Which Medications Can Cause Swollen Lymph Nodes? Understanding Drug-Induced Lymphadenopathy

October 12, 2025 •

4 min read

While most cases of swollen lymph nodes are caused by infections, a less common but important cause is a reaction to medication. Understanding which medications can cause swollen lymph nodes is crucial, as this reaction, known as drug-induced lymphadenopathy, can sometimes indicate a severe hypersensitivity syndrome.

Quick Summary

This article explores various medications known to trigger lymph node swelling, including antiepileptics and antibiotics. It details the underlying immune mechanisms, such as DRESS syndrome, and provides key information on recognizing symptoms, diagnosing the condition, and its typical management.

Key Points

DRESS Syndrome: Drug-induced lymphadenopathy can be a symptom of a severe, systemic reaction called DRESS syndrome, which includes fever, rash, and organ damage.
Anticonvulsants are Common Culprits: Medications like phenytoin, carbamazepine, and newer antiseizure drugs are well-documented causes of drug-induced lymphadenopathy.
Delayed Onset: Symptoms of drug-induced lymphadenopathy, especially DRESS, can appear weeks or even months after starting a medication, complicating diagnosis.
Careful Diagnosis is Crucial: Due to overlapping symptoms with more serious diseases like lymphoma, a careful medical history and potentially a lymph node biopsy are necessary for proper diagnosis.
Immediate Drug Discontinuation: Under medical supervision, the primary treatment is to immediately stop the drug causing the reaction; this is often curative, but severe cases may require additional treatment.
Allopurinol Risk: The gout medication allopurinol is a notable and potentially life-threatening cause of DRESS syndrome.

The lymphatic system is a vital part of the body's immune defense, with lymph nodes acting as filters for foreign particles and pathogens. When your immune system detects an infection, your lymph nodes often swell in response. However, in some cases, certain medications can trigger a similar reaction, causing the lymph nodes to enlarge. This condition is known as drug-induced lymphadenopathy, and it can range from a mild, benign reaction to a sign of a life-threatening systemic syndrome.

Understanding Drug-Induced Lymphadenopathy

Drug-induced lymphadenopathy often occurs as part of a delayed hypersensitivity reaction, where the immune system mistakenly identifies a drug or its metabolite as a threat. One of the most serious forms of this reaction is Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DIHS). This severe reaction is characterized by a triad of symptoms: fever, a skin rash, and internal organ damage, often accompanied by generalized lymph node swelling.

Unlike an infection, DRESS syndrome has a delayed onset, with symptoms typically appearing 2 to 8 weeks after starting the offending medication. The reaction can persist or flare up even after the drug has been discontinued, which can lead to misdiagnosis. Due to the systemic nature of the reaction, which can affect the liver, kidneys, lungs, or heart, early recognition and management are critical.

Specific Medications and Classes Implicated

Anticonvulsants

Several anti-epileptic drugs (AEDs) are famously linked to drug-induced lymphadenopathy, with symptoms potentially mimicking lymphoma.

Phenytoin (Dilantin): Historically, phenytoin is one of the most well-documented causes of drug-induced lymphadenopathy. Patients may develop fever, rash, and swelling of lymph glands in the neck, armpit, or groin. This can occur as part of a full-blown DRESS syndrome.
Carbamazepine (Tegretol): Similar to phenytoin, carbamazepine is a known trigger for hypersensitivity reactions and associated lymphadenopathy. There is a high degree of cross-reactivity among these aromatic anticonvulsants.
Lamotrigine, Levetiracetam, and Clobazam: More recently, the FDA has issued warnings regarding the potential for levetiracetam and clobazam to cause DRESS syndrome, which includes fever, rash, and swollen lymph nodes.

Antibiotics and Antimicrobials

While antibiotics are often used to treat lymphadenopathy caused by bacterial infections, they can also cause it as a side effect.

Sulfonamides (e.g., Trimethoprim/sulfamethoxazole): This class of antibiotics has long been associated with hypersensitivity reactions, including lymphadenopathy.
Penicillin: A widely used antibiotic, penicillin can cause an allergic reaction that manifests with swollen lymph nodes.
Cephalosporins: Several cephalosporin antibiotics have been noted to cause lymph node swelling as part of a hypersensitivity reaction.
Minocycline: A case study identified minocycline as the cause of DRESS syndrome, resulting in significant lymphadenopathy.

Cardiovascular Medications

Some medications used to treat hypertension and other heart conditions can also cause this side effect.

Hydralazine (Apresoline): This blood pressure medication is a known cause of drug-induced lymphadenopathy.
Atenolol (Tenormin): As a beta-blocker, atenolol has been linked to swollen lymph nodes in rare cases.
Captopril: This ACE inhibitor can cause hypersensitivity reactions that include lymphadenopathy.

Other Notable Medications

Allopurinol: Used for gout and kidney stones, allopurinol is a common cause of DRESS syndrome and associated lymphadenopathy.
Sulindac: A non-steroidal anti-inflammatory drug (NSAID) used for arthritis, sulindac has also been implicated.
Quinidine: A medication used for heart rhythm issues that can cause drug-induced lymphadenopathy.

Comparison: Drug-Induced vs. Other Causes

To aid in differentiation, the following table compares key characteristics of drug-induced lymphadenopathy (specifically DRESS) with common infectious causes and more serious conditions like lymphoma.


Feature	Drug-Induced Lymphadenopathy (DRESS)	Infectious Lymphadenopathy	Lymphoma
Onset	Delayed, typically 2-8 weeks after starting the drug.	Rapid, within days of infection.	Gradual, often over weeks or months.
Associated Symptoms	Fever, widespread rash, organ damage (liver, kidney), eosinophilia.	Fever, sore throat, cough, localized rash near infection.	Fever, night sweats, unexplained weight loss.
Lymph Node Location	Often generalized, affecting multiple areas (neck, armpit, groin).	Localized to the area draining the infection.	Can be localized or generalized, often persistent.
Resolution	Slow resolution after stopping the drug; may require corticosteroids.	Resolves as the infection clears, often with antibiotics.	Requires specific cancer treatment (e.g., chemotherapy, radiation).
Biopsy Findings	Inflammatory infiltrate with eosinophils and atypical cells; architecture is usually preserved.	Signs of inflammation and immune response specific to the pathogen.	Malignant cells, effaced nodal architecture.

Diagnosis and Management

Diagnosing drug-induced lymphadenopathy relies on a careful medical history, physical examination, and laboratory tests. A detailed review of all medications, including recent changes, is critical. Blood tests may show elevated eosinophil counts (eosinophilia) and atypical lymphocytes. Given the clinical overlap with more severe conditions like lymphoma, differentiating between them can be challenging, and a lymph node biopsy may be required.

The most important step in managing a suspected case is to immediately discontinue the offending medication under a doctor's supervision. Never stop prescribed medication without consulting a healthcare professional, as abrupt discontinuation can be dangerous (e.g., in the case of anticonvulsants). For severe reactions like DRESS syndrome, supportive care and systemic corticosteroids are often necessary to manage organ damage. Symptoms usually resolve after drug withdrawal, but a slow, careful recovery is typical. For more information on DRESS syndrome, you can visit the National Organization for Rare Disorders.

Conclusion

While relatively rare, drug-induced lymphadenopathy is an important adverse effect to consider when lymph nodes swell without an obvious infectious cause. Patients should be aware that various medications, particularly anticonvulsants and certain antibiotics, can cause this reaction. The potentially life-threatening nature of DRESS syndrome highlights the importance of open communication with your healthcare provider about all your medications and any unusual symptoms. Prompt diagnosis and discontinuation of the culprit drug are the cornerstones of successful management, ensuring a return to health.

Frequently Asked Questions

If your lymph nodes swell after starting a new medication, especially weeks later, discuss it with your doctor. Symptoms of a drug-induced reaction, like DRESS syndrome, often include fever, a rash, and eosinophilia, which can help differentiate it from an infection.

Certain antibiotics, such as sulfonamides (e.g., trimethoprim/sulfamethoxazole), penicillin, cephalosporins, and minocycline, have been known to cause swollen lymph nodes as a side effect.

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome is a severe, rare, and potentially life-threatening drug-induced hypersensitivity reaction. It involves fever, widespread rash, swollen lymph nodes, and potentially dangerous damage to internal organs like the liver or kidneys.

The main treatment is discontinuing the drug that caused the reaction under a doctor's guidance. For severe reactions like DRESS, systemic corticosteroids may be used, along with other supportive therapies.

After stopping the culprit medication, the swelling can take time to resolve. In cases of DRESS syndrome, symptoms can take weeks to months to fully subside, and a slow, gradual recovery is common.

It is less common, but some over-the-counter medications, particularly NSAIDs like sulindac, can potentially cause this reaction in rare cases.

Contact your doctor or healthcare provider immediately. They will evaluate your symptoms, medical history, and medication list to determine the cause and recommend a safe course of action. Do not stop your medication on your own.