Persistent cough in a young woman

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Problem 32 Persistent cough in a young woman

Richard A. Stapledon

A 37-year-old woman of Caucasian origin presents with an irritating cough of 3 months’ duration and recent episodes of small amounts of blood-stained sputum. She is a non-smoker. She has consulted her family doctor twice during this period and has had only a modest response to successive courses of antibiotics. She has also noticed some lethargy and more recently occasional night sweats.
On examination she appears mildly unwell, has evidence of recent weight loss and a temperature of 38.2°C. No other abnormal findings were elicited.

Q.1

What further history should be obtained?

You question the patient further. Five years ago she spent 2 years as a volunteer teacher in Malawi. When she returned she underwent TB screening and had a ‘positive’ tuberculin skin test and a normal chest X-ray. At the time, the clinic placed her on a 6-month course of isoniazid preventive therapy, which she had apparently completed.

You arrange a chest X-ray. The PA and lateral views are shown in Figures 32.1 and 32.2.

image

Figure 32.1

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Figure 32.2

Q.2

What does the chest X-ray show? What might the findings suggest? Would any other imaging be of help?

Q.3

What simple investigation would you request urgently? Are there any other investigations that may assist in making the diagnosis?

Your suspicions have been aroused, and you admit her to an isolation ward for investigation and treatment. Later, your lunch is interrupted by a call from the microbiology laboratory advising that the smear from her sputum is heavily positive for acid-fast bacilli (AFBs).

Q.4

Why does this result necessitate an urgent call? What should you do now? What additional investigations are indicated?

Q.5

What treatment would you recommend initially and why? What are the main treatment concerns?

Q.6

Are there any other issues that you need to address promptly?

Your patient is surprised and concerned that she is sick, and wants to know if this could have been prevented.

Q.7

Could this illness have been prevented?

Answers

A.1 A careful history in a patient with persistent cough and haemoptysis may provide clues about a possible diagnosis before any definitive investigations are undertaken.

Causes include:

• Lung abscess/pneumonia.
• Bronchiectasis.
• Active tuberculosis (TB).
• Mycetoma.
• Lung cancer (e.g. carcinoid).
• Chronic bronchitis.
• A-V malformation.
• No cause is found in up to 30% of cases.

This patient’s fever and night sweats strongly imply an infective cause. The more chronic nature of her history suggests that tuberculosis must be excluded. Disease caused by a non-tuberculous mycobacterium can present a similar clinical picture to TB but in this instance is considered less likely to be the causative agent. Lung abscess or malignancy would also seem less likely. You need to specifically enquire about any TB risk factors:

• Known close contact with a TB case (especially family).
• Past residence or visits to a high-risk country for an extended period, including India, Asia, Africa and Aboriginal and Torres Strait Islander people(s).
• History of previous treatment for TB disease or ‘preventive’ treatment for latent TB infection.
• Causes of immunosuppression such as HIV infection, immunosuppressive medications particularly TNF agents and steroids.

A.2 The chest X-ray shows a cavitating lesion in the left upper lobe, with some air space opacity in slightly contracted upper lobes.

These chest X-ray findings are highly suspicious of post-primary TB disease, especially in this clinical context. However, no chest X-ray pattern is absolutely diagnostic. Lung malignancies need to be considered and may also co-exist.

TB disease that follows primary infection can produce lower zone infiltrates, hilar or mediastinal lymph node enlargement or pleural effusions. More varied and less specific features can be seen in up to a third of cases, particularly the elderly and immunosuppressed. This can include those of primary disease, a miliary pattern, solitary or multiple nodules or even ‘normal’ chest films. Remember, TB is the ‘great mimicker’.

The radiological changes seen so far are highly suspicious of pulmonary tuberculosis and a CT scan is unlikely to provide any more definitive information. The CT scan is more sensitive than the standard chest X-ray in the examination of the lung parenchyma, mediastinum and pleura. It may be useful in those patients with less obvious or atypical features, or suspicion of other diagnoses such as cancer.

A.3 An urgent sputum sample is required to screen for acid-fast bacilli (AFBs). Collection of the specimen should be in a well-ventilated area, and the patient placed in isolation. A further two morning specimens on consecutive days must also be requested. One specimen alone will fail to detect about 20% of smear-positive cases and about 50% of culture-positive cases. For the patient unable to produce sputum, inhalation of nebulized hypertonic saline should be undertaken. Otherwise bronchoscopy and lavage has a good yield and would also be indicated in the sputum smear-negative case with these symptoms and chest X-ray findings.

An elevated ESR, normocytic anaemia and depressed sodium are non-specific findings which may be present.

The tuberculin skin test or interferon gamma release assay (IGRA) are rarely indicated. These tests cannot distinguish latent TB infection from active disease and false-negative results occur in as many as 20% of active cases. Similarly, false-positive results are an issue for those from high-prevalence regions as high rates of reactivity in these populations can be expected.

Nucleic acid amplification tests (NAAT) have been recently developed, making it possible to detect Mycobacterium tuberculosis complex from a smear positive specimen and a proportion of smear negative specimens in 24 hours. Due to the urgent treatment and public health implications, nucleic acid amplification could be requested if your clinical suspicion of TB is high but other results are less certain. NAAT are not alternative to conventional methods, as culture is essential for drug-resistance testing. Some NAAT systems are able to detect rifampicin resistance simultaneously which is a marker of multidrug-resistant TB and etc. may be useful in overseas born patients from high burden TB settings.

A.4 TB is the likely diagnosis, requiring the following measures:

• Isolation, in a room with negative pressure ventilation if available, and treatment.
• Strict infection control measures need to be followed. Those with smear-positive cavitary disease who cough frequently as in this case represent the most infectious cases.
• Sputum culture will provide a definitive answer and importantly allow for drug susceptibility testing.
• Urine should be tested for AFBs as a positive urine culture is not an uncommon finding in pulmonary TB cases.
• Screening for HIV infection is important, given the history of residence in an endemic area. HIV associated TB continues to have a substantial impact on TB control in many high burden countries.
• The possibility of undiagnosed diabetes also should not be overlooked. Checking for evidence of impaired renal or hepatic function and a baseline ophthalmology review are important with respect to treatment choices.

A.5 Standard drug treatment for drug susceptible TB is a 4 drug combination of isoniazid, rifampicin, pyrazinamide and ethambutol for an initial 2 months followed by isoniazid and rifampicin for a further 4 months (the initial 4 drug combination also covers for possible isoniazid resistance, the most likely in a TB endemic area). Pyridoxine is often recommended as a supplement to isoniazid to prevent peripheral neuropathy especially in pregnant women or those with diabetes, renal disease, HIV infection or nutritional deficiency.

Important treatment principles need to be followed to prevent disease relapse and acquired drug resistance:

• Always use combination treatment to which the organism is fully susceptible.
• Treatment adherence is essential and direct observation (directly observed therapy – DOT) should be considered in all patients especially in the initial 2-month intensive phase.
• Never add one drug alone to a failing regimen.
• Duration needs to be for a minimum of 6 months (dependent on drug susceptibility, tolerance and extent/site of disease).
• Correct application of these rules results in a failure rate of less than 2–5%.
• Adverse drug reactions are relatively frequent but severe forms uncommon (Table 32.1).
• Discharge of this patient can occur when there is evidence of good clinical improvement, cough reduction or absence, the quantity of AFBs on smear microscopy is substantially reduced and treatment is assured. Regular follow-up is required to monitor disease response, check for side-effects and assess compliance.

Table 32.1 Important side-effects and drug interactions

Drug Side-Effect Interaction
Isoniazid Peripheral neuropathy, hepatitis, rash Anticonvulsants (increased level)
Rifampicin Hepatitis, rash, flu-like syndrome, thrombocytopenia Warfarin, oral contraceptives, oral hypoglycaemics, anticonvulsants (reduced level)
Pyrazinamide Hepatitis, rash, arthralgia, gout  
Ethambutol* Optic neuritis  

* Use three times weekly or avoid in those with renal impairment or avoid in those with renal impairment.

A.6 Prompt notification to the relevant public health authority is required for surveillance purposes and to facilitate contact investigation. The infectious risk of this person is potentially high, based on her clinical presentation (persistent cough and cavity on chest X-ray) and positive sputum smear result. It is important to promptly identify close contacts, particularly children less than 5 years old and the immunosuppressed; the risk of progression to disease if infected is greatest in these latter groups.

Contact tracing for notifiable diseases should be performed by a specialized service as there is a delicate balance between preservation of patient confidentiality and protecting public health.

A.7 You suspect that this woman became infected during her 2-year stay in Africa. The doctor correctly assumed the tuberculin result reflected TB exposure (no evidence of disease) and advised isoniazid ‘preventive’ treatment. Isoniazid for 6 months (minimum) is generally recommended, but 9 months is optimal and preferred for children and the HIV-infected. If resistance to isoniazid is strongly suspected or known then rifampicin alone for 4 months is the recommended option. Failure to prevent disease may have reflected poor compliance or an isoniazid-resistant strain.

This case also highlights the need to ‘think TB’ particularly in individuals from high-prevalence populations or with a history of close TB contact.

Revision Points

Pulmonary Tuberculosis

Causative Organism

• Mycobacterium tuberculosis Complex.

Mode of Transmission

• Inhalation of airborne droplet nuclei.

Incidence

• Uncommon in industrialized countries: rates >5–10 : 100 000.
• 90% of cases occur in resource-poor countries: rates >50–100 : 100 000.

Risk Groups

• People from endemic areas.
• Recent close contacts of infectious cases.
• The socially disadvantaged.
• The elderly, particularly those with medical co-morbidities or who are on immunosuppressants.
• HIV co-infected patients.

Pathology

• Primary TB infection is usually asymptomatic.
• Risk of progression is about 5% within the first 2 years; average lifetime disease risk of 10–15% dependent on age and immune status.
• If HIV co-infected the risk of developing active TB is 10% per year.
• Most disease in low endemic countries is pulmonary from reactivation of latent infection (post primary or secondary).
• Extrapulmonary disease occurs in 15–20% but is more frequent with increasing immune suppression. The more common sites include lymph nodes, pleura, bone and kidney.
• The classic histological feature is necrotizing epithelioid granuloma.

Immunopathology

• Immune responses in TB are complex and mediated mainly by T cells. They cause either a necrotic hypersensitivity or immune protective reaction but the factors responsible for these responses are not well understood.

Clinical

• Classic presentation of pulmonary disease is not always the case. Atypical presentations are frequent in the elderly and immunosuppressed, and TB should always be in the back of the mind as a differential diagnosis.

Diagnosis

• Chest X-ray abnormalities can be consistent with active pulmonary TB but are not diagnostic. Atypical features will be present in up to 30% of cases and CT scan may assist.
• The tuberculin skin test or IGRA blood test cannot distinguish active TB from latent infection.
• Sputum smear microscopy is rapid but insensitive for detection of AFBs, i.e. may miss cases, but should be positive in 40–60% of pulmonary cases.
• Culture remains the gold standard but confirmation takes 7–21 days in smear-positive specimens and 3–6 weeks in smear-negative specimens. Drug susceptibility testing (DST) requires a further 10–15 days.

Treatment

• Multi-drug treatment is essential to cover resistance, and directly observed therapy strongly recommended at least in the initial 2 month phase.

Public Health

• Notification is usually a legislative requirement and allows for contact investigation.

Prevention

• Treatment of those recently infected/exposed (no active disease) is up to 90% effective.
• Patients who become immunosuppressed and who also have a clear history of prior exposure to TB should be considered for anti-TB medication as a secondary preventive measure.
• BCG vaccination in the uninfected has protective benefit in neonates and young children but its value to adults remains unclear. It is considered in TST- or IGRA-negative health workers who are at high risk of exposure to MDRTB cases. This is because of the unproven benefit of preventive therapy if infected with an MDR strain.

Issues to Consider

• What would you do if a patient with infectious TB refused treatment?
• What is the role of screening programmes in the detection of tuberculosis?
• Why has TB not been eliminated in high income countries and why should we remain vigilant?

Further Information

, www.nlm.nih.gov/medlineplus/tuberculosis.html. A National Library of Medicine website. Comprehensive coverage of tuberculosis with links to a wide variety of sites dealing with many aspects of this disease

, www.who.int/gtb. A superb web resource from the World Health Organization dealing with the global fight against tuberculosis infection

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