Unusual manifestation of pulmonary Verruconis gallopava infection with synchronous reactive pericardial effusion in a non-transplanted patient

Abstract

Verruconis gallopava is an emerging causative agent in solid organ transplant patients, increasing in prevalence both in non-transplanted patients and also in immunocompetent ones, albeit rarely. In this case report, we describe an unusual V. gallopava infection in a patient with steroid-dependent autoimmune haemolytic anaemia. The chest CT scan revealed a mass-like consolidation in the superior segment of the right lower lobe, and bronchoscopic examination confirmed V. gallopava from bronchoalveolar lavage. The histopathology showed non-necrotising granulomatous inflammation concurrent with septate-pigmented hyphae, which is compatible with dematiaceous fungi. After 3 weeks of posaconazole treatment, the patient developed a new pericardial effusion. Further investigations, including culture, cytology and histopathology, yielded negative results, leading to suspicion of reactive pericardial effusion associated with V. gallopava pulmonary infection. The patient received antifungal therapy for 9 months, after which a follow-up chest CT scan showed complete resolution of consolidation and pericardial effusion.

Background

Dematiaceous moulds are increasingly recognised as a causative microorganisms in immunocompromised host, particularly in post-transplantation patients. Verruconis gallopava, previously known as Ochroconis or Dactylaria gallopava, is thermotolerant and commonly found in soils and decaying materials. While it is a known pathogen in immunocompromised and immunocompetent states, the lung is the most common site of infection. Disseminated infections involving the central nervous system and skin have also been reported, with a high mortality rate.^{1 2} However, cardiac infection with V. gallopava is rare. We describe a patient with steroid-dependent AIHA who developed V. gallopava pulmonary infection with concurrent reactive pericardial effusion during antifungal treatment.

Case presentation

A woman in her 70s with a history of steroid-dependent idiopathic autoimmune haemolytic anaemia (AIHA) received four cycles of rituximab and danazol followed by maintenance medication with 10 mg of prednisolone and 200 mg of danazol. During AIHA treatment, she developed fever and cough, and a CT of the chest showed a 5 cm lobulated mass with internal air in right lower lobe (RLL). Bronchoalveolar lavage (BAL) identified Nocardia veterana, and she was treated with a single strength of cotrimoxazole once daily. Two months later, a follow-up CT chest showed resolution of the RLL lesion. However, 4 months after that, a new pulmonary opacification appeared at the superior segment of RLL. The patient denied any symptoms of fever, cough, dyspnoea or weight loss. Her medical history included hypertension, diabetes mellitus and dyslipidaemia, as well as a left upper lung nodule that was pathologically proven to be benign after surgical resection.

The chest radiograph showed a lobulated opacification overlying the right hilum, a new 9 mm nodule in the right middle lung zone. The left lung volume was small, and the left hemidiaphragm was elevated, likely due to postlobectomy changes (figure 1A, B). The chest CT scan revealed a 2.9 cm mass-like consolidation with a bulging contour in the RLL. In addition, a few small nodules were seen in the same area, as well as several subcentimetre intrathoracic lymph nodes. No osteolytic or osteoblastic lesion were observed (figure 1C, D).

Figure 1.

A–E showed abnormalities from chest radiography and chest CT scan at initial diagnosis. A chest radiograph revealed lobulated opacification overlying the right hilum, a new 9 mm nodule in the right middle lung zone, a small left lung volume with elevation of the left hemidiaphragm, most likely from post-LUL, and mild cardiomegaly and calcified tortuous aorta. (A, B) A 2.9 cm mass-like consolidation with bulging contour and associated few small nodules in the superior segment of the right lower lobe was and 1.4 cm well-defined consolidation at the right middle lobe discovered on a chest CT scan. (C, D, E). LUL, left upper lobectomy.

Bronchoscopy with endobronchial ultrasound-guided transbronchial biopsy and BAL was performed at the newly detected mass-like consolidation at the superior segment of RLL. V. gallopava was identified from both BAL and tissue fungal cultures. The PCR for fungal detection by Internal Transcribe Sequences (ITS) gene amplification was also positive for V. gallopava. The pathology showed non-necrotising granulomatous inflammation with pigmented yeasts and hyphae with septations from Gomori methenamine silver (GMS), periodic acid-Schiff (PAS) and Fontana Masson stain, which was compatible with dematiaceous fungi (figure 2). The drug susceptibility of antifungal agents in our case was demonstrated in the investigation panel. She has been treated with 300 mg of oral posaconazole (delayed-release tablet). After 3 weeks of antifungal therapy, she developed dyspnoea on exertion and a new pericardial effusion was detected on the CT chest while mass-like consolidation was gradually improving (figure 3A, B). At that time, the drug level of posaconazole was monitored and was within the therapeutic range. The patient had undergone pericardiocentesis and subsequently pericardial window. Pericardial cytology showed only atypical mesothelial-like cells. Cultures of pericardial fluid for bacteria, mycobacterium and fungi showed negative results. Additionally, no evidence of fungal infection or malignancy was found in the pericardial tissue. The beta D glucan level in the pericardial fluid and serum was 67.3 pg/mL and 46.1 pg/mL, respectively, which did not show active evidence of fungal infection. (The cut-off value considering fungal infection should be greater than 80 pg/mL in all clinical specimens.) Therefore, reactive pericardial effusion associated with V. gallopava infection was suspected. Micafungin was initially added for empirical treatment for nearly 80 days, concurrent with posaconazole. After administration of combined antifungal agents and pericardial drainage, the pericardial effusion was resolved entirely with no recurrence of mass-like consolidation at RLL from the chest CT scan (figure 3C).

Figure 2.

The histopathology of lung biopsy from the right lower lobe showed non-necrotising granulomatous inflammation with the presence of pigmented yeasts and hyphae with septations from GMS (A), H&E (B) PAS (C) and Fontana Masson stain (D) which were compatible with dematiaceous fungi from melanin detection. GMS, Gomori methenamine silver; PAS, periodic acid-Schiff.

Figure 3.

The chest CT scan, lung window (A) and mediastinal window (B), after treatment with posaconazole for 3 weeks, showed newly developed pericardial effusion with interval decreased size of consolidation at the superior segment of RLL. The chest CT scan after treatment with posaconazole for 9 months showed complete resolution of consolidation and pericardial effusion (C).

Investigations

• A chest radiograph revealed lobulated opacification overlying the right hilum, a new 9 mm nodule in the correct middle lung zone. A small left lung volume and elevation of the left hemidiaphragm were noted, likely from post-lobectomy (figure 1 A, B).

• The chest CT scan revealed a 2.9 cm mass-like consolidation with a bulging contour and associated few small nodules in the superior segment of the RLL with several subcentimetre intrathoracic lymph nodes. There was neither an osteolytic nor osteoblastic lesion (figure 1 C, D).

• Bronchoscopy with endobronchial ultrasound-guided transbronchial biopsy and BAL was performed at the newly detected mass-like consolidation at the superior segment of RLL. V. gallopava was identified from both BAL and tissue fungal cultures. The PCR for fungal detection by ITS gene amplification from BAL was also positive for V. gallopava. The pathology showed non-necrotising granulomatous inflammation with pigmented yeasts and hyphae with septations from GMS, PAS and Fontana Masson stain, which was compatible with dematiaceous fungi (figure 2).

• In the chest CT scan after 3 weeks of oral posaconazole, new pericardial effusion was detected despite improving mass-like consolidation at the superior segment of RLL (figure 3A, B)

• The posaconazole drug level was within the therapeutic range.

• Pericardial cytology showed only atypical mesothelial-like cells and negative results from pericardial fluid cultures for bacteria, mycobacterium and fungus. Moreover, there is no evidence of fungal infection or malignancy from pericardial tissue.

• The beta D glucan level from pericardial fluid and serum was 67.3 and 46.1 pg/mL (cut-off value is more than 80 pg/mL)

• The drug susceptibility of antifungal agents in our case is as the followings; posaconazole 0.03 mcg/mL, anidulafungin 0.06 mcg/mL, itraconazole 0.06 mcg/mL, micafungin 0.015 mcg/mL, caspofungin 0.25 mcg/mL and voriconazole 0.25 mcg/mL. These results indicate susceptibility to posaconazole.

• The chest CT scan after nearly 80 days of intravenous micafungin concurrent with oral posaconazole, the pericardial effusion was resolved entirely with no recurrence of mass-like consolidation at RLL from the chest CT scan (figure 3C).

• Subculture from lung biopsy demonstrated dry, flat brownish-black colonies. Lactophenol cotton blue staining showed brownish thick wall hyphae with cylindrical conidiospores (figure 4A, B).

Figure 4.

Subcuture from lung biopsy demonstrated dry, flat brownish black colonies (A). Lactophenol cotton blue staining showed brownish thick wall hyphae with cylindrical conidiospores (B).

Treatment

Initially, micafungin was added as empirical treatment for nearly 80 days, along with posaconazole, due to suspected reactive pericardial effusion associated with V. gallopava infection. This suspicion was based on the lack of evidence of fungal pericarditis from both pericardial fluid and pericardial tissue.

Outcome and follow-up

After administration of combined antifungal agents and pericardial drainage, the pericardial effusion was completely resolved with no recurrence of mass-like consolidation at RLL from the chest CT scan (figure 3C).

Discussion

Dematiaceous fungi, fungi with dark pigmentation, are increasingly recognised as causative microorganisms in the immunocompromised host. V. gallopava, previously known as Ochroconis or D. gallopava,¹ is found in hot environments, soil and decaying materials and can infect individuals with both immunocompromised^2–8 and immunocompetent.^9–12 Among the Verruconis and Ochroconis species, V. gallopava is the most common species isolated from clinical samples, including BAL and sputum.¹³ The property of thermotolerance is believed to be a significant virulent factor that can cause systemic or disseminated infection in humans.^{14 15} V. gallopava has been commonly identified as an emerging opportunistic pathogen in recipients of solid organ transplants.^{2–5 8} However, as seen in our case, V. gallopava can also infect in patients with immunocompromised status, with previous literature reported in patients with haematologic malignancy, chronic granulomatous disorders and HIV.^{2 7 16} Only a few cases of immunocompetent individual infected with V. gallopava have been reported.^9–12

The pathogenesis of V. gallopava infection is likely due to the inoculation of contaminated fungal spores into the lower respiratory tract. Clinical manifestations of V. gallopava infection can range from mild to life-threatening and can involve a single organ or multiple organs including the brain, spleen and skin. Multiple organ and extrapulmonary involvement are associated with poor clinical outcomes and high mortality rates.^{1 2 17} The clinical features of V. gallopava pulmonary infection reported in previous literature include shortness of breath, chest tightness, fever, productive cough or expectoration of pigment produced by the fungus.¹¹ However, most patients with pulmonary infections are asymptomatic at presentation, as seen in our case.¹⁷

Cardiac involvement, especially pericarditis due to pathogenic fungi, is reported infrequently in approximately 1% of all forms of pericarditis.¹⁸ Histoplasma species is the most common fungus reported in the literature that can cause acute pericarditis.^19–21 Cryptococcus neoformans was also reported to cause fatal pericarditis in an immunocompromised host.²² However, only one case of V. gallopava endocardial infection was reported.⁸ Our case demonstrated the rare presentation of V. gallopava infection as the patient developed a new pericardial effusion with cardiac tamponade after 3 weeks of posaconazole therapy. Due to the negative results of investigations, including fungus culture, pericardial cytology and pericardial tissue, reactive pericardial effusion associated with V. gallopava pulmonary infection was suspected.

The radiological findings of V. gallopava infections reported in previous literature include cavitary lesions, consolidation and pulmonary nodules.2 3 6–10 12 Additionally, a case of V. gallopava infection in a patient with radiological findings resembling bronchiectasis, including air-fluid levels and bronchial wall thickening, has been reported.¹¹ As in our case, the finding of mass-like consolidation from the chest CT scan was non-specific and could not be distinguished from other organisms. In our case, tissue sampling, BAL culture and histopathological findings were necessary for diagnosing V. gallopava infections. However, given the potential of environmental contaminants of dematiaceous fungi, the isolation from clinical specimens must be cautiously interpreted when used to define the true pathogen.²³

Given the lack of recommendations regarding the optimal antifungal regimens, the choice of antifungal agent is primarily determined by the susceptibility pattern in the individual case. Seyedmousavi investigated the susceptibilities in an extensive collection of thermophilic fungi to eight antifungal drugs, of which echinocandins and posaconazole showed the greatest in vitro activity.¹⁴ As in our case, V. gallopava showed susceptibility to posaconazole, so we chose it as the initial treatment. In contrast, in the case series of Ochroconis gallopava infection in transplant recipients, good clinical outcome were achieved with amphotericin B followed by long-term azole therapy or surgical resection in the selected cases.²⁴ Due to immunocompromised status and multiorgan involvement, lifelong posaconazole was considered in our patient. The follow-up chest CT scans 9 months after treatment showed no recurrence of pulmonary opacity or pericardial effusion.

Learning points.

• Verruconis gallopava infection is increasingly prevalent among transplanted patients and non-transplanted patients with concurrent immunosuppressive agent use.

• The symptom of V. gallopava infection could vary from mild to life-threatening.

• Early diagnosis and treatment are crucial to avoid dissemination that can be associated with poor clinical outcome.

• Pericardial involvement is a rare presentation in V. gallopava infection.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).