Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 13-6

Sixteen-Year-Old Boy

PRATICHI K. GOENKA

HISTORY OF PRESENT ILLNESS

A 16-year-old male was transferred from a referral hospital for management of evolving respiratory failure. He was in his usual state of good health until 1 week prior to admission. He had been helping friends renovate a house and developed sore throat, swollen glands in his neck, malaise, occasional vomiting, and fever to 102°F. His mother noted changes in his voice that this time. He went to his primary physician who noted “kissing tonsils” and a pharyngeal exudate and diagnosed mononucleosis. He was started on oral prednisone and sent home with follow-up the next day. The next day, his voice was improved, and the regimen was continued.

He was seen in the emergency room at a community hospital 1 day prior to admission because of ongoing swelling of his glands and the development of chest pains and trouble sleeping (increased pain while lying down). A chest radiograph was initially reported as negative, but the family was called the next day because the reviewing radiologist felt that there was cardiomegaly. The patient returned to his primary physician and was referred for evaluation of chest pain, shortness of breath, orthopnea, fever, chills, and diaphoresis. In the emergency room, his respiratory rate was 40/minute and his SpO2 = 83% in room air. He had scattered petechiae on his trunk, face, and extremities. Echocardiogram showed mildly enlarged heart, small pericardial effusion, no vegetations. Blood urine and pleural fluid cultures were sent, and he was started on levofloxacin, ceftriaxone, vancomycin, and doxycycline. The patient continued to deteriorate and required endotracheal intubation.

MEDICAL HISTORY

Immunizations were not up-to-date. He had not received his tetanus booster or the hepatitis B vaccine series. There were no pets in the home but the patient had exposure to friends’ cats and dogs. There were no known tick exposures. The patient lived with his mother and three brothers. The only ill contact was his mother who had a sore throat.

PHYSICAL EXAMINATION

T 39°C; HR 110 bpm; RR 20/min (ventilator rate); BP 110/70 mmHg

On examination the patient was intubated and sedated. There were multiple 1-2 cm submandibular lymph nodes and generalized swelling of neck and face. There was no hepatosplenomegaly. The scrotum and extremities were very edematous. A foley catheter was in place. There were no splinter hemorrhages or subcutaneous nodules on the extremities. There were a few scattered petechiae on trunk.

DIAGNOSTIC STUDIES

The WBC count was 25 600/mm3 (31% band forms, 50% segmented neutrophils, and 16% lymphocytes). The hemoglobin was normal but the platelet count was 33 000/mm3. Serum electrolytes were consistent with mild acute renal failure. ALT and AST were 99 U/L and 81 U/L, respectively. There was mild PT and PTT prolongation.

COURSE OF ILLNESS

CT of the chest (Figure 13-10) suggested a likely cause, especially in the context of constellation of pharyngitis, neck pain, and clinical deterioration accompanied by face and neck swelling.

DISCUSSION CASE 13-6

DIFFERENTIAL DIAGNOSIS

This case was remarkable in that what started as a simple febrile illness with generalized adenopathy and neck swelling rapidly advanced to pneumonia, pneumothoracic pleural effusion, and respiratory failure. One of the initial questions in the evaluation of any neck mass should be “Is there evidence for airway compromise?” In this case, pursuing those questions and the rapid deterioration of the patient led to the appropriate diagnosis. In assessing the neck swelling it may be important to assess other sites in the pulmonary system including airways and lungs. At the beginning of the course, the differential diagnosis included streptococcal pharyngitis, mononucleosis, adenovirus, CMV, and other mono-like virus illness. As the process advanced and as a pulmonary component was identified, other organisms both viral and bacterial (aerobic and anaerobic) were considered. The presence of pleural fluid prompted its research to identify the organism. Fusobacterium necrophorum was eventually isolated.

DIAGNOSIS

The CT revealed a filling defect in the left internal jugular vein (Figures 13-10A and 13-10B). The filling defect is initially visualized in Figure 13-10A and completely visualized in Figure 13-10B. This finding was consistent with an internal jugular vein thrombus causing partial venous obstruction. There were also multiple, ill-defined peripheral, many with central cavitation and a small left pleural effusion (Figure 13-10C). The lung nodules were consistent with septic emboli. The patient was diagnosed with Lemierre syndrome. Isolation of a Fusobacterium species from the pleural fluid further suggested the diagnosis of Lemierre syndrome or septic thrombophlebitis of the internal jugular vein.

Lemierre syndrome consists of acute tonsillo-pharyngeal adenopathy, neck pain, fever, and the development of supportive thrombophlebitis of the internal jugular vein. Neck swelling may be moderate to more severe and accompanied by severe neck pain. Patients may also develop septic pulmonary emboli as the patient in this case. The organism that typically causes this syndrome is Fusobacterium; an obligatory anaerobic Gram-negative bacillus that can be part of normal oral or gastrointestinal flora. Other reported causes of septic thrombophlebitis include Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus milleri group bacteria (e.g., Staphylococcus inter-medius). Other infections caused by Fusobacterium spp. include bacteremia, otitis media, mastoiditis, peritonsillar abscess, and less commonly, septic arthritis and meningitis. Neurologic manifestations of Lemierre syndrome occur as a consequence of intracranial infection or lateral sinus thrombosis complicating mastoiditis; this complication is related to the anatomical proximity and the thin bone that separates the mastoid from the lateral sinus.

Image

FIGURE 13-10. CT of the neck and chest showing: A. An initial filling defect in the left internal jugular vein (arrow). B. More complete filling defect of the left internal jugular vein (arrow). C. Pulmonary nodules with central cavitation.

INCIDENCE AND EPIDEMIOLOGY OF LEMIERRE SYNDROME

This is a rare condition that appears in only isolated case reports in the literature. The condition occurs in adolescents and young adults.

CLINICAL MANIFESTATIONS

The infection begins as a simple tonsillopharyngeal infection and then advances. Neck swelling and pain are localized to enlarge submandibular nodes at first and then become more generalized. The course often evolves to pulmonary involvement. Septic emboli may develop and be showered to other body sites causing symptoms in the central nervous system and elsewhere. The syndrome had been uniformly fatal. However, with early detection by CT scan and aggressive antibiotic therapy, good results have been reported.

DIAGNOSTIC APPROACH

When the specific origin of neck swelling cannot be determined a CT scan or MRI of the neck is indicated to determine the location and nature of the swelling. In Lemierre syndrome, the findings of suppurative thrombophlebitis are central to the diagnosis. CT or MRI images may demonstrate a filling defect in the involved vessel (as seen in Figures 13-10A and B) or inflammatory changes in and surrounding the vessel itself. CT scanning may also reveal septic emboli to the CNS, lungs, or elsewhere (Figure 13-10C demonstrates lung nodules consistent with pulmonary septic emboli). Recovery of the organism from abscess drainage or from pleural fluid will confirm the Fusobacteriumisolate. A positive blood culture along with imaging findings consistent with thrombophlebitis cinches the diagnosis of Lemierre syndrome.

TREATMENT

Antibiotic treatment for Lemierre ultimately depends on the causative bacterium. Fusobacterim spp. are typically susceptible to penicillin, metronidazole, and clindamycin. Piperacillin-tazobactam or ampicillin-sulbactam is used when broader therapy is required empirically while awaiting identification of the organism. Surgical debridement of necrotic tissues and drainage of pleural empyema may be required. Children with ongoing development of pulmonary septic emboli may require placement of an inferior vena cava filter (e.g., Greenfield filter). The role of routine anticoagulation therapy in internal jugular venous thrombosis is controversial. Potential indications for anticoagulation include cerebral infarction or sinus venous thrombosis. Treatment may need to be prolonged over several weeks. There have not been any large case series or clinical trials to determine the best course of therapies. Mortality is relatively uncommon, occurring in fewer than 5% of affected patients.

SUGGESTED READINGS

1. Alvarez A, Schreiber JR. Lemierre’s syndrome in adolescent children—anaerobic sepsis with internal jugular vein thrombophlebitis following pharyngitis. Pediatr. 1995;96:354-359.

2. Weesner CL, Cisek JE. Lemierre syndrome: the forgotten disease. Ann Emerg Med. 1993;22:256-258.

3. Moreno S, Garcia AJ, Pinilla B, et al. Lemierre’s disease: postanginal bacteremia and pulmonary involvement caused by Fusobacterium necrophorum. Rev Infec Dis. 1989;11:319-324.

4. DeSena S, Rosenfeld DL, Santos S, et al. Jugular thrombophlebitis complicating bacterial pharyngitis (Lemierre’s syndrome). Pediatr Radiol. 1996;26:141-144.

5. Sinave CP, Hardy GJ, Fardy PW. The Lemierre syndrome: suppurative thrombophlebitis of the internal jugular vein secondary to oropharyngeal infection. Medicine (Baltimore). 1989;68:85-94.

6. Megged O, Assous MB, Miskin H, Peleg U, Schlesinger Y. Neurologic manifestations of Fusobacterium infections in children. Eur J Pediatr. 2013;172:77-83.