Cellulitis
Acute bacterial infection of the dermis and subcutaneous tissue, most often caused by beta-hemolytic streptococci or Staphylococcus aureus.
Also known as: cellulitis, skin infection, soft tissue infection, SSTI
Overview
Non-purulent or purulent bacterial infection of the deeper dermis and subcutaneous fat, characterized by warm, erythematous, edematous, tender skin without sharp borders. Distinguished from erysipelas (more superficial, sharply demarcated) and necrotizing fasciitis (deep, rapidly progressive, systemic toxicity).
Epidemiology
Among the most common reasons for emergency visits and hospitalization for skin and soft tissue infection. Annual incidence ~200 per 100,000. Recurrence common (~30% within 3 years) especially in patients with lymphedema or prior cellulitis.
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Risk factors
- Skin barrier breakdown: tinea pedis, eczema, trauma, surgical wounds, IV drug use, insect bites
- Chronic edema/lymphedema (post-mastectomy, post-saphenous vein harvest, filariasis, obesity)
- Venous insufficiency, peripheral arterial disease
- Diabetes mellitus (especially with peripheral neuropathy)
- Immunocompromise
Pathophysiology
Bacteria enter through breaks in the skin and proliferate in the dermal/subcutaneous space. Streptococcal cellulitis spreads rapidly via hyaluronidase and streptokinase, often without purulence. Staphylococcal infection (including MRSA) more often produces abscess and purulent drainage. Systemic toxicity reflects cytokine release and bacteremia in severe cases.
Clinical presentation
Symptoms
- Localized warmth, erythema, edema, tenderness — usually a single extremity
- Spreading borders without sharp demarcation
- Fever, chills, malaise in moderate/severe disease
- Possible regional lymphangitis ('red streaking') and lymphadenopathy
Signs / physical exam
- Warm, indurated, erythematous skin with poorly defined edges
- Possible purulent drainage from puncture site or abscess
- Lymphangitic streaking toward draining nodes
- Look for portal of entry (tinea pedis, ulceration, IV site)
Classic findings
Unilateral lower-leg cellulitis is extremely common; bilateral lower-leg 'cellulitis' is almost never cellulitis — consider stasis dermatitis, lipodermatosclerosis, or contact dermatitis.
Differential diagnosis
- DVT — Unilateral leg swelling and pain, calf tenderness, Homans sign — but erythema usually less prominent; duplex ultrasound
- Stasis dermatitis — Bilateral, chronic, hemosiderin staining, weeping/crusting; not warm or tender; often misdiagnosed as cellulitis
- Contact or allergic dermatitis — Pruritic > tender, vesicular or scaling, sharp borders matching exposure
- Necrotizing fasciitis — Pain out of proportion, rapid progression, bullae, crepitus, systemic toxicity; surgical emergency
- Erysipelas — Bright red, sharply raised borders ('orange peel'), more superficial; usually streptococcal
- Septic arthritis — Joint effusion, restricted ROM; arthrocentesis
- Gout — Acute monoarticular, especially first MTP; uric acid crystals on synovial fluid
Diagnostic workup
Diagnostic criteria
Clinical diagnosis. IDSA stratifies into mild, moderate, severe and purulent vs non-purulent for treatment selection.
Labs
- CBC, BMP, lactate if systemic toxicity
- Blood cultures only if severe sepsis, immunocompromise, water exposure, animal/human bites, or unusual organism suspected
- Wound culture if purulent drainage or abscess (incise and drain first)
- Consider HSV/HSV PCR if recurrent 'cellulitis' on the face/genitals
Imaging
- Bedside ultrasound to differentiate cellulitis (cobblestoning) from abscess (anechoic collection)
- Plain films for foreign body, soft tissue gas (necrotizing infection), or osteomyelitis
- CT/MRI if necrotizing fasciitis suspected (but do NOT delay surgical consultation for imaging)
Diagnostic algorithm
| Presentation | Likely Pathogen | First-line Outpatient | First-line Inpatient |
|---|---|---|---|
| Non-purulent, mild | Beta-hemolytic strep | Cephalexin or dicloxacillin | Cefazolin |
| Non-purulent, severe | Strep ± gram-negative | Hospitalize | Vancomycin + piperacillin-tazobactam |
| Purulent/abscess | S. aureus (MRSA possible) | I&D + TMP-SMX or doxycycline | I&D + vancomycin |
| Cat/dog bite | Pasteurella | Amoxicillin-clavulanate | Ampicillin-sulbactam |
| Water exposure | Aeromonas / Vibrio | Doxycycline + ciprofloxacin | Doxycycline + ceftriaxone |
Treatment
First-line
- Non-purulent cellulitis (likely beta-hemolytic strep):
- • Mild outpatient: oral beta-lactam — cephalexin 500 mg PO QID, dicloxacillin 500 mg PO QID, or penicillin VK
- • Moderate: IV cefazolin or ceftriaxone
- • Severe (systemic toxicity, rapid progression): IV vancomycin + piperacillin-tazobactam pending evaluation for necrotizing infection
- Purulent cellulitis / abscess (MRSA coverage required):
- • Incision and drainage is the cornerstone for abscess
- • Outpatient MRSA-active oral options: TMP-SMX DS 1-2 tabs PO BID, doxycycline 100 mg PO BID, clindamycin 300-450 mg PO QID, linezolid 600 mg PO BID
- • Inpatient MRSA coverage — vancomycin, linezolid, daptomycin
- • Beta-lactam for skin — cefazolin, cephalexin, dicloxacillin (for strep coverage when MRSA also possible — pair with TMP-SMX or doxycycline)
- Typical duration 5-7 days; extend if slow response (DICE/Aboltins data support 5 days for uncomplicated cellulitis)
Second-line / adjunct
- Special exposures:
- • Water exposure: add coverage for Aeromonas (freshwater) or Vibrio (saltwater) — doxycycline + ceftriaxone or fluoroquinolone
- • Cat/dog bite: amoxicillin-clavulanate (Pasteurella multocida)
- • Human bite: amoxicillin-clavulanate (Eikenella corrodens)
- Recurrent cellulitis (≥3 episodes/year) — consider chronic prophylaxis with low-dose penicillin or erythromycin (PATCH trial)
Complications
- Bacteremia and sepsis
- Local abscess formation
- Necrotizing fasciitis (if missed or progressing)
- Lymphangitis, lymphedema (recurrent), elephantiasis nostras verrucosa
- Endocarditis (especially with bacteremic Staphylococcus aureus)
- Osteomyelitis (especially diabetic foot)
PANCE pearls
- Treat predisposing tinea pedis — interdigital fissures are a recurrent portal of entry; eradicating the entry portal reduces recurrence (note: the PATCH trials demonstrated benefit from prophylactic penicillin, not antifungals).
- Bilateral lower-extremity 'cellulitis' is rare; reconsider the diagnosis (stasis dermatitis is the great mimicker).
- Cellulitis often appears worse on day 1-2 of antibiotics as bacterial lysis releases mediators — do not switch antibiotics for warmth/redness alone in the first 48 hours.
- Outline the erythema with a marker on admission to monitor progression objectively.
- Severe pain out of proportion, bullae, crepitus, or systemic toxicity → necrotizing fasciitis; immediate surgical consult.
References
- IDSA 2014 — Stevens et al., Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections (Clin Infect Dis)
- PATCH I/II — Thomas et al., Penicillin to prevent recurrent leg cellulitis (NEJM 2013)
- Aboltins 2014/Hepburn — Trials supporting 5-7 day antibiotic courses for uncomplicated cellulitis
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