We report the case of a 37-year-old woman, known to be HIV positive and on antiretroviral therapy for 9 months, who presented to us with breathlessness. She also had dry cough, weight loss, vomiting, loose stools, and progressive fatigue of 3 weeks’ duration. She was hardly able to walk 30 m when she got admitted with us. Vitals were as following: SPO2: 87% on room air, hear rate: 112/min, and respiratory rate: 34/min. Respiratory system examination revealed bilateral basal crepitations. Laboratory investigations were as following: Hb: 9.3 g/dL, total white cells: 4.43 × 109 cells/L, platelets 133 × 109 cells/L, lactate dehydrogenase: 173 U/L; C-reactive protein: 128.5 mg/L, and procalcitonin: 28.36 ng/ml. Absolute CD4 count was 65 cells/m. She was COVID reverse transcription–polymerase chain reaction negative. The patient was admitted to the intensive care unit and initiated on noninvasive ventilation with 60% FiO2.
Chest radiograph showed bilateral miliary nodules with a cavity in the right upper lobe of lung [Figure 1a]. Computed tomography showed a thick-walled cavity in the right upper lobe of the lung with ground-glass opacity and a few pneumatoceles and multiple enlarged necrotic mediastinal lymph nodes [Figure 1b and c]. Ultrasound abdomen showed hepatosplenomegaly. Sputum for acid-fast bacilli (smear) and Xpert mycobacterium tuberculosis (MTB)/RIF ultra assay was negative. Fibreoptic bronchoscopy [Figure 2a] and bronchoalveolar lavage (BAL) were obtained from the right upper lobe. BAL mycobacterial culture and Xpert MTB/RIF Ultra assay were negative. BAL cytology by Papanicolaou smear showed unstained round structures with occasional budding, suspicious for Cryptococcus [Figure 2c] which was confirmed with special stain for fungus Gomori methenamine silver. India ink staining showed capsulated budding yeast cells [Figure 2b]. A cryptococcal antigen lateral flow assay (BIOSYNEX Crypto PS) was performed on BAL. Both low and high-titer bands were positive [Figure 2d]. Blood culture also grew Cryptococcusneoformans. She was diagnosed with disseminated cryptococcosis and initiated on oral isavuconazole. The patient improved clinically and was discharged on oral antifungals.
C. neoformans is an opportunistic pathogen in immunocompromised hosts and usually causes meningitis and less commonly pulmonary infections. The patient under discussion had Cryptococcus in BAL and blood which is an uncommon finding. C neoformans may also cause pneumonia in immunocompetent patients, but mostly, it will resolve without therapy. But in the immunocompromised patient, C neoformans which is initially localized to the lung can eventually cause disseminated infection as found in our patient. The only chance of early recovery and cure in such cases will be an early diagnosis. The detection of cryptococcal antigen has been found to be a useful adjunct to diagnosis in patients with C neoformans meningitis and fungemia. Bronchoscopy with BAL has become a standard part of assessment in immunocompromised patients with respiratory symptoms. Although the examination of the BAL specimen may aid in the diagnosis of C neoformans infection, there may be a delay in diagnosis unless the organism is seen on cytologic examination of the BAL specimen. If not seen, cultures take about a week for a definitive diagnosis. Cryptococcal antigen test enhances the ability to rapidly diagnose C neoformans infection in the lung, In the present case, BAL cytology showed C neoformans on Grocott methenamine silver stain, which was immediately confirmed with antigen test and eventually blood culture grew C neoformans.
Liposomal amphotericin B (LAB) is a drug of choice for the treatment of disseminated C neoformans. She presented when India was facing an acute shortage of LAB and was started on isavuconazole (ISAV). ISAV is a drug with a broad-spectrum antifungal activity that is approved for the treatment of invasive aspergillosis and mucormycosis by the US Food and Drug Administration. In a study by Thompson etal., ISAV was validated as a valuable alternative to currently available agents for dimorphic fungi like Cryptococcus. Our patient improved with treatment and was discharged on oral ISAV.
The current case is an exception in many ways. Tuberculosis (TB) would be the most likely cause of a thick-walled cavity and miliary opacity in an endemic country like India. However, the patient repeatedly tested negative for pulmonary TB. BAL cytology and Crypto PS were positive which clinched the diagnosis. We would like to conclude that, though rare, cryptococcosis should be considered in the differential diagnosis of miliary opacity on chest X-rays, especially in immunocompromised hosts.
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