Hamill L, Keijzers G, Robertson S, et al. Anti-inflammatories as adjunct treatment for cellulitis: a systematic review and meta-analysis. CJEM. 2024 May 26. doi: 10.1007/s43678-024-00718-z. (Systematic review)

OBJECTIVES: Existing guideline recommendations suggest considering corticosteroids for adjunct treatment of cellulitis, but this is based on a single trial with low certainty of evidence. The objective was to determine if anti-inflammatory medication (non-steroidal anti-inflammatory drugs [NSAIDs], corticosteroids) as adjunct cellulitis treatment improves clinical response and cure.

METHODS: Systematic review and meta-analysis including randomized controlled trials of patients with cellulitis treated with antibiotics irrespective of age, gender, severity and setting, and an intervention of anti-inflammatories (NSAIDs or corticosteroids) vs. placebo or no intervention. Medline (PubMed), Embase (via Elsevier), and Cochrane CENTRAL were searched from inception to August 1, 2023. Data extraction was conducted independently in pairs. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2. Data were pooled using a random effects model. Primary outcomes are time to clinical response and cure.

RESULTS: Five studies (n = 331) were included, all were adults. Three trials reported time to clinical response. There was a benefit with use of an oral NSAID as adjunct therapy at day 3 (risk ratio 1.81, 95%CI 1.42-2.31, I2 = 0%). There was no difference between groups at day 5 (risk ratio 1.19, 95%CI 0.62-2.26), although heterogeneity was high (I2 = 96%). Clinical cure was reported by three trials, and there was no difference between groups at all timepoints up to 22 days. Statistical heterogeneity was moderate to low. Adverse events (N = 3 trials) were infrequent.

CONCLUSIONS: For patients with cellulitis, the best available data suggest that oral nonsteroidal anti-inflammatory drugs (NSAIDs) as adjunct therapy to antibiotics may lead to improved early clinical response, although this is not sustained beyond 4 days. There is insufficient data to comment on the role of corticosteroids for clinical response. These results must be interpreted with caution due to the small number of included studies.

REGISTRATION: Open Science Framework:   https://osf.io/vkxae?view_only=fb4f8ca438a048cb9ca83c5f47fd4d81 .

Discipline Area Score
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Dermatology 6 / 7
Infectious Disease 5 / 7
Comments from MORE raters

Dermatology rater

Although the summarized evidence is of low quality, this overview is helpful in an everyday clinical situation.

Dermatology rater

Very interesting. Patients often want to take a pain reliever. This suggests that it may be helpful systematically for the initial few days of the infection.

Hospital Doctor/Hospitalists rater

As a practicing inpatient hospitalist and as a former primary care physician, this information is very useful. This is a frequent complaint in outpatient practice. This will potentially help reduce multiple visits/calls to the clinic for unresolved symptoms and premature escalation of care, as the article suggests.

Infectious Disease rater

NSAIDS are expected to improve symptoms of cellulitis and are not expected to improve cure rates. Only 331 patients were included for a very common problem. Benefit at 3 days, but not 5 days, probably because the degree of inflammation decreases beyond 3 days. A larger sample size is needed to demonstrate benefit, if present. Which NSAID and which dose and duration should be used? I suggest any NSAID at the lowest approved dose for 3 days.

Internal Medicine rater

Setting aside any methodologic issues with this review, like statistically combining studies using prednisolone with studies using ibuprofen, and more detail about how “clinical response” was defined and measured given that ibuprofen has pain-relieving properties independent to any specific effect on cellulitis, I don’t think this is the kind of result that matters to primary care clinicians. The small benefit at 3 days, not present at 2 or 4 or 5 days, hardly seems to justify adding a second medication to the routine treatment regimen for patients with cellulitis.

Internal Medicine rater

A small systematic review discussing the utility of anti-inflammatories such as NSAIDs and steroids for cellulitis. When used as adjunct therapy, NSAIDs showed a signal that there may be benefit, but it's not sustained beyond 4 days. There was insufficient evidence to comment on steroids. An interesting study, but I am unlikely as a hospitalist to change practice based on its conclusions.
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