Indian Journal of Medical Microbiology Medknow Publications on behalf of Indian Association of Medical Microbiology ISSN: 0255-0857 EISSN: 1998-3646 Vol. 23, Num. 3, 2005, pp. 207-208

Indian Journal of Medical Microbiology, Vol. 23, No. 3, July-September, 2005, pp. 207-208

Correspondence

Corticosteroid induced Cryptococcus meningitis

Kumari P.R., Shahapur P.R., Rao P.S.

Dept of Microbiology, Kasturba Medical College, Manipal – 576104, Karnataka

Correspondence Address: Dept of Microbiology, Kasturba Medical College, Manipal – 576104, Karnataka, psraos82@yahoo.co.in

Date of Submission: 10-Sep-2004
Date of Acceptance: 19-Oct-2004

Code Number: mb05064

Dear Editor,

Cryptococcosis is a disease of high morbidity and mortality, often presenting as meningitis in immunocompromised patients. Currently, acquired immunodeficiency syndrome is the most important predisposing factor in approximately 80-90% of cryptococcal infections.[1] Cryptococcosis also occurs in patients, who are not infected with human immunodeficiency virus (HIV), like those who are on prolonged high dose or therapeutic dose corticosteroid therapy, patients with lymphoreticular malignancies[2] as well as sarcoidosis even in the absence of corticosteroid therapy. We are reporting a case of cryptococcal meningitis in a HIV seronegative, 13 year old girl with autoimmune hemolytic anaemia for which she underwent longterm corticosteroid therapy.

Patient was admitted with acute symptoms of severe constricting type of headache, vomiting since 10 days and intermittent episodes of altered behaviour, seizures and fever of 7 days duration; the patient was admitted. She was a known case of autoimmune haemolytic anemia on corticosteroid therapy (prednisolone- 4.5 mg/kg body weight/day) since one year. On examination, the child was febrile having exohpthalmos, cushingoid facies, striae over legs and buttocks, erythema over face and enlarged posterior cervical lymph nodes. On central nervous sytem (CNS) examination, she was conscious with waxing and waning of sensorium, neck stiffness, upper motor neuron facial palsy, right twelfth cranial nerve palsy and generalized hypotonia. Reflexes could be just elicited. On examination cardiovascular system, respiratory and gastrointestinal systems were normal. Routine blood investigation revealed Hb - 4.2 gm%, TLC 5600/Cu.mm, DLC - N 80%, L 18%, and M 2%, ESR-50 mm/1st one hour. Her random blood glucose was 153 mg/dL. HIV ELISA was negative. Cerebrospinal fluid (CSF) analysis showed glucose-28 mg/dL, protein-30 mg/dL and no cells.

Microscopic examination of cerebrospinal fluid (CSF) by gram staining revealed gram positive budding yeast cells and India ink preparation demonstrated capsulated budding yeast cells. Culture of CSF on Sabouraud dextrose agar (SDA) grew mucoid yeast colonies after 72 hours of incubation at 37°C as well at 22 °C which was identified as Cryptococcus neoformans by standard mycological techniques.[3] The organism was not isolated in blood culture. Cryptococcus neoformans capsular polysaccharide antigen by latex agglutination test (Crypto-LA Test, Laboratories Fumouze) was detected in serum and CSF. In the diagnosis of cryptococcal meningitis, the patient was started on antifungal treatment with IV amphotericin B 600 mg/day for one week. Repeat CSF examination was positive for Cryptococcus neoformans both by culture and latex agglutination test (LAT). The patient was given IV fluconazole 400 mg/day for three weeks. Patient showed clinical improvement, though LAT both for CSF and serum showed persistent positivity with a decline in antigen titre from 3+ to 1+. As her condition improved steadily, she was discharged with oral fluconazole 100 mg daily for 10 weeks. The patient was followed for up to one year with review every 10 weeks. Even with one year of treatment with amphotericin B and fluconazole, LAT of serum and CSF persistently showed 1+ positivity as well as positive CSF culture, though the patient was symptom free.

Cryptococcus neoformans is recognized as the most frequent cause of fungal infection of the CNS in immunocompetent as well as in immunocompromised persons. Majority of the patients who develop cryptococcal meningitis are HIV seropositive[4]. There are reports of cryptococcosis developing in HIV seronegative but immunocompromised[2]. Host becomes vulnerable to cryptococcosis whenever there is defect in T cell mediated host defence mechanisms. In this case, prolonged corticosteroid therapy for the management of autoimmune haemolytic anemia might have caused profound immunosuppression and predisposed for the development of cryptococcal meningitis.

A six week course of amphotericin B combined with flucytosine has been considered the treatment, of choice for cryptococcal meningitis with a good prognosis. In spite of adequate treatment, unlike in other reports, the blood and CSF examination remained positive both for cryptococcus antigen by LAT and CSF culture, even up to one year of follow up in our case, indicating necessity for prolonged treatment with antifungal drugs. Long term suppressive treatment, although not effective in preventing relapse, as it is seen in our case, may improve survival. This observation in our case also highlights the importance of periodic assessment of the immune status of the patients and subsequent modification of the management to prevent the development of cryptococcal meningitis.

REFERENCES

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