A previously healthy, fully immunized, 2-year-old girl presented with fever for 7 days in addition to progressive fatigue, fussiness, decreased appetite and a limp. In the 24 hours before presentation, she had difficulty sitting up, refusal to walk and 2 episodes of emesis. She did not have any upper respiratory symptoms, conjunctivitis, mucosal changes, rash, bowel or bladder dysfunction, urinary symptoms, diarrhea, lymphadenopathy or extremity swelling.
An exposure history revealed no known ill contacts, no known tuberculosis exposures, no recent travel outside of the family’s residence in the Sierra Foothills of California, no animal exposures other than the family’s indoor pet cat, no known tick bites and no intake of unpasteurized dairy products. Her medical history was largely unremarkable except for minor dental trauma 1 month before presentation, which resulted in immediate oropharyngeal bleeding and ultimately a necrotic tooth. The tooth was monitored by her dentist without treatment and had fallen out on its own before admission. Family history was also unremarkable.
Upon initial examination, the child was ill appearing and irritable but consolable by parents. She had a temperature of 39.7 °C, heart rate of 153 beats/min, respiratory rate of 28 breaths/min, blood pressure of 100/62 mm Hg and oxygen saturation level of 100% in ambient air. She had dry lips and a dry tongue without associated erythema. She had no evidence of conjunctivitis. Her neck was supple and without cervical adenopathy. Her abdomen was soft and nontender with normal bowel sounds and no palpable masses. Extremities were nonedematous with full range of motion. She was able to ambulate but had a limp favoring her left leg. She had no other neurologic deficits. No rash or abnormal skin findings were present.
Laboratory investigations showed a white blood cell count of 15,000/mm3 with 68.8% neutrophils, 21.2% lymphocytes and 8.9% monocytes; hemoglobin of 9.4 g/dL and platelet count of 268/mm3. Her C-reactive protein was 301.3 mg/L, procalcitonin was 34.4 ng/mL and erythrocyte sedimentation rate was 75 mm/h. Chemistry panel showed a sodium of 132 mEq/L, potassium of 3.4 mEq/L, protein of 6.2 g/dL, albumin of 3.1 g/dL, alanine aminotransferase of 22 U/L and aspartate transaminase of 16 U/L. A respiratory viral panel was negative. Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction and coronavirus disease 2019 IgG antibodies were negative. Radiographs of the pelvis, right femur, right tibia/fibula and right ankle were all normal. Bilateral hip ultrasound (US) showed no effusion or abscess. She was admitted for further investigation and was treated empirically with intravenous cefazolin for suspected osteoarticular infection.
After admission, she had persistent fevers and refusal to bear weight despite antibiotics. Further laboratory investigations were performed including HIV-1 p24 Ag and HIV-1/2 antibodies (negative), Bartonella IgM/IgG antibodies (negative), Francisella tularensis IgG antibody (negative) and Brucella IgM/IgG antibodies (negative). Blood cultures from admission remained negative. Further imaging and biopsy revealed the diagnosis.
For Denouement see P. 604.
(Pediatr Infect Dis J 2022;41:604–605)
Continued from P. 603.
Despite an initial concern of a bone or joint infection, difficulty localizing the focus by clinical examination and a lingering suspicion of alternative diagnoses led to the decision to perform a full-body magnetic resonance imaging (Fig. 1). There was no evidence of either osteomyelitis or septic arthritis, but a solitary, well-circumscribed, heterogeneous hepatic mass measuring 6.3 cm by 5.9 cm by 5.3 cm was found. Additional laboratory tests were sent. Lactate dehydrogenase was slightly elevated (474 U/L), and serum alpha-fetoprotein was normal (<0.6 ng/mL). Coccidioides IgM/IgG antibodies and Echinococcus granulosa IgG antibody were all negative.
Due to concern for hepatoblastoma, the patient underwent US-guided liver biopsy, which yielded several milliliters of thick, opaque and sanguineous fluid. Tissue samples revealed histologic features indicative of a pyogenic liver abscess (PLA). Cultures grew a moderate amount of Streptococcus intermedius, susceptible to penicillin; no anaerobes were isolated. A subsequent US-guided abscess drainage removed an additional 20 mL of thick serosanguinous and purulent fluid. Repeat cultures again grew a viridans Streptococcus; no further speciation was performed as this was assumed to be the same isolate as the initial culture. An immunodeficiency evaluation including quantitative immunoglobulins, T- and B-cell subsets and neutrophil oxidative index was normal. The patient was treated with a total of 2 weeks of parenteral cefazolin and was transitioned to oral amoxicillin at discharge. By 6 weeks after presentation, therapy was discontinued as her examination and inflammatory markers had returned to normal. A repeat abdominal US at 2 months after presentation demonstrated complete resolution of her abscess.
S. intermedius is one of 3 streptococcal species along with S. anginosus and S. constellatus that make up the S. anginosus (formerly S. milleri) group, a type of viridans streptococci. These organisms are Gram-positive, catalase-negative cocci as well as nonmotile facultative anaerobes that have variable hemolysis patterns on sheep blood agar and are often associated with a butterscotch or caramel-like smell. They are widely known as commensal flora of various mucosal sites including the oropharynx, gastrointestinal tract, female genitourinary tract and respiratory tract; however, they are becoming increasingly known for their ability to act as serious, and at times fatal, pathogens. Of the 3 species, S. intermedius is the most likely to lead to abscess formation and, in particular, has been associated through multiple case reports and retrospective studies with the development of brain and liver abscesses.1–4
Specific bacterial characteristics and virulence factors that contribute to S. intermedius’ propensity for abscess development include the expression of hydrolytic enzymes, like hyaluronidase, which allow for tissue liquefaction and pus formation; encapsulation, which aids in preventing phagocytosis; superantigen expression, which results in lymphocyte apoptosis and biofilm formation, which decreases antibiotic susceptibility. S. intermedius also contains the unique virulence factor, intermedilysin, a cytolytic toxin, which makes it a strictly human-specific pathogen.2–5
Although the relationship between pyogenic infections and the S. anginosus group has been described in the literature, the occurrence of PLA of any etiology, particularly in the pediatric population, is exceedingly rare with 1 case study citing an incidence between 0.007% and 0.04% of all hospital admissions per year.6 The prevalence of particular microorganisms causing PLA varies depending on geographic location, age of the patient and presence of underlying risk factors.7,8 In general, the majority of PLA are due to Klebsiella pneumoniae (particularly in Asia), Escherichia coli, Staphylococcus aureus, S. anginosus group and Entamoeba histolytica. Polymicrobial PLA are most common in adults, whereas S. aureus and S. anginosus appear to be most common in pediatric populations.6,8–10
The majority of PLA cases described in children have been in either immunocompromised patients (especially patients with chronic granulomatous disease, HIV, diabetes, sickle cell disease, hepatobiliary/pancreatic disease or liver transplant) or patients from developing countries.6–9 As such, an immune evaluation is warranted in any pediatric patient with a liver abscess, particularly evaluation for chronic granulomatous disease. There have been, however, a handful of pediatric PLA cases in immunocompetent children, including cases secondary to S. intermedius.6,9
Most liver abscesses in pediatric patients result either from direct extension from the biliary/intestinal tract or from hematogenous spread.2,8,11 Our suspicion is that our patient’s abscess resulted from hematogenous seeding following her dental accident with tooth necrosis that occurred 1 month before the onset of her symptoms. A retrospective pediatric study in Mexico identified S. intermedius as the second most common cultivable isolate (6 of 21 samples) from primary teeth with necrotic pulps.12 In addition, this pathogenesis is consistent with the handful of case reports in the adult literature describing S. intermedius liver abscesses associated with concurrent dental infection and/or recent dental procedures. Reddy et al13 described a 50-year-old immunocompromised patient with S. intermedius PLA after having 2 teeth extracted 1 month before admission in the absence of other identifiable sources for possible infectious origin. Neumayr et al14 and Wagner et al15 described 2 separate cases of S. intermedius PLA associated with active dental disease: a healthy 18-year-old with multiple liver abscesses in the setting of pyogenic dental infection with an open root canal and an immunocompetent 39-year-old without significant comorbidities who had liver and brain abscesses in the setting of aggressive periodontitis with S. intermedius isolated from oral smear, liver and ventricular drainage and blood cultures. Lastly, there have been 2 reports of S. intermedius PLA associated with routine dental cleanings in the last 8 years: a 21-year-old immunocompetent patient who presented 3 months after a dental cleaning in septic shock secondary to S. intermedius bacteremia and multiple associated liver abscesses and a 65-year-old African American patient with hypertension, peptic ulcer disease, reflux disease and history of cholecystitis and choledocholithiasis who was found to have PLA 11 months after a tooth extraction and 1.5 months after a routine dental cleaning; both blood and fluid cultures were positive for S. intermedius.16,17
Clinical features of PLA are typically nonspecific and include fever (89.6%), chills (69%) and abdominal pain (72.2%). However, only about 30% of patients present with all 3 symptoms.6,18 We did not identify any prior reports, adult or pediatric, in which the presenting symptoms for PLA were fever and limp, as was the case with our patient. This atypical presentation, which was suggestive of a bone or joint infection, adds to the uniqueness of our case and emphasizes the importance of maintaining a broad differential for fever of unknown etiology.
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