ABSTRACT Disseminated cryptococcosis is infrequent in immunocompetent children. Pulmonary and central nervous system are the commonly involved sites of infection in an immunocompromised host. We report a fatal case of disseminated cryptococcosis in an immunocompetent host presenting as fever of unknown origin with miliary shadows on chest radiograph, mimicking tuberculosis. In countries with the heavy burden of tuberculosis, a high index of suspicion is needed for early diagnosis of its close mimics like disseminated cryptococcosis. miliary lung shadow, disseminated cryptococcosis, child INTRODUCTION Cryptococcosis is a life-threatening systemic fungal infection caused by capsulated yeast, Cryptococcus neoformans. It occurs worldwide as a sporadic infection, transmitted by inhalation of the yeast into lungs from an environmental source such as soil contaminated with bird excreta. This infection predominantly affects immunocompromised host, much frequently adults than children. Few reports of this infection in immunocompetent children exist [1, 2]. We report a similar case of disseminated cryptococcosis in an immunocompetent child. CASE REPORT A 5-year-old girl, previously healthy, presented with complaints of insidious onset intermittent fever, non-productive cough and progressive abdominal distension for 2 months. Examination revealed respiratory distress, hypoxia and bilateral chest crepitations. Other significant findings included generalized lymphadenopathy, moderate hepatosplenomegaly and anasarca. She did not have any history of headache, vomiting or alteration of sensorium. There was no history of contact with bird excreta. Initial investigations revealed normal liver, renal and cardiac function. Chest radiograph showed bilateral miliary shadows (Fig. 1A). Ultrasound of abdomen revealed multiple retroperitoneal nodes, hepatosplenomegaly with multiple hypoechoic lesions in spleen. Possibilities of disseminated tuberculosis and malignancy were considered and evaluated. Gastric aspirate for acid fast bacilli, contact survey, Mantoux test were negative. Hematological investigations revealed hemoglobin 9.5 g/dl, total white blood cell count 15 400 cells/cumm and platelet count 2.4 × 105/cumm. Peripheral smear showed normocytic normochromic RBCs, and no abnormal cells were seen. Biopsy of retroperitoneal lymph node showed non-caseating granulomas with cryptococcal colonies. Meanwhile, child had one episode of generalized tonic–clonic seizure followed by progressive worsening of sensorium. Child was intubated and started on mechanical ventilation. There were no pupillary asymmetry, and the fundus examination was normal. Anti-raised intracranial pressure (ICP) measures like elevation of head end, midline position of head, adequate sedation and analgesia were started. Osmotherapy with 3% hypertonic saline was also started. Repeated lumbar drainage was done twice to relieve raised intracranial tension but could not be done further in view of hemodynamic instability. Cere-brospinal fluid (CSF) cell count was 100 cells/cumm with lymphocytic predominance, with hypoglycorrhachia and elevated protein of 194 mg/dl. CSF for India ink preparation was positive, and wet preparation showed budding yeast cells. The child was started on amphotericin B and flucytosine, and supportive care was continued. CSF and broncho alveolar lavage cultures on Sabouraud’s dextrose agar grew C. neoformans var neoformans (Fig. 1B). Screening for immunodeficiency, HIV ELISA was negative; serum immunoglobulin levels were IgG 1305 mg/dl, IgA 223 mg/dl and IgM 62 mg/dl; CD4 count was 1150 cells/cumm (CD4% 27.1%) and CD8 count was 980 cells/cumm (CD8% 24.8%); and interferon gamma receptor levels were all in normal limits. However, general condition of the child deteriorated progressively, and child succumbed to her illness. Lung biopsy and liver biopsy showed foamy macrophages with intracellular Cryptococcus (Fig. 2A and B). Fig. 1. View largeDownload slide (A) Miliary lung shadows on chest radiograph. (B) Culture showing cream-coloured, smooth, mucoid colonies of C. neoformans. Fig. 1. View largeDownload slide (A) Miliary lung shadows on chest radiograph. (B) Culture showing cream-coloured, smooth, mucoid colonies of C. neoformans. Fig. 2. View largeDownload slide (A) Liver biopsy (H&E, ×400): showing parenchymal foci of lymphohistiocytic infiltrate with numerous organisms having refractile walls, and some showing budding. (B) Lung biopsy (mucicarmine, ×400): the polysaccharide capsules were stained pink by the stain. Fig. 2. View largeDownload slide (A) Liver biopsy (H&E, ×400): showing parenchymal foci of lymphohistiocytic infiltrate with numerous organisms having refractile walls, and some showing budding. (B) Lung biopsy (mucicarmine, ×400): the polysaccharide capsules were stained pink by the stain. DISCUSSION Disseminated cryptococcosis is often thought to be an opportunistic infection in immunocompromised patients. There have been recent reports of this infection in immunocompetent children [1, 2]. The insidious onset and presentation with non-specific symptoms often delay the diagnosis. Diagnostic retroperitoneal lymph node biopsy was key point for our diagnosis, as the common diagnoses like disseminated tuberculosis and lymphoreticular malignancy were ruled out. Pulmonary nodules, either solitary or multiple, with surrounding ground-glass opacity are the most common CT findings in pulmonary cryptococcosis . A miliary pattern of lung shadow as in the index case has rarely been reported in disseminated cryptococcosis . In countries with heavy burden of tuberculosis, clinical presentation of generalized lymphadenopathy with miliary shadows on chest radiography might strongly suggest disseminated tuberculosis; high index of suspicion should be kept for alternative diagnosis like cryptococcosis even in an immunocompetent host. Management of elevated ICP is one of the critical determinants of outcome in patients with cryptococcal meningitis. It is recommended to measure the CSF opening pressure during the initial lumbar puncture. If the CSF pressure is >25 cmH2O, repeated CSF drainage is recommended to relieve the elevated ICP. Mannitol, acetazolamide and corticosteroids have not been found to be useful.  In the index patient, repeated lumbar drainage was used as a treatment strategy in management of intracranial hypertension. The choice and duration of antifungal therapy depend on the HIV status, immunosuppression and the organ of involvement. Treatment regimen in general includes an induction therapy with amphotericin B and flucytosine, followed by maintenance and consolidation therapy with fluconazole for 8 weeks and 1 year, respectively.  Despite the various treatment regimens, a high mortality rate has been reported. In HIV-positive patients, the 2-week mortality rate was 20–42% even after administration of amphotericin B, and an advanced disease was associated with a higher mortality . The immunocompetent patients had a higher mortality as compared with the immunosuppressed counterparts, as the symptoms are often non-specific and the diagnosis tends to be missed. Mortality as high as 27% has been reported among immunocompetent hosts.  Predictors of mortality in these patients were cryptococcemia and CSF opening pressure >25 cmH2O, both of which were present in the index patient. The key cornerstone lies in high index suspicion for early diagnosis and initiation of treatment. CONCLUSION Disseminated cryptococcosis rarely occurs in immunocompetent children and can present as miliary shadows on chest radiograph. References 1 Jaın BB , Bose D , Mondal R , et al. Disseminated cryptococcosis in an immunocompetent child . Turk Patoloji Derg 2017 ; 33 : 77 – 80 . Google Scholar PubMed 2 Bothra M , Selvaperumal P , Kabra M , et al. Disseminated cryptococcosis . Indian Pediatr 2014 ; 51 : 225 – 6 . Google Scholar Crossref Search ADS PubMed 3 Zinck SE , Leung AN , Frost M , et al. Pulmonary cryptococcosis: CT and pathologic findings . J Comput Assist Tomogr 2002 ; 26 : 330 – 4 . Google Scholar Crossref Search ADS PubMed 4 Wen Y , Deng S , Zhu Y , et al. Miliary pattern on chest imaging in an immunocompetent child . Indian J Pediatr 2014 ; 81 : 1253 – 4 . Google Scholar Crossref Search ADS PubMed 5 Saag MS , Graybill RJ , Larsen RA , et al. Practice guidelines for the management of cryptococcal disease . Clin Infect Dis 2000 ; 30 : 710 – 8 . Google Scholar Crossref Search ADS PubMed 6 Kambugu A , Meya DB , Rhein J , et al. Outcomes of cryptococcal meningitis in Uganda before and after the availability of highly active antiretroviral therapy . Clin Infect Dis 2008 ; 46 : 1694 – 701 . Google Scholar Crossref Search ADS PubMed 7 Brizendine KD , Baddley JW , Pappas PG. Predictors of mortality and differences in clinical features among patients with cryptococcosis according to immune status . PLoS One 2013 ; 8 : e60431. Google Scholar Crossref Search ADS PubMed © The Author . Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
Journal of Tropical Pediatrics – Oxford University Press
Published: Oct 1, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera