What is the initial approach to work up a patient with lymphadenitis?

Workup of Lymphadenitis

Begin with a focused history targeting infection risk factors, duration of symptoms, and systemic features, followed by physical examination to differentiate localized from generalized lymphadenopathy, then proceed with laboratory testing and imaging based on clinical presentation and risk stratification. 1, 2

Initial Clinical Assessment

History

• Duration of lymphadenopathy (persistence >2-4 weeks warrants escalation of workup) 3, 2, 4
• Systemic symptoms: fever, night sweats, unintentional weight loss (concerning for malignancy or systemic infection) 1, 3, 2
• Immunocompromise status: HIV, diabetes, immunosuppressive medications (increases risk for atypical organisms including non-tuberculous mycobacteria) 1, 5
• Exposure history: animal contacts, travel, occupation, recent vaccines, tuberculosis exposure 2, 4
• Medication history and drug use 2, 4
• Sexual history and family history 2

Physical Examination

• Differentiate localized versus generalized lymphadenopathy (≥2 involved regions suggests systemic disease) 2, 4
• Node characteristics concerning for malignancy: size >1.5-2 cm, hard consistency, fixed/matted to surrounding structures, ulceration of overlying skin 3, 2, 4
• High-risk locations: supraclavicular, epitrochlear (>5 mm), popliteal, and iliac nodes are abnormal and warrant aggressive workup 3, 4
• Examine all node-bearing areas: cervical, supraclavicular, axillary, inguinal regions, plus assess for hepatosplenomegaly 3
• Overlying skin changes and multiple/bilateral nodal disease suggest more aggressive infection requiring surgical management 5

Laboratory Evaluation

Initial Laboratory Tests

• Complete blood count with differential to assess for leukocytosis, left shift, or other abnormalities suggesting systemic infection 1, 2
• Blood cultures if patient appears systemically ill, has fever, or shows signs of bacteremia (obtain before initiating antibiotics) 1
• Basic metabolic panel to assess renal function and electrolytes, particularly if systemic antibiotics will be required 1
• C-reactive protein and erythrocyte sedimentation rate for inflammatory markers 2
• Tuberculosis testing (PPD or IGRA) 2

Additional Testing When Malignancy or Systemic Disease Suspected

• Lactate dehydrogenase (critical prognostic marker for lymphoma) 3
• Comprehensive metabolic panel including liver function 3
• Hepatitis B, C, and HIV serology (required before immunotherapy/chemotherapy if malignancy suspected) 3
• β2-microglobulin (prognostic marker for hematologic malignancies) 3

Imaging Studies

Initial Imaging

• Ultrasound to identify underlying abscess formation requiring drainage 1
• Chest X-ray if pulmonary involvement suspected 2

Advanced Imaging (When Indicated)

• CT or MRI if deep tissue involvement, osteomyelitis, or necrotizing infection suspected 1
• CT chest/abdomen/pelvis with contrast if systemic disease suspected 3
• PET-CT for evaluation of suspicious findings on other imaging modalities or when malignancy is a concern 3

Tissue Sampling Strategy

Indications for Biopsy

• Persistence >2 weeks without significant fluctuation (concerning for malignancy) 3
• Failure to resolve after course of antibiotics 3
• High-risk features: supraclavicular location, age >40 years, systemic symptoms, hard/fixed nodes 3, 4

Biopsy Approach

• Fine-needle aspiration (FNA) is preferred over open biopsy for initial tissue sampling 3
• Core needle biopsy when easily accessible nodes are unavailable 3
• Excisional biopsy yields higher diagnostic yield for histological findings compared to FNA, particularly for NTM lymphadenitis 5
• Immunophenotyping is essential for differentiating lymphoma subtypes 3
• Cytogenetic/molecular genetic analysis (FISH) to identify chromosomal translocations if lymphoma suspected 3
• Bone marrow aspirate and biopsy (≥20 mm size) if lymphoma or leukemia suspected 3

Management Approach

Empiric Antibiotic Therapy

• Consider antibiotics if benign or self-limiting etiology (bacterial lymphadenitis) is suspected, particularly in children with acute unilateral cervical lymphadenitis and systemic symptoms 2, 4
• Avoid prescribing additional antibiotics without signs of bacterial infection, as this may delay diagnosis of malignancy 3

Specialist Consultation

• Infectious disease consultation if patient has signs of systemic infection, immunocompromise, or fails to improve within 48-72 hours 1
• Otolaryngology referral for persistent cervical lymphadenopathy ≥2 weeks or failure to resolve after antibiotics 3
• Hematology/oncology consultation if malignancy suspected based on risk factors or imaging findings 3

Critical Pitfalls to Avoid

• Never assume a cystic neck mass is benign without obtaining definitive diagnosis, as this can delay diagnosis of malignancy 3
• Avoid corticosteroids as they can mask histologic diagnosis of lymphoma or other malignancy 2, 4
• Do not rely solely on benign ultrasound findings—continued evaluation is necessary until definitive diagnosis obtained 3
• Failure to recognize bacteremia or deeper infection can lead to serious complications including sepsis 1
• More aggressive management with surgical excision and antibiotics is recommended for those with overlying skin changes and extensive nodal disease, particularly in NTM lymphadenitis 5