Practical approach to monitoring and prevention of infectious complications associated with systemic corticosteroids, antimetabolites, cyclosporine, and cyclophosphamide in nonmalignant hematologic diseases

Abstract

Corticosteroids constitute a first-line therapy for adults and children suffering from nonmalignant immune-mediated hematologic diseases. However, high disease relapse rates during the tapering period or upon drug discontinuation result in long-term corticosteroid use that increases the risk of infection. This same concept applies to other immunosuppressive agents, such as antimetabolites, calcineurin inhibitors, and cyclophosphamide. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection. Screening and antimicrobial prophylaxis against tuberculosis, hepatitis B, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia (PJP) might be indicated in patients who are scheduled to be on high-dose corticosteroids for >4 weeks (>30 mg of prednisone-equivalent dose [PEQ]) or in patients chronically treated (≥8 weeks of continuous or intermittent corticosteroid use) with moderate doses (≥15 to <30 mg PEQ). Antimetabolites (azathioprine, mycophenolate) increase the risk of progressive multifocal leukoencephalopathy (PML); however, other opportunistic infections and viral reactivation have also been reported. In case of new onset of neurological symptoms, PML needs to be considered, and an urgent neurology consultation should be obtained. Cyclophosphamide-induced myelosuppression can lead to serious infections related to neutropenia. PJP prophylaxis should be considered with combination therapy of cyclophosphamide and corticosteroids until a PEQ dose ≤ 5 mg/d is reached. Data on infectious risk when cyclosporine is used in patients with nonmalignant hematologic diseases are lacking. Discontinuation of any immunosuppressive agent during an episode of infection is recommended. In all patients, adherence to an age-based immunization schedule is appropriate.

COVID-19 and corticosteroids: a narrative review

“…Hematological diseases: lymphoma, leukemia, autoimmune hemolytic anemia and idiopathic thrombocytopenia (Malpica and Moll 2020 ).…”

“… Endocrine diseases: Addison disease, acute adrenal insufficiency, and congenital adrenal hyperplasia (Bondy 2020 ) Gastrointestinal disorders: ulcerative colitis, Crohn disease, and autoimmune hepatitis (Filaretova et al 2005 ). Hematological diseases: lymphoma, leukemia, autoimmune hemolytic anemia and idiopathic thrombocytopenia (Malpica and Moll 2020 ). Rheumatological disorders: rheumatoid arthritis, systemic lupus erythematosus, polymyositis, vasculitis and polymyalgia rheumatica (Fokam et al 2021 ).…”

Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus

“…Corticosteroids are used as supportive care in patients with solid tumours and hematologic malignancies. Dosages of 10 mg prednisolone equivalent (PEQ) or more per day for at least 14 days have been described to increase the risk of VZV reactivation [ 76 ]. In a large population-based cohort study of patients with different diseases (cancer, asthma, autoimmune diseases), the HR for herpes zoster was 2.37 compared to a matched population not taking corticosteroids [ 77 ].…”

“…Therefore, even though no evidence from randomized trials exists, it might be reasonable to consider patients on corticosteroids, particularly with high doses long term (and/or if concomitantly treated or heavily pre-treated with immunosuppressive agents) for antiviral pharmacological prophylaxis (CIIu) (Table 5 ). Antiviral prophylaxis might be continued for up to 6 months after corticosteroids have been terminated [ 76 ].…”

Pneumocystis pneumonia with respiratory failure in a HIV-negative patient following short course of low-dose to moderate-dose prednisolone for a dermatological condition

“…In non-HIV-related Pneumocystis jirovecii pneumonia (NH-PJP), glucocorticoid exposure is the primary contributor in 57%–87% of published cases 4 5. There is a gradient of PJP risk, depending on the dose and duration of glucocorticoid treatment, with moderate to high doses (20–30 mg prednisolone equivalent dose) that are taken over prolonged courses (eg, greater than 4 weeks), conferring greater risk 6 7. The combination of corticosteroids with other chemotherapeutic and immunosuppressive agents such as cyclophosphamide, methotrexate, rituximab, cytarabine, vincristine, fludarabine, and certain tyrosine kinase inhibitors and tumor necrosis factor inhibitors further augment risk of PJP 8…”