Nonpurulent Skin and Soft Tissue Infections: Erysipelas and Cellulitis

How to Cite This Chapter: Said H, Singhal N. Nonpurulent Skin and Soft Tissue Infections: Erysipelas and Cellulitis. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.18.73.1. Accessed April 16, 2024.
Last Updated: August 20, 2020
Last Reviewed: March 16, 2021
Chapter Information

DefinitionsTop

Cellulitis is defined as a skin and soft tissue infection (SSTI) involving the deeper dermis and subcutaneous tissues.

Erysipelas is an infection of the more superficial layers of the skin characterized by involvement of the epidermis, upper dermis, and superficial lymphatics.

Etiology and PathogenesisTop

Erysipelas is usually caused by beta-hemolytic streptococci, most commonly group A streptococcus.

Cellulitis is typically caused by:

1) Beta-hemolytic streptococci (typically group A streptococcus).

2) Staphylococcus aureus:

a) Methicillin-susceptible Staphylococcus aureus (MSSA).

b) Methicillin-resistant Staphylococcus aureus (MRSA).

In general, typical cellulitis is caused by beta-hemolytic streptococci. Cellulitis secondary to S aureus also occurs, especially in the context of a penetrating trauma, recent surgery, folliculitis, furuncles, carbuncles, and abscesses. Consideration of MRSA as a causative organism should be based on risk factors, which include known MRSA colonization, residing in a long-term care facility, injection drug use, sports, homelessness, hemodialysis, and recent hospitalizations. MRSA should be empirically covered in those who do not respond to therapy directed at MSSA, have an associated cutaneous abscess, or have risk factors and present with signs of systemic infection.

A variety of other organisms should be considered based on epidemiologic information, host factors, and relevant exposure history (Table 1). For example, patients with diabetes mellitus or immunodeficiency (eg, neutropenia), burns, puncture wounds, or water exposure can have increased likelihood of Pseudomonas aeruginosa infection.

Cellulitis typically affects middle-aged and older adults, while erysipelas is seen more commonly in young children and older adults. There are several risk factors predisposing patients to the development of nonpurulent SSTIs (Table 2). Infection is caused by pathogen invasion through a disruption to the skin barrier.

Clinical Features and Natural HistoryTop

SSTIs can be categorized as mild, moderate, or severe (Table 3).

Depending on the layer of skin involved, the clinical syndrome can be classified as either erysipelas or cellulitis.

Erysipelas is a well-demarcated, erythematous, warm, painful rash with raised borders involving the upper dermis and superficial lymphatics. It is often acute in onset and can be associated with systemic symptoms. It typically involves the lower extremity, but when it affects the face, it has a prototypical “butterfly” distribution along the nasal bridge and cheeks.

Cellulitis is generally a poorly demarcated, erythematous, hot, painful rash, most commonly involving the lower extremity, although it can occur anywhere. Associated lymphangitic streaking and regional lymphadenopathy can be seen. It may develop insidiously over the course of days. In some instances systemic symptoms, pain, or both may precede the development of a rash.

Both clinical entities can be associated with the development of skin dimpling (“peau d’orange”), superficial petechiae, and edema.

Depending on the causative organism, clinical features can vary (Table 1). For example, cellulitis caused by Vibrio vulnificus typically have hemorrhagic bullae.

DiagnosisTop

Erysipelas and cellulitis remain clinical diagnoses. In a systemically well, immunocompetent patient, blood cultures are not recommended, as they are generally positive <5% of the time.

Swabs of associated open wounds or exudate from lesions or tissue biopsy can be sent for Gram staining and culture to direct definitive antimicrobial therapy; however, these investigations are not a prerequisite for initiation of antibiotics.

In patients with systemic symptoms, underlying immunocompromise (eg, malignancy in patients receiving chemotherapy, neutropenia, severe cell-mediated immunodeficiency), immersion injuries, animal bites, or features of a severe/deep soft tissue infection, blood cultures and wound swabs or tissue biopsy for Gram staining and culture should be performed. Additional blood tests (outlined below) should be considered in these patient populations.

Any concerns for a severe soft tissue infection or toxic shock syndrome should prompt additional blood tests evaluating for end-organ hypoperfusion and sequelae of both conditions, including a complete blood count (CBC), electrolytes, creatinine, venous blood gas, lactate, liver function tests, creatine kinase (CK), international normalized ratio (INR), partial thromboplastin time (PTT), and fibrinogen.

While an x-ray can be performed to look for subcutaneous gas, imaging cannot be used to definitively exclude necrotizing fasciitis or other necrotizing soft tissue infection; surgical exploration is required. Provided that there is no delay in definitive management and the patient does not demonstrate profound hemodynamic instability, computed tomography (CT) or magnetic resonance imaging (MRI) can be helpful for delineating the extent of infection to aid in surgical planning. Evaluation for abscess using ultrasonography can be used, particularly in patients with palpable, fluctuant masses or those who do not improve with appropriate antibiotic therapy.

Differential Diagnosis

Cellulitis is often misdiagnosed, and several other infectious and noninfectious clinical entities should be considered:

1) Infectious: Septic arthritis, necrotizing fasciitis, myonecrosis, osteomyelitis, herpes zoster, erythema migrans.

2) Noninfectious: Deep vein thrombosis, chronic venous stasis or stasis dermatitis, contact dermatitis, lipodermatosclerosis, gout, drug rash or reaction, insect bite.

Life-threatening alternative diagnoses that should be excluded include severe SSTIs, such as necrotizing fasciitis and myonecrosis. Toxic shock syndrome can occur secondary to cellulitis or necrotizing fasciitis:

1) Necrotizing fasciitis (both monomicrobial and polymicrobial) should be considered in any patient with cellulitis, as it is a surgical emergency requiring urgent debridement. Clinical features include:

a) Hemodynamic instability.

b) Pain out of proportion to clinical findings.

c) Skin findings: Crepitus, bullae, obvious necrosis.

d) Woody, hard firmness to subcutaneous tissues.

e) Sensory deficits.

2) Clostridial myonecrosis (or gas gangrene) should be considered in patients with fever, severe pain, and rapid clinical deterioration with associated skin changes like crepitus or bullae (or both). Clostridial myonecrosis can occur spontaneously (usually from a gastrointestinal source, eg, malignancy) or following trauma or surgery.

Toxic shock syndrome is characterized by significant hemodynamic instability and multisystem organ failure, most often secondary to group A streptococcus, with the usual site of origin being from an SSTI. Early recognition is key, as it impacts further infection control precautions and management.

TreatmentTop

1. Empiric antimicrobial therapy: The choice of therapy is dependent on the severity of infection. Empiric therapy for mild to moderate cellulitis should include both S aureus and Streptococcus pyogenes. Erysipelas does not usually require S aureus coverage and therapy can be directed at beta-hemolytic streptococci using penicillin or amoxicillin. Severe infections should be managed with empiric broad-spectrum antibiotics and prompt investigation for necrotizing fasciitis.

Evaluate the patient for MRSA risk factors to determine if MRSA coverage is warranted. In the presence of risk factors, those that either have trauma or breaches in the skin, do not respond to MSSA treatment, or present with severe infection should be treated with antibiotics that include MRSA coverage. In cases of mild cellulitis without skin breaches, most individuals respond to therapy directed at MSSA and beta-hemolytic streptococci, even if they are colonized with MRSA.

If cultures are indicated, results should guide narrowing of therapy, as appropriate.

In the absence of concerns for MRSA, typical cellulitis can be managed with a first-generation cephalosporin (cephalexin in mild cases, cefazolin in moderate; Table 4).

Duration of therapy should be decided based on clinical response. Uncomplicated cellulitis is typically treated for 5 days, provided there is evidence of clinical improvement during that period; 5 days of treatment are as effective as 10 days in this case.Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Hepburn MJ, Dooley DP, Skidmore PJ, Ellis MW, Starnes WF, Hasewinkle WC. Comparison of short-course (5 days) and standard (10 days) treatment for uncomplicated cellulitis. Arch Intern Med. 2004 Aug 9-23;164(15):1669-74. doi: 10.1001/archinte.164.15.1669. PMID: 15302637. Indicators of treatment response include resolution of systemic symptoms and reduction in pain. Erythema may initially spread in the first 48 to 72 hours but should not continue to extend rapidly. If antibiotics were initiated IV, step down to oral therapy should be assessed once the patient shows evidence of clinical improvement, as indicated.

If there is no clinical improvement or if there is deterioration after 48 to 72 hours of antibiotics, the following should be considered: antimicrobial resistance necessitating a change in antibiotics or the presence of an abscess requiring source control.

2. Source control: In patients with evidence of a fluctuant mass, clinical purulence, or failure to improve after 48 to 72 hours of antibiotic therapy, ultrasonography should be performed to exclude the presence of an abscess. Definitive management of a collection is incision and drainage.

3. Optimization of predisposing conditions:

1) Identify and treat predisposing conditions, such as edema, obesity, dry skin or eczema, and venous insufficiency. This includes topical emollients, leg elevation, weight loss, and compression stockings.

2) Interdigital toe spaces should be examined for evidence of tinea pedis, fissuring, scaling, and maceration and should be treated to reduce colonization of pathogens and decrease the incidence of recurrent infection. Underlying tinea pedis should be treated with topical antifungal therapy (eg, clotrimazole).

3) Rarely, in patients with 3 to 4 episodes of cellulitis per year despite attempts to treat and control predisposing factors, antibiotic prophylaxis can be considered. This should be weighed against potential adverse effects, drug interactions, and patient preferences. Antibiotic prophylaxis should be continued for as long as the predisposing factors are present. Oral penicillin V (250-500 mg bid) or amoxicillin (250 mg bid) can be used for suspected recurrent beta-hemolytic streptococcal infections. Cephalexin (500 mg bid) can be used for recurrent MSSA infections.

Tables
Top

Table 10.3-1. Pathogens causing cellulitis and relevant exposures/risk factors

Pathogen

Relevant exposure

Clinical presentation

Common pathogens

Beta-hemolytic streptococci

– Disruption to skin barrier

– Known toe web space abnormalities can result in reservoirs for beta-hemolytic streptococci

– Poorly demarcated erythematous rash ± regional lymphadenopathy

Staphylococcus aureus

– Penetrating trauma

– Nasal, perianal, skin colonization

– Existing dermatologic conditions (eg, atopic dermatitis)

– Poorly demarcated erythematous rash ± regional lymphadenopathy

– May have purulent drainage and/or surrounding furuncle, carbuncle, folliculitis, or abscess

Less common pathogens

Pseudomonas aeruginosa

– Moist environments, hot tubs, hospitalized patients, puncture/wet wounds, nail trauma, injection drug use

– Burn wound infections

– Patients with diabetes and chronic open ulcers

– Cellulitis post penetrating injury/puncture wound

– Cellulitis in patients with neutropenia

– Ecthyma gangrenosum in immunocompromised host

Clostridium spp

– Soil contact

– GI surgery, GI malignancy

– Cellulitis with evidence of crepitus and dark, thin, foul-smelling drainage (patients are often systemically well)

– Clostridial myonecrosis (rapidly spreading, severe infection with muscle involvement)

Aeromonas hydrophila

– Typically associated with traumatic aquatic injury in warm freshwater lakes, streams, rivers (brackish water)

– Contact with medicinal leeches

Cellulitis is nonspecific in appearance and can vary in severity

Vibrio vulnificus

– Contact with salt water or brackish water

– Contact with drippings from raw seafood

– Hemorrhagic bullae in area of cellulitis, often associated with bacteremia

– More severe disease associated with underlying liver disease, diabetes, or hemochromatosis

Erysipelothrix rhusiopathiae

 

 

– Contact with saltwater marine life (also associated with freshwater fish); often acquired occupationally

– Contact with infected animals (eg, swine, poultry)

– Subacute cellulitis typically involving hand or fingers that handled fish/shellfish

– Typically occurs in summer

– Causes erysipeloid disease (clearly defined, advancing bright red to purple lesions with shiny, smooth surfaces and central clearing)

Pasteurella multocida

Cat bites (common), occasionally dog bites

Rapidly developing cellulitis (usually within 24 h) ± purulent drainage

Capnocytophaga canimorsus

Dog bites

Cellulitis with septic shock in patients with functional/anatomic asplenia, cirrhosis, alcohol abuse, immunocompromise

Very rare pathogens

Bacillus anthracis

– Contact with infected animals/animal products

– Target of bioterrorism

– Rare in developed world; sporadically occurs in farmers in Africa, Middle East, Caribbean

– Edematous pruritic lesion with subsequent ulceration and swelling

– Ulcer develops necrotic eschar

Francisella tularensis

 

 

Contact with or bite from infected animals (especially cats), arthropod bites (particularly ticks)

– Ulceroglandular syndrome (ulcered lesion with central eschar at site of inoculation and localized, tender lymphadenopathy)

– Associated systemic symptoms

Mycobacterium marinum

– Contact with freshwater or salt water, fish tanks, swimming pools

– Usually acquired via traumatic injury

– Often called “fish tank granuloma”

– Typically involving upper extremity and slow growing

– Papular lesion that becomes ulcerative at site of inoculation; ascending lymphatic spread can be seen

– “Sporotrichoid appearance”

– Systemic toxicity usually absent

Mycobacterium fortuitum

 

 

– Exposure to freshwater footbaths/pedicures/nail salons

– Razor shaving strongly associated

– Post augmentation mammoplasty and open-heart surgery

– Usually 3-4 weeks after inoculation; initial papule that becomes a boil, then ulcerates and forms multiple boils rapidly (<7 days)

– Can cause granulomas on skin surface

GI, gastrointestinal.

Table 10.3-2. Risk factors for nonpurulent skin and soft tissue infections

– Skin barrier disruption (trauma, abrasions, existing ulcers or chronic wounds, injection drug use, dermatologic conditions [eg, eczema, psoriasis])

– Lymphedema

– Chronic venous stasis or stasis dermatitis

– Obesity

– Immunosuppression

– Diabetes mellitus

– Toe web space abnormalities (eg, tinea pedis)

– Onychomycosis

Table 10.3-3. Severity of skin and soft tissue infections

Severity

Clinical features

Mild

Patient systemically well

Moderate

Evidence of SIRSa

Severe

Patient has any of the following:

– Failed prior antibiotic therapy (± incision and drainage)

– Systemic signs of infection or hypotension

– Immunocompromise (eg, chemotherapy, organ transplant, neutropenia)

– Clinical signs of deeper infection (eg, necrotizing fasciitis)

a SIRS: Acute onset of ≥2 of:

1) Temperature >38.3°C or <36°C.

2) Heart rate >90 beats/min.

3) Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg.

4) WBC count >12,000/microL or <4000/microL, or >10% of immature neutrophils in differential WBC count.

PaCO2, partial pressure of carbon dioxide in arterial blood; SIRS, systemic inflammatory response syndrome; WBC, white blood cell.

Table 10.3-4. Treatment of nonpurulent skin and soft tissue infections

Severity

Treatment options

Mild

– Cephalexin 500 mg PO qida,c

– Amoxicillin/clavulanate 875/125 mg PO bid

– Cloxacillin 250-500 mg PO every 6 h

– Alternatives with MRSA coverage: SMX-TMP 1-2 double-strength tablets PO bidb,c; doxycycline 100 mg PO bid; clindamycin 600 mg PO tidd

Moderate

– Cefazolin 1-2 g IV every 8 hc

– Ceftriaxone 1-2 g IV every 24 h

– Alternatives with MRSA coverage: vancomycin 15-20 mg/kg IV every 12 hc; clindamycin 600 mg IV every 8 hd

Severe

– Piperacillin/tazobactam 4.5 g IV every 8 h,c and

– Vancomycin 25-30 mg/kg IV once, then 15-20 mg/kg IV every 12 hc,e

– In case of suspected necrotizing fasciitis, add clindamycin 900 mg IV every 8 hf

If vancomycin cannot be used, consultation with infectious diseases is recommended before initiation of alternative agents, such as linezolid or daptomycin.

Antimicrobial therapy should be modified if there are risk factors for resistant organisms or concern for a polymicrobial infection.

a Larger adults may require higher doses.

b Variable streptococci coverage, would not be used as empiric monotherapy (limited data).

c In patients with normal renal function.

d Clindamycin may be considered if clindamycin local resistance is <10%-15% and/or there are other compelling indications. It should be avoided as a first-line option.

e Maximum, 2 g per dose.

f This is typically continued for 48-72 hours after the patient has been hemodynamically stable for 48-72 h.

bid, 2 times a day; IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus; PO, oral; qid, 4 times a day; SMX-TMP, sulfamethoxazole/trimethoprim; tid, 3 times a day.

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