Cervical Lymphadenitis Russell J. McCulloh and Brian Alverson Hospital Pediatrics 2011;1;52 DOI: 10.1542/hpeds.

2011-0016

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Hospital Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 2012. Hospital Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2011 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 2154-1663.

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EIA is a recurring section of Hospital Pediatrics where expert pediatric hospitalists give their interpretation of the recent evidence in reference to common clinical questions encountered in their daily practice.

ILLUSTRATIVE CASE

Cervical Lymphadenitis

Introduction: Cervical lymphadenitis may have multiple etiologic factors and can pose a diagnostic dilemma for pediatric hospitalists. This case and review of the literature explores various causes, diagnostic methods, and treatment options available to the pediatrician caring for children with lymphadenitis. Case: An 18-month-old male infant originally presented with swelling in the right neck near the angle of the jaw which gradually developed over 4 to 5 days. He was rst taken to his primary care provider who noted multiple enlarged, nontender, submandibular lymph nodes and prescribed amoxicillin. However, because of increasing swelling after several days of antibiotic use, the patient was taken to the emergency department where he was prescribed, and completed, rst a 10-day course of amoxicillin/clavulanate, and subsequently, a 7-day course of azithromycin. The patients neck swelling failed to improve, though he never developed signicant fever or prominent tenderness. Question: Is the patients clinical course up to this point suggestive of typical bacterial lymphadenitis, with treatment failure or is it suggestive of something less typical? Discussion: Cervical lymphadenopathy is common in children and is usually caused by transient reactive hyperplasia from an acute viral illness.1,2 In acute bacterial cervical lymphadenitis, the presentation is usually unilateral lymphadenopathy with signs of inammation, often accompanied by fever and pain at the site of infection, which this patient did not have. The pathogens most commonly found in acute bacterial lymphadenitis are Staphylococcus aureus and Streptococcus pyogenes.3,4 Recent literature reports that S aureus, in particular community-acquired methicillinresistant S aureus (CA-MRSA), is increasingly common.5,6 A 2007 review of 62 patients undergoing surgical drainage for acute cervical lymphadenitis showed that of 49 culture-positive cases, 36% yielded methicillin-sensitive S aureus (MSSA), 27% yielded methicillin-resistant Staphylococcus aureus (MRSA), and 22% yielded group A beta-hemolytic streptococci (GABHS).7 However, rates of culture positivity for CA-MRSA in surgical specimens have been found to be as high as 40% to 60%.7-11 While in the outpatient setting, reasonable initial antibiotic choices available to the primary care physician could include cephalexin, amoxicillin/clavulanate, or clindamycin,12-14 for the pediatric hospitalist treating suspected bacterial lymphadenitis, initial therapy should include CA-MRSA treatment that is based on local resistance patterns.15 However, given that this patient did not have fever or pain, and has persistent lymphadenopathy, his course is suggestive of an alternative cause. Case Continued: This patients medical history was unremarkable. His family history was negative for chronic infections. The family denied recent travel or pet exposure, and the patient lived in an urban area with limited outdoor exposure. Of note, his
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AUTHORS Russell J. McCulloh, MD1, Brian Alverson, MD1

1

Hasbro Childrens Hospital, Providence, Rhode Island www.hospitalpediatrics.org doi:10.1542/hpeds.2011-0016 Address correspondence to Russell J. McCulloh, MD, Hasbro Childrens Hospital of Rhode Island Hospital, Division of Pediatric Infectious Diseases, 593 Eddy Street, Providence, RI 02903; Phone: 401-444-8360; Fax: 401-444-5650; Email: rmcculloh@lifespan.org HOSPITAL PEDIATRICS (ISSN Numbers: Print, 0031 - 4005; Online, 1098 - 4275). Copyright 2011 by the American Academy of Pediatrics

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HOSPITAL Pediatrics

AN OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF PEDIATRICS

rifampin with healing of the area but with residual scarring. Discussion: Subacute infectious cervical lymphadenitis occurs over the course of 2 to 4 weeks or more and a very different set of pathogens are usually considered (Table 1).3 Common agents in the United States include nontuberculous mycobacteria, cat-scratch disease (B henselae), and rarely, opportunistic fungal and parasitic infections, including T. gondii infection. Unlike acute bacterial lymphadenitis, these infections less frequently suppurate and are more often associated with diffuse lymphadenopathy.1
FIGURE 1 Patients neck swelling seen at the time of admission.

father had recently been incarcerated, but he denied any symptoms of cough, fever, or weight loss. Because of his failure to improve after two courses of antibiotics, he was referred to an otolaryngologist who prescribed oral clindamycin. However, 3 days later, the patient returned to the emergency department with fever and a change in the character of his neck swelling from rm and nontender to a uctuant, warm mass with overlying erythema (Figure 1). He was admitted to the hospital where he underwent ultrasonography of the neck, which revealed right submandibular lymph nodes with air/uid levels suggestive of suppurative lymphadenitis. Question: Was clindamycin an appropriate choice at the otolaryngology visit? How does treatment proceed now that the child is admitted? Discussion: The patient has failed outpatient therapy with amoxicillin/ clavulanate which can be used for treating MSSA and GABHS lymphadenitis. At this point, treatment of CA-MRSA lymphadenitis is indicated. Clindamycin

can be used for initial treatment of CA-MRSA skin and soft tissue infections, but use of an alternative agent is recommended when local resistance patterns are greater than 10%.15 Other reasonable treatment regimens could include cotrimoxazole.10 Both linezolid and vancomycin should be considered in patients suspected of having CA-MRSA and signicant illness symptoms.15 Given the persistence of lymphadenopathy for several weeks and the now suppurative character of the nodes on ultrasonography, we should also consider surgical drainage.3 Case Denouement: The patient underwent incision and drainage of the lymph nodes. Laboratory testing for Bartonella henselae, Toxoplasma gondii, and blood cultures were negative. A puried protein derivative test at admission found 5 mm of induration, and a culture specimen from the incision and drainage yielded acid-fast bacilli (AFB), which was later identied as Mycobacterium avium complex. The patient began a 4-month regimen of ethambutal, clarithromycin, and

In subacute infections, serologic testing for B. henselae, cytomegalovirus, Epstein-Barr virus, and human immunodeciency virus should be considered as well as skin tuberculin testing, which can be positive in both M. tuberculosis as well as nontuberculous mycobacteria (NTM) infection.2,16 Ultrasonography has proven to be an effective modality to facilitate diagnosis and track clinical improvement in cases of nonsurgical management.16 In cases in which therapy is not effective, biopsy, ne-needle aspiration, or excision is warranted.17 For any surgical specimens, testing should include cultures for bacteria, fungi, and AFB as well as Gram and tissue staining for fungi, B. henslae (WarthinStarry stain), and AFB.2 For NTM, excisional biopsy may be both diagnostic and curative,18 but the surgery carries some risk of nerve damage.19 However, many providers prefer surgical excision over incision and drainage of lymph nodes infected with NTM,20,21 likely because of risks of chronic draining stulas and poor cosmetic outcome associated with incomplete removal of infected tissue.22 Antibiotic treatment of NTM most frequently involves a macrolide plus adjunctive agents such as
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TABLE 1 Common Infectious Causes of Cervical Lymphadenitis Listed by Most Common Clinical Presentation
Acute, bilateral lymphadenitis Viral upper respiratory infections Streptococcus pyogenes pharyngitis Varicella zoster virus Herpes simplex virus Rubella Rubeola Acute, unilateral lymphadenitis Staphylococcus aureus Streptococcus pyogenes without pharyngitis Chronic, bilateral lymphadenitis Epstein-Barr virus Cytomegalovirus Toxoplasma gondii Human immunodeciency virus Chronic, unilateral lymphadenitis Nontuberculous mycobacteria Bartonella henslae Mycobacterium tuberculosis

4. Ahonkhai VI, Omokoku B, Rao M. Acute cervical lymphadenitis in hospitalized pediatric patients: predominance of Staphylococcus aureus in infancy. J Natl Med Assoc. 1984;76(4):367-369. 5. Ossowski K, Chun RH, Suskind D, Baroody FM. Increased isolation of methicillinresistant Staphylococcus aureus in pediatric head and neck abscesses. Arch Otolaryngol Head Neck Surg. 2006;132(11):1176-1181. 6. Shapiro A, Raman S, Johnson M, Piehl M. Community-acquired MRSA infections in North Carolina children: prevalence, antibiotic sensitivities, and risk factors. N C Med J. 2009;70(2):102-107. 7. Guss J, Kazahaya K. Antibiotic-resistant Staphylococcus aureus in communityacquired pediatric neck abscesses . Int J Pediatr Otorhinolaryngol. 2007;71(6):943-948. 8. Duggal P, Naseri I, Sobol SE. The increased risk of community-acquired methicillinresistant Staphylococcus aureus neck abscesses in young children. Laryngoscope. 2011;121(1):51-55. 9. Brook I. Role of methicillin-resistant Staphylococcus aureus in head and neck infections. J Laryngol Otol. 2009;123(12):13011307. 10. Inman JC, Rowe M, Ghostine M, Fleck T. Pediatric neck abscesses: changing organisms and empiric therapies. Laryngoscope. 2008;118(12):2111-2114. 11. Velargo PA, Burke EL, Kluka EA. Pediatric neck abscesses caused by methicillinresistant Staphylococcus aureus: a retrospective study of incidence and susceptibilities over time. Ear Nose Throat J. 2010;89(9):459461. 12. Dulin MF, Kennard TP, Leach L, Williams R. Management of cervical lymphadenitis in children. Am Fam Physician. 2008;78(9): 1097-1098. 13. Leung AK, Robson WL. Childhood cervical lymphadenopathy. J Pediatr Health Care. 2004;18(1):3-7. 14. Elliott DJ, Zaoutis TE, Troxel AB, Loh A, Keren R. Empiric antimicrobial therapy for pediatric skin and soft-tissue infections in the era of methicillin-resistant Staphylococcus aureus. Pediatrics. 2009;123(6):e959-e966. 15. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment

of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18-e55. 16. Niedzielska G, Kotowski M, Niedzielski A, Dybiec E, Wieczorek P. Cervical lymphadenopathy in childrenincidence and diagnostic management. Int J Pediatr Otorhinolaryngol. 2007;71(1):51-56. 17. Knight PJ, Reiner CB. Supercial lumps in children: what, when, and why? Pediatrics. 1983;72(2):147-153. 18. Lindeboom JA, Kuijper EJ, Bruijnesteijn van Coppenraet ES, Lindeboom R, Prins JM. Surgical excision versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children: a multicenter, randomized, controlled trial. Clin Infect Dis. 2007;44(8):1057-1064. 19. Claesson G, Bennet R, Eriksson M, Petrini B. Nerve dysfunction following surgical treatment of cervical non-tuberculous mycobacterial lymphadenitis in children. Acta Paediatr. 2011;100(2):299-302. 20. Timmerman MK, Morley AD, Buwalda J. Treatment of non-tuberculous mycobacterial cervicofacial lymphadenitis in children: critical appraisal of the literature. Clin Otolaryngol. 2008;33(6):546-552. 21. Pilkington EF, MacArthur CJ, Beekmann SE, Polgreen PM, Winthrop KL. Treatment patterns of pediatric nontuberculous mycobacterial (NTM) cervical lymphadenitis as reported by nationwide surveys of pediatric otolaryngology and infectious disease societies. Int J Pediatr Otorhinolaryngol. 2010;74(4):343-346. 22. Spyridis P, Maltezou HC, Hantzakos A, Scondras C, Kafetzis DA. Mycobacterial cervical lymphadenitis in children: clinical and laboratory factors of importance for differential diagnosis. Scand J Infect Dis. 2001;33(5):362-366. 23. Starke JR. Management of nontuberculous mycobacterial cervical adenitis. Pediatr Infect Dis J. 2000;19(7):674-675. 24. Amir J. Non-tuberculous mycobacterial lymphadenitis in children: diagnosis and management. Isr Med Assoc J. 2010;12(1):49-52. 25. Lindeboom JA. Conservative wait-and-see therapy versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children. Clin Infect Dis. 2011;52(2):180-184.

rifampin or ethambutal which should be tailored to specic sensitivity patterns of the isolates detected.23,24 However, debate still exists on optimal antibiotic management of NTM and whether it is even necessary.25 Conclusion: Pediatric lymphadenitis presents a diagnostic challenge to the treating physician, requiring assessment of multiple clinical and historical factors. A clear understanding of the various underlying etiologic factors and their typical presentation can guide the hospitalist in clinical decision-making, including when to use surgical modalities for diagnosis and treatment.

References
1. Peters TR, Edwards KM. Cervical lymphadenopathy and adenitis. Pediatr Rev. 2000; 21(12):399-405. 2. Leung AK, Davies HD. Cervical lymphadenitis: etiology, diagnosis, and management. Curr Infect Dis Rep. 2009;11(3):183-189. 3. Gosche JR, Vick L. Acute, subacute, and chronic cervical lymphadenitis in children. Semin Pediatr Surg. 2006;15(2):99-106.

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Cervical Lymphadenitis Russell J. McCulloh and Brian Alverson Hospital Pediatrics 2011;1;52 DOI: 10.1542/hpeds.2011-0016

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including high resolution figures, can be found at: http://hosppeds.aappublications.org/content/1/1/52 This article cites 25 articles, 5 of which you can access for free at: http://hosppeds.aappublications.org/content/1/1/52#BIBL This article, along with others on similar topics, appears in the following collection(s): Administration/Practice Management http://hosppeds.aappublications.org/cgi/collection/administration :practice_management_sub Standard of Care http://hosppeds.aappublications.org/cgi/collection/standard_of_c are_sub Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: /site/misc/Permissions.xhtml Information about ordering reprints can be found online: /site/misc/reprints.xhtml

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