Pulmonary mucormycosis in immunocompetent hosts diagnosed by bronchioalveolar lavage

Abstract

Mucormycosis is a rare infection caused by Mucorales fungi belonging to Zygomycetes class. It can present with spectrum of symptoms and signs based of organ involvement. Common forms of mucormycosis includes rhinocerebral, cutaneous, gastrointestinal, pulmonary, disseminated and miscellaneous forms involving bones, breast, kidney and central nervous system. Pulmonary mucormycosis usually present with fever, cough, haemoptysis and is usually seen in immunocompromised patients like patients with diabetes or leukaemia, or those on chemotherapy or immunosuppressive therapy and rare in immunocompetent patients (6.25% of cases). Pulmonary mucormycosis can be diagnosed by radiological imaging studies, bronchoalveolar lavage (BAL) and histopathological evaluation of biopsy of the lesion; however, the gold standard is a positive fungal culture. Here, we describe two cases of pulmonary mucormycosis diagnosed by BAL in an immunocompetent patient.

Background

Mucormycosis is a rare infection caused by Mucorales fungi belonging to Zygomycetes class. It was previously known as Zygomycosis; however, the term is abolished presently.¹ Mucorales are ubiquitous and saprophytic fungi present in soil and decaying matter.² They grow at 28°C to 30°C under aerobic conditions, with an incubation period of 2–5 days. The spores can enter the host either by inhalation or through abraded skin.³ Mucormycosis can involve various systems and have varied clinical presentations which includes rhinocerebral, cutaneous, gastrointestinal, pulmonary, disseminated and miscellaneous forms involving bones, breast, kidney, central nervous system and so on.^{4 5}

Pulmonary mucormycosis refers to mucormycosis involving the lungs, and is more common in immunocompromised hosts like patients with diabetes or leukaemia, or those on chemotherapy or immunosuppressive therapy.⁶ Only 6.25% of patients do not have any of these predisposing factors.⁷ The disease is acquired by inhalation of spores which can lead to disseminated infection by hematogenous or lymphatic spread.⁸ The symptoms of pulmonary mucormycosis include dyspnoea, cough, chest pain and fever. Complications may include cavitation and/or massive haemoptysis, which occurs due to angioinvasion and necrosis, and can be fatal if a major blood vessel is involved. Pulmonary mucormycosis can be diagnosed by radiological imaging studies, bronchoalveolar lavage (BAL) and histopathological evaluation of biopsy of the lesion; however, the gold standard is a positive fungal culture.⁹

In this study, we describe two cases of pulmonary mucormycosis in immunocompetent host diagnosed by BAL.

Case presentation

Case 1

A 50-year-old woman, not a known case of diabetes, tuberculosis, not on immunosuppressive therapy, came with problems of blood in sputum in the past 1 month. On evaluation, she was diagnosed to have right middle lobe bronchiectasis. The haemoptysis gradually worsened over 2 weeks.

She was moderately built and nourished and her vitals were stable. On auscultation, rhonchi were heard in the right infra-axillary area. Her chest radiograph showed consolidation in right mid-zone (figure 1A). CT scan showed consolidation and air bronchogram in the right middle lobe (figure 1C). Peripheral blood evaluation showed leucocytosis and a raised erythrocyte sedimentation rate. Videobronchoscopy revealed endobronchial fungating mass causing luminal obstruction in the lateral segment of right middle lobe.

Figure 1.

(A) Chest radiograph (posteroanterior (PA) view, lateral view not available) showing consolidation in the right midzone and (B) decrease in size of the lesion after initiation of treatment. (C) CT thorax showing areas of consolidation and air bronchogram. (D) Bronchoalveolar lavage fluid analysis showing fungal elements having irregular thick aseptate hyphae with wide angle branching in an acute inflammatory background (arrows showing fungal colonies; arrowheads showing neutrophils).

BAL fluid cytology showed fungal elements having irregular thick aseptate hyphae with wide angle branching suggestive fungal infection favouring Mucormycosis (figure 1D). Biopsy from the endobronchial mass were inconclusive, possibly due to sample from the non-representative area. Fungal cultures were positive for Mucormycosis.

The patient was treated with intravenous amphotericin 2100 mg for 21 days and discharged with oral posaconazole. On follow-up after 2 weeks, patient was relieved from her symptoms and repeat chest radiograph showed decrease in size of the lung mass (figure 1B).

Case 2

A 65-year-old woman came with problems of breathlessness in the past 3 months and haemoptysis in the last 1 month, with gradual exaggeration of symptoms over last 2 weeks. She was a previous treated case of pulmonary tuberculosis, 6 years ago. She had no comorbidities.

Rhonchi were auscultated in the interscapular area on right side of the chest. Peripheral blood examination showed mild leucocytosis. Videobronchoscopy revealed a fungating mass in medial subsegment of superior basal segment of right lower lobe (figure 2A). BAL fluid analysis showed thick aseptate fungi with wide angle branching in a background of dense neutrophils and mucoid material, suggestive of Mucormycosis (figure 2B). Biopsy of the lung mass were inconclusive, due to inadequacy of the tissue sampled. However, fungal culture came out to be positive for Mucormycosis. The patient was advised treatment with amphotericin and surgical excision of the involved segment, but she wanted to be referred to a local hospital close to her stay. Unfortunately, we could not follow-up the case.

Figure 2.

(A) Videobronchoscopy image showing a fungating mass in medial subsegment of superior basal segment of right lower lobe. (B) Bronchoalveolar lavage fluid analysis showing thick aseptate fungi with wide angle branching in a mucoid background with few neutrophils and benign endobronchial cells (arrow showing the fungal colony; arrowheads showing neutrophils).

Discussion

Pulmonary mucormycosis is a rare and fatal opportunistic infection occurring more often in an immunocompromised host. Due to angioinvasion, it can lead to life-threatening complication like massive haemoptysis.¹⁰ The above described cases are different in a way that they are occurring in an immunocompetent host and also, they are diagnosed by BAL. The patients were screened negative for HIV and HbSAg and HbA1c was also within the normal limits. The pathogenesis of fungal infection depends on interaction of host factors such as epithelial defence mechanisms and virulence of the organism. Fungal infection commonly occurs in immunocompromised individuals where mucosal defence mechanisms have been altered due to prior injury, infections and drugs. In our case 1, we could not find any underlying immunocompromised state. However, in case 2, history of tuberculosis might have acted as an indirect chronic insult to the epithelial defence which triggered the infection.

Both the patients have typically presented with haemoptysis. The other symptoms may include fever, cough, dyspnoea and chest pain. Radiological features described in the literature are consolidation, cavitation, isolated mass, or cavity with fungal ball.¹¹ Wedge-shaped infarcts may also be seen, particularly following angioinvasion of pulmonary blood vessels and thrombosis. ‘Reverse halo sign’ is a characteristic CT finding appreciated in the early course of disease.⁸ MRI can also help determine the extent of involvement of lung parenchyma by the lesion.

The symptoms, signs and radiological features are non-specific, and hence confirmation of diagnosis requires identification of the characteristic morphology of the fungus or demonstration of the organism in fungal culture from specimens obtained from the site of infection. Samples can be obtained by radiographically guided percutaneous needle aspirate and by transbronchial biopsies of lesions. But this procedure cannot be done in patients with thrombocytopenia or in patients with coagulopathies.¹² There is little available literature that describes the utility of BAL in the diagnosis of mucormycosis. The hyphae of Mucorales organisms are typically irregular, broad, ribbonlike and non-septate with right-angle branching.¹³ Naran et al have described the presence a few rosettes of needle shaped birefringent polarizable crystals in bronchial brush cytology.¹⁴ Various types of crystals such a calcium oxalate, calcium salts of fatty acids and monosodium urate may be associated with the fungal infection.

Differential diagnosis of pulmonary mucormycosis includes bacterial, viral and other fungal pneumonias.¹⁵ In presence of a fungating mass, as in our study, biopsy and histopathological evaluation of the lesion can help to rule out lung malignancy.¹⁶ Early and accurate diagnosis of pulmonary mucormycosis is necessary to avoid its sequalae and fatal outcomes. Also, early treatment can reduce mortality by 45% with surgery (removal of devitalised tissue) and 70%–80% with medical line of management alone (oral and/or intravenous antifungals).¹⁷

Patient’s perspective.

Case 1: “I had complaints of blood in my phlegm for quite some time, which did not settle down with multiple medications. When I visited this hospital, I was asked to be admitted and undergo camera test to look at the status of my lungs. I was very anxious and frightened prior to the procedure as cancer was always on my mind. However, after the procedure, within few hours I was told that I have a fungal infection in my lungs which was curable. I was happy that my illness was diagnosed quickly and treated accordingly. I am symptomatically much better and am able to carry out my daily activities.”

Learning points.

• Diagnosis of pulmonary mucormycosis has always been a challenge to the pathologists.

• Bronchoalveolar lavage can sample a larger area of the tracheobronchial tree as compared with other diagnostic tests like bronchial brush cytology.

• Also, it is a minimally invasive technique unlike fine needle aspiration cytology or biopsy.

• Thus, we can infer that bronchoalveolar lavage is a quick, non-invasive and effective diagnostic tool to diagnose pulmonary mucormycosis.