3]. The most prevalent etiological agent of ABPM is Aspergillus spp., such as Aspergillus fumigatus, whereas other fungi can cause ABPM [4]. In Japan, a research project established under the Japan Agency for Medical Research and Development (AMED) program proposed the clinical practice guideline in 2020 [5]. The validation of this guideline in the real world was reported in 2021, and the diagnostic criteria showed higher sensitivity and specificity for diagnosing ABPM than Rosen-Patterson criteria and International Society for Human and Animal Mycology criteria [1]. In the present report, we describe a case of ABPM caused by Schizophyllum commune, which is a basidiomycetous fungus (mushroom). This is uncommon, but has occasionally been reported in Japan.

Case presentation

A 46-year-old female, who was an office worker, presented with left chest pain and right chest referred pain. The medical history included severe food allergies to various allergens, bronchial asthma, and hysterectomy. In the past, the patient had been transported to the hospital by ambulance due to anaphylaxis caused by buckwheat and mugwort. Regular medications included fluticasone/formoterol, epinastine chloride, and shoseiryuto. In a previous clinic, the patient was diagnosed with pneumonia, and received ceftriaxone and minocycline. The following month, chest computed tomography (CT) revealed persistent pneumonia, and jelly-like sputum was observed. The patient was referred to our hospital with suspected obstructive pneumonia of the left lower lobe.

At the time of first visiting, the patient showed body temperature of 36.9°C, blood pressure of 156/97 mmHg, and SpO₂ of 98% (room air). White blood cell count was 8900/μL with segmented neutrophils of 78.0%, lymphocytes of 16.0%, monocytes of 4.0%, eosinophils of 0.0%, and basophils of 2.0%. CRP was 0.08 mg/dL. BioFire FilmArray Respiratory 2.1 Panel (bioMérieux) test results were negative. Urine Legionella antigen and urine pneumococcal antigen tests were negative. The total IgE was 2890 IU/mL. The Aspergillus antigen test was negative, and the anti-Aspergillus IgG level was 11 AU/mL (cut-off value; <0.5). Allergy tests were positive for various allergens, including Aspergillus (Table 1). X-ray radiography revealed decreased transparency, suspected atelectasis, in the left lower lung field (Fig. 1A). Chest CT revealed bronchiectatic changes and atelectasis was observed in the left lower lung field (Fig. 1B). Bronchoscopy revealed mucosal swelling and a mucus plug (Fig. 2A), and the mucus plug could be removed (Fig. 2B). Strong eosinophil invasion was observed in the mucus plug specimen with hematoxylin-eosin staining (Fig. 2C), but mold was not detected with periodic acid-Schiff (PAS) staining.

Table 1.

Serum allergen-specific IgE levels in the patient.

Allergen	IgE (UA/mL)a	class
Aspergillus	17.88	5
Alternaria	2.08	3
Cockroach	1.38	2
House dust	1.36	2
Moth	1.22	2
House dust mite	1.10	2
Candida	1.08	2
Shrimp	0.86	2
Peanuts	0.65	2
Crab	0.60	2
Malassezia	0.53	2
Mugwort	0.50	2
Buckwheat	0.48	1
Banana	0.34	1
Sesame	0.28	1

Only positive results were shown.

^a< 0.27 is negative.

Fig. 1.

Chest X-ray radiograph at the first visit showed consolidation and decreased transparency in the left lower lobe suggesting atelectasis (A), and after treatment, the decreased transparency in the left lower lobe had improved (C). Chest computed tomography at first visit revealed bronchiectasis and atelectasis in the left lower lobe (B), and after treatment, disappearance of atelectasis (D).

Fig. 2.

Bronchoscopy showed mucosal swelling and thick mucus plugs (A), and the mucus plug was able to be removed by suctioning (B). A large number of eosinophils were observed in the mucus plugs with hematoxylin-eosin staining (C).

Microbial culture tests were performed using suction sputum and bronchial lavage fluids. Gram stain and microbial culture showed α-streptococci (2 +) and Gram-positive cocci (1 +), which were considered to be commensal bacteria, and Ziehl-Neelsen stain was negative in both specimens. Allergic bronchopulmonary Aspergillosis (ABPA) was suspected from the outset. Regarding the isolation of fungi, the specimens were cultured on Sabouraud dextrose agar (Beckton-Dickinson Japan) at 35°C for 2 days, followed by incubation at 30°C. Although incubation under the same conditions was continued for up to 14 days, no Aspergillus species were isolated from any of respiratory specimens. Mold colonies (+/-) were slightly observed in the bronchial lavage fluid culture on the third day. After 20 days, the mold was identified as Schizophyllum spp. using MALDI-TOF mass spectrometry (score: 1.97) with software 4.1.100, library 12 for bacteria, and library 5 for fungi (Biotyper, Bruker). The species identification was determined by the gene sequence of the internal transcribed spacer (ITS) region containing the 5.8S rRNA gene. Direct sequencing of the PCR product was performed using the primer set of ITS1-F_KYO2 and ITS4 [6]. The obtained sequences showed 100% identity with S. commune in the BLAST database search. Cultures on Sabouraud dextrose agar (Fig. 3A) showed cotton-wool-like primary mycelia but not secondary mycelia, namely fruiting bodies. Lactophenol cotton blue staining revealed hyphae with spicules and no clamp connections (Fig. 3B).

Fig. 3.

S. commune culture on Sabouraud dextrose agar (A). Hyphae observed with lactophenol cotton blue staining (B).

Erythromycin and carbocysteine were initially administered (Fig. 4). According to the Guideline for Allergic Bronchopulmonary Mycosis [1,5], seven of the ten clinical diagnostic criteria were met, therefore the patient was diagnosed with ABPM caused by S. commune. Anti-S. commune IgG index was 0.2145 (>0.0281 is strongly positive), and anti-S. commune IgE index was 0.2995 (>0.0042 is strongly positive) by a research-based enzyme-linked immunosorbent assay [7]. On the other hand, IgE against Asp f 1, which was a specific marker of ABPA caused by Aspergillus fumigatus [8], was negative (<0.10 IU/mL), and Aspergillus antigen was negative. Taking the test results together, it was suggested ABPM caused by S. commune rather than ABPA. On day 13, oral prednisolone (PSL) at 30 mg once daily and sulfamethoxazole (400 mg)-trimethoprim (80 mg) (ST) once daily were started, and PSL and ST were continued for approximately 7 and a half months with a gradually decreasing dosage of PSL (Fig. 4). On day 26, oral administration of itraconazole (ITCZ) capsule formulation was initiated at a dose of 200 mg once daily and continued for approximately 10 months. At 11 months, the X-ray radiogram and CT showed that the decreased transparency in the lower left lung field tended to disappear (Fig. 1C, D). No recurrence has been observed since then.

Fig. 4.

Treatment course of the patient. EM, erythromycin; CC, carbocysteine; ITCZ, itraconazole; PSL, prednisolone; ST, sulfamethoxazole-trimethoprim.

Discussion

S. commune is one of the most common mushrooms belonging to the phylum Basidiomycetes, subphylum Agaricomycotina, class Agaricomycetes, subclass Agaricomycetidae, order Agaricales, and family Schizophyllaceae. It is present in rotted wood and distributed worldwide. In a recent literature review of 20 cases [9] with the addition of five more recent case reports [[10], [11], [12], [13], [14]], 18 of 25 cases (72%) were reported in Japan. Furthermore, there are certain numbers of case reports in Japanese that are not included in PubMed or MEDLINE. Therefore, ABPM caused by S. commune may be more common in Japan than in other countries. Wooden houses and furniture are common in Japan, and humid climates could lead to frequent exposure to fungi that grow on rotted wood.

In the present case, seven of the ten clinical diagnosis criteria [1,5] were met: 1. bronchial asthma (Current or previous history of asthma or asthmatic symptoms), 3. 2890 IU/mL of IgE (Elevated total serum IgE levels; ≥417 IU/mL), 4. high anti-S. commune IgE (Immediate cutaneous hypersensitivity or specific IgE for filamentous fungi), 5. high anti-S. commune IgG (Presence of precipitins or specific IgG for filamentous fungi), 6. S. commune growth in bronchial lavage fluid culture (Filamentous fungi growth in sputum culture or bronchial lavage fluids), 8. bronchiectasis (Fig. 1B) (Central bronchiectasis on CT), and 9. mucus plugs on bronchoscopy (Fig. 2 A, B) (Presence of mucus plugs in central bronchi, based on CT/bronchoscopy or mucus plug expectoration history). The other three criteria were not met: 2. Peripheral blood eosinophilia (≥500 cells/mm³), 7. Presence of fungal hyphae in bronchial mucus plugs, and 10. High attenuation mucus in the bronchi on CT. The absence of eosinophils in peripheral blood may be due to the regular use of inhaled steroid for asthma treatment.

In the present case, mold was only slightly detected in the bronchial lavage fluid culture. No mold was found in the sputum culture or microscopic analysis of the mucus plug. The patient may have developed symptoms with extremely low amounts of the agent under a strong allergic predisposition. This suggests that bronchial lavage fluid culture was effective in this case. In the microscopic analysis of hyphae, the clamp connection, which is a typical structure of basidiomycetous fungi, was not observed (Fig. 3B), and secondary mycelia, namely fruiting bodies, were also not observed (Fig. 3A). It is considered that there was no mating partner, thus the mycelium remained in its primary state. In this case, estimation based on the morphology of hyphae and mycelia is difficult. The lack of typical morphological features makes it difficult to identify basidiomycetes, and they may be misidentified as zygomycetes, which have poor conidial production. Additionally, the patient was positive for both anti-Aspergillus IgG and anti-Aspergillus IgE. Therefore, the etiological agent was difficult to identify in the present case. In this case, Aspergillus species were not recovered at all, even after continuing fungal culture for two weeks. MALDI-TOF mass spectrometry was effective in identifying Schizophyllum spp. Furthermore, the gene sequence of the ITS region [6] was useful for identifying S. commune. Indeed, Aspergillus hypersensitivity may be common in patients with ABPM caused by S. commune. There has been a report of ABPM patient in whom both A. fumigatus and S. commune were cultured [15]. In the present case, the patient was negative for anti-Asp f 1 IgE (a disease marker of ABPA caused by A. fumigatus), Aspergillus antigen in serum, and Aspergillus species in the respiratory specimen cultures, thus ABPA was considered unlikely.

Similar to ABPA, the combination of glucocorticoids and fungicides, such as ITCZ, is recommended [5,16]. Summarizing a recent literature review [9] with the addition of five case reports in 2025 [[10], [11], [12], [13], [14]], 12 of 25 cases were treated with ITCZ and PSL, and four cases were treated with voriconazole and PSL. PSL and ITCZ were administered orally in the present case. As this patient had a history of severe allergies, ABPM should be included in the differential diagnosis. It is possible for ABPM to recur. Therefore, it is necessary to pay attention to mold and mushroom exposure in daily life.

Conclusion

While case reports of ABPM caused by S. commune are found sporadically, reports from Japan are particularly notable. The appearance of secondary mycelia is useful for identifying S. commune; however, the isolate in this case consisted of primary mycelia lacking distinctive characteristics, making identification based on morphology difficult. While MALDI-TOF mass spectrometry allowed for identification at the genus level, ITS gene sequencing enabled definitive identification of the species. Identification of basidiomycetes based on mycelial morphology is challenging, as it can be misidentified as zygomycetes that produce few conidia. In this case, ITCZ therapy was planned when fungal culture was positive; however, treatment with ITCZ might have been ineffective against ABPM caused by zygomycetes. Therefore, we believe that proper culture and species identification are essential in cases where the isolate lacks distinctive morphological features.

CRediT authorship contribution statement

Yasuo Ohkoshi: Writing – review & editing, Writing – original draft, Visualization, Investigation, Data curation. Hiromi Murabayashi: Investigation, Data curation. Kohei Sakai: Investigation, Data curation. Haruna Onodera: Investigation, Data curation. Yasunari Takakuwa: Investigation, Data curation. Midori Hashimoto: Investigation, Data curation. Akira Watanabe: Writing – review & editing, Investigation. Shin-ichi Yokota: Writing – review & editing, Writing – original draft, Visualization.

Ethics declaration

Written informed consent to take part in the study and to publish the article has been obtained from all participants or their legal representatives. The privacy rights of participants have been observed.

This study included organ or tissue donors. This study includes human biological material and consent was obtained by donors, or their next of kin or legal representatives, for use in this study and for publication of the article. The samples used in this research were not sourced from executed prisoners or prisoners of conscience.

This study was performed in compliance with relevant laws, regulatory frameworks and guidelines where the research took place. Ethics committee approval was not required under relevant laws and institutional guidelines. We have confirmed them.

This research follows the CARE guidelines and the CARE checklist.

Ethics statement

Written informed consent was obtained from the patient for the publication of clinical details.

Funding

No funding was received for this research.

Declaration of Generative AI and AI-assisted technologies in the writing process

None.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.