Holly D Smith, MD

Dr Smith is an assistant professor in the Department of Pediatrics, McGovern Medical School, Houston, Texas.

	An 8-year-old girl is admitted to the hospital with complaints of right ear pain, right leg pain, left arm pain, and fever after a week of worsening symptoms.

	One week prior to admission, the girl had presented to her pediatrician with 7days of right ear pain. She was diagnosed with otitis media and given an antibiotic, of which her mother could not remember the name. She was not having fever at that time.

	Five days prior to admission, the patient noticed pain in her right ankle after minor trauma. She was brought to an emergency department (ED), diagnosed with an ankle fracture based on abnormal X-rays, and placed in a splint. The next day, she followed up with an orthopedic surgeon and the ankle was placed in a cast.

	Three days prior to admission, the girl began having fever to 104°F along with nausea and vomiting, and she presented to a different ED where she was diagnosed with strep pharyngitis and given azithromycin.

	On the day of admission, secondary to continued fever, vomiting of up to 5 times daily, neck pain, left arm pain, and worsening pain in her right ankle, she was again taken to the ED. Labs and X-rays were done. She was given a normal saline bolus, intravenous (IV) morphine, IV ketorolac, IV clindamycin, ondansetron, and then transferred for admission to the children’s hospital.

	The patient’s past medical history was significant for allergic rhinitis and an appendectomy at age 2 years. She lives with her mother and grandmother, has no pets, and hasn’t traveled.

	On admission, the patient’s vital signs showed an oral temperature of 101.2°F; heart rate of 110 beats/minute; blood pressure of 110/69 mm Hg; and respiratory rate of 20 breaths/minute. Her weight was 45.9 kg (>95%) and her height was 136 cm (50%). She was not in distress but appeared to not feel well. Her right tympanic membrane was erythematous and bulging. She moved her neck easily to the right but had pain with movement to the left. There was no cervical lymphadenopathy.

	Her left arm appeared normal but was tender to palpation and movement in all areas of the elbow and forearm. There was no redness or swelling of the elbow or forearm. The right leg was in a cast below the knee. There were 2, 2 mm to 3 mm slightly raised macules that were yellowish in the center with surrounding erythema on the end of her right great toe.

	When the patient presented to the transferring hospital ED, her sodium was 134mEq/L (normal range [NR],135-145 mEq/L) and potassium was 2.9mEq/L (NR, 3.5-5.1 mEq/L). Her white blood cell count (WBC) was 12,600 wbc/mcL (NR, 4.5-13.5 wbc/mcL) with 80% neutrophils (NR, 34%-64%); hemoglobin,9.8 g/dL (normal mean corpuscular volume, normal mean corpuscular hemoglobin concentration,NR,11.5-15.5 g/dL);and platelet count of154,000/mL (NR, 133-450/mL). In the admitting hospital, her albumin was found to be 2.0 g/dL (NR, 3.8-5.4 g/dL); erythrocyte sedimentation rate (ESR) was over 100 mm/hour (NR, 0-10 mm/hour); and C-reactive protein was 171 mg/L (NR, <3 mg/L).

	The patient had several objective physical findings including high fever; right otitis media and pain with neck movement; left elbow/arm pain; right foot/leg pain; and pustular rash on the right foot. She also had several laboratory abnormalities including increased neutrophils; a normocytic, normochromic anemia; normal platelets; a low albumin level; and significantly elevated inflammatory markers.

NEXT: More information on the diferential diagnosis

	The anemia, hypoalbuminemia, and elevated inflammatory markers suggested the patient had a significant inflammatory process. The differential diagnosis of fever and extremity pain is fairly extensive (Table). Hematogenous osteomyelitis, leukemia, and endocarditis with septic emboli to the extremities were strongly considered in this order.

	Because of the patient’s primary complaint of limb pain and fever, the physicians considered osteomyelitis and consulted Orthopedic Surgery. They recommended to rule out leukemia due to fever and the involvement of more than one limb. In a child, leukemia can cause multifocal bone pain because of decreased production of all blood cell lines and leukemic infiltration. Such a child also can have intermittent fever that may result from production of cytokines or infection due to leukopenia. When leukemia is suspected, a peripheral smear should be ordered and indirect tests of tumor lysis such as lactate dehydrogenase and uric acid should be done. A bone marrow biopsy is required for definitive diagnosis, so Hematology was consulted. Given that the patient had a normal complete blood cell count except for mild anemia and a peripheral blood smear without blasts, Hematology believed leukemia was unlikely.

	Next, the patient’s physicians returned to their initial thought of hematogenous osteomyelitis. She had a high fever and pain in her right lower extremity, which is commonly seen with osteoarticular infections. More than 80% of osteoarticular infections occur in lower extremities and 20% have a history of injury or fall in the recent past.

In 1999, Kocher and colleagues developed a clinical prediction scale that included the following 4 criteria: fever, refusal to bear weight, white blood cell count above12,000wbc/mcL, and an ESR over 40 mm/hour. The diagnostic sensitivity for acute osteomyelitis was 93% for 3 criteria and 99% for 4 criteria.

Recommended: Acute otitis media warrants 10 days of antibiotics

	Plain films can be obtained with extremity pain and fever but the sensitivity of radiography for detecting osteomyelitis is only 50%.

 This patient had multiple X-rays of her right lower extremity and left upper extremity at the transferring hospital ED that were read as normal. When the site of acute infection can be determined, magnetic resonance imaging (MRI) is the best imaging method because of the excellent images of soft tissues, bones, and joints.

Because her right foot/ankle was the site of the most pain, and because she had fever, the patient underwent a right ankle MRI with and without contrast. It showed fluid collections in the anterior ankle compartment and flexor digitorum muscle, which were concerning for abscesses due to hematogenous spread (Figure1). The patient was taken to the operating room where the 2 abscesses were drained. The wound culture grew many group A beta-hemolytic strep. To assist with antibiotic choice and duration of therapy, Infectious Diseases was consulted. Her antibiotics were switched from IV cefepime and vancomycin to ampicillin/sulbactam.

	Because of the abscesses and embolic-appearing lesions on the patient’s right foot, the physicians considered endocarditis. Infected vegetations on heart valves are known to embolize to other parts of the body. With right-sided endocarditis, a patient can develop septic pulmonary emboli. When vegetations on are the left side, septic emboli can travel to the brain or anywhere else in the body such as the extremities. Because of the concern for septic emboli, the patient underwent a transthoracic echo that was negative for vegetations but that showed a tiny patent foramen ovale with a left-to-right shunt. Septic emboli can pass through this patent foramen ovale, but the question became from where did they originate?

	Because of intermittent low-grade fevers (100.4°F to 101.8°F) for 5 days despite drainage of the right ankle and foot abscesses, wide-spectrum IV antibiotics, and persistent pain of right ear and neck, a computed tomography (CT)scan of the temporal bones and an MRI of the brain and neck were obtained. The CT showed right otomastoiditis (Figure 2) and thrombophlebitis of the right sigmoid sinus, jugular vein, and transverse sinus (Figures 3 and 4). Otolaryngology took the patient to the operating room for a right myringotomy with pressure equalization tube placement, right mastoidectomy, and facial nerve monitoring. To decrease the risk of idiopathic intracranial hypertension resulting from cerebral venous thrombosis, Hematology recommended starting enoxaparin.

	Because the patient had mastoiditis, thrombophlebitis of nearby vessels, evidence of embolization with a septic left elbow, and abscesses of the right ankle and foot that grew group A beta-hemolytic strep, the patient was diagnosed with Lemierre syndrome (LS), also known as postanginal sepsis or human necrobacillosis.

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Lemierre syndrome was best characterized by the French microbiologist Dr. Andre Lemierre in 1936. This is a rare head and neck infection that most commonly affects healthy adolescents and young adults but that can occur in younger and older patients.

 It traditionally starts with a pharyngeal infection but can rarely be due to mastoiditis.

 From the mastoid air cells, the infection spreads to the local venous system including the internal jugular vein, and clot formation can occur.

The etiology of hypercoagulability in LS is not completely understood but infection seems to be a potent mediator.

Finally, there is metastatic spread most commonly to the lungs and large joints, but it can also cause abscesses in the liver, spleen, kidney, brain, heart, muscles, and soft tissues.

 but there have been 6 cases attributed to 

, the most common group A beta-hemolytic strep, reported in the literature.

As in this patient, initial symptoms of LS are related to the primary infection (sore throat or ear pain) along with fever, nausea, and vomiting. A week later, patients develop symptoms of vascular involvement. Internal jugular thrombophlebitis may cause pain in the sternocleidomastoid muscle.

 Finally, approximately 2 weeks into the illness, patients develop symptoms of metastatic spread, which may be respiratory distress, joint pain, liver and renal abnormalities, or soft tissue abscesses such as in the patient in this case.

	Treatment is usually 4 to 6 weeks of parental antibiotics and 3 months of anticoagulation therapy.

 Depending on the initial source of infection such as otitis media/mastoiditis, surgical intervention such as pressure equalization tube placement and mastoidectomy may be indicated. Also, surgery may be indicated to drain metastatic infection/abscesses such as this patient required.

	Because the patient continued to complain of intermittent left elbow pain, she had an MRI of her elbow, which showed a small-to-moderate joint effusion. A CT-guided arthrocentesis of her left elbow was done, and the fluid suggested a septic arthritis. She underwent an incision and drainage of the elbow. She was transferred to a long-term assisted care hospital for prolonged antibiotics.

	The patient continued on IV ampicillin/sulbactam for a total of 8 weeks when a brain and neck MRI was repeated, which showed further inferior extension of the right sigmoid and internal jugular vein thrombosis but decreased inflammation. Intravenous antibiotics were continued for another 2 weeks, then switched to oral amoxicillin/clavulanic acid for an additional 2 months.

Next: Girl's papular rash will not respond to treatment

	Antibiotics were discontinued once the patient had a normal exam and normal inflammatory markers. Enoxaparin was continued for a total of 5 months and was stopped because of loss of insurance. The patient was lost to follow-up because of a change in insurance.

	Prior to the antibiotic era, such as when Lemierre described this disease process in 1936, this syndrome was almost always fatal. Now with advanced imaging modalities, IV antibiotics, and surgical subspecialists, most patients recover. However, morbidity remains high, usually because there is delay in diagnosis and septic emboli have occurred.

	Whereas this illness was originally described as a complication of pharyngitis because of 

 in adolescents and young adults, LS can be seen as a complication of mastoiditis attributed to 

 in children. Therefore, primary care pediatricians should be aware of this rare complication of otitis media.

	1. Arnold JC, Bradley JS. Osteoarticular infections in children. 

	2. Kocher MS, Zurakowski D, Kasser JR. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. 

	3. Tumeh SS, Aliabadi P, Weissman BN, McNeil BJ. Disease activity in osteomyelitis: role of radiography

	4. Baig MA, Rasheed J, Subkowitz D, Vieira J. A review of Lemierre syndrome. 

	5. Ridgeway JM, Parikh DA, Wright R, et al. Lemierre syndrome: a pediatric case series and review of literature. 

	6. Stokroos RJ, Manni JJ, de Kruijk JR, Soudijn ER. Lemierre syndrome and acute mastoiditis. 

	7. Goldenberg NA, Knapp-Clevenger R, Hays T, Manco-Johnson MJ. Lemierre’s and Lemierre’s-like syndromes in children: survival and thromboembolic outcomes. 

	8. Aspesberro F, Siebler T, Van Nieuwenhuyse JP, Panosetti E, Berthet F. Lemierre syndrome in a 5-month-old male infant: case report and review of the pediatric literature. 

	9. Harris CM, Johnikin M, Rhodes H, et al. Lemierre’s syndrome resulting from streptococcal induced otitis media and mastoiditis: a case report. 

	10. Chirinos JA, Lichtstein DM, Garcia J, Tamariz LJ. The evolution of Lemierre syndrome: report of 2 cases and review of the literature. 

	11. Wilson P, Tierney L. Lemierre syndrome caused by 

	12. Anton E. Lemierre syndrome caused by 

	13. Blumberg D, Brazzola P, Foglia CF, Fiore E, Bianchetti MG. Lemierre syndrome caused by group A 

	14. Shah RK, Wofford MM, West TG, Shetty AK. Lemierre syndrome associated with group A streptococcal infection. 

	15. Frizzola MA, Hertzog JH. Lemierre syndrome in a 22-month-old due to 

	Dr Smith is an assistant professor in the Department of Pediatrics, McGovern Medical School, Houston, Texas. Dr Scully is a second-year pediatric critical care fellow in the Department of Pediatrics, McGovern Medical School, Houston. The authors have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.

Articles

An 8-year-old girl is admitted to the hospital with complaints of right ear pain, right leg pain, left arm pain, and fever after a week of worsening symptoms. 

Author | Holly D Smith, MD

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