Introduction

Cellulitis is a common diagnosis in the acute medical setting and in primary care with an incidence of around 3% through the UK. It is therefore an important condition to be familiar with.

Cellulitis is a bacterial infection which affects the dermis and the deeper subcutaneous tissues. It is commonly cause by Streptococcus or, less commonly, Staphylococcus aureus. There is no specific investigation for the diagnosis of the condition instead it is a clinical diagnosis. Investigations are used to determine the severity of the disease and help decide on the most appropriate setting for management.

As cellulitis is a bacterial infection, treatment is with appropriate anti-microbial therapy. Penicillin based antibiotics are recommended treatment based on the most common causative organisms but local microbiology advice should be sought.

Epidemiology

  • Incidence: 1500.00 cases per 100,000 person-years
  • Peak incidence: 50-60 years
  • Sex ratio: 1:1
Condition Relative
incidence
Cellulitis1
Deep vein thrombosis0.07
Osteomyelitis0.01
Necrotising fasciitis0.001
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

When considering cellulitis, there are key features to elicit in the history and to find on exam which would support the diagnosis.

Any disruption to normal skin integrity increases the risk of cellulitis. The most common risk factors include (listed in order of frequency):
  • Venous insufficiency and peripheral vascular disease
  • Obesity.
  • Skin breaks (such as recent cuts or insect bites).
  • Lymphoedema.
  • Previous cellulitis.
  • Surgery to the lower limb including saphenectomy.
  • Tinea pedis.
  • Skin conditions that disrupt the dermis (eczema, psoriasis or chronic venous ulcers)
  • Type two diabetes mellitus.
  • IVDU.
  • Alcoholism
  • Immunosuppression
  • Pregnancy

Pathophysiology

Cellulitis develops when bacteria enters the deep layers of the dermis through a break in the skin. This may be a local fungal infection, break in the skin or due to poor venous return. The exact pathology is poorly understood but it is proposed that the infection relates to an inflammatory response due to bacterial exotoxins.

The bacterial pathogens that cause cellulitis have been studied more extensively. The most common pathogen is Streptococcus. The strains of Streptococcus that are most commonly associated with cellulitis are Streptococcus pyogenes or Group A beta- haemolytic streptococci. Streptococcus induced cellulitis is thought to cause a rapid and diffuse erythema and is associated with lymphangitis.

Staphylococcus aureus, as well as methicillin-resistant strains, are the second most common causative organism. This is often described as beginning at a focal point of infection, such as an abscess or discrete entry point, and then spread outward.

As the bacteria infiltrate the dermis and subcutaneous tissue, it induces an inflammatory response. Histologically, the changes are non-specific. These include:
  • Lymphatic dilation
  • Neutrophil dense infiltrates.


Clinical features

The classic features of cellulitis relate to the underlying inflammatory process. Swelling, erythema, warmth, and tenderness are the common hallmarks of a cellulitic infection. The rash is most likely to be in the lower limbs (70% of cases from an epidemiological study) as opposed to the upper limbs and be unilateral. It is likely to have occurred over a period of hours.

Cellulitic rashes are erythematous and have a reasonably well-defined margin. In more severe cases, there may be skin breakdown, ulcer formation, or sloughing of the affected area. Localised lymph node swelling may occur.

As a general rule for cellulitic rash:
  • Bilateral rash is less likely to be cellulitis
  • Cellulitis occurs acutely, if the rash has occurred slowly over months then reconsider the diagnosis.
  • A rapidly progressive and blistering rash should prompt consideration of necrotising fasciitis.

Further examination should be to review the skin to assess for potential points of entry of a pathogen such as wounds, local skin infection or recent injection sites.

More severe cases of cellulitis will present with evidence of systemic upset. This is in relation to the release of bacterial toxins and may cause hypotension, tachycardia, confusion, or respiratory distress. Other signs of systemic upset are:
  • Nausea
  • Fever (prevalence ranges from 22.5-77.3%)
  • Rigours
  • Malaise


Investigations

There is no definitive test for cellulitis as the diagnosis is clinical. In stable patients with no systemic upset or co-morbidities that put them at risk of complications, there is no necessity for further investigations and they may be treated with oral antibiotics as an outpatient under primary care.

In those with a systemic response or where further investigation is clinically indicated then the following baseline investigations are recommended:
  • Full blood count
    • Specifically to look for leucocytosis. This is a non-specific marker of infection. The diagnosis is clinical and blood tests are not routinely performed unless being managed in secondary care. A leucocytosis or neutrophilia infers a more severe infection and guides treatment options, as well as providing an estimate of hospital stay. However, only half of patients presenting with clinically diagnosed cellulitis have a raised white cell count.
  • Urea and electrolytes
    • Assessing for an acute kidney injury which would indicate a systemic response and therefore a more severe infection.
  • CRP or ESR
    • While not specific for cellulitis, these tests are an indicator of the severity of the cellulitic infection. CRP is an acute phase reactant protein that is raised during the presence of an inflammatory response. A recent study has shown that the CRP level is associated with longer inpatient stays and is raised in 97% of patients. ESR is less commonly used but is also a non-specific marker of an inflammatory response. It is reportedly raised in 85% of clinically diagnosed cellulitis. However, a normal ESR or CRP does not exclude cellulitis.
  • Wound swab
    • Only if there is an open or weeping wound; or an obvious entry point.

Consider further investigations in selected patients such as:
  • Blood cultures
    • Yield of a pathogen is quoted as being less than 5% but should be considered in those with a significant systemic response, in the immunosuppressed or where atypical pathogens are a possible cause.


Differential diagnosis

Cellulitis is normally a clinical diagnosis with no definitive test for the condition. Therefore it is important to exclude potential mimics of the condition before starting treatment. Studies that have evaluated the clinical diagnosis of cellulitis have shown that around 30% of care may be misdiagnosed.

As a general rule, bilateral cellulitis is rare and if both legs are felt to be affected then the diagnosis should be reconsidered.

Mimics of cellulitis include:
  • Deep vein thrombosis: this may present with an acutely tender and swollen calf and can be mistaken for cellulitis.
    • Lack of true erythema should prompt revaluation of the diagnosis
  • Varicose or venous stasis eczema : normally presents bilaterally and is a reaction to chronic peripheral oedema, varicose veins or other conditions which may affect venous return. The eczema is thought to be a reaction to plasma leaking into the surrounding tissue.
    • If the presentation is bilateral with oedema, itch and a crusting rash then consider varicose eczema.
  • Lipodermatosclerosis: this refers to inflammation of the subcutaneous fat layer and may cause pain, swelling or erythema. It is less likely to have systemic features of infection. This does not require antibiotic treatment.
    • In the absence of systemic upset, consider lipodermatosclerosis.
  • Erysipelas: clinically difficult to differentiate between cellulitis. The majority of papers and guidance treat erysipelas and cellulitis as the same condition. Erysipelas is defined as a superficial skin infection and affects the dermis and the more superficial subcutaneous tissues. As it is more superficial than cellulitis, it appears very fiery, is painful, and is more clearly demarcated than cellulitis. The treatment is the same.
  • Superficial thrombophlebitis: this is an inflammatory disease of the superficial veins. It tends to present with erythema, tenderness, and a discrete, palpable lump in the distribution of a vein.
    • A discrete rash following a superficial vein with no systemic upset should prompt consideration of superficial thrombophlebitis
  • Necrotising fasciitis:This is a serious condition with a high mortality. This is a deep seated infection with rapid destruction of muscle tissue. and should be considered if the cellulitis is associated with extensive blistering, severe pain, swelling, and a rapidly progressive rash. An urgent surgical opinion is required.
    • In a rapidly progressive rash with severe pain and systemic response not in keeping with the clinical picture, necrotising fasciitis should be considered
  • Septic arthritis: most likely presents with an acutely swollen, erythematous, and painful joint. The skin appearances may mimic cellulitis due to the erythema
    • If the erythema is over a joint space with accompanied swelling then consider septic arthritis. The affected joint will have a reduced range of movement.

Management

Cellulitis is a bacterial infection and the primary management is through targeted anti-microbial therapy. Treatment is aimed at eliminating the bacterial from the pathogen through antibiotic therapy. General management of cellulitis is aimed at improving analgesia and swelling in the affected area.

The most common bacterial pathogens are Beta-haemolytic streptococci or Staphylococcus aureus. Therefore flucloxacillin is the recommended antibiotic. It may be given orally on an outpatient basis in uncomplicated and systemically well patients. From NICE and CREST guidance, uncomplicated patients are those without a predisposition to complications from cellulitis or severe infection. These patients are generally managed in primary care.

If there is evidence of systemic illness or with a co-morbidity associated with a poorer outcome then intravenous antibiotics should be considered and these patients are generally managed in secondary care.

CREST guidelines suggest categorising patients into the following groups to aid treatment decisions:
  • stage 1:uncomplicated infection with no co-morbidities. Treat with oral flucloxacillin
  • Stage 2: systemically unwell patients or those with co-morbidities. Treat with intravenous antibiotics, either in hospital for 48 hours or through an outpatient service.
  • Stage 3: those with significant systemic features (such as tachycardia, confusion or hypotension) or unstable co-morbidities which may impair treatment. These patients should be managed intensively in the hospital.
  • Stage 4: patients will have life-threatening infection or sepsis. Management for patients in this category should be with discussed with local microbiology services to guide treatment.

In those with a penicillin allergy, clarithromycin is a suitable alternative if a true allergy is confirmed.

For those that are treated with intravenous antibiotics, consider switching to an oral agent when the following features are met:
  • Apyrexial or pyrexia settling
  • Co-morbidities optimised
  • Erythema reducing
  • Inflammatory markers trending down

The duration of antibiotics should be guided by the response and extent of infection. In uncomplicated cases, 7- 14 days is the most common duration of treatment.

General management of the affected area includes analgesia; marking and documenting of the affected area; management of pyrexia and adequate hydration.

Complications

The complications of cellulitis may be divided into those that may occur due to the acute infection and those that may occur after resolution.

Complications that may result directly from the acute infection are:
  • Systemic infection: there is the risk of the initial pathogen entering the blood stream and causing systemic illness. This would likely be demonstrable through a SIRS response.
  • Subcutaneous abscess formation:
  • Myositis
  • Fasciitis
  • Death

Following the resolution of cellulitic changes, there is the possibility of developing recurrence of cellulitis which occurs in 29% of people within the years of their initial illness.
  • 7% of patient may develop chronic lower limb oedema following resolution of the initial illness