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Cellulitis

Cellulitis is an acute bacterial infection of the dermis and subcutaneous tissues. It is a common condition, leading to 100 000
admissions per year in England alone, and accounting for 18% of out-of-hospital antibiotic prescriptions.

Though we see it often, diagnosis can remain tricky, with one study showing that 30% of patients referred to secondary care with
cellulitis were incorrectly diagnosed.

In this article, we will draw on information from NICE guidance on antimicrobial prescribing for cellulitis (NICE 2019, NG141), NICE
CKS on acute cellulitis (updated 2016, accessed January 2019) and a useful management review from the BJGP (BJGP
2018;68:595).

Are you sure it is cellulitis?

A US study of 259 people diagnosed and admitted via the Emergency Department with cellulitis found that the diagnosis was wrong
rather often! (JAMA 2017;317:760).

30% of people did not have cellulitis.

The most common ‘misdiagnosis’ was diagnosing stasis dermatitis as cellulitis.
20% did not need admission, and the vast majority of these were given unnecessary antibiotics.
This study only included those hospitalised – the authors speculate that there may be significant over-diagnosis in those
managed in primary care too.
Extrapolating this to the US population as a whole (quite a big leap given the small numbers in the study, we feel!), the study
calculated that, in the US each year, the unnecessary use of antibiotics for ‘cellulitis’ could cause 9000 cases of hospital-
acquired infections, 1000–5000 cases of C. difficile and 2–6 cases of anaphylaxis.

The authors do acknowledge how difficult cellulitis is to diagnose – the clinical features are non-specific, and are present in
inflammatory conditions, and after insect bites and stings, as well as infection. There are no validated tools to help diagnose
cellulitis.

So, worth pausing before you print that prescription: what else could it be? Would early review be better than a
prescription at this stage?

Diagnosis

The diagnosis of cellulitis is clinical. Usually, we will see acute onset of red, hot, painful skin, with swelling and possible blister
formation. Systemic symptoms of infection may accompany the skin changes.

Differential diagnosis:

Venous thromboembolism.
Acute gout.
Septic arthritis.
Venous eczema or insufficiency.
Lymphoedema.
Lipodermatosclerosis.
Superficial thrombophlebitis.

So, how can we avoid overdiagnosis with such a wide differential and so few diagnostic tests?

The BJGP suggests some useful rules of thumb to consider:

Bilateral red leg is rarely due to an infectious cause.

Varicose eczema causes epidermal changes which can help distinguish it from cellulitis:
Haemosiderin deposition leading to red/brown discolouration of skin.
Scaling of skin with crusting and itching.
The leg raise test: with the patient lying horizontal, elevate the affected leg to 45 degrees for 1–2 minutes. The erythema of
cellulitis persists, whereas erythema secondary to vascular causes will commonly fade.

NICE suggests swabbing for microbiology investigation if there is broken skin AND one of:

Penetrating injury.
Exposure to water-borne organisms.
Infection was acquired outside the UK.
Failure to respond to initial antibiotic management.

NICE does not advise any further investigations, but it may be appropriate to consider blood tests for FBC and CRP if there is
concern about the severity of the infection.

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Treatment

Oral antibiotics 5–7 day course of antibiotics: flucloxacillin (clarithromycin

if penicillin-allergic).
If impaired circulation is a consideration, NICE
(consensus) advice was to consider a higher dose, off
label, of flucloxacillin at 1g QDS.
For facial cellulitis, prescribe co-amoxiclav instead
(metronidazole and clarithromycin if penicillin-allergic).
Intravenous antibiotics NICE suggests we ‘consider’ referral to secondary care for
initiation of IV antibiotics if:
Systemically unwell, pain disproportionate to severity or
infection spreading despite treatment.
There are associated comorbidities such as peripheral
vascular disease or diabetes (NICE suggests community-
based IV antibiotics for this group).
Are IV antibiotics better than oral?
A 2010 Cochrane review showed that outcomes from oral
antibiotics are as good as from IVs in the management of
acute cellulitis.
Cellulitis in those with lymphoedema NICE 2019 guidance does not recommend variation from usual
treatment from this group (other than considering higher doses
of oral antibiotics as above).
However, NICE CKS points out that these patients are at higher
risk of delayed recovery or complications from their cellulitis,
and gives slightly different recommendations:
Amoxicillin 500mg tds for a minimum of 14 days
(clarithromycin If penicillin-allergic).
This is expert consensus, based on limited evidence
that amoxicillin may have better tissue penetration in
lymphoedematous tissue than flucloxacillin, and
amoxicillin also provides good coverage against
streptococci which are the commonest bacterial cause
of cellulitis (LSN cellulitis consensus document 2016).
Add flucloxacillin if there are any signs of Staph aureus
infection (pus, folliculitis, crusted dermatitis).
Continue antibiotics until all signs of acute inflammation
have resolved - no less than 14 days from initial clinical
response. Skin discolouration may persist for many
months in this group and may not need ongoing
antibiotics.

When to review

Review at 48h: if there is any systemic deterioration or spreading of infection (taking into account that skin redness may extend
slightly at first), consider admission.

Review at 7d: consider extending the course of antibiotics for a further 7 days if there has not been significant improvement.

Persisting erythema can be caused by inflammation rather than ongoing infection, which can make this a difficult
management decision in practice. There is little firm evidence to guide decisions about antibiotic duration.

Recurrent cellulitis
Approximately one-third of patients with cellulitis will suffer recurrent episodes. How best to manage this group remains a clinical
challenge.

NICE comments that the recommendation to use prophylactic antibiotics is based on ‘limited and conflicting evidence’. It advises
GPs that do not initiate prophylaxis in primary care.

Consider referring patients who have more than 2 episodes of cellulitis at the same site in 12 months to
secondary care for possible antibiotic prophylaxis.
If prophylaxis is considered, review 6-monthly and consider stopping.
Phenoxymethylpenicillin 250mg BD (or erythromycin 250mg BD if penicillin-allergic).

One small UK RCT recruited 274 people who had had at least 2 episodes of leg cellulitis, and randomised them to either low-dose
penicillin (250mg twice daily) or placebo for 12m (NEJM 2013;368:1695).

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Low-dose penicillin almost halved the rate of recurrence during treatment: for every 5 people you treat, you prevent 1
episode of cellulitis (CI 4–9).
Once treatment stopped, the group who had had penicillin had fewer episodes of recurrence than those who had been in the
placebo group, but the benefits wane over time, and are non-existent 2 years after stopping penicillin.
There were no adverse events.
Those with a BMI >33 didn’t seem to get as much benefit, and the authors suggest higher doses of antibiotics might be
needed in this subgroup.
Those with 3 or more previous episodes of cellulitis, and those with significant pre-existing oedema, also didn’t get as much
benefit.

Review underlying triggers, and manage risk factors such as oedema, obesity and immobility.

Optimise skin health: one UK study showed that 28% of patients with cellulitis had concurrent skin disease such as fungal infection
or eczema; managing these may help avoid recurrences.

Most patients are unaware they are at higher risk of recurrence, and this could be a good opportunity for patient education on skin
care and how to reduce future risks. The British Association of Dermatologists has produced a useful PIL on cellulitis which can be
found in the online resources section below.

Cellulitis
Cellulitis is a commonly seen condition with a wide differential diagnosis.
Consider alternative causes if leg discolouration and swelling are bilateral.
A 5-day course of oral antibiotics may be adequate for uncomplicated cellulitis in the
community.
Consider high doses (off-label) of oral antibiotics in those with comorbidities such as
diabetes and PVD.
Recurrent cellulitis may require antibiotic prophylaxis, initiated in secondary care.

http://www.bad.org.uk/for-the-public/patient-information-leaflets/cellulitis-and-erysipelas

We make every effort to ensure the information in these articles is accurate and correct at the date of publication, but it is of necessity of a brief and general nature, and
this should not replace your own good clinical judgement, or be regarded as a substitute for taking professional advice in appropriate circumstances. In particular check
drug doses, side-effects and interactions with the British National Formulary. Save insofar as any such liability cannot be excluded at law, we do not accept any liability
for loss of any type caused by reliance on the information in these articles.

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