|Year : 2010 | Volume
| Issue : 3 | Page : 250-252
Early onset primary pulmonary cryptococcosis in a renal transplant patient
B Tarai, V Kher, P Kotru, A Sabhikhi, P Barman, A Rattan
SRL Clinical Reference Laboratory, Gurgaon, Haryana, India
|Date of Submission||10-Sep-2009|
|Date of Acceptance||05-Apr-2010|
|Date of Web Publication||17-Jul-2010|
SRL Clinical Reference Laboratory, Gurgaon, Haryana
Source of Support: None, Conflict of Interest: None
We report a case of primary pulmonary cryptococcosis in a post-renal transplant patient. A 65-year-old male renal transplant patient was admitted to the hospital with a low grade fever of 1 month, radiologically mimicking tuberculosis (TB). Broncho-alveolar fluid (BAL) shows capsulated yeast, and Cryptococcus neoformans was grown on culture supported by cytology and histopathological examination. Cryptococcal antigen was positive (32-fold) in serum and was negative in cerebrospinal fluid (CSF). The patient was given amphotericin B and 5-flucytosine and clinical improvement was seen on a weekly follow up. The serum cryptococcal antigen test might contribute to the early detection and treatment of pulmonary cryptococcosis. The results of antifungal susceptibility were aid in selecting the drug of choice for treatment.
Keywords: Antifungal susceptibility, cryptococcal antigen, pulmonary cryptococcosis
|How to cite this article:|
Tarai B, Kher V, Kotru P, Sabhikhi A, Barman P, Rattan A. Early onset primary pulmonary cryptococcosis in a renal transplant patient. Indian J Med Microbiol 2010;28:250-2
|How to cite this URL:|
Tarai B, Kher V, Kotru P, Sabhikhi A, Barman P, Rattan A. Early onset primary pulmonary cryptococcosis in a renal transplant patient. Indian J Med Microbiol [serial online] 2010 [cited 2020 May 30];28:250-2. Available from: http://www.ijmm.org/text.asp?2010/28/3/250/66489
| ~ Introduction|| |
Cryptococcosis caused by Cryptococcus neoformans, once considered a rarity, is now being diagnosed with increasing frequency as a result of the pandemic of human immune deficiency (HIV) virus infection. , It has also been sporadically reported in HIV-negative patients in the background of organ transplant and chemotherapy-related immunosuppression, reticuloendothelial malignancies, and corticosteroid therapy. ,, The spectrum of disease caused by C. neoformans ranges from pulmonary infection to disseminated disease frequently involving the central nervous system, and occasionally skin and bone. Resistance to cryptococcosis depends primarily on cell-mediated immunity. In immunocompromised host, cryptococcal meningitis and disseminated cryptococcosis are much more frequently seen than pulmonary infection alone. According to Campell's  review, till date 101 cases of cryptococcosis have been reported in the literature. This case report describes a typical patient with early onset pulmonary cryptococcosis after 7 months of post-renal transplantation. However, radiological features of our case mimicked pulmonary tuberculosis. And since he was post-transplant on immunosuppressive therapy, it was decided to look for alternate causes. This report describes the case of a 65-year-old male patient with isolated pulmonary cryptococcosis who was diagnosed early and hence was started on specific treatment at an early stage.
| ~ Case Report|| |
A 65-year-old male diabetic patient after 7 months of renal transplant was admitted to hospital care on 23 February 2009. Ours is a 200 bedded tertiary care hospital situated in New Delhi, India. The patient was on immunosuppressive therapy with tacrolimus, azathioprine, and steroid after renal transplantation. He was on insulin since last 6 to 7 years for diabetes. The patient presented with history of low-grade fever that persisted for about a month and cough for 2 weeks. There was no clinical history of pneumonia. On CT scan, there was evidence of multiple confluent nodular opacities and patchy parenchymal opacities seen in bilateral lung parenchyma, more evident on the right side in upper and lower lobes. Fluffy centrilobular opacities were seen diffusely involving bilateral lung parenchyma with tree-in-bud appearance. A small thin-walled cavitary lesion was seen in posterior segment of right upper lobe. Pleural involvement was evident with mild right side and minimal left side effusion, seen along with diaphragmatic and posterior basal spaces. With all the above findings, radiologist suggested of infective aetiology-possibility of tuberculosis.
The patient was HIV negative. Routine investigation revealed a normal haemogram with total leukocyte count of 5,300/mm 3 and serum electrolytes, blood urea nitrogen (BUN), and creatinine were normal. His mean plasma glucose level was 193.3% and glycosylated haemoglobin was 7.6%. The patient was investigated for sepsis screen which includes BACTEC blood culture, high-sensitivity C-reactive protein (HsCRP), and procalcitonin. BACTEC blood culture was negative and procalcitonin was normal except a slight raise in the HsCRP level.
Gram stain of Broncho-alveolar fluid (BAL) fluid revealed numerous polymorphonuclear cells (PMNS) but no organism were detected. BAL fluid was sent for AFB smear and culture and both were negative. Therefore, the patient was not started with any anti-tubercular therapy. Pneumocystis jerovicii was negative on periodic acid Schiff (PAS) and toludine Blue 'O' stain.
Fungal smear and culture was performed using the patient's BAL fluid. On direct smear preparation, budding yeast cells were detected and on India ink, a clear halo around the yeast cells was noted [Figure 1]c. On culture, yeast was grown after 3 days of incubation and it was identified by rapid yeast panel on Microscan (SIEMENS, USA) as C. neoformans within 4 h. The anti-fungal susceptibility test of the isolate was performed using Sensititre Yeastone plate (TREK Diagnostics Systems) which is a colorimetric microdilution broth method that provides minimum inhibitory concentration (MIC) results. The antifungal susceptible pattern of C. neoformans of this patient is mentioned in [Table 1].
The serum Cryptococcal antigen titre was also performed and was found positive (1:32). However, CSF Cryptococcal antigen was negative and culture was sterile. Routine CSF biochemistry was normal except for raised protein concentration. Adenine deaminase was normal in the CSF.
BAL fluid (grossly haemorrhagic) smears showed neutrophils, broncho-alveolar cells, and cystic macrophages in a background of RBCs. Many fungal spores morphologically resembling Cryptococcus sp. were present within macrophages as well as extracellularly. The section of transbroncheal biopsy stained with haematoxylin and eosin showed bronchial mucosal tissue and adjacent alveoli. The alveoli were distended by clusters of round yeast forms surrounded by a thick capsule [Figure 1]a and b. This was evident on PAS and GMS stain. These yeast forms ranging in size from approximately 2΅ to 4 ΅ were identified within macrophages and also extracellularly. Mucicarmine stain demonstrated the presence of capsule. However, there was no evidence of inflammatory response in the section.
After the diagnosis of pulmonary cryptococcosis, the patient was started with liposomal Amphotericin B 1mg/kg/day for 3 weeks with 5-flucytosine 37.5 mg/kg/day. The patient was in weekly follow up and improving well.
| ~ Discussion|| |
Five to fifty-nine per cent of organ transplant recipients were reported with invasive fungal infections.  Fungal infections are one of the important complications after organ transplantation and the overall incidence of cryptococcal infection varies from 2 to 3% with 2.8% in renal transplant recipients.  The unique neurotropism and predilection of C. neoformans to cause CNS infection are well recognized; CNS has been the most common site for cryptococcal infections. Pulmonary cryptococcosis is an uncommon clinical or laboratory finding.
The most frequent and sometime only radiological findings of pulmonary cryptococcosis were found to be unilateral, nodular, or cavity infiltrates.  Our patient was presented with only 1 month of low grade fever and radiological findings mimicking TB without any other clinical symptoms. The patient did not develop cryptococcemia which was ruled out by negative blood culture report and normal serum-procalcitonin level. Low grade of fever was assumed due to focal lesion in the lung and pleural involvement. The patient was on the initial stage of the cryptococcal infection and there was no dissemination to CNS as the CSF cryptococcal antigen was negative. The absence of fungal septicaemia or dissemination in our patient could trace the pathogen to be a non-virulent C. neoformans.
After transplantation, cryptococcal infection was considered early onset if it occurred within 12 months and was late-onset if it occurred after 12 months. The median times to onset are 25-35 month in case of renal transplantation.  The time of onset varied significantly for different types of organ transplant recipients. Our patient was an early onset case developed within 7 months of post-transplantation. This may be due to combined immunosuppressive factors i.e. diabetes and immunosuppressive therapy. Patients on tacrolimus or cyclosporine developed C. neoformans infection earlier than those who were on azathioprine therapy. However, our patient received both azathioprine and tacrolimus.
The latex agglutination test for the cryptococcal antigen has been instrumental in the diagnosis of cryptococcal meningitis. The assay has high sensitivity and specificity. The sensitivity of this assay in pulmonary or disseminated disease is unknown. The presence of the cryptococcal antigen in serum can, as in this case, be highly significant (Kawfan et al).  A positive cryptococcal antigen in serum with suspicious pulmonary lesions might suggest a cryptococcal infection, and an aggressive diagnostic approach for definitive cryptococcal infection in such clinical experience can be rewarding . It is not uncommon to treat such patients for tuberculosis empirically.
The therapeutic implication depends on diagnosing the fungal pathogen. If cryptococcosis is established, a careful search for meningeal involvement should be performed, which was negative in our case. In a symptomatic cryptococcal pulmonary disease, antifungal therapy is indicated according to the susceptibility results. Therapeutic option includes 5-flucytosine in combination with lower total doses of amphotericin B.
We conclude that pulmonary lesions in immunocompromised patients should be aggressively investigated for tissue diagnosis as was done in our case, leading to early diagnosis and effective treatment.
| ~ References|| |
|1.||Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS-100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 1995;8:515-48. [PUBMED] [FULLTEXT] |
|2.||Saag MS, Powderly WG, Cloud GA, Robinson P, Grieco MH, Sharkey PK, et al. Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group. N Engl J Med 1992;326:83-9. [PUBMED] |
|3.||Shih CC, Chen YC, Chang SC, Luh KT, Hsieh WC. Cryptococcal meningitis in non-HIV infected patients. QJM 2000;93:245-51. [PUBMED] [FULLTEXT] |
|4.||Zhu LP, Shi YZ, Weng XH, Muller FM. Case reports. Pulmonary cryptococcosis associated with cryptococcal meningitis in non-AIDS patients. Mycoses 2002;45:111-7. |
|5.||Prasad KN, Agarwal J, Nag VL, Verma AK, Dixit AK, Ayyagari A. Cryptococcal infection in patients with clinically diagnosed meningitis in a tertiary care center. Neurol India 2003;51:364-6. [PUBMED] |
|6.||Cambell GD. Primary pulmonary cryptococcosis. Am Rev Resp Dis 1966;236-43. |
|7.||Kanj SS, Welty-Wolf K, Madden J, Tapson V, Baz MA, Davis RD, et al. Fungal infections in lung and heart-lung transplant recipients. Report of 9 cases and review of the literature. Medicine (Baltimore) 1996;75:142-56. [PUBMED] [FULLTEXT] |
|8.||Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: Variables influencing clinical characterstics and outcome. Emerg Infect Dis 2001;7:375-81. [PUBMED] [FULLTEXT] |
|9.||Kaufman L, Blumer S. Value and interpretation of serological tests for the diagnosis of cryptococcosis. Appl Microbiol 1968;16:1907-12. [PUBMED] [FULLTEXT] |
|This article has been cited by|
||Pulmonary Cryptococcosis in HIV- sero-negative patients: case series from India
| ||Shimpi Chopra,Malini R. Capoor,Rupali Mallik,Sonal Gupta,Animesh Ray,Geetika Khanna,J. C. Suri,D. Bhattacharya,Samudrala Raghavan |
| ||Mycoses. 2015; : n/a |
|[Pubmed] | [DOI]|