ABSTRACT
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.
Subject(s)
Cryptococcus neoformans , HIV Infections , Meningitis, Cryptococcal , Female , Humans , Adult , Meningitis, Cryptococcal/drug therapy , Meningitis, Cryptococcal/chemically induced , Meningitis, Cryptococcal/diagnosis , Fingolimod Hydrochloride/adverse effects , HIV Infections/drug therapy , Antifungal Agents/adverse effectsABSTRACT
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.
Subject(s)
Meningitis, Cryptococcal , Psoriasis , Humans , Interleukin-17 , Meningitis, Cryptococcal/chemically induced , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/drug therapy , Psoriasis/drug therapy , Severity of Illness Index , Treatment OutcomeABSTRACT
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.
Subject(s)
Fingolimod Hydrochloride , Meningitis, Cryptococcal , Databases, Factual , Female , Fingolimod Hydrochloride/adverse effects , Humans , Incidence , Male , Meningitis, Cryptococcal/chemically induced , Meningitis, Cryptococcal/drug therapy , Middle Aged , United StatesSubject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Meningitis, Cryptococcal , Abatacept/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Humans , Meningitis, Cryptococcal/chemically induced , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/drug therapy , Treatment OutcomeABSTRACT
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.
Subject(s)
Histoplasmosis/chemically induced , Invasive Fungal Infections/chemically induced , Meningitis, Cryptococcal/chemically induced , Polycythemia Vera/drug therapy , Pyrazoles/adverse effects , Guam , Histoplasmosis/complications , Histoplasmosis/pathology , Humans , Immune Tolerance/drug effects , Immunocompromised Host , Invasive Fungal Infections/complications , Invasive Fungal Infections/pathology , Male , Meningitis, Cryptococcal/complications , Meningitis, Cryptococcal/pathology , Middle Aged , Nitriles , Pyrimidines , VeteransABSTRACT
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 8â 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.
Subject(s)
Dexamethasone/adverse effects , Glucocorticoids/adverse effects , Meningitis, Cryptococcal/chemically induced , Opportunistic Infections/chemically induced , Adolescent , Antifungal Agents/therapeutic use , Diagnosis, Differential , Drug Therapy, Combination , HIV Seronegativity , Humans , Magnetic Resonance Imaging , Male , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/drug therapy , Opportunistic Infections/diagnosis , Opportunistic Infections/drug therapy , Tuberculosis, Miliary/diagnosisSubject(s)
Anti-Inflammatory Agents/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Meningitis, Cryptococcal/chemically induced , Meningoencephalitis/chemically induced , Meningoencephalitis/microbiology , Methotrexate/adverse effects , Prednisone/adverse effects , Anti-Inflammatory Agents/therapeutic use , Antirheumatic Agents/therapeutic use , Female , Humans , Methotrexate/therapeutic use , Middle Aged , Prednisone/therapeutic useSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cryptococcus neoformans/isolation & purification , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Meningitis, Cryptococcal/diagnosis , Aged , Amphotericin B/therapeutic use , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antibodies, Monoclonal, Murine-Derived/adverse effects , Antifungal Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cryptococcus neoformans/drug effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Drug Therapy, Combination , Fatal Outcome , Flucytosine/therapeutic use , Humans , Male , Meningitis, Cryptococcal/chemically induced , Meningitis, Cryptococcal/drug therapy , Rituximab , Time Factors , Vidarabine/administration & dosage , Vidarabine/adverse effects , Vidarabine/analogs & derivativesSubject(s)
Antineoplastic Agents, Hormonal/adverse effects , Cryptococcosis/chemically induced , Fungemia/chemically induced , Prednisone/adverse effects , Sezary Syndrome/drug therapy , Skin Neoplasms/drug therapy , Abscess , Aged , Cryptococcosis/diagnosis , Dermatomycoses/chemically induced , Dermatomycoses/microbiology , Dermatomycoses/pathology , Female , Fungemia/diagnosis , Fungemia/microbiology , Humans , Meningitis, Cryptococcal/chemically induced , Meningitis, Cryptococcal/diagnosis , Sezary Syndrome/complications , Skin Neoplasms/complicationsSubject(s)
Antibodies, Monoclonal, Murine-Derived/adverse effects , Antibodies, Monoclonal/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Meningitis, Cryptococcal/chemically induced , Aged , Cryptococcus neoformans/isolation & purification , Humans , Infliximab , Male , Rituximab , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
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.
Subject(s)
Brain Neoplasms/complications , Dexamethasone/adverse effects , Glioma/complications , Immunosuppression Therapy/adverse effects , Meningitis, Cryptococcal/chemically induced , Opportunistic Infections/chemically induced , Adult , Aged , Amphotericin B/therapeutic use , Anti-Inflammatory Agents/adverse effects , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Antineoplastic Agents, Alkylating/adverse effects , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Cerebrospinal Fluid/microbiology , Cryptococcus neoformans/drug effects , Dacarbazine/adverse effects , Dacarbazine/analogs & derivatives , Fatal Outcome , Fluconazole/pharmacology , Fluconazole/therapeutic use , Flucytosine/therapeutic use , Glioma/drug therapy , Glioma/pathology , Humans , Lomustine/adverse effects , Male , Meningitis, Cryptococcal/cerebrospinal fluid , Meningitis, Cryptococcal/pathology , Opportunistic Infections/cerebrospinal fluid , Opportunistic Infections/pathology , Temozolomide , Treatment OutcomeSubject(s)
AIDS-Related Opportunistic Infections/chemically induced , Acquired Immunodeficiency Syndrome/complications , Anti-Retroviral Agents/adverse effects , Inflammation/chemically induced , Meningitis, Cryptococcal/complications , Reverse Transcriptase Inhibitors/adverse effects , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/immunology , Adult , Anti-Retroviral Agents/therapeutic use , CD4 Lymphocyte Count , Cohort Studies , Cryptococcus/isolation & purification , Female , Humans , Kaplan-Meier Estimate , Male , Meningitis, Cryptococcal/chemically induced , Recurrence , Retrospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Syndrome , Time Factors , Treatment OutcomeABSTRACT
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.
Subject(s)
Antibodies, Monoclonal/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Meningitis, Cryptococcal/chemically induced , Aged , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/immunology , Female , Humans , Immunocompromised Host , Infliximab , Male , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
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.
Subject(s)
Anti-HIV Agents/adverse effects , HIV Infections/physiopathology , Meningitis, Cryptococcal/chemically induced , Radiculopathy/chemically induced , Adult , Amphotericin B/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anti-Retroviral Agents/adverse effects , Ceftriaxone/therapeutic use , Ciprofloxacin/therapeutic use , Female , Humans , Lamivudine/adverse effects , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/etiology , Nevirapine/adverse effects , Radiculopathy/diagnosis , Radiculopathy/etiology , Stavudine/adverse effectsABSTRACT
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).
Subject(s)
Antineoplastic Agents/adverse effects , Brain Abscess/chemically induced , Meningitis, Cryptococcal/chemically induced , Neuroaspergillosis/chemically induced , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Brain Abscess/drug therapy , Brain Abscess/pathology , Child, Preschool , Fatal Outcome , Humans , Magnetic Resonance Imaging , Male , Meningitis, Cryptococcal/drug therapy , Meningitis, Cryptococcal/pathology , Neuroaspergillosis/drug therapy , Neuroaspergillosis/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complicationsABSTRACT
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.
Subject(s)
AIDS-Related Opportunistic Infections/chemically induced , Acquired Immunodeficiency Syndrome/drug therapy , Antiretroviral Therapy, Highly Active/adverse effects , Immune Reconstitution Inflammatory Syndrome/complications , Meningitis, Cryptococcal/chemically induced , AIDS-Related Opportunistic Infections/cerebrospinal fluid , Adult , CD4 Lymphocyte Count , Cryptococcus neoformans , Female , Humans , Immune Reconstitution Inflammatory Syndrome/cerebrospinal fluid , Immune Reconstitution Inflammatory Syndrome/immunology , Meningitis, Cryptococcal/cerebrospinal fluid , Viral LoadABSTRACT
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.