When Should You Evaluate Lymphadenopathy?

Patient Presentation
A 10-year-old female came to clinic with “swelling in her armpit.” She was healthy except for eczema flares, but noted the swelling about 6 days ago and it is described as somewhat painful. She also had a low grade fever about the same time.
On her review of systems she had no weight loss, night sweats, or malaise. She did have some red bumps on her arm recently that were bigger than her normal eczema flares. She has no recent travel history, she has a pet cat and guinea pigs at school.
The pertinent physical exam shows normal vital signs and growth parameters. She has shoddy anterior and inguinal adenopathy. She has a 1.5 cm solitary left axillary node that is firm, and mobile with minimal overlying induration and pain. She has a mild lichenified rash medially on her elbow that is somewhat excoriated, red and raised appearing. The rest of her examination is normal.
The patient was treated for mild impetigo with Cephalexin antibiotic. After 2 weeks she returned and the axillary lymph node had not decreased in size. She had no fever and the impetigo had resolved.
The work-up at that time included complete blood count which showed a white blood cell count of 14 X 1000/mm2, erythrocyte sedimentation rate of 15 mm/hr and liver function tests which were normal. Additionally she had a tuberculosis skin test placed that was negative. An immunofluorescence antibiody assay eventually returned positive for Bartonella henselae and the diagnosis of Cat Scratch Disease was made.
She was treated with Azithromycin antibiotics and was to return in two weeks for re-evaluation.

Discussion
Cat Scratch Disease is caused by Bartonella henselae, a slow-growing, gram-negative bacillus. It commonly occurs in people younger than 20 years of age. Cats are common reservoirs especially kittens. Cat fleas transmit the organism between cats but there is no known person-to-person transmission.
Diagnosis is generally made by immunofluorescence antibody. Treatment is primarily symptomatic with resolution usually within 2-4 months. Antibiotics may speed resolution, but painful supprative nodes may need drainage for relief.

Almost everyone has a few palpable lymph nodes at any time. Palpable lymph nodes are normal in anterior cervical, axillary and inguinal regions in healthy children.
Lymphadenopathy is enlargement of the lymph nodes beyond this normal state. Practically this is any node >1.0 cm in greatest diameter, but certain nodes should be considered enlarged at different sizes (i.e. epitrochlear nodes > 0.5 cm, inguinal nodes > 1.5 cm, submandibular nodes > 1.5 cm).
The history and physical examination are particularly important in determing the differential diagnosis and ultimately the timing, workup and treatment of lymphadenopathy.

History

  • Duration
    • Short (< 2 weeks) – likely to be infectious
    • Long (> 2 weeks but < 1 year) – likely to be infectious, malignancy, autoimmune, drug reaction
    • Very long (> 1 year) likely to be pathologic but not malignancy
  • Location
    • Localized – likely to be infectious
    • Regional – likely to be infectious
    • Generalized – more likely pathologic (e.g. malignancy, autoimmune, etc.)
    • Head and Neck – likely infectious
    • Mediastinal – likely pathologic
    • Abdominal – likely pathologic
    • Inguinal – likely infectious
  • Associated symptoms – each may be associated with infectious, malignant, autoimmune, or immunodeficiency diseases
    • Pain
    • Fever
    • Weight loss (> 10% over 6 months)
    • Night sweats
    • Pruritis
    • Myalgia/arthralgia
    • Rashes
    • Malaise
  • Other history
      Pets – especially cats for Cat Scratch Disease

    • Travel – including Tuberculosis exposure
    • Possible immunodeficiency such as HIV
    • Family history of similar problems
    • Previous treatments such as antibiotics and how patient responded
    • What do parents think might be going on? What are parents most worried about?

Physical Examination

  • Nodes themselves
    • Location – local, regional, generalized lymphadenopathy
    • Size
    • Character – e.g. firm, rubbery, etc. is subjective and may or may not be helpful
    • Fixed or non-fixed may be more helpful
    • Erythema and tenderness – likely infectious

      Note:
      Generalized, firm, discrete, non-tender, fixed tend to be more ominous causes such as malignancy
      Localized, warm, tender, matted, erythematous – tend to be associated with infections

  • Other Signs
    • Signs of anemia – tachycardia, pale conjunctiva – may be associated with malignancy, autoimmune diseases
    • Dermatological changes – petechiae, bruising, bleeding – may be associated with malignancy
    • Weight/growth – poor growth may be associated with malignancy

The differential diagnosis of lymphadenopathy is large. Common categories include:

  • Infectious
    • Bacterial – Staphylococcus, Streptococcus, Cat Scratch Disease, Toxoplasmosis, Syphilis, Tuberculosis, Atypical mycobacterium, Brucellosis, Tularemia, Leptospirosis

    • Viral – Epstein Barr Virus, Cytomegalovirus, HIV, Rubella, Hepatitis B
    • Fungal – Aspergillosis, Candida, Histoplasmosis
  • Malignant – Leukemia, Lymphoma, Metastatic
  • Autoimmune – Rheumatoid arthritis, Systemic Lupus Erythematosis, Serum Sickness, Sarcoidosis
  • Immunodeficiency – HIV
  • Drug reactions – Phenytoin, Hydralazine, Allopurinol
  • Endocrine – Hyperthyroidism
  • Other benign/pathologic processes – Storage diseases, Embryological cysts

Learning Point
When should lymphadenopathy be evaluated depends on the history, physical examination, differential diagnosis, level of suspicion of serious underlying pathology and the anxiety of the patient, parent and health care provider. There is not one single approach.

A general approach is outlined below.


Figure 14 – Diagram showing an algorighm for evaluation of lymphadenopathy

Patients generally should be considered for referral if:

  • Unexplained generalized lymphadenopathy

  • Any supraclavicular or popliteal node that is palpable
  • Significant constitutional symptoms
  • Hepatic or splenic enlargement
  • Anemia or bleeding
  • Unresponsiveness to antibiotic treatment
  • Not decreasing in size after appropriate period of observation

The evaluation of lymphadenopathy may include a number of tests as indicated by the history, physical examination, differential diagnosis, index of suspicion and the anxiety of the patient, parent and health care provider.
These may include:

  • Laboratory – complete blood count with differential, erythrocyte sedimentation rate or C-reactive protein, lactate dehydrogenase, uric acid, liver function tests
  • Purified Protein Derivative skin test for Tuberculosis
  • Viral titers
  • Other titers – Toxoplasmosis, Bartonella henselae
  • Chest radiograph
  • Consultation with surgery, oncology, rheumatology, infectious disease, radiology
  • Biopsy

Questions for Further Discussion
1. What are the indications for a fine needle aspiration?
2. What are the indications for an incisional or excisional biopsy?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: Cat Scratch Disease.

Morland B. Lymphadenopathy. Arch Dis Child 1995;74(5):476-479.

Perkins SL, Segal GH, Kjeldsberg CR. Work-up of Lymphadenopathy in Children. Sem Diag Pathol. 1995;12(4):284-287.

Twist CJ, Link MP. Assessment of Lymphadenopathy in Children. Ped Clin North Amer. 2002:49;1009-25.

American Academy of Pediatrics. Cat-Scratch Disease, In Pickering LD, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2003;232-234.

Umapathy N, De R, Donaldson I. Cervical Lymphadenopathy in Children. Hospital Medicine. 2003;64(2):104-7.

Leung AKC, Robson WLM. Childhood Cervical Lymphadenopathy. J Pediatr Health Care. 2004;18:3-7.

Nield LS. Lymphadenopathy in Children: When and How to Evaluate. Clin Pediatr. 2004;43:25-33.

Author
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa

Date
April 25, 2005