Can cefuroxime cause generalized lymphadenopathy in adults, and what is the appropriate management?

Cefuroxime-Induced Generalized Lymphadenopathy: Recognition and Management

Cefuroxime can cause generalized lymphadenopathy as part of severe hypersensitivity reactions, most notably Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome and serum sickness-like reactions (SSLR), and the drug must be immediately discontinued when this occurs. 1, 2

Clinical Recognition of Cefuroxime Hypersensitivity

DRESS Syndrome Presentation

• Generalized lymphadenopathy occurs as part of DRESS syndrome, typically developing 2-8 weeks after cefuroxime initiation, accompanied by fever, facial edema, widespread skin rash, eosinophilia, and potential multi-organ involvement (liver, kidney, lungs) 1
• The constellation includes hepatosplenomegaly, hematologic abnormalities (particularly eosinophilia >1000/μL or >10%), and systemic symptoms including gastrointestinal disturbances 1
• Lymph nodes in DRESS are typically mobile, bilateral, and associated with systemic features rather than being hard, matted, or fixed 3

Serum Sickness-Like Reaction

• SSLR to cefuroxime presents with generalized pruritic rash, arthralgias, fever, and can include lymphadenopathy, typically occurring 7-21 days after drug exposure 2
• Unlike true serum sickness, SSLR does not involve immune complex deposition but mimics the clinical presentation 2

Lymphomatoid Hypersensitivity Reaction

• A rare cutaneous T-cell lymphoma-like reaction has been documented with cefuroxime, presenting with erythematous and purpuric rashes along with atypical lymphoid infiltrates that can be mistaken for malignancy 4
• This pseudolymphoma reaction resolves completely after drug cessation 4

Immediate Management Algorithm

Step 1: Discontinue Cefuroxime Immediately

• Stop cefuroxime as soon as drug-induced lymphadenopathy is suspected—continuing the drug risks progression to life-threatening multi-organ failure 1
• Document the reaction thoroughly for future avoidance 1

Step 2: Assess Severity and Organ Involvement

• Obtain complete blood count with differential (looking for eosinophilia >1000/μL, atypical lymphocytes) 1
• Check liver function tests (transaminases, bilirubin), renal function (creatinine), and lactate dehydrogenase 1
• Measure C-reactive protein and erythrocyte sedimentation rate to assess systemic inflammation 3
• Evaluate for fever, night sweats, and unintentional weight loss to help differentiate from malignancy 3

Step 3: Differentiate from Other Causes

• Generalized lymphadenopathy (involving ≥2 non-contiguous lymph node regions) suggests systemic disease rather than localized infection 3
• In the context of recent cefuroxime use with fever, rash, and eosinophilia, drug reaction is the leading diagnosis 1, 2
• Consider alternative diagnoses if lymph nodes are >2 cm, hard, matted, or if epitrochlear/supraclavicular nodes are involved, as these features suggest malignancy or granulomatous disease 3

Step 4: Symptomatic Treatment

• Systemic corticosteroids are the mainstay of treatment for DRESS syndrome and SSLR (typically prednisone 0.5-1 mg/kg/day, tapered over weeks to months based on response) 1, 2
• Critical pitfall: Avoid corticosteroids if malignancy has not been adequately ruled out, as they can mask histologic diagnosis of lymphoma 3
• Provide supportive care including antihistamines for pruritus and antipyretics for fever 2

Step 5: Monitor for Resolution and Complications

• Lymphadenopathy and systemic symptoms typically resolve within 10-14 days after drug cessation, though DRESS can have a prolonged course requiring weeks to months 1, 4
• Monitor liver and renal function serially, as organ dysfunction may worsen initially despite drug withdrawal 1
• If lymphadenopathy persists beyond 4 weeks after drug cessation or worsens despite treatment, proceed to imaging (ultrasound, CT) and consider biopsy 3

Cross-Reactivity and Future Antibiotic Selection

Cephalosporin Cross-Reactivity

• Cross-reactivity exists among cephalosporins—intradermal testing has demonstrated positive reactions to cefazolin, ceftazidime, and ceftriaxone in patients with cefuroxime-induced DRESS 5
• Avoid all cephalosporins in patients with documented cefuroxime hypersensitivity reactions involving lymphadenopathy 5

Safe Alternatives

• Penicillins (benzylpenicillin, amoxicillin) may be tolerated, as intradermal testing shows negative results in most cephalosporin-allergic patients, though caution is warranted 5
• For infections where cefuroxime would typically be used (e.g., early Lyme disease), substitute with doxycycline 100 mg twice daily for 10-14 days or amoxicillin 500 mg three times daily for 14 days 6, 7
• Avoid first-generation cephalosporins entirely, as they are ineffective for many indications where cefuroxime is used (e.g., Lyme disease) and carry similar cross-reactivity risk 8, 5

Key Clinical Pitfalls

• Do not attribute generalized lymphadenopathy to a benign viral illness if the patient is taking cefuroxime—drug reaction must be excluded first 1, 3
• Do not perform lymph node biopsy before discontinuing cefuroxime—the histology may show atypical lymphoid infiltrates mimicking lymphoma, leading to misdiagnosis 4
• Do not restart cefuroxime or related cephalosporins for "drug challenge"—rechallenge can precipitate severe, potentially fatal reactions 1
• Recognize that DRESS can occur even after the drug has been stopped, as the reaction may develop up to several weeks after the last dose 1