Cervical lymphadenopathy in children

Cervical lymphadenopathy (LAD) is a > 1 cm enlargement of lymph nodes in the neck. In children, cervical LAD is common and most often represents an inflammatory response to an acute infection, such as a viral upper respiratory infection or strep throat. Less commonly, it can signal a more serious underlying condition (e.g., malignancy, mycobacterial infection, autoimmune disease). Benign nodes are typically small and mobile, while concerning nodes may be large, firm, fixed, and/or accompanied by constitutional symptoms. Diagnosis is primarily clinical, but diagnostic evaluation (e.g., laboratory studies, imaging, lymph node biopsy) may be required in the case of red flag features or diagnostic uncertainty. Management is directed at the underlying cause (e.g., observation for viral infections; antibiotics for suspected bacterial lymphadenitis). Prompt specialist referral is indicated for features suggesting malignancy or other systemic conditions.

• Cervical lymphadenopathy is an enlargement of any cervical lymph node to > 1 cm in diameter or a palpable supraclavicular lymph node of any size. ^[1][2]
• The jugulodigastric lymph node is an exception; a diameter up to 1.5 cm is normal in children < 12 years of age. ^[1][2]

Cervical LAD in children is most often caused by an infectious etiology. Approximately 45% of otherwise healthy children have isolated cervical LAD on physical examination. ^[1][3]

Acute cervical LAD ^[1][4][5]

Cervical LAD in children is considered acute if present < 2 weeks. ^[1][6]

Infectious causes

• Viruses
  • Common respiratory viruses (e.g., adenovirus, influenza virus, respiratory syncytial virus, rhinovirus, coronavirus)
  • Enterovirus (i.e., coxsackievirus)
  • Rubella
  • Measles
  • HSV
  • Varicella zoster virus
• Bacteria
  • Staphylococcus aureus
  • Streptococcus pyogenes
  • Oral anaerobes
  • Less commonly, Haemophilus influenzae, Group B Streptococcus , and Corynebacterium diphtheriae

Noninfectious causes

• Kawasaki disease
• Serum sickness
• Immunizations (e.g., DTaP, polio, typhoid fever vaccines)

Most acute cervical LAD in children is due to viral respiratory infections or acute bacterial lymphadenitis caused by Staphylococcus aureus or Streptococcus pyogenes. ^[1][4]

Subacute and chronic cervical LAD ^[1][4][5]

Cervical LAD in children is considered subacute if present for 2–6 weeks and chronic if present for ≥ 6 weeks. ^[1][6]

Infectious

• Viruses
  • EBV and CMV: most common
  • HIV
• Bacteria
  • Bartonella henselae
  • Mycobacterium tuberculosis
  • Nontuberculous mycobacteria (e.g., Mycobacterium avium-intracellulare, Mycobacterium scrofulaceum)
  • Pasteurella multocida
  • Nocardia brasiliensis
  • Treponema pallidum
• Protozoa: Toxoplasma gondii
• Fungi (e.g., Candida, Histoplasma, Coccidioides, and Aspergillus spp.)

Noninfectious

• Autoimmune conditions, e.g.:
  • Juvenile idiopathic arthritis
  • Systemic lupus erythematosus
• Malignancy, e.g.:
  • Leukemia
  • Lymphoma
  • Neuroblastoma
  • Rhabdomyosarcoma
  • Metastatic nasopharyngeal cancer ^[2]
• Self-limited inflammatory conditions, e.g.:
  • PFAPA syndrome ^[7]
  • Necrotizing lymphadenitis
  • Rosai-Dorfman-Destombes disease

Cervical LAD lasting > 6 months without change in size and character or associated systemic symptoms has a low likelihood of being neoplastic in origin. ^[1][3]

Focused history ^[1][5]

• Onset, duration, and progression (e.g., change in size or character) of enlarged lymph nodes
• Associated symptoms
  • Localized pain and/or tenderness
  • Constitutional symptoms
  • Symptoms suggesting a primary source of infection, e.g.:
    • URI symptoms (e.g., sore throat, rhinorrhea, cough)
    • Bacterial infection in the head and neck region (e.g., acute tonsillitis and pharyngitis, periodontal disease)
    • Periodontal disease
  • Red flags for cervical LAD in children
  • Growth faltering ^[4]
• Exposures to: ^[5]
  • Illness (e.g., tuberculosis)
  • Travel
  • Animals (e.g., cats or cat feces, rabbits, sheep)
  • Recent vaccination (e.g., with DTaP, polio, typhoid fever vaccines)
• Relevant medical history (e.g., immunosuppressed state)

Focused examination ^[4]

• Vital signs, general appearance
• Head and neck examination, including:
  • Palpation of head and neck lymph nodes
    • Size
    • Tenderness, warmth, erythema
    • Consistency (e.g., soft, fluctuant, firm, rubbery)
    • Mobile vs. fixed
    • Unilateral vs. bilateral
  • Signs of underlying etiology in the drainage region (including the oropharynx and dentition) ^[4]
• Assessment for red flags for cervical LAD in children

Examine all lymph node regions in children with cervical LAD, as systemic infections (e.g., due to EBV, CMV, HIV, or M. tuberculosis), autoimmune conditions, and malignancy may cause generalized LAD. ^[3][5]

Red flags for cervical LAD in children ^[1][5]

The following features prompt evaluation for serious underlying etiology (e.g., malignancy, granulomatous disease, autoimmune conditions).

• Lymph node characteristics
  • Size > 2 cm and/or rapidly enlarging lymph nodes
  • Supraclavicular lymph node and/or lower cervical chain lymph nodes (any size)
  • Lymph nodes that are hard, firm, rubbery, matted, or fixed
  • Lymphadenopathy > 4 weeks)
  • Generalized lymphadenopathy
• Associated features, including:
  • B symptoms
  • Hepatosplenomegaly
  • Bruising
  • Rash
  • Arthralgia and/or myalgia
• Children ≥ 8 years of age (red flag for malignancy)

Supraclavicular LAD and posterior cervical triangle LAD carry a much higher risk for malignancy or tuberculosis infection than anterior cervical LAD. ^[2][4]

General principles ^[1][5]

• Diagnostic studies are not routinely recommended.
• Consider targeted diagnostics as needed based on the most likely underlying etiology.
• Refer to a pediatric specialist (e.g., infectious disease, ENT, hematology-oncology, rheumatology) for:
  • Atypical infection (e.g., unresponsive to antibiotics)
  • Red flags for cervical LAD in children
  • Diagnostic uncertainty
• See "Common causes of cervical LAD in children" for characteristic diagnostic findings.

Reactive LAD caused by a viral URTI is the most common cause of acute cervical LAD in children and is diagnosed clinically.^[1][5]

Laboratory studies ^[4][5]

Perform laboratory studies based on suspected underlying etiology of cervical LAD in children, e.g.:

• Bacterial infection
  • CBC
  • Blood culture (in febrile or ill-appearing patients)
  • Specific diagnostics for suspected causative organism, e.g.:
    • Diagnostics of acute tonsillitis
    • Diagnostics for tuberculosis
    • Diagnostics for cat scratch disease
  • Fine-needle aspiration and Gram stain, acid-fast stain, and cultures of lymph node material for anaerobic and aerobic bacteria and mycobacteria
• Viral infection
  • EBV serology
  • Diagnostics for CMV
  • HIV testing
• Malignancy: CBC, peripheral smear, LDH
• Inflammatory conditions: inflammatory markers (e.g., ESR, CRP)

Imaging ^[5][8][9]

Imaging is not routinely indicated in the evaluation of cervical LAD in children.

• Diagnostic uncertainty: ultrasound neck with or without color Doppler ultrasound
  • Preferred first-line modality in children
  • Useful to differentiate between reactive lymphadenopathy and malignancy
  • See "Lymph node ultrasound findings" for details.
• Suspected malignancy or deep neck infection
  • CT scan neck with IV contrast
  • MRI neck with or without IV contrast
• Suspected lymphoma or granulomatous disease: chest x-ray

Biopsy ^[5][5][10]

• Indications
  • LAD of unclear etiology lasting > 4 weeks and unresponsive to antibiotic therapy
  • Red flags for cervical LAD in children
  • Diagnostic uncertainty
• Modalities
  • Excisional biopsy: preferred if lymphoma is suspected
  • Core needle biopsy: Consider as an alternative to excisional biopsy in selected patients.
  • Fine-needle aspiration (FNA) biopsy: Consider for persistent LAD of unclear etiology.

Outpatient management is usually appropriate. ^[5]

• Isolated cervical LAD with no red flag features in an otherwise healthy child: reassurance and observation
• Identify and treat the underlying cause, e.g.:
  • Acute lymphadenitis likely due to a viral URTI: observation with follow-up in 2–4 weeks ^[4]
  • Acute lymphadenitis likely due to a bacterial infection
    • Initiate antibiotic therapy (e.g., empiric antibiotic therapy for acute unilateral pyogenic cervical lymphadenitis, antibiotic therapy for GAS pharyngitis).
    • Tailor antibiotics when culture and sensitivities are available.
  • See "Common causes of cervical LAD in children" for details.
• Consider symptomatic and supportive care (e.g., antipyretics, nonopioid oral analgesia in children) as needed.
• Referrals
  • Suspected malignancy: urgent referral to hematology-oncology
  • Suspected periodontal disease: pediatric dentist
  • Other specialists (e.g., infectious diseases, surgery, rheumatology) for additional studies and management of:
    • Persistent LAD after observation for suspected viral etiology
    • Inadequate response to antibiotic therapy within 72 hours
    • Atypical infection (e.g., Mycobacterium tuberculosis, nontuberculous mycobacteria, fungal infection) ^[4]
    • Suspected rheumatologic condition

Admit acutely ill children to hospital and consult a specialist (e.g., infectious diseases, critical care). Begin initial management of pediatric sepsis, if indicated.

Avoid corticosteroids in patients with suspected acute lymphadenitis until a definitive diagnosis is made; corticosteroids can alter the histopathological appearance of lymphoma or malignancy. ^[5]

Mild infection

• Oral empiric antibiotic coverage for Staphylococcus aureus and Streptococcus pyogenes ^[1][5][11]
• Options include:
  • Clindamycin (off-label) ^[1][3][12]
  • Cephalexin (off-label in infants)^[1][3][12]
  • Amoxicillin/clavulanate ^[1][3][12]
• Duration of therapy: 7–14 days ^[6]

Severe infection ^[11]

• Start empiric IV antibiotics in consultation with specialists; options include:
  • Nafcillin (for nonpurulent infections only; off-label) ^[12][13]
  • Cefazolin ^[12][13]
  • Clindamycin ^[12][13]
• Consider percutaneous aspiration ; refer to surgery for abscess drainage. ^[4][11][14]

Suspected periodontal disease ^[4][11]

• Administer empiric antibiotics that cover anaerobic infection (e.g., amoxicillin/clavulanate ; , clindamycin off-label).
• Refer to a pediatric dentist.

Suspected MRSA infection ^[4]

• Uncomplicated infection: oral trimethoprim sulfamethoxazole ^[5][12][13]
• Complicated cases: IV vancomycin (consult specialists) ^[12][13]

Symptoms typically improve within 72 hours of initiating antibiotics. Complete resolution of lymph node enlargement may take several weeks. ^[6]

Common causes of acute cervical LAD in children

The most common causes of acute unilateral cervical lymphadenitis in children are Staphylococcus aureus and Streptococcus pyogenes; the most common causes of acute bilateral cervical lymphadenitis are viral infections and GAS infections. ^[1][4]

Common causes of subacute and chronic cervical LAD in children

• Congenital and developmental neck masses ^[2][4][8]
  • Thyroglossal duct cyst
  • Branchial cleft cyst
  • Dermoid cyst, epidermoid cyst
  • Cystic hygroma
  • Laryngocele
  • Fibromatosis colli and congenital muscular torticollis
  • Vascular malformations and tumors
• Neoplastic masses ^[2]
  • Thyroid cancer
  • Tumors of the salivary glands
  • Benign soft tissue tumor (e.g., pilomatrixomas, lipomas, fibromas, neurofibromas)
  • Rhabdomyosarcoma
  • Neuroblastoma ^[26]
  • Metastatic nasopharyngeal carcinoma
• Other neck masses ^[4]
  • Parotitis (e.g., due to mumps)
  • Cervical rib
• See also "Mimics" in “Lymphadenopathy.”