What is the appropriate management for a patient presenting with fever and inguinal lymphadenopathy?

Management of Fever with Inguinal Lymphadenopathy

Start empiric doxycycline 100 mg orally twice daily for 21 days if sexually transmitted infection (STI) is suspected, but first rule out malignancy and non-infectious causes through careful clinical assessment and targeted diagnostic workup. 1

Initial Clinical Assessment

The character of the lymph nodes determines your immediate approach:

• Painless, hard, fixed, or matted nodes suggest malignancy (particularly penile cancer or lymphoma) and require biopsy rather than empiric antibiotics 2, 1
• Tender, mobile nodes with fever suggest infectious etiology (LGV, bacterial lymphadenitis, or reactive adenopathy) 2, 1
• Nodes >2 cm or supraclavicular location raise concern for malignancy or granulomatous disease 3
• Unilateral vs bilateral involvement helps narrow differential—unilateral is more common with LGV 2

Critical History Elements

Obtain specific details that guide diagnosis:

• Sexual history: Recent unprotected intercourse, multiple partners, or men who have sex with men increases likelihood of LGV or other STIs 2, 1
• Genital lesions: Ask about current or recent ulcers (even if self-limited), as most LGV patients no longer have the primary chancre when presenting with adenopathy 2
• Animal exposures: Dog contact with wounds can cause Capnocytophaga infection presenting with fever and inguinal adenopathy 4
• Duration: Lymphadenopathy >4 weeks warrants imaging and laboratory studies regardless of other features 3
• Constitutional symptoms: Fever, night sweats, and unintentional weight loss suggest systemic disease including lymphoma 2, 3

Diagnostic Workup

If STI is Suspected (tender nodes, sexual risk factors):

• Serologic testing for LGV: Complement fixation titers >1:64 support diagnosis 1
• Chlamydia testing: Urethral or cervical swabs 1
• Consider fine-needle aspiration: Can identify metastatic disease >2 mm and has increasing diagnostic yield with ultrasound guidance 2, 1
• Buboes may require aspiration through intact skin to prevent ulceration 1

If Malignancy is Suspected (hard/fixed nodes, systemic symptoms):

• CT or MRI: Assess size, extent, relationship to structures, and evaluate for pelvic/retroperitoneal nodes and distant metastases 2
• Biopsy: Fine-needle aspiration, core needle, or excisional biopsy depending on clinical scenario 2, 3
• Avoid corticosteroids as they mask histologic diagnosis of lymphoma 3

If Etiology Unclear:

• Complete blood count, CRP, ESR: Evaluate for systemic inflammation or hematologic malignancy 3
• Blood cultures: Hold for prolonged incubation if brucellosis suspected (up to 4 weeks) 2
• Tuberculosis testing: Especially with travel history or endemic exposure 3

Empiric Antibiotic Treatment

First-Line for STI-Related Adenopathy:

Doxycycline 100 mg orally twice daily for 21 days covers LGV and most bacterial causes 2, 1

Alternative Regimens:

• Erythromycin 500 mg orally four times daily for 21 days: For pregnant/lactating women or doxycycline contraindications 2, 1
• Azithromycin 1 g orally once weekly for 3 weeks: Likely effective for LGV though data are limited 1

Specific Conditions:

• Chancroid: Azithromycin 1 g orally as single dose 1
• Granuloma inguinale: Trimethoprim-sulfamethoxazole one double-strength tablet twice daily for minimum 3 weeks 1
• Streptococcal lymphadenitis: Penicillin plus surgical drainage if fluctuant 5

When Antibiotics Are NOT Appropriate

Do not give empiric antibiotics if:

• Nodes are hard, fixed, or matted (proceed to biopsy) 2, 1
• Lymphadenopathy persists >4 weeks without infectious symptoms (requires full workup) 3
• Systemic symptoms suggest lymphoma (fever, night sweats, weight loss with mediastinal involvement) 2, 6
• Patient has known cancer history with new adenopathy 6

Follow-Up and Treatment Failure

• Reassess at 3-7 days: If no improvement, consider incorrect diagnosis, coinfection, HIV, non-compliance, or antimicrobial resistance 1
• Continue until complete resolution: Patients should be followed clinically until all signs and symptoms resolve 1
• Treat sexual partners: Anyone with contact within 30 days before symptom onset should be examined, tested, and treated 1
• Sexual abstinence: Until both patient and partners complete treatment and are symptom-free 1

Special Populations

• Pregnant/lactating women: Use erythromycin regimen, never doxycycline 2, 1
• HIV-infected patients: Same regimens but may require prolonged therapy with delayed resolution 1
• Immunocompromised patients: Consider disseminated mycobacterial infection (MAC) which can present with suppurative inguinal adenopathy as immune reconstitution syndrome 2