Bacterial, mycobacterial, and protozoal infections of the skin

Impetigo

Impetigo is a common, contagious superficial skin infection caused by streptococci, staphylococci, or both. Although seen in all age groups, the disease is most common in infants and children. Lesions may involve any body surface but occur most often on the exposed parts of the body, especially the face, hands, neck, and extremities.

There are two classic forms of impetigo: bullous and nonbullous (or crusted). Nonbullous impetigo accounts for more than 70% of cases. It begins with a 1- to 2-mm erythematous papule or pustule that soon develops into a thin-roofed vesicle or bulla surrounded by a narrow rim of erythema. The vesicle ruptures easily with release of a thin, cloudy, yellow fluid that subsequently dries, forming a honey-colored crust, the hallmark of nonbullous impetigo ( Fig. 14.1 ). The infection is easily spread by autoinoculation ( Fig. 14.2 ) through fingers, towels, or clothing, with resultant satellite lesions in either adjacent areas or other parts of the body. Individual lesions may extend peripherally with central clearing, resulting in annular or gyrate morphologies. Nonbullous impetigo historically was caused primarily by group A β-hemolytic streptococci (GABHS) but now is also most commonly caused by S. aureus, except for endemic tropical regions, where GABHS may still predominate. Anaerobic organisms may also be recovered from lesions of nonbullous impetigo.

Bullous impetigo, which is nearly always caused by S. aureus, presents as flaccid, thin-walled bullae or, more commonly, tender, shallow erosions surrounded by a remnant of the blister roof ( Figs. 14.3 and 14.4 ). Common locations include the diaper region ( Fig. 14.5 ), face, and extremities. Lesions of bullous impetigo can be thought of as a localized form of staphylococcal scalded skin syndrome (SSSS) (see Staphylococcal Scalded Skin Syndrome section), the characteristic lesions being the result of the same exfoliative toxin as implicated in that condition. Neonatal pustulosis (see Chapter 2 ), another condition favoring the diaper region and other fold areas in infants, is usually caused by S. aureus and presents with small pustules on an erythematous base that rupture easily upon swabbing.

Fever and regional lymphadenopathy may occur later in the course of impetigo but appear to be more common with the nonbullous type caused by GABHS. Potential complications of both bullous and nonbullous impetigo include sepsis, osteomyelitis, septic arthritis, lymphadenitis, and pneumonia. Cutaneous streptococcal disease may be associated with guttate psoriasis, scarlet fever, and poststreptococcal glomerulonephritis when a nephritogenic strain of GABHS is implicated.

An important reservoir for staphylococci is the upper respiratory tract of asymptomatic persons. Asymptomatic nasal carriage occurs in 20% to 40% of normal adults and up to 80% of patients with atopic dermatitis. The perineum is another common site of carriage, albeit not as common as the nares. These carriers spread the agent to the skin of infants and young children, probably with their hands. The reservoir for streptococci involved in skin infections appears to be skin lesions of other individuals, not the respiratory tract of affected or asymptomatic persons. Factors such as trauma and insect bites probably contribute to the pathogenesis of this infection.

Treatment for impetigo depends on the clinical presentation. Untreated, the disorder may last for 2 to 3 weeks with continuous spread and development of new lesions. In severe cases there may be large, crusted vegetations with deep extension and ulceration. Gentle cleansing, removal of crusts, and drainage of blisters and pustules may help prevent local spread of disease. If crusts are firmly adherent, warm soaks or compresses are useful.

Topical antibiotics may be useful in the treatment of mild, localized disease caused by S. aureus . With streptococcal or more severe staphylococcal infections, however, systemic antibiotics produce a swifter response and fewer failures. Bacitracin, polymyxin, gentamicin, and erythromycin are all effective topical agents and are relatively nonallergenic. Bacitracin, however, is a potential contact allergen, and this should be remembered in patients treated with this agent who develop worsening erythema and evidence of contact dermatitis. ^, In addition, treatment failures are common when bacitracin is used for impetigo. Neomycin is another effective topical agent, although reports of contact allergy have traditionally appeared to be more common with this agent than with other topical antimicrobials (see Chapter 3 ). Mupirocin exerts a high level of bactericidal activity against a broad spectrum of Gram-positive organisms, including S. aureus and GABHS, and has little or no potential for irritation, side effects, or cross-reaction with other antibiotics. It is effective against methicillin-resistant S. aureus (MRSA), although some resistance to mupirocin has emerged in recent years, especially after prolonged use. In a study of 249 children with documented S. aureus isolates on culture, 31% of all isolates were resistant to mupirocin; some factors that correlated with resistance included prior mupirocin use, MRSA, and atopic dermatitis. Some studies have demonstrated equal or greater effectiveness of topical mupirocin over oral erythromycin in the treatment of impetigo in children. ^, Mupirocin is typically applied three times daily for 7 to 10 days. Nasal carriage of S. aureus may be reduced with the use of intranasal mupirocin, which should be considered in known carriers with recurrent impetigo or in the setting of epidemic outbreaks. Retapamulin, a pleuromutilin-class topical antibiotic for the treatment of skin and skin-structure infections, has been demonstrated effective against both S. aureus and GABHS and is another treatment option for localized impetigo. ^, Retapamulin is also active against MRSA and many anaerobes, including Propionibacterium species, Bacteroides species, and Clostridium species. The benefits of retapamulin include its lower propensity toward the development of resistance and twice-daily dosing. Ozenoxacin is a novel topical quinolone cream for impetigo and has shown efficacy in both bullous and nonbullous types and against both S. aureus (including MRSA) and GABHS. ^,

Oral therapy for impetigo should be with an agent that covers both S. aureus and GABHS because distinguishing between these etiologies clinically is often not possible. In areas with a low prevalence of erythromycin-resistant S. aureus , erythromycin ethylsuccinate or erythromycin estolate are reasonable options. If known erythromycin resistance is present in the community, alternative oral agents with a good track record include a penicillinase-resistant penicillin (i.e., cloxacillin or dicloxacillin), amoxicillin plus clavulanic acid, a first-generation (i.e., cephalexin) or second-generation (i.e., cefprozil) cephalosporin, clindamycin, or in some cases, other macrolide antibiotics (i.e., clarithromycin or azithromycin). Oral therapy is used by most clinicians when the involvement is more widespread and/or severe.

In severe or recalcitrant cases, a skin swab for bacterial culture and sensitivity testing should be performed. The epidemiology of community-associated MRSA (CA-MRSA) (see later) infection must be considered in this setting, as highlighted by multiple observations of the increased prevalence of this pathogen. These patients often lack traditional risk factors for MRSA, and the isolates may be more susceptible to clindamycin and trimethoprim-sulfamethoxazole. ^,

A review of the National Ambulatory Medical Care Survey data on office visits for impetigo from 1997 to 2007 revealed that a majority of the 4 million patients were treated by nondermatologists (pediatricians, internists, emergency room and family physicians) and systemic antibiotics were the most commonly prescribed therapy, followed by topical antibiotics. A Cochrane review found that topical mupirocin and topical fusidic acid (not available in the United States) were equally or more effective than oral treatment in the studies that met their inclusion criteria. This highlights a potential opportunity for physician education, because increased utilization of topical therapy for patients with more limited impetigo could decrease the morbidity associated with oral antibiotic treatment, in line with the principles of antibiotic stewardship.

Lesions of impetigo caused by GABHS are shallow and usually heal well, and rheumatic fever does not occur after streptococcal skin infection. In contrast, acute glomerulonephritis and scarlet fever can occur after cutaneous streptococcal infection. As in the case of nephritis after streptococcal pharyngitis, only certain serologic types, different from those producing nephritis as a sequalae of streptococcal pharyngitis, appear to result in this complication of cutaneous infection. This complication is uncommon except for certain epidemics resulting from nephritogenic strains of streptococci. Although systemic antibiotics help eliminate cutaneous streptococci, they do not appear to prevent glomerulonephritis caused by streptococcal impetigo. In general, however, with the changing bacteriology and the fact that staphylococci are a more common cause of both types of impetigo, concerns about postimpetigo glomerulonephritis have been greatly reduced.

Methicillin-resistant staphylococcus aureus infections

The epidemiology of S. aureus skin and soft-tissue infections (SSTIs) has changed over recent decades, with an increasing prevalence of CA-MRSA infections observed in both the United States and elsewhere. Since the initial descriptions of children lacking predisposing risk factors with CA-MRSA infection in the late 1990s, marked increases in S. aureus isolates with this characteristic were observed, both in endemic and epidemic forms. By the middle of the first decade of the twenty-first century, up to 50% of community-associated S. aureus infections in many US centers were being identified as MRSA. Increases in the number of children hospitalized with MRSA infections were also observed, but fortunately, the mortality rate for these children remained relatively low. In recent years, the trend in S. aureus in adults has been a decline in the proportion caused by MRSA. One study reviewing S. aureus susceptibility data in pediatric patients over 2005–2014 suggested that a similar trend exists, with a decreasing proportion of MRSA infections (primarily SSTIs), although increased clindamycin resistance was documented. Another study of S. aureus isolates in Chicago over 2006–2014 also suggested a decrease in the incidence of MRSA SSTI in both adults and children. However, another review of invasive MRSA infections (defined as isolation of MRSA from a normally sterile body site) in children between 2005 and 2010 showed that these infections, which appear to predominate in young infants and black children, experienced an increase in incidence. These data highlight the importance of considering regional trends and susceptibility patterns when deciding on empiric therapies (or awaiting testing results).

MRSA originated after the introduction of a mobile genetic element, staphylococcal chromosomal cassette (SCC) carrying the mecA gene, into strains of methicillin-sensitive S. aureus (MSSA). This gene encodes an altered penicillin-binding protein. In distinction to hospital-associated MRSA, CA-MRSA is generally classified as such when there is no history of prior MRSA infection or colonization, when the positive culture was obtained in the outpatient setting or isolated within 48 hours of hospitalization, and when the patient lacks an exposure history (i.e., to a healthcare facility, chronic care facility, or indwelling catheter). ^, Molecular characteristics of the isolate are also useful in distinguishing the strains. Many CA-MRSA strains produce Panton–Valentine leukocidin (PVL), a toxin that kills neutrophils, although this toxin is also produced by some of the other more-sensitive strains of S. aureus . ^, The exact role of PVL in CA-MRSA infections remains controversial, although it appears to be increasingly associated with follicular infections (see Furuncles and Carbuncles section).

CA-MRSA infections seem to disproportionately affect children, young adults, and individuals from ethnic minority and low socioeconomic groups. Spread is facilitated by crowding, skin-to-skin contact, skin compromise, and shared personal hygiene items. Cutaneous CA-MRSA infections are common in athletes, most notably collegiate football players. The potential clinical manifestations associated with CA-MRSA infection are listed in Box 14.1 . The constellation of disorders caused by infection with CA-MRSA have been grouped under the designation of SSTIs. Empiric outpatient therapy decisions for CA-MRSA infections should incorporate the type and site of infection, prevalence of the organism in the community, and local antibiotic susceptibility patterns. Abscesses (including furuncles and carbuncles), which are collections of pus within the dermis and deeper skin layers, are a common manifestation of CA-MRSA infection ( Figs. 14.6 and 14.7 ) and are most commonly located on the buttocks. Incision and drainage of abscesses is often useful and sometimes sufficient as monotherapy for purulent uncomplicated infections. However, better studies are required to determine the role of antibiotics in treating abscesses that have been adequately drained.

The most commonly utilized oral antibiotics in the United States are trimethoprim-sulfamethoxazole, clindamycin, doxycycline, linezolid, rifampin, and the fluoroquinolones. Fusidic acid is also utilized in the United Kingdom, Australia, and other countries. Inducible clindamycin resistance has increased in recent years and should be considered when testing reveals clindamycin susceptibility and erythromycin resistance. In these instances, a “D test” should be performed and used to guide the choice of therapy. In a prospective randomized study of oral clindamycin versus oral trimethoprim-sulfamethoxazole for uncomplicated staphylococcal skin infections (77% of which were MRSA), the cure rate was similar in both groups. Management of colonization has been attempted with intranasal mupirocin and skin disinfection (i.e., with chlorhexidine washes), with variable success. Persistent colonization with MRSA in outpatients is associated with increased household colonization pressure (colonization of household contacts). There is a high rate of recurrent colonization after clearance of MRSA SSTIs. In addition, MRSA colonization and infection have been increasingly observed in companion animals, especially cats and dogs, and may serve as reservoirs for human infection.

Ecthyma

Ecthyma is a deep or ulcerative type of pyoderma commonly seen on the lower extremities and buttocks of children and is caused most often by GABHS. It may occur as small punched-out ulcers or a deep spreading ulcerative process. The disorder begins in the same manner as impetigo, often occurring after infected insect bites or minor trauma, but penetrates through the epidermis to produce a shallow ulcer. The initial lesion is a vesiculopustule with an erythematous base and firmly adherent crust. Removal of the crust reveals a lesion deeper than that seen in impetigo with an underlying saucer-shaped ulcer and raised margin ( Fig. 14.8 ). The lesions are painful and heal slowly over a few weeks, often with scar formation. When multiple, lesions of ecthyma may be confused with child abuse related to cigarette burns. S. aureus (including MRSA) may occasionally be cultured from the lesions, and epidemic outbreaks have been reported, occasionally in association with poststreptococcal glomerulonephritis or other systemic sequelae. ^, Treatment consists of warm compresses and the appropriate systemic antibiotic.

Ecthyma gangrenosum is a cutaneous finding that may be seen in patients with Pseudomonas aeruginosa bacteremia. Most of the affected individuals have an underlying immunodeficiency (either congenital or acquired) or a history of cancer chemotherapy. There are reports of ecthyma gangrenosum in apparently healthy, immunocompetent children (often with diaper-area involvement), but the diagnosis should prompt a thorough investigation for occult immunodeficiency. ^, Neutropenia may be a risk factor for ecthyma gangrenosum. The characteristic lesions are hemorrhagic papules with a pink or violaceous rim ( Fig. 14.9 ) that progress to bullae, ulcers, and necrotic plaques. Eschar formation eventually occurs ( Fig. 14.10 ), and old lesions heal with scarring. The diagnosis can be confirmed by Gram stain and bacterial culture of lesions or blood cultures, which are positive for P. aeruginosa . Treatment with appropriate antipseudomonal therapy (i.e., aminoglycoside and an antipseudomonal penicillin) should be instituted early.

Folliculitis

The term folliculitis refers to an infection of hair follicles. The clinical appearance varies according to the location and depth of follicular involvement. Deeper follicular infections (furuncles and carbuncles) are discussed later. Superficial folliculitis (Bockhart impetigo), an infection of the follicular ostium, begins with superficial small, yellow-white pustules, often with a narrow red areola ( Fig. 14.11 ) and a hair shaft protruding from the center of the lesion. It occurs most commonly in children and usually is seen on the buttocks ( Fig. 14.12 ) and extremities, especially the thighs. Most lesions are painless, occur in crops, and heal over 7 to 10 days with postinflammatory hyperpigmentation. S. aureus is by far the most common pathogen; other possible etiologies include streptococci, Gram-negative organisms, and even dermatophytes. In immunocompromised children, commensal organisms may cause folliculitis, including Pityrosporum and Demodex (see Chapter 18 ). Superficial folliculitis is not always infectious in origin. “Sterile folliculitis” may be seen after skin contact with oil or other occlusive products and results in follicular plugging and inflammation. A classic example of sterile folliculitis is the scalp pustulosis occasionally associated with application of hair oils.

Superficial folliculitis usually responds to gentle cleansing with antibacterial soaps and the application of topical antibiotics such as clindamycin, erythromycin, or mupirocin. More extensive or resistant cases should be treated with a systemic antibiotic (a penicillinase-resistant penicillin or cephalosporin, depending on local resistance patterns). In such instances, bacterial culture should be obtained before the initiation of systemic therapy. Sodium hypochlorite (bleach) baths or washes on a twice- to three-times weekly basis may be useful for individuals or families with recurrent folliculitis or furunculosis (see later), although some newer data suggest that this nonirritating concentration may not truly be antibacterial. The typical recommended concentration for bleach baths is ¼ to ½ cup of bleach (around 5% to 6% sodium hypochlorite) dissolved in a full bathtub (around 40 gallons) of water.

Folliculitis barbae

Folliculitis barbae (sycosis barbae) is a term used to describe a deep-seated folliculitis of the beard area involving the entire depth of the follicle and perifollicular region ( Fig. 14.13 ). A pruritic papule is usually the initial lesion, with the process spreading from one follicle to another by trauma from scratching and/or shaving. The disorder is characterized by follicular papules and pustules and with progression, erythema, crusting, and boggy infiltration of the skin. Although occasionally other bacteria may be isolated, the etiology is usually S. aureus . The use of an electric rather than traditional razor or complete avoidance of shaving can sometimes be helpful in prevention and treatment of this condition. Warm compresses and topical antibiotics are often sufficient to control minor forms of sycosis barbae. If the condition is severe or recurrent, several weeks of systemic antibiotics may be necessary.

Pseudomonal folliculitis (hot tub folliculitis)

Pseudomonal folliculitis is a form of folliculitis caused by P. aeruginosa that occurs after exposure to poorly chlorinated hot tubs, whirlpools, or swimming pools. It has also been reported in association with a contaminated water slide, a contaminated loofah sponge, swimming in a children’s pool filled with well water, after exposure to household rubber gloves used for cleaning, and after shower or bath exposure. ^, It is characterized by erythematous, follicular pustules and vesiculopustules that occur most often on the trunk, buttocks, and legs ( Fig. 14.14 ), especially in sites occluded by swimming garments. Lesions usually develop within 1 to 2 days after exposure. Mild constitutional symptoms may be present, including fever, malaise, headache, and arthralgias. More serious associations, including urinary tract infection and pneumonia, have also been reported. ^, Lesions of hot tub folliculitis generally subside spontaneously over 7 to 10 days. Antipseudomonal antibiotic therapy (i.e., with ciprofloxacin) may be necessary in severe cases. Preventive measures include maintenance of appropriate chlorination, frequent water changes, and thorough scrubbing of whirlpool baths and hot tubs with each water change. Importantly, 21% of 108 water and swab samples of hot tubs and indoor swimming pools were positive for P. aeruginosa in one study, and 96% of these isolates were multidrug resistant. The Centers for Disease Control and Prevention recommend maintaining the concentration of free chlorine in swimming pools to between 1 and 3 parts per million (ppm) and the pH at 7.2 to 7.8.

Hot hand–foot syndrome (also known as Pseudomonas hot foot syndrome ) presents with painful, erythematous palmoplantar nodules ( Fig. 14.15 ) after exposure to water containing a high concentration of P. aeruginosa and may be seen in conjunction with hot tub folliculitis. ^, When pustules are present, the organism can be easily cultured from skin swab material. An epidemic occurred in children exposed to the same community wading pool with a floor that was coated with abrasive grit and which, along with the inlets and a drain, yielded P. aeruginosa on culture. This disorder may be related to (or the same condition as) idiopathic palmoplantar hidradenitis of childhood (see Chapter 20 ). Similar palmoplantar inflammatory lesions have been reported in otherwise healthy children infected with Mycobacterium abscessus , also in association with exposure to public swimming pools (see Nontuberculous [“Atypical”] Mycobacterial Infections section).

Eosinophilic pustular folliculitis/eosinophilic folliculitis of infancy

Eosinophilic pustular folliculitis (EPF; Ofuji disease) is a dermatosis of unknown cause characterized by erythematous patches with follicular papules and pustules, often in an annular or serpiginous arrangement, with occasional peripheral eosinophilia and leukocytosis. It was classically reported in Japanese individuals, although it may be seen in people of diverse ethnic backgrounds, and men appear to be affected more than women. Although this disorder is not bacterial in origin, it is included here because it is in the differential diagnosis of folliculitis. EPF may involve any surface area, including the face, trunk, and extremities. A form of EPF is recognized as an extremely pruritic dermatosis in adult patients with human immunodeficiency virus (HIV) infection, usually presenting late in the course of infection.

A distinct form of EPF occurs in otherwise healthy infants and toddlers and has been called eosinophilic folliculitis of infancy. It presents with recurrent crops of itchy follicular pustules of the scalp (most commonly; Fig. 14.16 ), trunk, and extremities with eventual spontaneous involution (see Chapter 2 ). The outbreaks occur in a cyclical fashion and may last from 3 months to 5 years, occasionally longer. Peripheral eosinophilia may be present. Whereas adults tend to have annular, serpiginous, or polycyclic lesions, the prominent scalp involvement and failure to form annular rings appear to distinguish the infantile form. Occasionally, eosinophilic folliculitis of infancy may be a presenting feature of the hyperimmunoglobulin-E (hyper-IgE) syndrome (see Chapter 3 ).

Treatment options for EPF include topical corticosteroids, antihistamines, oral erythromycin, dapsone, indomethacin, colchicine, topical tacrolimus, and ultraviolet B (UVB) phototherapy, which have each been used with variable success. The majority of patients respond to treatment with the former two agents; in one study of 51 patients treated with low- to medium-potency topical steroids, 46 (90%) responded well. The other treatments have been demonstrated successful but carry a greater risk of adverse effects.

Furuncles and carbuncles

Furuncles (or “boils”) are painful, deep infections of the hair follicle in which purulent material extends into the dermis and subcutaneous tissues, forming perifollicular abscesses (see earlier). These lesions have a tendency toward central necrosis and suppuration. They are caused by S. aureus and are seen most often in older children and adults. They usually develop from a preceding folliculitis with deeper extension into the dermis and subcutaneous tissue. Chronic carriers of S. aureus are particularly predisposed, and familial spread of PVL-producing MSSA isolates has been observed and may be associated with greater numbers and more intensely erythematous lesions. Furuncles caused by CA-MRSA infection have increased in incidence in the United States and are strongly related to production of the PVL virulence factor. Furuncles are most common in areas of skin that are hairy and subject to friction and maceration, particularly the back, axillae, thighs, buttocks, and perineum. They present as tender, red nodules ( Fig. 14.17 ) that gradually become fluctuant and, if untreated, may have a purulent blood-tinged discharge. There is a high rate of contagion in patients with furunculosis.

Carbuncles are larger, deep-seated staphylococcal abscesses composed of aggregates of interconnected furuncles that drain at multiple points on the cutaneous surface ( Fig. 14.18 ). They are usually seen in males on the posterior neck, back, thighs, and buttocks and extend into the deeper dermis and subcutaneous tissues, reaching a larger size than furuncles (up to 10 cm in diameter). They undergo necrosis and suppuration more slowly than furuncles and may present with severe pain and constitutional symptoms. Several factors predispose to the development of furuncles and carbuncles ( Box 14.2 ).

The treatment of furuncles and carbuncles depends on the extent and location of lesions. The mainstay of therapy is systemic antistaphylococcal antibiotics with incision and drainage of fluctuant lesions. Cultures with sensitivity testing should be considered, especially in geographic areas with an increasing prevalence of staphylococcal resistance. Lesions caused by MRSA may respond (as discussed) to incision and drainage alone. Topical antibiotics (as discussed for impetigo and folliculitis) are not sufficient for the treatment of furuncles and carbuncles, given the depth of the process. The triple regimen of chlorhexidine skin disinfection (21 days), mupirocin applied to the nares (5 days), and oral clindamycin (21 days) was found to be very effective with a prolonged remission in nearly 90% of patients in an open-label study that included patients with both MSSA and MRSA furunculosis. Many practitioners recommend dilute sodium hypochlorite baths or washes for patients with recurrent disease (see Folliculitis section). Lastly, attention to predisposing factors with appropriate treatment or modification (as feasible) is indicated.

Cellulitis

Cellulitis is an acute infection of the skin, particularly the subcutaneous tissues, characterized by poorly demarcated erythema, warmth, swelling, and tenderness. The borders of cellulitis are not elevated or sharply defined, which helps contrast it from the more superficial form called erysipelas (see Erysipelas section). Cellulitis is a common public health burden, with hospitalization frequently undertaken.

Cellulitis is a dermal and subcutaneous infection that usually occurs after some form of skin trauma, including puncture wounds, lacerations, dermatitis, burns, varicella, or dermatophyte infections. It presents with markedly red, tender, warm swelling of the skin with an infiltrated appearance ( Fig. 14.19 ), and the most common location is the lower extremities. Constitutional symptoms, including malaise and fever, are often present. The most common causes of cellulitis are S. aureus and GABHS, although occasionally other bacterial agents may be implicated. MRSA appears to be a rare cause of nonsuppurative cellulitis when extrapolated from staphylococcal patient-colonization data, although colonization may not be a primary risk factor in the pathogenesis of this infection. In young children, particularly those under 2 years of age, Haemophilus influenzae type b (Hib) was traditionally implicated in a facial cellulitis termed buccal cellulitis, although this form is now less common since licensure of the conjugated Hib vaccine. Buccal cellulitis characteristically reveals a dusky red to blue discoloration of the involved skin. Children with H. influenzae cellulitis may be quite toxic, with accompanying upper respiratory tract symptoms and bacteremia or septicemia. Streptococcus pneumoniae is another potential etiology of facial cellulitis in children, occurring especially in those under 36 months of age who are at risk for pneumococcal bacteremia. Because 96% of the serotypes (in one large series of S. pneumoniae facial cellulitis) are included in the 13-valent pneumococcal conjugate vaccine (PCV13) recommended for routine vaccination in infants 2 months of age and older (as well as the prior heptavalent conjugated vaccine), this cause of cellulitis is becoming less relevant. ^, Lastly, in children younger than 3 months of age, cellulitis is most commonly caused by group B streptococci (GBS) and is more likely to be associated with invasive disease, including bacteremia and meningitis. These children require blood, urine, and cerebrospinal fluid (CSF) sampling and cultures as part of their initial evaluation.

Periorbital cellulitis is a unique form of cellulitis that deserves special mention here, given the potential confusion with orbital cellulitis and the associated complications. Periorbital (preseptal) cellulitis is a form of the disease that presents with erythema and swelling of the periorbital tissues. It may appear after skin trauma, in which case it is usually caused by S. aureus or GABHS infection, or may result from cutaneous spread of pathogens from the paranasal sinuses or bloodstream, where it may result from Hib or S. pneumoniae infection. If the infection traverses the orbital septum (a continuation of the periosteum of the bony orbit to the margins of the upper and lower eyelids), it may result in orbital cellulitis, a more serious condition that may be complicated by abscess formation or cavernous sinus thrombosis. Patients with orbital cellulitis may experience proptosis, ophthalmoplegia, and decreased visual acuity in addition to the cutaneous findings. Computed tomography (CT) and ophthalmologic examinations are indicated if orbital cellulitis is suspected. The microbiology of periorbital and orbital cellulitis has also changed with the advent of Hib immunization, and Hib is now an uncommon cause of these disorders, being supplanted by streptococcal species (including S. pneumoniae and GABHS) and S. aureus . In a retrospective study of 85 children with periorbital or orbital cellulitis, the majority of isolates were MRSA, 85% of which were PVL positive. However, a retrospective review of 101 children in Canada diagnosed with orbital cellulitis revealed that of the 30 patients who required surgical drainage, 4 (13.3%) grew H. influenza from abscess fluid, highlighting that this pathogen still remains an occasional cause of this infection.

Treatment of cellulitis depends on the clinical presentation and knowledge (and identification, when possible) of the affecting organisms. The diagnosis of cellulitis is generally a clinical one, although fine-needle aspiration with Gram stain and bacterial culture may be helpful when unusual organisms are suspected (i.e., the immunocompromised host). Knowing the epidemiology of various etiologic agents in specific presentations and age groups is important in initiating appropriate therapy, as skin surface swab cultures may be misleading and blood cultures are usually negative (less than 8% in one large systematic review). ^, Antibiotic therapy that covers GABHS and S. aureus will be appropriate in most cases of routine, nonfacial cellulitis. Typical options for nonpurulent cellulitis (more likely to be caused by GABHS) include cephalexin, dicloxacillin, penicillin VK, amoxicillin/clavulanate, and clindamycin. ^, For patients with purulent cellulitis (more likely to be caused by S. aureus ), empiric treatment options include cephalexin, dicloxacillin, amoxicillin/clavulanate, trimethoprim-sulfamethoxazole, doxycycline, and clindamycin. ^, In geographic areas with high rates of CA-MRSA, antibiotic selection should include coverage against this organism. There is no consensus on the choice between oral and intravenous antibiotics, although blood cultures, intravenous antibiotics, and hospitalization have traditionally been recommended for children at high risk for cellulitis complications (i.e., immunocompromised), and it is recommended that patients with systemic signs of infection (temperature >38° C, tachycardia, tachypnea, or abnormal white blood cell count with >12,000 or <4,000 cells/μL) be treated parenterally. ^, Short-course intravenous antibiotic therapy has been used in emergency department (ED) settings but may be associated with a higher failure rate and longer ED stay.

In children with facial or periorbital cellulitis, the possibility of S. pneumoniae and Hib infection should be considered in conjunction with the patient’s age and immunization status, and antibiotics should be chosen accordingly. Imaging (most often contrast-enhanced CT or diffusion-weighted magnetic resonance imaging [MRI]) is recommended in these patients to define the extent of involvement and help guide appropriate therapy. In infants younger than 3 months of age with cellulitis, GBS should be presumed as a potential etiologic agent, and in these infants, as well as the patient with periorbital or orbital cellulitis who is young, toxic, or shows signs of meningeal irritation, laboratory evaluation for sepsis and meningitis should be performed. Hospitalization with parenteral antibiotic therapy (and ophthalmologic consultation in those with orbital cellulitis) is indicated in these latter settings.

Erysipelas

Erysipelas is a superficial cellulitis of the skin with marked lymphatic involvement, resulting in most cases from GABHS. The organism usually gains access by direct inoculation through a break in the skin, but occasionally hematogenous infection may occur. The initial lesion begins as a small area of erythema that gradually enlarges to reveal a characteristic warm, painful, shiny, bright red infiltrated plaque with a distinct and well-marginated border. The face, scalp, and hands are the most common sites of involvement, although erysipelas may involve any skin surface. Penicillin, or a macrolide antibiotic in patients with penicillin allergy, is the drug of choice for therapy. In occasional patients, S. aureus may be a co-pathogen, in which case antimicrobial therapy directed against this organism is necessary. Erysipelas-like erythema may occasionally be the presenting sign of familial Mediterranean fever (see Chapter 25 ).

Perianal streptococcal dermatitis

Perianal streptococcal dermatitis (PSD, also known as perianal dermatitis, perianal cellulitis, perianal streptococcal cellulitis, and streptococcal perianal disease ) is a well-defined entity that may be often overlooked. It presents as sharply circumscribed perianal erythema with occasional fissures, purulent discharge, and/or functional disturbances. GABHS is the etiology in most cases of PSD, although S. aureus and coliform bacteria have also been recovered. ^, An epidemic outbreak in a daycare center has been reported. In one series of 26 patients with perianal dermatitis, S. aureus was the most common isolate and clinically was notable for concurrent papules and pustules on the buttocks and extension of the erythema to the adjacent buttock skin.

The skin findings in PSD are variable, from a dry pink appearance to bright red erythema ( Fig. 14.20 ) with a wet surface and occasionally the presence of a white pseudomembrane. The surface is often tender to touch, and associated symptoms include rectal itching or discomfort, painful defecation, blood-streaked stools, and constipation. In males, balanoposthitis ( Fig. 14.21 ) or in females, vulvovaginitis may be present. Fever is notoriously rare in patients with PSD. Streptococcal pharyngitis may concomitantly be present in patients with PSD, but the exact associations between pharyngitis, PSD, and streptococcal colonization is unclear. There is some suggestion that specific GABHS isolates may have a tropism for perineal tissues, but the mechanism of infection is not yet clear. Guttate psoriasis (see Chapter 4 ), which is classically associated with streptococcal pharyngitis, may also be associated with PSD, and in any patient with new-onset guttate psoriasis, a thorough anogenital examination should be performed. Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS)–like presentation has been suggested as potentially linked to PSD in some children.

The differential diagnosis of PSD is broad and includes psoriasis, candidiasis, seborrheic dermatitis, cutaneous Crohn’s disease, pinworm infestation, and sexual abuse. The diagnosis can be confirmed by bacterial culture of a perianal swab, but when performing cultures to confirm the diagnosis of PSD, it is important to notify the laboratory of the microbe (GABHS) in question, because several labs utilize media selective for enteric pathogens with rectal swabs. Treatment with oral penicillin V, amoxicillin, a first-generation cephalosporin, or a macrolide or azalide (i.e., erythromycin, clarithromycin, or azithromycin) for patients allergic to penicillin is usually effective, with or without concomitant topical mupirocin. Some have suggested, however, that the risk of clinical recurrence is greater in patients treated initially with penicillin or amoxicillin. Oral cefuroxime was demonstrated to be more effective than penicillin in one study and is another reasonable option. If staphylococcal infection seems more probable clinically or is isolated in culture, the antibiotic regimen should be adjusted accordingly.

Blistering dactylitis

Blistering dactylitis (also known as blistering distal dactylitis ) is a unique bullous manifestation of GABHS infection or, occasionally, other bacteria, including S. aureus and GBS. It is rarely reported in association with MRSA infection. In its classic form, blistering dactylitis presents as a painful, tense, superficial blister on an erythematous base ( Fig. 14.22 ), most often located over the volar fat pad of the distal phalanx of a finger or several fingers. It is most common in children between the ages of 2 and 16 years, although it is also reported in adults, most notably immunocompromised ones. The blisters may occasionally extend to involve the dorsal surfaces of the fingers. Systemic manifestations, including fever, are rare. The differential diagnosis of blistering dactylitis includes bullous impetigo, herpetic whitlow, traumatic blistering, burns, and epidermolysis bullosa. Coexistent whitlow and blistering dactylitis have been reported. The diagnosis is confirmed by Gram stain and culture of blister fluid. If herpes infection is suspected, direct fluorescent antibody testing, polymerase chain reaction (PCR), or viral culture should be performed. Streptococcal blistering dactylitis is successfully treated with penicillin or erythromycin, but given recognition of the increasing role that staphylococci may play in the etiology, empiric antimicrobial therapy to cover for both organisms is recommended.