Unlike the other therapeutic agents discussed in this chapter that need to be stopped
immediately upon signs of serious infection, abruptly discontinuing glucocorticoids may be
detrimental to the patient taking exogenous steroids. Depending on the severity of the illness,
glucocorticoids may indeed need to be supplemented to address hypothalamic stress caused
by the illness itself. Decisions of hypothalamic support should be made on a case-by-case basis
with decision-making between the critical care specialist, rheumatologist, infectious diseases
specialist, and perhaps an endocrinologist.
Virtually all cells have glucocorticoid cell membrane and cytoplasmic receptors. The
effects of glucocorticoids on the immune system are several:
l The appearance of increased white blood cell count is due to de-margination of
leukocytes from the vascular endothelium.
l De-margination of white cells results in decreased leukocyte entry, and thus activity,
into areas of inflammation and infection.
l Decreased macrophage and neutrophilic phagocytosis interfere with microbial killing
and antigen presentation.
l The steroid/receptor interaction ultimately interferes with the genetic expression of
cytokines, chemokines, and adhesion molecules central to initiating and maintaining
an inflammatory response. Nuclear factor kappa beta (key transcription factor) is
prevented from attaching to the promoter regions of the genes expressing the above
inflammatory agents.The risk of serious infection in the patientreceiving exogenous corticosteroids is a real
one. Due to steroid effects on innate and adaptive immunity, these patients may present in a
very atypical manner with normal signals of the inflammatory response such as fever,
itching, rash, or discrete pulmonary lesions, for example, being muted. Corticosteroids act
further upstream in the body’s immune response and more widely than most of the biologics
listed below. Therefore, patients receiving moderate-to-high–dose steroids have been
reported to be vulnerable to each of the microbial entities that are listed in the following
section for biologic therapy. It is important to maintain a high level of suspicion and conduct
a thorough investigation for the unusual suspects and have a low threshold to begin empiric
therapy.
BIOLOGIC AGENTS
The introduction of biologic agents has produced an astounding transformation by halting or
slowing the progression of diseases, such as rheumatoid arthritis (RA), psoriatic arthritis,
spondyloarthropathy, collagen vascular disease, inflammatory bowel disease, and multiple
sclerosis resulting in marked decrease of disability and improvement in quality of life and
health outcomes. Anti-tumor necrosis factor (TNF) therapy is associated with the develop-
ment of serious life-threatening infections in additionto other documented effects such as
immunogenicity, heart failure, malignancy, and demyelinating disease. Interestingly, we
have not seen a similar incidence of serious infections in the newer non-TNF-mediating
therapies. This may be due to lessons learned from the postmarketing experience of TNF
inhibitors with resultant cautionary measures taken. Further susceptibility to infection is
likely conferred by concomitant use of other immunosuppressive therapies, such as
glucocorticoids and disease-modifying agents such as methotrexate, coexistent morbidities
(3), age (4), and underlying immune dysfunction inherent to many autoimmune diseases (5).
It is important to recognize that the patient numbers reflected here are small in comparison to
the vast number of patients receiving biologic therapy. Until we understand better infectious
disease patterns with the use of these agents, it is important to maintain a high index of
suspicion for serious infection with both the usual and the unusual suspects presenting in
usual and unusual ways.Very importantly, with signs or symptoms of potentially serious infection,
biologic agents must be discontinued. We also advocate that with the exceptions of
hydroxychloroquine and the presence of transplantation, all other immunosuppressants,
such as methotrexate, mycophenolate, cyclosporineetc., be discontinued in the presence of
serious infection.
Infections Related to Steroids and Biologics in Critical Care 377