Selulitis

01Pathophysiology

Cellulitis is an acute, non-purulent infection of the dermis and subcutaneous tissue. It develops when bacteria gain access to the deeper skin layers through a breach in the epidermal barrier. This breach can be obvious (a laceration, surgical wound, or ulcer) or subtle (microscopic fissures from tinea pedis or dry, cracked skin). Tinea pedis is one of the most commonly overlooked and testable entry points.

Once bacteria invade the dermis and subcutaneous fat, they proliferate and trigger an intense innate immune response. Bacterial toxins and host inflammatory mediators (histamine, prostaglandins, cytokines) cause vasodilation and increased vascular permeability. This directly explains the clinical presentation: erythema results from vasodilation, warmth from increased local blood flow, swelling from extravasation of fluid into the interstitial space, and pain from stimulation of nociceptors by inflammatory mediators.

The hallmark feature that distinguishes cellulitis from erysipelas is the depth of infection. Erysipelas is confined to the upper dermis and superficial lymphatics, producing sharp, raised, well-demarcated borders because the infection spreads along a defined anatomical plane. Cellulitis extends deeper into the dermis and subcutaneous tissue, where tissue planes are less distinct, resulting in poorly defined, flat borders that blend gradually into normal skin. This is a critical visual distinction tested repeatedly on exams.

The unilateral lower extremity is the most common site because venous stasis, dependent edema, and skin breakdown are most prevalent there. Bilateral involvement should immediately raise suspicion for a non-infectious mimic such as stasis dermatitis, not bilateral cellulitis.

Streptococci produce hyaluronidase and streptokinase, enzymes that break down connective tissue matrix and fibrin clots, respectively. This facilitates rapid lateral spread through tissue and explains the characteristic pattern of an expanding, erythematous plaque with lymphangitic streaking.

02Classification and Clinical Manifestation

Classification by Purulence

Classification by Severity (IDSA Guidelines)

Clinical Manifestation by Anatomic Subtype

03Diagnostic Workup

Cellulitis is fundamentally a clinical diagnosis. The combination of unilateral, expanding erythema with warmth, tenderness, and edema in the right clinical context (skin break, risk factors) is sufficient. This is a point examiners frequently test: you do not need labs, cultures, or imaging to diagnose straightforward cellulitis.

Blood cultures are one of the most overtested items in clinical practice and on exams. For uncomplicated cellulitis in an immunocompetent patient, blood cultures are not recommended because the positivity rate is extremely low (approximately 2%) and results rarely alter management. Blood cultures become appropriate in the following scenarios: the patient is immunocompromised (chemotherapy, HIV with low CD4, organ transplant), there are signs of systemic toxicity or sepsis (high fever, hypotension, tachycardia, altered mental status), the cellulitis follows an animal or human bite (polymicrobial including Pasteurella, Eikenella), or the infection developed after a saltwater or freshwater immersion injury (concern for Vibrio vulnificus or Aeromonas).

Point-of-care ultrasound is the appropriate next step when you suspect a subcutaneous abscess. Clinically, an abscess may feel fluctuant, but in early or deep collections, the surface exam can be misleading. Ultrasound will show a well-defined, hypoechoic or anechoic fluid collection that confirms the need for incision and drainage. This distinction is critical because an abscess will not resolve with antibiotics alone.

If the patient presents with features suggestive of necrotizing fasciitis (pain out of proportion to the skin findings, rapid progression over hours, crepitus on palpation, dusky or hemorrhagic bullae, systemic toxicity), the workup changes urgently. CT with IV contrast can reveal gas tracking along fascial planes, and the LRINEC score (Laboratory Risk Indicator for Necrotizing Fasciitis) can help stratify risk using WBC, hemoglobin, sodium, glucose, creatinine, and CRP. However, imaging should never delay surgical exploration if clinical suspicion is high. The gold standard for necrotizing fasciitis is surgical exploration, not any imaging study.

For orbital cellulitis, a CT of the orbits with IV contrast is the best initial imaging study to distinguish it from preseptal cellulitis and to identify a subperiosteal abscess requiring drainage.

04Management and Treatment

Acute stabilization begins with assessing severity. For a patient who is hemodynamically stable, afebrile, and immunocompetent with a limited area of involvement, outpatient management with oral antibiotics is appropriate. The critical first decision is whether the cellulitis is purulent or non-purulent, because this determines the likely organism and therefore the antibiotic choice.

For non-purulent cellulitis, the target organism is beta-hemolytic streptococci. Cephalexin 500 mg PO four times daily is the standard outpatient regimen. Dicloxacillin 500 mg PO four times daily is an equivalent alternative. In patients with a true penicillin or cephalosporin allergy, clindamycin 300-450 mg PO three times daily is appropriate, though increasing streptococcal resistance to clindamycin in some regions is a consideration. The standard course is 5 days, with reassessment and extension to 10-14 days if the infection has not begun to improve.

For purulent cellulitis (especially with associated abscess or purulent drainage), MRSA must be covered empirically. TMP-SMX DS (160/800 mg) one to two tablets PO twice daily or doxycycline 100 mg PO twice daily are the recommended oral options. An important caveat: TMP-SMX has limited streptococcal coverage. If the clinical picture has both purulent and spreading non-purulent components, some experts recommend combining TMP-SMX with a beta-lactam to cover both MRSA and streptococci.

If an abscess is present, incision and drainage is the primary treatment and is more important than antibiotic selection. A small, uncomplicated abscess (less than 2 cm) in a healthy patient may resolve with I&D alone, though current IDSA guidelines now recommend adjunctive antibiotics even for small abscesses.

Moderate-to-severe cases requiring hospitalization are treated with IV antibiotics. For non-purulent disease, IV cefazolin 1-2 g every 8 hours is first-line. For purulent or MRSA-suspected disease, IV vancomycin dosed at 15-20 mg/kg every 8-12 hours (targeting trough levels of 15-20 mcg/mL) is the standard. Once the patient shows clinical improvement (decreasing erythema, defervescence, improving pain), transition to oral therapy to complete the course.

Adjunctive measures are frequently tested:

• Limb elevation above the level of the heart reduces edema and promotes lymphatic drainage.

• Mark the borders of erythema with a skin marker and record the time. This allows objective tracking of whether the infection is progressing or responding to therapy.

• Treat the portal of entry: if tinea pedis is the predisposing factor, prescribing a topical antifungal (e.g., terbinafine cream) reduces recurrence.

• For patients with recurrent cellulitis (two or more episodes at the same site within 12 months), prophylactic antibiotics are appropriate. Penicillin V 250 mg PO twice daily or penicillin G benzathine 1.2 million units IM every 4 weeks is used for secondary prophylaxis.

Contraindications and cautions to be aware of:

• Doxycycline is contraindicated in pregnancy and in children under 8 years due to risk of permanent dental staining and impaired bone growth.

• TMP-SMX should be avoided in the third trimester of pregnancy (risk of neonatal kernicterus) and in patients with severe renal impairment or hyperkalemia (it blocks the epithelial sodium channel and causes potassium retention).

• Vancomycin requires renal dose adjustment and trough monitoring. It is associated with nephrotoxicity and Red Man syndrome (a histamine-mediated infusion reaction, not a true allergy, managed by slowing the infusion rate).

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common way students lose points on cellulitis questions is by ordering blood cultures for uncomplicated cellulitis. In a stable, immunocompetent patient with a straightforward clinical presentation, blood cultures are unnecessary. Their yield is extremely low, and selecting them as a "next best step" is a distractor designed to test whether you understand that cellulitis is a clinical diagnosis.

The second major trap involves bilateral lower extremity erythema. When a vignette describes bilateral, symmetric erythema of both legs, the answer is almost never cellulitis. This presentation should redirect your thinking toward stasis dermatitis. True bilateral cellulitis is exceedingly rare, and exam writers use this detail deliberately to separate students who recognize the pattern from those who do not.

A third high-yield trap is the failure to distinguish purulent from non-purulent cellulitis when selecting antibiotics. A vignette describing spreading erythema without drainage or abscess (non-purulent) should be treated with a beta-lactam such as cephalexin. If you reflexively choose TMP-SMX or doxycycline for every cellulitis question, you will miss the non-purulent cases, because TMP-SMX has unreliable streptococcal coverage.

The periorbital versus orbital cellulitis distinction is a favorite testing point. The key discriminators are proptosis, pain with extraocular movement, and ophthalmoplegia, all of which indicate orbital (postseptal) involvement and demand urgent CT imaging and IV antibiotics. Preseptal cellulitis lacks these findings and is managed less aggressively. Getting this wrong in either direction is a predictable trap.

Finally, always consider necrotizing fasciitis when the vignette describes a patient whose pain is disproportionately severe relative to the skin findings, especially if there is rapid progression, crepitus, or the patient appears septic. The next best step in that scenario is emergent surgical consultation and exploration, not more antibiotics or imaging. Delay in recognizing necrotizing fasciitis is the highest-stakes error on this topic.

The core competency being tested across all cellulitis questions is pattern recognition of the classic presentation (unilateral, poorly demarcated, no fluctuance), appropriate restraint in diagnostic testing, correct antibiotic selection based on purulence, and the ability to identify red flags that shift the diagnosis to something more dangerous.