CASE REPORT |
https://doi.org/10.5005/jp-journals-11010-1110 |
Silent Invader—Unrevealing Lethal Encounter with Pulmonary Mucormycosis: A Rare Case Report
1–3,5–9Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
4Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Corresponding Author: Venkat Raj, Department of TB and Respiratory Diseases, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, Phone: +91 8778134927, e-mail: gvenkatraj1996@gmail.com
Received: 11 January 2024; Accepted: 14 May 2024; Published on: 18 June 2024
ABSTRACT
A 61-year-old male having type 2 diabetes presented in the chest outpatient department with complaints of cough with expectoration, fever for 20 days, coughing out blood, and shortness of breath for 10 days. High-resolution computed tomography (HRCT) of the thorax revealed cavity consolidation in the left upper lobe showing reverse halo sign. Moreover, broad aseptate hyphae branching at right angles were observed in the potassium hydroxide (KOH) wet mount of bronchoalveolar lavage (BAL) sample, suggesting Mucorales. We labeled the case as pulmonary mucormycosis and treated with liposomal amphotericin B with correction of hyperglycemia. The patient initially responded well; however, he succumbed later due to the invasive course of the disease.
How to cite this article: Raj V, Shah D, Bhatia M, et al. Silent Invader—Unrevealing Lethal Encounter with Pulmonary Mucormycosis: A Rare Case Report. Indian J Respir Care 2024;13(2):124–127.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
Keywords: Broad aseptate hyphae, Case report, Endobronchial lung biopsy, Invasive course, Klebsiella pneumoniae, Liposomal amphotericin B, Multidisciplinary approach, Pulmonary mucormycosis, Reverse halo sign, Salvage
INTRODUCTION
Mucormycosis (formerly zygomycosis) is a life-threatening fungal infection in severely immunocompromised and uncontrolled diabetic patients. The causative fungi, Mucorales, primarily affect the rhino-orbital-cerebrum; however, they also affect the lung parenchyma, skin, and kidney.1 The rhino-cerebral form of mucormycosis is commonly seen in patients having uncontrolled diabetes mellitus and SARS-CoV-2 infected patients. Pulmonary mucormycosis is a rare manifestation in hematological malignancies, and that too is very much uncommon in patients having uncontrolled diabetes. Here, we report a case of pulmonary mucormycosis in an old male having uncontrolled diabetes mellitus who had fatal hemoptysis and succumbed to death despite aggressive treatment.
CASE DESCRIPTION
A 61-year-old male was admitted to the chest and tuberculosis ward with complaints of cough with expectoration, fever for 20 days, coughing up blood, and shortness of breath for 10 days. He is a known case of type 2 diabetes mellitus and has been on irregular treatment for the past 10 years.
Chest X-ray revealed consolidation with central cavitation in the left mid and lower lung zones. High-resolution computed tomography (HRCT) of the thorax showed cavity consolidation in the left upper lobe and superior segment of the lower lobe showing reverse halo sign (Fig. 1) with multiple random nodules with consolidation in the left lower lobe (Fig. 2).
Fig. 1: High-resolution computed tomography of the thorax showing cavity with consolidation in the left upper lobe and superior segment of the lower lobe with multiple nodules and a reverse halo sign
Fig. 2: High-resolution computed tomography of the thorax showing cavity consolidation with internal septations in superior segment of the left lower lobe and consolidation with tree-in-bud in other segments of the left lower lobe
On the day of admission, blood parameters showed a total leukocyte count (TLC) of 18,540 cells/mm3 with predominance of neutrophils, and glycated hemoglobin (HbA1c) was 16%. Renal function and liver function tests were within normal limits, and urine routine microscopy showed glucose ++ with no ketone bodies. The sequential organ failure assessment (SOFA) score was 7, and four minor criteria were positive in severe community-acquired pneumonia (CAP) score. Hence, the patient was shifted to high dependency unit (HDU) and started with intravenous (IV)-antibiotics-meropenem (1 gm 8th hourly), linezolid (600 mg 12th hourly), moxifloxacin (400 mg 24th hourly), and voriconazole (200 mg BD). His serum procalcitonin (PCT) was raised at 0.75 ng/mL, and D-dimer was 1250 ng/mL. Two-dimensional echocardiography (2D-ECHO) and bilateral lower limb color Doppler were done to rule out vascular thrombosis, which came out to be normal.
On the 2nd day of admission, the patient’s counts were still in the higher range. On direct microscopic examination of early morning sputum, broad aseptate hyphae having right-angle branching, morphologically resembling to Mucorales, were observed in the potassium hydroxide (KOH) wet mount (Fig. 3). Numerous polymorphs with gram-negative rods were seen in the Gram stain of the sputum sample. Moreover, Klebsiella pneumoniae sensitive to only amikacin was also isolated over routine culture.
Fig. 3: Sputum KOH mount showing broad aseptate hyphae branching at right angles
The patient was diagnosed as a case of CAP (pulmonary mucormycosis with K. pneumoniae). Injection meropenem (1 gm 8th hourly) was continued, and injection amikacin (750 mg 24th hourly) was added in place of linezolid and moxifloxacin. Injection liposomal amphotericin B (300 mg once daily) was started immediately. The patient became afebrile, and hemoptysis was getting controlled in the subsequent days. On the 4th day of admission, fiberoptic bronchoscopy (FOB) was performed, which showed fresh blood coming from LB6 segment (Fig. 4) and necrotic mucosa in between LB9 and LB10 (Fig. 5). Endobronchial lung biopsy (EBLB) was taken that also revealed broad aseptate hyphae in the KOH wet mount. We also had magnetic resonance imaging (MRI) of the head and neck to rule out disseminations; luckily, no such disseminations were observed. On the same day, cardiothoracic surgeon’s opinion was taken, and they advised left lower lobectomy/pneumonectomy.
Fig. 4: Bronchoscope image showing edematous mucosa with fresh blood coming from superior segment of the left lower lobe (LB6)
Fig. 5: Bronchoscope image showing necrotic mucosa between lateral and posterior basal segments of the left lower lobe
Our patient was improving very well clinically with the medical therapy, so invasive procedures such as angioembolization were not performed, but unfortunately, on the 6th day of admission, the patient had multiple large bouts of hemoptysis and collapsed. Even after vigorous resuscitation, the patient could not be revived.
DISCUSSION
Mucorales, the causative agent of mucormycosis, is an environmental saprotroph, that resides in dead and decaying material.1 Among Mucorales, Rhizopus arrhizus is the most common cause of human infections. However, others such as Rhizomucor, Rhizopushomothallicus, Apophysomyces, and Saksenaea sp. have been reported to cause human infections in the literature. Worldwide, mucormycosis affects 0.02–9.5 cases per 1,00,000 population with a higher mortality rate.2 However, 70 times higher prevalence rate has been estimated in India.3
The inhaled sporangiospores of the Mucorales primarily infect the paranasal sinuses; therefore, rhino mucormycosis with extension to surroundings like orbit and cerebrum is the most common form. Moreover, the inhaled sporangiospores may also enter lung parenchyma and result in pulmonary mucormycosis, especially in patients having preexisting cavitary lesions. Other forms like cutaneous mucormycosis usually occur due to traumatic implantation of the sporangiospores, whereas renal mucormycosis is usually a consequence of hematogenous dissemination.4 The immunocompetent individuals usually do not manifest clinical symptoms, whereas in immunosuppressed individuals, especially neutropenic, uncontrolled hyperglycemic, and SARS-CoV-2 infected patients, mucormycosis manifests as a life-threatening illness with higher mortality and permanent disfiguring among survivors. The pathognomonic feature of pulmonary mucormycosis is the rapid proliferation and angioinvasion resulting in vascular thrombosis, which ultimately leads to tissue necrosis.4
Neutrophils are the major defense cells against the Mucorales. Moreover, the state of hyperglycemia upregulates the expression of glucose-regulated protein 78 (GRP78) receptors, resulting in enhanced fungal adhesion with subsequent dissemination.5 Recently, the COVID-19 pandemic caused by the SARS-CoV-2 virus has been associated with mucormycosis. Here, the intake of steroids, zinc, and inhaled oxygenation has been attributed to COVID-19 associated mucormycosis.6
Pulmonary mucormycosis cases are diagnosed clinically, radiologically, and microbiologically. Usually, as per the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, pulmonary mucormycosis in patients with some form of immunosuppression had been categorized into proven and probable.7 Moreover, putative pulmonary mucormycosis has been termed in patients having SARS-CoV-2 infection. However, the patients usually do not have any form of immunosuppression.8 Microbiological diagnosis is made by demonstration of characteristic broad aseptate hyphae with right-angle branching in the background of clinical (persistent fever, cough, hemoptysis, pleuritic chest pain) and radiological evidence (lobar consolidation, cavities, multiple nodules, reverse halo sign).
Pulmonary mucormycosis cases are managed by a multidisciplinary approach comprising pulmonologist, radiologist, microbiologist, and cardiothoracic surgeons. The key parts of pulmonary mucormycosis treatment are: (1) antifungal treatment, (2) correction of risk factors, and (3) surgery. Early initiation of antifungal treatment is very much essential in reducing mortality. Liposomal amphotericin B (5 mL/kg/day and 10 mL/kg/day for central nervous system infection) is considered the first-line therapy, with regular monitoring of renal function and serum electrolytes. Azoles such as isavuconazole and posaconazole are also approved for the treatment of pulmonary mucormycosis, mainly as salvage therapy.9 The combination therapy of amphotericin B with posaconazole or echinocandins showed some positive results in limited retrospective studies, but there were no other prospective or randomized control studies to support this beyond a marginal recommendation.10 The duration of treatment is still controversial. However, liposomal amphotericin B should be given until complete clinical and radiological resolution, followed by step-down therapy with isavuconazole or posaconazole.
Interventions such as bronchial artery embolization (BAE) are lifesaving procedures for patients with massive hemoptysis and chronic hemoptysis. It has a high success rate of 76.9–100%, with a recurrence rate of 7.4–56.7%. It serves as a bridge between medical and surgical therapy. Unfortunately, due to affordability issues, our patient was not able to undergo BAE.11
Recent guidelines strongly support early surgical treatment with adjunctive medical therapy whenever feasible. In a review article by Prakash et al., it showed that the percentage of mortality reduced in the surgery plus amphotericin B arm (32.4%) than the single intervention arm (54.4 and 60.9%).12 Early surgeries are not able to be performed because of the severity of the disease, sudden death after diagnosis, high operative risks, etc.13 Despite these, the mortality rate in pulmonary mucormycosis ranges from 50 to 70% but exceeds up to 90% with extrathoracic dissemination.14 Therefore, education among the treating physicians and prompt diagnosis with aggressive treatment can reduce mortality.
LEARNING POINTS AND CONCLUSION
Knowing the angioinvasiveness of the Mucorales, early steps should have been taken to secure the airway and isolate the healthy lung with double-lumen tube intubation, and procedures like angioembolization should have been done to prevent massive hemoptysis, even though our patient had initial symptomatic improvement with medical therapy.15
This case insists on the necessity of an aggressive combined medical and surgical treatment approach to salvage the patient. There is an emergence of pulmonary mucormycosis cases worldwide. Therefore, prompt knowledge, education among the pulmonologist, and multidisciplinary approach involving the microbiologist, endocrinologist, cardiothoracic surgeon can reduce morbidity and mortality.
ORCID
Munesh K Gupta https://orcid.org/0000-0002-2107-1727
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