A 24-year-old man who regularly bites his fingernails accidentally tears out a small piece of the corner of the nail on his right index finger. The damaged skin starts to bleed lightly, so the man presses on the area with a tissue until the bleeding stops. Two days later, the man notices that the finger has become infected. A small area of skin near the corner of the nail is red and swollen. The skin is yellowish-white in the center of this area, where the swelling is most noticeable. The man, who knows just enough about infections to be dangerous, opts to treat himself. He "lances" the center of the swollen area with a needle that he sterilized by heating it in a candle flame. Pus then oozes out of the opening, confirming the presence of infection. The man presses and squeezes the area around the infection to force as much of the pus out the injured area as he can. He removes the exuded pus with a sterile cotton ball, cleans the finger with a topical antiseptic (Bactine) and covers the area with a small bandage.

Five days later, the man develops a fever and severe pain in his forearm. His arm is swollen, red, and warm to the touch, so he gets worried and goes to the nearby walk-in clinic for advice. On examination, he appears sweaty and hot. His temperature is 40.4ºC. There is a patchy red rash with poorly delineated edges on his right arm. The rash extends from the elbow to the shoulder. Lymph nodes in the axilla are enlarged and tender. The physician takes the patient's recent history and learns about the nail infection incident.

Question 3.1: What is your diagnosis?

Most microbial diseases that affect the skin characteristically produce well defined lesions (vesicles, pustules, papules, bullae, crusted lesions, etc.), rather then the diffuse reddening of the skin that is present in this case. If this is a microbial problem, then, the lack of defined lesions should help to narrow the diagnosis considerably. One possibility that fits the symptoms quite closely is cellulitis, an acute inflammatory condition of the skin (subcutaneous tissue) that is characterized by localized pain, erythema, swelling, and heat. The fact that the patient recently had a pyogenic (pus-producing) infection in the same arm is also suggestive because infections like this can lead to septicemia and other consequences, such as cellulitis.

Question 3.2: What are the most likely causative agents?

Over 90% of cellulitis cases are caused by Staphylococcus aureus and group A streptococci (primarily Streptococcus pyogenes). In other words, most cases are caused by indigenous microbial species that colonize the skin and appendages. Staphylococcal and streptococcal cellulitis sometimes present with nearly identical symptoms, so it may be difficult to distinguish between them on the basis of clinical observations alone. As a rule, though, cellulitis caused by S. aureus tends to spread out directly from a central localized infection (at the point of entry into the skin), such as an abscess, folliculitis, or infected foreign object (e.g., a splinter or an indwelling intravenous catheter). In contrast, S. pyogenes cellulitis is often a more rapidly spreading, diffuse process, in which the visible skin symptoms do not necessarily surround or extend directly from the original point of entry into the skin. S. pyogenes cellulitis is also more likely to be associated with fever and lymphangitis (inflammation of the lymphatic vessels). The symptoms of this case, then, are more characteristic of S. pyogenes cellulitis than S. aureus cellulitis, but it not possible to certain without additional information.

Question 3.3: How can you identify the causative agent?

If there is drainage, an open wound, or an obvious portal of entry, you can usually get definitive information by Gram staining and culturing material from the affected area. (The portal of entry isn't always apparent in cellulitis cases, especially those caused by streptococci.) In the absence of these opportunities, you can do needle aspiration of the leading edge of the reddened area or a punch biopsy of the cellulitis tissue itself in hopes of obtaining a useful specimen for the lab, but cultures from these samples are positive in only about 20% of cases. This observation may mean that relatively low numbers of bacteria can cause cellulitis and that the expanding area of redness within the skin is primarily a reaction to extracellular microbial toxins or mediators of inflammation (e.g., cytokines) that are produced by host in response to the presence of the microorganism. Cellulitis may be accompanied by bacteremia, so it is generally worth ordering a blood culture in addition to the above procedures.

Test Results:

In the present case, the original site of infection on the patient's finger sill contained some fluid, so this was sampled and cultured. Blood cultures were ordered as well. The lab isolated S. pyogenes from both samples.

Question 3.4: Does this agent cause any similar diseases?

S. pyogenes is the primary cause of erysipelas, which also produces superficial, spreading, warm, erythematous areas on the skin. However, the lesions associated with erysipelas are usually quite distinct in appearance from those that occur with cellulitis. They are indurated and have elevated margins. In addition, the margins of the lesions are sharply demarcated from the surrounding unaffected tissues. Other skin diseases caused by S. pyogenes are not similar to cellulitis or erysipelas because they either produce distinct pustules or involve the extensive destruction of muscle and fat tissue.

Question 3.5: What other agents cause this disease?

As noted earlier, >90% of cellulitis cases are endogenous; that is, they are caused by members of the normal microflora on the skin, primarily S. aureus and S. pyogenes. Haemophilus influenzae type b has also been associated with cellulitis (primarily periorbital cellulitis in children), but this may change with continued use of the vaccine. A wide variety of exogenous bacteria (organisms that are not member of the normal skin flora) can cause cellulitis as well. These causative agents tend to occupy unique niches in nature and, thus, are generally associated with different specific sources of infection. As a result, a detailed patient history that includes relevant epidemiological data can provide important clues about the etiology of exogenous infections. For example, cellulitis associated with dog or cat bites or scratches is often caused by Pasteurella multocida, while cellulitis related to a deep, penetrating wound (e.g., one caused by stepping on a nail) is often associated with Pseudomonas aeruginosa.