Transcript Approach to lymphadenopathy

APPROACH TO
LYMPHADENOPATHY
Presented by: Hamad Alkhalaf,
General Pediatric Fellow
Children’s Hospital of Eastern Ontario
Date: May 10, 2013
Objectives
• Define lymphadenopathy
• Develop a systematic approach to the evaluation and
management of lymphadenopathy
• Discuss the differential diagnosis of localized and
generalized lymphadenopathy
• Recognize worrisome features of lymphadenopathy
Introduction
• Lymph nodes, in conjunction with the spleen, tonsils
adenoids, thymus, and peyer’s patches, are highly
organized centers of immune cells that filter antigen from
the extra cellular fluid.
• Body has 600 lymph nodes.
• Examining the lymph node is an important aspect of the
general physical examination of any pediatric patient .
Introduction
• Lymph nodes are normal structures and a certain lymph
nodes may palpable in healthy children.
• Because of its association with malignancy,
lymphadenopathy can be a major source of parental
anxiety.
Anatomy of Lymph node:
Anatomy of Lymph node:
• Lymph (ultra filtrate of blood) is collected in lymphatic
capillaries present throughout the body except the brain
and heart.
• Lymph moves slowly under a low pressure ultimately
drained into either:
 right lymphatic duct (lymph from the pt upper body)
 thoracic duct (rest of the body)
• These ducts ultimately drain into the venous system (Rt
and Lt subclavian veins)
Anatomy of Lymph node:
• A working knowledge of the nodal basins and the
anatomy of the regions they drain is helpful in formulating
a differential diagnosis for lymphadenopathy
Pathogenesis
• Lymph node enlargement can be caused by the following
mechanisms:
1. proliferation of normal cells that comprise the
lymph node (in response to antigen stimuli)
a. benign hyperplasia
b. vascular engorgement and edema
secondary to local cytokine release
c. suppuration secondary to tissue necrosis
Pathogenesis
2. Entry of large number of cells exogenous to the node
like:
a. neutrophils
b. metastatic neoplastic cells
3. Deposition of foreign materials like lipid storage disease
Epidemiology
• In one review, lymphadenopathy present in:
44% well child visits
64% sick visits
(in children < 5 years of age )
Herzog LW, Prevalence of lymphadenopathy of the head and neck in infants and children. Clin Pediatr
(Phila) 1983; 22:485
• Prevalence of malignancy among the patients seen in
primary care setting is relatively rare.
Epidemiology
• In contrast, prevalence of malignancy in
lymphadenopathy biopsies performed in pediatric referred
centers ranges from 13 – 27%
Lake AM, Oski FA. Peripheral lymphadenopathy in childhood. Ten-year experience with excisional biopsy. Am
J Dis Child 1978; 132:357
Soldes OS, Younger JG, Hirschl RB. Predictors of malignancy in childhood peripheral lymphadenopathy. J
Oediatr Surg 1999; 34:1447
• In the largest series studies, 239 children underwent
peripheral lymph node biopsies for evaluation of
lymphadenopathy
Epidemiology
• The following etiologies were noted
1. idiopathic reactive hyperplasia (52%)
2. Granulmatous disease (cat scratch, atypical
mycobacterium, TB, fungal, histocytosis in 33%)
3. malignancy (13%) 2/3 of them has Hodgkins
disease
4. Chronic dermatopathic or bacterial infections (3%)
Epidemiology
• The prevalence of lymphadenopathy varies with age and
site
• Small occipital and post auricular nodes, for example, are
common in infants, but not an older children
• In contrast, cervical and inguinal nodes are more common
after 2 yrs of age
Epidemiology
• Epitrochlear and supraclavicular adenopathy are
uncommon at any age
• In neonates, lymph nodes are barely perceptible
•M=F
• Race is not a factor in most lymphadenopathy
Epidemiology
• Uncommon causes of lymphadenopathy should be
considered in certain areas
e.g. HIV in Africa
TB and other tropical diseases in developing
nations
Important definitions
• Normal lymph node diameter is up to
- 1 cm (in most regions)
- 0.5 cm (epitrochlear region)
- 1.5 cm (inguinal region)
• Lymphadenopathy
Pathologic swollen lymph node (regardless of the cause)
• Lymphadenitis
Inflamed lymph node usually by infectious cause
Important definitions
• Localized lymphadenopathy
Abnormal enlargement of one (or two contagious) LN
• Generalized lymphadenopathy
abnormal enlargement of two or more noncontiguous LN
Important definitions
• Acute lymphadenopathy
< 2 weeks duration
• Subacute lymphadenopathy
2 – 6 weeks duration
• Chronic lymphadenopathy
> 6 weeks duration
Bacterial lymphadenitis
Cat scratch
tularemia
atypical mycobacteria
Kawasaki
First visit evaluation
• Stepwise management (detailed Hx, full Physical
examination +/- less invasive tests) aid in selecting
appropriate patients for further workup.
History
• HPI
duration and location of lymphadenopathy
local symptoms
- cough, pharyngitis, dental problems, recent onset of
fever, contact with sick pts, skin lesions
Associated constitutional symptoms
- prolonged fever, wt loss, night sweats, skin rash, bone
or joint symptoms
History
• Exposure hx (food, animal, travel)
a. ingestion of unpasteurized animal milk (brucella,
TB)
b. Animal contact: cats (cat scratch disease &
toxoplasmosis), goats (brucellosis), rabbits
(tularemia), prairie dogs (bubonic plague), tick bites,
flea, and mosquito bites (lyme disease, bubonic
plague, tularemia)
c. travel hx (e.g. tularemia, TB, measles, rubella,
leishmaniasis, typhoid fever)
History
• Past History
 Recurrent infections, skin abscess, supporative adenitis
(CGD, HIV)
 Autoimmune disease (autoimmune lymphoproliferative
syndrome)
 B.Asthma ( churg –strauss syndrome)
History
• Immunization status
- diphteria, measles, rubella
• Medications
- Amoxicillin rash in EBV
- Recent steroid therapy
History
Allopurinol
Drugs that cause
lymphadenopathy
Atenolol
Captopril
Carbamazepine
Cephalosporins
Gold
Hydralazine
Penicillin
Phenytoin
Primidone
Pyrimethamine
Quinidine
Sulfonamides
Sulindac
History
• Family hx
malignancy, autoimmune, inflammatory, storage
diseases
• Social hx
Recent immigration
Physical Examination
• General appearance (including vital signs)
• Growth parameters (wt loss of > 10% is a red flag)
• Head
- scalp infection (tinea capitis)
- conjunctival injection (Kawasaki disease,
oculoglandular syndrome)
- nasal obstruction (rhabdomyosarcoma,
nasopharyngeal carcioma, URTI)
- Oropharynx and ears (dental proplems,
pharyngitis, herpetic gingivostomatitis)
- neck (range of motion, other LN
involvement, transillumination)
Examine all lymph nodes
• Assess location, size, consistency, fixation, tenderness,
other lymph nodes involvement.
Lymph node
group
Causes
Occipital
Common: scalp infections (including tinea capitis, lice), insect
bites, seborrhea, roseola (human herpesvirus 6, HHV6)
Less common: Rubella, acute lymphoblastic leukemia)
Posterior auricular
Rubella, roseola (HHV6, HHV7)
Anterior auricular
(preauricular)
Common: Eye or conjuctival infections (e.g. adenovirus,
oculoglandular syndrome)
Less common: cat scratch disease, tularemia, listeriosis
Submental
Tongue, gum, buccal mucosal, and dental infections (eg,
gingivostomatitis), group B streptococcal infection (in infants
<2 months of age)
Submaxillary
(submandibular)
Tongue, gum, buccal mucosal, and dental infections; dental
caries; chronically cracked lips)
Examine all lymph nodes
Lymph node
group
Causes
Cervical
Anterior: common: Viral upper respiratory infections,
infections of pharynx, oral cavity, or head and neck; primary
bacterial adenitis, tuberculosis, Epstein-Barr virus,
cytomegalovirus, cat scratch disease, tularemia,
nontuberculous mycobacterium, mycobacterium tuberculosis
Less common: Kawasaki disease, tularemia, toxoplasmosis,
non-infectious causes (eg, Hodgkin’s disease,
lymphosarcoma, neuroblastoma, rhabdomyosarcoma,
sarcoidosis)
Posterior: Toxoplasmosis, Epstein-Barr virus, rubella.
Supraclavicular
Malignancy (lymphoma or metastatic disease)
Examine all lymph nodes
Lymph node
group
Causes
Axillary
Common: Cat scratch disease, pyogenic infections of upper
arms, brucellosis, reactive response to disruption in skin
integrity
Less common: Brucellosis, Yersinia pestis, rat-bite fever,
toxoplasmosis, rheumatologic disease of the hand or wrist
Epitrochlear
Common: Viral diseases, sarcoidosis, tularemia, infection of
hands
Less common: cat scratch disease, tularemia, secondary
syphilis, rheumatologic disease of the hand or wrist.
Inguinal
Common: Genital herpes, primary; syphlis, gonococcal
infection, lymphoma
Less common: Yersinia pestis, chancroid, lymphogranuloma
venereum
Popliteal
Local infection
Physical Examination
• Chest
Additional sounds (histoplasmosis, LCH, Churg-strauss)
Respiratory distress
Physical Examination
• Abdomen
Hepatosplenomegaly
a. infections (EBV, CMV, HIV, leishmaniasis, TB,
syphilis, lyme disease)
b. Autoimmune (JIA, SLE, serum sickness,
lymphoproliferative disorders)
c. Malignancy (leukemia, lymphoma, secondary
metastasis)
d. lipid storage diseases (Gaucher’s ,Nieman pick disease)
Abdominal mass (neuroblastoma, rhabdomyosarcoma)
Physical Examination
• Genitalia
 signs of STDs.
• Skin
 generalized rash (viral, Kawasaki)
 localized lesions (cat scratch disease, Tularemia,
staph aureus, GAS, HSV, etc)
 insect or mosquito bites
 petechiae or bruises (Bone marrow involvement)
Important considerations
• Formulating your DDx requires consideration of several
important clinical features:
1. age of the patient
2. size of the nodes
3. location of the nodes
4. quality of the nodes
5. localized vs generalized
6. time course of the lymphadenopathy
7. associated symptoms (including worrisome
features)
Important considerations
1) Patient age
Lymph nodes generally are not palpable in newborns
Congenital lesions can mimic lymphadenopathy
- cystic hygroma
- branchial cleft cysts
- thyroglossal duct
- Congenital cervical rib
Cystic hygroma
Branchial cleft cysts
Thyroglossal duct
Important considerations
• Cont, Patient age

DDXs of lymphadenopathy changes according to
the age
e.g. cervical or supraclavicular lymph node
enlargement
> 10 yrs of age  consider Hodgkin’s lymphoma
< 10 yrs of age  Rx and observe

Sexually transmitted disease (late adolescence and
adulthood)
Important considerations
2) Size of lymph nodes
 normal VS pathological
 tend to be larger in young children
(frequent Antigenic exposure)
 the risk of underlying malignancy increases with
increasing size of lymph node
( > 2 cm is concerning in older children)
Important considerations
3) Location of lymph node
 Important in formulating your DDxs
e.g. axillary (cat scratch disease)
 Supraclavicular lymph node enlargement
warrants carful evaluation
 Inguinal and axillary lymph nodes are less
worrisome
Important considerations
4) Quality of lymph nodes
 signs of inflammation (infectious)
 occasionally, malignancy can cause node
tenderness (hemorrhage into the node)
 soft, easily compressible and free mobile (usually
benign)
 hard, firm lymph nodes (malignancy)
 malted lymph nodes (TB, sarcoidosis)
Important considerations
5) Localized VS generalized
 localized lymphadenopathy is more common in a
primary care practice than generalized
lymphadenopathy
 most common sites for localized
lymphadenopathy involved cervical lymph nodes,
followed by inguinal nodes
Causes of generalized lymphadenopathy
Causes of generalized lymphadenopathy
Causes of generalized lymphadenopathy
Causes of generalized lymphadenopathy
Causes of generalized lymphadenopathy
Causes of generalized lymphadenopathy
Important considerations
6) Time course of lymphadenopathy
 acute VS subacute VS chronic
 response to antibiotic trial
 progression of lymph node
- if > 4 – 6 weeks review your DDx
- if > 6 – 12 weeks consider urgent referral
 lymph nodes that have been present for a very
long duration in a well pt are not likely to be
malignant (except Hodgkin disease)
Important considerations
7) Worrisome features
 Soldes and colleagues identified most common
predictors for malignancy which include
1. larger nodes > 2 cm
2. more than 2 sites of adenopathy
3. older age > 12 yrs (malignant)
> 8 yrs (benign)
4. supraclavicular lymphadenopathy
Important considerations
• Cont.
5. adenopathy in CXR
6. blast cells in peripheral smears
• other important features
 wt loss (> 10 % of wt)
 abnormal 2 cell lines in CBC
 prolonged or intermittent unexplained fever.
soldes OS,Younger JG,Hirschi RB. Predictors of malignancy in childhood
peripheral lymphadenopathy. J pediatr surgery.1999,34:1447-1452
Work up
• Initial work up:
- CBC (diff)
- peripheral smear
- CRP, ESR, LDH, uric acid
- LFT, Renal functions
- CXR
Work up
• Specific tests
- Throat c/s
- viral studies (EBV, CMV)
- B.henselae titres
- PPD
- Autoimmune work up (ANA, Ds DNA)
- U/S
Work up
• Invasive tests:
 BMA
 lymph node biopsy (excisional type preferred)
 biopsy of rash (if present)
Approach for Generalized LAD
Approach for Cervical LAD
Approach to axillary LAD
Approach to
inguinal LAD
Home message
• History and physical exam alone are very important in
triage of patients with lymphadenopathy
• Minimal laboratory and radiologic studies can help identify
other important risk factors
• Consider referral in any patient with unexplained
lymphadenopathy > 6 weeks
• Always remember red flags of lymphadenopathy
References
• 1- Up to date .
• 2- Nelson Textbook of pediatrics 19th Edition (2011) .
• 3- Red Book 29th Edition ( 2012).
• 4- pediatrics In Review 2008; 29;53
56-
7-
DOI 10.1542/pir.29-2-53
Medscape Reference ( May 2012)
Current pediatrics Diagnosis and treatment 21th
Ediation ( 2012).
Zetelli Atlas of Pediatric Physical& Diagnosis 6th
Edition ( 2012)
Questions??