1. Lymphadenitis Amina Ahmed, MD Levine Children’s Hospital November 17, 2011

2. Definitions • Lymphadenopathy • Lymph node enlargement • Infectious, inflammatory or neoplastic • Lymphadenitis • Localized inflammatory process • Unilateral, bilateral • Acute or chronic • Pyogenic or granulomatous

3. Lymphadenopathy • Most healthy children have palpable lymph nodes • Considered enlarged if > 10 mm • > 5 mm epitrochlear is abnormal • > 15 mm inguinal is abnormal • Palpable supraclavicular nodes in the absence of cervical adenopathy are abnormal • Palpable popliteal nodes are abnormal

4. Lymphatic Drainage of Nodes

6. Lymphatic Drainage of Head and Neck

7. Infectious Causes of Lymphadenopathy in Children

8. Noninfectious Causes of Lymphadenopathy in Children

9. Etiology of Lymphadenitis • History • Duration of illness • Skin lesions or trauma • Epidemiology • Age, ethnicity • Travel, pets • Physical examination • Dental disease • Ocular or oropharyngeal lesions • Noncervical adenopathy • Hepatomegaly or splenomegaly

10. Infectious Causes of Lymphadenitis • Acute bilateral cervical lymphadenitis • Response to pharyngitis • Part of generalized lymphoreticular response • Acute unilateral lymphadenitis • Pyogenic bacterial infection • Subacute or chronic lymphadenitis

11. Acute Bilateral Cervical Lymphadenitis • Pharyngitis • S. pyogenes • Viral upper respiratory tract infections • Epstein-Barr virus • Cytomegalovirus • Herpes simplex • Adenoviral syndrome • HIV • Enterovirus • HHV-6 • Rubella

12. Pyogenic Lymphadenitis • Acute (< 2 weeks duration) • S. aureus • Streptococcus pyogenes, S. agalactiae • Francisella tularensis • Pasteurella multocida • Yersinia pestis • Subacute (≥ 2 weeks duration) • Bartonella henselae • Non-tuberculous mycobacteria (NTM) • M. tuberculosis • Toxoplasmosa gondii

13. Pyogenic Causes of Adenitis Principles and Practice of Infectious Disease; Long S, ed.

14. Acute Unilateral Cervical Lymphadenitis • S. pyogenes • Associated with impetigo or streptococcosis • Lymphangitis more common with GAS • S. aureus • Longer duration of disease before diagnosis • More likely to suppurate, longer time to resolution

15. Subacute Lymphadenitis • Approximately 2-3 week duration • Painless or minimally tender • Discoloration of overlying skin may occur • Suppuration and drainage may occur

16. Subacute Lymphadenitis • Cat-scratch disease (B. henselae) • Toxoplasmosis • Mycobacteria • Nontuberculous mycobacteria (NTM) • Tuberculosis • BCG adenitis • Tularemia (F. tularensis) • Typically increasing adenopathy, suppuration

17. Case 1 : Red Neck • 3 week old with fever and submandibular swelling with erythema • Evaluation? • Empiric treatment?

18. Case 1 : Red Neck • Differential • GBS • S. aureus • Evaluation • Blood culture • LP • Empiric treatment • Ampicillin • Nafcillin • Vancomycin

19. GBS Cellulitis-Adenitis Syndrome • Late-onset GBS disease • Typically 2-11 weeks of age • Abrupt onset of fever and facial or submandibular swelling • Ipsilateral OM • Bacteremia in 90% of cases • Meningitis in 25%

20. Case 2 : When Antibiotics Fail • 23 month old admitted with submandibular adenitis • Treated with amoxicillin-clavulanate for 7 days without improvement • Temperature 101.9

21. Case 2 • Differential diagnosis • Acute adenitis • S. aureus • MSSA, MRSA • S. pyogenes • Empiric treatment • Further management

22. Cervical Adenitis: S. aureus, S. pyogenes • Account for 40-80% of cases of acute cervical adenitis • Most common in 1-4 y of age • Recent URI- pharyngitis, tonsillitis, AOM • Primary sites • Submandibular (50-60%) • Upper cervical (25-30%) • Submental (5-8%) • ~ 25% suppurate (mainly S. aureus)

23. Management of Acute Cervical Adenitits • Empiric therapy for S. aureus, S. pyogenes (7-10 d) • No improvement • ? MRSA, ? anaerobes  consider aspiration • Broaden antimicrobial coverage • ? Suppuration (abscess) • US or CT • Drainage, excision • No improvement  subacute • ? CSD  B. henselae titers • ? NTM

24. MSSA versus MRSA • MSSA • -lactamase production • Only 5% susceptible to penicillin • Susceptible to semisynthetic penicillins and cephalosporins • MRSA • Altered PBP2a • Resistant to all -lactam antibiotics • Susceptible to vancomycin, clindamycin (variable)

25. Antimicrobial Treatment of MRSA

26. Case 3 : All in the Family • 8 y old girl referred to hematology-oncology for evaluation of inguinal adenopathy • Node present for 3 weeks • Tender only when walking • Family went camping 2 weeks before onset • Father and sister also had adenopathy

27. Case 3 • Subacute adenitis • B. henselae • Toxoplasmosis • NTM, MTB • F. tularensis • Evaluation • Management

28. Cat-Scratch Disease • Etiologic agent is Bartonella henselae • Approximately 25,000 cases annually in US • Cats are the reservoirs and the vectors • 10-30% cats are bacteremic (kittens > cats) • Flea transmission from cat to cat • > 90% of patients have had contact with a cat • 50-80% have been scratched

29. Cat-Scratch Disease • Overview of 1,200 patients with CSD • 87% < 18 y • 85% with single node • Noncontiguous adenopathy in 2% • Suppuration in 12% • Other family members affected in 3.5% • 60 had atypical disease Am J Dis Child 1985; 139: 1124-33

30. Clinical Presentation of 2,083 Patients with CSD Curr Infect Dis Rep 2000; 2: 141-46

31. Lymphadenitis : Typical CSD • Primary lesion at site of inoculation • Papule  vesicle  crusting in 1-4 weeks • May be resolved at presentation of adenitis • Lymphadenitis • 5 d to 2 mo after inoculation • Solitary (50%) or regional (50%) • Axillary > cervical > submandibular • Minimal tenderness • Overlying skin not warm or erythematous • Constitutional symptoms in 25-50% • Regresses in 4-8 weeks

32. Location of Lymphadenopathy in Patients with CSD

33. Diagnosis of Cat-Scratch Disease • Clinical • Serology • IgG ≥ 1:64 is seroreactive • IgG ≥ 1:512 or 4 fold increase is diagnostic • Absence of IgM does not exclude diagnosis

34. Diagnosis of Cat-Scratch Disease • Histology • Necrotizing granulomas • Warthin Starry silver stain may detect organisms • Isolation of B. henselae is difficult • PCR for tissue in research settings

35. Management of Typical CSD • Antibiotics not recommended for mild to moderately ill immunocompetent patient • Self-limited; resolves in 2-3 mo • Consider treatment for large, bulky nodes • Azithromycin? Doxycycline? • Surgical excision is not necessary for diagnosis or management

36. Treatment of Cat-Scratch Disease • In vitro susceptibility to multiple antibiotics • Clinically response to antibiotics is minimal • Anectodal reports suggest response to: • TMP-SMX • Rifampin • Ciprofloxacin • Gentamicin Pediatr Infect Dis J 1992: 11: 474-8

37. Azithromycin for CSD • Randomized, double-blind, placebo-controlled trial • 14 treated with azithromycin • 15 treated with placebo • In 7/14 azithromycin and 1/15 placebo-treated patients, 80% reduction in node volume at 30 d -Difference not significant after 30 d • Clinical outcome not otherwise different Pediatr Infect Dis J 1998; 17: 447-52

38. 8 year old boy being evaluated in GI Clinic for constipation 2 week history of rash and lymphadenopathy in neck and axilla Grandmother had brought home a kitten… Here…Kitty, Kitty!

39. Case 4 : Lump in my throat • A 2 year old presents with cervical lymphadenitis. She is afebrile and otherwise asymptomatic • After a 10 days of amoxicillin and 10 days of amoxicillin-clavulanate, the lymphadenitis is unchanged • A TST is reactive at 8 mm. The patient’s CXR is normal. • How do you proceed with further management?

40. Case 4 • Subacute (≥ 2 weeks duration) • Bartonella henselae • Non-tuberculous mycobacteria (NTM) • Mycobacterium tuberculosis (MTB) • Toxoplasmosa gondii • Further evaluation

41. Mycobacterial Lymphadenitis • M. tuberculosis complex • M. tuberculosis • M. bovis • Nontuberculous mycobacteria (NTM) • Most common M. avium complex

42. NTM versus MTB Lymphadenitis • NTM lymphadenitis much more common than MTB • Similar clinical presentation • TST may be reactive in either • CXR may be normal in TB • Histologically identical • Differentiation requires isolation of pathogen

43. MTB Lymphadenitis • All ages • Localized adenopathy (scrofula) • Supraclavicular, cervical, submandibular • Systemic symptoms minimal • Generalized adenopathy • Cervical, supraclavicular • Systemic symptoms present • Primary pulmonary focus on CXR in 30-70% • Treatment is chemotherapy

44. NTM Lymphadenitis • Immunocompetent children 1-4 y of age • Portal of entry is usually oropharynx or skin • Cervical adenitis - most common manifestation of NTM infection • Unilateral anterior cervical or submandibular • Skin characteristically becomes violaceous • Pain and constitutional symptoms minimal • 50% suppurate, 10% drain • Excision is the treatment of choice • Do not incise and drain • If not amenable to surgery- dual or triple drug treatment

45. NTM versus MTB Lymphadenitis • TST < 15 mm, CXR normal, no reactive TSTs in household- more likely NTM • Excision for diagnosis and treatment • If reactive TSTs in household • Aspiration or excision for diagnosis • Evaluation for TB in patient and sources

46. Diagnosis of NTM Lymphadenitis • Excision of node is the treatment of choice and provides clues to diagnosis • Necrotizing granulomas • AFB stains may be positive • Definitive diagnosis and differentiation from TB requires isolation by culture

47. NTM Lymphadenitis • RCT of surgical excision versus antibiotic therapy • Diagnosis by culture or PCR • 50 children- surgery • 50 children- clarithromycin/rifabutin for 12 wks • Cure rate of 96% for surgery versus 66% for antibiotics • Surgical excision is more effective than antibiotic treatment for children with NTM cervical adenitis Clin Infect Dis 2007; 4: 1057-64

48. Management of NTM Lymphadenitis • Excision is the treatment of choice • DO NOT INCISE AND DRAIN! • DO NOT FORGET TO CULTURE! • Lymphadenopathy not amenable to excision • Experience with clarithromycin or azithromycin in combination with ethambutol and rifabutin • DO NOT USE SINGLE AGENT THERAPY!

49. 9 year old with ulcerative lesion of ring finger and painful elbow Patient reports cutting finger while picking up glass MRI shows multiple epitrochlear nodes No response to cefazolin Case 5 : Who Dunnit?

50. Epitrochlear adenitis S. aureus, S. pyogenes B. henselae F. tularensis Patient later reported being licked by a cat…or maybe bitten by a cat Tissue culture growing gram-negative rods Case 5