What is the treatment approach for a pediatric patient presenting with lymphadenitis?

Pediatric Lymphadenitis: Comprehensive Clinical Overview

Epidemiology and Clinical Presentation

Lymphadenitis is one of the most common presentations in pediatric practice, with distinct etiologies based on age, location, and clinical characteristics.

Key Epidemiologic Features

• Nontuberculous mycobacterial (NTM) cervical adenitis is the most common form of NTM disease in children, with approximately 300 culture-confirmed cases annually in the United States (likely underestimated) 1
• Peak incidence occurs between 1-5 years of age, with most cases under 3 years 1
• Shows modest female predominance and nearly all reported cases are in whites 1
• Mycobacterium avium complex (MAC) accounts for approximately 80% of culture-proven NTM lymphadenitis, a shift from 30 years ago when M. scrofulaceum predominated 1, 2
• In Scandinavia and northern Europe, M. malmoense and M. haemophilum have emerged as major pathogens after MAC 1

Clinical Characteristics by Etiology

Acute Bacterial Lymphadenitis:

• Rapid onset with fever, tenderness, and overlying erythema 3
• Staphylococcus aureus (49% of culture-positive cases) and Group A Streptococcus (43%) are predominant pathogens in low-MRSA prevalence settings 4
• Methicillin-resistant S. aureus seen in only 6% of cases in Australasia/Europe 4

NTM Lymphadenitis:

• Insidious onset, rarely associated with systemic symptoms 1
• Unilateral involvement in 95% of cases, nodes generally not tender 1, 2
• Most commonly affects submandibular, submaxillary, cervical, or preauricular lymph nodes 1
• Nodes may enlarge rapidly and even rupture with sinus tract formation 1
• Contrast-enhanced CT typically shows asymmetric adenopathy with ring-enhancing masses involving fat and skin but minimal inflammatory stranding 1

Tuberculous Lymphadenitis:

• In the United States, only 10% of culture-proven mycobacterial cervical lymphadenitis in children is due to M. tuberculosis 1
• In adults, more than 90% of culture-proven mycobacterial lymphadenitis is tuberculous 1, 5
• History of TB exposure, positive family screening, and abnormal chest radiograph are key distinguishing features 1

Diagnostic Approach

Initial Assessment

Critical diagnostic steps include:

• Tuberculin skin test (PPD) in all suspected mycobacterial cases to distinguish tuberculous from NTM lymphadenitis 1, 3
• Children with NTM lymphadenitis show variable PPD reactions; up to one-third demonstrate ≥10 mm induration 1
• Assess specific risk factors: overlying skin changes, multiple or bilateral nodal disease, preauricular location, duration of symptoms 3, 6
• Obtain Gram stain and culture from aspirated material if node is fluctuant or suppurative 3

Imaging Considerations

• Chest radiography only in symptomatic patients 1
• For larger lymph nodes (≥5 cm) or difficult anatomical sites, consider MRI or CT 2
• Contrast-enhanced axial CT of NTM lymphadenitis shows characteristic ring-enhancing masses 1

Tissue Sampling

• Fine needle aspiration (FNA) may be used for initial evaluation but has limitations 2
• Surgical excision yields positive histological findings more frequently than FNA (P = 0.016) 6
• NTM identified in only 45.8% of episodes via culture or molecular sequencing, with M. abscessus most commonly found (47.8%) 6

Critical Distinction: TB vs. NTM

This distinction is absolutely critical as it determines treatment and public health implications 1, 2:

• No history of TB exposure in NTM (family screening negative) 1
• Normal chest radiograph in NTM 1
• PPD reactions variable in NTM (can be ≥10 mm in one-third) 1
• If strongly positive PPD (e.g., 15 mm) with granulomatous disease, initiate anti-TB therapy while awaiting culture results, especially with TB risk factors 1, 3

Treatment by Etiology

Acute Bacterial Lymphadenitis

For uncomplicated acute bacterial lymphadenitis, initiate empiric oral antibiotic therapy targeting S. aureus and Group A Streptococcus 3:

• Clindamycin OR amoxicillin-clavulanate for 7-14 days 3
• In low-MRSA prevalence settings, narrow-spectrum beta-lactam therapy (flucloxacillin or first-generation cephalosporins) is effective with low relapse rates 4
• For fluctuant lesions, percutaneous needle aspiration plus antibiotics resolves infection without need for incision and drainage 3, 7

For complicated disease (abscess/collection present):

• Early imaging, prompt surgical intervention, and infectious diseases consultation recommended 4
• Treatment more variable with higher rates of clindamycin use 4
• Prolonged length of stay and longer antibiotic durations typically required 4

Nontuberculous Mycobacterial Lymphadenitis

Complete excisional surgery without chemotherapy is the definitive treatment of choice for NTM cervical lymphadenitis, with approximately 95% success rate 1, 3, 2:

• This applies to disease caused by MAC and M. scrofulaceum 1
• Successful treatment frequently follows diagnosis with fine needle aspiration or incisional biopsy 1

Critical surgical principles:

• Primary complete excision is essential - failure to do so leads to significantly higher rates of re-operation (91% vs. 30%), persistent lymphadenitis (77% vs. 30%), and sinus formation (26% vs. 5%) 8
• Median time from onset to operation should be approximately 6 weeks 8

Alternative/Adjunctive Medical Therapy:

• For recurrent disease or high surgical risk (e.g., preauricular nodes with facial nerve involvement risk), use clarithromycin-based multidrug regimen 1, 3, 2
• Typical regimen: clarithromycin plus rifampin for 6-12 months 9
• Antibiotics lead to resolution in approximately 7 months with good tolerance (adverse effects in 36.8% of episodes, mostly transient transaminase elevations) 9
• Antibiotics effective as sole therapy in 34.48% of cases 9
• Overlying skin changes and multiple/bilateral nodal disease significantly associated with de novo disease or recurrence (P = 0.034 and 0.084), warranting more aggressive management with both surgery and antibiotics 6

For large or difficult-to-resect NTM lymphadenitis:

• Consider clarithromycin in combination with corticosteroids to reduce risk of disseminated disease 2

Tuberculous Lymphadenitis

A 6-month regimen is recommended for initial treatment of tuberculous lymphadenitis caused by drug-susceptible organisms 1:

• 2 months of INH, RIF, PZA, and EMB followed by 4 months of INH and RIF 1
• If PZA cannot be used, continuation phase must be increased to 7 months 1
• Affected lymph nodes may enlarge during appropriate therapy or after treatment without bacteriological relapse 1
• New nodes can appear during or after treatment 1
• For fluctuant nodes about to drain spontaneously, aspiration or incision and drainage is beneficial 1

Special Etiologies

Cat Scratch Disease (Bartonella henselae):

• Azithromycin: 500 mg day 1, then 250 mg for 4 additional days (patients >45 kg) OR 10 mg/kg day 1, then 5 mg/kg for 4 more days (patients <45 kg) 3

Tularemia (severe cases):

• Streptomycin 15 mg/kg IM every 12 hours OR gentamicin 1.5 mg/kg IV every 8 hours 3

Bubonic Plague:

• Streptomycin 15 mg/kg IM every 12 hours OR doxycycline 100 mg orally twice daily 3

Lyme Disease (Borrelial Lymphocytoma):

• Oral antibiotics for 14 days: doxycycline, amoxicillin, or cefuroxime axetil 3

Special Populations

Immunocompromised/Neutropenic Patients

• Immediate hospitalization with empiric vancomycin plus antipseudomonal antibiotics 3
• For high-risk febrile neutropenia, use monotherapy with antipseudomonal beta-lactam or carbapenem 1
• Reserve addition of second Gram-negative agent or glycopeptide for clinically unstable patients or when resistant infection suspected 1

Infants <3 Months

• Consider antibiotics if bacterial etiology suspected or fever ≥38.5°C with signs of systemic toxicity or sepsis 3

HIV-Infected Patients

• MAC lymphadenitis seen particularly as manifestation of immune reconstitution syndrome 1
• Cervical, mediastinal, or intraabdominal nodes may be involved 1
• Macrolide-based therapy (azithromycin or clarithromycin) plus ethambutol, with or without rifabutin for disseminated MAC 5

Critical Pitfalls to Avoid

Surgical Pitfalls

Never perform incisional biopsy or drainage alone for NTM lymphadenitis - this creates chronic fistulae, sinus tract formation, and persistent clinical disease 1, 3, 5:

• Incisional biopsy alone has been followed by persistent disease in the majority of cases 1
• Primary incomplete excision leads to 91% re-operation rate vs. 30% with complete excision 8

Medical Management Pitfalls

Never use anti-TB drugs without macrolides for NTM lymphadenitis - this leads to treatment failure 1, 3, 5:

• Anti-TB drugs alone (without clarithromycin) frequently followed by persistent disease 1

Diagnostic Pitfalls

• Always obtain cultures before starting antibiotics when possible 3
• Do not empirically treat with antibiotics in absence of signs suggesting acute bacterial infection (rapid onset, fever, tenderness, overlying erythema) 2
• Recognize that preauricular location carries significant facial nerve injury risk during excision - consider medical therapy first in this location 3
• Avoid rinsing or drinking tap water for several hours before respiratory specimen collection to prevent M. gordonae contamination 1

Diagnostic Confusion

• Children may present with only fever and unilateral enlarged cervical lymph node, which can be mistakenly treated as bacterial lymphadenitis with antibiotics when NTM is the actual cause 2
• Kawasaki disease must be considered in children with cervical lymphadenopathy ≥1.5 cm, even if other principal clinical features not initially present 2

Follow-Up and Monitoring

Timing and Reassessment

• Schedule follow-up within 2 weeks to evaluate for resolution, progression, or persistence 2
• If lymph node has not completely resolved, proceed to definitive workup as partial resolution may represent infection in underlying malignancy 2
• Symptoms persisting beyond 2-4 weeks or child failing to improve with supportive care prompts reassessment for underlying conditions 3
• If cervical lymph node completely resolves, schedule one additional follow-up in 2-4 weeks to monitor for recurrence 2

Return Precautions

Parents should return immediately for 3:

• Irritability or lethargy
• Decreased urine output
• Intractable vomiting

High-Risk Features Requiring Definitive Workup

• Lymph node ≥1.5 cm persisting ≥2 weeks without significant fluctuation places child at increased risk for malignancy or chronic infection 2
• Fixed, firm, or ulcerated nodes are suspicious and warrant further investigation 2
• Reactive cervical lymphadenopathy from respiratory infections typically resolves within days of completing treatment 2

Adjunctive Therapies

For Bronchiectasis Associated with Nodular/Bronchiectatic MAC

• Bronchodilators, postural drainage, smoking cessation 1
• Autogenic drainage, oscillating positive expiratory pressure devices, high-frequency chest compression devices for mucus clearance 1
• Nutrition and weight gain optimization 1
• Exercise and cardiovascular fitness 1

Corticosteroids

• Recommended as adjunctive therapy for tuberculous pericarditis during first 11 weeks of anti-TB therapy 1
• Avoid in unexplained lymphadenopathy as they can mask histologic diagnosis of lymphoma or malignancy 5