A recent review has highlighted the importance of shared decision-making as a key pillar in the prevention of acute infection in patients treated with long-term steroids.

Glucocorticoids are effective at quelling inflammation and are widely used to manage inflammatory and immune-mediated diseases including inflammatory bowel disease, asthma and rheumatic diseases. The use of glucocorticoids is, however, associated with significant side-effects including osteoporosis, adrenal suppression and opportunistic infection. While these adverse effects are generally considered to be driven by dose, duration, route of administration and intensity of steroid treatment, the authors of this recent review believe that this dose-dependent model may not tell the whole story when considering opportunistic infection.  

They set out to:

• Understand the risk of opportunistic infections in patients taking glucocorticoids by:
  • Examining the cellular and clinical effects of steroids
  • Understanding the interaction with host biological factors such as comorbidities and concomitant medications
• Discuss the challenges of quantifying increased risk of opportunistic infection
• Propose strategies to prevent acute infections or reactivation of latent infections

The review incorporated studies across diverse patient cohorts (including rheumatic diseases, inflammatory bowel disease and systemic lupus erythematosus), with heterogeneous co-morbidities and concomitant medication profiles. The authors explored the quantitative and qualitative immunosuppressive effects of steroids, and the impact that long-term steroid exposure has on the risk of opportunistic infection.  

The results highlighted the complex pathways through which glucocorticoids impart their effect, altering the recruitment and activity of most types of immune cells including eosinophils, T- and B-cells. Quantifying the impact of steroids on the risk of opportunistic infections was complicated by the following factors:

• Lack of consistency in how studies reported steroid dose, duration and administration
• The broad range of glucocorticoids used in the different studies, with differing degrees of immunosuppression
• The prednisone equivalent score used to normalize this variable immunosuppression, which doesn’t fully capture the heterogeneous effects of the different steroid treatments, making it difficult to accurately quantify any correlation between steroids and opportunistic infection
• Conflicting data on the correlation between glucocorticoid dose and risk of opportunistic infections
• Patients with diverse and complex presentations that could contribute to their risk of infection including:
  • Disease involvement, e.g., immunologic dysfunction in patients
  • Comorbidities, e.g., coexisting immunodeficiencies
  • Concomitant immunosuppressive medications, e.g., methotrexate, anti-TNFs and disease-modifying antirheumatic drugs that confound the risk analysis of infection from glucocorticoids

Effective assessment of the risk of opportunistic infections requires shared care and a multi-disciplinary approach

Interventions to prevent infections or disease progression caused by opportunistic pathogens in patients receiving glucocorticoid treatment are essential. However, implementation is difficult without the ability to identify which patients would benefit from such interventions. In the absence of tools to determine patients’ “net state” of immunosuppression, clinicians are forced to rely on the dose-dependent, prednisone-equivalent method to identify patients at risk of infection.

The ability to effectively determine risk of opportunistic infections in the future would benefit from more detailed information on how different steroid treatments affect the immune function. Clinical calculators that consider all aspects of steroid treatment (dose, potency, length of exposure) and incorporate patient specific elements (e.g., comorbidities, coexisting immunodeficiencies and concomitant immunosuppressive therapies) also need to be developed. New technologies that can measure cell-mediated immunity could also provide a more accurate prediction of an individual patient's risk of opportunistic infection.

While predictive models are developed, the researchers recommend a multifactorial approach that includes limiting steroid use, screening for asymptomatic infections, antimicrobial prophylaxis and immunizations.

The authors strongly recommend implementing shared decision-making that involves an ongoing and open discussion between patients and clinicians about disease symptoms, comorbidities, previous medications and the patient's personal and environment risks to ensure patients can minimize their risks of developing opportunistic infections.  

Learn more about navigating the risks of opportunistic infections

Reference

1. Daniel B Chastain, Megan Spradlin, Hiba Ahmad, Andrés F Henao-Martínez, Unintended Consequences: Risk of Opportunistic Infections Associated With Long-term Glucocorticoid Therapies in Adults, Clinical Infectious Diseases, Volume 78, Issue 4, 15 April 2024, Pages e37–e56, https://doi.org/10.1093/cid/ciad474