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
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
Lymphatic Drainage of Nodes
Lymph Node
Group
Area of Drainage
Potential Etiologies
Occipital
Back of scalp/neck
Tinea capitis
Seborrheic dermatitis
Rubella
Preauricular
Lateral eyelids
Lateral conjuctivae
Skin above cheek
Adenovirus
Parinaud’s syndrome due to
CSD, tularemia, HSV
Axillary
Hand, arm
Chest wall, breast
CSD
Epitrochlear
Ulnar aspect hand and
forearm
Local pyogenic infection
CSD, tularemia
Popliteal
Lateral foot, lower leg,
knee joint
Local pyogenic infection
Lymphatic Drainage of Head and Neck
Lymph Node Group
Area of Drainage
Occipital
Back of scalp/neck
Submental
Central lower lip, floor of mouth, skin of chin
Submandibular
Buccal mucosa, side of nose, medial palpebral
commisure, upper lip, anterior tongue
Superior deep cervical
Occipital scalp, auriculae, back of tongue,
trachea, thyroid, esophagus
Inferior deep cervical
Dorsal scalp and neck, superfical pectoral
region, superior deep cervical nodes
Supraclavicular
Right: left lower lobe, lingula, right lung
Left: left upper lobe, abdomen
Infectious Causes of Lymphadenopathy in Children
Location of Affected Nodes
Cause
Bacterial
Cervical
Mediastinal
Abdominal
S aureus

S. pyogenes

M. tuberculosis




NTM




B. henselae



Anaerobic bacteria


Yersinia

F. tularensis

Syphilis


Epstein-Barr virus

Cytomegalovirus

Herpes simplex

Adenovirus

Human immunodeficiency virus

Human herpes virus 6

Rubella


Parasitic






Histoplasmosis

Sporotrichosis


Coccidioidomycosis

Blastomycosis

Toxoplasmosis


Coxsackie
Fungal


Brucellosis
Viral
Generalized



Noninfectious Causes of Lymphadenopathy in Children
Location of Affected Nodes
Cause
Malignancy
Cervical
Mediastinal
Abdominal
Generalized
Hodgkin's Disease




Non-Hodgkin’s Lymphoma




Leukemia


Thyroid tumors

Neuroblastoma

Metastatic disease

Lymphoproliferative disorders
Other

Parotid tumors


Immunodeficiency diseases



Collagen vascular disease


Sarcoidosis
Congenital


Rhabdomyosarcoma
Kawasaki syndrome






Histiocytosis X

Storage disorders

Serum sickness

Branchial cleft cyst

Cystic hygroma

Bronchogenic cyst

Thyroglossal duct cyst

Epidermoid cyst

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



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

Pharyngitis


S. pyogenes
Viral upper respiratory tract infections
 Epstein-Barr virus
 Cytomegalovirus
 Herpes simplex
 Adenoviral syndrome
 HIV
 Enterovirus
 HHV-6
 Rubella
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
Organism
S. pyogenes
S. agalactiae
S. aureus
NTM
B. henselae
T. gondii
Anaerobes
Neonate
2 mo – 1y
1-4 y
5-18 y
-
-
+
++
++
+
-
-
+
++
++
+
-
-
++
+
-
+
++
++
-
-
+
+
-
-
+
++
Principles and Practice of Infectious Disease; Long S, ed.
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

Approximately 2-3 week duration

Painless or minimally tender

Discoloration of overlying skin may occur
 Suppuration and drainage may occur
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

3 week old with fever
and submandibular
swelling with erythema

Evaluation?

Empiric treatment?
Case 1 : Red Neck

Differential

GBS



S. aureus
Evaluation

Blood culture

LP
Empiric treatment

Ampicillin

Nafcillin

Vancomycin
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



23 month old admitted with
submandibular adenitis
Treated with amoxicillinclavulanate for 7 days
without improvement
Temperature 101.9
Case 2

Differential diagnosis
 Acute adenitis

S. aureus


MSSA, MRSA
S. pyogenes

Empiric treatment

Further management
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


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
 -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)
Antimicrobial Treatment of MRSA
Macrolides
Increasing resistance- not reliable
Clindamycin
Used widely
Inducible resistance; increasing resistance
TMP-SMX
Not FDA approved; limited experience
Not active against GAS
Susceptibility rates high
Add rifampin for large lesions, -lactam for GAS
Rifampin
Susceptibility high
Use only in combination with other agents
Tetracyclines
Not approved in pediatric patients
Linezolid
Expensive
Save it!
Fluoroquinolones
Resistance increasing
Not approved in prepubertal children
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

Subacute adenitis

B. henselae

Toxoplasmosis
NTM, MTB

F. tularensis


Evaluation

Management
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 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 features
Numbers
Percentage
1784
86
1271
61
299
14
Parinaud’s oculoglandular syndrome
125
6.1
Encephalopathy
51
2.4
Systemic disease, severe, chronic
48
2.3
Neuroretinitis
30
1.4
Erythema nodosum
15
0.7
Thrombocytopenic purpura
7
0.3
Hepatosplenomegaly
7
0.3
Osteomyelitis
8
0.3
Typical presentation
Inoculation lesion
(skin, eye mucous membrane)
Atypical manifestations
Curr Infect Dis Rep 2000; 2: 141-46
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
Location of Lymphadenopathy in Patients with CSD
Location
No. (%) of
Patients
Total upper extremity
Axillary
Epitrochlear
610 (46.1)
586
24
Total neck and jaw
Cervical
Submandibular
340 (26.1)
191
149
Total groin
Inguinal
Femoral
Preauricular
Postauricular
Clavicular
Chest
228 (17.5)
143
85
87 (6.6)
2
31
4
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 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



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

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



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…
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

Subacute (≥ 2 weeks duration)



Bartonella henselae
Non-tuberculous
mycobacteria (NTM)

Mycobacterium tuberculosis

Toxoplasmosa gondii
(MTB)
Further evaluation
Mycobacterial Lymphadenitis


M. tuberculosis complex
 M. tuberculosis
 M. bovis
Nontuberculous mycobacteria (NTM)
 Most common M. avium complex
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



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



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 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


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 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


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

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 gramnegative rods
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
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
Clinical Forms of Tularemia
Clinical Manifestation
Features
Glandular
Most common manifestation (50-80%)
May have papule or ulcer distal to node
Multiple or groups of nodes
Oculoglandular
Nodular conjunctivitis
Preauricular adenopathy
Oropharyngeal
Diphtheria-like illness; fever
Typhoidal
Ingestion of contaminated food
Sepsis-like manifestation
Pneumonia
Aerosol exposure
Rare in children
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




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 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




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


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 Lymphadenitis

Further evaluation
 US
 Needle aspiration
 Biopsy
 Excisional preferred to incisional if
unsure of diagnosis
 Early if malignancy suspected
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
Treatment of Lymphadenitis
Possible Pathogens
Empiric treatment
S. aureus/ S. pyogenes
Cellulitis, symptoms
With suppuration
Clindamycin, vancomycin
Incision and drainage
S. agalactiae/S.aureus
Nafcillin, clindamycin, vancomycin
S. agalactiae- penicillin, ampicillin
Anaerobes
Add clindamycin or metronidazole
B. henselae
Symptomatic; consider azithromycin
NTM
Excision of node
M. tuberculosis
Four-drug antituberculosis regimen
F. tularensis
Gentamicin, streptomycin
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?




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 TB?

Subacute adenitis
 Pyogenic abscess?
 CSD
 NTM
 MTB
 Tularemia
 Anaerobes
Acid fast bacilli
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
pasteurized
got
milk?
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
Case
• 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

Acute bilateral cervical
adenopathy


S. pyogenes
Viral
 EBV
 CMV
 Adenovirus

Evaluation

Treatment
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
Case




13 year old with submental
adenitis
Fever, toxic appearing
Vancomycin and ceftriaxone
initiated
Blood culture: GNR
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: Anaerobes


Can lead to septic thrombophlebitis of jugular veins,
septic pulmonary emboli
 Lemierre syndrome
 Bull neck
Systemic toxicity
 Positive blood cultures (Fusobacterium)