Infections due to staphylococcus aureus
Furunculosis
A furuncle is a deep-seated inflammatory nodule with a pustular center that develops around a hair follicle [see Figure 10]. With involvement of several adjacent follicles, a mass called a carbuncle may form, with pus discharging from multiple follicular orifices. This infection typically develops on the back of the neck and appears more commonly in patients with diabetes than in the general population. Moist heat is usually adequate for small furuncles, which ordinarily drain spontaneously. Incision and drainage are appropriate for large or multiple furuncles and for all carbuncles. Systemic antibiotics are unnecessary unless there is fever or substantial surrounding cellulitis.
Some patients have recurrent episodes of furunculosis. Although a few patients have definable abnormalities in host defenses, such as neutrophil disorders, most are otherwise healthy people who, like 20% to 40% of the population, carry S. aureus in the anterior nares. From this site or occasionally from the perineum or axilla, organisms can spread and enter the skin, presumably through minor, usually inapparent, trauma. Successful prevention of recurrent infection requires eradication of these bacteria from their site of residence, but most sys-temic antibiotics do not achieve adequate levels of drug in the anterior nares. An exception is clindamycin, which, when given as a single daily dose of 150 mg for 3 months, is very effective in preventing subsequent episodes.21 A less effective alternative is mupirocin ointment, applied in the anterior nares twice daily for 5 days each month.22
Figure 10 A furuncle, or boil, occurs as an acute, painful, localized staphylococcal abscess surrounding a hair follicle.
Skin infections caused by the resident cutaneous flora
The normal cutaneous flora helps prevent infection by other organisms through the mechanisms mentioned above: occupying available sites of residence, competition for nutrients, establishment of a low pH, and the elaboration of antibacterial substances. Occasionally, however, the resident skin flora causes cutaneous infections, especially with trauma or alterations in the stratum corneum. Examples are erythrasma, pitted keratolysis, trichomycosis axillaris, and most cases of cutaneous abscesses.
Cutaneous Abscesses
Cutaneous abscesses are collections of pus within the dermis and deeper skin tissues. They probably occur as a result of trauma. Sites of trauma associated with cutaneous abscesses may be apparent, as with sites of injections in illicit-drug users,23 or they may be minor and unnoticed. S. aureus, usually in pure culture, causes about 25% of cutaneous abscesses, especially in the axillae, on the hand, and on the breasts of women after childbirth.24 In other sites, however, the predominant organisms are anaerobes. Anaerobes occur either alone or in the mixture of anaerobes and aerobes that constitutes the normal regional flora; they are sometimes accompanied by microbes from adjacent mucous membranes. In anogenital infections, such as scrotal, inguinal, vaginal, buttock, and perirectal abscesses, the organisms are commonly fecal bacteria, including streptococci, anaerobic gram-positive cocci, and anaerobic gram-negative bacilli, such as Bacteroides fragilis. On the extremities, trunk, neck, and head, the usual microbes include co-agulase-negative staphylococci, anaerobic gram-positive cocci, and Propionibacterium acnes, an anaerobic gram-positive bacillus. These organisms ordinarily possess little virulence, but when introduced into the dermis or subcutaneous tissue by trauma or through a disrupted cutaneous surface, they may become pathogenic.
Cutaneous abscesses usually cause a painful, fluctuant, red, tender swelling, on which may rest a pustule. Treatment is incision and drainage of the area. Gram stain and culture of the pus are ordinarily unnecessary, as are topical antimicrobials. Systemic antibiotics are reserved for patients with extensive surrounding cellulitis, neutropenia, cutaneous gangrene, or systemic manifestations of infection, such as high fever.
Erythrasma
Porphyrin-producing coryneform bacteria, which are gram-positive bacilli that constitute part of the normal cutaneous flora, cause a superficial, usually asymptomatic, skin disorder called erythrasma. One particular species, corynebacterium minutissimum, has often been cited as the sole cause of this infection, but its precise role, if any, remains unclear. The most common site of erythrasma is between the toes, especially in the fourth interdigital space, where it causes fissuring, maceration, and scaling, resembling tinea pedis. Other locations are in-tertriginous areas, such as the axillae, groin, submammary area, and intergluteal cleft. In these regions, the lesions are usually scaly, brownish-red, sharply circumscribed patches. In hot, humid climates, more extensive disease may occur. The definitive diagnostic technique is examination of the skin with a Wood light, which, because the organisms produce por-phyrins, reveals a coral-red fluorescence. Culture of the lesions, which requires special media, is unnecessary. Because they possess some activity against gram-positive bacteria, topical azoles, such as miconazole and clotrimazole, are effective in the treatment of this infection. Topical erythromycin or clin-damycin is also effective. Oral erythromycin (250 mg q.i.d. for 2 weeks) is an alternative.25
Pitted Keratolysis
C. minutissimum and a gram-positive coccus, Micrococcus sedentarius, either alone or together, cause a disorder that may affect the soles—typically in pressure-bearing areas—or, occasionally, the palms.26 Pitted keratolysis consists of small pitted erosions about 1 to 7 mm in diameter that may be present on reddened plaques and are often more apparent after soaking in water for a few minutes. This infection occurs with increased moisture, such as caused by excessive sweating, occlusive footwear, or frequent contact with water. It appears more commonly in hot, humid climates than in more temperate ones. An impressive malodor of the feet is often apparent, and although the disorder may cause no symptoms, some patients complain of itching, tenderness, or sliminess of the feet. As in erythras-ma, topical azoles, such as clotrimazole and miconazole, are effective, as are topical erythromycin and clindamycin.
Trichomycosis axillaris
Trichomycosis axillaris is characterized by colored concretions of axillary hair that result from infection of the hair shafts by large colonies of various species of Corynebacterium. The nodules may be yellow, black, or red; and because the organisms may invade the cuticle, the hair can become brittle. The same process occasionally affects the facial or pubic hair.27 Excessive sweating, poor hygiene, and failure to use an axillary deodorant are predisposing factors. Shaving the hair is effective treatment; other options include topical erythromycin or clindamycin.
Infections due to other bacteria
Necrotizing Fasciitis
Necrotizing fasciitis, a necrotizing infection of the subcutaneous tissue, can be caused by streptococci; more often, however, the responsible organisms are a combination of aerobic bacteria—such as gram-negative enteric organisms (e.g., Escherichia coli) and gram-positive cocci—and anaerobes, including B. frag-ilis.28 Necrotizing fasciitis usually occurs after a penetrating wound to the extremities. The injury is typically deep, but sometimes, infection occurs after apparently trivial trauma, such as abrasions or lacerations. The necrotizing process may develop from extension of an adjacent infection, especially in the second most common location, the anogenital area. There, infection typically arises from a perianal abscess; as an extension of a periurethral gland infection, especially in men with urethral strictures; through retroperitoneal suppuration from perforated abdominal viscera; or as a complication of a preceding surgery. Necrotizing infection involving the genitalia is called Fournier gangrene.
These infections typically begin with fever, systemic toxicity, severe pain in the affected site, and the development of a painful, red swelling that rapidly progresses to necrosis of the subcutaneous tissue and overlying skin. Early on, the pain may appear disproportionate to the clinical findings. In some cases involving S. pyogenes infection, the characteristics of the strep-tococcal toxic-shock syndrome may appear29 [see 7:I Infections Due to Gram-Positive Cocci]. When anaerobes or certain aerobic gram-negative bacilli cause the infection, gas may form in tissues, evident as crepitus on physical examination or visible on radiographic studies. Although the disease may resemble uncomplicated cellulitis, the following signs and symptoms should suggest the presence of a necrotizing subcutaneous infection: edema beyond the apparent limits of the infection; rapid development of bullae and ecchymoses; cutaneous gangrene; fluctuance; crepitus; and radiographically visible gas. Computed tomography or magnetic resonance imaging may be helpful in some cases in detecting the infection and defining its extent. Aspiration of the affected tissue may yield purulent fluid, which on Gram stain demonstrates only gram-positive cocci in chains when S. pyogenes is responsible or reveals a variety of many different organisms when a mixed infection is present. The findings on Gram stain and culture of pus should dictate antibiotic choice, but a good initial program is gentamicin in combination with clindamycin. Most important is incision and drainage of the affected area, which should include removal of any necrotic tissue. Often, the amount of disease revealed at surgery is much greater than was apparent on the preoperative clinical examination, because the infection typically extends far beyond the borders of cutaneous inflammation. Repeat operation after 24 hours is typically prudent to detect new areas of infection and necrotic tissue.
Folliculitis
Folliculitis is an inflammation at the opening of the hair follicle that causes erythematous papules and pustules surrounding individual hairs [see Figure 11]. The most common location is the trunk. The initiating factor seems to be occlusion of the opening of the follicle, which may occur from contact with chemicals, such as oils or cosmetics; overhydration of the skin from excessive moisture; or repetitive trauma, such as friction from tight-fitting clothing, which elicits hyperkeratosis and fol-licular plugging. Subsequently, inflammation develops, which may be provoked by bacteria, yeast, or other nonmicrobial substances trapped beneath the occluded ostium.
Among bacteria, S. aureus is often suspected but rarely found. When bacteria are present in the pustules, the culture usually yields normal skin flora. In these patients, oral eryth-romycin or doxycycline may be effective in eradicating the lesions. Another cause is M. furfur, a yeast that is a normal resident on the skin. In other patients, the avoidance of oily substances on the skin or tight clothing leads to resolution of the problem.
Occasionally, Pseudomonas aeruginosa is responsible, as a consequence of inadequate disinfection of hot tubs, swimming pools, or whirlpools.30 This gram-negative bacillus grows well in hot water. Outbreaks occur an average of 48 hours after exposure, with a range of several hours to several days. Erythem-atous, pruritic papules, often with a pinpoint central pustule, appear in areas exposed to the contaminated water; lesions are particularly numerous in regions occluded by tight-fitting swimming suits. The lesions disappear spontaneously over several days, leaving no scars; ordinarily, no topical or systemic therapy is necessary. Some patients have sore throat, rhinitis, earache, and headache, but fever or bacteremia is very rare. Cultures of the skin lesions and the contaminated water usually yield the organism.
Figure 11 Folliculitis is a superficial or deep inflammation of the hair follicles, appearing at follicular openings as small pustules surrounded by erythema (a). Folliculitis may also occur as an isolated lesion (b).
Cutaneous Anthrax
Spores of Bacillus anthracis sent through the mail in the fall of 2001 as an act of bioterrorism caused cases of inhalational and cutaneous anthrax in several states. Otherwise, anthrax has been very rare in the United States over the past few decades. Ordinarily, this bacterium resides in the soil, where it forms spores that can persist for years. When ingested— primarily by herbivores (cattle, horses, sheep, and goats) grazing on contaminated land—these spores may cause infection. This veterinary disease is most frequent in tropical and subtropical areas, but extensive vaccination can markedly diminish its frequency.
Except for cases associated with bioterrorism [see 8:V Bioter-rorism], humans usually develop anthrax from exposure to affected animals or their products, such as hides. Occasional laboratory-acquired cases also occur. The cutaneous form develops when spores enter the skin through abrasions and then transform into bacilli, which produce toxins that cause local tissue edema and necrosis. Macrophages can transport spores to regional lymph nodes, but bacteremia is uncommon. After an incubation period of about 1 to 7 days, a painless, pruritic papule forms at the entry site, most commonly the head, neck, and extremities. Over the next few hours the lesion enlarges, and a ring of erythema may form around it. In 1 to 2 days, vesicles appear, surrounding the papule and containing numerous bacteria but few neutrophils. Painless, gelatinous, nonpitting edema then encircles the lesion, often spreading extensively to adjacent skin and soft tissue [see Figure 12]. This pronounced edema is especially characteristic of anthrax. After enlarging, the vesicles become hemorrhagic and rupture. In the depressed center of the lesion, a black eschar forms and sloughs within 1 to 2 weeks, leaving a shallow ulcer that heals with minimal, if any, scarring. In the early days of illness, patients commonly have headache, malaise, and fever. Regional lymph nodes often enlarge, causing pain and tenderness.
Diagnosis B. anthracis, a broad, encapsulated gram-positive rod, is visible on Gram stains of material from a skin lesion as single organisms or chains of two or three bacilli. It grows readily at 37° C on blood agar media. Skin biopsies reveal necrosis, hemorrhage, and massive edema. Organisms are demonstrable with tissue Gram stain or immunohistochemical staining for the bacteria’s cell wall antigen. Because it requires acute and convalescent blood specimens, serologic testing for antibodies to B. anthracis is unhelpful for immediate diagnosis but may establish a retrospective diagnosis of suspected but unconfirmed cases.
Treatment Treatment for cutaneous anthrax unassociated with bioterrorism is penicillin V (500 mg q.i.d. orally) or amoxicillin (500 mg t.i.d. orally) for mild cases and, for more severe disease, penicillin G (6 to 8 million units I.V. daily). For penicillin-allergic patients or cases arising from bioterrorism, the recommended therapy is oral ciprofloxacin (500 mg b.i.d.) or doxycycline (100 mg b.i.d). Antibiotic therapy does not alter the course of eschar formation and healing, but it does decrease the risk of systemic disease. Ordinarily, the duration of therapy is 7 to 10 days, but the recommended regimen for cases associated with bioterrorism is 60 days because of the possibility of simultaneous aerosol exposure.31
Figure 12 Cutaneous anthrax lesion, seen on the seventh day after infection.
Viral Infections
Warts
Warts, or verrucae, are caused by human papillomaviruses (HPVs), a subgroup of DNA-containing papovaviruses, of which there are more than 70 types. Humans are the only known reservoir; transmission probably occurs from close contact with infected people or possibly from exposure to sloughed, infected epidermal cells. The virus presumably enters through small breaks in the skin. The incubation period is difficult to discern but is probably several months. Autoinocu-lation from one portion of the body to another also occurs. Cell-mediated immunity appears important in controlling these infections, which can be very extensive and refractory to treatment in immunocompromised patients.
Verrucae vary according to location. They include the common, elevated wart (verruca vulgaris), typically appearing on the hands; the flat wart (verruca plana), on the face and legs; the moist wart (condyloma acuminatum), in the anogenital area; and the callus-covered plantar wart (verruca plantaris), on the sole of the foot. A histologic feature that distinguishes a wart from other papillomas is the presence in the upper epidermis of large, vacuolated cells that contain numerous viral particles.
Verruca Vulgaris
The common wart consists of single or multiple skin-colored papules, which often have a hyperkeratotic, papillary surface. They are commonly present on the fingers. The estimated nationwide prevalence of hand warts is 3.5% for people 18 to 64 years of age; the greatest frequency (5.5%) occurs in men 18 to 24 years of age. The warts may be filiform, with a small base and a thin projection of several millimeters, especially on the face.
Liquid nitrogen is a common initial treatment of choice for many warts. Administered with a cotton-tipped applicator or cryospray device, liquid nitrogen freezes the lesion, causing it to blister and subsequently dissolve. More than one application at 2- to 3-week intervals may be necessary for large or periun-gual warts. Electrodesiccation and curettage or laser surgery are effective for persistent or recurrent lesions.
Verruca Plana
The flat wart is a skin-colored or light-brown, slightly elevated, smooth papule commonly seen on the face and the dorsum of the hand. These may be difficult to treat, but freezing with liquid nitrogen, application of trichloroacetic acid, or painting the lesions with 10% salicylic acid and 10% lactic acid in flexible collodion may be effective.
Verruca Plantaris
The plantar wart is often painful and disabling. A mosaic wart, a variant of verruca plantaris, consists of multiple discrete or confluent superficial lesions and is often difficult to treat. A plantar wart that is covered by a callus can be distinguished from an ordinary callus by paring off the surface keratin; multiple, pinpoint dots, representing thrombosed vessels, or bleeding points from surface capillaries will become apparent if it is a wart. Paring of the wart can be followed by immediate treatment with liquid nitrogen, the application of strong acid (50% trichloroacetic acid), or the nightly administration of salicylic acid in plasters, an acrylic vehicle, or collodion.
Figure 13 Condyloma acuminatum may appear as a large cauliflower-like mass that resembles a malignant tumor.
Condyloma Acuminatum
Anogenital warts consist of skin-colored or gray, discrete or confluent cauliflower-like excrescences that may cause no symptoms or produce itching, burning, pain, or tenderness [see Figure 13]. The incidence is highest in young adults; most often, it is a sexually transmitted disease, though some anogenital warts may develop from autoinoculation or may be acquired in other ways.
Infection with some types of HPV predisposes to malignancy. Most cases of squamous carcinoma of the cervix are caused by HPV, especially HPV-16 and HPV-18, but fortunately, these types represent only a small percentage of the isolates from anogenital warts. Genital verrucous carcinoma, also called giant condyloma acuminatum of Buschke-Lowenstein, is a low-grade genital malignancy caused by HPV-6 and HPV-11. Squamous carcinoma of the anus is associated primarily with HPV-16.
Anogenital warts may be difficult to eradicate, and several treatments are often necessary.33 Therapies administered by clinicians include liquid nitrogen, podophyllin resin, trichloro-acetic or bichloroacetic acid, surgical removal, laser therapy, or intralesional interferon. Patient-applied treatments are podo-phyllotoxin, which the patient applies twice daily for 3 days, or imiquimod cream, used at bedtime three times a week for up to 16 weeks. Another approach involves fluorouracil (5-FU) cream administered twice daily for 1 to 3 weeks. This medication is particularly suitable for large wart plaques and warts of the ure-thral meatus, but side effects, including discomfort and painful erosions, are common.
Figure 14 Benign lesions of bowenoid papulosis, as seen on the shaft of the penis, may histologically resemble carcinoma in situ.
Bowenoid Papulosis
Bowenoid papulosis consists of benign-appearing erythem-atous or pigmented papules in the anogenital area that histo-logically resemble Bowen disease (squamous cell carcinoma in situ) [see Figure 14]. Its course, however, is not aggressive, and the papules should be treated as anogenital warts (see above). HPV-16 is a common cause, however, and malignancy does occasionally develop, especially in women.
