A Case of Fingolimod-associated Cryptococcal Meningitis.

BACKGROUND: Leukopenia, a rare adverse effect of Fingolimod therapy, paves the way for opportunistic infections. In this study, we reported rare fingolimod associated cryptococcal meningitis. CASE PRESENTATION: A 39-year-old woman with RRMS was referred to the emergency department. The patient's major complaints were headache, fever, weakness, and progressive loss of consciousness within the last two days prior to the referral. The patient had a history of hospitalization due to RRMS [two times]. In the second hospitalization, interferon Beta-1a was replaced with Fingolimod. Using polymerase chain reaction, Cryptococcus neoformans was detected in CSF. Liposomal amphotericin B and fluconazole [800 mg per day] were started. Six weeks later, the patient was discharged without any major complaints. CONCLUSION: Albeit fingolimod associated cryptococcal meningitis is a rare event, Fingolimod therapy in patients with MS should be performed cautiously. Regular follow-ups may give rise to a timely diagnosis of probable fingolimod associated cryptococcal meningitis. Fingolimod therapy can lead to lymphocytopenia and various infections. We, therefore, suggest that intermittent blood lymphocyte counts as well as monitoring of clinical manifestations among MS patients treated with Fingolimod to avoid additional neurological and physical disabilities in these patients.

Cryptococcal meningitis associated with interleukin-17 inhibitor use for psoriasis.

Invasive fungal infection is a rare but serious potential consequence of biologic therapy. Herein, we report a case of cryptococcal meningitis in an otherwise immunocompetent patient receiving ixekizumab for the treatment of severe plaque psoriasis. We also discuss the relevant immunologic role of interleukin-17, the potential for synergistic effects when transitioning biologic therapies, and clinical considerations when treating patients with such medications. To the best of our knowledge, this is the first case of cryptococcal meningitis reported in a patient treated with ixekizumab.

Cryptococcal Meningitis Reported With Fingolimod Treatment: Case Series.

BACKGROUND AND OBJECTIVES: To describe the characteristics of patients with MS reporting cryptococcal meningitis (CM) while treated with fingolimod. METHODS: The Novartis safety database was searched for cases with CM between January 26, 2006, and February 28, 2020. The reporting rate of CM was estimated based on the case reports received and exposure to fingolimod in the postmarketing setting during the relevant period. RESULTS: A total of 60 case reports of CM were identified, mostly from the United States. The median age was 48 years, and 51.8% were women. Most of the patients had recovered or were recovering at the time of final report. A fatal outcome occurred in 13 cases. During the study period, the rate of CM in patients with MS receiving fingolimod was estimated to be 8 per 100,000 patient-years (95% CI: 6.0; 10.0). The incidence of CM seemed to increase with duration of treatment; however, this relationship remains uncertain due to wide CIs and missing data. DISCUSSION: The causal relationship between fingolimod treatment and CM is not yet fully understood. The CM mortality rate in fingolimod-treated patients is similar to that reported in HIV-negative patients. Vigilance for signs and symptoms of CM in patients receiving fingolimod, particularly the new onset of headaches and altered mental status, is essential. Early diagnosis and treatment are critical to reducing CM-associated mortality.

A case report of disseminated histoplasmosis and concurrent cryptococcal meningitis in a patient treated with ruxolitinib.

BACKGROUND: Ruxolitinib is a highly potent janus kinase inhibitor that places its users at risk for various bacterial infections and viral reactivation. However new reports are also emerging that suggest greater immunosuppression and risk for fungal disease. CASE PRESENTATION: We report the case of a 51 year-old veteran from Guam, treated with ruxolitinib for polycythemia vera, who developed disseminated histoplasmosis and concurrent cryptococcal meningitis. CONCLUSION: This case draws attention to the degree of immunosuppression that may be seen with this drug and the need for heightened vigilance for opportunistic infections in those treated with inhibitors of janus kinase/signal transducers and activators of transcription (JAK/STAT) such as ruxolitinib.

Corticosteroid-induced cryptococcal meningitis in patient without HIV.

Cryptococcus neoformans is the most frequent cause of fungal meningitis in humans. Cryptococcus affects people of all ages and has a worldwide distribution. It is the fourth most common infection in AIDS (CD4 counts <100/mm3). Cases also occur in patients with other forms of immunosuppression and in apparently immunocompetent individuals. Chronic high-dose steroid may precipitate such an immunocompromised state and thus create susceptibility to fungal infections. In our case, we describe a 14-year-old boy who was on steroids for tubercular meningitis for a period of 8 weeks after which he developed cryptococcal meningitis. Attention is drawn to the increasing number of reported cases of this disease which have been associated with steroid therapy and this possibility should be remembered when investigating patients with tubercular meningitis especially if they are being treated with steroids.

Cryptococcal meningitis in patients with glioma: a report of two cases.

OBJECTIVE AND IMPORTANCE: We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the efficacy of prophylactic antibiotic and/or antifungal regimens in this patient population due to their increased risk of opportunistic infections. CLINICAL PRESENTATION: A 73-year-old man with a history of glioblastoma multiforme (GBM), on dexamethasone and status post radiation therapy and two cycles of temozolamide, presented with decreased level of consciousness for 24 h and was found to have cerebrospinal fluid (CSF) and blood cultures positive for Cryptococcus neoformans. A 33-year-old man with a history of anaplastic astrocytoma, on dexamethasone and status post radiation therapy, four cycles of temozolomide and two cycles of Lomustine (CCNU), presented with headache, dizziness and photophobia and was found to have CSF and blood cultures positive for Cryptococcus neoformans. INTERVENTION: Both patients were treated with an initial regimen of amphotericin B and flucytosine for a minimum of two weeks and switched to fluconazole for 6 months to 1 year of treatment. CONCLUSION: Patients with high-grade glioma treated with long-term corticosteroid therapy and chemotherapy are at increased risk of developing opportunistic infections. The two patients reported here developed cryptococcal meningitis and sepsis. Prophylactic regimens with either fluconazole or itraconazole currently exist that effectively decrease the incidence of both cryptococcal infections. Further investigations into the risk:benefit ratio of primary prophylactic therapy in this patient population may prove beneficial.

Cryptococcal meningitis in a patient treated with infliximab.

Infliximab, a tumor necrosis factor-alpha inhibitor, is increasingly used for the therapy of different inflammatory conditions. We report the first case of cryptococcal meningitis in a patient treated with infliximab and other immunosuppressive agents, and review a further 5 reported cryptococcal infections. All of them involved fungal pneumonia. Outcome was favorable in all cases.

Cryptococcal meningoradiculitis: an atypical presentation after initiation of antiretroviral therapy.

Atypical presentations of cryptococcal infection have been described as clinical manifestations of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients following commence of antiretroviral therapy (ART). The authors describe a patient presenting with cryptococcal meningoradiculitis two weeks after initiation of ART. In patients with advanced HIV disease, immune reconstitution induced by ART can precipitate onset of atypical clinical manifestations in those patients with latent cryptococcal infection of the central nervous system.

Fungal brain abscesses in leukemia.

Invasive fungal infections remain a life threatening complication in children with hematological malignancies. The brain represents a common site of hematogenously disseminated infections from an extracranial focus. We report our experience in the diagnosis, radiological aspects and therapeutic approach of fungal brain abscesses in 2 children receiving chemotherapy for acute lymphoblastic leukemia (ALL).

[Inflammatory reconstitution immune syndrome associated to antiretroviral therapy and meningeal cryptococcosis]. / Síndrome de restauración inmune asociado a tratamiento antirretroviral y criptococosis meníngea. Caso clínico.

The objective of high activity antiretroviral therapy (HAART) in patients with AIDS, is to obtain immune restoration. This means a reduction of the viral load and restitution of the CD4 cell count. A decreased rate of HIV replication improves both the number and function of CD4 cells. Nevertheless, this treatment sometimes results in the reappearance of previous symptoms from treated conditions due to opportunistic infections (ie: tuberculosis, criptococcosis, hepatitis, Pneumocystis jirovesi, toxoplasmosis, etc) or non infectious condition such as sarcoidosis, Graves disease or Kaposi sarcoma. This is known as Inflammatory Reconstitution Immune Syndrome (IRIS). We report a 37 year-old woman in stage C3-AIDS with a previous criptococcal meningitis. She was treated, achieving a marked improvement with treatment and subsequent suppressive therapy with fluconazole 200 mg/day. IRIS appeared after 8 months of ongoing antiretroviral therapy with immune restoration with the development of aseptic meningitis and intracranial hypertension. The opportunistic agent could not be identified by cultures. Additional laboratory tests excluded toxoplasmosis, tuberculosis, bacterial cerebral abscesses, syphilitic cerebral gummas, and lymphoma. Brain CT and magnetic resonance studies were compatible with brain vasculitis and leptomeningitis. The patient condition improved with general measures, such as a repeated lumbar punctures and non steroidal anti-inflammatory drugs. We conclude that this patient had an IRIS due to a Cryptococcus neoformans antigen.

Síndrome de restauración inmune asociado a tratamiento antirretroviral y criptococosis meníngea: Caso clínico / Inflammatory reconstitution immune syndrome associated to antiretroviral therapy and meningeal cryptococcosis

The objective of high activity antiretroviral therapy (HAART) in patients with AIDS, is to obtain immune restoration. This means a reduction of the viral load and restitution of the CD4 cell count. A decreased rate of HIV replication improves both the number and function of CD4 cells. Nevertheless, this treatment sometimes results in the reappearance of previous symptoms from treated conditions due to opportunistic infections (ie: tuberculosis, criptococcosis, hepatitis, Pneumocystis jirovesi, toxoplasmosis, etc) or non infectious condition such as sarcoidosis, Graves disease or Kaposi sarcoma. This is known as Inflammatory Reconstitution Immune Syndrome (IRIS). We report a 37 year-old woman in stage C3-AIDS with a previous criptococcal meningitis. She was treated, achieving a marked improvement with treatment and subsequent suppressive therapy with fluconazole 200 mg/day. IRIS appeared after 8 months of ongoing antiretroviral therapy with immune restoration with the development of aseptic meningitis and intracranial hypertension. The opportunistic agent could not be identified by cultures. Additional laboratory tests excluded toxoplasmosis, tuberculosis, bacterial cerebral abscesses, syphilitic cerebral gummas, and lymphoma. Brain CT and magnetic resonance studies were compatible with brain vasculitis and leptomeningitis. The patient condition improved with general measures, such as a repeated lumbar punctures and non steroidal anti-inflammatory drugs. We conclude that this patient had an IRIS due to a Cryptococcus neoformans antigen.