Causes of Painful Lymph Nodes
Painful lymph nodes are most commonly caused by infections, but can also result from inflammatory conditions, malignancies, and other systemic disorders that require prompt evaluation and management. 1
Infectious Causes
Bacterial Infections
- Acute bacterial lymphadenitis: Often presents with warmth, erythema, tenderness, and systemic signs like fever 1
- Commonly associated with pharyngitis, dental infections, or skin infections
- Streptococcal infections (including Group C and G) can cause pharyngitis with painful cervical lymphadenopathy 1
- Cat-scratch disease (Bartonella henselae): Causes regional lymphadenopathy approximately 3 weeks after inoculation, with nodes that may suppurate in about 10% of cases 2
Viral Infections
- Viral pharyngitis, mononucleosis, CMV, and other viral illnesses
- May present with more generalized lymphadenopathy compared to bacterial causes
Mycobacterial Infections
- Tuberculosis: In adults, more than 90% of culture-proven mycobacterial lymphadenitis is due to M. tuberculosis 1
- Nontuberculous mycobacterial (NTM) lymphadenitis: Typically presents as unilateral lymphadenopathy that may enlarge rapidly and even rupture 1
- Approximately 80% of cases are due to Mycobacterium avium complex (MAC)
- Most common in children between 1-5 years of age
Non-Infectious Causes
Inflammatory/Autoimmune Conditions
- Kawasaki disease: Can present with unilateral cervical lymphadenopathy (≥1.5 cm diameter) as one of its principal clinical features 2
- Rosai-Dorfman-Destombes disease: Typically presents with massive, painless bilateral cervical lymphadenopathy 1
Malignancies
- Lymphomas (Hodgkin's and non-Hodgkin's)
- Metastatic cancers: Head and neck cancers can metastasize to posterior cervical lymph nodes 1
- Leukemias
Iatrogenic Causes
- Medication reactions
- Post-vaccination: COVID-19 vaccination can cause transient lymphadenopathy (though more commonly in axillary or supraclavicular nodes) 1
Evaluation Approach
Risk Assessment
- High-risk features for malignancy 3:
- Age older than 40 years
- Male sex
- White race
- Supraclavicular location (always suspicious for underlying malignancy) 4
- Presence of systemic symptoms (fever, night sweats, unexplained weight loss)
- Hard, fixed, or matted nodes
Diagnostic Algorithm
Determine if localized or generalized:
For localized lymphadenopathy:
- Examine for local infection sources (skin, oral cavity, ears)
- Consider regional drainage patterns to identify potential causes
For persistent lymphadenopathy (>1 month):
Management Considerations
- Acute unilateral cervical lymphadenitis: Antibiotics may be appropriate, especially in children with systemic symptoms 3
- Observation: If the patient is clinically stable without suspicion of malignancy, observation for 3-4 weeks may be appropriate 4
- Biopsy: Options include fine-needle aspiration, core needle biopsy, or open excisional biopsy 3
- Corticosteroids: Limited usefulness and should not be used without an appropriate diagnosis 3
Important Caveats
- Palpable supraclavicular, popliteal, and iliac nodes are always abnormal, as are epitrochlear nodes greater than 5 mm in diameter 3
- In HIV-positive patients, lymphadenopathy may be due to HIV infection itself, opportunistic infections, or malignancies 1
- Tumor flare reactions in patients with lymphoproliferative disorders (particularly CLL) can cause painful lymph node enlargement during treatment initiation 2
- Avoid premature use of corticosteroids before establishing a diagnosis, as they may mask symptoms of serious underlying conditions
By systematically evaluating painful lymphadenopathy with attention to location, associated symptoms, and risk factors, clinicians can efficiently determine the underlying cause and implement appropriate management.