1. Approach to lymphadenopathy
Presented by: Hamad Alkhalaf,
General Pediatric Fellow
Children’s Hospital of Eastern Ontario
Date: May 10, 2013

2. 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

3. 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 .

4. 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.

5. Anatomy of Lymph node:

6. 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)

7. 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

10. 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

11. 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

12. 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.

13. 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

14. 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%)

15. 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

16. 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

17. Epidemiology
Uncommon causes of lymphadenopathy should be considered in certain areas
e.g. HIV in Africa
TB and other tropical diseases in developing nations

18. 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

19. Important definitions
Localized lymphadenopathy
Abnormal enlargement of one (or two contagious) LN
Generalized lymphadenopathy
abnormal enlargement of two or more noncontiguous LN

20. Important definitions
Acute lymphadenopathy
< 2 weeks duration
Subacute lymphadenopathy
2 – 6 weeks duration
Chronic lymphadenopathy
> 6 weeks duration

21. Bacterial lymphadenitis

22. Cat scratch

23. tularemia

24. atypical mycobacteria

25. Kawasaki

26. First visit evaluation
Stepwise management (detailed Hx, full Physical examination +/- less invasive tests) aid in selecting appropriate patients for further workup.

27. 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

28. 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)

29. History
Past History
 Recurrent infections, skin abscess, supporative adenitis (CGD, HIV)
 Autoimmune disease (autoimmune lymphoproliferative syndrome)
 B.Asthma ( churg –strauss syndrome)

30. History Immunization status - diphteria, measles, rubella Medications
- Amoxicillin rash in EBV
- Recent steroid therapy

31. History Drugs that cause lymphadenopathy Allopurinol Atenolol
Captopril
Carbamazepine
Cephalosporins
Gold
Hydralazine
Penicillin
Phenytoin
Primidone
Pyrimethamine
Quinidine
Sulfonamides
Sulindac
Drugs that cause lymphadenopathy

32. History
Family hx
malignancy, autoimmune, inflammatory, storage diseases
Social hx
Recent immigration

33. 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)

34. 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)

35. 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)

36. 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

37. Physical Examination Chest
Additional sounds (histoplasmosis, LCH, Churg-strauss)
Respiratory distress

38. 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)

39. Physical Examination Genitalia Skin  signs of STDs.
 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)

40. 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)

41. 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

42. Cystic hygroma

43. Branchial cleft cysts

44. Thyroglossal duct

45. 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)

46. 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)

47. 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

48. 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)

49. 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

50. Causes of generalized lymphadenopathy

51. Causes of generalized lymphadenopathy

52. Causes of generalized lymphadenopathy

53. Causes of generalized lymphadenopathy

54. Causes of generalized lymphadenopathy

55. Causes of generalized lymphadenopathy

56. 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)

57. 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

58. 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:

59. Work up Initial work up: - CBC (diff) - peripheral smear
- CRP, ESR, LDH, uric acid
- LFT, Renal functions
- CXR

60. Work up Specific tests - Throat c/s - viral studies (EBV, CMV)
- B.henselae titres
- PPD
- Autoimmune work up (ANA, Ds DNA)
- U/S

61. Work up Invasive tests:  BMA
 lymph node biopsy (excisional type preferred)
 biopsy of rash (if present)

62. Approach for Generalized LAD

63. Approach for Cervical LAD

66. Approach to axillary LAD

67. Approach to inguinal LAD

68. 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

69. 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
DOI /pir
5- Medscape Reference ( May 2012)
6- Current pediatrics Diagnosis and treatment 21th Ediation ( 2012).
7- Zetelli Atlas of Pediatric Physical& Diagnosis 6th Edition ( 2012)

70. Questions??