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The articles published in August 2020 entitled ‘tuberculosis (TB) or not TB?’ and ‘sarcoidosis with multiorgan involvement’ under the ‘image’ section have particularly caught our attention. The unfortunate occurrence of misdiagnosis of patients with TB infection, which has transpired into different pathologies of non-identical entities, have evidently demonstrated the possibility of a heterogeneous spectrum of tuberculosis manifestation. In the practice of otolaryngology, the diagnosis of extrapulmonary TB (ETB) typically imposes challenges owing to its variable clinical presentation and arduous sampling yielding.
TB is a potentially fatal disease triggered by Mycobacterium tuberculosis. It remains as one of the leading causes of mortality, despite with worldwide use of a live attenuated vaccine and effective pharmacological regimen. According to WHO, there were approximately 10 million people afflicted with TB globally in 2019.1 M. tuberculosis primarily involves the pulmonary region. Its clinical manifestation includes chronic cough with or without haemoptysis, which often accompanied by constitutional symptoms of fever, night sweats and weight loss. On the other hand, the signs and symptoms of ETB can be subtle and non-specific.
The most typical form of ETB encountered by otolaryngologists is scrofula, better known as TB lymphadenitis.2 The disease was regarded with awe in antiquity as ‘the king’s evil’, where the royal touch was surmised to be the cure until the 18th century.3 In developed countries, the commonly affecting age group lies between the third and fifth decades.2 A vast majority of scrofula (88%) is located at the posterior triangle or supraclavicular area.4 Scrofula may present as a single unilateral swelling or multiple painless insidious neck masses, often accompanied by systemic features such as low-grade fever, weight loss and fatigue. The consistency of a rubbery, firm mass tends to mimic metastatic lymphadenopathy. Cough is not a prominent feature in defiance of a high incidence of the concomitant pulmonary lesion.5
The occurrence of TB in the middle ear is unusual, constituting 0.04% of all cases of chronic otitis media.6 The bacilli can disseminate via the performed pathway where it traverses the eustachian tube, through haematological seedlings from other TB foci or direct implantation across a perforated tympanic membrane.6 A broad spectrum of manifestations ranging from painless otorrhoea to mastoiditis with facial palsy has been demonstrated. History of TB contact, concomitant or previous pulmonary TB, intractable otitis media refractory to antibiotics treatment implicates the possibility of M. tuberculosis infection. Tell-tale clinical features include necrotic components on otoscopic examination, abundant granulation tissue, multiple perforations of the tympanic membrane with whitish exudates not readily aspirated.
TB larynx is the rarest extrapulmonary site of TB.7 Clinical presentations of TB larynx include insidious onset of dysphonia (90%), odynophagia (30%) and rarely dyspnoea.7 Under the naked eye, the appearance of a TB larynx can be described as ulcerative, polypoidal or ulcerofungative. In the early stage, the laryngeal mucosa may look oedematous and erythematous. The disease may further progress to a classically known ‘coated larynx’ appearance, in which the lesion is covered with a greyish, purulent layer.7 The lack of pathognomonic features in TB larynx tend to be deceiving and can mimic malignancy or other granulomatous diseases.
The diagnosis of ETB should be made based on at least one culture-positive specimen, or positive histology, or strong clinical evidence consistent with an active ETB.8 However, the isolation of M. tuberculosis from clinical samples is deemed difficult due to the paucibacillary nature of the disease. Fine-needle aspiration cytology is conventionally used as the first-line diagnostic technique of scrofula owing to its convenience and safety profile, although with its limitations. In countries with high prevalence of M. tuberculosis infection, the histological demonstration of epithelioid granuloma with or without caseation even in the absence of acid-fast bacilli succinctly indicates TB.9 The diagnostic yield can be further increased with a combination of a culture or Mantoux test.
Culture of tissue specimen has been regarded as the gold standard for diagnosing TB. It offers the advantage of species identification, phenotypic drug susceptibility test, as well as genotyping for molecular epidemiology studies.9 However, its sensitivity varies with the site of infection in cases of ETB. Apart from the complexity of procedure and biosafety profile, its high turnaround time remains a significant downside culminating to a delay in diagnosis.9 On the other hand, staining and microscopic smear examination are fast, cost-effective and easy to perform. Various methods, including Ziehl- Nelson stain, fluorescence stain and light-emitting iodine-based fluorescence microscopy, have been described.
In comparison to the recommended fluorescence microscopy, conventional Ziehl- Nelson stain is of limited diagnostic value in the majority of paucibacillary ETB samples.9 Mantoux test or skin test is an inexpensive method of diagnosis based on cellular immune response, although with its drawback. A positive test may imply active TB, a past infection, Bacillus Calmette-Guérin vaccination or sensitisation by environmental mycobacteria. However, immunocompromised patients may give rise to a negative result, thus resulting in false negatives. Interferon-γ release assays and nucleic acid implication test may aid to improve the diagnosis of ETB with a considerable cost.9
TB continues to beget threats to the nation’s economic growth and healthcare industries, especially in developing and endemic countries. A high index of suspicion of ETB remains pivotal to avert misdiagnosis and delay in management. Close surveillance for treatment-related complications include audiology, ophthalmological and nervous system assessment, renal and liver function test, and the evaluation of the infected site must be performed routinely to prevent a potentially disastrous consequence from the treatment. We wish to heighten the awareness of TB as a great masquerader. The approach and management should be tailored based on the location and the clinical evaluation.
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Contributors GJT was responsible in manuscript drafting, reviewing and editing. AM was responsible in manuscript reviewing and editing. FDZ was responsible in supervising, manuscript reviewing and editing. All authors read and approved the final version for submission.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.