Tuberculous Lymphadenitis
Model Case Presentation
Patient Demographics
Name: Master Arjun, Age: 8 years, Gender: Male, Informant: Mother (Reliable)
Chief Complaints
- Swelling in the right side of the neck — 3 months
- Low-grade fever on and off — 2 months
- Loss of appetite and weight loss — 2 months
History Summary
The child's mother first noticed a small, painless lump on the right side of the neck 3 months ago. The swelling has gradually increased in size. No acute pain, no redness initially. For the past 2 months the child has had low-grade evening fever with night sweats, loss of appetite, and noticeable weight loss (~2 kg). No cough, no hemoptysis, no breathlessness at present.
Significant history: Contact with a sputum-positive TB adult — paternal grandfather diagnosed with pulmonary TB 6 months ago and lives in the same household. BCG scar present. Born at term, NVD, uneventful perinatal period. Immunizations up to date. No prior TB treatment. No history of animal or unpasteurized milk exposure. Not on steroids or immunosuppressants. HIV serostatus unknown.
Examination Summary
| Parameter | Finding | Significance |
|---|---|---|
| Weight | 18 kg (expected ~25 kg) | Failure to thrive / weight loss |
| Temperature | 37.9°C (evening) | Low-grade fever |
| HR | 90/min | Normal |
| RR | 22/min | Normal |
| BCG scar | Present (left arm) | Vaccinated; does not exclude TB |
| Pallor | Mild | Chronic disease anemia |
Neck examination: Right posterior cervical and submandibular region — multiple lymph nodes, largest ~3 × 3 cm. Nodes are firm, non-tender, matted (fixed to each other), and mildly fixed to underlying tissue. Overlying skin shows early purplish discoloration at the center of the largest node — suggestive of impending collar-stud abscess formation. No active sinus or ulcer. No contralateral or axillary lymphadenopathy.
Respiratory: Chest clear on auscultation. No wheeze or crepitations. Chest expansion symmetrical.
Abdomen: Liver 2 cm below RCM, soft (reactive). No splenomegaly. No ascites.
✅ Complete Diagnosis
Tuberculous Cervical Lymphadenitis (Scrofula) — Stage 4 (Early Collar-Stud Abscess Formation) — Right Posterior Triangle and Submandibular Group — with Constitutional Symptoms and History of Close Contact with Sputum-Positive PTB.
📝 History — Exam Q&A
Tuberculous lymphadenitis is the most common form of extrapulmonary TB, accounting for ~35% of all extrapulmonary TB cases. Among all sites of lymph node TB, the cervical group is the most commonly affected (accounting for ~60–90% of peripheral TB lymphadenitis).
Local: Painless, slowly progressive neck swelling (the hallmark). Pain may occur if secondary infection supervenes.
Constitutional (B-symptoms):
- Low-grade evening fever with night sweats
- Weight loss and loss of appetite (anorexia)
- Malaise and easy fatigability
Note: Up to 57% of patients may present without systemic symptoms, making the painless neck swelling the sole complaint.
History of close contact with a sputum-smear positive TB patient — particularly a household contact — is the single most important risk factor. Ask specifically about:
- Who the contact is (family member, caregiver)
- Duration and proximity of contact
- Whether the contact has been diagnosed and started on treatment
- Whether the child has been screened (Mantoux, chest X-ray)
| Feature | TB Lymphadenitis | Acute Pyogenic Lymphadenitis |
|---|---|---|
| Onset | Insidious (weeks to months) | Acute (days) |
| Pain | Usually painless (cold) | Painful, tender |
| Fever | Low-grade, evening | High-grade, acute |
| Node consistency | Firm to rubbery, matted | Tender, warm, erythematous |
| Overlying skin | Purplish/violaceous (late) | Red, hot, shiny |
| Abscess pus | Cold abscess — cheesy, odourless | Hot, purulent, malodorous |
| Response to antibiotics | None | Good (partial to complete) |
- No cough / hemoptysis — rules out significant active pulmonary TB in the child (though hilar nodes may be present)
- No bone pain / limping — rules out skeletal TB
- No headache / vomiting / altered sensorium — rules out TB meningitis
- No abdominal pain / distension — rules out abdominal TB
- No prior ATT — important to document to rule out drug resistance
- No animal or unpasteurized milk exposure — rules out M. bovis
- No cat exposure — rules out Cat-scratch disease (Bartonella henselae)
- BCG vaccination status — recorded but does not exclude TB
- No immunosuppression — HIV, steroid use, malnutrition (all increase risk)
TB cervical lymphadenitis occurs by one of two routes:
- Hematogenous/lymphatic spread from a primary pulmonary focus (most common in children). The primary complex (Ghon's focus + hilar nodes) seeds cervical nodes via the lymphatics or bloodstream.
- Direct inoculation via the oropharyngeal/tonsillar route — M. tuberculosis or M. bovis from contaminated milk infects tonsillar tissue → cervical lymph node drainage. More common in younger children and in countries where bovine TB is prevalent.
The cervical nodes drain the entire head and neck, accounting for their frequent involvement.
Scrofula (from Latin scrofa = brood sow) is the historical term for tuberculosis of the cervical lymph nodes. It is the most recognizable form of peripheral TB lymphadenopathy. During the Middle Ages, it was called the "King's Evil" because touching by the king was believed to cure it. Today, the term is used synonymously with cervical TB lymphadenitis.
In children, TB lymphadenitis is seen across all age groups but is rare in infancy (<1 year). It is more common in the 5–14 year age group. In Indian pediatric studies, there is a mild male preponderance (male:female ~1.5:1), though adult series show a slight female predominance. Children from endemic areas, with household contact, or with malnutrition are disproportionately affected.
| Category | Conditions |
|---|---|
| Infectious | TB (M. tuberculosis), NTM (M. avium complex), Cat-scratch disease (Bartonella), EBV (infectious mononucleosis), CMV, Toxoplasmosis, HIV |
| Malignant | Hodgkin's lymphoma, Non-Hodgkin's lymphoma, Neuroblastoma, Metastatic nodes (rare in children) |
| Inflammatory | Sarcoidosis, Kawasaki disease, Kikuchi-Fujimoto disease, Systemic JIA |
| Congenital neck masses | Branchial cyst, Cystic hygroma, Thyroglossal cyst (not lymph nodes — but may mimic) |
💡 Red Flags Favouring Malignancy
Supraclavicular location, node >3 cm, firm/hard, non-tender, rapidly growing, hepatosplenomegaly, mediastinal widening on CXR, absence of TB contact, failure to respond to ATT → consider lymph node biopsy urgently.
🩺 Examination — Exam Q&A
Examine from behind the patient (standard for neck lymph nodes). Assess:
- Number: Single or multiple
- Site/Group: Anterior triangle, posterior triangle, submandibular, submental, preauricular, occipital, supraclavicular
- Size: In cm (measure largest node)
- Shape: Oval (usually normal) vs rounded (abnormal)
- Surface: Smooth or irregular
- Consistency: Soft / rubbery / firm / hard
- Matting: Whether nodes are fused/stuck to each other — highly characteristic of TB
- Mobility: Mobile vs fixed to skin or deep tissue
- Tenderness: Tender (acute infection) vs non-tender (TB, malignancy)
- Overlying skin: Normal / erythematous / purplish / sinus / ulcer
- Fluctuation: Abscess formation
Also examine: all other lymph node groups (generalized vs localized), liver, spleen, chest for primary focus.
Matting — multiple enlarged lymph nodes that are adherent to each other (fused together) due to periadenitis (inflammation of the perinodal tissue). They feel like a single irregular mass but can be made out as individual nodes on careful palpation. Matting is the hallmark of TB lymphadenitis and distinguishes it from reactive and malignant nodes.
| Stage | Description | Key Feature |
|---|---|---|
| Stage I | Enlarged, firm, mobile, discrete nodes | Non-specific reactive hyperplasia; nodes separate |
| Stage II | Nodes enlarged, fixed to each other and to surrounding tissues | Periadenitis — matting (hallmark) |
| Stage III | Central softening; caseation within nodes | Cold abscess formation (fluctuant, non-tender, non-erythematous) |
| Stage IV | Abscess penetrates deep fascia, collects under skin | Collar-stud abscess — bilocular (deep + superficial component connected through fascial defect) |
| Stage V | Skin ruptures | Discharging sinus tract / scrofuloderma |
💡 Collar-Stud Abscess
Named after the old-fashioned collar stud (button). The deep component (larger) communicates with the superficial component (smaller, under skin) through a narrow fascial defect — giving a bilocular "dumbbell" appearance. The superficial part fluctuates while the deep part is fixed. Aspirating only the superficial part leads to recurrence.
Scrofuloderma is a form of secondary cutaneous tuberculosis where TB from an underlying focus (usually a lymph node) breaks through the overlying skin, forming a chronic ulcer. Clinically:
- Bluish-red, indurated nodule overlying the affected node
- Breaks down to form a chronic, undermined ulcer with granulating tissue at the base
- Skin edges are irregular, overhanging (undermined), and purplish/livid in color
- Discharge is caseous (cheesy, odourless)
- Heals with irregular, stellate (puckered) scarring
It is the most common form of cutaneous TB in children.
The posterior cervical triangle (posterior to sternocleidomastoid) and submandibular nodes are most commonly affected. The upper deep cervical (jugulo-digastric) group is also frequently involved. The anterior triangle is involved less often. Supraclavicular involvement, while possible in TB, should raise suspicion for malignancy and warrants urgent biopsy.
- Wasting / failure to thrive — weight below expected for age
- Low-grade fever — typically in the evening
- Pallor — anemia of chronic disease
- BCG scar — documents vaccination (note: does not exclude TB)
- Mild hepatomegaly — reactive or due to systemic TB dissemination
- Absence of cyanosis, clubbing — helps distinguish from other causes
- Reduced breath sounds / dullness — if concurrent pleural effusion or consolidation
| Feature | TB (M. tuberculosis) | NTM (M. avium complex) |
|---|---|---|
| Age | Any age (uncommon <1 yr) | Younger (<5 years typically) |
| Site | Posterior cervical, submandibular | Submandibular, parotid region |
| Systemic symptoms | Often present (fever, weight loss) | Usually absent — child appears well |
| Contact history | Positive household contact in ~17–40% | No person-to-person transmission |
| Skin color | Purplish (late) | Early violaceous discoloration — distinctive |
| Mantoux (TST) | Positive (>10 mm) in ~85–97% | Often weakly positive (5–10 mm) or negative |
| IGRA | Positive in ~91% | Negative in ~97% |
🔬 Investigations — Exam Q&A
Mantoux test (TST): 0.1 mL of 1 TU of PPD (Purified Protein Derivative) is injected intradermally on the volar aspect of the left forearm. Read at 48–72 hours by measuring the diameter of induration (not erythema) in mm, in the transverse axis.
| Induration | Interpretation (India — IAP) |
|---|---|
| <5 mm | Negative (TB unlikely) |
| 5–9 mm | Weakly positive (may be BCG or NTM) |
| ≥10 mm | Significant — suggests TB infection |
| ≥5 mm in immunocompromised / known TB contact | Significant |
In TB lymphadenitis, Mantoux is positive in ~85–96% of children.
🚨 Causes of False-Negative Mantoux
Miliary TB, severe malnutrition, HIV/immunosuppression, recent viral illness or vaccination (measles, varicella), incorrect technique, incubation period of TB, steroid use, very young infants. A negative test does NOT exclude TB.
Interferon-Gamma Release Assays (IGRAs) — blood tests that measure IFN-γ released by sensitized T-cells in response to M. tuberculosis-specific antigens (ESAT-6 and CFP-10).
Available tests: QuantiFERON-TB Gold Plus (QFT-Plus) and T-SPOT.TB.
| Feature | Mantoux (TST) | IGRA |
|---|---|---|
| BCG interference | Yes — false positives with BCG | No — not affected by BCG |
| NTM interference | Yes — some NTM cross-react | No — highly specific for MTB |
| Visits needed | 2 (injection + reading) | 1 (blood draw only) |
| Cost | Cheap | Expensive |
| Use in TB lymphadenitis | Strongly positive in ~91% | Strongly positive in ~91%; helps differentiate from NTM |
In India, Mantoux remains the standard test. IGRA is preferred when BCG-vaccinated status confounds TST interpretation.
- Hilar / mediastinal lymphadenopathy — widened mediastinum or lobulated hilar shadow (most common finding of primary TB in children)
- Ghon's focus — small parenchymal opacity, usually in mid-zone
- Ranke's complex — calcified Ghon's focus + calcified hilar node (evidence of healed primary TB)
- Consolidation, collapse, or miliary pattern (if disseminated)
- Normal CXR — does NOT exclude TB lymphadenitis; CXR can be normal in ~78% of peripheral TB lymphadenitis cases
💡 Ranke Complex vs Ghon Complex
Ghon complex = Ghon focus (parenchymal lesion) + enlarged draining hilar lymph node. Ranke complex = calcified Ghon focus + calcified hilar node = radiological evidence of healed/resolved primary TB.
Fine Needle Aspiration Cytology (FNAC) is the preferred initial diagnostic procedure. A 22–25 gauge needle is used to aspirate material from the lymph node without surgical incision. It is cheap, minimally invasive, and repeatable.
Cytological patterns in TB lymphadenitis:
- Pattern I — Epithelioid granulomas without necrosis: Clusters of epithelioid histiocytes + Langhans giant cells (early stage)
- Pattern II — Epithelioid granulomas with necrosis (caseation): Amorphous pink granular material + epithelioid cells — most diagnostic
- Pattern III — Necrosis alone: Caseous material with sparse cells (AFB stain positive in higher proportion)
FNAC sensitivity for TB lymphadenitis: ~84–98%; specificity: ~100%; diagnostic accuracy: ~99%
AFB smear from FNAC aspirate is positive in 20–40% of cases. ZN staining is done on the aspirate.
Excision biopsy is the gold standard for histological diagnosis. Features:
- Caseating granulomas — the hallmark. Granulomas contain:
- Langhans giant cells — large multinucleated cells with peripherally arranged nuclei in a "horseshoe" or "wreath" pattern
- Epithelioid cells — activated macrophages with abundant eosinophilic cytoplasm and oval nuclei
- Peripheral rim of lymphocytes and fibroblasts
- Central caseous necrosis — amorphous, pink, acellular, cheese-like material (caseation = "cheese-like" in Latin)
- AFB stain (Ziehl-Neelsen) may show acid-fast bacilli as red rods on blue background
Non-caseating granulomas → think sarcoidosis, NTM, cat-scratch disease.
CBNAAT (Cartridge-Based Nucleic Acid Amplification Test) = GeneXpert MTB/RIF: A rapid molecular test that simultaneously detects M. tuberculosis DNA AND rifampicin resistance (as a marker for MDR-TB), using real-time PCR.
- Sample: FNAC aspirate or fresh biopsy tissue
- Result time: ~2 hours
- Sensitivity for extrapulmonary TB lymph node: ~80–86%
- Specificity: ~98–99%
- Advantage: Also detects RIF resistance → guides MDR-TB treatment
- Recommended by WHO and NTEP (National TB Elimination Programme, India) as first-line test for extrapulmonary TB
Ultrasound (USG) neck:
- First-line imaging — no radiation, inexpensive
- TB nodes: enlarged, rounded, hypoechoic, loss of echogenic hilum, central necrosis/cystic change
- Matting of nodes — multiple nodes with loss of intervening fat planes
- Guides FNAC — ultrasound-guided FNAC increases diagnostic yield
- Identifies collar-stud abscess and sinus tracts
CT neck (with contrast):
- Rim-enhancing nodes with central low-density necrosis — characteristic of TB
- Matted node clusters with relative absence of perinodal fat stranding (vs pyogenic where fat stranding is marked)
- Identifies deep space involvement, mediastinal nodes, and guides surgical planning
- CBC: Lymphocytosis (relative), normocytic normochromic anemia (anemia of chronic disease), normal or mildly raised TLC
- ESR: Raised (15–100 mm/1st hr) — non-specific but reflects inflammatory activity
- CRP: Elevated (non-specific)
- Liver function tests: Baseline before ATT (hepatotoxicity monitoring)
- HIV test: Mandatory in all TB patients — alters treatment duration and drug selection
- Blood culture: Not routinely done; may be positive in miliary/disseminated TB
The gold standard for definitive diagnosis is culture of M. tuberculosis (on Löwenstein-Jensen (LJ) medium or liquid MGIT/BACTEC 960 culture system) from the lymph node aspirate or biopsy tissue. However, culture takes 4–8 weeks and has limited sensitivity in paucibacillary disease. In practice:
- Histopathology of excision biopsy (showing caseating granulomas) = gold standard for histological diagnosis
- Culture = gold standard for microbiological confirmation and drug sensitivity
- FNAC + Mantoux + CXR + CBNAAT = practical diagnostic workup in a resource-limited setting
Since children often have paucibacillary disease (low bacterial load), microbiological confirmation may be unavailable. A clinical / probable diagnosis can be made based on:
- Chronic painless cervical lymphadenopathy (>3 weeks, non-responding to broad-spectrum antibiotics for 2 weeks)
- Significant Mantoux (≥10 mm)
- History of close TB contact
- Constitutional symptoms (fever, weight loss, night sweats)
- Suggestive CXR (hilar adenopathy, Ghon's complex)
- FNAC showing granulomas (even without AFB on smear)
- Exclusion of other causes
Diagnosis is further supported by a positive response to ATT (therapeutic trial — nodes should reduce in size within 2–3 months of starting ATT). IAP and NTEP guidelines support clinical diagnosis and empirical ATT when criteria are met.
💊 Management — Exam Q&A
TB lymphadenitis is classified as extrapulmonary TB and treated with the standard 6-month regimen:
Standard Regimen — 2HRZE / 4HR
Intensive Phase (2 months): Isoniazid (H) + Rifampicin (R) + Pyrazinamide (Z) + Ethambutol (E) — daily
Continuation Phase (4 months): Isoniazid (H) + Rifampicin (R) — daily
| Drug | Dose (Daily) | Key Side Effect |
|---|---|---|
| Isoniazid (H) | 10 mg/kg/day (max 300 mg) | Peripheral neuropathy, hepatotoxicity. Give Pyridoxine (Vitamin B6) supplement. |
| Rifampicin (R) | 15 mg/kg/day (max 600 mg) | Hepatotoxicity, orange discoloration of secretions, drug interactions (CYP450 inducer) |
| Pyrazinamide (Z) | 35 mg/kg/day (max 2 g) | Hyperuricemia, hepatotoxicity, arthralgia |
| Ethambutol (E) | 20 mg/kg/day (max 1 g) | Optic neuritis (monitor visual acuity and color vision) — use with caution in young children |
Fixed-Dose Combinations (FDC) are preferred. Treatment given under DOTS (Directly Observed Treatment, Short course) under NTEP in India.
Corticosteroids are not routinely indicated for TB lymphadenitis. They may be used in specific situations:
- Paradoxical reaction (immune reconstitution inflammatory syndrome — IRIS) — nodes enlarge after starting ATT despite the patient improving clinically. Occurs especially in the first 2–3 months of treatment. Prednisolone 1–2 mg/kg/day for 4–6 weeks with gradual taper is used.
- Airway compression due to massive mediastinal lymphadenopathy
- Pericardial or meningeal TB (clearly indicated)
The paradoxical reaction does NOT indicate treatment failure — do NOT stop or change ATT.
Surgery plays a limited but important role. ATT is the mainstay. Surgical indications and procedures:
| Indication | Procedure |
|---|---|
| Diagnostic (when FNAC inconclusive or fails) | Excision biopsy (preferred over incisional biopsy) |
| Cold abscess (Stage III) | Needle aspiration (repeated if needed) — preferred over I&D to avoid sinus formation |
| Collar-stud abscess (Stage IV) | Aspiration of superficial and deep components; may need surgical excision of fascia |
| Non-healing sinus (Stage V) | Sinus excision + wound curettage |
| Persistent disease after adequate ATT | Excisional surgery for diagnosis (rule out MDR-TB, malignancy) |
🚨 Do NOT perform Incision and Drainage (I&D)
Simple I&D of a TB cold abscess is contraindicated as it leads to chronically discharging sinuses that are difficult to manage. Needle aspiration is preferred.
A paradoxical reaction (also called Immune Reconstitution Inflammatory Syndrome or IRIS) is the enlargement or appearance of new TB lesions after starting effective ATT, despite the child being otherwise improving clinically.
Occurs in ~15–25% of children with TB lymphadenitis, typically 4–8 weeks after starting ATT.
Mechanism: As ATT kills bacilli and reduces antigenic load, the host immune system recovers and mounts a vigorous inflammatory response against remaining antigens → nodes enlarge, new nodes may appear, cold abscess may develop.
Management: Continue ATT (do not stop). Add prednisolone 1–2 mg/kg/day if severe. Distinguish from true ATT failure (where AFB smear/culture may turn positive again).
Clinical monitoring:
- Monthly visits — assess weight gain, constitutional symptoms, node size
- Node should start reducing by 2–3 months
- Complete resolution may take 6–12 months (even after completing ATT)
Investigations:
- LFTs at baseline and if hepatitis symptoms appear (jaundice, vomiting, abdominal pain)
- Visual acuity and color vision — if on Ethambutol (monthly in young children)
- Uric acid — if pyrazinamide side effects suspected
Criteria for ATT-induced hepatotoxicity (stop drugs): Serum ALT/AST >3× ULN with symptoms, or >5× ULN without symptoms. Reintroduce drugs one by one after recovery.
All close household contacts of a sputum-positive TB patient should be screened. For children who are contacts:
- If symptomatic → Full workup for active TB → treat if TB confirmed
- If asymptomatic, Mantoux <5 mm, CXR normal: Repeat Mantoux in 8–12 weeks; if still negative → BCG if not vaccinated
- If asymptomatic, child <5 years, exposed to smear-positive index case: Give Isoniazid Preventive Therapy (IPT) — Isoniazid 10 mg/kg/day for 6 months (regardless of Mantoux result in children <5 years or immunocompromised)
- Children 5–14 years with Mantoux ≥5 mm and no active disease → IPT 6 months
MDR-TB (Multi-Drug Resistant TB): Resistance to at least Isoniazid and Rifampicin simultaneously. Suspect if:
- Contact with known MDR-TB patient
- Prior ATT failure (non-response after 5 months of treatment)
- Relapse after previously treated TB
- GeneXpert detects rifampicin resistance
Management of MDR-TB: Refer to DRTB Centre. Regimen includes second-line drugs — Bedaquiline, Linezolid, Clofazimine, Cycloserine, etc. (longer, more toxic, specialized management). In India under NTEP: BPaL or BPaLC regimens for paediatric MDR-TB.
With standard 6-month ATT, the cure rate is excellent (~83–90%). Nodes progressively decrease in size over 2–6 months. Complete resolution may take up to 12 months. Key points:
- Some residual fibrosis or calcification of nodes may persist on imaging — does not indicate treatment failure
- Scrofuloderma ulcers heal with irregular, stellate (puckered) scarring
- Collar-stud abscesses that are appropriately aspirated resolve without permanent disfigurement
- Prognosis worsens significantly in HIV co-infection or MDR-TB
🔭 Recent Advances — Exam Q&A
India renamed RNTCP (Revised National TB Control Programme) as NTEP (National TB Elimination Programme) in 2020, with the target of eliminating TB (incidence <1 per million) by 2025 (ahead of the WHO's 2030 End TB target).
Key changes under NTEP:
- Daily regimen: Shift from thrice-weekly (intermittent) to daily fixed-dose combination (FDC) therapy for all TB patients
- CBNAAT/GeneXpert as first-line test for all presumptive TB cases (especially extrapulmonary)
- Nikshay portal: Digital notification and tracking of all TB patients
- Nikshay Poshan Yojana: ₹500/month nutritional support for all TB patients on treatment
- Bedaquiline and Delamanid available for paediatric MDR-TB
- BPaL/BPaLC regimens for drug-resistant TB
The SHINE (Shorter Treatment for Minimal Tuberculosis in Children) trial (published 2022, Lancet) showed that for children with non-severe TB (which includes uncomplicated peripheral lymphadenitis), a 4-month regimen (2HRZE/2HR) was non-inferior to the standard 6-month regimen.
Eligibility for 4-month regimen (WHO 2022 recommendation):
- Children <16 years
- HIV-negative or HIV-positive on ART with CD4 >100
- Non-severe TB: Peripheral lymphadenopathy, intrathoracic lymphadenopathy without airway compression, uncomplicated pulmonary disease
This is a significant advance — shorter treatment improves adherence and reduces drug toxicity.
- GeneXpert MTB/RIF (CBNAAT): Detects MTB + rifampicin resistance in ~2 hours. WHO and NTEP recommended as first-line test for extrapulmonary TB including lymph node aspirates. Sensitivity ~80–86% for lymph node TB.
- GeneXpert Ultra: Newer, more sensitive version with improved detection from paucibacillary samples (e.g., pediatric TB). Being scaled up.
- Truenat MTB Plus: Indian-made, cartridge-based NAAT — approved by WHO as initial test. Point-of-care test, can be used at peripheral health centres.
- Line Probe Assay (LPA — GenoType MTBDRplus): Detects resistance to H and R (and fluoroquinolones in LPA-sl). Used on culture isolates or direct smear-positive specimens. Faster than culture-based DST.
- Whole Genome Sequencing (WGS): Research setting — comprehensive resistance profiling, strain typing, transmission mapping.
BCG (Bacille Calmette-Guérin) remains the only licensed TB vaccine. It protects against severe forms (miliary TB, TB meningitis) in children but has variable efficacy against pulmonary TB in adults. Newer vaccines in trials:
- M72/AS01E (GSK): Phase 2b trial showed ~50% efficacy against pulmonary TB in latently infected adults (2019, NEJM). Phase 3 trials ongoing.
- BCG revaccination: Trials in adolescents showing some protective effect.
- MVA85A: Modified Vaccinia Ankara expressing Ag85A — subunit vaccine boost for BCG-vaccinated individuals. Phase 2 trials.
- VPM1002: Recombinant BCG expressing listeriolysin — improved safety and immunogenicity. Phase 3 trials in India and South Africa.
- Bedaquiline (Bdq): ATP synthase inhibitor — the first new anti-TB drug in 40 years. WHO-recommended for MDR-TB and now available for children ≥5 years (weight ≥15 kg) in India through NTEP. Part of BPaL (Bedaquiline + Pretomanid + Linezolid) 6-month regimen for pre-XDR and XDR-TB.
- Delamanid (Dlm): Nitroimidazole — inhibits mycolic acid synthesis. Approved for MDR-TB in children ≥3 years (WHO 2016). Available in India under NTEP.
- Pretomanid: Part of BPaL regimen — used in extensively drug-resistant (XDR) TB.
These newer drugs enable shorter, safer, and more effective regimens for children with drug-resistant TB.
⚡ Key Points — Quick Revision
One-Liners for Exam
- Most common extrapulmonary TB: Lymphadenitis; most common site = cervical
- Scrofula: Old term for TB cervical lymphadenitis ("King's Evil")
- Hallmark sign on palpation: Matting of nodes (periadenitis)
- 5 stages (Jones & Campbell): Reactive hyperplasia → Periadenitis → Cold abscess → Collar-stud abscess → Sinus/Ulcer
- Collar-stud abscess: Bilocular abscess (deep + superficial) connected through fascial defect
- Scrofuloderma: TB breaking through overlying skin → undermined ulcer with purplish edges; most common cutaneous TB in children
- Most important risk factor: Close household contact with sputum-positive TB patient
- Mantoux significant: ≥10 mm induration (≥5 mm in immunocompromised); positive in ~85–96% of TB lymphadenitis
- FNAC findings: Caseating granulomas — Langhans giant cells + epithelioid cells + central caseous necrosis
- Langhans giant cell: Nuclei arranged in horseshoe/wreath pattern at periphery (distinguish from foreign body giant cell where nuclei are central)
- Gold standard histology: Caseating granuloma on excision biopsy
- Gold standard microbiology: Culture of M. tuberculosis
- First-line molecular test (NTEP): CBNAAT (GeneXpert MTB/RIF) — detects MTB + RIF resistance in ~2 hours
- CXR finding: May be normal in ~78%; hilar lymphadenopathy or Ranke's complex when positive
- Ranke complex: Calcified Ghon focus + calcified hilar node = healed primary TB
- Standard ATT regimen: 2HRZE / 4HR (6 months total)
- SHINE trial (2022): 4-month regimen (2HRZE/2HR) non-inferior for non-severe TB (incl. peripheral lymphadenitis) in children
- Do NOT do I&D of cold abscess — causes chronic sinus. Needle aspiration preferred.
- Paradoxical reaction (IRIS): Nodes enlarge after starting ATT; do NOT stop ATT; add steroids if severe
- IPT (Isoniazid Preventive Therapy): INH 10 mg/kg/day × 6 months for contacts <5 years or immunocompromised
- NTM vs TB lymphadenitis: IGRA negative in 97% of NTM; NTM — child appears well, no contact, early violaceous skin
- MDR-TB definition: Resistant to Isoniazid + Rifampicin simultaneously
- NTEP target: Eliminate TB in India by 2025
💡 Drug Mnemonics
HRZE = "Have Rest, Zero Exercise" — Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E)
Ethambutol side effect: "E-ye" — Optic neuritis (watch the Eye!)
Rifampicin: "Rifampicin Reddens everything" — turns urine, sweat, tears orange-red (warn parents!)
Pyrazinamide + Uric acid: "Pyrazinamide = Pyro (burning joints) + Uric acid"