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Lymphadenitis. Amina Ahmed, MD Levine Children’s Hospital November 17, 2011. Definitions. Lymphadenopathy Lymph node enlargement Infectious, inflammatory or neoplastic Lymphadenitis Localized inflammatory process Unilateral, bilateral Acute or chronic Pyogenic or granulomatous.

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lymphadenitis

Lymphadenitis

Amina Ahmed, MD

Levine Children’s Hospital

November 17, 2011

definitions
Definitions
  • Lymphadenopathy
    • Lymph node enlargement
    • Infectious, inflammatory or neoplastic
  • Lymphadenitis
    • Localized inflammatory process
      • Unilateral, bilateral
    • Acute or chronic
    • Pyogenic or granulomatous
lymphadenopathy
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
etiology of lymphadenitis
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
infectious causes of lymphadenitis
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
acute bilateral cervical lymphadenitis
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
pyogenic lymphadenitis
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
pyogenic causes of adenitis
Pyogenic Causes of Adenitis

Principles and Practice of Infectious Disease; Long S, ed.

acute unilateral cervical lymphadenitis
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
subacute lymphadenitis
Subacute Lymphadenitis
  • Approximately 2-3 week duration
  • Painless or minimally tender
  • Discoloration of overlying skin may occur
    • Suppuration and drainage may occur
subacute lymphadenitis1
Subacute Lymphadenitis
  • Cat-scratch disease (B. henselae)
  • Toxoplasmosis
  • Mycobacteria
    • Nontuberculous mycobacteria (NTM)
    • Tuberculosis
    • BCG adenitis
  • Tularemia (F. tularensis)
    • Typically increasing adenopathy, suppuration
case 1 red neck
Case 1 : Red Neck
  • 3 week old with fever and submandibular swelling with erythema
  • Evaluation?
  • Empiric treatment?
case 1 red neck1
Case 1 : Red Neck
  • Differential
    • GBS
    • S. aureus
  • Evaluation
    • Blood culture
    • LP
  • Empiric treatment
    • Ampicillin
    • Nafcillin
    • Vancomycin
gbs cellulitis adenitis syndrome
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%
case 2 when antibiotics fail
Case 2 : When Antibiotics Fail
  • 23 month old admitted with submandibular adenitis
  • Treated with amoxicillin-clavulanate for 7 days without improvement
  • Temperature 101.9
case 2
Case 2
  • Differential diagnosis
    • Acute adenitis
      • S. aureus
        • MSSA, MRSA
      • S. pyogenes
  • Empiric treatment
  • Further management
cervical adenitis s aureus s pyogenes
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)
management of acute cervical adenitits
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
mssa versus mrsa
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)
case 3 all in the family
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
case 3
Case 3
  • Subacute adenitis
    • B. henselae
    • Toxoplasmosis
    • NTM, MTB
    • F. tularensis
  • Evaluation
  • Management
cat scratch disease
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
cat scratch disease1
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

clinical presentation of 2 083 patients with csd
Clinical Presentation of 2,083 Patients with CSD

Curr Infect Dis Rep 2000; 2: 141-46

lymphadenitis typical csd
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
diagnosis of cat scratch disease
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
diagnosis of cat scratch disease1
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
management of typical csd
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
treatment of cat scratch disease
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

azithromycin for csd
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

here kitty kitty
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!
case 4 lump in my throat
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?

case 4
Case 4
  • Subacute (≥ 2 weeks duration)
    • Bartonella henselae
    • Non-tuberculous mycobacteria (NTM)
    • Mycobacterium tuberculosis (MTB)
    • Toxoplasmosa gondii
  • Further evaluation
mycobacterial lymphadenitis
Mycobacterial Lymphadenitis
  • M. tuberculosis complex
    • M. tuberculosis
    • M. bovis
  • Nontuberculous mycobacteria (NTM)
    • Most common M. avium complex
ntm versus mtb lymphadenitis
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
mtb lymphadenitis
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
ntm lymphadenitis
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
ntm versus mtb lymphadenitis1
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
diagnosis of ntm lymphadenitis
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
ntm lymphadenitis1
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

management of ntm lymphadenitis
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!
case 5 who dunnit
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?
case 5
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
tularemia
Tularemia
  • Etiologic agent is Francisella tularensis
  • 100-200 cases per year in the United States
  • Transmission
    • Ticks
    • Contact with rabbits
    • Contact with rodents/domestic animals
    • Poorly cooked road kill or game meats
tularemia1
Tularemia
  • Cutaneous inoculation (papule)  ulcer  regional nodes  bacteremia
  • Most common sign is regional adenopathy
    • Inguinal most common in adults; cervical in children
    • Untreated, nodes suppurate and drain
  • Constitutional symptoms common in children
    • Fever in 80-90%
    • Malaise, chills, fatigue
diagnosis of tularemia
Diagnosis of Tularemia
  • Serology
    • IgG > 1:160 is presumptive
    • 4 fold increase is diagnostic
  • Histology
    • Follicular hyperplasia, caseating granulomas
  • Isolation from tissue, blood, sputum
    • Biosafety level 2 required for isolation
case 6 like mother like daughter
Case 6 : Like mother, like daughter
  • 16 year old Vietnamese girl with cervical adenitis
  • Referred to pulmonologist TST placed  referred to surgeon
  • CXR normal
  • MRI of chest shows mediastinal adenopathy
ntm versus mtb lymphadenitis2
NTM versus MTB Lymphadenitis
  • Approach to child with suspected TB adenitis:
    • Risk factors for TB (contact, country of origin, etc.)
    • TST
    • CXR
    • Needle biopsy or excision for culture
    • Specimens from other sites for culture
  • Approach to child with adenitis, reactive TST:
    • Investigation of household with TSTs
    • CXR
    • Needle biopsy or excision for culture
m tuberculosis adenitis
M. tuberculosis Adenitis
  • Most frequent form of extrapulmonary disease (30-60%)
    • More common in Asians, females
  • Localized or part of more generalized process
    • Typically unilateral, supracalvicular or cervical node
      • Painless, red, firm
      • CXR frequently normal
  • Diagnosis
    • FNA versus excisional biopsy (with cultures!)
    • PCR (tissue, PBMC)- variable yield
  • Treatment- as for MTB
management of acute lymphadenitis
Management of Acute Lymphadenitis
  • Empiric therapy for S. aureus, S. pyogenes
    • Consider local susceptibilities
  • If no response to treatment
    • Symptomatic consider parenteral therapy
    • ? Abscess  drainage needed
    • Subacute node  consider NTM, CSD
      • B. henselae serology
      • TST, CXR
      • CBC with differential
management of acute lymphadenitis1
Management of Acute Lymphadenitis
  • Further evaluation
    • US
    • Needle aspiration
    • Biopsy
      • Excisional preferred to incisional if unsure of diagnosis
      • Early if malignancy suspected
management of subacute adenitis
Management of Subacute Adenitis
  • Evaluation for alternate infectious etiologies
    • CSD- Bartonella titers
    • NTM or MTB- TST, CXR
    • Toxoplasmosis serology
      • Diagnosis usually made by biopsy
  • FNA or biopsy for diagnosis
content specifications covered
Content Specifications Covered
  • Recognize the clinical manifestations of cat-scratch disease, including FUO
  • Formulate a differential diagnosis in a patient with suspected CSD, (eg, nontuberculous myocobacterial infection, tuberculosis, sarcoidosis)
  • Know how to diagnose CSD
  • Know the epidemiology of CSD (ie, recent contact with cats, often kittens)
  • Know how to identify and interpret a positive TST
  • Understand the diagnosis and treatment of cervical adenitis secondary to NTM
  • Know the major clinical manifestations of NTM in immunocompetent children
  • Identify the clinical manifestations of Toxoplasma gondii infections acquired after birth
case tb or not tb
Case : TB or not TB?
  • 2 year old Hispanic female with neck swelling
  • Treated 2 weeks with antibiotics with no improvement
  • New node noted in region
    • Referred to a surgeon
    • Surgeon recommended medical management
  • TST reactive at 12 mm
case tb or not tb1
Case : TB or not TB?
  • Subacute adenitis
    • Pyogenic abscess?
    • CSD
    • NTM
    • MTB
    • Tularemia
    • Anaerobes
denoument
Denoument
  • Differentiation between NTM and MTB adenitis requires isolation of the pathogen
    • Caseating granulomas identified
    • AFB noted on histology
  • Treatment initiated
    • Isoniazid, rifampin, pyrazinamide, ethambutol
  • MTB isolated
    • Resistance to PZA
slide74

pasteurized

gotmilk?

mycobacterium bovis
Mycobacterium bovis
  • Causative agent of TB in cattle
  • Transmission
    • Ingestion of unpasteurized milk products
    • Aerosolization, inoculation
    • Cow cow, cow human, human cow
  • Rare cause of TB in industrialized countries
    • < 0.1% of TB in the United States
slide77
14 year old with 1-2 week history of fever, sore throat

Swelling of neck in last 3 days

Admitted for difficulty swallowing and dehydration

Case
slide78
Acute bilateral cervical adenopathy

S. pyogenes

Viral

EBV

CMV

Adenovirus

Evaluation

Treatment

Case
infectious mononucleosis ebv
Infectious Mononucleosis : EBV
  • Seroprevalence 50% to 90% among 5 year olds
  • Primary infection in children subclinical
    • In adolescence, 30-50% symptomatic
  • Pharyngitis, cervical adenopathy are hallmarks
    • Posterior cervical, anterior cervical
  • Diagnosis
    • Heterophile antibody
      • Not useful in children < 4 y or
    • EBV titers
slide80
Case
  • 13 year old with submental adenitis
  • Fever, toxic appearing
  • Vancomycin and ceftriaxone initiated
  • Blood culture: GNR
acute lymphadenitis anaerobes
Acute Lymphadenitis: Anaerobes
  • Most frequent in older children /adolescents
  • Poor dentition or periodontal disease
  • Anaerobes isolated in up to 38% of aspirates from children with optimal culture techniques
acute lymphadenitis anaerobes1
Acute Lymphadenitis: Anaerobes
  • Can lead to septic thrombophlebitis of jugular veins, septic pulmonary emboli
    • Lemierre syndrome
    • Bull neck
  • Systemic toxicity
    • Positive blood cultures (Fusobacterium)