Chapter 278 Even at physiologic concentrations, glucocorticoids are immunomodulatory, leading to a shift in cytokine production from a proinflammatory to an antiinflammatory pattern. Pharmacologic doses are immunosuppressive and inhibit cellular and humoral responses (Sternberg, 2001); however, the cellular response is thought to be most compromised. Poor cellular immune responses could enhance the pathogenic potential of some infectious organisms, prevent cell-mediated clearance of organisms, and perpetuate inflammation secondary to persistence of organisms and activation of other inflammatory pathways. Glucocorticoids commonly are thought to decrease phagocytic and oxidative functions of phagocytic cells in a dose-dependent manner, thereby compromising the ability to kill ingested organisms. These general properties support the use of glucocorticoids in patients with infectious disease and raise concerns about the potential side effects and complications associated with their use. A survey of the human literature on the use of glucocorticoids as adjunctive treatment for infectious disease puts into perspective many of the uncertainties in veterinary medicine. Conclusions regarding the benefits of glucocorticoids given to humans with infectious disease vary depending on the infectious agent studied, the age of the patient group studied, the dose and/or duration of glucocorticoid therapy, the parameters assessed (e.g., immunologic or infectious agent parameters such as cytokine levels or quantity of infectious agent detected), the presence of other infectious agents, and by extension, perhaps, of other concurrent diseases. Many human studies either involve small numbers of patients or lack appropriate controls. One helpful review (McGee and Hirschmann, 2008) of published randomized, double-blinded studies comparing corticosteroids with placebo in the treatment of human infectious diseases categorized the role of glucocorticoids as either improving survival with some infections (e.g., bacterial meningitis, pneumocystis pneumonia), reducing long-term disability (e.g., bacterial arthritis), improving symptoms (herpes zoster, many others), providing no or uncertain benefit, or causing harm (viral hepatitis, cerebral malaria). The range of outcomes described in people indicates that no “one size fits all” approach is appropriate for the use of glucocorticoids in small animals with infectious diseases and suggests that blanket avoidance of glucocorticoids in patients with infectious disease is not clinically appropriate. Clinicians have proposed that antiinflammatory doses of glucocorticoids for 5 to 7 days may be effective in ameliorating cough associated with uncomplicated infectious tracheobronchitis but do not shorten significantly the clinical course of disease. It is recognized commonly that after initial administration of antifungal agents to patients with fungal pneumonia (i.e., blastomycosis and histoplasmosis) respiratory signs can worsen presumably as a consequence of heightened inflammation associated with fungal death. Glucocorticoids are thought to prevent treatment-induced inflammation from occurring. In people who develop hypoxemia or respiratory distress after initiation of antifungal therapy for histoplasmosis, or who develop other inflammatory complications of the infection, treatment with glucocorticoids is recommended (Wheat et al, 2007). However, the evidence to support this recommendation is primarily physician experience and isolated reports instead of prospective, controlled clinical studies. A preliminary report of dogs with severe respiratory blastomycosis treated with either nonsteroidal antiinflammatory drugs (NSAIDs) or glucocorticoids, in addition to antifungal therapy, found no difference in clinical outcomes between the two treatment groups (Munks et al, 2011). A group of dogs treated with only antifungal drugs was not described, so it is difficult to know if antiinflammatory therapy had a positive impact on the clinical course of affected dogs. In a retrospective study of chronic histoplasmosis in dogs (Schulman, McKiernan, and Schaeffer, 1999), clinical signs of coughing from airway obstruction associated with hilar lymphadenomegaly resolved more quickly with administration of immunosuppressive dosages (2 to 4 mg/kg q24h) of prednisone alone or prednisone and antifungal drugs compared with those in dogs treated with antifungal chemotherapy alone (less than 3 weeks compared with approximately 9 weeks). In this study the glucocorticoid-treated dogs did not show evidence of dissemination of disease.
Rational Use of Glucocorticoids in Infectious Disease
Mechanism of Action
Glucocorticoids in Humans with Infectious Disease
Glucocorticoids in Small Animals with Infectious Disease
Respiratory Infections
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