Elizabeth Talbot, Laura Elyse Shevy Skin and soft tissue infections (SSTIs) are among the most common reasons for which patients seek outpatient care and require antibiotics. Such visits have increased over the last several years to now exceed 6.3 million annually.1 Health care providers who know the clinical presentation of SSTIs, their causative pathogens, and local antibiotic susceptibility patterns will maximize treatment efficacy and avoid inducing resistance to the limited armamentarium of antimicrobial therapies available. The management of SSTIs is best conceptualized on the basis of the presence or absence of pus. Purulent SSTIs include abscesses, furuncles, and carbuncles; nonpurulent SSTIs include erysipelas and necrotizing fasciitis.1 Cellulitis may cross these categories because it may be secondary to skin ulcers or other lesions that themselves produce pus, and so cellulitis is further subdivided into purulent and non-purulent types. This chapter reviews all the SSTIs, although emphasis is placed on the diagnosis and management of cellulitis. Purulent SSTIs include abscesses, furuncles, and carbuncles. Abscesses are collections of pus that may be within the dermis or deeper layers. Typically they are painful or tender to palpation and appear as raised lesions that may be fluctuant, red, and/or nodular. There is often a central pustule with erythematous margins, which represents inflammation rather than spreading infection (i.e., cellulitis). Epidermoid cysts are collections of keratinous material and usually contain skin flora; these may also become inflamed and rupture into the dermal layer. Furuncles, commonly known as boils, are infections that arise at the hair follicle and extend deep into the dermis, where an abscess forms. This is distinguished from folliculitis, which extends only as deep as the epidermis. A carbuncle forms when several adjacent furuncles coalesce, forming an inflammatory mass with pus draining from multiple follicles. These are seen more frequently in persons with diabetes. Most often, skin abscesses are polymicrobial infections, consisting of bacteria from local skin flora and the adjacent mucous membranes. Approximately 25% of the time, Staphylococcus aureus may occur as a mono-pathogen. Furuncles and carbuncles are most commonly caused by S. aureus. Community-acquired (CA) methicillin-resistant S. aureus (MRSA) rates are dependent on local resistance patterns. In the setting of severe immunocompromise, such as patients with neutropenic fever or human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) with depressed CD4 count, or among patients with tropical travel, animal bites, and other exposures, the differential diagnosis of these SSTIs is extensively expanded, and consideration should be given to involving infectious disease specialists.2 Nonpurulent SSTIs include impetigo, ecthyma, erysipelas, and cellulitis; cellulitis is discussed later. Impetigo is a toxin-mediated skin infection caused by S. aureus or Streptococcus causing dermal-epidermal junction cleavage. Ecthyma is a deeper infection, also typically caused by S. aureus and Streptococcus species. Initially, vesicular lesions rupture and form round erythematous crusting ulcers that often are surrounded by erythema and edema. Owing to the depth of these lesions, a scar forms. Erysipelas is an SSTI limited to the superficial dermis including lymphatics, whereas cellulitis involves the deeper dermis and subcutaneous fat. These terms are often used interchangeably, especially in Europe, but erysipelas is most correctly distinguished from cellulitis by the former’s restriction to the superficial dermis and lymphatics.1 In contrast, cellulitis rapidly spreads and extends deeply from the dermis to the subcutaneous tissue. When it is left untreated, cellulitis may progress to more severe soft tissue infection and osteomyelitis and may even become limb- or life-threatening.2 Cellulitis typically begins when pathogens find a portal of entry through nonintact skin, as is seen after traumatic laceration; at sites of diabetic, vascular, or other types of skin ulceration; in chronic dermatoses with skin breakdown such as macerated tinea pedis; surgical wound infections; or even at sites of insect bites. Cellulitis may, however, develop with no recognized trauma in otherwise normal-appearing skin. Predisposing risk factors for cellulitis include venous or lymphatic compromise from previous episodes of cellulitis, peripheral edema, previous radiation to an affected area, history of lymph node resection, lymphedema such as occurs after radical mastectomy and lymph node dissection in the upper extremity, and obesity. Most cases of cellulitis and erysipelas in adults are caused by group A β-hemolytic streptococci. Non–group A streptococci are more likely pathogens in patients with underlying abnormalities of the lymphatic system, such as lymphedema. S. aureus is less likely to be causal but should be considered in the setting of penetrating trauma, sites of injection drug use, surgical site infections, indwelling catheter skin infections, or other preexisting open wounds.1 Other pathogens may also be implicated in cellulitis, when cellulitis occurs as a complication of animal bites, with injuries occurred in fresh water or saltwater, or in immunocompromised hosts. The Infectious Diseases Society of America classifies the severity of SSTIs into mild, moderate, and severe.1 A mild SSTI is defined as occurring in an immunocompetent patient with hemodynamic stability who appears nontoxic: patients with these infections can typically be treated on an outpatient basis with appropriate incision and drainage, and often without need for antibiotics. Moderate SSTIs are those occurring in an immunocompetent patient with systemic symptoms and signs. Severe SSTIs are defined as those (1) refractory to oral antibiotics and, if purulent, refractory to incision and drainage; (2) in patients demonstrating hemodynamic alteration including temperature higher than 38° C, heart rate greater than 90, respiratory rate greater than 24, leukocytosis greater than 12,000 or leukopenia below 400 cells/µL; and (3) in immunocompromised patients. In general, moderate and severe SSTIs require admission for management. The common initial presentation of impetigo is vesiculopustular or even bullous lesions. When the lesions rupture and exude their contents, they create the classic honey-colored crusts. Clinically, erysipelas tends to have more clearly demarcated borders of inflammation than cellulitis. Either may have lymphangitic streaking present. The most commonly affected areas in erysipelas include the lower legs, face, and ears (the ears have no dermis; therefore, superficial infection of the ears is erysipelas by default). Facial erysipelas may follow a streptococcal infection of the upper respiratory tract.3 The lower extremity is the most common site of cellulitis, although it can occur anywhere. The initial clinical presentation of cellulitis is characterized by spreading erythema, induration, warmth, and pain and may be associated with systemic symptoms such as fevers, chills, and malaise.1,2 Bullae, abscesses, erosions, necrosis, and even focal areas of hemorrhage manifesting as ecchymosis or petechiae may develop within cellulitis. The site of entry of the bacteria may be evident as breaks in the skin or ulcerations. Careful inspection of the interdigital areas is crucial in the physical examination for lower extremity cellulitis, because macerated tinea pedis may have provided the portal of entry for bacteria. Left untreated, this predisposes to recurrent cellulitis. Regional lymph nodes may be enlarged and tender, a condition called lymphadenitis. Lymphangitic streaking may occur in the direction of a regional lymph node. Edema of the area can manifest as dimpling of the overlying skin, called peau d’orange (orange peel). For mild and apparently uncomplicated infections, only Gram stain and culture of the drained purulent material need be performed. In typical cases of SSTIs, empirical treatment may also be tried without such data. Epidermoid cysts need not be cultured. Microbiologic diagnosis should be undertaken in moderate or severe infections, for those refractory to current antibiotic treatment,1 and in cases involving multiple sites of infection, cutaneous gangrene, or extensive surrounding cellulitis. Appropriate additional laboratory investigations include complete blood count (CBC) with differential, creatinine, bicarbonate, creatine phosphokinase, and blood cultures.1 If a definitive microbiologic diagnosis is not readily evident from the Gram stain and cultures of purulent material or via blood cultures, other potential methods for identifying the pathogen(s) include needle aspirate, punch biopsy, and material sent from intraoperative procedures, should surgical consultation be necessary. Diagnosis is largely by clinical recognition. The causal pathogen may be determined by culturing any existing vesicular fluid, pus, ulcer, or erosions; this is indicated to evaluate bacteriology and susceptibility patterns. If no obvious cultivable source is present, however, empirical treatment is pursued. Punch biopsy for pathology may be necessary if noninfectious causes are in the differential diagnosis. Laboratory investigations are not warranted in otherwise healthy children and adults with cellulitis. Blood cultures have been found to be of low yield, identifying the causal organism 5% or less of the time.4,5 The yield of skin biopsy for culture is also low in nonpurulent SSTIs (around 20%), so isolation of the causative agent is usually not attempted in otherwise healthy adults, and treatment is empirical (see later). However, blood cultures and cultures of any pus or bullae are more useful and should be performed in patients with moderate to severe nonpurulent SSTI, extensive body surface involvement, underlying comorbidities including immunodeficiencies, previous splenectomy, diabetes, lymphedema, malignancy, neutropenia, specific exposures such as animal bites or water-associated injuries, and recurrent or refractory cellulitis. In patients with longer-standing disease or in whom more deep-seated infection is suspected, radiography may be helpful to evaluate for underlying osteomyelitis and even occult abscess. Although radiographs may delineate subcutaneous emphysema in gas-producing infections, they do not have sufficient sensitivity to reliably detect necrotizing fasciitis or gas gangrene and should not delay emergent surgical management of such clinically apparent infections. Because SSTIs have a variety of causes and corresponding management, a detailed history of exposures and comorbidities is key for developing a pathogenic differential diagnosis. Such history includes areas of residence, detailed travel history, immune status, recent surgeries, trauma, antimicrobial therapy, hobbies, lifestyle, and animal and animal bite exposures. Mimics of purulent SSTIs (i.e., abscesses, furuncles, and carbuncles) include bursitis (infectious or inflammatory), inflamed epidermoid cyst, tophaceous gout, and other inflammatory processes. The differential diagnosis of erysipelas and cellulitis includes other infections such as bursitis, osteomyelitis, erythema migrans, and herpes zoster, as well as inflammatory conditions including eczema, psoriasis, contact dermatitis, urticaria, and erythema nodosum. Other potential noninfectious mimics include stasis dermatitis, deep venous thrombosis, thrombophlebitis, acute gout, drug reactions, insect bite or sting hypersensitivity, and neoplastic changes.1 More severe, life-threatening infections, such as necrotizing fasciitis, gas gangrene, staphylococcal scalded skin syndrome, and toxic epidermal necrolysis, must also be differentiated from cellulitis. Cellulitis may also be superimposed on concurrent skin disease, such as stasis dermatitis, hemosiderin staining, and lipodermatosclerosis associated with venous insufficiency. The purulent skin infections as well as purulent bursitis may manifest with surrounding inflammatory changes clinically reminiscent of cellulitis. However, these infections are primarily purulent SSTIs, and the local erythema is more likely a result of inflammation than active infection. Differential Diagnosis Cellulitis
Cellulitis
Definition and Epidemiology
Pathophysiology
Purulent Skin and Soft Tissue Infections
Nonpurulent Skin and Soft Tissue Infections
Clinical Presentation and Physical Examination
Purulent Skin and Soft Tissue Infections
Nonpurulent Skin and Soft Tissue Infections
Diagnostics
Purulent Skin and Soft Tissue Infections
Nonpurulent Skin and Soft Tissue Infections
Differential Diagnosis
Purulent Skin and Soft Tissue Infections
Nonpurulent Skin and Soft Tissue Infections
