Cellulitis, erysipelas

1. Description of the problem

What every clinician needs to know

Patients with uncomplicated cellulitis rarely require admission to the ICU. Infections requiring ICU admission usually involve deeper tissues and more severe infections such as myositis or fasciitis or deep soft tissue abscess.

Any patient with “cellulitis” and severe pain in the area or abnormalities of vital signs should be suspected of having myositis or fasciitis or deep soft tissue abscess.

Clinical features of the condition

Cellulitis is an acute inflammation of the skin and subcutaneous tissues with swelling, warmth and redness but little or no pain. The lesions usually do not have a sharp border.

(Erysipelas is a superficial form of cellulitis involving lymphatics; it has a peau d’orange appearance and a sharp border. It characteristically appears on the face.)

Cellulitis can be divided into three broad categories with different causative organisms, treatments and prognoses:

Cases that occur “out of the blue”, without antecedent trauma or an evident break in the skin (“simple cellulitis”). (In most of these cases the cellulitis is “primary”, i.e. it is the initial site of infection. Occasionally, the skin lesion occurs as a secondary manifestation of a primary bacteremia.)
Cases that occur around chronic ulcers, such as diabetic foot ulcers or decubiti
Cases that occur after trauma (including bites) or exposure to fresh water or seawater

“Simple” cellulitis (spontaneous, no history of trauma, no break in the skin)

Typically occurs spontaneously, in a distal extremity, especially the leg, in a patient with abnormalities of the venous or lymphatic system
May be recurrent at the same site
Is almost always unifocal (cellulitis occurring simultaneously at more than one site should suggest bacteremic illness with secondary skin manifestations)
Is usually caused by streptococci (group A, B, C or G), sometimes by Staphylococcus aureus
Causes little pain (moderate or severe pain should suggest more serious infection such as myositis, fasciitis or deep soft tissue abscess.)
Causes little fever, abnormality of vital signs or elevation in WBC (marked abnormalities in these features should suggest primary bacteremic infection with secondary cellulitis)

Cellulitis surrounding a diabetic foot ulcer or decubitus ulcer

Is usually caused by skin organisms (S. aureus) or, if below the waist, by fecal flora (gram-negative enteric bacilli, anaerobes)
Rarely produces severe systemic effects
An exception is “cellulitis” in the perineal area involving the scrotum or penis, which often involves deep tissues and must be treated with aggressive surgical debridement (see
Fournier’s gangrene under Myositis and Fasciitis)

Cellulitis around traumatic skin lesions

Trauma provides a portal for unusual organisms and a pathway to deeper tissues; therefore, infections following trauma may be complicated by myositis, fasciitis or deep soft tissue abscess. They can be divided into those allowing exposure to soil organisms and those following bites or exposure to seawater or fresh water, with different causative agents and empiric treatments.

Exposure to soil organisms

Infections after “dirty” trauma often involve soil organisms such as clostridia and gram-negative soil bacilli (e.g. Pseudomonas)
Clostridia and some other bacteria may produce gas in the tissues (“crepitant cellulitis”).
It may be difficult to determine if pain after a traumatic injury is due to trauma itself or to deeper infection (myositis, fasciitis, deep abscess or gangrene).
Pain increasing in the hours after injury suggests spreading deep infection (see myositis, fasciitis) and should not be attributed to the initial lesion.
A truly foul odor signifies infection involving anaerobes.

Infection following bite wounds

Infection after cat bites usually is caused by Pasteurella multocida.
Infection after dog bites and human bites (including “clenched fist injuries”) may involve S. aureus, gram-negative bacilli or anaerobes.

Infection after exposure to seawater or fresh water

The portal of entry may be through microabrasions or through obvious skin lesions.
Exposure to seawater, especially in a patient with cirrhosis, raises the possibility of Vibrio vulnificus infection. The lesions are usually bullous and hemorrhagic. Ingestion of raw shellfish by patients with cirrhosis may cause bacteremic infection by V. vulnificus with secondary skin lesions.
Exposure to fresh water may lead to infection by Aeromonas species.

Key Management Points

Assess pain and swelling: severe pain or swelling suggests myositis, fasciitis or deep soft tissue infection requiring surgical intervention.
Assess for crepitus: its presence suggests clostridial or other anaerobic infection or enteric gram-negative bacterial infection.
Assess vital signs and WBC: marked abnormalities suggest deeper infection or bacteremia with secondary cellulitis.
Assess distribution: simple cellulitis rarely involves more than one non-contiguous site. Involvement of more than one site suggests bacteremic (or fungemic) illness with secondary skin manifestations or a noninfectious mimic of cellulitis (e.g. erythema nodosum, Sweet syndrome).
Obtain a history of trauma, exposure to animal or human bites, or to seawater or fresh water: a positive history suggests unusual pathogens.

2. Emergency Management

Most cases of cellulitis without significant local pain or marked abnormalities of vital signs or WBCs do not require intensive care or emergency measures. Features that suggest more serious or more complicated lesions are listed below.

Indications for Emergency Management: “RED FLAGS”

Marked pain in the site, or pain progressively increasing after a traumatic injury, should suggest myositis, fasciitis or deep soft tissue infection: obtain prompt surgical consultation (see myositis and fasciitis).
Crepitus or evidence of gas on imaging suggests infection by anaerobes (e.g. clostridia) or gram-negative enteric bacilli and may need surgical debridement.
Injuries involving the hand may involve tendon sheaths or other deep compartments, threatening function: obtain prompt surgical consultation.
Marked abnormalities in vital signs or WBCs suggest bacteremic illness or deeper infection: obtain blood cultures.
If there is an accessible wound site or draining lesion, obtain gram stain and cultures from the site (remembering that surface cultures may simply reflect colonizing organisms).
Traumatic injury, especially involving soil organisms or after an animal bite, suggests the possibility of infection by Clostridium tetani: verify status of tetanus immunization and immunize if appropriate.
In all cases, administer empiric antibiotic treatment based on usual infecting organisms (see Specific Treatment).

3. Diagnosis

The diagnosis of cellulitis is made clinically. It is the presumed diagnosis when there is redness, warmth, mild swelling but little or no pain in a localized area of skin. There may be an obvious inciting cause (trauma, a bite wound, or a predisposing skin lesion such as a decubitus ulcer).
Cases without an obvious inciting cause, i.e. spontaneous or “simple” cellulitis, typically occur in a distal extremity, usually a leg, with preexisting venous or lymphatic abnormalities.
The causative agent is usually difficult to identify in cases of simple cellulitis with no break in the skin. Aspiration or biopsy of the margin of the lesion yields a causative organism in only one quarter or less of cases: in those instances, the causative agent is usually a streptococcus (group A, B, C or G) or occasionally S. aureus.
In lesions resulting from trauma or bites or around decubitus ulcers, there is usually material to be swabbed or aspirated: however, the microorganisms detected on gram stain or culture could reflect organisms colonizing the surface rather than those in deeper tissues. Surgical debridement will usually yield material from the depths of the lesion that is more likely to reflect the true pathogen(s).
The key issue is to be aware of deeper and more serious infections that may masquerade as cellulitis, i.e. myositis, fasciitis, deep abscess, and, in the case of perineal lesions, Fournier’s gangrene.

Differential diagnosis

The differential diagnosis includes the broad category of deeper infections, bacteremic illness, and Lyme disease.

Deeper infections: severe or progressively increasing pain or marked abnormalities of vital signs or WBC suggest the possibility of myositis, fasciitis or deep soft tissue abscess.
Bacteremic illness: more than one lesion, not contiguous, and marked abnormalities of vital signs or WBC suggest skin lesions secondary to a primary bacteremic illness or a noninfectious illness.
Lyme disease: a spreading cellulitic lesion, occurring in the appropriate setting (endemic area, spring or summer), often at a site unusual for simple cellulitis (e.g. on the torso or thigh), should suggest the possibility of erythema migrans.
Cellulitis mimics: there are many, including insect stings, drug reactions, immunological disorders, Sweet syndrome, pyoderma gangrenosum and erythema nodosum.

Confirmatory tests to consider

Deeper infection (myositis, fasciitis, deep abscess): obtain surgical consultation; consider MRI or CT scan or, for muscle abscess, ultrasound exam.
Bacteremic illness: obtain blood cultures.
Lesions with draining or open wounds: obtain material from the lesion for gram stain and culture.
Lyme disease: a serological test for Lyme disease may be positive but is quite likely to be negative at the time erythema migrans is apparent. The diagnosis should be based on the clinical setting and not on serological testing.

4. Specific Treatment

The treatments below are empiric, i.e. intended to address the usual infecting organisms. Treatment should be modified on the basis of the results of cultures and sensitivity tests.

Simple cellulitis

Treat for infection by streptococci (group A, B, C or G) and possibly S. aureus with IV antibiotics:

Penicillin G (covers streptococci)
OR oxacillin or nafcillin or cefazolin or ceftriaxone (these agents also cover methicillin-susceptible S. aureus but not MRSA). Because about 50% of community-acquired S. aureus infections are now MRSA, vancomycin is preferred.
May substitute vancomycin for possibility of MRSA, especially if cellulitis arose from a pustule or began as an “insect bite” (which suggests MRSA)
Elevate the involved extremity above the heart for some hours of the day if possible for better drainage.

Cellulitis surrounding a diabetic foot ulcer or decubitus ulcer

Treat for infection by S. aureus and fecal flora (anaerobes, gram-negative enteric bacilli, possibly enterococci) with IV antibiotics:

Vancomycin PLUS extended-spectrum penicillin (ampicillin-sulbactam or piperacillin-tazobactam) or meropenem
For cellulitis in the perineal area, consider possible Fournier’s gangrene (see Myositis and Fasciitis)

Cellulitis after traumatic injury

If the traumatic injury is likely to be relatively clean and minor, e.g. after a cut with an unsoiled knife, may treat for infection by S. aureus and streptococci, e.g. with oxacillin, nafcillin or cefazolin. Might substitute vancomycin for the possibility of infection by MRSA.

If there has been exposure to soil organisms, e.g. after road trauma, treat empirically for S. aureus, anaerobes, and environmental gram-negative bacilli such as Pseudomonas aeruginosa:

Vancomycin (for MRSA) PLUS piperacillin-tazobactam or meropenem (for anaerobes and Pseudomonas aeruginosa)
If there is evidence of gas in the tissues or of clostridia on gram stain, add clindamycin to suppress toxin formation.
Verify immunization status: administer tetanus toxoid or tetanus immune globulin or both, as indicated, for “dirty” wounds.

Cellulitis following bite wounds

Cat bite: Pasteurella multocida is usually the cause. The organism is resistant to early-generation cephalosporins and clindamycin. Treat with penicillin G or ampicillin-sulbactam or ceftriaxone.
Dog bite or human bite: Aim treatment at S. aureus, oral anaerobes or enteric gram-negative bacilli. Treat with a broad-spectrum penicillin such as ampicillin-sulbctam or piperacillin-tazobactam. May add vancomycin for the possibility of MRSA.

Cellulitis following exposure to seawater or fresh water

Seawater: Treat for infection by Vibrio vulnificus, especially if patient has cirrhosis or lesions are bullous and hemorrhagic. Ceftazidime or ciprofloxacin.
Freshwater: Treat for infection by Aeromonas species. Ciprofloxacin.

Management of refractory cases

Poor venous or lymphatic drainage: The response of simple cellulitis is much enhanced if the extremity is raised above the level of the heart for some hours of the day.
Misidentification of the infecting organism: If blood cultures and cultures of material from the lesion are unrevealing, consider biopsy of the lesion for pathological diagnosis and culture. An attempt should be made to identify not only ordinary bacteria but also fungi and mycobacteria as well as noninfectious processes.
Failure to recognize deeper infection: Reconsider the possibility of myositis, fasciitis or deep soft tissue abscess. Imaging (e.g. MRI) and possibly surgical exploration should help to resolve the issue.
Misidentification of a noninfectious process as infectious: Consider biopsy of the lesion to identify noninfectious entities such as cutaneous lymphoma, Sweet’s disease, erythema nodosum and pyoderma gangrenosum.

5. Disease monitoring, follow-up and disposition

Most forms of cellulitis respond well to antibiotic treatment together with adequate drainage and debridement, if indicated.
The lesions of simple cellulitis usually begin to recede within a few days, though they may take longer, especially if the involved extremity, especially the leg, is not elevated.
The response of other forms of cellulitis depends on the nature and extent of the injury and the virulence of the infecting organisms.
Rarely, cellulitis caused by Pasteurella multocida (after a cat bite) may be complicated by endocarditis.
The antibiotic regimen may be simplified and the route of administration changed to the oral route once a satisfactory clinical response is evident. In general, antibiotics should be administered until signs of active infection are absent. This usually takes 1-2 weeks.
There is no standard recommendation in terms of follow-up and disposition. In most instances, a follow-up outpatient visit a few days or a week after the end of antibiotic treatment seems reasonable.

Pathophysiology

Simple cellulitis typically presents in the leg and is usually caused by streptococci of groups A, B, C or G. The predisposing factor is usually some abnormality of the venous or lymphatic system. Incompetent veins in the lower extremity, saphenous vein surgery, or axillary node dissection are examples. In typical streptococcal cellulitis of the leg, it is thought that streptococci gain entrance through microfissures between the toes. Interdigital fungal infection may be a predisposing factor and should be looked for.

Once cellulitis has occurred, damage to the lymphatics predisposes to future attacks in the same area.

The pathogenesis of cellulitis as a consequence of bacteremia, trauma, bites or environmental exposures is self-evident.

Epidemiology

N/A

Prognosis

See “Disease Monitoring” above.

Special considerations for nursing and allied health professionals.

N/A

What's the evidence?

Swartz, MN. “Cellulitis”. N Engl J Med. vol. 350. 2004. pp. 904-912. This concise review discusses the common causes, differential diagnosis, and recommended treatments for cellulitis.

“Vibrio illnesses after hurricane Katrina — multiple states, August-September 2005”. Morbidity and Mortality Weekly Report. vol. 54. Cellulitis due to Vibrio species is severe and can be life-threatening.

Stevens, DL, Bisno, AL, Chambers, HF. A comprehensive review and guideline for diagnosis and management. The review by Swartz (above) also provides a helpful guide.

Newell, PM, Norden, CW. “Value of needle aspiration in bacteriologic diagnosis of cellulitis in adults”. J Clin Micro. vol. 26. 1988. pp. 401-404. Needle aspiration yielded a causative pathogen in only 10% of cases. The references by Stevens et al, and by Swartz (above) also cite numerous studies with a low yield in cases without a draining site.

Falagas, ME, Vergidis, PI. “Narrative review: diseases that masquerade as infectious cellulitis”. Ann Intern Med. vol. 142. 2005. pp. 47-55. Many noninfectious illnesses may mimic infectious cellulitis, including insect stings, drug reactions, eosinophilic cellulitis, Wells syndrome, Sweet syndrome, pyoderma gangrenosum and erythema nodosum.

McLaine, RJ, Husted, TL, Hebbeler-Clark, Solomkin, JS. “Meta-analysis of trials evaluating parenteral antimicrobial therapy for skin and soft tissue infections”. Clin Infect Dis. vol. 50. 2010. pp. 1120-1126. This review emphasizes the deficiencies in design of most studies of parenteral therapy for skin and soft tissue infections. Thus, clinicians are forced to rely on indirect evidence in the choice of antibiotics.

Jenkins, TC, Sabel, AL, Sarcone, EE. “Skin and soft-tissue infections requiring hospitalization at an academic medical center: opportunities for antimicrobial stewardship”. Clin Infect Dis. vol. 51. 2010. pp. 895-903. The study contains useful information for physicians concerned about the wasteful use of resources. There was considerable use of unnecessary diagnostic tests and inappropriately broad antimicrobial treatment. However, in the absence of randomized trials, the optimal durations of treatment remain a matter of guesswork.

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