Cervical Lymphadenopathy in Children
Cervical Lymphadenopathy in Children Dr Katharine Hamlett, Miss Neil Killick, Dr Vineeta Joshi, Mr Vikas Malik
Introduction
Lymphadenopathy is defined as the disease of lymph nodes whereby there is an atypical number , size or consistency of nodes (1). Lymphadenopathy with signs of inflammation is typically referred to as Lymphadenitis (2).
Enlargement of cervical lymph nodes (LNs) is a common presenting sign in children and can present a diagnostic challenge. Studies have found that many as 38-45% of healthy children have palpable neck LNs (3). Whilst benign pathology is more common, malignancies are possible and a source of significant parental concern/anxiety. A structured approach allows for consistency in management and can allay parental concerns. There are numerous causes of lymphadenopathy (table 1). In contrast to adults, infective and congenital aetiology are more prevalent in children (4).
In this article we discuss the anatomy, pathophysiology, aetiology, and suggest an evidence based, practical approach to the investigation and management of cervical lymphadenopathy in children.
Anatomy
Anatomical division of lymph nodes based on the American Medical Association Consensus statement (figure 1) can indicate the source of primary pathology due to lymphatic drainage and allows for communication between colleagues at MDT discussions.
Pathophysiology
Lymph nodes are structured collections of immune cells that act as a filter for antigens in extracellular fluid (6). There are numerous lymphocytes and antigen-presenting cells in LNs which help to identify and filter antigens found in places such as the blood, skin and gastrointestinal tract.
Neonates start with scarcely detectible LNs but this rapidly changes in childhood. In contrast to adults, children have a very variable LN mass due to the constant exposure to new pathogens (7). In the first 12 years of life, lymphoid mass increases rapidly in size to double that of an adult at puberty (8). During adolescence, atrophy of this mass occurs and continues into adult life (6).
The mechanism of lymphadenopathy is frequently divided into the following (2):
Reactive hyperplasia of lymph node cells in response to a stimulus e.g. viral lymphadenitis
The inward migration of inflammatory cells in response to bacterial infection
Tumour invasion into the lymphoid tissue e.g. metastases and lymphoma
Aetiology
There are numerous causes of paediatric cervical lymphadenopathy (table 1). Citak et al found that out of 282 children studied with cervical lymphadenopathy that had benign disease, only 36% had a specific identifiable aetiology. Of these, the most prevalent causes were Cytomegalovirus, Infectious Mononucleosis and Acute Lymphadenitis (9). In another study by Bozlak et al, the most common malignant cause for cervical lymphadenopathy found was Lymphoma, which was mainly in older children (10).
History and Examination
In children presenting with a neck mass, a comprehensive history and head and neck examination should always be carried out to help narrow down a diagnosis. This should include the assessment of peripheral LNs and a general physical examination (11). As seen in table 2, there are many differential diagnoses of neck masses in children. Patient age is a key factor in ascertaining diagnoses as different disease processes have characteristic age associations.
Infections
History of immunisations, medications, foreign travel and pets may also help to determine diagnosis e.g. in cat-scratch disease, parasites etc. A study by Neidzielska et al found that the most common associated symptom of children with cervical lymphadenopathy was fever, occurring in 24.1% (4).
Malignancy
The history should include onset, duration and speed of growth of the LN, as this may help to determine the likely diagnosis. For example, in HL, there is slow growth in LNs, whereas the change is more rapid in NHL (10). Duration and size of the lesion is significant because a lesion present for greater than 4 weeks has an elevated probability of being malignant in nature (12). A cohort study by S. Bozlak et al found that predictive factors for malignancy were LNs greater than 30mm, rubbery textured nodes, elevated serum CRP and LDH and increased growth in the node at follow-up (10). Position of the lymph node is also significant as supraclavicular nodes in children are usually indicative of malignancy (10). The site of the swelling, including whether it is unilateral or bilateral is also useful in determining cause.
Autoimmune Diseases
A small subset of patients with lymphadenopathy will have an autoimmune aetiology. Systemic features such as a fever persisting beyond 5 days, strawberry coloured tongue with fissuring of lips, bilateral conjunctivitis (non-purulent), angioedema with induration on the hands and feet and dysmorphic-looking skin rashes are signs of Kawasaki disease (13). SLE often presents with the characteristic malar rash, lymphadenopathy, fever , weight loss, fatigue and occasionally Raynaud’s phenomenon (14). Joint management with the Paediatric team is essential.
Investigation and Management
Studies suggest that children with LNs measuring less than 20mm diameter , with no red flag symptoms or with obvious signs of infection can be observed for 10-14 days (15). If there is enlargement or the node does not regress, further investigations should be done including at least the basic serum tests and appropriate imaging.
Blood Tests:
Bloods tests should include FBC, U&Es and CRP to assess for infective pathology. Trial with antibiotic therapy is then often adopted if infection markers are elevated.
Microbiology:
Specific serological tests for CMV , HIV , EBV and Bartonella may also be done based upon the presenting history. Tuberculosis (TB) testing can be performed if the child is at risk. A throat swab may also help identify infective oropharyngeal causes and help guide treatment.
Imaging:
Ultrasound is a valuable tool to assess enlarged LNs in children due to lack of radiation exposure, ease of access and simplicity to perform in trained hands. Chest X-Rays may be required to identify changes associated with diseases such as Histiocytosis, Sarcoidosis or TB (15).
Surgery:
If after 4 weeks there is no improvement, an excisional biopsy is the next step (15). Excisional biopsy is the gold standard as fine needle aspiration is often challenging to execute in an awake child and is frequently nondiagnostic (4).