Buried deep within the Infectious Diseases Society of America guidelines for treating patients with skin and soft tissue infections is a weak recommendation to consider adjunctive systemic corticosteroid treatment in nondiabetic patients presenting with uncomplicated cellulitis. (Clin Infect Dis. 2014;59:e10; http://bit.ly/2HIvic7.)
Mired as we've been for so many years in the debates over the most appropriate empiric antibiotic therapy for this common presentation (cephalexin four times a day; keep Bactrim at bay unless there is suppuration and abscess), the use of concomitant corticosteroids hasn't been part of the mainstream EM approach to cellulitis. Growing face validity, however, makes its incorporation something that should more frequently find its way into routine practice.
Consider the daily presentation of a patient with a fiery red cellulitic leg or painful and warm sheen over the arm. The clinical diagnosis of cellulitis is a straightforward one, though previous investigations have demonstrated that ultrasound may be a helpful diagnostic tool to identify those with occult suppuration.
Overwhelmingly, cellulitis is caused by streptococci of various groups, where pathogens gain entry into the dermis through breaks in the skin. Cellulitis is accompanied by dermal edema, lymphatic dilation, and diffuse, heavy neutrophil infiltration around blood vessels. (JAMA. 2016;316:325.)
The invading organisms drive significant inflammatory reaction, but further immunologic response likely arises from bacterial antigens and extracellular products, such as streptokinase, DNAse, and hyaluronidase, an observation borne from multiple studies demonstrating underwhelming success rates in culturing pathogenic bacteria from cellulitis and relatively low concentrations of organisms when isolated.
I was taught in residency to outline the erythematous margins of a patient's cellulitis with a surgical marker and to send him home with stern warnings to return should redness, pain, or swelling begin to creep beyond the strictly drawn borders or if symptoms hadn't improved within a few days, perhaps suggesting treatment failure and the need to escalate therapy.
A few years into practice, however, I've watched too often as patients bounce back with even the slightest progression of red beyond marked margins or when 24 hours of antibiotics haven't worked wonders on their painful red wounds. We're often put into the difficult situation of parsing which patients represent true treatment failures and which are simply traversing the natural course of healing and who can be expected to continue to thrive as outpatients with continuation of current therapy.
Fear of Side Effects Unfounded
The idea of adjunctive oral corticosteroid treatment found purchase decades ago with the publication of a double-blind randomized trial of 112 patients hospitalized with cellulitis. Immunocompetent patients received antibiotics coupled with a week-long taper of prednisolone or placebo. Those randomized to the steroid group had significant decreases in time to healing, length of hospital stay, and duration of intravenous antibiotic therapy. (Scand J Infect Dis. 1997;29:377.)
Long-term follow-up of these patients showed no difference in relapse or recurrence. Another retrospective case-control study of nearly 500 admitted patients discharged from a large community hospital with a principal diagnosis of cellulitis found that a short course of prednisone (40-60 mg/day for 3-5 days) was associated with shorter length of stay. (44th Annual IDSA. Abstract 179, Oct 13, 2006; http://bit.ly/2TSaHc7.)
Multiple recent trials investigating steroid use in patients with sepsis and septic shock (APROCCHSS, HYPRESS, ADRENAL) have consistently hinted toward at least equivocal outcomes and likely small benefits when steroids are provided alongside appropriate antibiotics and supportive therapies. One thorough review of blinded RCTs of patients with a broad range of infections found that steroids were shown to improve survival in a host of severe conditions while decreasing long-term disability or significantly relieving symptoms in nearly every other examined syndrome. (Arch Intern Med. 2008;168:1034.)
Clinician fears of immunosuppressive or significant side effects seem unfounded given recurring demonstrations of improved patient-oriented outcomes when steroids are used alongside appropriate antimicrobials.
Frustratingly, few data exist specifically examining the success of prednisone or other glucocorticoids for treating cellulitis. ClinicalTrials.gov lists a number of planned investigations that don't seem to have found their way to publication. IDSA guidelines, review articles, and recommendation groups cite the one small RCT and call for additional investigations.
Nonetheless, the limited literature available is likely sufficient to employ adjunctive corticosteroid use pending the publication of any new or contrary data because the combination of steroids with antibiotics has proven itself an effective strategy in a litany of infectious processes. Incorporation of steroids into the treatment algorithm for patients with uncomplicated cellulitis holds the potential to alleviate symptoms more rapidly and decrease bounceback questions of treatment failure without any significant downside.
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Dr. Pescatoreis the director of emergency medicine research for the Crozer-Keystone Health System in Chester, PA. He is also the host with Ali Raja, MD, of the podcast EMN Live, which focuses on hot topics in emergency medicine:http://bit.ly/EMNLive. Follow him on Twitter@Rick_Pescatore, and read his past columns athttp://bit.ly/EMN-Pescatore.