Cellulitis

Key facts:

Authors: Damian James Mayo, Kris Ghosh, Andrew Sherley-Dale
Top Tip: Cellulitis is usually quite mild, but if not stopped in its tracks, can become life-threatening                                           

Key Differential Diagnoses

• Stasis eczema (esp 'bilateral cellulitis')
• Necrotising fasciitis
• Osteomyelitis
• DVT

Key Investigations

• Wound swab (if open wound)
• FBC, ESR, CRP
• U+E, LFT, Bone, Glucose
• BC

Key Treatment

• (Mild, outpatient) PO FLUCLOXACILLIN 500mg-1g qds; Penicillin Allergy: PO DOXYCYCLINE 200mg od OR PO ERYTHROMYCIN 500mg qds
• (Moderate, outpatient) IV CEFTRIAXONE 2g od; see 'Risk Stratification ' below
• (Severe, inpatient) IV FLUCLOXACILLIN 2g qds iv (± IV GENTAMICIN 5 mg/kg od + PO RIFAMPICIN 600mg bd OR IV CLINDAMYCIN 600mg qds; Penicillin Allergy: IV VANCOMYCIN 1g bd ± (IV GENTAMICIN 5 mg/kg od + PO RIFAMPICIN 600mg bd)
• IV line (+fluids, if dry)

Key Management Decisions

• Admit?
• MRI (osteomyelitis or necrotizing fasciitis)
• Surgery (necrotizing fasciitis)

Background

Introduction

• Cellulitis is a bacterial infection of the skin and subcutaneous tissue
• It can be acute or subacute
• It is usually caused by streptococci (especially Streptococcus pyogenes) or Staphylococci
• A routine wound swab is unhelpful as it will almost always grow S.aureus or S.epidermidis
• Symptoms and signs are pain, rapidly spreading erythema, and oedema; fever may occur, and regional lymph nodes may enlarge
• Diagnosis is by appearance; cultures are sometimes helpful but awaiting these results should not delay empirical therapy (with antibiotics)
• It is usually a relatively minor syndrome, an easily treatable medical sub-emergency. Appropriate cases can be treated with once-daily IV antibiotics, as an outpatient
• Prognosis is usually excellent with timely treatment but if cellulitis is inadequately treated it can lead to fatal complications. So the condition should be taken seriously
• Necrotising fasciitis is a rare but important differential diagnosis (>30% mortality; higher in the elderly). It can present initially in a similar manner but exquisite pain disproportionate to the clinical findings is characteristic
• XRs are usually not required though may be considered if osteomyelitis is suspected

Definition

• Deep infection of connective tissue, usually skin and subcutaneous tissues, in which there is obvious oedema   

Periorbital (orbital) cellulitis

• The orbital region can also be affected by cellulitis. This can be caused by an external focus of infection (eg a wound); or an infection that extends from the nasal sinuses or teeth, or metastatic spread from infection elsewhere
• Symptoms include eyelid pain, discoloration, and swelling; also causes fever, malaise, proptosis, impaired ocular movement, and impaired vision

• Diagnosis is based on history, examination, and CT or MRI. Treatment is with antibiotics and sometimes surgical drainage
  Note: orbital cellulitis is an emergency: spread to the cavernous sinus can have catastrophic consequences

Typical cellulitis

L leg cellultis

Stasis ezcema (most common differential diagnosis, often bilateral)

Epidemiology

• Little is known
• No predilection for one sex or race 

Sites

• One limb (usually)
• Two limbs (occasionally, depends on cause)    
• Non limb tissues (eg face, as above)

Causes
(common organisms)

• Gp A, β-haemolytic streptococci (eg Streptococcus pyogenes)
• Staphylococcus aureus
  NB: The organism cannot be predicted from the appearance of the affected area

Causes (unusual organisms)

• Methicillin-resistant S. aureus (MRSA) has become more common in the community. Historically, MRSA was typically confined to patients who were exposed to the organism in a hospital or nursing facility. MRSA infection should now be considered in patients with community-acquired cellulitis, particularly in those with cellulitis that is recurrent or unresponsive to monotherapy. Also:
• Gp B streptococci: eg S. agalactiae; especailly in older patients with diabetes
• Gram-negative bacilli: eg Haemophilus influenzae in children; and Pseudomonas aeruginosa in patients with diabetes or neutropenia, hot tub or spa users, and hospitalised patients 
• Pasteurella multocida: bites from from cats; and Capnocytophaga sp (dogs)
• Aeromonas hydrophila (fresh water)
• Vibrio vulnificus (warm salt water)
• Fungi

Risk factors

Identifiable break in skin, usually from:

• Trauma (eg laceration, burn, or bite) 
• Or ulceration (eg leg)
• Or concomitant skin disorder (atopic eczema, fungal infections eg tinea pedis) 
• Obesity, immunosuppression, PVD
  Note: cellulitis can occur in a patient with no DM; and frequently no obvious risk factors, or skin break

Symptoms

• Red, hot, painful rash; can be acute or subacute
• Signs systemic infection (fever, malaise, acute confusion, nausea and rigors)
  NB: these symptoms may precede the skin changes (sometimes by several hours)
• Enlarged lymph nodes or inflammed lymphatics (lymphangitis)
  NB: if very rapidly spreading, consider necrotising fasciitis

Key questions

• "When did the rash start?"   
• "How has it developed?"
• "Have you had this before?" (repeated episodes of cellulitis can impair circulation and lead to lymphoedema)      

Signs

• Fever
• Red, hot, painful, rash, with oedema and tender skin; can have appearance of skin of an orange ('peau d'orange')
  ± petechiae (common), vesicle or bullae formation (can rupture); sometimes with necrosis of involved skin
• Enlarged nodes (lymphangitis) same limb

Investigation

Routine wound swab is unhelpful as it will almost always grow S.aureus or S.epidermidis

Blood

• FBC (WC usually raised), CRP, ESR
• U+E, LFT, Bone, Glucose
• BC            

Other

• MSU and CXR, if diagnostic confusion
• Wound swab if visible portal of entry for bacteria (eg open wound)
• Mark extent of rash with marker pen, as baseline

Specialist investigation

• MRI (if considering osteomyelitis or necrotizing fasciitis)

Differential diagnosis

4 most important differential diagnoses:

1. Stasis eczema; chronic and often bilateral; common in elderly
2. Necrotizing fasciitis; look for crepitus, severe pain (inappropriate for extent of rash), sensation loss; needs urgent surgery; urgent biopsy and/or MRI, if will not delay diagnosis or Rx; [Ref]
3. Osteomyelitis; think about diagnosis in patient with DM and foot ulcers
   [Ref]
   Note: a normal XR does not exclude osteomyelitis; you need a NM bone scan and/or MRI
4. Deep venous thrombosis (do they have any risk factors? See table below)
   
   Other: infected eczema/psoriasis, ruptured Baker's Cyst, rarely gangrene, acute gout, adverse drug reactions, metastatic cancer (carcinoma erysipeloides)

Differentiating Cellulitis and Deep Venous Thrombosis  

Treatment

Appropriate cases can be treated with oral antibiotics, as an outpatient

Treatment (first line)

Drugs 

• (mild, outpatient) PO FLUCLOXACILLIN 500 mg-1 g qds; Penicillin Allergy: PO DOXYCYCLINE 200 mg od OR PO ERYTHROMYCIN 500 mg qds
• (moderate, outpatient) IV CEFTRIAXONE 2 g od; see 'Risk Stratification ' below
• (severe, inpatient) IV FLUCLOXACILLIN 2 g qds iv (± IV GENTAMICIN 5 mg/kg od + PO RIFAMPICIN 600 mg bd OR IV CLINDAMYCIN 600mg qds; Penicillin Allergy: IV VANCOMYCIN 1 g bd ± (IV GENTAMICIN 5 mg/kg od + PO RIFAMPICIN 600 mg bd)
• IV line (+fluids, if dry)

Stop

• Consider stopping immunosuppression (after DW prescriber)

Treatment (second line)

Drugs

• DW microbiology

Procedures

• Elevate leg
• (If severe sepsis/shock) urinary catheter, CVP line, arterial line

Prescribing issues

• If use VANCOMYCIN or GENTAMICIN, do levels at 48 hrs, 2 days, 4 days etc. RIFAMPICIN has many important interactions (eg reduced effective dose of thyroxine)
• In an immunocompromised patient, use a neutropenic regime

Admit?

May be required but should not be routine; consider if you can manage in the community. Consider admission if:

• Severe or rapidly deteriorating cellulitis (eg affecting extensive areas of skin or which is spreading), or an uncertain diagnosis with sinister signs or symptoms (eg possible necrotizing fasciitis)
• Comorbidities that complicate or delay healing (eg PVD, chronic venous insufficiency, morbid obesity, immunosuppression, IV drug use)
• Other factors: frail, elderly; facial cellulitis; periorbital cellulitis (+refer to ophthalmologist); failure to respond to oral antibiotics; recurrent cellulitis

Bed plan

• Medical admission ward
• ± ITU
• ± Dermatology

Referrals

• General surgery ASAP, if suspect necrotising fasciitis
• Orthopaedics, if suspect osteomyelitis
• Dermatology, if not improving in 48h
• Microbiology, if not improving in 48h

The Rest

Complications

• Severe sepsis/shock
• Local abscesses may require incision and drainage
• Recurrences in the same area are not common; if occurs, sometimes leading to lymphatic damage with the risk of lymphoedema
• Rarely, can lead to necrotizing subcutaneous infection, requiring rapid surgical intervention
• Also rarely, bacteraemia with metastatic foci of infection (disciitis, endocarditis)

Follow-up

• GP (7 days AB); if no substantial improvement, assess compliance, and continue Rx for further 7 days
• If swabs were taken, use sensitivity results to guide Rx
• Dermatology (re) referral, if extended treatment is ineffective

Risk stratification: who can be managed as an outpatient

[Ref]

2° Prevention + Health promotion

• (If obese) lose weight
• (If diabetic) look at feet every day, and seek help if any small lesion develops
• Treat tinea pedis (risk factor)

Don't forget

• Patients can (and do) die of cellulitis

Red flags

• Reduced conscious level, confusion
• Speed of rash spreading
• Severe sepsis/shock
• Excessive pain (think alternative diagnoses eg necrotising fasciitis)

References