Lymphadenopathy

In kids Posted by Ahmad Azizov on July 20, 2020

Lymphadenopathy

Lymphadenopathy is the enlargement and hardening of lymph nodes. When lymphadenopathy is infectious or inflammatory in etiology, this is known as lymphadenitis. A common presentation for lymphadenitis is red skin on top of the lymph node with edema, tenderness and pain. 

Diagram 1. Posterior cervical lymphadenopathy 

The lymphatic system

  • Lymph vessels
    • Interstitial fluid trapped in the cells is transported back into the circulation via the lymphatic system
    • Similar to the veins, skeletal muscle movement and a series of one-way valves ensure that lymph can flow against gravity
    • Additionally, peristalsis of lymphatic capillaries serves this function as well. 
  • Lymphoid organs.
    • These contain lymphocytes and a number of other cells that play a role in immunity
    • Primary lymphoid organs - create lymphocytes 
      • Bone marrow - B lymphocytes 
      • Thymus - T lymphocytes 
    • Secondary lymphoid organs - proliferate lymphocytes
      • Lymph nodes - 600 in the body 
        • Act as filters for the lymph 
        • Lymph flow>multiple afferent lymph vessels>single efferent lymph vessel
        • Anatomy
          • Cortex 
            • Contains follicles 
            • Follicles are the site of B cell activation 
            • Follicular dendritic cells are also in this section 
              • They collect antigens and make it easier for the B cells to be activated
              • These cells are implicated in HIV
            • Primary follicles 
              • Inactive 
              • B cells and follicular dendritic cells 
            • Secondary follicles 
              • Activated 
              • Germinal center 
              • B cell growth and proliferation
          • Paracortex 
            • Contains
              • T cells 
                • Can be activated by antigen bound dendritic cells 
              • High endothelial venules 
                • Entrance points for B and T cells 
          • Medulla 
            • Contains sinuses 
              • Sites of macrophages 
            • Medullary chords 
              • Contain plasma cells that synthesize antibodies
        • Site of infection 
          • Activated dendritic cells and free antigens enter lymph from the infection site
          • B and T cells meet their unique antigen matches in the lymph nodes 
        • Immune cells inside inject antibodies into efferent lymph
        • Lymph nodes enlarge due to infection or antigen stimulation due to 
          • Lymphocytes proliferate inside lymph nodes 
          • Hyperplasia of lymph node cells
          • Tissue edema 
      • Spleen - important for the destruction of encapsulated bacteria
        • Unlike lymph nodes, the spleen filters the blood and not the lymph
        • Blood enters from the splenic artery 
          • White pulp 
            • Exposure to B and T lymphocytes 
            • Exposure to macrophages 
          • Red pulp 
            • Filters the blood through sinusoids  
            • Removes old red blood cells 
            • Stores 30-40% of platelets 
      • Peyer's patches in the ileum 
      • Appendix 
      • Tonsils 

Approach to the lymph node exam

History 

Usually, lymphadenopathy in kids is associated with systemic signs such as fever. Age of the patient, location, onset time of the lymph node swelling, risk factors and medication history are important history details for lymphadenopathy. 

  • Age 
    • Children under 5 with swollen lymph nodes are likely to have an infectious cause
    • Neonates with lymphadenopathy should be investigated for toxoplasmosis, syphilis and cytomegalovirus
    • Older patients have increased likelihood for malignancy such as a lymphoma 
  • Location 
    • Cervical lymphadenopathy
      • Commonly associated with viral upper respiratory illness
    • Supraclavicular lymphadenopathy
      • Always abnormal 
      • Malignancy risk high 
      • Lymphoma, TB, sarcoidosis 
    •  Generalized lymphadenopathy 
      • Swelling of 2 or more non-neighbouring lymph nodes
      • Most related to benign self-limited viral illness or bacterial
  • Onset time 
    • Acute (<4 weeks)
      • Acute viral or bacterial infection 
    • Chronic (>4 weeks) 
      • More likely to be a malignancy or a chronic infection 
    • Look at the drainage area for sites of infection 
      • Sore throat, congestion, red eyes with discharge, oral ulcers, etc.
  • Risk factors 
    • Sick contacts
    • Immunization status 
    • Allergies
    • Travel history for TB and leishmaniasis
    • Contact with animals  
      • Disease Animal Infection
        Cat scratch disease Kittens Skin 
        Toxoplasmosis  Cat Ingestion from cat feces
        Tularemia  Multiple animals such as rodents and insects Tick bite 
        Brucellosis  Farm animals  Unpasteurized milk products 
        Histoplasmosis Birds and bats  Inhalation of the bird's nest
  • Medications
    • Penicillin, cephalosporins, phenytoin, carbamazepine = can cause generalized lymphadenopathy 
    • Recent vaccination
      • Measles, rubella, diphtheria 

Physical exam 

Start with vitals and the presence of systemic signs (fever, chills, night sweats, poor weight gain). Systemic signs can be caused by infections such as TB, HIV or lymphoma.  

  • Inspection 
    • Swelling 
    • Skin changes 
      • Erythema 
      • Edema 
    • Drainage area exam 
      • Head, neck for scalp infections 
      • Ears for otitis media 
      • Mouth for oral ulcers, pharyngitis, dental problems 
    • Rashes or petechia 
  • Palpation 
    • Size
      • Lymph nodes > 2 cm 
        • More likely to be caused by a serious disease
    • Location
    • Fixation
    • Tenderness
    • Mobility
    • Consistency
    • Abdominal exam
      • Splenomegaly
      • Hepatomegaly
      • Abdominal masses - neuroblastoma  

Normal lymph node sizes vary in different parts of the body even in healthy individuals. 

Region Normal lymph node size
Cervical <1cm 
Axillary  <1cm
Inguinal  <1.5cm
Epitrochlear region <0.5cm

In general, children have more large lymph nodes because their immune system is constantly being exposed to new antigens never encountered before. 

Table 2. Concerning and non-concerning lymph nodes
Concerning signs for malignancy Less concerning signs 
Generalized Localized
Size >2cm <1-2 cm depending on the location 
Firm  Red
Non-tender Tender
Rubbery Warm 

Systemic symptoms 

  • Fever lasting more than 1 week
  • Weight loss
  • Mediastinal widening
Fluctuating 
Location: Occipital, supraclavicular, mediastinal and posterior cervical nodes Location cervical, inguinal and axillary

Investigations 

  • CBC with differential 
  • CRP, ESR
  • Rule out specific infections 
    • Monospot
    • CMV
    • EBV
    • Toxoplasma 
    • Bartonella titres
    • TB
    • HIV
  • Liver and kidney function and urinalysis
  • Malignancy
    • Lactate, uric acid, calcium, phosphate, magnesium 
  • Biopsies 
    • Bone marrow
    • Liver
    • Lymph node 

Imaging 

  • Chest x-ray 
    • Mediastinal adenopathy 
    • Pulmonary disease
      • TB
      • Lymphomas 
      • Neuroblastoma 
  • U/S
    • Ultrasound of the node 
    • Can diagnose abscesses 
  • CT chest or abdomen 
    • Especially important for supraclavicular lymphadenopathy (associated with chest and abdominal disease) 
  • Nuclear medicine scanning 
    • Lymphomas 

Differential diagnosis 

  • Generalized - 2 or more non-neighbouring lymph node swelling 
    • Infectious 
      • Viral
        • Upper respiratory tract infection 
        • Measles
        • Varicella 
        • Rubella 
        • Hepatitis 
        • HIV 
        • EBV 
        • CMV
        • Adenovirus 
      • Bacterial 
        • Syphilis 
        • TB
        • Typhoid fever 
      • Fungal 
        • Histoplasmosis
      • Protozoal 
        • Toxoplasmosis 
    • Non-infectious 
      • Rheumatological 
        • Sarcoidosis 
        • Rheumatoid arthritis 
        • Systemic lupus erythematous 
      • Serum sickness
      • Rosai-Dorfman disease
      • Storage diseases
        • Niemann-Pick disease, Gaucher disease 
    • Malignant 
      • Leukemia 
      • Lymphoma 
      • Neuroblastoma 
    • Drugs
      • Phenytoin
      • Allopurinol 
    • Hyperthyroidism 
  • Localized - 1 or more neighbouring lymph node swelling 
    • Cervical 
      • Infectious 
        • Viral upper respiratory infection 
        • EBV or CMV
        • GAS pharyngitis 
        • Staph aureus infection of lymph nodes 
        • Kawasaki disease
        • Rubella 
        • Catscratch disease
        • Toxoplasmosis 
        • TB
      • Neoplastic 
        • Acute leukemia 
        • Lymphoma 
        • Neuroblastoma 
        • Rhabdomyosarcoma 
    • Submaxillary + submental 
      • Oral and dental infections 
      • Acute lymphadenitis 
    • Occipital
      • Lice 
      • Local skin infection 
      • Rubella 
      • Roseola 
    • Preauricular 
      • Local skin infection 
      • Chronic ophthalmic infection 
    • Mediastinal 
      • Lymphoma 
      • Sarcoidosis 
      • Cystic fibrosis 
      • Granulomatous disease 
    • Supraclavicular 
      • Lymphoma 
      • TB
      • Histoplasmosis
      • Coccidioidomycosis
    • Axillary 
      • Local infection 
      • Cat scratch disease
      • Brucellosis 
      • Vaccine reactions 
      • non-Hodgkin lymphoma 
      • Juvenile arthritis 
      • Hidradenitis suppurativa
    • Abdominal 
      • Acute mesenteric adenitis 
      • Lymphoma 
    • Inguinal 
      • Local infection 
      • Diaper dermatitis 
      • Syphilis 

Management 

Management depends on the likely etiology of the lymphadenopathy. Glucocorticoids can reduce the size, but this does not cure the underlying issue and should be avoided until a definitive diagnosis is made.

  • Reactive lymphadenopathy  
    • This is a secondary lymph node swelling due to an infection in the drainage area 
    • Common in pharyngitis and upper respiratory infection 
    • Antibiotics that cover group A strep and staph aureus
    • Re-evaluate in 2-4 weeks and biopsy if the node is unchanged 
  • Suspected malignancy
    • Excisional biopsy 
  • Lymphadenitis 
    • Bacteria invade and proliferate in the lymph node 
    • Lymph node fine needle aspirate for culture 

All information provided on this website is for educational purposes and does not constitute any medical advice. Please speak to you doctor before changing your diet, activity or medications. 


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