Cellulitis is an ambulatory care sensitive condition (ACSC). Its effective management and treatment should prevent admission to hospital; cellulitis is usually diagnosed in primary care and treated at home (NHS England, 2017). Each year, 100 000 people in England are admitted to hospital with cellulitis of the lower leg (Santer et al, 2018).
Misdiagnosis of lower leg cellulitis is common. Around 33% of people diagnosed with cellulitis usually have other conditions and around 90% of people who are misdiagnosed are inappropriately treated with antibiotics (Levell, 2011; Weng et al, 2017; Patel et al, 2019a; O'Brien and White, 2021).
It is vital to accurately diagnose this condition, as an incorrect diagnosis can expose the person to hazards of antibiotic therapy, increase antibiotic resistance and cause delays in providing appropriate effective treatment (Hirschmann and Raugi 2012a; 2012b). Figure 1 illustrates the consequences of incorrect diagnosis.
Around 50% of cases that are misdiagnosed as cellulitis are venous eczema, lymphoedema and lipodermatosclerosis, as they are commonly confused with cellulitis (David et al, 2011; Level et al, 2011).
What is cellulitis?
Cellulitis is an acute infection of the dermal and subcutaneous layers of the skin, often occurring after a local skin trauma (Bailey and Kroshinsky, 2011).
Cellulitis can affect any part of the skin, but is more common in the lower legs (Figure 2). In recent years, the growth of outpatient parenteral antimicrobial therapy (OPAT) has led to many people, who would once have been admitted to hospital to have cellulitis treated with intravenous antibiotics, to be treated at home or in community OPAT clinics (Chapman et al, 2019; Dimitrova et al, 2021). Despite the growth of OPAT, the number of people admitted to hospital with cellulitis continues to grow. This is due to an ageing population who are more vulnerable to cellulitis. Figure 3 is based on hospital episode statistics and illustrates the rise in hospital admissions (Santer et al, 2018). Around 30 000 people (30% of the total admissions) are inappropriately admitted to hospital, as they do not have cellulitis (Levell et al, 2011; Wingfield, 2012; Yarbrough et al, 2015; Jain et al, 2017; Weng et al, 2017; Patel et al, 2019b; Edwards, 2020). Figure 4, based on Levell et al (2011), illustrates the correct diagnoses of people misdiagnosed with cellulitis.
Why do clinicians struggle to diagnose cellulitis accurately?
Cellulitis can be perceived by clinicians as difficult to diagnose because it shares some features with other conditions. Diagnosis is based on history taking, examination and checking blood results for inflammatory markers (Santer et al, 2018; Sullivan and de Barra, 2018; Patel et al, 2019a; 2019b). Many conditions diagnosed by clinicians have similar features and the model used by medical staff and nurses practicing at advanced levels includes checking history, examination, tests and determining diagnosis (Figure 5). Figure 6 illustrates the diagnostic process in relation to red legs.
Florence Opoku (2015) devised a checklist to help less-experienced clinicians diagnose cellulitis more accurately (Figure 7).
Clinical features
Cellulitis is caused by a bacterial infection. The bacteria that most commonly cause cellulitis are Streptococci (especially Streptococci pyogenes) and Staphylococcus aureus. Gram-negative bacilli, Strep. pneumoniae and anaerobes such as pseudomonas can also cause cellulitis (Stevens and Bryant, 2016). Infection develops rapidly. The clinical features of cellulitis include:
- Fever
- Pain
- May experience chills, be sweaty and feel unwell
- Unilateral leg swelling
- Erythematous, inflamed and clear area of demarcation
- Tenderness
- One, or a few, bullae
- Leg shape is normal
- Cause is usually unknown, but break in skin, ulcers, trauma, athlete's foot are implicated
- White cell count is high, C-Reactive Protein (CRP) is high, and blood culture is usually negative.
Diagnosis
Cellulitis is diagnosed on the basis of clinical findings and history. The person will usually have clinical indications of infection such as fever, malaise, nausea, shivering, rigors and red sore skin with a clear line of demarcation, and possibly bullae (Santer et al, 2018; Opoku, 2015). Marking the border with an indelible pen enables you to observe improvement or deterioration. If left untreated, cellulitis will rapidly progress beyond the marked area. Enlarged lymph glands in the groin and lymphangitis (red streaking of the skin spreading proximally from the area of cellulitis) may be present. Complications include subcutaneous abscesses, septicaemia, poststreptococcal glomerulonephritis and death (David et al, 2011; Levell et al, 2011; Nazarko, 2016).
The person may have a lesion such as a leg ulcer, a cut, or a scratch on the skin that enabled bacteria to breach the skin's defences and caused an infection.
Most people who develop cellulitis are older people; however, people who inject drugs are also at risk of cellulitis and abscesses (Wright et al, 2020). People who swim in fresh or salt water may also develop cellulitis (Diaz, 2014).
Baseline observations of temperature, pulse blood pressure and respirations should be recorded. A full blood count will show raised inflammatory markers, and the white cell count and C-Reactive Protein (CRP) will be elevated (Wingfield, 2012).
Cellulitis normally affects one leg. If the person has unilateral leg swelling and clinical features of cellulitis are absent, the clinician should consider alternative diagnoses of deep vein thrombosis or a Baker's cyst (Nazarko, 2019).
Cellulitis of both legs are extremely rare; when both legs are affected, clinicians should consider venous eczema, contact dermatitis and lipodermatosclerosis as more likely diagnoses (Tidman, 2012).
Bilateral red legs: alternative diagnoses
The clinician should consider alternative diagnoses if the person has two red legs. The most common cause of bilateral red legs is venous eczema (Levell et al, 2011). Sometimes, people with bilateral red legs are misdiagnosed as having ‘bilateral cellulitis’and are admitted and treated with antibiotics. The redness and swelling often resolve with bedrest and elevation of the legs. The person is considered cured and discharged. The person is then frequently admitted for recurrent cellulitis; this exposes the person to the hazards of hospitalisation and inappropriate antibiotic therapy, ultimately failing to recognise and address the real issues (Quirke et al, 2017; O'Brien, 2021). The clinician should consider venous eczema and lipodermatosclerosis in the first instance. Table 1 outlines the features of lipodermatosclerosis, venous eczema and cellulitis.
Table 1. Clinical features of lipodermatosclerosis, venous eczema and cellulitis
| Lipodermatosclerosis | Venous Eczema | Cellulitis | |
|---|---|---|---|
| Symptoms | No fever | No fever | May have fever |
| Pain and discomfort | Itching | Painful | |
| History of varicose veins or deep vein thrombosis | History of varicose veins or deep vein thrombosis | No relevant history | |
| Signs | Does not feel generally unwell | Normal temperature | May experience chills, sweaty, feel unwell |
| Bilateral | Bilateral | Unilateral | |
| Erythematous, inflamed | Erythematous, inflamed | Erythematous, inflamed | |
| No tenderness | No tenderness | Tenderness | |
| Hardening and thickening of the skin | Vesicles | One, or a few, bullae | |
| Woody feel to skin | Crusting | Skin does not feel woody | |
| Small white star shaped scarred areas (atrophie blanche) | Lesions on other parts of the body, particularly other leg and arms | Absent | |
| Changes in pigment may be present (haemosiderin staining) | Changes in pigment may be present (haemosiderin staining) | Absent | |
| Legs shaped like inverted champagne bottles | Varicose veins may be present | Leg shape normal | |
| Lesions on other leg | Lesions on other leg | No lesions elsewhere | |
| Portal of entry | Not applicable | Not applicable | Usually unknown, but break in skin, ulcers, trauma, athlete's foot implicated |
| Investigations | White cell count normal CRP normal in chronic lipodermatosclerosis and slightly elevated in acute lipodermatosclerosis | White cell count normal CRP normalSkin swabs—Staphylococcus aureus common | White cell count highCRP High |
| Blood culture negative | Blood culture negative | Blood culture usually negative |
Treatment of cellulitis
It is important to determine the severity of infection and the presence of any indications of systemic inflammatory response syndrome (SIRS), as this guides treatment (Sullivan and de Barra, 2018). Eron and colleagues (2003) devised a system for classifying types of cellulitis and how these can be treated. This system uses four categories of infection, determines treatment and place of treatment (Table 2).
Table 2. Classification of cellulitis
| Class | Description | Oral or intravenous antibiotics | Place of care |
|---|---|---|---|
| One | Patients have no signs of systemic toxicity, have no uncontrolled long term conditions and can usually take oral antibiotics at home | Oral | Home |
| Two | Patients are either unwell or well, but have a condition such as peripheral vascular disease, chronic venous insufficiency or morbid obesity which affect recovery | Intravenous | Originally 48 hours of hospital treatment but increasingly physician assessment or nurse specialist initiated under local outpatient parenteral antimicrobial therapy policies |
| Three | Patients may be unwell and have symptoms such as acute confusion, tachycardia, breathlessness, hypotension or may have unstable conditions that may interfere with a response to therapy or have a limb threatening infection due to vascular compromise | Intravenous | Hospital |
| Four | Patients have septicaemia or severe life threatening infection such as necrotizing fasciitis | Intravenous | Hospital |
The Dundee classification, builds on and updates the work of Eron and colleagues (2003). It is based on a retrospective review of 205 consecutive patients. It takes comorbidities into account but does not believe obesity and peripheral-vascular disease necessarily indicate that a person requires hospital admission (Marwick et al, 2011). It provides an updated definition of systemic inflammatory response syndrome (SIRS), along with standardised and validated early warning scores (Phoenix et al, 2012). The authors found that many of those with the least severe cellulitis were being over-treated and that many of those with the most severe cellulitis were being under-treated. The authors have changed the classification of cellulitis in Ninewells hospital and now use three classifications. Classification is based on assessment of severity and treatment decisions and are based on SIRS and Standardized Early Warning Score (SEWS)-this mirrors the National Early Warning Score (NEWS) used in England. SIRS criteria comprise of:
- Temp<36 or >38°C
- heart rate >90 beats/min
- respiratory rate >20 breaths/min
- white blood cell count <4 or >12/mm3.
One point should be allocated for each of the criteria and a score of two or more is indicative of SIRS. A SEWS score of ≥4 in a patient with sepsis is used to indicate the most severely unwell patients.
The National Institute for Health and Care Excellence Clinical Knowledge Summaries (NICE CKS) (2021) guidance advises that people with class IV cellulitis, those with class III and significant systemic upset, those with rapidly deteriorating cellulitis, immunocompromise or significant lymphoedema, should be treated in hospital. People who are under 1 years old or very frail should also be admitted. People with suspected orbital or periorbital cellulitis should be admitted and treated by ophthalmologists. Clinicians are advised to seek specialist advice and consider admission if the person is severely unwell, as they could have an uncommon pathogens. For example, if the person has been exposed to water-borne organisms, or an infection acquired outside the UK, or a penetrating injury, or has lymphangitis or if the person is not responding to oral antibiotics. If a person is unable to take oral antibiotics, clinicians should explore giving intravenous antibiotics in the community, if appropriate.
Currently there is insufficient research to determine the optimal antibiotic choice, route and duration of therapy (Phoenix et al, 2012; Kilburn et al, 2020). These are influenced by population changes and rising antibiotic resistance. Our population is ageing and living with increasing levels of comorbidity. Old people are more vulnerable to Clostridioides difficile infection and clinicians need to be mindful of such risks when prescribing antibiotics. Table 3 (NICE CKS, 2021) summarises current guidance on treatment.
Table 3. Current treatment recommendations by organism
| Clinical presentation | Causative organism | Recommended antimicrobial therapy | Therapy suitable for use in case of penicillin allergy |
|---|---|---|---|
| Typical cellulitis | Streptococcus pyogenes | Amoxicillin or flucloxacillin |
|
| Typical cellulitis (Outpatient parenteral antimicrobial therapy) | Streptococcus pyogenes | Ceftriaxone | Clarithromycin or clindamycin |
| Typical cellulitis | Pus forming Staphylococcus aureus | Flucloxacillin | Erythromycin or clarithromycin or clindamycin |
| Cat bite | Pasteurella multocida | Co-amoxiclav | Doxycycline and metronidazole |
| Dog bite | Capnocytophaga sp | Co-amoxiclav | Clindamycin |
| Freshwater | Aeromonas hydrophila | Ciprofloxacillin | Tetracycline sulfonamide, cotrimoxazole |
| Saltwater | Vibrio vulnificus | Doxycycline |
Treating contributory factors
The risk factors for cellulitis include chronic oedema, leg ulcers and fungal infections such as tinea pedis (athlete's foot). It is important to treat contributory factors in order to reduce the risk of recurrent cellulitis (Stevens et al, 2014; Dalal et al, 2017; Patel et al, 2019)
Diagnosis and treatment of eczema
NICE CKS (2021) defines venous eczema (also known as varicose, gravitational or stasis eczema) as ‘…an inflammatory condition characterized by red, itchy, scaly, or flaky skin, which may have blisters and crusts on the surface’ (Figure 7).
Venous disease is common in adults; it affects an estimated 33% of adults and venous eczema is a symptom of venous disease (Grudzińska and Czuba, 2014). Its symptoms range from mild to severe. If it is not well-managed, the person can develop venous eczema, infection and leg ulceration. Advanced venous disease is rising because of an ageing population and rising levels of obesity. Ageing is associated with increased risk of venous disease and around 10% of people aged 70 years and over have venous eczema (van Langevelde et al, 2010; Chi and Raffetto, 2015). Most UK adults are overweight or obese (Moody, 2015) and there is an increased risk of venous disease in this population (NICE CKS, 2022).
Venous eczema is part of a continuum of venous disease. This has been graded using a framework of symptoms. It is known as the Clinical Etiological Anatomical Pathological (CEAP) classification (Eklof et al, 2004) (Table 4).
Table 4. Clinical Etiological Anatomical Pathological (CEAP) classification of chronic venous disorders
| Classification | Symptoms |
|---|---|
| C0 | No visible or palpable signs of venous disease |
| C1 | Telangiectasies (spider veins) or reticular veins |
| C2 | Varicose veins, distinguished from reticular veins by a diameter of 3 mm or more |
| C3 | Oedema |
| C4C4aC4b | Changes in skin and subcutaneous tissue secondary to chronic venous disease, divided into 2 sub-classes to better define the differing severity of venous disease:
|
| C5 | Healed venous ulcer |
| C6 | Active venous ulcer |
Principles of diagnosis and treatment
Venous eczema, like cellulitis, is a clinical diagnosis. Clinicians can diagnose venous eczema, identify and treat problems and work with the person to maintain health and well-being and improve their quality of life (Figure 8).
Eczema is treated with emollients. Ideally, the skin should be washed with water and an emollient rather than with soap. If an infection is present, antibiotic therapy may be required. Red inflamed skin can be treated with topical steroids (British National Formulary, 2022) (Figure 9). Swelling can be treated with compression therapy if it is safe to use (Nazarko, 2016b).
Treating scale and lichenified skin
Chronic eczema causes skin changes such as dryness and thickened areas. Thickening of eczematous skin is known as lichenification. Hyperkeratotic skin should be removed to promote comfort and skin health. Mechanical debridement was once popular, but the old methods of removing dead tissue with wet or dry gauze is now considered to be potentially harmful (Vowden, 2011). Newer methods are improving treatment.
An active debridement pad (Debrisoft, from Activa Healthcare) uses a fleece-like contact layer to mechanically remove debris, necrotic tissue, slough and exudate (Gray et al, 2011). This has been shown to be effective in 94% of cases in patients treated on three occasions, approximately 4 days apart (Bahr et al, 2011).
The UCS debridement cloth—a pre-moistened single-use cloth from Medi UK can also be used to debride wounds and remove scales from the skin. It has a mild cleansing agent that moistens and softens, making debridement more effective (Downe, 2014). A single treatment can provide significant debridement and does not cause pain or discomfort (Figure 10). It can be especially useful in removing dry dead tissue on legs. Emollient therapy is more effective when scale and lichenified skin is removed as emollients can penetrate the skin and hydrate it more effectively.
Lipodermatosclerosis diagnosis and treatment
Lipodermatosclerosis is a skin change that develops as a result of chronic venous disease (see Table 1 for details and classification). NICE CKS (2022) defines lipodematosclerosis as resulting from ‘chronic inflammation and fibrosis of the dermis and subcutaneous tissue of the lower legs’.
There are two types-acute and chronic. Acute lipodermatosclerosis is also known as sclerosing panniculitis. The person has painful inflammation above the ankles, which may be mistaken for cellulitis or phlebitis. This is an inflammatory condition, not an infective condition. Treatments include: stanozolol (2 mg bid for 8 weeks), topical steroids, topical capsaicin, weight loss, compression and improved mobility (Osti, 2018; NICE CKS, 2022).
Chronic lipodermatosclerosis usually develops gradually. It is characterized by painful, hardened, tight, red or brown skin. The skin feels ‘woody’. The skin is usually affected from the ankles upwards and the leg can look like an inverted champagne bottle (Figure 11). The main treatments are compression therapy to correct venous stasis and high potency topical steroids to reduce inflammation. The person may benefit from surgery to treat venous disease such as endovenous laser ablation or sclerotherapy. Weight reduction, if overweight, will improve venous flow. Other treatments include ultrasound therapy, fibrinolytic agents such as stanozolol and pentoxyfylline to increase blood flow. Intralesional triamcinolone injections may be used to reduce inflammation. If the person has pain, capsaicin and horse chestnut extract may be applied topically (Osti, 2018; NICE CKS, 2022).
Conclusion
When a person has a red leg, the clinician may immediately think of cellulitis. It is important that the clinician takes a history and carries out a clinical examination before determining diagnosis and treatment options. If the diagnosis is incorrect, the treatment will be ineffective and the person's quality of life will ultimately be affected.
Key points
- Around a third of people diagnosed with cellulitis do not actually have cellulitis
- Bilateral cellulitis is incredibly rare and generally such a diagnosis suggests that the person has another condition
- Inaccurate diagnosis affects the individual and is a waste of precious resources
- It is vital that clinicians consult others with greater expertise when diagnosis is in doubt.
CPD reflective questions
- What have you learnt from reading this article and how will it influence your day to day practice?
- What would make you consider that a diagnosis of cellulitis was incorrect
- What can you do to enable people with venous eczema to manage this condition?