محاضرة من اعداد د.ولاء مناع القيت فى يوم الاحد 30-11-2014 فى مستشفى حميلت كفر الشيخ

1. Approach to Child with Lymphadenopathy
BY:
Dr, WALAA SALAH
MANAA
SPECIALEST OF PEDIATRIC
مـستشفى حمـيات كـفر الشـيخ

2. Outline
• Introduction
• Anatomy
• Pathophysiology
• Generalized lymphadenopathy
• Regional lymphadenopathy
• Investigation
• Management

3. Introduction
• Lymphatic system
– Network of organs, lymph nodes, lymph ducts and
lymph vessel that make and drain lymph from
tissues to the bloodstream.
– This lymphoid tissue concerned with immune
function in defending body against antigen.
• Primary lymphoid organ (thymus & bone marrow)
• Secondary lymphoid organ (lymph nodes, tonsil &
others)
• Lymphoid tissue enlarges until puberty & progressively
atrophy throughout life
• Functions
– Removal of interstitial fluid from tissues, collection
of lymph plasma
– Absorption & transport of fatty acids and fats
– Formation of a defense mechanism for the body

4. Distinguishing between localized and
generalized lymphadenopathy is important
in formulating a differential diagnosis.
In primary care patients with unexplained
lymphadenopathy
75%localized lymphadenopathy
25%generalized lymphadenopathy.

5. Findings from a Dutch study revealed a 0.6% annual
incidence of unexplained lymphadenopathy in the
general population.
Of 2,556 patients in the study who presented with
unexplained lymphadenopathy to their family
physicians, 256 (10 %) were referred to a
subspecialist and 82 (3.2 %) required a biopsy, but
only 29 (1.1 %) had a malignancy.

6. Groups of Lymph
Nodes

7. Lymphadenopathy
• Enlargement of lymph node
• Normal lymph nodes are discrete,
non tender, and mobile without
fixation to underlying tissues.
• Significant enlarged:
– >1 cm in cervical and
axillary,
– >1.5cm in inguinal nodes

8. Lymphadenopathy
• Generalized lymphadenopathy (enlargement
of >2 noncontiguous node regions) is caused
by systemic disease
• Regional lymphadenopathy is most
frequently the result of infection in the
involved node and/or its drainage area

9. Pathophysiology
• Localized response from
lymphocyte and macrophage –
viral/ bacterial infection
• Localized infiltration by
inflammatory cells in response
to infection of nodes-lymphadenitis
• Proliferation of neoplastic
lymphocyte or macrophages-neoplasm

10. Generalized
Generalized
adenopathy
Inflammation
Infective
Infant: Syphilis,
Toxoplasmosis, CMV, HIV
Child: Viral infection, EBV,
CMV, Toxoplasmosis
Autoimmune
Child: SLE, JRA, Sarcoidosis,
Fungal infection, Plaque, Chronic
granulomatous disease
Malignancy
Primary
Secondary

11. Generalized
enlargement of more than 2 noncontiguous lymph node groups
Infectious
• Viral (most common): URTI, measles, varicella, rubella, hepatitis, HIV, EBV, CMV,
adenovirus
• Bacterial: syphilis, brucellosis, tuberculosis, typhoid fever, septicemia
• Fungal: histoplasmosis, coccidioidomycosis
• Protozoal: toxoplasmosis
Non-infectious inflammatory diseases
• Rheumatologic diseases: Sarcoidosis, rheumatoid arthritis, SLE
• Storage diseases: Neimenn-Pick disease, Gaucher disease
• Serum sickness
Malignant: leukemia, lymphoma, neuroblastoma
Drug reaction ???????????
Hyperthyroidism

12. Infectious Mononucleosis (Glandular Fever)
o Caused by Epstein Barr Virus
o Signs/Symptoms
– Prolong fever
– Exudative pharyngitis
– Painless generalized lymphadenopathy
– Splenomegaly
o Diagnosis
o 50% lymphocytosis with >10% Atypical lymphocytes on peripheral blood
smear
– Positive monospot test (Paul Bunnell test)
– Serum heterophile Antibody definitive (positive at 2-6weeks)
o Complication: splenic rupture, respiratory obstruction, encephalitis, lymphoma
o Treatment
o Mainly supportive
– Tonsillar hypertrophy → produce airway obstruction: need to place
nasopharyngeal tube and start high dose steroids
– Do not give amoxicillin → develop an iatrogenic rash in 80% of patients.

13. Cytomegalovirus
• From Herpesviridae family
• Infectious mononucleosis like
syndrome
• CF: fatigue, malaise, myalgia,
headache, fever,
hepatosplenomegaly, elevated liver
enzymes
• Ix: atypical lymphocytosis in
peripheral blood smear, CMV DNA
PCR
• Tx: not indicated for
immunocompetent persons

14. Suppurative Bacterial Lymphadenitis
• Staphylococcus aureus and Group A Streptococcus
• Common history reveals recent
 URI
 Earache
 Sore Throat/Toothache
 Skin Lesions: erythema and tender of overlying
skin
• Tx: Oral or IV antibiotics depending on severity of
infection
• If not resolving or getting worse Ultrasound or CT
scan to evaluate for abscess
• Surgical I&D vs Surgical Excision if abscess

15. TB Lymphadenitis
o Most commonest form of extrapulmonary
manifestation of TB in children
o Tonsillar, anterior cervical, submandibular, and
supraclavicular nodes secondary to extension of the
primary lesion of TB (lung/abdomen)
o Inguinal, epitrochlear, or axillary regions result from
regional lymphadenitis associated with tuberculosis of
the skin or skeletal system.
o Characteristic: firm, discrete and nontender – often feel
fixed to overlying tissue→ disease progress, multiple
node infected (matted)
o Unilateral
o Reactive tuberculin test
o Dx: fine – needle aspiration of node (through histologic
and bacterial conformation)
o Response well to anti – TB therapy
Tuberculosis lymphadenitis

16. Cat Scratch Disease
• Bartonella Henselae
o Commonest cause of chronic lymphadenitis
• 90% have had exposure to cat bite or scratch
o CF: Red papules over scratch area +
lymphadenopathy
o Nodes involved: tender, overlying erythema,
enlarged, (10-40%) suppurative
o Axillary nodes are most frequently affected,
followed by cervical, submandibular, and
preauricular nodes.
• Diagnosis with serology for antibodies or PCR
• Management: supportive.

18. • Toxoplasma gondii
• Mechanism
Toxoplasmosis
– Consumption of undercooked meat
– Ingestion of oocytes from cat feces
• Symptoms
– Malaise, fever, sore throat, myalgias
– 90% have cervical lymphadenitis
• Diagnosis by serologic testing
• Complications
– myocarditis
– pneumonitis
• Risk of TORCH infection to fetus
• Treatment with pyrimethamine or sulfonamides

19. Kawasaki Disease
• Lymphomucocutaneous Disease
• Five Characteristics of Disease (4/5 for diagnosis)
 Fever >5 days
 Cervical lymphadenopathy (usually unilateral)
 Erythema and edema of palms and soles with desquamation
of skin
 Nonpurulent Bilateral Conjunctivitis
 Strawberry Tongue
• Complications
Coronary artery aneurysms
Coronary artery thromboses
Myocardial infarction
• Treatment
o IVIG and Aspirin
• **Be sure to get Echo and EKG is Kawasaki disease is suspected

20. Storage diseases
Gaucher disease
o multisystemic lipidosis characterized by hematologic problems,
hepatosplenomegaly, and skeletal involvement
o results from the deficient activity of the lysosomal hydrolase, acid β-glucosidase
o CFx:
• easily bruising owing to thrombocytopenia
• chronic fatigue secondary to anemia
• hepatomegaly with or without elevated liver function test results
• splenomegaly
• bone pain
Niemann-Pick disease
o 3 types:
• Type A & B deficient activity of acid sphingomyelinase
• Type C is defective cholesterol transport
o Characterized by a normal appearance at birth. Hepatosplenomegaly, moderate
lymphadenopathy, and psychomotor retardation are evident by 6 mo of age,
followed by neurodevelopmental regression.
o With advancing age, the loss of motor function and the deterioration of
intellectual capabilities are progressively debilitating; and in later stages, spasticity
and rigidity are evident.
o Affected infants lose contact with their environment - DEATH

21. • Most common form of reactive lymphadenopathy
• Common virus’ involved:
1. Adenovirus
2. Rhinovirus
3. Coxsackie virus A and B
4. EBV
• Lymphadenopathy often bilateral, diffuse, non-tender
• Other Signs/Symptoms are consistent with URI
• Management is expectant but they are often biopsied due to slow
regression
• Nodal architecture and hilar vascularity are normal on pathologic
examination
Viral Lymphadenitis

22. • Treponema pallidum
• Vertical transmission, sexual contact with infectious
lesion, blood product
• 4 stages: primary, secondary, latent and tertiary
• Primary:
– glands of penis, vulva or cervix
– Other: anus, fingers, oropharynx, tongue
– Regional lymphadenopathy
• 2nd: localized or diffuse mucocutaneous rash, patch
alopecia condylomata with generalized non tender
lymphadenopathy
• 3rd: CNS involvement or CVS
• Tx: IM Benzathine Penincillin
Syphilis

24. Localized
enlargement of a single node or multiple contiguous nodal regions
Cervical (most common adenopathy in children, often INFECTIOUS cause):
•Infectious
•Viral upper respiratory infection
•Infectious mononucleosis (EBV, CMV)
•Group A Streptococcal pharyngitis
•Acute bacterial lymphadenitis (eg: Staphylococcus aureus)
•Kawasaki disease (unilateral cervical lymph node > 1.5 cm)
•Rubella
•Cat scratch disease
•Toxoplasmosis
•Tuberculosis, atypical mycobacteria
•Neoplastic (malignant childhood tumours develop in the head and neck in ¼ of cases)
•Neuroblastoma, Leukemia, non-Hodgkins, and Rhabdomyosarcoma are most common in
those < 6 years old.
•In older children, Hodgkin’s and non-Hodgkin’s lymphoma are more common.
•Acute leukemia, Neuroblastoma, Rhabdomyosarcoma

25. Differential Diagnosis
•Oral and dental infections
•Acute lymphadenitis
Submaxillary and
submental
•Pediculosis capitis (lice)
•Tinea capitis/local skin infection
•Rubella
•Roseola
Occipital
•Local skin infection
•Chronic ophthalmic infection
Preauricular (rarely
palpable in children)

26. Differential Diagnosis
Mediastinal (not directly
palpable; assess indirectly via
presence of supraclavicular
adenopathy.
• May manifest as cough, dysphagia,
hemoptysis, or SVC syndrome
• ALL
• Lymphoma
• Sarcoidosis
• Cystic fibrosis
• Granulomatous disease (tuberculosis,
histoplasmosis, coccidioidomycosis)

27. • Local infection
• Cat scratch disease
• Brucellosis
• Reactions to immunizations
• Non Hodgkin lymphoma
• Juvenile rheumatoid
arthritis
Axillary

28. Differential Diagnosis
Abdominal
• (may manifest as abdominal pain, backache, urinary frequency,
constipation, or intestinal obstruction due to intussuception)
•Acute mesenteric adenitis
• Lymphoma
Inguinal
• Local infection
•Diaper dermatitis
• Syphilis
• Genital herpes

29. Clinical approach

30. History
1- Onset-course- duration of (fever & LN)apathy.
2-fever pattern & duration :
*recurrent fever brucellosis. Hodgkin L.
*Relapsing fever in TB.
3-History of contact with animal
(cat scratch fever-rat bite fever-brucellosis-TB.)

31. History
4-History of travelling
(malaria-kala azar-plague-trypanosomiasis.)
5-history of sexual activity (STD)
6-Diet raw milk, processed meat
(brucella -toxopl.)
7-Drug history???

32. Medications That May Cause
Lymphadenopathy
Allopurinol
Atenolol
Captopril
Carbamazepine
Cephalosporins
Gold
Hydralazine
.
Penicillin
Phenytoin
Primidone
Pyrimethamine
Quinidine
Sulfonamides
Sulindac
Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas P.
Clinical approach to lymphadenopathy.

33. 8-Weight loss and toxemia-
(TB-malignancy).
9-FUO
(TB-brucella-malignancy-collagen
disease.

34. Examination
Site ……drained area.
Size……..large (real pathology).
Small may be present without pathology especially
in inguinal(bare footed persons…&axillary in hand hard
workers.
Consistency
soft =acute infection..
firm = chronic infection+ malignancy.
Hard = malignancy.
Cystic = pus or caseation.
tenderness = infection
Mobility fixed =malignacy….mobile benign lesion..

35. Skin over fixed (malignancy-infective ulcer.)
Matted chronic infection (TB)

36. Evaluation of Suggestive S & S Associated with Lymphadenopathy
Mononucleosis-type
syndromes
Fatigue, malaise, fever, atypical
lymphocytosis
Epstein-Barr virus* Splenomegaly in 50% of patients Monospot, IgM EA or VCA
Toxoplasmosis* 80 to 90% of patients are
asymptomatic
IgM toxoplasma antibody
Cytomegalovirus* Often mild symptoms; patients may
have hepatitis
IgM CMV antibody, viral
culture of urine or blood
Initial stages of HIV
infection*
"Flu-like" illness, rash HIV antibody
Cat-scratch disease Fever in one third of patients; cervical
or axillary nodes
Usually clinical criteria; biopsy
if necessary
Pharyngitis due to group A
streptococcus,
gonococcus
Fever, pharyngeal exudates, cervical
nodes
Throat culture on appropriate
medium
Tuberculosis lymphadenitis* Painless, matted cervical nodes PPD, biopsy
Secondary syphilis* Rash RPR
Hepatitis B* Fever, nausea, vomiting, icterus Liver function tests, HBsAg

37. Lymphogranuloma venereum Tender, matted inguinal nodes Serology
Chancroid Painful ulcer, painful inguinal nodes Clinical criteria, culture
Lupus erythematosus* Arthritis, rash, serositis, renal, neurologic, hematologic
disorders
Clinical criteria, antinuclear antibodies,
complement levels
Rheumatoid arthritis* Arthritis Clinical criteria, rheumatoid factor
Lymphoma* Fever, night sweats, weight loss in 20 to 30% of patients Biopsy
Leukemia* Blood dyscrasias, bruising Blood smear, bone marrow
Serum sickness* Fever, malaise, arthralgia, urticaria; exposure to antisera
or medications
Clinical criteria, complement assays
Sarcoidosis Hilar nodes, skin lesions, dyspnea Biopsy
Kawasaki disease* Fever, conjunctivitis, rash, mucous membrane lesions Clinical criteria

38. Less common causes of lymphadenopathy
Lyme disease* Rash, arthritis IgM serology
Measles* Fever, conjunctivitis, rash, cough Clinical criteria, serology
Rubella* Rash Clinical criteria, serology
Tularemiala* Fever, ulcer at inoculation site Blood culture, serology
Brucellosis* Fever, sweats, malaise Blood culture, serology
Plague Febrile, acutely ill with cluster of tender nodes Blood culture, serology
Typhoid fever* Fever, chills, headache, abdominal complaints Blood culture, serology
Still's disease* Fever, rash, arthritis Clinical criteria, antinuclear antibody,
rheumatoid factor
Dermatomyositis* Proximal weakness, skin changes Muscle enzymes, EMG, muscle biopsy
Amyloidosis* Fatigue, weight loss Biopsy
*--Causes of generalized lymphadenopathy.
EA=early antibody; VCA=viral capsid antigen; CMV=cytomegalovirus; HIV=human immunodeficiency virus; PPD=purified protein derivative; RPR=rapid plasma reagin; HBsAg=hepatitis B
surface antigen; EMG=electromyelography.

39. Associated S
Fever –
malaise-rash-cough-diarhea
&S. infectio
n
Acute
Measles
CMV
EBV
Typhoid
Brucellosi
s
Chronic
T.B.
Musculoskel
etal
+multiple
system
affection
+long
duration
Collagen
diseases.
SLE.
Rh.Arhetitis.
Still’s disease
Marked cachexia &
anemia
Malignanc
y
e.g.
Lymphoma
Leukemia

40. After history,examination &
investigation We have final diagnosis
yes
no
2-3 w
……..why?
To give a chance for
acute disease to be
subsided
subside
d
investigation

41. investigati
on
Non specific
investigation Specific
1-CBP, peripheral blood smear investigation
ESR
2-Rule out infectious causes: Monospot, CMV,
EBV, & toxoplasma, Bartonella titres, TB skin
test, Anti-HIV test, CRP, ESR
3-Hepatic and renal function + urine analysis
(systemic disorders that can cause
lymphadenopathy)
4-Lactate dehydrogenase, uric acid, calcium,
phosphate, magnesium if malignancy suspected
5-US guided lymph node biopsy

42. Bone marrow,
Nuclear medicine scanning
is helpful in the
evaluation of lymphomas

43. Biopsy
indications

44. Specific investigation
i.e. Extensive imaging of drained areas
2-Supraclavicular 3-axillary 4-inguinal
1-Cervical
L.N.
e.g.laryngeal view during laryngoscopy
CT,MRI & Endoscopy of head & neck
e.g. Reconstructed CT scan of the neck
demonstrates a midline cystic lesion

45. Specific
investigation
i.e. Extensive imaging of drained areas
Cervical L.N.
axillary inguinal
2-Supraclavicular
CT & Endoscopy of chest abd. pelvis .1

46. Specific
investigation
i.e. Extensive imaging of drained areas
Cervical L.N. Supraclavicular inguinal
3-axillary
X-Ray chest-CT chest-mammography
Chest CT scan of the left lower lobe showing
cavitary pneumonia
Mammogram showing calcification

47. Specific
investigation
i.e. Extensive imaging of drained areas
Cervical L.N. Supraclavicular
4-inguinal
axillary
CT lower limb & pelvis Tuberculosis of the bladder

48. If we have no specific
diagnosis
Tissue biopsy
F.N.A.C Excisional
biopsy

49. Red flags in L.N.
apathy
1-Supraclavicular L.N.
2-If associated with:
Prolonged fever.
FUO.
Toxemia.
w.t. loss.
Cashexia.
3- hard &tender L.N. of
significant size
4-Non recessive
L.N. =after (2-3
W).or disappear of
fever
5-Matted or
fixed to the
surrounding
structure.
6-If associated to significant
pathology in the drained areas
e.g. SCC

50. Management
• Treatment with antibiotics. Bacterial infection results
in large nodes that are warm, erythematous, and
tender. Start on antibiotics that cover the bacterial
pathogens frequently implicated in lymphadenitis,
including staphylococcus aureus and streptococcus
pyogenes. Reevaluate in 2-4 weeks. Biopsy if
unchanged or larger.
• If malignancy is a strong possibility excisional biopsy
should be considered immediately.
• If lymphadenitis is present, aspirate may be needed
for culture.

51. Management
• Treat the underlying cause.
• If no specific cause – Antibiotic (10day course), if still
persist- give another course of other antibiotic
• Antifungal, anti-TB
• Chemotherapy- for malignancy
• HAART- for HIV
• Incision & drainage – nodes with suppuration