Cellulitis

Acute spreading bacterial infection of the dermis and subcutaneous fat, with ill defined margins. It is mainly caused by beta haemolytic streptococci (group A, and also groups C and G) and Staphylococcus aureus (MSSA and MRSA).

• About 70 to 80% of cases affect the lower limb. The face, arm, abdominal wall (in obesity) and peri wound or peri stoma skin make up most of the rest.
• Entry is through a breach in the skin barrier: tinea pedis, interdigital fissures, ulcers, surgical wounds, insect bites, eczema, trauma, injection sites. Oedema, lymphoedema, venous insufficiency, obesity, diabetes, previous cellulitis, saphenous vein harvest and lymph node dissection all predispose.
• Recurrence is common: 20 to 30% of patients have another episode within 1 to 3 years, because each episode damages lymphatics and leaves residual oedema.
• Exposure specific organisms change the choice of drug:
  • Animal bites: Pasteurella multocida, Capnocytophaga canimorsus (splenectomy, alcohol excess).
  • Freshwater: Aeromonas hydrophila.
  • Seawater or raw shellfish with chronic liver disease: Vibrio vulnificus (rapid, haemorrhagic bullae, mortality above 25% if bacteraemic).
  • Fish and meat handlers: Erysipelothrix rhusiopathiae.
  • Hot tubs, diabetic foot, neutropenia: Pseudomonas aeruginosa.
  • Severe immunosuppression: Cryptococcus, atypical mycobacteria, Gram negative bacilli.
• Non-purulent cellulitis is usually streptococcal. Cellulitis with pus, an abscess or an open wound is usually S. aureus, so MRSA must be considered.

• Unilateral, red, warm, swollen, tender skin with a poorly demarcated, spreading edge. There may be peau d'orange change, vesicles, bullae, petechiae or superficial erosions.
• Lymphangitis (red streaks proximally) and tender regional lymphadenopathy are common. Fever and rigors occur in 30 to 50%, and may precede the skin signs by hours.
• Severity grading:
  • Mild: local signs only, no systemic upset.
  • Moderate: fever above 38 C, heart rate above 90, or a spread of more than 10 cm, but stable.
  • Severe: hypotension, confusion, respiratory rate above 22, lactate above 2 mmol/L, rapidly progressive spread, or suspected necrotising infection.
• Red flags for necrotising fasciitis, an emergency:
  • Pain out of proportion to the appearance.
  • Skin anaesthesia.
  • Dusky or grey skin, haemorrhagic bullae.
  • Crepitus.
  • Rapid proximal spread over hours.
  • Shock despite antibiotics, or no improvement at 24 to 48 hours.
• Other red flags: periorbital swelling with proptosis, painful or limited eye movement or reduced vision (orbital extension); facial cellulitis near the nose (cavernous sinus thrombosis); infection over a prosthetic joint.
• Differential diagnosis:
  • Venous stasis dermatitis and lipodermatosclerosis (bilateral, chronic, no fever).
  • Deep vein thrombosis (can coexist).
  • Contact dermatitis, gout, erythema migrans, drug eruption.
  • Panniculitis, eosinophilic cellulitis, acute lipodermatosclerosis.
  • Septic arthritis or osteomyelitis beneath the skin.
  • Necrotising fasciitis.
  • Lymphoedema flare.
• Bilateral lower limb "cellulitis" is almost always stasis dermatitis or oedema and not infection.
• Complications: abscess, bacteraemia, septic shock, necrotising fasciitis, osteomyelitis, septic arthritis, thrombophlebitis, compartment syndrome, chronic lymphoedema, and rarely post-streptococcal glomerulonephritis.

• The diagnosis is clinical. Mark the margin with a skin pen and record the date and time so progression can be judged.
• Take a full history of exposures (water, animals, travel, injection drug use), diabetes, immune status, anticoagulants and previous episodes.
• Mild disease needs no tests. In moderate or severe disease or immunosuppression send:
  • Full blood count.
  • CRP: above 100 mg/L suggests deeper or severe infection.
  • Urea, creatinine, glucose, lactate, and liver tests if Vibrio is a risk.
• Blood cultures are positive in fewer than 5 to 10%. Send two sets in systemic illness, immunocompromise, animal bite, water exposure, or lymphoedema with fever.
• Swab any open wound, pus or drained abscess. Needle aspiration of intact skin gives a low yield and is not useful.
• Ultrasound for suspected abscess (fluid collection with cobblestoning) or deep vein thrombosis.
• MRI or CT if necrotising infection, osteomyelitis or deep abscess is suspected. Gas in tissues on X-ray or CT is diagnostic of a gas forming or necrotising process.
• A laboratory risk score for necrotising infection (CRP, white count, haemoglobin, sodium, creatinine, glucose) of 6 or more should raise suspicion, but a low score does not exclude it. Surgical exploration is the diagnostic test when clinical suspicion is high.
• Check HbA1c or fasting glucose in all patients with no known diabetes.

• General measures:
  • Elevate the limb higher than the level of the heart.
  • Treat the portal of entry (tinea pedis with terbinafine 1% cream once or twice daily for 1 to 2 weeks, fissures, ulcers).
  • Analgesia with paracetamol 1 g orally 6 hourly (maximum 4 g per day), adding codeine or tramadol if needed.
  • Apply compression only after the acute pain and infection have settled and arterial supply is confirmed adequate.
  • Give prophylactic dose low molecular weight heparin to admitted patients with reduced mobility.
• Mild to moderate non-purulent cellulitis (oral, outpatient), for 5 days, extended to 7 to 10 days if improvement is slow:
  • Flucloxacillin 500 mg to 1 g orally 6 hourly. Child: 12.5 to 25 mg/kg 6 hourly (maximum 1 g per dose), on an empty stomach.
  • Cefalexin 500 mg orally 6 hourly. Child: 12.5 to 25 mg/kg 6 hourly.
  • Non-severe penicillin allergy: cefalexin 500 mg orally 6 hourly (child 12.5 to 25 mg/kg 6 hourly).
  • Severe penicillin allergy: clindamycin 300 to 450 mg orally 6 to 8 hourly (child 7 to 10 mg/kg 8 hourly) or clarithromycin 500 mg 12 hourly.
• Purulent cellulitis or MRSA risk (previous MRSA, injection drug use, close contacts with boils): drain any abscess first, then give:
  • Co-trimoxazole 160/800 mg, 1 to 2 tablets orally 12 hourly, plus a streptococcal active drug such as amoxicillin 500 mg 8 hourly.
  • Doxycycline 100 mg orally 12 hourly (not in pregnancy or under 8 years), plus a streptococcal active drug.
  • Clindamycin 300 to 450 mg orally 6 to 8 hourly as a single agent covering both.
• Moderate to severe disease, systemic toxicity, failed oral therapy, immunosuppression, rapidly spreading or facial disease: admit and give intravenous therapy:
  • Flucloxacillin 1 to 2 g IV 6 hourly (child 25 to 50 mg/kg 6 hourly, maximum 2 g).
  • Cefazolin 1 to 2 g IV 8 hourly (child 25 to 50 mg/kg 8 hourly).
  • Suspected MRSA: vancomycin 15 to 20 mg/kg IV 8 to 12 hourly, adjusted to trough or AUC and renal function, with a loading dose of 25 to 30 mg/kg in critical illness; or linezolid 600 mg IV or orally 12 hourly (monitor platelets if more than 10 to 14 days); or daptomycin 4 mg/kg IV once daily.
  • Switch to oral therapy when afebrile for 24 to 48 hours and the skin is clearly improving. Total duration 5 to 7 days, longer if slow to respond.
• Necrotising fasciitis suspected: this is an emergency. Give resuscitation, then meropenem 1 g IV 8 hourly (or piperacillin tazobactam 4.5 g IV 6 hourly), plus vancomycin 15 to 20 mg/kg IV 8 to 12 hourly (loading dose 25 to 30 mg/kg), plus clindamycin 600 to 900 mg IV 8 hourly (toxin suppression), and arrange immediate surgical debridement. Do not delay surgery for imaging. Mortality is 20 to 30% even with treatment.
• Exposure specific regimens:
  • Animal bite: amoxicillin clavulanate 875/125 mg orally 12 hourly (or 500/125 mg 8 hourly) for 5 to 7 days; IV amoxicillin clavulanate 1.2 g 8 hourly if severe. In penicillin allergy use doxycycline 100 mg 12 hourly plus metronidazole 400 mg 8 hourly.
  • Seawater or Vibrio risk: doxycycline 100 mg IV or orally 12 hourly plus ceftriaxone 1 to 2 g IV daily, with early surgical review.
  • Freshwater (Aeromonas): ciprofloxacin 500 mg orally 12 hourly (400 mg IV 12 hourly) or ceftriaxone 1 to 2 g IV daily.
  • Fish or meat handler (Erysipelothrix): amoxicillin 500 mg to 1 g orally 8 hourly or benzylpenicillin 1.2 to 2.4 g IV 6 hourly, for 7 to 10 days.
  • Pseudomonas risk: piperacillin tazobactam 4.5 g IV 6 hourly or ceftazidime 2 g IV 8 hourly.
• Special groups:
  • Pregnancy: flucloxacillin, cefalexin, cefazolin and clindamycin are acceptable. Avoid doxycycline and fluoroquinolones. Avoid co-trimoxazole in the first trimester and near term.
  • Renal impairment: reduce the doses of cefalexin, cefazolin and vancomycin to creatinine clearance, and monitor vancomycin levels.
  • Diabetes: intensify glucose control, examine the feet, and cover for Gram negative and anaerobic organisms if there is a foot wound.
  • Elderly: lower threshold for admission, watch for delirium and dehydration, and adjust doses for renal function.
  • Immunosuppression: take cultures early, use broader empirical cover, and have a low threshold for biopsy.
• Review at 48 to 72 hours. The erythema may spread slightly in the first 24 to 48 hours despite correct treatment. If there is no improvement by 48 to 72 hours, re-examine for abscess (ultrasound), necrotising infection, resistant organism (change to MRSA cover), deep vein thrombosis, osteomyelitis or an alternative diagnosis.
• Admit if: systemic toxicity, hypotension, rapid spread, facial or periorbital involvement, immunosuppression, failed oral therapy, inability to take oral drugs, or social circumstances preventing safe follow up.
• Prevention of recurrence:
  • Treat oedema, lymphoedema, obesity, tinea pedis and eczema, and keep skin moisturised.
  • After 2 or more episodes in 12 months despite these measures, start prophylaxis: phenoxymethylpenicillin 250 to 500 mg orally 12 hourly, or benzathine benzylpenicillin 1.2 million units IM every 3 to 4 weeks, for 6 to 12 months or longer. In penicillin allergy use erythromycin 250 mg orally 12 hourly.
  • Protection lasts only while the drug is taken, and recurrences return in about half of patients after stopping.
• Follow up: review at 1 to 2 weeks and again at 4 to 6 weeks. Refer to dermatology, vascular or lymphoedema services for persistent oedema, recurrent infection or an ulcer that does not heal.