Year : 2008 | Volume
: 51 | Issue : 4 | Page : 553--555
Cryptococcal granulomas in an immunocompromised HIV-negative patient
Juhi Taneja, Aradhana Bhargava, Poonam Loomba, Vinita Dogra, Archana Thakur, Bibhabati Mishra
Department of Microbiology, GB Pant Hospital, JL Nehru Marg, New Delhi - 110 002, India
Department of Microbiology, GB Pant Hospital, JL Nehru Marg, New Delhi 110 002
Disseminated cryptococcosis usually occurs in immunocompromised individuals with defective cell-mediated immunity, most commonly seen with HIV infection. We present a case of disseminated cryptococcosis in an HIV-negative male patient who presented with headache, fever, altered sensorium of short duration and multiple cutaneous lesions. An emergency CT scan of the head showed multiple intracranial and intraventricular granulomas. Routine laboratory investigations were within the normal range. A CSF examination revealed capsulated yeasts on India ink and a culture yielded cryptococcus neoformans. A cryptococcal antigen test by latex agglutination kit was positive. A biopsy revealed multiple capsulated yeasts cells in the cutaneous lesions, which were consistent with cryptococcus neoformans. The patient was successfully treated with Amphotericin B and Fluconazole with regression of cranial and cutaneous lesions.
|How to cite this article:|
Taneja J, Bhargava A, Loomba P, Dogra V, Thakur A, Mishra B. Cryptococcal granulomas in an immunocompromised HIV-negative patient.Indian J Pathol Microbiol 2008;51:553-555
|How to cite this URL:|
Taneja J, Bhargava A, Loomba P, Dogra V, Thakur A, Mishra B. Cryptococcal granulomas in an immunocompromised HIV-negative patient. Indian J Pathol Microbiol [serial online] 2008 [cited 2021 Dec 1 ];51:553-555
Available from: https://www.ijpmonline.org/text.asp?2008/51/4/553/43760
Cryptococcosis is a systemic granulomatous infection disease caused by the encapsulated yeast-like fungus, Cryptococcus neoformans ( C. neoformans) . Two varieties and five serotypes of C. neoformans were recognized, but the varieties have now been accorded species status: var. neoformans , now C. neoformans (serotype A, D and AD; based on capsular polysaccharide antigens) and var. gattii , now C. gattii ( serotypes B and C). The incidence of cryptococcal infection is increasing dramatically among immunosuppresed patients, either due to HIV infection or corticosteroid induced immunosuppression.  Common presentations of cryptococcosis are related to pulmonary, central nervous system (CNS) and skin involvement. Rarely, liver, prostate and bone marrow involvement can occur.  We report a case of cerebral and intraventrical granuloma cryptococcal infection in a HIV-negative male presenting with headache, fever and altered sensorium of short duration with multiple cutaneous lesions.
A 42-year-old male patient presented in the emergency section of our hospital with altered sensorium of 4 days durations with complaints of headache and fever of 2 months duration with a few episodes of vomiting. Two weeks before admission, he developed a sudden onset of weakness on the left half of his body. There was no history of any significant illness in the past.
On examination, the patient was febrile (99ºF); his pulse and blood pressure were normal (86/min and 130/80mm Hg, respectively). The patient had multiple painless cutaneous nodules over the face, neck and upper extremities, measuring 2-4 cm in size of 2 weeks duration [Figure 1]. The patient did not have lymphadenopathy or hepatosplenomegaly. A neurological examination showed drowsiness and positive Kernig's sign. Cranial nerve functions and sensory functions were intact. A motor system examination showed left-sided hemiparesis.
An examination of his blood showed a hemoglobin level of 14.7 gm % with a total leukocyte count of 18,600/ cu mm, the differentials N88 L010 M02 with an adequate number of platelets. Other laboratory values were serum creatinine 0.7 mg, blood urea 26 mg, blood sugar (random) 127 mg, serum sodium ions 148 meq/L and serum potassium ions 3.7 meq/L. Blood and urine cultures, a malarial parasite test and a chest X- ray were all unremarkable. Fundi showed papilloedema. An emergency contrast enhanced CT head scan of the patient showed multiple intracranial and intraventricular granulomas [Figure 2].
An examination of cerebrospinal fluid showed white cells 10 cells/µL lymphocytes, proteins 66 mg/dl and glucose 95 mg/dl, India ink stain was positive for capsulated round yeast cells and mucicarmine positive capsule. A cryptococcal antigen test by latex agglutination kit (CALAS, Meridian Bioscience) was positive. A CSF culture on Sabouraud's dextrose agar yielded growth of C. neoformans that was nonfermentative, hydrolyzed starch, assimilated inositol and produced urease. Concanavine-glycine thymol blue agar was used to discriminate C. gattii from C. neoformans isolates.
Serology for anti-HIV-1 and HIV-2 was negative by multiple enzyme immunoassays (Erba Diagnostics, Germany; J. Mitra and Co. Pvt. Ltd.), a finding consistent with the absence of risk factors for HIV infection. The absolute CD4 count was 295 cells/µl on two occasions. Distribution of the different serum immunoglobulins (IgG, IgM, IgA and IgE) was carried out to rule out other causes of immunodeficiency. The total leukocyte count was within normal limits, as well as the absolute neutrophil, eosinophil and basophil counts. The patient did not have hypergammaglobulinemia as typically seen in patients infected with HIV. The patient was diagnosed as a case of idiopathic CD4 + lymphocytopenia since there was an absence of any defined immunodeficiency.
A skin biopsy revealed multiple capsulated yeasts cells in the cutaneous lesions, which were consistent with C. neoformans . Thus, a diagnosis of disseminated cryptococcosis in a HIV-negative host was made.
The patient was treated with intravenous amphotericin B (30 mg/day). He tolerated the drug very well with good clinical improvement. He did not develop any significant complications. At the end of the therapy (63 days; cumulative dose 1.89 g of amphotericin B), there was regression of cranial and cutaneous lesions and the CSF culture was sterile after 6 weeks of therapy. During his stay in the hospital, the patient was given occupational therapy. He was discharged and given oral fluconazole 400 mg/day for the next 10 weeks. On follow-up, the patient was recovering and symptom-free.
C. neoformans has a worldwide distribution. Predisposing factors for cryptococcal infections are defective cell-mediated immunity such as that which occurs in patients with AIDS, corticosteroid use, organ transplant recipients, patients with chronic leukemia and lymphomas and sarcoidosis.  Several defects in cell-mediated immune response have been described.  An increasing association of cryptococcosis in immunocompetent patients was observed in a few cases in India.  However, CD4+ T-lymphocyte depletion in patients without any evident HIV infection has been described by the Centers for Disease Control in 1992.  Similar reports are described and reviewed by other authors. ,
The principal sites of cryptococcal infection are pulmonary, CNS and disseminated disease. Disseminated cryptococcosis is defined as the recovery of C. neoformans from blood, sterile body fluids, or tissues other than pulmonary tissue. Cutaneous manifestations occur in 10-15% of cases and were the predominant feature of disseminated cryptococcosis in our patient. Cutaneous lesions described in the patient affected the face and neck as papules. The diagnosis of cutaneous cryptococcosis relied on skin histopathology.
Unusual forms of this disease like granulomas of the brain or spinal cord are occasionally seen.  A unique feature in this case was the presence of intraventricular and intracerebral mass lesions demonstrated by post-contrast CT. There are previous reports of intraventricular granuloma in the literature as reviewed by Aoki and Vijayan, et al. , The findings on the CT scan are by no means pathognomic of cryptococcosis. Thus, the importance of CSF cultures and serological studies cannot be over emphasized.
A resection of the mass lesion followed by intravenous amphotericin B with or without 5-fluorocytocine is recommended.  Our patient had multiple mass lesions and was managed with intravenous conventional amphptericin B. Follow-up CSF cultures became sterile after 6 weeks of therapy and a CT scan revealed regression of mass lesions.
In conclusion, the possibility of a fungal granuloma needs to be considered in an indolent lesion in an immunocompromised state other than AIDS. The present case highlights the importance of careful examination, including CSF cultures and serological studies.
|1||Powderly WG. Cryptococcal meningitis and AIDS. Clin Infect Dis 1993;17:837-42.|
|2||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.|
|3||Pappas PG, Perfect JR, Cloud GA, Larsen RA, Pankey GA, Lancaster DJ, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 2001;33:690-9.|
|4||Vilchez RA, Irish W, Lacomis J, Costello P, Fung J, Kusne S. The clinical epidemiology of pulmonary cryptococcosis in non-AIDS patients at a Tertiary Care Medical Center. Medicine (Baltimore) 2001;80:308-12.|
|5||Capoor MR, Nair D, Deb M, Gupta B, Agarwal P. Clinical and mycological profile of cryptococcosis in a tertiary care hospital. Indian J Med Microbiol 2007;25:401-4.|
|6||Centers for Disease Control and Prevention. Unexplained CD4+ T lymphocyte depletion in persons without evident HIV infection. MMWR Morb Mortal Wkly Rep 1992;41:541-5. |
|7||Zaharatos GJ, Behr MA, Libman MD. Profound T-lymphocytopenia and cryptococcemia in a human immunodeficiency virus-seronegative patient with disseminated tuberculosis. Clin Infect Dis 2001;33:E125-8.|
|8||Zonios DI, Falloon J, Huang CY, Chaitt D, Bennett JE. Cryptococcosis and Idiopathic CD4 Lymphocytopenia. Medicine 2007;86:78-92.|
|9||Vijayan N, Bhatt GP, Dreyfus PM. Intraventricular cryptococcal granuloma: A case report with review of the literature. Neurology 1971;21:728-34.|
|10||Aoki N. Intraventricular cryptococcal granulomas: Case report. Neurol Med Chir (Tokyo) 1989;29:251-4.|
|11||Bayardelle P, Giard N, Maltais R, Delorme J, Brazeau M. Success with amphotericin B and 5 fluorocytosine in treating cerebral cryptococcoma accompanying cryptococcal meningitis. Can Med Assoc J 1982;127:732-3.|