Can Lamictal (lamotrigine) cause swollen lymph nodes?

Can Lamotrigine Cause Swollen Lymph Nodes?

Yes, lamotrigine can cause swollen lymph nodes as part of a serious hypersensitivity reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or Drug-Induced Hypersensitivity Syndrome (DIHS). 1, 2, 3

Understanding the Mechanism

Lymphadenopathy (swollen lymph nodes) associated with lamotrigine occurs as part of a systemic hypersensitivity syndrome, not as an isolated finding. 3, 4 This reaction typically develops 2-6 weeks after initiating lamotrigine therapy and represents a potentially life-threatening adverse drug reaction. 5

Clinical Presentation Pattern

The hallmark features of lamotrigine hypersensitivity syndrome include:

• Fever (often high and spiking) 3, 4
• Generalized rash (typically morbilliform/maculopapular) 2, 4
• Tender lymphadenopathy (swollen lymph nodes) 3, 4, 5
• Facial edema (particularly periorbital swelling) 4, 5
• Hepatitis (elevated liver enzymes) 3, 5
• Eosinophilia and atypical lymphocytosis 4, 5

The presence of systemic symptoms such as fever or lymphadenopathy is a critical factor in determining the severity of the rash and indicates a serious reaction requiring immediate drug discontinuation. 1

Critical Risk Factors

The risk of developing this syndrome is significantly increased when lamotrigine is combined with valproic acid (valproate). 2, 4 Valproic acid inhibits lamotrigine metabolism, leading to elevated lamotrigine levels and increased toxicity risk. 2 One case demonstrated that lymphadenopathy and rash can develop even after the last dose of lamotrigine when combined with valproate, and the reaction may persist until valproate is also discontinued. 2

Diagnostic Considerations

Importantly, the histologic findings in lymph nodes can mimic lymphoma, with CD30+ lymphocytic infiltrates that may be mistaken for systemic lymphoma. 6 Pathologists and clinicians must recognize this "lymphomatous" presentation as a drug reaction rather than true malignancy. 6

Immediate Management Algorithm

When lymphadenopathy occurs with lamotrigine:

1. Assess for mucosal involvement, facial swelling, fever, or other systemic symptoms that indicate DRESS/DIHS syndrome 1

2. Immediately discontinue lamotrigine if any systemic symptoms are present 1, 5

3. Consider discontinuing valproic acid if co-administered, as it may prolong the reaction 2, 4

4. Initiate systemic corticosteroid therapy for moderate to severe reactions 2, 5

5. Monitor liver and renal function, as acute hepatic and renal failure can develop 5

Critical Contraindications

Any history of rash with previous lamotrigine use is an absolute contraindication to rechallenge. 1, 7 The presence of mucosal involvement is an absolute contraindication to any future lamotrigine use. 1 Rechallenge should only be considered if the previous rash was definitively mild, non-serious, and lamotrigine was uniquely effective for a severe psychiatric condition with no alternatives. 1

Common Pitfalls to Avoid

• Do not dismiss symptoms as viral illness: The slow evolution and clinical similarity to infectious illnesses may delay diagnosis 5
• Do not continue lamotrigine hoping symptoms will resolve: Prompt recognition and withdrawal is essential to prevent progression to life-threatening complications 5
• Do not assume the reaction has passed if lamotrigine was recently stopped: Symptoms can appear after the last dose, particularly when valproate is co-administered 2
• Do not overlook the diagnosis when lymph node biopsy shows lymphomatous features: This can be a presentation of drug reaction, not true lymphoma 6