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Pulmonary, Critical Care, and Sleep Pearls |

A 19-Year-Old College Student With Headache, Photophobia, and Flulike Illness FREE TO VIEW

Mohamed Ramez Mourad, MD; Olivia M. Siwoski, MD; Kyle R. Brownback, MD
Author and Funding Information

aDivision of Pulmonary and Critical Care Medicine, University of Kansas Medical Center, Kansas City, KS

bDepartment of Internal Medicine, University of Kansas Medical Center, Kansas City, KS

CORRESPONDENCE TO: Kyle R. Brownback, MD, University of Kansas Medical Center, Division of Pulmonary and Critical Care Medicine, 3901 Rainbow Blvd, Mail Stop 3007, Kansas City, KS 66160


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2017;151(4):e95-e98. doi:10.1016/j.chest.2016.10.047
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Published online

Case Presentation  A 19-year-old previously healthy man presented, minimally responsive, in respiratory distress to an ED after a 2-week history of headache, photophobia, and neck stiffness. Associated symptoms included low-grade fevers, malaise, and dark urine. He had no recent travel, ill contacts, consumption of undercooked meat, new sexual contacts, or illicit drug use. The patient resided in a campus dormitory and did not consume alcohol or tobacco.

Figures in this Article

The patient required intubation and admission to the ICU. He was aggressively volume resuscitated for hypotension and started on broad-spectrum antibiotics and vasopressors. Because of persistent tachycardia, fever, and leukocytosis with worsening renal function, he was transferred to our hospital 3 days after presentation.

Vital signs on arrival at our facility: BP, 80/50 mm Hg; heart rate, 114 beats/min; respiratory rate, 37 breaths/min; oxygen saturation, 90% on mechanical ventilation. He was somnolent, but responsive to voice. Assessment of head, eyes, ears, neck, and throat: eyelid edema bilaterally; neck supple, with no lymphadenopathy or jugular venous distention. Cardiac: palpable precordial heave, rapid but regular rhythm, and no murmurs, rubs, or gallop. Chest: bilateral crackles without wheezes. Abdomen: mildly distended but nontender to palpation, with spleen palpable 2 cm below the costal margin. Extremities: trace pedal edema, unremarkable skin.

The CBC revealed the following: hemoglobin, 10.7 g/dL; WBC count, 14.7 K/μL; platelet count, 72 K/μL. His basic metabolic panel showed the following: sodium, 132 μM; potassium, 4.5 μM; chloride, 102 μM; carbon dioxide, 19 μM; BUN, 64 mg/dL; and creatinine, 5.02 mg/dL. Total bilirubin was elevated to 3.2 mg/dL but liver-associated enzymes were normal. Troponin was 0.22 ng/mL and lactate was 1.5 mM. Urinalysis revealed turbid urine with 2+ proteins, 3+ blood, and no leukocytes or bacteria. Cerebrospinal fluid study results were unremarkable. Blood culture results were positive for Fusobacterium necrophorum.

An ultrasound assessment of the jugular veins produced normal results. A CT scan of the chest showed multiple peripheral nodular opacities (Fig 1). A CT scan of the abdomen revealed enteritis and a hepatic lesion compatible with a hemangioma or abscess. MRI confirmed the presence of a hepatic abscess (Fig 2).

Figure 1
Figure Jump LinkFigure 1 CT scan of the chest, revealing multiple pulmonary nodules consistent with septic emboli.Grahic Jump Location
Figure 2
Figure Jump LinkFigure 2 MRI of the abdomen, demonstrating, within the left lobe of the liver, a heterogeneous hyperintense mass (arrow) measuring 4.5 × 3.0 cm.Grahic Jump Location

Despite initiation of meropenem and linezolid, the patient continued to spike fevers daily and renal function worsened. Further testing demonstrated elevated ferritin at 926 mg/dL, and a bone marrow biopsy was performed, demonstrating increased histiocytosis with hemophagocytosis.

What is the diagnosis?

Diagnosis: Enteritis with Fusobacterium necrophorum sepsis and hemophagocytic lymphohistiocytosis

Fusobacterium necrophorum is a gram-negative anaerobic bacillus that was first isolated from animals in the late nineteenth century. This organism is an inhabitant of the gastrointestinal tract in humans and is responsible for 21% of cases of pharyngitis and 23% of peritonsillar abscesses. It is also found within the oral cavity and vagina. Fusobacterium may cause invasive infections following disruption of mucosal barriers induced by viral or other bacterial infections, and uses lipopolysaccharides to enhance its virulence. One of the classic presentations of Fusobacterium necrophorum infection is Lemierre syndrome, also known as postanginal shock, defined as septic thrombophlebitis of the internal jugular vein. This syndrome most commonly afflicts young adults, with 51% of patients in their second decade of life. Common presenting symptoms include fever, rigors, and pharyngitis. These patients have cervical lymphadenopathy and internal jugular vein thrombophlebitis, which may progress to septic emboli and septic shock. The diagnosis is confirmed by blood cultures growing Fusobacterium necrophorum in an anaerobic blood culture bottle and evidence of thrombosis of the internal jugular vein on ultrasound examination.

Additional presentations of Fusobacterium necrophorum include a wide spectrum of infections, ranging from bacteremia to empyema and osteomyelitis. Fusobacterium species are the second most common cause of pyogenic hepatic abscess. In contrast to patients with classic Lemierre syndrome, many patients with Fusobacterium bacteremia are older and with underlying malignancies, typically arising from the gastrointestinal tract. Fusobacterium species are routinely components of polymicrobial infections, including abscesses of the skin, liver, and brain. Common coexisting bacterial species include Peptostreptococcus, Prevotella, Bacteroides, and Streptococcus.

First-line therapy for Fusobacterium infections is carbapenem antibiotics, although metronidazole or penicillin/β-lactamase inhibitor combinations may be used. Surgical debridement and drainage of abscesses are often necessary. As many of these infections are polymicrobial, using broad-spectrum antibiotics with coverage of coexisting gram-negative bacilli and anaerobic bacteria should be routine practice. Most patients with Lemierre syndrome require prolonged hospitalization in addition to intensive care, with an overall mortality rate of 5%. The prognosis is quite variable in the spectrum of other fusobacterial infections.

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of abnormal activation and proliferation of morphologically benign macrophages and lymphocytes, leading to a massive cytokine storm that induces intense inflammation and end-organ failure that can potentially be life-threatening. It can be divided into two different clinical scenarios: primary HLH and secondary HLH. Primary HLH, also known as familial hemophagocytic lymphohistiocytosis, is a heterogeneous autosomal recessive disorder seen in pediatric populations, with 70% of cases occurring before the age of 1 year. Mutations are found in genes encoding perforin and syntaxin in these cases, with an incidence of 1 in 50,000 with equal sex distribution. Secondary HLH can occur after strong immunologic activation in adult patients, such as systemic infection and malignancy. There has been one prior report of HLH occurring secondary to fusobacterial infection. There are no specific data on the incidence of secondary HLH, given the heterogeneity of this process, but it is thought to be underrecognized.

Diagnosis of secondary HLH requires fulfillment of five of eight criteria: fever, splenomegaly, cytopenias involving two of three cell lineages in peripheral blood, hypertriglyceridemia, ferritin > 500 ng/mL, hemophagocytosis seen in the bone marrow or lymph nodes, low natural killer cell activity, and soluble interleukin (IL)-2 receptor > 2,400 U/mL. Treatment of secondary HLH consists of managing the underlying process with potential addition of corticosteroids and etoposide. HLH, if untreated, is potentially fatal, with a mortality rate of 8% to 24% depending on the causative factor and presence of comorbidities. Outcomes are particularly poor when HLH is associated with an underlying malignancy, with an average survival of 1.4 months following diagnosis.

Clinical Course

The patient presented with Fusobacterium necrophorum bacteremia and was found to have septic pulmonary emboli and hepatic abscess. The primary source was likely the gastrointestinal tract, given the diffuse enteritis seen on the abdominal CT scan and lack of preexisting pharyngitis or thrombophlebitis on serial imaging. As he failed to defervesce on appropriate antibiotics and had progressive renal failure and cytopenias, we determined the patient’s ferritin level to screen for HLH, and found it to be significantly elevated. A bone marrow biopsy was performed, which revealed normocellular bone marrow as well as increased histiocytosis with hemophagocytosis, consistent with the diagnosis of HLH. In addition, the patient had an increased concentration of the α-chain of soluble IL-2 receptor, further supporting the diagnosis of HLH. Because of the patient’s tenuous clinical state and severe septic shock, etoposide was not given and the patient was started on dexamethasone alone. Following this intervention, the patient’s fevers and heart rate slowly trended down as did his ferritin, triglycerides, WBC count, liver enzymes, and creatinine. The hepatic abscess was drained percutaneously, and culture results remained negative. The patient was subsequently extubated, weaned of vasopressors, and transferred out of the ICU. He transitioned to ertapenem with plans to continue antibiotics for 4 weeks as an outpatient. He was started on an oral dexamethasone taper and was discharged after a 3-week hospitalization to home.

  • 1.

    Fusobacterium necrophorum is a rare cause of sepsis, with presentations including bacteremia, pharyngitis, tonsillar abscess, septic emboli, and hepatic abscesses that may afflict immunocompetent patients.

  • 2.

    Lemierre syndrome is a common presentation, with septic thrombophlebitis arising from the internal jugular vein, often progressing to septic shock, and with high mortality if unrecognized.

  • 3.

    Screen for secondary HLH in the setting of nonresolving sepsis, persistent fevers, or cytopenias, by determining ferritin and triglyceride levels.

  • 4.

    Secondary HLH treatment consists of treating the underlying process, with the potential addition of corticosteroids and etoposide.

Financial/nonfinancial disclosures: None declared.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.


Figures

Figure Jump LinkFigure 1 CT scan of the chest, revealing multiple pulmonary nodules consistent with septic emboli.Grahic Jump Location
Figure Jump LinkFigure 2 MRI of the abdomen, demonstrating, within the left lobe of the liver, a heterogeneous hyperintense mass (arrow) measuring 4.5 × 3.0 cm.Grahic Jump Location

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