Supported by an unrestricted educational grant from Lederle, a division of Wyeth-Ayerst Laboratories

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Volume III, Issue 2 - October 1996

Impetigo contagiosa is caused by Streptococcus pyogenes and bullous impetigo is due to Staphylococcus aureus. Both skin lesions may have an early bullous stage but then appear thick and crusty with a golden brown color. Streptococcal lesions are most common in children 2 to 5 years of age. Epidemics may occur in settings of poor hygiene and particularly in children from lower socioeconomic conditions in tropical climates. It is important to recognize impetigo because of its relationship to post-streptococcal glomerulonephritis. Both types of impetigo heal without scarring. Ecthyma, also caused by S aureus or S pyogenes, may begin as a vesicle or bullae but promptly evolve to a crusted appearance with superficial ulceration. Like impetigo, ecthyma is most common in patients with poor hygiene.

Superficial dermatophyte infections (eg, ringworm) can occur on any skin surface and are diagnosed by skin scrapings stained with KOH. Primary dimorphic fungal infections such as blastomycosis and sporotrichosis initially appear as crusted skin lesions resembling dermatophyte infections although they are usually associated with enlargement of one or several proximal lymph nodes. Similarly, disseminated Coccidioides immitis commonly involves skin. Biopsy and culture should be performed on crusted lesions in patients who have traveled to or inhabited an area where C immitis is endemic.

Infections associated with vesicle formation are caused by viral proliferation within the epidermis. Varicella vesicles have a "dew drop on a rose petal" appearance and occur in crops randomly about the trunk, extremities, and face over the course of 3 to 4 days. Herpes zoster occurs in a single dermatome and is preceded by pain several days before the appearance of vesicles. Zoster occurs predominantly in elderly patients and AIDS patients, whereas 95% of varicella cases occur in young children. Vesicles due to Herpes simplex are found on or around the lips (Herpes simplex I) or genitals (Herpes simplex II) but may appear on the head and neck in young wrestlers (Herpes gladitorum) or on the digits (Herpetic whitlow) in healthcare workers. Coxsackie A-16 characteristically causes vesicles on the hands, feet, and mouth in children. Orf is caused by a DNA virus related to smallpox and infects the digits of individuals who work around goats and sheep. Smallpox is currently only of historical significance due to great international cooperation spearheaded by the World Health Organization and the availability of a simple but effective vaccine.

Staphylococcal scalded-skin syndrome (SSSS) occurs predominantly in neonates and is caused by a toxin from phage group II S aureus. SSSS must be distinguished from toxic epidermal necrolysis (TEN), which occurs primarily in adults, is drug-induced and has a higher mortality. Punch biopsy with frozen section is useful since the cleavage plane in SSSS is the stratum corneum whereas in TEN it is the stratum germinativum. Necrotizing fasciitis and gas gangrene also induce bullae formation early in their course. Halophilic vibrio infection can be as aggressive and fulminant as necrotizing fasciitis. Helpful clues are a history of exposure to water from the Gulf of Mexico or Atlantic seaboard or a patient with cirrhosis who has ingested raw seafood.

Hair follicles serve as entry portals for a number of bacteria, although S aureus is the most common cause of localized folliculitis. A furuncle or boil begins as a localized folliculitis that slowly progresses to form an intracutaneous abscess with a pustular center. A carbuncle is composed of several contiguous furuncles. Styes and chalazions, abscesses of the eyelid, are associated with hair follicles and usually caused by S aureus. Sebaceous glands empty into hair follicles and if ducts become blocked (sebaceous cyst) may resemble staphylococcal abscesses or may become secondarily infected. Hidradenitis suppurativa can also mimic infected hair follicles particularly in the axillae. Chronic folliculitis is uncommon except in acne vulgaris where normal flora (eg, Propionibacterium acnes) plays a role.

Diffuse folliculitis occurs in two distinct settings. The first, "hot-tub folliculitis" is caused by Pseudomonas aeruginosa in water insufficiently chlorinated and maintained at temperatures between 37 degrees and 40 degrees C. Infection is self-limited although bacteremia and shock have been reported. The second type of diffuse folliculitis occurs when a skin surface is exposed to water infested with freshwater avian schistosomes. Warm water and alkaline pH are suitable for the free-swimming miracidia--the intermediate host between snail and man. Miracidia readily penetrate hair follicles or pores but quickly die. These dead miracidia elicit a brisk allergic reaction causing intense itching and erythema.

Erysipelas, caused exclusively by S pyogenes, is characterized by an abrupt onset of fiery, red swelling of the face or extremities. Distinctive features are its well-defined margins, particularly along the nasolabial fold, rapid progression, and intense pain. Flaccid bullae may develop during the second to third day of illness but extension to deeper soft tissues is rare. Surgical debridement is rarely necessary and treatment with penicillin is effective. Swelling may progress despite appropriate treatment, although fever, pain, and the intense red color diminish. Desquamation of the involved skin occurs 5 to 10 days into the illness. Infants and elderly adults are most commonly afflicted and the severity of systemic toxicity may vary. Erysipelas may be less severe today than older reports from the turn of the century.

Cellulitis is an acute inflammatory skin condition characterized by localized pain, erythema, swelling, and heat. Bacteria may gain access to the epidermis through cracks in the skin, abrasions, cuts, burns, insect bites, surgical incisions and intravenous catheters. Cellulitis caused by S aureus spreads centripetally from a localized infection such as an abscess, folliculitis, surgical incision, or foreign body (ie, a sliver, prosthetic device, or intravenous catheter). In contrast, cellulitis due to S pyogenes is a more rapidly spreading, diffuse process frequently associated with lymphangitis and fever. Infection may follow a skin abrasion, insect bite, chickenpox, burn, or foreign body. However, an entry portal may not be evident. Recurrent streptococcal cellulitis of the lower extremities may be caused by Group A, C, or G streptococci in association with chronic venous stasis, saphenous venectomy for coronary artery bypass surgery, or chronic lymphedema resulting from elephantiasis, lymph node dissection, or Milroy's disease. Recurrent staphylococcal cutaneous infections are more common in individuals who have eosinophilia and elevated serum levels of IgE (Job's syndrome) and among nasal carriers of staphylococci.

Streptococcus agalactiae causes cellulitis in patients with diabetes mellitus or peripheral vascular disease. Haemophilus influenzae causes periorbital cellulitis in children in association with sinusitis, otitis media, or epiglottitis. It is unclear whether this form of cellulitis will become less common, as has meningitis, due to impressive efficacy of the H influenzae type B vaccine. Many other bacteria also cause cellulitis. Fortunately these occur in such unique settings that a good history provides useful clues for diagnosis. Cellulitis associated with cat bites and, to a lesser degree, dog bites, is commonly caused by Pasteurella multocida, although in the latter case Staphylococcus intermedius and DF-2 (Capnocytophaga canimorsus) must also be considered. Cellulitis and abscesses associated with dog and human bites also contain a variety of anaerobic organisms. Pasteurella is notoriously resistant to dicloxacillin and nafcillin but sensitive to all other b-lactam antimicrobials as well as quinolones, tetracycline, and erythromycin. Ampicillin/clavulanate, ampicillin/sulbactam, and cefoxitin are good choices for animal or human bite infections due to their activity against the above organisms, anaerobes in general, and Eikenella corrodens in particular. Aeromonas hydrophila causes a very aggressive cellulitis in tissues surrounding lacerations sustained in freshwater lakes, rivers, and streams. This organism remains sensitive to aminoglycosides, fluoroquinolones, chloramphenicol, trimethoprim/sulfamethoxazole, and third-generation cephalosporin. It is resistant to ampicillin, however.

Pseudomonas aeruginosa causes three types of soft-tissue infections: ecthyma gangrenosa in neutropenic patients, hot-tub folliculitis, and cellulitis following penetrating injury. Most commonly, P aeruginosa is introduced into the deep tissues by stepping on a nail and this scenario is referred to as the sweaty tennis shoe syndrome. Treatment includes surgical inspection and drainage, particularly if the injury also involves a bone or joint capsule. Choices for empiric treatment pending antimicrobial susceptibility data include aminoglycosides, third-generation cephalosporins (ceftazadime, cefoperazone, or cefotaxime), semisynthetic penicillins (ticarcillin, mezlocillin, or piperacillin) or fluoroquinolones, though the latter drugs are not indicated in children less than age 13. Gram-negative rod cellulitis, including P aeruginosa described above, is most common in hospitalized immunocompromized hosts. Cultures and sensitivities are critically important because of multidrug resistance.

Erysipelothrix rhusiopathiae, which causes cellulitis in bone renderers and fish mongers, remains susceptible to penicillin, erythromycin, clindamycin, tetracycline, and cephalosporins. It is resistant to sulfonamides and chloramphenicol. Fish food containing the water flea, Daphne, is contaminated with Mycobacterium marinum which may cause cellulitis or granulomas on skin surfaces exposed to the water in aquariums and following injuries in swimming pools. Rifampin plus ethambutol has been an effective treatment in some, although no comprehensive studies have been undertaken. In addition, some strains of M marinum are susceptible to tetracycline or trimethoprim/sulfamethoxazole.

The etiology of cellulitis can be suspected based upon the epidemiologic data supplied above. Where there is drainage, an open wound or an obvious entry portal, Gram stain and culture provide a definitive diagnosis. In the absence of these findings, the bacterial etiology of cellulitis is difficult. Even with needle aspiration of the leading edge or punch biopsy of the cellulitis itself, cultures are positive in only 20% of cases. This suggests relatively low numbers of bacteria may cause cellulitis and the expanding area of erythema within the skin may be the direct result of extracellular toxins or soluble inflammation mediators elicited by the host.

Necrotizing fasciitis, formerly called streptococcal gangrene, may be associated not only with Group A streptococcus but also with mixed aerobic/anaerobic bacteria or as part of gas gangrene caused by Clostridium perfringens. Early diagnosis may be difficult since pain or unexplained fever may be the only presenting symptom and sign, respectively. Next, swelling followed by brawny edema and tenderness develop. With progression, dark red induration of the epidermis appears along with bullae filled with blue or purple fluid. Later, skin becomes friable and takes on a bluish, maroon, or black color due to extensive thrombosis in blood vessels supplying the dermal papilla. Infection spreads rapidly along fascial planes and through venous and lymphatic channels. Necrotizing fasciitis due to mixed aerobic/anaerobic bacteria but not S pyogenes may have gas in the deep tissue. Patients in the later stages are toxic and frequently manifest shock and multiorgan failure. Prompt surgical exploration down to the deep fascia and muscle is essential. Necrotic tissue must be surgically removed and a tissue Gram stain performed to establish whether Group A streptococcus, mixed aerobic/anaerobic bacteria, or clostridium species are present (see gas gangrene below).

Necrotizing fasciitis caused by mixed aerobic/anaerobic bacteria begins with a breach in integrity of a mucous membrane barrier such as the mucosa of the gastrointestinal or genitourinary tract. The cause can be carcinoma, diverticulosis, thrombosed hemorrhoid, anal fissure, or a urethral tear. Frequently, necrotizing fasciitis develops in patients with peripheral vascular disease, diabetes mellitus, or following either surgery or penetrating injury to the abdomen. Leakage into the perineal area results in a syndrome called Fournier's gangrene which is characterized by massive swelling of the scrotum and genitals with extension into the perineum, anterior abdominal wall, and lower extremities.

Necrotizing fasciitis caused by S pyogenes has increased in frequency and severity since 1985. Streptococcal necrotizing fasciitis often begins deep at the site of nonpenetrating minor trauma such as a bruise or muscle strain. Seeding of the site by transient bacteremia is likely although most deny antecedent streptococcal infection. Toxicity is severe and in 25% to 30% of patients renal impairment may precede the development of shock. In 20% to 40% of cases of streptococcal necrotizing fasciitis, myositis occurs concomitantly so, as in gas gangrene (see below), serum creatinine phosphokinase values may be markedly elevated.

Muscle involvement can occur in relation to bacterial infection; virus infection: influenza, dengue, Coxsackievirus B (pleurodynia); or parasitic invasion: Trichinella spiralis (trichinosis), Taenia solium (cysticercosis), Toxoplasma gondii (toxoplasmosis). Although myalgia can occur in most of these infections, severe muscle pain is the hallmark of pleurodynia, trichinosis and bacterial infection. Acute rhabdomyolysis predictably occurs with bacterial infection but may also be associated with influenza, echovirus, Coxsackievirus B, and Legionella.

Pyomyositis is usually due to S aureus, common in tropical areas and rare in temperate climates, and often without a known portal entry. Risk factors in nontropical areas include diabetes mellitus, collagen vascular disease, and immunosuppression. Infection remains localized and unless strains produce toxic shock syndrome toxin 1 or certain enterotoxins shock does not occur. Because these infections are deep, there is frequently no cutaneous erythema or warmth, although tenderness and swelling are usually present. In contrast, S pyogenes may induce a primary myositis referred to as streptococcal necrotizing myositis, associated with severe systemic toxicity. Patients frequently have bacteremia, shock, and organ failure. Such infections have recently been described as part of the streptococcal toxic shock syndrome.

Gas gangrene usually occurs following penetrating injuries severe enough to result in introduction of soil into wounds and an interrupted blood supply. Such cases of traumatic gangrene are usually caused by Clostridium perfringens, Clostridium septicum, or Clostridium histolyticum. Rarely, latent or recurrent gangrene can occur years after penetrating trauma likely due to dormant spores that reside at the previous injury site. Spontaneous nontraumatic gangrene has recently been recognized more frequently among patients with neutropenia, gastrointestinal malignancy, diverticulosis, or following abdominal radiation therapy. These cases are caused by C septicum, a spore-forming Gram positive anaerobe that is much more aerotolerant than C perfringens. This latter factor likely explains why the organism can initiate infection in normal tissue anywhere in the body.

Early, aggressive surgical debridement is necessary for survival and provides important diagnostic material. Antibiotic choices for mixed aerobic and anaerobic necrotizing infections would include ampicillin/sulbactam or cefoxitin as single agents, or combinations such as ampicillin, gentamicin, and clindamycin; or ampicillin/sulbactam, gentamicin, and metronidazole. Severe Group A streptococcal infections as well as gas gangrene caused by C perfringens or C septicum should respond to a variety of penicillins based upon in vitro susceptibility data. Yet, in experimental models of both infections, penicillin lacks efficacy. Interestingly, clindamycin has much greater efficacy, partly due to its ability to suppress toxin synthesis, resist the inoculum effect, and be indifferent to growth stage of the organism.

Infections of the skin and soft tissue offer the astute clinician a rewarding challenge. Using simple tools such as a history, physical examination, radiographic procedures, and appropriate microscopic examination, a definitive diagnosis can readily be made. However, as the virulence of pathogens wax and wane, as antibiotic resistance progresses, and as host responsiveness changes as a result of immunocompromising diseases, we will forever be challenged to describe novel presentations, new etiologies and innovative treatments.

Dennis L. Stevens, PhD, MD
Chief, Infectious Disease Section
Veterans Affairs Medical Center
Boise, Idaho
Professor Of Medicine
University Of Washington
Seattle, Washington

Suggested Reading

1. Cellulitis and superficial infections. In: Principles and Practice of Infectious Diseases. New York: Churchill Livingstone, 1990:796-807.
2. Clostridial infections. In: Atlas of Infectious Diseases. Philadelphia: Ch