A 42-year-old man who works for a local construction contractor develops a sizeable and painful swollen area on the back of his neck. The swollen area is painful and large enough that it causes him considerable discomfort if he tries to button his shirt collar. A mild fever adds to the man's discomfort, so he comes to your walk-in clinic for advice.

His vital signs are normal, except for some fever (38.9ºC). The swollen area on his neck is located at the hairline and measures 2.4 x 3.7 cm. The center of this area is somewhat soft to the touch and appears to contain a substantial amount of pus. The overall appearance of the swollen area is that of an unusually large pustule surrounded by a distinct rash. There are no other remarkable physical findings.

The man is asked about his medical history. He remembers that, several days ago, his wife noticed some minor irritation surrounding the hair follicles in the area that is now swollen. Except for occasional appearances of boils on his skin over the past few years, the man has enjoyed very good health.

Question 4.1: What is your diagnosis?

The physical appearance, location, and impressive size of the man's swollen area are highly suggestive, as is the fact that this problem may have started out as folliculitis (inflammation around hair follicles). The man most likely has a carbuncle, an unusually large, typically pus-filled, skin lesion that frequently develops on the back of the neck, especially in middle-aged or elderly men. The man's history of occasional boils on the skin is consistent with this diagnosis.

Question 4.2: What tests should you do?

If you want to confirm the diagnosis, the easiest approach is to obtain some fluid from the lesion and send it to the lab for Gram staining and culturing.

Test Results:

Aspiration of the center of the man's lesion with a needle yielded nearly 1.5 ml of pus. A Gram stain of this material revealed the presence of numerous Gram-positive cocci that tend to occur in clusters of cells. The lab cultures a Gram-positive, coccoid bacterium from the pus sample. It is catalase positive and coagulase positive. The lab identifies the isolate as Staphylococcus aureus.

Question 4.3: How did this infection come about?

Most staphylococcal skin infections are caused by endogenous flora; that is, strains of S. aureus that are harbored in the nose or other sites of colonization. The bacterium may be transported to the skin (on fingers, towels, or whatever), or it may simply be resident on the skin. (Individuals vary in regard to whether their normal skin flora includes S. aureus, as well as in the density of S. aureus cells that may be present. This man's history of boils may indicate that he does harbor S. aureus on his skin, possibly in relatively high numbers.) In any event, the bacterium manages to enter a hair follicle and grow there, where it is somewhat protected from the human body's usual defense mechanisms. Growth of the bacterium results in the formation of a microabscess within the follicle, eventually leading to inflammation of the surrounding area and eruption of pus. This condition is called folliculitis. If it is not controlled, the abscess may enlarge to form a furuncle, which is better known as a common boil. When a number of boils form in close proximity (because several adjacent hair follicles become infected at the same time), they may cluster together to produce a large, muiltifocal infection, and this is the carbuncle seen in the present case.

Question 4.4: What is the pathologic process that leads to abscess formation?

Abscess formation is initiated when tissue is destroyed by the invading bacterium. This triggers a massive influx of neutrophils, some of which die and release lysosomal enzymes that cause further tissue damage. The infected region is then walled off from the surrounding healthy tissue as coagulase produced by S. aureus catalyzes the deposition of fibrin and as fibroblasts are stimulated to produce a fibrous capsule. The result is a well contained, but also quite well organized, infection that contains a mixture of necrotic white blood cells and large numbers of bacterial cells (commonly known as pus).

Question 4.5: Is this a dangerous disease?

Staphylococcal infections are generally confined to the skin. However, carbuncles are relatively deep lesions that cause intense inflammation of surrounding and underlying connective tissue. If untreated, they can lead to septicemia and, less often, osteomyelitis.

Question 4.6: What other problems does this agent cause?

S. aureus is one of those bacteria that can produce an almost unbelievably wide range of diseases in the human body. Aside from those mentioned above, diseases that affect the skin in one way or another include scalded skin syndrome, Ritter's disease, bullous impetigo, cellulitis, and (only rarely) erysipelas. Strains that can produce certain types of exotoxins can cause toxic shock syndrome (TSS) or staphylococcal food poisoning. Respiratory tract infections caused by S. aureus include staphylococcal pneumonia, pleural empyema, pharyngitis, tracheitis (mostly in children), and chronic sinusitis (especially sphenoid sinusitis). S. aureus infections of the central nervous system include purulent meningitis, brain abscesses, subdural empyema, spinal abscesses, intracerebral epidural abscesses, and septic intracranial thrombophlebitis. S. aureus is also associated with endovascular infections (acute endocarditis and other vascular diseases), bacteremia (which can lead to many of the other infections listed here), musculoskeletal infections (acute osteomyelitis, chronic osteomyelitis, septic arthritis, septic bursitis, pyomyositis, etc.), and urinary tract infections (relatively rare; mostly associated with indwelling urinary catheters).

Question 4.7: What virulence factors does this agent possess?

As might be expected from the wide variety of diseases that this bacterium can cause (above), S. aureus possess a host of virulence factors. Structural components that act is important virulence factors include the capsule (avoidance of phagocytosis), peptidoglycan (endotoxin-like activity), and protein A (inhibits antibody-mediated clearance). Toxins produced by S. aureus include various cytotoxins that kill leukocytes, erythrocytes, macrophages, fibroblasts, etc. (cytotoxins alpha, beta, delta, and gamma; PV leukocidin); exfoliative toxins (ETA, ETB), enterotoxins (A -E, G - I); and the toxic shock syndrome toxin (TSS-1). S. aureus enzymes that can be important in pathogenesis include coagulase (fibrin clot formation), hyaluronidase (spreading factor; allows rapid spread of bacterium through tissues), lipases (degrades lipids), nucleases (degrades DNA), and penicillinase (degrades penicillin). S. aureus strains vary in regard to the number of and specific combination of virulence factors they possess. As a result, they also vary in regard to the severity and range of diseases that can produce in humans.

Question 4.8: How should you treat this case?

An abscess like this should be incised and drained of pus. This should be followed by systemic administration of an antibiotic that is effective against S. aureus. Unfortunately, the more or less relentless spread of antibiotic resistance among strains of S. aureus is one of the most significant challenges facing clinicians today, especially since the appearance of methicillin resistant strains (MRSA), some of which are now resistant to vacomycin as well. The current regimen of choice for carbuncles is nafcillin 1-2 g IV q4h (for severe infections with systemic toxicity) or dicloxacillin or cephalexin 250-500 mg PO quid (for milder infections). Alternative treatments include cefazolin 1 g IV q8h, clindamycin 600 mg IV q8h or 300 mg PO tid, vancomycin 1 g IV q12h (if the patient has severe penicillin allergy, or if MRSA is suspected). Antibiotic therapy should be continued until the infection is fully resolved (usually 7-10 days).

Question 4.9: What is the prognosis?

In all likelihood, the man will make a full recovery with minimal scarring of the skin. However, furuncles can be recurring (and frustrating) problem, as demonstrated by this patient's history of previous boils. If he tends to have recurrent development of boils, then there is entirely possible that another carbuncle will develop at some point in the future.