3 | DISCUSSION
Mucormycosis represents a group of infections caused by the fungi belonging to the order Mucorales and family Mucoraceae.1,6 Pulmonary mucormycosis accounts for ~25% of cases of mucormycosis with more than 50% mortality.2 The most frequent mode of infection is through inhalation of pervasive spores into the bronchioles and alveoli, which typically results in the rapid development of pneumonia or endobronchial disease. Risk factors for mucormycosis include diabetes mellitus (DM), systemic corticosteroid medication, neutropenia, hematologic malignancies, stem cell transplant, and other immunocompromised statuses. Among the risk factors, DM is the most common predisposing factor. Our patient was diabetic however his glucose level was well controlled with subcutaneous insulin.
In comparison to bacterial infections, fungal infections in people with cirrhosis are still relatively rare. In cirrhotic patients, infections caused by Candida, Cryptococcus, Aspergillus, and Coccidioidomycosis have all been documented.7 Only a few instances of invasive mucormycosis in these patients have been documented.8,9 Neutropenia and thrombocytopenia are frequently present in cirrhotic individuals and may act as risk factors for fungus infections.
The presentation of pulmonary Mucormycosis might be acute, subacute, or chronic. Patients with pulmonary mucormycosis commonly present with fever, cough, dyspnea, and chest pain. Hemoptysis occurs due to vascular invasion which is usually fatal. Pancoast syndrome, progressive subcutaneous emphysema, bronchial perforation, chronic mediastinitis, or Horner’s syndrome are rare presentations of pulmonary Mucormycosis.10-14
The radiological evidence of pulmonary mucormycosis is mostly non-specific. An abnormal chest x-ray is found in more than 80% of patients.15 Radiological presentations include infiltrates, consolidation, cavitation, single or multiple nodules or masses, air crescent sign, halo sign, reversed halo sign, lymphadenopathy, pleural effusion, pulmonary artery pseudoaneurysms, and bronchopleural fistula. Cavitations are found in as many as 40% of patients, but air crescent sign is uncommon. The right lung is more commonly involved than the left, and there is a predilection for the involvement of the upper lobes, although the reason for this remains unknown.16,17
Our patient presented with a fever, cough, and breathlessness for 2 weeks. On examination, cervical lymphadenopathy was present with features suggestive of CLD. Systemic respiratory system examination was normal and chest X-ray and HRCT scan of chest findings were suggestive of the cavitary lesion. Though sputum for Gram staining showed Klebsiella spp. and fungal stain showed budding yeast cells with pseudo-hyphae. The patient was treated with injectable ceftriaxone and oral itraconazole for 2 weeks according to the C/S without any significant improvement.
The gold standard for the diagnosis of pulmonary mucormycosis is the demonstration of characteristic hyphae (broad, non-septate, ribbon-like hyphae, with right-angled branching) and histopathologic changes (vascular invasion with tissue necrosis and neutrophilic infiltration of the tissue) in a biopsy specimen.18 As our patient, the intravenous antibiotics and oral antifungal treatment were ineffective, then cervical lymph node FNAC was performed that showed non-caseating granuloma. So, for further evaluation, a CT-guided biopsy from a left-sided cavitary lesion was performed to confirm the diagnosis. Histopathological specimens of lung tissue showed features suggestive of Mucormycosis.
Pulmonary mucormycosis is associated with bacterial pneumonia in 30% of cases, which can delay the diagnosis of the fungal infection.19 The sensitivity of microscopic examination of sputum and sputum culture is low, and the false positive rate is high. Our patient’s sputum examination showed Klebsiella growth and we treated the patient according to the culture and sensitivity without any significant improvement. Polyenes (Amphotericin B and Liposomal amphotericin B) are the first-line agents for the treatment of mucormycosis, and Liposomal amphotericin B is the choice of treatment as it improves the response rates and survival compared to amphotericin B.
In the present case, oral posaconazole was used rather than polyenes due to financial constrain. Posaconazole is metabolized mainly by the liver through glucuronidation, and it elevates liver function tests by approximately 1–5 %. No dose adjustment is necessary in patients with hepatic impairment.4 Our patient received itraconazole for a short bridging period of 20 days without significant improvement and then finally posaconazole was started with a strict follow-up. During follow up patient improved clinically and radiologically without any documented side effects during the 3 months of treatment with posaconazole.
There are approximately 18 case reports of mucormycosis with decompensated CLD. Among them HCV in 8 patients; HBV in 2; autoimmune hepatitis in 2; alcoholic liver disease in 4; and unknown etiology 2.20 None of them had lymph node involvement. This may be the first reported case of pulmonary mucormycosis with CLD with cervical lymph node involvement. The etiology of CLD of our patient was non-B non-C (NBNC).
The principal limitation of our report is that we did not obtain definitive culture confirmation of Mucorales from the biopsy material. However, the culture yield rate for this organism is relatively low, and as it can be falsely negative in up to 50% of mucormycosis cases. The low culture yield rate may be the result of the deleterious effects of tissue grinding, interactions with other organisms, and/or less-than-optimal culture temperature.21 Different molecular methods are used for the confirmation of mucormycosis diagnosis. Among them, PCR of Mucorales can be performed on tissue biopsy and blood samples. They can confirm diagnosis earlier than the conventional mycological method. Although serum PCR sensitivity is lower than in tissue, it is highly specific.22 We couldn’t perform PCR on tissue or blood samples due to a lack of facilities.