Scrofula: Diagnosis and Treatment
What is Scrofula?
Scrofula is tuberculous cervical lymphadenitis caused by Mycobacterium tuberculosis, presenting as painless, progressive cervical lymph node enlargement that may progress to abscess formation and skin involvement (scrofuloderma). 1, 2
Clinical Presentation and Risk Factors
Scrofula typically manifests as:
- Painless, progressively enlarging cervical lymph nodes that may become matted 2, 3
- Potential progression to cold abscess formation with overlying skin involvement 1
- May occur with or without pulmonary tuberculosis symptoms 1, 3
High-risk populations include:
- Foreign-born individuals from TB-endemic countries 3
- HIV-positive patients (scrofula may represent disseminated TB) 2, 3
- Patients with prior positive tuberculin skin test 3
- Immunocompromised individuals 2
Diagnostic Approach
Initial Evaluation
Obtain a detailed history focusing on TB risk factors including country of origin, HIV status, prior TB exposure, and constitutional symptoms (fever, night sweats, weight loss). 2, 3
Perform chest radiography on all patients to rule out pulmonary tuberculosis, as this fundamentally alters isolation and contact tracing requirements. 4, 3
Microbiological Diagnosis
Obtain tissue or aspirate from the affected lymph node for:
- Acid-fast bacilli (AFB) smear microscopy 4
- Mycobacterial culture (gold standard) 1
- Nucleic acid amplification testing (NAAT) for rapid M. tuberculosis identification 5
At least three specimens should be submitted when possible to maximize diagnostic yield. 4
HIV Testing
All patients diagnosed with scrofula must be assessed for HIV infection, as this alters treatment duration, monitoring, and prognosis. 4, 2 HIV counseling and testing should be strongly encouraged if risk factors are present. 4
Distinguishing from Nontuberculous Mycobacteria
While M. scrofulaceum historically caused childhood cervical lymphadenitis, it has largely been replaced by Mycobacterium avium complex (MAC) and is now rarely seen. 4 Molecular identification (DNA probes or 16S rRNA sequencing) may be required to differentiate M. tuberculosis from nontuberculous mycobacteria. 4
Treatment Regimen
Standard Four-Drug Therapy
Initiate treatment immediately upon diagnosis with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months (intensive phase), followed by isoniazid and rifampin for 4 additional months (continuation phase), for a total duration of 6 months. 4, 6, 7, 8
The fourth drug (ethambutol) can be discontinued once drug susceptibility testing confirms no resistance to isoniazid and rifampin. 5
Dosing Specifics
- Isoniazid: 300 mg daily (adults >30 kg); 10 mg/kg daily in children (maximum 300 mg) 7
- Rifampin: Per standard TB treatment protocols 6
- Pyrazinamide: Per standard TB treatment protocols 4
- Ethambutol: 15 mg/kg daily for initial treatment; 25 mg/kg daily for retreatment 8
Directly Observed Therapy
All antituberculosis medications should be administered using directly observed therapy (DOT), where a healthcare provider or trained observer watches the patient swallow each dose. 4, 7 This is critical to prevent treatment failure and drug resistance development.
Special Populations
HIV-Positive Patients:
- Assess for antiretroviral therapy (ART) indications during TB treatment 4
- Initiate cotrimoxazole prophylaxis 4
- Consider consultation with an HIV/TB specialist given drug interaction complexity 4
- Screen for malabsorption and monitor drug levels if advanced HIV disease 7
Pregnant Women:
- Use isoniazid, rifampin, and ethambutol (avoid streptomycin due to ototoxicity risk) 7
- Pyrazinamide is not routinely recommended due to inadequate teratogenicity data 7
Monitoring During Treatment
Obtain repeat cultures at 2 months to assess treatment response. 4, 5 Approximately 80% of patients with drug-susceptible TB will have negative cultures at this timepoint. 5
Monitor for adverse drug reactions:
- Hepatic enzymes weekly for 2 weeks, then every 2-4 weeks during the first 2 months 9
- Visual acuity and color discrimination monthly if on ethambutol (especially at 25 mg/kg dosing) 8
- Renal function if using ethambutol or injectable agents 9
Patients with positive cultures at 2 months require evaluation for:
Isolation and Contact Investigation
Patients with scrofula alone (without pulmonary involvement) are generally not considered infectious and do not require airborne isolation. However, if chest radiography reveals pulmonary TB, standard airborne precautions apply until three consecutive negative AFB sputum smears are obtained. 4, 5
When pulmonary TB is confirmed, close contacts (those sharing common ventilation systems for prolonged periods) should undergo tuberculin skin testing or IGRA. 4 Previously tuberculin-negative contacts should be retested 8-12 weeks after exposure ends. 10
Critical Pitfalls to Avoid
Never initiate single-drug therapy or add a single drug to a failing regimen, as this invariably leads to drug resistance. 5, 9 Always add at least two, preferably three, new drugs when treatment failure occurs.
Do not delay treatment initiation while awaiting culture results if clinical suspicion is high. 5, 9 The consequences of untreated TB far outweigh the risks of empiric therapy.
Always perform drug susceptibility testing on positive cultures. 4, 6 If local isoniazid resistance exceeds 4%, maintain the four-drug regimen until susceptibility results are available. 5
Do not assume scrofula is the only site of TB involvement. 1, 3 Chest radiography is mandatory to exclude pulmonary disease, which has different transmission implications.
Ensure HIV testing is performed, as co-infection fundamentally alters management. 4, 2 HIV-positive patients may require extended treatment duration and have higher risk of treatment failure.
Case Reporting
All confirmed or suspected TB cases must be reported to local or state health departments as required by law. 4 This enables appropriate public health response and contact tracing.