Nonpurulent Skin and Soft Tissue Infections: Erysipelas and Cellulitis

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 and cellulitis are typically caused by pathogen invasion through a disruption in the skin barrier.

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).

Cellulitis is often caused by beta-hemolytic streptococci. Cellulitis secondary to S aureus is also common, 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, including known MRSA colonization, residing in a long-term care facility, injection drug use, contact 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 is more common in 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).

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 presents as 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 most commonly involves the lower extremity, with the face being the next most common site, in which case it can have 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 acutely or 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 has hemorrhagic bullae.

DiagnosisTop

Erysipelas and cellulitis remain clinical diagnoses. In a systemically well, immunocompetent patient, blood cultures are not routinely 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 ideally 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 radiography 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. In the presence of a specific exposure resulting in cellulitis, empiric antibiotics should be modified to account for relevant pathogens.

Evaluate the patient for MRSA risk factors to determine if MRSA coverage is warranted. In the presence of risk factors, those who have either 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 (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. Cross ELA, Jordan H, Godfrey R, et al. Route and duration of antibiotic therapy in acute cellulitis: A systematic review and meta-analysis of the effectiveness and harms of antibiotic treatment. J Infect. 2020 Oct;81(4):521-531. doi: 10.1016/j.jinf.2020.07.030. Epub 2020 Jul 31. PMID: 32745638. 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, stepping 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. In cases of necrotizing fasciitis, surgical debridement of necrotic tissue is critical.

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
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