Clinical Reference / Therapeutic Strategies / Erysipelas/Cellulitis

Erysipelas/Cellulitis


Key Points

  • Erysipelas and cellulitis are infections of the dermis and subcutaneous layers of the skin that are rapidly progressive and are often accompanied by systemic signs, such as fever, leukocytosis, and elevated markers of systemic inflammation.
  • Both erysipelas and cellulitis require systemic antibiotic therapy.
  • The clinical presentation of erysipelas and cellulitis are similar, presenting with unilateral erythema, edema, warmth, and tenderness. Systemic signs of inflammation (fever, malaise, leukocytosis) are almost always seen. There are several distinguishing features listed below.
  • Erysipelas affects the lower extremities (76% of cases) but commonly has facial involvement (17%), is unilateral, sharply demarcated, typically involves more superficial lymphatics within the dermis to give a waxy or intensely superficial edematous (peaud’orange) appearance.
  • Cellulitis commonly affects the lower extremities, typically affects one limb, and may result from an underlying abscess or trauma.
  • Trauma, surgery, preexisting skin disease, and chronic lymphedema may be risk factors for cellulitis.
  • There is an important non-infectious differential diagnosis of cellulitis, including contact dermatitis, venous stasis dermatitis, deep vein thrombosis, and vasculitis. Venous stasis dermatitis is commonly bilateral, and is not accompanied by signs of systemic inflammation.
  • Most cases of cellulitis are caused by streptococci. Staphylococcus aureus is an important consideration in cases of cellulitis associated with trauma or an underlying abscess.

Introduction

Cellulitis can occur as a primary disease entity or it can complicate a preexisting dermatosis (i.e., microbes may enter the skin via either an inapparent or an obvious portal of entry). It accounts for 10% of infection-related hospitalizations in the United States (US), and is a common presentation for ambulatory visits in the US. The choice of parenteral versus oral therapy is influenced by the presentation of fever, leukocytosis, and/or lymphangitis, and by the location of the infection (e.g., classic erysipelas of the face). Rapidly progressive disease, cellulitis that complicates preexisting edema of the lower extremities, cellulitis with significant neutrophilia, and cellulitis in immunosuppressed, diabetic, and neutropenic patients requires parenteral therapy. Although initial therapy is dictated by the likelihood that the causative organisms are streptococci or, less likely, S. aureus, in immunocompromised individuals many other organisms may be responsible. More serious soft tissue infections, such as early necrotizing fasciitis, may resemble cellulitis. The following situations require alternative management strategies than those outlined below since they may be caused by unusual organisms: buccal cellulitis (Haemophilus influenzae), diabetic foot ulcer associated cellulitis (gram-negative organisms and anaerobes), human bites (oral anaerobes, Eikenella, Streptococcus viridans), dog and cat bites (Pasteurella multocida, Capnocytophaga canimorsus), cellulitis associated with salt water exposure (Vibrio vulnificus), cellulitis associated with exposure to fresh water (Aeromonas), and cellulitis in a butcher (Erysipelothrix).

Erysipelas is a superficial form of cellulitis that involves superficial lymphatics located within the upper dermis. Beta-hemolytic streptococci are the most common cause, followed by group B, C, and G streptococci, and rarely by staphylococci or other bacterial organisms.

Initial Evaluation

Erysipelas

Cellulitis

Differential diagnosis

Deep vein thrombosis

Venous stasis dermatitis

Staphylococcal scalded skin syndrome

Leukocytoclastic vasculitis

Panniculitis

Contact dermatitis

Treatment

First-line treatment: In all cases, the therapeutic strategy is to eliminate the pathogenic microorganism using an effective antimicrobial agent. Penicillin antibiotics remain first-line for erysipelas. There is recent evidence supporting the use of particular antibiotic classes for uncomplicated skin infections, including cellulitis. Limited data suggests that macrolide antibiotics may be more effective penicillins for cellulitis; given the increase in macrolide resistance, caution should be used when considering macrolide monotherapy. There is similarly limited data to support the use of intravenous antibiotics over the use of oral antibiotics; in fact, there are small studies demonstrating that oral therapies may be in some cases more effective than intravenous treatment. Small studies may also support the use of prophylactic antimicrobial therapy with penicillin antibiotics following an episode of leg cellulitis in patients who are high risk for recurrence.

Patients with systemic symptoms, significant neutrophilia, diabetes mellitus, immunosuppression, neutropenia, erysipelas of the face, associated with decubitus ulcers, or cellulitis on dependent extremities should be hospitalized and parenteral therapy is recommended.

First steps (for both erysipelas and cellulitis)

If any pustules, crusts, erosions, or ulcerations are present, culture them. Pending laboratory evaluation and in the absence of material for Gram stain or culture, direct therapy against both coagulase-positive S. aureus and S. pyogenes. Coverage for beta-hemolytic streptococci should always be included in cases with high suspicion such as erysipelas. In systemically ill patients, blood cultures may are critical to identify the relevant organisms.

Oral treatment for erysipelas and cellulitis

  • For patients who are not systemically ill, or outpatients, treat with oral dicloxacillin 500 mg 4 times daily, oral cephalexin 500 mg four times daily, cefadroxil 1 g daily. Treat for 7 to 10 days. If beta-hemolytic streptococci is suspected, consider alternatives such as clindamycin 300 to 450 three or times daily alone, or amoxicillin 500 mg three times daily combined with doxycycline or minocycline 100mg twice daily, or combined with trimethoprim-sulfamethoxazole.
  • For penicillin-allergic patients, or in cases where methicillin-resistant aureus (MRSA) is suspected, choose from the following agents: clindamycin 150 mg three times daily or 300 mg twice daily (up to 300 to 450 mg three to four times daily), sulfamethoxazole/trimethoprim double strength twice daily, doxycycline or minocycline 100 mg twice daily. A comparison of clindamycin 150mg three times daily versus sulfamethoxazole/trimethoprim double strength twice daily found equivalent efficacy for uncomplicated skin infections, including cellulitis, even in a treatment population with 77% MRSA isolate rate.

Parenteral treatment for systemically ill patients

  • For systemically ill patients, consider intravenous therapy as first-line. Nafcillin 1-2 g intravenously every 4 hours is the parenteral drug of choice. Alternatives include cefazolin 1.0 g IV every 6–8 hours for 48–72 hours, ceftriaxone 1.0 g IV every 24 hours, either followed by oral therapy. Penicillin A 3-6 million units orally in three divided doses or intravenous therapy with penicillin G (10-20 million units every 6 to 8 hours) for 5-7 days, followed by oral amoxicillin 3-4.5 g daily for a total of 10-20 days. It is strongly recommended to utilize coverage for beta hemolytic streptococci (with penicillin, amoxicillin, ceftriaxone or cefazolin) if there is high suspicion for that organism (such as erysipelas). In cases where antibiotic-resistance is suspected, including methicillin-resistant Staphylococcus aureus (MRSA), strongly consider antibiotic coverage guided by available data on local antibiotic resistance patterns (known as an antibiotigram). In cases with no response or progression of cellulitis, consider agents such as ampicillin-sulbactam or ertapenem, or addition of pseudomonal coverage (such as piperacillin-tazobactam, cefepime or ceftazidime, imipenem or meropenem).
  • In penicillin-allergic individuals, an alternative therapy is vancomycin 30 mg/kg/day intravenously in two divided doses is the parenteral drug of choice for MRSA. Linezolid 600 mg intravenous or orally twice a day is an alternative treatment for MRSA-related cellulitis. Linezolid (similar to clindamycin) has potent activity in blocking bacterial toxin production. Alternatives include daptomycin, clindamycin, dalbavancin or telavancin (the latter two are related to vancomycin).

Ancillary steps

  • Infected dependent extremities should be elevated.
  • For pain, adequate analgesia should be provided.

Subsequent steps

  • Successfully treated cellulitis should begin to respond to the above therapy within 48–72 hours; erythema, edema, pain, and leukocytosis should be reduced and the patient typically defervesces. Failure to respond promptly may indicate infection by an antibiotic-resistant strain or an unusual organism. If cultures and sensitivities have been obtained, adjust therapy accordingly (see above).
  • Regardless of a prompt clinical response, continue therapy for the full course to prevent both emergence of resistant strains and recurrent infections.

Pitfalls

  • Bilateral lower extremity cellulitis is highly uncommon; an alternative diagnosis should be considered. Cellulitis or erysipelas in the absence of fever and/or leukocytosis is also unusual.
  • An increasing number of staphylococcal isolates referred to as MRSA are resistant to semisynthetic penicillins and cephalosporins. If the patient has a history of MRSA infection, begin therapy with agents effective against MRSA.
  • Only a minority of staphylococcal isolates are sensitive to erythromycin, so this agent and other macrolides (azithromycin, clarithromycin) are not recommended for cutaneous cellulitis until sensitivity of the infecting agent is confirmed.
  • Failure to respond promptly to appropriate antibiotic therapy should raise other diagnostic possibilities (e.g., an unusual organism, necrotizing fasciitis, panniculitis, pyomyositis, or superficial thrombophlebitis or deep vein thrombosis).
  • Infections commonly recur when the full course of therapy has not been completed.

When to consult a dermatologist

  • When the diagnosis of cellulitis or erysipelas is not clear.
  • If a patient has a history of recurrent cellulitis or erysipelas and may require some type of prophylactic regimen.
  • For management of an underlying cutaneous disease that predisposes the patient to recurrent cellulitis.

Clinical Cases

Case 1

  • 21-year-old male
  • History of trauma to the leg while playing sports
  • Three days later developed progressively worsening redness and warmth around the site of trauma
  • Febrile, feels unwell
  • No prior medical history

Initial evaluation

  • Erythema, edema, warmth, and tenderness to palpation on the right leg with sharply defined borders
  • Systemically ill-appearing young male, diaphoretic
  • Temperature 38.5 degrees Celsius, other vital signs are stable
  • Blood work reveals a marked leukocytosis
  • Admit to hospital for intravenous antibiotics (nafcillin)

Next day

  • After one day of treatment, he defervesced, and clinical signs of erythema and swelling are reduced
  • Discharged to home with a 10-day course of cephalexin 500 mg four times daily
  • Follow-up evaluation in outpatient clinic in 10 days (resolved)

Case 2

  • 40-year-old woman
  • Rapid onset of erythema and swelling of the left ear
  • Febrile, feels unwell
  • No history of trauma to the ear
  • No topical medications or cosmetics applied to the ear

Initial evaluation

  • Systemically ill-appearing, febrile
  • Bright erythema and marked edema of the left ear, extending from the pinna onto the helical rim
  • Blood work reveals a leukocytosis, elevated ESR
  • Admit to hospital for IV antibiotics (penicillin G)

Next day

  • Patient feeling better
  • Significant reduction in erythema and edema of the left ear
  • Fever resolved
  • Discharge with 10-day course of oral amoxicillin
  • Follow-up in 10 days in outpatient clinic (resolved)

References

Bailey E, Kroshinsky D (2011) Cellulitis: diagnosis and management, Derm Therapy, 24:229-239.

Kilburn SA, Featherstone P, Higgins B, Brindle R (2010) Interventions for cellulitis and erysipelas, Cochrane Database of Systematic Reviews, 6(10): CD004299.

Krasagakis K, Valachis A, Maniatakis P, et al (2010) Analysis of epidemiology, clinical features and management of erysipelas, Int J Derm, 49:1012-1017.

Miller LG, Daum RS, Creech B, et al (2015) Clindamycin versus Trimethoprim-Sulfamethoxazole for uncomplicated skin infections, NEJM, 372:1093-1103.

Strazzula L, Cotliar J, Fox LP, Hughey L, Shinkai K, Gee SN, Kroshinsky D (2015) Inpatient dermatology consultation aids diagnosis of cellulitis among hospitalized patients: a multi-institutional analysis, JAAD, 73:70-75.

Williams HC, Crook AM, Mason JM, U.K. Dermatology Clinical Trials Network’s PATCH I Trial Team (2013) Penicillin to prevent recurrent leg cellulitis, NEJM, 369:881-882.