Chapter VI.13. Cellulitis
James C. Lin, MD, FAAP
May 2013

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The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Leo U. Pascua. This current second edition chapter is a revision and update of the original authorís work.


A 6-year-old male with a past medical history of eczema presents to the emergency department with a chief complaint of a red rash over the inner left thigh. The area is warm, mildly swollen and tender with a central lump filled with a whitish fluid. He started having tactile fevers, irritability, and a mild limp today which prompted the mother to bring him for evaluation. He has been scratching at mosquito bites that he had gotten while weekend camping about 1 week ago.

VS T 38.5, P 110, R 26, BP 120/70. Growth parameters are normal for age. He is fussy but distractible. He has a left upper inner thigh erythematous lesion measuring 3 x 4 cm. The skin over the area is mildly indurated, warm, brightly erythematous, and tender. Near the center of the lesion, a 1x2 cm raised and fluctuant pustule filled with purulent material is noted. There is no joint involvement. 1 cm lymphadenopathy is palpable in the left inguinal region.

The pustule is incised and drained and a gram stain with bacterial wound culture is sent. The affected area is marked to identify clinical change following intervention. Based on community antibiogram profiles, he is prescribed clindamycin, topical mupirocin, and anti-pyretics. He is instructed to restrict activity and elevate the affected leg at home. In follow-up the next day, the erythematous region is slightly lighter in color and less warm to touch. His fevers are less frequent, tenderness is improving, and limping is resolved. On follow-up day 2, the fever has resolved and the cellulitis appears to be clearly improving. His parents are instructed to finish the course of antibiotics. He is next seen in follow-up 7 days later, at which time, his cellulitis is resolved.


The acute inflammatory reaction of cellulitis stems from granulocytic infiltrations, hyperemia, and capillary leakage. This is the basis for the skin changes inherent in cellulitis and the systemic reaction of fever. The patient may also guard the tender area. If the cellulitic area overlies a joint, the patient may display resistance or anxiety with limb movement because of the subcutaneous changes and not because of joint involvement.

Risk factors include any condition which disrupts the skin barrier. Such conditions commonly include trauma, insect bites, or dermatologic disorders like eczema. The specific appearance of the cellulitic region can provide important clues to the organism(s) involved, with implications for treatment and prognosis. Clinical presentation, treatment, and prognosis differ depending on the causative organism and location of the cellulitis. The remainder of this chapter will be stratified by these factors.

Lab tests are generally not very helpful in cellulitis. Most cases of early or mild cellulitis, especially those without fever, do not require laboratory testing. If there is an abscess or pustule, incision and drainage with a wound culture of the purulent discharge can be helpful for focused and appropriate antibiotic therapy. A CBC or inflammatory markers might help assess infection severity and establish a trend for follow-up lab testing if improvement is unclear. A blood culture is indicated for patients with significant fevers, suspected deeper soft tissue infection, or clinically ill-appearing. A gram stain of a leading edge aspirate (injecting a small amount of non-bacteriostatic saline into the leading edge of the cellulitis and then aspirating back the saline) is not recommended.

Since introduction of the Hib vaccine, antibiotic treatment is targeted against the most common pathogens, mainly group A streptococcus (GAS) and Staphylococcus aureus (S.aureus). GAS is sensitive to penicillin and cephalosporins. S.aureus treatment must take into account local resistance patterns, as community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) is now a common pathogen. There is less CA-MRSA resistance to clindamycin and trimethoprim-sulfamethoxazole. Macrolides have been used in the past, but GAS and S. aureus have high resistance rates to erythromycin. Because of changing and rising bacterial resistance patterns, follow-up examinations to assess clinical status is are indicated for all patients within 48-72 hours. Typical antibiotic durations are anywhere from 7-10 days for uncomplicated cellulitis.

Staph aureus cellulitis and abscess

S. aureus cellulitis is typically smaller (than GAS cellulitis) and is frequently associated with an abscess or pustule. In many cases, the abscess is the major problem as resolution can only occur with incision and drainage. Heat applied to abscess can increase likelihood of spontaneous rupture. For simple uncomplicated abscesses, incision and drainage is the only indicated therapy and no antibiotics are required. However, if there is extensive surrounding cellulitis, rapid progression, multiple areas of involvement, systemic symptoms, associated co-morbidities, or lack of response to previous incision and drainage, antibiotic therapy is indicated. Gram stain and wound culture of a purulent cellulitis is essential for organism identification and sensitivity profiling.

Empiric antibiotic therapy should include coverage for CA-MRSA until wound culture results can focus antibiotic therapy. Preferred first line treatment is clindamycin, although palatability and insurance coverage can be an issue. Trimethoprim-sulfamethoxazole can also be an option (and is paired with a beta-lactam antibiotic for GAS coverage) but has been associated with an increased incidence of treatment failure. Other oral options include tetracycline (if age appropriate) or linezolid. There is some early evidence supporting returning to beta-lactam antibiotic use for simple purulent cellulitis after incision and drainage cases despite detection of CA-MRSA but firm recommendations can not be made at this time. Topical antibiotics can assist with healing but only mupirocin has anti-MRSA activity. Reports of mupirocin resistance are growing and should be considered part of routine sensitivity profiles.

If methicillin densitive Staphylococcus sureus (MSSA) is identified on wound culture and sensitivity profiles, antibiotics should be modified and beta-lactam antibiotics should be used in treatment. Intravenous options include nafcillin or oxacillin. Generally, first generation cephalsporins such as cephalexin are prescribed for treating uncomplicated MSSA cellulitis.

Patients who have recurrent cases of S. aureus cellulitis or abscess should undergo patient and household decolonization education. Patients should keep wounds covered with clean and dry bandages. Regular bathing and cleaning of hands with soap and water or alcohol based hand gel after touching affected areas should be emphasized. There should be no re-use of towels or razors which have come into contact with infected skin. Cleaning of high touch surfaces such as counters, door knobs should occur regularly. Decolonization of all household members with nasal mupirocin and chlorhexidine or diluted bleach baths can be considered to decrease incidence of recurrent infection.

Group A strep cellulitis and impetigo

Group A beta-hemolytic streptococci (GABHS, also known as Strep S. pyogenes) cellulitis is a painful, erythematous, indurated infection of the skin and subcutaneous tissues. It is classically described as large lesions, erythroderma in color (magenta), slightly raised at the border, with a small, central open skin lesion from the inciting event. Because of inflammatory factors and capillary leakage, small blisters filled with culture negative serous fluid can develop. Frequently, for perioral or perinasal cellulitis or impetigo, a `golden crust' discharge can occur and is exclusively caused by GABHS. Abscess formation occurs less commonly than other pathogens but can occur. Frequently wound and surface cultures can not be obtained. Optimal treatment for GABHS is a penicillin or first generation cephalosporin antibiotic for an uncomplicated cellulitis or impetigo. However, GABHS is one of the leading causes of necrotizing fasciitis and extreme care must be taken to differentiate between a simple cellulitis and a necrotizing process. GAS has been referred to as the `flesh eating bacteria' because of its involvement in necrotizing infections.

Erysipelas

Erysipelas is an acute, well-demarcated aggressive infection of the skin with lymphangitis involving the face (associated with pharyngitis) and extremities (wounds). The affected skin is brightly erythematous, indurated, tender, and the advancing margins of the lesions have raised, firm borders. The reason for the different appearance is infection of the upper dermis and lymphatics compared to the deeper dermis or tissues in a GAS cellulitis. The skin lesion usually is associated with fever, vomiting, and irritability. Typically, beta-hemolytic streptococcus is the inciting bacteria and in some cases, streptococci break through the lymphatic barrier (lymphangitis), and subcutaneous abscesses, bacteremia, and metastatic foci of infection are observed. Care must be taken to differentiate erysipelas from a necrotizing process in the deeper tissue. Intravenous treatment should be focused with beta-lactam antibiotic therapy like cefazolin or ceftriaxone until clinical improvement is secured.

Lymphangitis

Lymphangitis is an inflammation of the lymphatics draining an area of infection (i.e. a cellulitic site). On exam, tender red streaks extend proximally from the infected site. S. aureus and GAS are the most frequent pathogens but other gram negative bacteria and more exotic bacteria can cause a nodular lymphangitis. Treatment is based on the inciting bacterial etiology.

Haemophilus influenzae type b cellulitis

H. influenzae type b (Hib) used to account for in 5-14% of the cellulitis cases in young children and typically occurred in children 2 years of age or younger. Fortunately, there has been a substantial decline in the incidence of invasive infection caused by Hib with the practice of routine immunization to the point where Hib infection is almost non-existent. However if a patient is unimmunized or incompletely immunized, Hib should be considered. A common location for Hib cellulitis is the periorbital and buccal region. Hib is covered by third- generation cephalosporins (e.g., ceftriaxone) and by broad spectrum oral drugs, such as amoxicillin-clavulanate and cefuroxime.

Risk of osteomyelitis and septic arthritis

Although the risk of osteomyelitis and septic arthritis is fairly rare unless a penetrating wound is present, the relationship between osteomyelitis and cellulitis deserves special attention, in that a progression to osteomyelitis from cellulitis mandates a far more aggressive and prolonged antibiotic course, not to mention possible orthopedic surgical debridement. Thus, when a diagnosis of cellulitis is made, the comorbid presence of osteomyelitis must also be strongly considered especially when corroborated by a history of a penetrating wound. At the very least, cellulitis accompanied by point tenderness or joint pain is highly suggestive of osteomyelitis. Attempts at diagnosis are complicated by the fact that cellulitis of structures in proximity to bone can mimic osteomyelitis. Inflammatory markers such as ESR and C-reactive protein are non-diagnostic as they can be elevated in both conditions.

To effectively discern cellulitis with possible underlying osteomyelitis, MRI scanning is the test of choice with a nuclear medicine bone scan as alternative diagnostic testing.

If the history, physical exam, or radiological studies suggest deep cellulitis near a joint, the level of suspicion is raised with regard to an infection in the respective joint, not to mention osteomyelitis, synovitis, septic bursitis and pyomyositis in nearby muscles. Cellulitis overlying a joint can interfere with studies crucial to the diagnosis of septic arthritis. If a cellulitic area is traversed during arthrocentesis for a workup for septic arthritis, the results can be confounded if organisms are introduced into a previously sterile uninvolved joint.

Orbital and periorbital cellulitis

Periorbital (preseptal) cellulitis involves inflammation of the lids and periorbital tissues without signs of true orbital involvement, such as proptosis or limitation of eye movement. It presents as a red and swollen infection limited to the superficial tissue layers anterior to the orbital septum. History can yield an antecedent respiratory infection or sinusitis. Historically, H. influenzae type b was an important cause. However, streptococcal organisms are currently the most common cause of periorbital cellulitis in the post Hib-vaccinated era. S. pneumoniae, S.aureus, and GABHS cause clinically indistinguishable preseptal cellulitis. The latter two pathogens are more likely when fever is absent and with an interruption of the integument (e.g.an insect bite). Coverage of CA-MRSA should be considered for these cases.

Distinguishing periorbital from orbital cellulitis can be difficult. If proptosis, extraocular movement dysfunction or pain, or visual deficits are clearly present, then orbital cellulitis is likely. However, in the absence of these findings, the diagnosis is unclear. In periorbital cellulitis, the lid swelling may be so severe, that it is not possible to tell if proptosis is present. A CT or MRI scan of the orbits will reliably distinguish periorbital from orbital cellulitis. Since the difference between the two can be important, a CT or MRI scan of the orbits has become routine in the evaluation of most patients with severe periorbital cellulitis and/or suspected orbital cellulitis.

Orbital cellulitis refers to a condition involving not only edema of the conjunctiva (chemosis), and inflammation and swelling of the eyelids, but also involvement of the tissues of the orbit, with subsequent proptosis (limitation of movement of the eye). In general, orbital cellulitis may follow direct infection of the orbit from a wound, metastatic deposition of organisms during bacteremia, or direct extension or venous spread of infection from contiguous sites such as the lids, conjunctiva, globe, lacrimal gland, nasolacrimal sac, or paranasal sinuses. The most common cause of orbital cellulitis in children is paranasal sinusitis, with the most frequent pathogenic organisms being H. influenzae, S. aureus, GAS, and S. pneumoniae. Orbital cellulitis must be recognized promptly and treated aggressively. Hospitalization and systemic broad spectrum antibiotic therapy are usually indicated. In some cases surgical intervention is necessary to drain infected sinuses, or a subperiosteal or orbital abscess. Intravenous antibiotic treatment, along with repeated eye exams (visual acuity, pupillary reactivity, extraocular movements, and visual fields) to evaluate possible progression of infection and/or involvement of the optic nerve should be utilized (10). As a worst case scenario, orbital cellulitis can lead to the complication of brain abscess, especially in the frontal lobe.

Animal and human bite cellulitis

Cellulitis and lymphangitis typically appears 24-36 hours after mammalian bite injuries. The etiologies of infections following mammalian bites are polymicrobial and consist of mixed anaerobic and aerobic bacteria. Because of the numerous bacterial species in mammalian oral cavities and on the victim's skin, contamination of bite injuries is universal. In addition to streptococcal and staphylococcal species, Pasteurella multocida is a known pathogen associated with animal bites. Greater care and intervention should be taken for cat bites as the focused point of the cat tooth acts like an injection of bacteria into the deeper subcutaneous tissue. Dog bites tend to be more `tearing' in nature. Rabies coverage in endemic areas should be considered unless the perpetrating animal is under quarantine by animal control. Amoxicillin-clavulanate is generally used for animal bites to cover Pasteurella, S. aureus and anaerobes. However it will not cover MRSA.

Cellulitis and immunodeficiency

The presence of cellulitis with concomitant immunodeficiency requires inpatient treatment. Deficient expression of leukocyte adherence glycoproteins can present as cellulitis or small (<1 cm) necrotic abscesses on any area of the body. In such cases, puncture wounds or skin surface trauma often precipitates cellulitis and abscess formation.

Defects in the normal host response may be reflected in study findings that are disproportionately severe when compared to relatively benign findings on the physical exam. For example, deep cellulitis may be quite impressive on a CT of a neutropenic patient who has only mild superficial swelling or erythema. Indeed, surface pus formation is unusual at sites of even severe cellulitis in such patients. Intravenous antibiotics are required due to the high risk of spread in an immunodeficient patient.

Cellulitis in the newborn

In the neonatal period, cellulitis can be a manifestation of invasive infection sepsis, cellulitis from scalp probes, or omphalitis. Cellulitis may also be the presenting sign of immunodeficiency in an infant. Cellulitis, delayed separation of the umbilical cord and gingivitis is consistent with an infant with leukocyte adhesion deficiency. Cellulitis of the labia majora, pyogenic skin infections, oral ulcerations, or abscesses has been the presenting manifestations of autoimmune neutropenia of infancy.

Cellulitis and tuberculosis

Rarely, cellulitis or skin discoloration overlying a fluctuant mass might be the presenting finding in tuberculosis of the superficial lymph nodes, often referred to as scrofula, the most common form of extrapulmonary tuberculosis in children. The tonsillar, anterior cervical, submandibular, and supraclavicular nodes become involved secondary to extension of a primary lesion of the upper lung fields or abdomen. The nodes usually enlarge gradually in the early stages of lymph node disease. They are firm (but not hard), discrete, and nontender. The nodes often feel fixed to underlying or overlying tissue. Disease is most often unilateral, but bilateral involvement may occur because of the crossover drainage patterns of lymphatic vessels in the chest and lower neck.


Questions

1. A 14 yo female presents with an abscess formation in her left axilla. She was placed on antibiotics 2 days prior to admission by her PMD. The lesion is 5 cm in diameter, erythematous, tender to palpation and fluctuant on exam. She is nontoxic appearing and her vital signs are stable. The next appropriate management step is:
. . . . . a. IV antibiotics
. . . . . b. Warm packs to site
. . . . . c. Analgesics
. . . . . d. CT of the site
. . . . . e. Incision and drainage

2. A 7 yo male presents to your office with a 5 day history of a weeping, tender red lesion on his right knee after falling off a skateboard. His vital signs are stable and he is afebrile. On exam, there is a 2 cm open lesion with pus and base erythema but without involvement of the right knee. Which of the following laboratory investigations would you obtain? CIRCLE ALL THAT APPLY
. . . . . a. Complete blood count with differential
. . . . . b. Blood culture
. . . . . c. Creatine kinase
. . . . . d. Wound gram stain, culture, and sensitivity profile
. . . . . e. X-ray of the knee

3. A 6 year old boy presents with his 3rd hospitalization for a cellulitis with abscess. He has grown methicillin resistant staphylococcus aureus (MRSA) from his wound culture. There is a 3 year old brother who also gets skin infections frequently. Of the following, what would you recommend to the family? CIRCLE ALL THAT APPLY
. . . . . a. Wash hands after handling wound
. . . . . b. Apply mupirocin to the nose twice a day
. . . . . c. Test the brother for MRSA and wash him in diluted bleach if positive
. . . . . d. Recommend the family use the same towel for the patient to clean his wounds every time.
. . . . . e. Wash the patient in chlorhexidine

4. A 4 year old male comes in to the Emergency Department after being bitten by a dog. The dog is being held in quarantine by animal control. The wound has been irrigated and sutured. What bacteria and antibiotic choice are most appropriate to the situation?
. . . . . a. GAS, Staph species, no antibiotics as it has been irrigated.
. . . . . b. GAS, Haemophilus species, antibiotic-keflex
. . . . . c. S. aureus, GAS, anaerobes, Pasturella, antibiotic-amoxicillin/clavulanic acid
. . . . . d. CA-MRSA, GAS, antibiotic-clindamycin


References

1. Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children: Executive Summary Clin Infect Dis 2011;52(3):285-292. doi: 10.1093/cid/cir034

2. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005;41(10):1373-1406.

3. Wald ER. Periorbital and Orbital Infections. Pediatr Rev 2004;25;312-320.


Answers to questions

Answers 1.e, 2.d, 3.abce, 4.c


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