Staphylococcal infections pose an important and increasingly complex problem for children and their physicians; we present a case of septic thrombophlebitis in an otherwise normal teenager.
Most neonates are colonized within the first week of life and 20% to 30% of healthy people carry at least 1 strain of Staphylococcus aureus in their nares. Autoinfection is common; minor infections, such as sties, pustules, and paronychia, may be the source of disseminated disease. It has been noticed that disseminated disease characterized by fever, persistent bacteremia despite antibiotics, and focal involvement of 2 or more separate tissue sites, occurs more commonly in young adolescent boys.1
Recently, more and more of community-acquired S. aureus is methicillin resistant and makes the approach to staphylococcal infections more challenging.
A 16-year-old Hispanic adolescent boy presented to the emergency department at Monmouth Medical Center with the chief complaint of left ankle and lower leg pain associated with limping, left foot swelling, and fever. Intermittent left ankle pain began 6 months before the visit and had gradually increased in severity and radiated to the leg. He also had a furuncle on the dorsal aspect of the left elbow that first appeared 5 days before the visit.
The patient is an immigrant who, despite being a teenager, was not attending school but was working in construction. He denied trauma to the ankle or working with a jackhammer. There was no other significant history.
On physical examination, his vital signs were the following: heart rate, 142 beats per minute; blood pressure, 152/75 mm Hg; and respirations, 24/min. He was well nourished and of muscular build: height, 175 cm; weight, 75 kg; and body mass index, 23 (75%). Positive findings included 2 × 2-cm ulceration with yellowish bloody discharge, erythema, edema, tenderness and cellulites of the left elbow, swelling of the left ankle, calor, tenderness of the medial aspect of the ankle, and limited range of motion of the joint but no erythema. No swelling or tenderness of the lateral ankle was noted.
Initial laboratory studies included the following: complete blood count/white blood cell count, 12,900; 63% neutrophils; 29% bands; 4% lymphocytes; 3% monocytes, 240,000 platelets; hemoglobin, 14.1 g/dL; hematocrit, 41.8; sedimentation rate, 30 mm/h; and C-reactive protein, 329 mg/dL. Cultures of the blood and elbow drainage were obtained. Synovial fluid was aspirated from the left ankle: red blood cell counts, 2600 cells/μL; white blood cell counts, 4725 cells/μL; 87% neutrophils; 1% lymphocytes; and 12% monocytes. The Gram stain and culture were negative.
The patient was admitted to the pediatric ward; ampicillin/sulbactam was started for a presumptive diagnosis of osteomyelitis versus septic arthritis. A few hours after admission, the blood culture was reported to be positive for gram-positive cocci, as was the elbow abscess culture. Antibiotics were changed to nafcillin and vancomycin. Magnetic resonance imaging of the left lower leg was done and was suggestive of myositis and fasciitis; the bone marrow was normal.
The patient remained febrile and tachycardic. An echocardiogram was performed to evaluate cardiac function; results were normal, and no vegetations were found. Later on the same day, the patient became hypotensive and was transferred to the intensive care unit with the diagnosis of early septic shock, soft tissue abscess around the elbow, and possible fasciitis or myositis. The patient underwent surgical exploration of the left leg. The fascia and muscles seemed normal; cultures and biopsies were obtained. Biopsy showed chronic focal inflammation of fibroadipose tissue and muscle and some evidence of focal chronic myositis. Special stains for bacteria and fungal and acid-fast organisms were negative. Staphylococcus aureus was recovered from cultures of blood, elbow discharge, leg tissue, and from a blood culture obtained 24 hours after admission. The isolates were susceptible to nafcillin, so vancomycin was discontinued. Activated protein C was started as treatment for septic shock.
Monitoring for drug toxicity consisted of frequent complete blood counts and monitoring of electrolytes, serum urea nitrogen, and creatinine and vancomycin levels; no evidence of toxicity was identified.
The patient required intubation and assisted ventilation because of acute respiratory distress syndrome and staphylococcal pneumonia as demonstrated by infiltrates and the development of pneumatoceles. Chest tubes were inserted because of the development of pneumothoraces. Additional studies were pursued to look for an intravascular focus: a left lower extremity deep vein thrombosis (DVT) was documented by Doppler ultrasound. The patient received anticoagulation therapy. An evaluation for coagulation disorders was negative.
For the next 2 weeks, the patient improved and underwent skin grafting of the left lower leg and physical therapy. He was discharged in good health on hospital day 41. Warfarin was continued. He remained well with no evidence of recurrence of infection or thrombosis for the next 6 months.
Staphylococcal infection causes a varied spectrum of diseases in children. However, disseminated disease is rare in healthy children. In the literature published in the 1950s through 1970s, there are reports of severe staphylococcal septicemia that were associated with serious underlying disease, intravenous drug abuse, or recent antibiotic or immunosuppressant therapy.2,3 In 1976, Shulman and Ayoub1 reported a series of 9 cases of severe disseminated staphylococcal sepsis during a period of 3 years in healthy 8- to 15-year-old children without risk factors. Similar to our patient, all but one had lung involvement, and two of them had skin lesions (1 upper lip furuncle and 1 toe infection). Fifty percent of the patients also had osteomyelitis.
The term acute disseminated staphylococcal disease (DSD) was first used by Hieber et al4 in 1977. The disease occurs primarily in previously healthy children aged 5 to 15 years, progresses rapidly, and carries mortality rates of 13% to 27%.5,6 The diagnostic criteria of DSD are infection at 2 or more anatomical sites and the isolation of S. aureus from the blood or from a site of infection. Lungs, bones, and joints are the most common organs involved in DSD, followed by skin and muscles, kidneys, liver, central nervous system, and heart.6
Many strains of S aureus release various exotoxins. Exotoxins act on cell membranes and may produce aggregation of platelets and spasm of smooth muscle. A variety of enzymes are released by staphylococci-among them, coagulase, which specifically interacts with fibrinogen and causes plasma to clot. These factors may predispose to the development of DVT adjacent to osteomyelitis caused by S aureus. Gorenstein et al7 reported 3 children who developed a triad of DVT, septic pulmonary embolus, and acute osteomyelitis with S. aureus recovered from blood and bone. In their study, they suggest that infected DVT with septic pulmonary embolism had a pivotal role in the development of DSD in these children. We did not document osteomyelitis in our patient; we expected it based on the leg swelling and adjacent serous arthritis. Ultrasound Doppler is sensitive in detecting DVT in the thigh and popliteal areas.8 Phlebography can detect both distal and proximal thrombi in the femoral and iliac veins. A high index of suspicion for this triad, prompt diagnosis, and aggressive treatment with appropriate antibiotics, anticoagulation, surgical drainage, and assisted ventilation when indicated are the cornerstones for potential cure in this life-threatening syndrome. Gonzalez et al9 reported on a series of 14 previously healthy adolescents with staphylococcal sepsis and coagulopathy. Most of the infections in that study were caused by methicillin-resistant S. aureus, and all the strains including the methicillin-sensitive S. aureus strains were carrying the Panton-Valentine leukocidin (PVL) gene. Yamasaki et al10 noted that young adolescents with PVL-carrying strains are more likely to have multiple furuncles, and the intensity of the erythema around the furuncles was more pronounced. The PVL gene-positive S. aureus is strongly associated with necrotic skin lesions and community-acquired pneumonia.10-12 Gonzalez et al9 noted that, although severe staphylococcal septicemia has been associated with serious underlying disease, intravenous drug use, or immunosuppressive therapy, there are few reports about staphylococcal septicemia in healthy adolescents in the absence of predisposing factors, as in our case. Interestingly, they also report a history of blunt trauma, as minor as fall from a bed and stumbled on a carpet, in 57% of their patients.
In our case, we believe that the initial event was the DVT of the left leg that, although unusual in healthy adolescents, could have been related to his occupation as a construction worker. It is possible that he had multiple minor injuries for which the patient did not seek medical attention either because he had no health insurance or because he is an adolescent and is therefore less likely to pay attention to his health condition.
In our case, the clinical hint was the persistently positive blood cultures (3 days), despite appropriate antibiotic therapy. This suggested an intravascular infection. After endocarditis was excluded as a diagnosis, DVT was identified. Septic thrombophlebitis explains the subsequent disseminated infection.
We report this case to emphasize the need to consider DVT in healthy children and adolescents.
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