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PubMedDate not supplied

Cryptococcal meningitis presenting concurrently with systemic lupus erythematosus.

Cryptococcal meningitis is a rare but well recognized complication of systemic lupus erythematosus (SLE). Since in all previously reported cases in the medical literature the patients developed this opportunistic infection as the result of immunosuppressive therapies, whether the intrinsic immunological abnormalities of SLE per se contribute to the susceptibility remains controversial. We report on a patient who presented concurrently with cryptococcal meningitis and cryptococcaemia at the time of her diagnosis of active SLE. This highlights the possibility that intrinsic immunological defects of SLE may be directly responsible for the predisposition to fungal infections. In addition, when SLE patients present with neurological symptoms, the possible presence of central nervous system (CNS) infection must be checked for, even if immunosuppressive treatment is not being considered.

Antifungal Agents↗

PubMed1978

Cryptococcal meningitis. Cure despite cryptococcemia.

Cure of cryptococcal meningitis accompanied by cryptococcemia was achieved with amphotericin B therapy. Cryptococcal meningitis is associated with substantial morbidity and mortality, especially when accompanied by evidence of extraneural infection. Experience with the patient reported suggests that associated cryptococcemia is not invariably associated with treatment failure.

Adult↗

PubMed1999

Serum cyrptococcal antigen: diagnostic value in the diagnosis of AIDS-related cryptococcal meningitis.

RATIONALE: The incidences of HIV-AIDS patients with opportunistic infections of the central nervous system are increasing. Of these, cryptococcal meningitis is the most important and serious. A simple method for the diagnosis of cryptococcal meningitis is needed despite its variable clinical features and the lack of a capacity in most health facilities in Thailand to exclude it from other diseases especially mass lesions in the brain. OBJECTIVE: To identify the capability and cut off point of serum cryptococcal antigen for diagnosis and screening of cryptococcal meningitis in HIV-AIDS patients. METHODS: One hundred consecutive cases of HIV-AIDS patients suspected of having central nervous system infections were prospectively recruited for the study. The serum of all patients were examined for cryptococcal antigen by latex agglutination test, the Pastorex Cryptococcus manufactured by Sanofi Diagnostic Pasteur, France. If a test was positive, the serum dilution was carried out using 10-fold serial dilution. Every patient went through pre-defined standard investigations to derive at a definite diagnosis. The gold standard for diagnosis of cryptococcal meningitis was the presence of encapsulated yeast forms in the cerebrospinal fluid or a positive culture for cryptococcal neoformans from the cerebrospinal fluid. RESULTS: Of 100 patients enrolled in this study, 58 patients had cryptococcal meningitis and serum cryptococcal antigen was detectable in 60 patients. If the cut-off point for a positive test was when the serum cryptococcal antigen titer was more than zero, then, the sensitivity of the test was 91.4 per cent, the specificity was 83.3 per cent, likelihood ratio if test positive (LR+) was 5.47, likelihood ratio if test negative (LR-) was 0.1, false positive was 16.7 per cent, false negative was 8.6 per cent. CONCLUSION: We conclude that serum cryptococcal antigen is a simple and rapid screening method for diagnosis of cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗

PubMed1990

Cryptococcal meningitis in the acquired immunodeficiency syndrome.

Cryptococcosis is the most common, deep-seated fungal infection in AIDS patients, and cryptococcal meningitis is the most frequently observed syndrome. AIDS patients with cryptococcal meningitis usually have an indolent presentation and nonspecific findings on physical examination. Routine laboratory tests are of little assistance in diagnosing cryptococcal meningitis. Cerebrospinal fluid (CSF) white blood cell counts tend to be low, and glucose and protein levels are nonspecific. Serum cryptococcal antigen (CRAG) is a sensitive test for cryptococcal meningitis, and CSF CRAG is usually also positive. Definitive diagnosis is made by culture of the CSF. Therapy of cryptococcal meningitis is changing to antifungal agents that are easy to administer as outpatient therapy. Amphotericin B continues to be the primary antifungal used in initial treatment of cryptococcal meningitis; addition of flucytosine is of no benefit. Recent data suggest oral fluconazole is effective as primary therapy, and may be superior to amphotericin B as maintenance therapy. Maintenance therapy decreases the incidence of relapse and increases survival.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Overview: treatment of cryptococcal meningitis.

Infections caused by Cryptococcus neoformans cause significant morbidity and high mortality, particularly among immunocompromised patients. Cryptococcal meningitis is an important cause of central nervous system disease and death in patients with AIDS. Although the introduction of amphotericin B has greatly improved the prognosis of patients with cryptococcal meningitis, 30 years of experience have revealed important clinical limitations, including modest efficacy, nephrotoxicity, other clinically significant toxicities, and the inconvenience of intravenous dosing. The discovery of the additive effects of amphotericin B and flucytosine in cryptococcosis resulted in some improvement in efficacy and reduction in amphotericin B-related toxicity. However, approximately 30% of patients with cryptococcal meningitis still fail to respond to therapy. Ketoconazole has not proved useful in treating cryptococcal meningitis. Accumulating evidence suggests that the antifungal triazoles fluconazole, itraconazole, and SCH 39304 represent an advance in the treatment of cryptococcal meningitis, particularly in AIDS patients. Preliminary clinical trials in patients with and without AIDS have indicated that fluconazole and intraconazole are effective and well tolerated as either initial or maintenance therapy. Two large comparative trials of fluconazole and amphotericin B in patients with cryptococcal meningitis (mostly those with AIDS) are under way.

Acquired Immunodeficiency Syndrome↗

PubMed2004

[Cryptococcal meningitis].

BACKGROUND: Cryptococcus neoformans causes systemic disease in patients with immunodeficiency. The incidence of cryptococcal meningitis has increased in parallel with that of HIV infection. Cancer is also a known predisposing factor. MATERIAL AND METHODS: We present two case reports and a review of the literature concerning the epidemiology, diagnostics and treatment of cryptococcal meningitis. RESULTS: The incidence of cryptococcal meningitis in Scandinavia seems to be lower than in other parts of the world. Clinical signs and symptoms are often uncharacteristic. Detection of antigen in spinal fluid is a sensitive and fast test. INTERPRETATION: Cryptococcal meningitis is a rare disease, often with uncharacteristic symptoms. Patients with haematological malignancies have a higher risk of contracting this disease. It is a differential diagnosis when neurological symptoms occur in these patients.

Adult↗

PubMed1991

Cryptococcal meningitis in Auckland 1969-89.

Twenty-six patients with cryptococcal meningitis were seen in Auckland between 1969 and 1989. The incidence of cryptococcal meningitis in Auckland residents was 0.12 cases/100,000/year. Ten (38%) of the patients were Maori or Pacific Island Polynesians. Nineteen (73%) had a predisposing cause, including immunosuppressive therapy in nine and the acquired immunodeficiency syndrome (AIDS) in seven. The most common presenting syndrome was a subacute or chronic meningitis. Other clinical syndromes included a slowly progressive ataxia, polyradiculopathy, and headache with vomiting. In two patients, the symptoms of meningitis were overshadowed by those of systemic cryptococcal infection. Delay in making the diagnosis was common. The most sensitive method for diagnosing cryptococcal meningitis was the cerebrospinal fluid cryptococcal antigen test. Antifungal therapy cured 17 of the 25 (68%) treated patients overall, 15 of the 19 (79%) without AIDS and six of the seven with no underlying disease.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Cryptococcal meningitis in two apparently immunocompetent Maltese patients.

Two cases of cryptococcal meningitis occurring in immunocompetent men are described. The first case involves a farmer in whom cryptococcal meningitis was rapidly diagnosed using direct microscopy, latex antigen tests and culture of cerebrospinal fluid (CSF). In the second case, initial mycological tests on CSF (direct microscopy and culture) were repetitively negative and latex antigen tests gave unconvincing results. The patient was started on triple antituberculosis therapy, on which he improved immediately; therapy was continued for 1 year with the patient remaining well. However, within 1 week of stopping therapy, he had to be readmitted with neurological signs and symptoms. Culture of CSF this time yielded Cryptococcus neoformans and the antigen test was consistently positive. These are the first reported cases of cryptococcal meningitis in immunocompetent patients in Malta.

Cerebrospinal Fluid↗

PubMed1982

Pseudooutbreak of cryptococcal meningitis.

A pseudooutbreak of cryptococcal meningitis was caused by the use of contaminated albumin solution used in the preparation of Papanicolaou-stained slides of cerebrospinal fluid. Organisms were seen in cytocentrifuge preparations, but not in India ink preparations of cerebrospinal fluid specimens. Cryptococcal antigen tests were positive and Cryptococcus neoformans was cultured from the albumin-treated cerebrospinal fluid specimens and from the albumin solution.

Cerebrospinal Fluid↗

PubMed2006

A case of AIDS associated cryptococcal meningitis with multiple cranial nerve neuropathies.

Cryptococcal meningitis is a common opportunistic infection among patients with AIDS. Cranial nerve neuropathies are well-known complications that occur due to increased intracranial pressure and inflammation of cranial nerves in such patients but have not been previously reported to involve more than four cranial nerves simultaneously. Our patient had involvement of five cranial nerves resulting in the complete loss of vision and hearing as well palsies of the third, sixth and seventh cranial nerves. He was treated with multiple antifungal medications. Repeated high volume lumbar punctures and Ommaya reservoir were used to lower intracranial pressure. At the time of discharge the patient had complete recovery of the functions of third, sixth and seventh cranial nerves bilaterally and partial recovery of hearing and vision.

AIDS-Related Opportunistic Infections↗

PubMed1988

Treatment of two cases of cryptococcal meningitis with fluconazole.

Two patients with cryptococcal meningitis were treated with the investigational triazole drug fluconazole (UK-49,858). Cerebrospinal fluid (CSF) levels of fluconazole were between 3.0 and 5.4 mg/l 2 h after an oral dose of 50 mg daily in the first patient and between 7.9 and 9.0 mg/l after an oral dose of 100 mg daily in the second patient. These levels were in the same range as plasma levels. The first patient, a 46-year-old renal transplant patient, was both clinically and microbiologically cured after 28 weeks of therapy (follow-up 14 months). In the second patient, a 15-year-old girl with chronic mucocutaneous candidiasis, fluconazole led to clinical cure of the meningitis, but failed to eradicate cryptococci from the CSF. These cases illustrate that fluconazole is useful for the treatment of cryptococcal meningitis, especially when prolonged treatment is indicated as in patients with immunodeficiencies.

Adolescent↗

PubMed1994

Measurement of cryptococcal antigen in serum and cerebrospinal fluid: value in the management of AIDS-associated cryptococcal meningitis.

The value of monitoring titers of cryptococcal antigen in serum and cerebrospinal fluid (CSF) during therapy for AIDS-associated cryptococcal meningitis was evaluated. Baseline and final titers of antigen in serum and CSF from participants in two studies of such therapy were categorized as increased (a rise of at least two dilutions), unchanged, or decreased (a fall of at least two dilutions). There was no correlation between outcome and changes in serum titers of cryptococcal antigen during treatment for acute meningitis or during suppressive therapy. During therapy for acute infection, an unchanged or increased titer of antigen in CSF was correlated with clinical and microbiological failure to respond to treatment; the correlation was especially strong among patients whose baseline titer of antigen was > or = 1:8 (P = .01). A rise in CSF antigen titer during suppressive therapy was associated with relapse of cryptococcal meningitis (P < .001). We conclude that serial monitoring of cryptococcal antigen, as conducted in these studies, has a limited role in the management of AIDS patients with cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗

PubMed1992

[Cryptococcal meningitis and AIDS. Clinical description of 10 patients].

We have studied 10 patients with cryptococcal meningitis and AIDS. Nine of them were intravenous drug users and four have been previously diagnosed of AIDS. In 60% of them cryptococcal meningitis was the first opportunistic infection, and as group represented only 6.3% of our 158 patients with AIDS on the same period. The most common symptoms were: malaise (100%), headache (80%), fever (60%), meningeal signs (50%). Two of them had focal neurological disease. CSF culture and serum cryptococcal antigen test were positive in 90%, the Indian ink in 77% and blood cultures in 30% of the cases, while indian ink preparation did it in 77%. MRI showed bilateral small lesions, deeply located, in 3 cases; it was also useful to prove optical tract lesions in a patient with blindness as a result of cryptococcal meningitis. We had treatment successes in 80% of the cases, all patients being treated with amphotericin B, alone in 4 and amphotericin B plus fluorocytosine in 6. Two patients died within the first 2 weeks. Maintenance therapy with fluconazole was effective and well tolerated, with 3 patients dying from causes other than cryptococcal meningitis. We recorded a survival rate over 12 months in 33% of patients.

Acquired Immunodeficiency Syndrome↗

PubMed1999

[Cryptococcal meningitis in a patient without known predisposing disease].

Cryptococcal meningitis is a rare disease. It may occur as a superinfection in AIDS patients or other immunosuppressed patients. We describe a case of cryptococcal meningitis in a non-immunosuppressed patient. Initial symptoms were fatigue, depression and headache. A correct diagnosis was made after two weeks based on microscopic examination of cerebrospinal fluid. The patient died after six days on antimycotic therapy. Cryptococcosis is a difficult diagnosis, as our case illustrates. Psychiatric symptoms are often the first clinical manifestations. Early diagnosis is crucial for the outcome. A short overview on cryptococcosis is given.

Diagnosis, Differential↗

PubMed1992

Therapy for cryptococcal meningitis in patients with AIDS.

Treatment of cryptococcal meningitis in patients with AIDS with amphotericin B plus flucytosine is associated with a failure rate of 20%-30%. In the absence of chronic suppressive therapy, 40%-60% of patients develop recurrent disease. Recent comparative studies have evaluated fluconazole, a new triazole antifungal agent. In primary therapy, fluconazole is associated with response rates of 35%-60%, which are equivalent to those seen with amphotericin B alone. However, a smaller study suggested that amphotericin B plus flucytosine was superior to fluconazole alone. Both studies identified risk factors associated with a poor outcome; these factors include lethargy or obtundation at presentation, a high titer of cryptococcal antigen titer in the cerebrospinal fluid, and a low leukocyte count in the cerebrospinal fluid. Fluconazole is highly effective in suppressing relapses of cryptococcal meningitis. Itraconazole has been investigated less extensively in the treatment of cryptococcosis but offers promise. Future studies need to address alternative approaches to the management of acute cryptococcal disease and primary prophylaxis for cryptococcal infection in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Cryptococcal meningitis in acute lymphoblastic leukemia.

The occurrence of cryptococcal meningitis in acute lymphoblastic leukemia (ALL), despite being immunosuppresed state is uncommon. We report a 28-year gentleman in the maintenance treatment phase of ALL developing cryptococcal meningitis. The diagnosis was made by positive India ink staining and detection of cryptola antigen by latex agglutination. The patient was successfully treated with amphotericin B. The rarity of this condition in ALL is briefly discussed.

Adult↗

PubMed1992

Oral SCH 39304 as primary, salvage, and maintenance therapy for cryptococcal meningitis in AIDS.

To determine the efficacy and toxicity of SCH 39304 in the treatment and suppression of cryptococcal meningitis, we conducted a prospective, noncomparative study in three groups of patients: patients with acute cryptococcal meningitis, patients with acute cryptococcal meningitis in whom other therapies have failed (salvage), and patients who required maintenance therapy. As primary therapy, the patients received up to 14 days or 1 g of amphotericin B followed by SCH 39304 200 mg once daily for 12 weeks. As maintenance therapy, the patients received SCH 39304 600 mg once weekly for 12 months. Of five salvage patients, none completed the study. Two patients died, two patients clinically deteriorated, and one patient was noncompliant. Two of three patients with acute cryptococcal meningitis completed the 12-week primary therapy, and one patient was discontinued from therapy because of a skin rash (95% confidence interval, 14-100%). All four patients who were receiving weekly maintenance therapy followed up to 27 weeks were clinically stable with no change in their serum cryptococcal antigen titer from baseline when the study was prematurely terminated. Elevation of liver function test results developed in three patients and skin rash developed in one patient. The unique pharmacologic and pharmacokinetic properties of SCH 39304 (low incidence of toxicity, long serum half-life, and good penetration into the cerebrospinal fluid) lend promise to pursue other triazole antifungals at higher doses as primary therapy and less frequent dosing for maintenance therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Ventriculoperitoneal shunt in cryptococcal meningitis with hydrocephalus.

Fourteen patients with cryptococcal meningitis were reviewed. All patients had a ventriculoperitoneal shunt for hydrocephalus. Early recognitions and prompt relief of hydrocephalus were useful for eight patients who showed rapid deterioration of consciousness or signs of cerebral herniation. There was no surgical response in four patients who had had weeks of confusion or mental change. It seems, therefore, that the duration of disturbance of consciousness or change of mentality before shunting is critical in determination of the outcome of the treatment. Ventricular shunting was effective in relieving papilledema in five patients. However, the surgery did not prevent the development of papilledema to optic atrophy and subsequent blindness in two patients. Hence, in addition to hydrocephalus with increased intracranial pressure, conditions such as direct invasion of the optic pathways by Cryptococcus neoformans or optochiasmatic arachnoiditis may be responsible for the visual failure. Ventricular shunting was also helpful in restoring paraparesis in one patient. Of the cerebrospinal fluid determinations, low protein concentration was a favorable indicator for surgery. Of the seven patients who received the surgical procedure before the start of antifungal therapy, four showed a significant improvement despite active infection of the central nervous system. None of the seven patients deteriorated because of the surgical operation. Thus, active stage of cryptococcal meningitis does not contraindicate the necessity of shunting, and premedication with antifungal drugs is unnecessary. Also, no shunt-related morbidity and mortality was seen in this study.

Adolescent↗