Tuberculosis — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mr Hung Tran, 58 years old, retired engineer, born in Vietnam, arrived in Australia 12 years ago. [1]

Presenting complaint: Six weeks of productive cough (yellow sputum, occasionally blood-streaked), 8 kilograms of weight loss, drenching night sweats, fatigue and exertional dyspnoea. Two episodes of streaky haemoptysis in the past week. [1]

Past history:

• Type 2 diabetes mellitus for 15 years — currently on metformin 1 g twice daily and gliclazide 80 mg daily; most recent HbA1c 78 mmol per mol (9.3 per cent).
• Atrial fibrillation — on warfarin 5 mg daily, INR target 2.0 to 3.0; last INR 2.4 one week ago.
• Stage 4 chronic kidney disease — eGFR 22 mL per min per 1.73 m squared, presumed diabetic nephropathy; baseline creatinine 240 micromoles per litre.
• Hepatitis B surface antigen positive — known for 10 years; not on antiviral therapy; last DNA 3 years ago was 2,000 IU per mL.
• 35-pack-year smoker (currently smoking 20 per day).
• No known drug allergies. [1]

Social history: Lives with his wife and two adult children (ages 28 and 25); none are unwell. Retired engineer; financially stable. Drinks 20 grams of alcohol daily. [1]

Examination findings: Cachectic (BMI 19), afebrile (36.9 degrees Celsius), heart rate 88 irregularly irregular, blood pressure 134/82, respiratory rate 18, oxygen saturation 94 per cent on room air. Finger clubbing present. Reduced right upper lobe chest expansion, dullness to percussion and bronchial breath sounds with inspiratory crackles at the right apex. No cervical lymphadenopathy. No hepatosplenomegaly. No signs of hepatic decompensation. [1]

Investigations:

• Chest radiograph: 4 cm right upper lobe cavity with surrounding fibronodular infiltrate and right upper lobe volume loss.
• Sputum acid-fast bacillus smear: 2 of 3 specimens strongly positive (3 plus).
• GeneXpert MTB/RIF: positive for Mycobacterium tuberculosis complex; NO rifampicin resistance detected.
• HIV serology: negative.
• Full blood count: normal.
• Liver function tests: normal (ALT 28, AST 24, ALP 95, bilirubin 12).
• Creatinine: 280 micromoles per litre (baseline 240).
• INR on admission: 2.6. [1]

Candidate's opening statement (model answer)

"Mr Hung Tran is a 58-year-old Vietnamese-Australian retired engineer presenting with six weeks of productive cough, haemoptysis, eight kilograms of weight loss and night sweats. His significant past history includes type 2 diabetes with poor control (HbA1c 78), stage 4 chronic kidney disease (eGFR 22), hepatitis B surface antigen positivity, atrial fibrillation on warfarin, and a 35-pack-year smoking history. [1]

His chest radiograph shows a right upper lobe cavity. Two of three sputa are strongly smear-positive for acid-fast bacilli and GeneXpert MTB/RIF is positive for Mycobacterium tuberculosis complex with no rifampicin resistance. He has drug-susceptible smear-positive cavitary pulmonary tuberculosis. [1]

My problem list is:

1. Smear-positive, drug-susceptible cavitary pulmonary tuberculosis — highly infectious, requires airborne isolation and standard six-month RIPE therapy
2. Hepatitis B co-infection — increased hepatotoxicity risk from the TB regimen
3. Type 2 diabetes with poor control — worsened by TB and altered by rifampicin
4. Stage 4 chronic kidney disease — requires ethambutol and pyrazinamide dose adjustment
5. Atrial fibrillation on warfarin — clinically significant rifampicin-warfarin interaction
6. Active 35-pack-year smoking and cachexia
7. Household contacts (wife and two adult children) requiring public health contact tracing [1]

My immediate management priorities are airborne isolation, notification of the TB service and public health, starting the standard RIPE regimen with renal and hepatotoxicity adjustments, anticipating and managing the rifampicin-warfarin interaction, monthly monitoring, and a concentric contact investigation of the household." [1]

Structured problem list and integrated management plan

Problem 1 — Smear-positive pulmonary tuberculosis

What to do:

• Admit to a negative-pressure airborne isolation room with N95/P2 respirator protection for staff and visitors.
• Notify the TB service, microbiology, infection control, and the public health unit (mandatory notifiable disease).
• Start standard RIPE therapy: rifampicin 600 mg daily, isoniazid 300 mg daily with pyridoxine 25 mg daily, pyrazinamide 25 mg/kg daily (renal-adjusted), ethambutol 15 mg/kg three times weekly (renal-adjusted) for 2 months; then rifampicin and isoniazid for 4 months (Nahid et al, 2016, PMID 27516382).
• Daily directly observed therapy or self-administered with weekly nursing support; VOT considered.
• Send mycobacterial culture (MGIT plus LJ) and full phenotypic and molecular drug susceptibility testing; perform a line-probe assay (GenoType MTBdrplus) on smear-positive sputum for rapid isoniazid resistance detection.
• Plan for 3 negative sputum smears on separate days (including one early morning) before discontinuing airborne isolation — typically 2 to 3 weeks.
• Because the disease is cavitary, check the 2-month sputum culture; if positive, extend the continuation phase to 7 months (total 9 months). [1]

Why: The diagnosis is confirmed. Standard therapy cures over 95 per cent of drug-susceptible cases when completed. Airborne isolation protects staff and other patients. Public health notification enables contact tracing. [1]

Problem 2 — Hepatitis B co-infection

What to do:

• Check hepatitis B DNA, e antigen and e antibody, and refer to hepatology for consideration of antiviral prophylaxis (entecavir or tenofovir) given the planned six-month course of hepatotoxic therapy.
• Monitor LFTs monthly and immediately for symptoms of hepatitis (nausea, vomiting, abdominal pain, jaundice).
• Stop all four drugs if ALT greater than 3 times ULN with symptoms, or greater than 5 times ULN without symptoms; exclude other causes of hepatitis; reintroduce sequentially (rifampicin, then isoniazid, then pyrazinamide) with LFTs at each step. [1]

Why: Hepatitis B co-infection significantly increases the risk of drug-induced hepatitis. Sequential reintroduction identifies the culprit and allows continuation with the other drugs plus an extension to 9 months if pyrazinamide is withheld. [1]

Problem 3 — Type 2 diabetes

What to do:

• Acute phase: sliding-scale insulin in hospital; metformin held (CKD and acute illness); gliclazide continued or held depending on intake.
• Liaise with the diabetes team; tighten glycaemic control once the patient is established on TB therapy and eating.
• Note that rifampicin induces sulfonylurea metabolism and may reduce the hypoglycaemic effect of gliclazide; insulin may be needed throughout therapy.
• Target HbA1c relaxed to under 64 mmol per mol in the acute illness to avoid hypoglycaemia in a cachectic patient with reduced intake. [1]

Why: TB worsens glycaemic control; poor glycaemic control worsens TB outcomes. Co-management with the diabetes team improves both. [1]

Problem 4 — Stage 4 chronic kidney disease

What to do:

• Ethambutol reduced to 15 mg/kg three times weekly after the first 2 weeks; monthly visual acuity and colour vision (Ishihara plates); patient educated to stop immediately and report any visual change.
• Pyrazinamide maintained at full dose or reduced to three times weekly in advanced CKD; monitor LFTs and uric acid.
• Rifampicin and isoniazid — no dose adjustment; pyridoxine 25 mg daily for neuropathy prophylaxis.
• Nephrology liaison; monthly renal function. [1]

Why: Ethambutol is renally cleared and accumulates in CKD, raising the risk of optic neuritis. Pyrazinamide metabolites accumulate and may worsen hepatic and uric-acid effects. [1]

Problem 5 — Atrial fibrillation on warfarin

What to do:

• Anticipate a marked fall in INR within 1 to 2 weeks of starting rifampicin (potent CYP2C9 inducer).
• Either substantially increase the warfarin dose (often double or triple) with INR monitored twice weekly during rifampicin therapy, or switch to therapeutic-dose LMWH (with caution in CKD where LMWH accumulates).
• Continue this patient on warfarin with intensive INR monitoring, because LMWH in eGFR 22 is harder to manage and accumulates.
• Counsel the patient that any other concomitant drug (statin, sulfonylurea, corticosteroid) may have reduced effect, and that the OCP (not relevant here) would be ineffective. [1]

Why: Rifampicin is the master drug-interaction trap of TB therapy. Unrecognised, it causes loss of anticoagulation and thromboembolic events; overcompensated, it causes haemorrhage when rifampicin is withdrawn and enzyme induction wanes. [1]

Problem 6 — Smoking and cachexia

What to do:

• Smoking cessation support (nicotine replacement therapy, varenicline if appropriate).
• Nutritional supplementation; weigh weekly; consider dietetics referral.
• Pneumococcal and influenza vaccination. [1]

Why: Smoking worsens TB outcomes and cachexia is a poor prognostic sign. Smoking cessation is the single most modifiable risk factor for long-term respiratory health. [1]

Problem 7 — Public health and contact tracing

What to do:

• Notify the case to the public health unit.
• Concentric contact investigation: highest priority to the household (wife and two adult children), who are screened with a symptom screen, IGRA (preferred) or TST at 8 to 10 weeks after last exposure, and chest radiograph.
• Close social and workplace contacts screened next.
• The patient is educated about cough hygiene, the importance of adherence, and the support available. [1]

Why: A smear-positive cavitary case infects approximately 10 to 15 close contacts per year in a low-burden setting. Early identification and treatment of recently infected contacts prevents progression to active disease. [1]

Communication and shared decision-making

• Culturally sensitive explanation of the diagnosis, the curability with six months of treatment, and the consequences of untreated TB to the patient and his family.
• Adherence counselling: the patient will need to take four drugs for 2 months and two drugs for 4 months, attend clinic monthly, and have blood tests and sputum tests at intervals.
• Side effect education: orange urine and sweat (rifampicin, benign); hepatitis symptoms (stop and report); visual symptoms on ethambutol (stop and report immediately); peripheral neuropathy (pyridoxine prophylaxis).
• Drug interaction counselling: warfarin dose will need significant adjustment; the patient must not start any new medication (including over-the-counter or herbal) without consulting the team.
• Social and family meeting with an interpreter if needed, and with the public health nurse, to discuss contact tracing, workplace implications, and the support available (financial, transport, language).
• Written information in Vietnamese and English about TB, the regimen, and the monitoring plan. [1]

Probing questions (model answers)

Examiner: "What are the indications for surgical intervention in pulmonary TB?" [1]

Candidate: "Surgery is rarely required in modern drug-susceptible TB because medical cure rates exceed 95 per cent. The indications are: (1) massive, life-threatening haemoptysis from a cavitary lesion eroding a bronchial artery — managed initially with bronchial artery embolisation, with surgical resection reserved for failure; (2) localised drug-resistant disease that has failed medical therapy — resection of a cavity or destroyed lobe reduces bacillary load and may render the patient culture-negative; (3) complications such as bronchopleural fistula, massive haemorrhage, or destroyed lung with secondary fungal infection (aspergilloma). The decision is always multidisciplinary with thoracic surgery, infectious diseases, and respiratory medicine." [1]

Examiner: "What is the role of corticosteroids in TB?" [1]

Candidate: "Corticosteroids are adjunctive therapy in three specific situations: tuberculous meningitis (Thwaites et al, 2004, PMID 15496623, improved survival), tuberculous pericarditis (to reduce constriction), and severe paradoxical reactions or IRIS in HIV-TB co-infection. Corticosteroids are NOT routinely used in pulmonary TB." [1]

Examiner: "How would your management change if the GeneXpert had detected rifampicin resistance?" [1]

Candidate: "That changes everything. I would not start standard RIPE. I would place the patient in airborne isolation, refer urgently to the multidisciplinary drug-resistant TB service, and await full phenotypic and molecular drug susceptibility testing including a line-probe assay for isoniazid, fluoroquinolone and injectable resistance. The modern approach is an all-oral regimen based on the resistance pattern, increasingly the BPaL or BPaLM regimen for eligible patients (Conradie et al, 2020, PMID 32130813). Treatment is individualised, longer, and delivered in close liaison with a specialist service. The contacts would also be managed as potentially MDR-exposed, with modified prophylaxis and follow-up." [1]

Examiner: "What is the role of directly observed therapy (DOT) in this patient?" [1]

Candidate: "DOT — having a trained observer watch each dose swallowed — is WHO-recommended as part of patient-centred care, with treatment support tailored to the patient. In ANZ it is offered selectively rather than universally. The indications for DOT include homelessness, substance use, prior non-adherence, cognitive impairment, prior treatment failure, and any risk of MDR-TB. This patient has multiple comorbidities and is on warfarin that needs intensive monitoring, so I would arrange a strong community support package — weekly nursing contact, video-observed therapy, an interpreter, and family involvement — rather than formal DOT. The decision is made jointly with the public health team." [1]

DCE Short Case

Instruction

"Examine this patient's respiratory system and cervical lymph nodes. Present your findings and discuss the diagnosis and management." [1]

Patient brief for the short case

Mrs Mai Nguyen, 68 years old, born in Vietnam, presenting with three months of cough, weight loss and a lump in the right side of the neck. [1]

Examination routine

1. Introduction, consent, exposure to the waist, position at 45 degrees.
2. End of bed: cachectic, no respiratory distress, no accessory muscle use.
3. Hands: finger clubbing present; no peripheral stigmata of endocarditis; no asterixis.
4. Pulse, blood pressure, respiratory rate, oxygen saturation.
5. Face and neck: oral hygiene normal (no candidiasis); right posterior cervical triangle contains a 2 cm, firm, matted, non-tender lymph node with no overlying skin change or sinus — consistent with scrofula; no other cervical, supraclavicular, axillary or inguinal lymphadenopathy.
6. Thorax: inspection (no scars); palpation (reduced right upper lobe chest expansion); percussion (dullness at the right apex); auscultation (bronchial breath sounds and late inspiratory crackles at the right apex, suggesting consolidation or cavity; normal breath sounds elsewhere; no wheeze).
7. Back: no spinal tenderness (exclude Pott disease); no sacral oedema.
8. Abdomen: no hepatosplenomegaly (exclude miliary disease); no ascites.
9. Lower limbs: no oedema; peripheral sensation and pulses intact. [1]

Presentation template (what the candidate says)

"Mrs Mai Nguyen is a cachectic 68-year-old woman with no respiratory distress. There is finger clubbing. In the right posterior triangle of the neck there is a 2 centimetre, matted, non-tender lymph node with no overlying skin change, consistent with scrofula. Examination of the chest reveals reduced right upper lobe expansion, dullness to percussion, and bronchial breath sounds with late inspiratory crackles at the right apex, consistent with consolidation or cavity. The remainder of the examination, including the back and abdomen, is unremarkable. [1]

My findings localise to the right upper lobe and the right cervical lymphatic chain. My differential diagnosis, in order of likelihood, is: (1) pulmonary tuberculosis with associated tuberculous lymphadenitis — supported by the upper lobe predominance, the cachexia, and the scrofula; (2) lung malignancy with metastatic cervical lymphadenopathy; (3) non-tuberculous mycobacterial disease, especially in an older woman from a high-burden country; (4) fungal infection such as histoplasmosis. I would also consider lymphoma presenting with cervical lymphadenopathy and a pulmonary infiltrate. [1]

My initial investigations are sputum for acid-fast bacillus smear, GeneXpert MTB/RIF and mycobacterial culture, a chest radiograph and CT of the thorax, HIV and hepatitis B and C serology, and a fine-needle aspiration or excision biopsy of the cervical lymph node for histology, AFB smear, mycobacterial culture and GeneXpert." [1]

Discussion questions

Examiner: "What is the yield of fine-needle aspiration versus excision biopsy in tuberculous lymphadenitis?" [1]

Candidate: "Fine-needle aspiration is the first-line test and has a histology yield of around 50 to 80 per cent for caseating granulomata and a culture yield of around 40 to 60 per cent. GeneXpert on FNA material has additional sensitivity for rifampicin resistance. Excision biopsy has the highest yield — over 90 per cent for histology — and is reserved for when FNA is non-diagnostic or when lymphoma cannot be excluded. Incisional biopsy is avoided because of the risk of a chronic discharging sinus." [1]

Examiner: "How would you treat this patient if the diagnosis is confirmed as drug-susceptible tuberculous lymphadenitis?" [1]

Candidate: "Standard RIPE therapy for 6 months: rifampicin, isoniazid, pyrazinamide and ethambutol for 2 months, then rifampicin and isoniazid for 4 months (Nahid et al, 2016, PMID 27516382). Surgical excision is reserved for diagnostic uncertainty, non-response, or a persistently discharging sinus. Most cases resolve with medical therapy; residual lymph node enlargement during therapy can be a paradoxical reaction and does not necessarily indicate failure." [1]

Examiner: "What is the role of the tuberculin skin test in this patient?" [1]

Candidate: "None, diagnostically. The TST and IGRA diagnose latent infection, not active disease. In a patient with confirmed active TB a positive TST simply confirms prior infection; a negative TST does not exclude active TB (up to 25 per cent of patients with active TB are anergic). The TST and IGRA have a role in screening the patient's contacts for latent infection." [1]