What is scrofula, a type of tuberculosis infection affecting the lymph nodes in the neck, typically seen in children and young adults?

What is Scrofula?

Scrofula is the historical term for tuberculous cervical lymphadenitis—a mycobacterial infection of the neck lymph nodes that presents as painless, slowly enlarging cervical masses, most commonly caused by Mycobacterium tuberculosis in adults and nontuberculous mycobacteria (NTM) in young children. 1

Historical Context and Modern Terminology

The term "scrofula" has ancient origins and was historically called "the King's Evil" because it was believed European monarchs could cure it by touch. 2 While the term persists in medical literature, modern classification distinguishes between:

• Tuberculous lymphadenitis (M. tuberculosis)—the classic "scrofula" 3, 4
• Nontuberculous mycobacterial (NTM) lymphadenitis—primarily MAC (Mycobacterium avium complex) and M. scrofulaceum 1

The organism M. scrofulaceum literally derives its name from this disease, though it now accounts for very few cases. 1

Epidemiology and Age-Related Patterns

Children (Ages 1-5 Years)

• NTM causes approximately 80% of culture-proven mycobacterial cervical adenitis in this age group, with MAC being the predominant organism 1, 5
• M. scrofulaceum historically caused many cases but has largely disappeared from clinical practice, possibly due to water chlorination changes 1
• Presentation is almost exclusively unilateral (95% of cases) and non-tender 1

Adults

• M. tuberculosis accounts for over 90% of mycobacterial cervical lymphadenitis in adults, making true tuberculous scrofula the dominant form 6, 3
• More commonly seen in minorities, women, and immunosuppressed patients, especially those with HIV 3
• In HIV-infected patients on antiretroviral therapy, suppurative cervical lymphadenopathy may represent immune reconstitution inflammatory syndrome (IRIS) 1, 5

Clinical Presentation

Classic Features

• Painless, insidious onset of cervical lymph node enlargement developing over weeks to months 1, 2
• Nodes are typically non-tender and unilateral (95%) 1
• Minimal or absent systemic symptoms in immunocompetent patients 1
• If neglected, progression to abscess formation, skin breakdown, and chronic draining sinuses 1, 2

Distinguishing Tuberculous from NTM Lymphadenitis

The most important clinical distinction is that tuberculous lymphadenitis in adults requires differentiation for treatment and public health tracking, while NTM disease in children is treated primarily with surgery. 5

Key differentiating features:

• Age: NTM predominantly affects children 1-5 years; TB more common in adults 1, 5
• Epidemiology: TB risk factors include foreign-born status, known TB exposure, positive family history 1
• Systemic involvement: TB may have pulmonary disease or other extrapulmonary manifestations 2, 3
• PPD tuberculin skin test: Strongly positive (≥15 mm) suggests TB, though this is not definitive 1

Diagnostic Approach

Critical Red Flags Requiring Urgent Workup

Duration ≥2 weeks, fixed/firm consistency, size >1.5 cm, and ulceration of overlying skin mandate urgent evaluation for malignancy rather than empiric antibiotics, as most adult neck masses are neoplastic. 5

Recommended Diagnostic Pathway

1. Tuberculin skin test (PPD) in all suspected mycobacterial cases 7

2. Chest radiograph to exclude pulmonary TB 7

3. Complete surgical excision (not incisional biopsy) for histopathology and culture 1, 5

   • Critical pitfall: Incisional biopsy or fine-needle aspiration alone causes chronic fistula formation in mycobacterial disease 5
   • Excisional biopsy provides tissue for AFB smear, culture, PCR, and histopathology 4

4. If cultures pending and PPD strongly positive (≥15 mm): Consider empiric anti-TB therapy while awaiting results, especially with TB risk factors 1

Treatment

For NTM Lymphadenitis in Children

Excisional surgery without chemotherapy is the recommended treatment, with a 95% success rate. 1, 7

• For recurrent disease or high surgical risk (e.g., facial nerve involvement with preauricular nodes): Consider clarithromycin-based multidrug regimen similar to pulmonary MAC disease 1
• Avoid: Incisional biopsy alone or anti-TB drugs without a macrolide, as these lead to persistent disease and sinus tract formation 1

For Tuberculous Lymphadenitis (True Scrofula)

Standard 4-drug TB therapy (isoniazid, rifampin, pyrazinamide, ethambutol) for 6-9 months 7, 2

• The Revised National Tuberculosis Control Programme recommends rifampicin and isoniazid three times weekly for 6 months, with pyrazinamide for the first 2 months 2
• Paradoxical reactions (worsening lymphadenopathy after treatment initiation) occur commonly, even in immunocompetent patients 1, 8
• For severe paradoxical reactions: Prednisone 1 mg/kg/day for 1-2 weeks, then taper 1
• Therapeutic ultrasound-guided nodal aspiration may be considered for massive adenopathy 8

For HIV-Associated Disease

• Disseminated MAC diagnosed via blood cultures in >90% of cases 1
• IRIS management: Continue both TB and antiretroviral therapy with symptomatic treatment; severe cases may require prednisone 1.25 mg/kg/day 1, 5

Common Pitfalls to Avoid

1. Prescribing empiric antibiotics without clear bacterial infection signs (warmth, erythema, tenderness, fever) delays malignancy diagnosis 5
2. Performing incisional biopsy instead of complete excision for suspected mycobacterial disease 5
3. Using anti-TB drugs without a macrolide for NTM disease leads to treatment failure 1
4. Attributing worsening adenopathy to treatment failure when it may represent paradoxical reaction 1, 8
5. Over-diagnosing based on clinical grounds alone without histological confirmation results in unnecessary treatment 2