Article
The delusive value of cryptococcal antigen assay in monitoring cryptococcal disease in a fatal case of meningoencephalitis by C. neoformans, sensitive to antifungal standard therapy
Klinische Progression und fataler Verlauf einer Meningoenzephalitis durch Cryptococcus neoformans, sensitiv auf alle Elemente der antimykotischen Standardtherapie trotz signifikanten Titerabfalls des Kryptokokken-Antigens in CSF und Serum
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Authors
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S. Mohammad-Khani
- Medizinische Hochschule Hannover, Klinik für Immunologie und Rheumatologie, Hannover, Germany
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B. Otremba
- Schwerpunktpraxis, Hämatologie und Onkologie, Oldenburg, Germany
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R. Klein
- Medizinische Hochschule Hannover, Neuropathologie, Hannover, Germany
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R.E. Schmidt
- Medizinische Hochschule Hannover, Klinik für Immunologie und Rheumatologie, Hannover, Germany
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M. Stoll
- Medizinische Hochschule Hannover, Zentrum Innere Medizin, Klinik für Immunologie und Rheumatologie, Hannover, Germany
| Published: | June 2, 2010 |
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Outline
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Background: Cryptococcus neoformans is the most common cause of life threatening meningoencephalitis in HIV-infected patients. Evidence of cryptoccocal antigen (CrA) in serum and cerebrospinal fluid (CSF) are reliable parameters in ensuring the diagnosis. In the majority of cases complete remission can be achieved by antifungal combination therapy with either amphotericin B (AmpB) + flucytosine (5-FC) or by AmpB + 5-FC + Fluconazole (FCZ) respectively. Response to treatment could be evaluated either by assessment of clinical improvement or by cryptococcal clearance in CSF. But the clearance of cryptococcal antigen in CSF or blood is delayed and therefore is not recommended as a surrogate marker for short term response to therapy.
Case report:Three weeks after first diagnosis of HIV infection and Pneumocystis carinii pneumonia antiretroviral treatment (HAART) was started at a nadir of 59 CD4+T-cells/µl and a viral load of log 5 in a 33 year old male. Despite successful viral suppression he presented with headache, emesis, lethargy and focal seizures. Lumbar punction revealed positive CSF-CrA (1:8192) and positive culture for C. neoformans var grubii. Isolates were sensitive to FCZ, 5-FU, and AmpB. Despite antifungal triple drug therapy in combination with corticosteroids and despite a significant decrease of CrA in CSF and blood within three weeks the patient worsened clinically. The progress by actively dividing fungus within increasing intracerebral lesions could be proven by biopsy. The outcome was fatal five weeks after initiation of antifungal therapy.
Conclusions: In cases of cryptococcal meningoencephalitis (CM) careful clinical observation, neuroimaging, determination of intralumbar or intracranial pressure, and direct confirmation of cerebrospinal fluid sterility by lumbar puncture is crucial, because cryptococcal antigen in serum and CSF – although a valuable parameter in initial diagnosis of AIDS-related CM with a high sensitivity of >90% is not a reliable parameter in the acute phase of disease.
