Elizabeth Jones and Charlotte Clements

Lymphadenopathy is pretty common in children and it can be a sign of nothing much (a reaction to a virus or bacterial infection), or something very serious (we’re talking malignancy, TB and other nasties). 

Having spent some time in our hospital’s rapid access clinic and seeing quite a few children who were referred for lymphadenopathy, I wanted to have a good structure for investigating and managing them appropriately – so after a lot of reading on the subject I’ve produced this article which serves as a guide (with some helpful flowcharts). Please note! This is to be used alongside clinical judgement, and as with everything in medicine there are no hard and fast rules.

First things first: Definitions

Lymphadenopathy is the enlargement of one or more lymph nodes. In the neonatal period this would be nodes bigger than 1cm and in older children bigger than 2cm.  Regional lymphadenopathy is the enlargement of lymph nodes in one area. Generalised lymphadenopathy is the presence of lymph nodes in two or more non-contiguous regions. Lymphadenitis is inflammation of lymph nodes. Lymph nodes can become enlarged over a couple of weeks and then regress and this reflects an acute process; it can also be chronic and last 6 weeks of more.

Aetiology

Lymphadenopathy happens because lymphocytes proliferate within the lymph nodes, or there is an influx of inflammatory or malignant cells into the lymph node. An enlarged lymph node can be painful (but doesn’t have to be).

A surgical sieve can be applied to help group the causes into sub-categories. The following table isn’t an exhaustive list, but is a good starting point.

As with all things clinical, start with a detailed history, followed by examination and then investigations only if needed to help make a diagnosis. I’ve listed some key areas of the history and examination to include in the workup of lymphadenopathy. 

Often the history and examination alone will point to a specific diagnosis – if this is the case further investigations might not be needed.   

A detailed history

• When, how and where did it start? Is it getting better or worse? And is it associated with pain? 
• Are there any associated symptoms such as cough and cold to suggest infection as a cause, or systemic features such as ‘B symptoms’ of lymphomatous disease?
• Has there been any recent foreign travel, or contact illness? This may make an infective cause such as EBV or Tuberculosis more likely 
• Is the child fully immunised and have they had recent vaccines? The BCG can cause lymphadenopathy.  
• Has the child got any significant past medical history or are they on any medications?
• Is there any family history of note or any pets? Cat scratch disease can cause localised lymphadenopathy. 

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Examination

Does the child look well or unwell? Do they have a temperature?

What is the weight and height; plot it and check trends. Weight loss can point to malignancy or tuberculosis. 

Do a routine examination of cardiovascular, respiratory, neurological and gastrointestinal system.

Is there any organomegaly? Is the lymphadenopathy limited to one region or generalised?  Generalised and supraclavicular lymphadenopathy is worrying. Supraclavicular lymphadenopathy usually indicates mediastinal disease as a result

of tuberculosis or malignant pathology. Generalised lymphadenopathy indicates a systemic process either as a result of significant viral infection, or malignancy or tubercular infection, particularly if over 3cm. 

Are there any skin changes or rashes? Check hair and scalp as lymphadenopathy can be missed in these regions and eczema can cause lymphadenopathy. 

Check ear nose and throat and inside mouth for any periodontal disease. Anaerobic oral bacteria with poor dental hygiene can cause lymphadenitis. 

Examining lymph nodes: use a look, feel and move approach.

Look: check the site and overlying skin

Feel: Measure the size. What do the edges and surfaces feel like and what is the consistency (are they fluctuant suggesting infection or hard)? Are they tender?

Move: Are they fixed to adjacent tissues which could indicate a malignant infiltration? 

Investigations

Blood tests: FBC and film/CRP/ESR/LFTs: This can help identify a malignant or inflammatory process. Certain viruses can cause hepatitis, and this will be reflected by deranged LFTs. 

Microbiology tests: Tissue cultures (throat swab, blood cultures or culture from a nodal aspirate)

Serology for viruses: EBV is common. Consider HIV (much less common)

Tuberculosis screening: Mantoux and Quanteferon testing. A strong tubercular intradermal skin test (over 15mm) indicates tubercular infection, whereas a less strong reaction could be in keeping with non tubercular mycobacterial infection or previous BCG vaccination. 

Imaging / other investigations

A chest x-ray can show mediastinal masses, hilar lymph nodes and point toward malignancy or tuberculosis. 

Ultrasound: A cervical lymph node USS may help provide clues about non-infective versus infective pathology by looking at shape, border and distribution of perfusion. It can also rule out congenital masses such as branchial cysts.  However, an ultrasound alone can’t reliably diagnose lymphadenopathy that is infective, malignant or tuberculosis – other investigations will be needed. An ultrasound of the abdomen can help identify an intra-abdominal mass or widespread lymphadenopathy. 

Biopsy: Unexplained large lymphadenopathy with red flags may need biopsy (at this point, the tertiary oncology service will need to be involved – they may advise more appropriate first line investigations depending on the likely diagnosis – for example with suspected leukaemia, a bone marrow aspirate is diagnostic and a lymph node biopsy is then not required). 

If a biopsy is performed it should be done by an experienced surgeon and they will usually do an excisional biopsy of the most abnormal node. This is to make sure that any malignant/immunological process is captured, and no sinus or fistula is formed if Tuberculosis or atypical mycobacteria is present. 

Red flags for serious underlying pathology

• Systemic symptoms
• Supraclavicular lymph nodes
• Generalised lymphadenopathy, no clear evidence of viral infection (by history or by blood tests)
• Lymph nodes that are over 1cm (in neonates) or over 2cm (in older children) and don’t respond to treatment or regress in a 4 week window of observation
• Abnormal chest X-ray
• Abnormal blood tests – cytopenia or blasts, or persistently raised inflammatory markers
• Fixed and non-tender nodes in the absence of other symptoms
• Nodes that get bigger (or that don’t reduce in size) during a 4 week observation period
• Absence of localised symptoms to explain the lymphadenopathy (e.g. ENT symptoms) – to be taken in context of full picture

These flow charts will help guide you through managing most cases of lymphadenopathy that present to the outpatient clinic.

Managing Generalised Lymphadenopathy and Supraclavicular lymphadenopathy

Managing Regional lymphadenopathy

Ongoing Management

Most of the time, lymphadenopathy is secondary to a viral or bacterial infection. If there is clearly a local bacterial infection (lymphadenitis), treat it with antibiotics. Oral antibiotics are usually OK if the child is systemically well. Antibiotic wise, co-amoxiclav or clindamycin are good choices because they cover staph and strep infections. (Your local micro guidance may be different – double check). 

Azithromycin can be added if you suspect cat scratch disease. 

If the lymph node / nodes are OVER 2cm in size and there is no clear infective pathology (or if there are any ‘red flags’ indicating possible malignancy or TB) then you do need to do some basic investigations. These investigations are also a good idea if the lymphadenopathy is persistent (even if there are small nodes under 2cm). 

If red flags develop that suggest malignancy, discuss with your local oncology service for advice and further investigations. 

As the flow charts indicate, a child with lymphadenopathy needs regular reviews within a four-week period – the literature suggests that (if there are no red flags) this is a safe time frame for observation to check for resolution or progression of symptoms. 

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Summary

Lymphadenopathy is common! And for most children, it is simply a sign of viral or bacterial infection that will either resolve on its own or with some antibiotics.

HOWEVER it can be a sign of something more worrying going on – this is why it is so crucial to make sure we don’t miss a potential problem which needs more intensive investigation and treatment.

• Always take a FULL history and FULLY examine the patient 
• Generalised lymphadenopathy, supraclavicular lymphadenopathy or nodes are larger than 2cm without clear infective pathology, need further investigations 
• Review your patient regularly to check the lymphadenopathy is resolving
• Red flags suggesting malignancy? Refer early to local tertiary oncology service

Elizabeth Jones, Paediatric Registrar, and Charlotte Clements, Paediatric Emergency Medicine Consultant

Extra Reading

1. King D, Ramachandra J, Yeomanson D. Lymphadenopathy in children: refer or reassure? Arch Dis Child Educ Pract Ed. 2014;99(3):101-110.
2. Leung AK, Robson WL. Childhood cervical lymphadenopathy. J Pediatr Health Care. 2004;18(1):3-7.
3. Nield LS, Kamat D. Lymphadenopathy in children: when and how to evaluate. Clin Pediatr. 2004;43(1):25-33.
4. Twist CJ, Link MP. Assessment of lymphadenopathy in children. Pediatr Clin North Am. 2002;49(5):1009-1025.
5. https://www.uptodate.com/contents/peripheral-lymphadenopathy-in-children-evaluation-and-diagnostic-approach