COVID-19 has aroused our interest in infectious diseases and medicine in general. However, it is undeniable that it has usurped most of the attention medicine has had for other illnesses. I've spoken to many people and it is quite surprising to hear that none has actually considered the possibility that some diseases have been pandemics for years. Some diseases have dominated the globe and continued their role in ravishing victims of the working class. Impoverished nations face these diseases day in and day out - their ubiquity reaches an extent of nonchalance. I'm referring to the likes of tuberculosis (TB) (caused by Mycobacterium tuberculosis, a bacterium) and HIV. In these cases, patient honesty is crucial. Without the disclosure of relevant facts, it is very difficult for clinicians to come to a correct diagnosis and subsequent decisions regarding management and follow-up. I speak this from personal experience and also observations of published case studies. I wholeheartedly urge patients to please try not to avoid questions in history-taking, regardless of how sensitive they are. Concerns can be expressed regarding the sensitivity of the question prior to answering. Clinicians, at the same time, can also explain to the patient why the question is necessary to making a diagnosis. A key feature of this process is a firm and reliable doctor-patient relationship. If both parties trust each other, communication can be made smoother and medical errors can be accordingly reduced.
Chest X-Ray of patient with post-primary tuberculosis (Extracted from Wikipedia) (post-primary meaning that it is a re-infection or reactivation of an older infection, determined by the predilection of the disease to the lung apices). On the scan, we can see bilateral lung apical opacities. Small nodular opacities can also be seen medially on the right (almost everything is flipped in radiology), overlapping with the vessels which branch from the hilum. On the left, additional opacities extend from the lateral aspect of the third rib to the medial aspect of the fifth rib. Accordingly, air bronchograms are present at the left lung apex. A cavitation (measured ____ x _____) can be seen on the left apical opacity. The right hemidiaphragm is also significantly higher than its left counterpart, where it cannot be adequately explained by nature, i.e. the liver on the right pushes the hemidiaphragm upwards. This might be due to more extensive disease and fibrotic changes (underlying the tissue opacification) on the right, leading to reduced lung volume. I would also check the costophrenic angles (unavailable on this scan) for signs of pleural effusion.
TB is branded 'The Great Masquerader' [1], owing to the fact that it has the potential to infect multiple systems. This is particularly true in 'endemic' countries - one of the high-burden TB states defined by the WHO*. TB that affects the lungs is called 'pulmonary' TB whereas the form that afflicts other systems, 'extrapulmonary' TB. The prevalence of the latter is marked especially in developing nations. A Korean study finds that its prevalence in the locality stands at roughly 20% of all TB cases, with most cases involving the pleura, then the lymph nodes. [2] A review showed that the percentage of extrapulmonary TB cases has risen in multiple localities. [3] A Spanish Study shows that cases increased from 30.6% of cases in 1991–1996 to 37.6% in 2003–2008 (lymphatic sites increased by 27%) [4]
The major risk factors for TB can usually be divided into two types: (a) the transmission of the disease, where the recipient is first exposed to the microbe, and (b) factors pertinent to the host. These can be immune-related or mechanic-related. [5] Immunodeficiency, such as HIV, can weaken the patient's ability to fend off the bacterium. Mechanic-related factors concern pulmonary TB only. They include cystic fibrosis and Kartagener Syndrome, where microbes cannot be easily removed from the respiratory tract. Cystic fibrosis involves sticky mucus, while Kartagener Syndrome entails dysfunction in cilia movement. [6, 7] Most of these factors are not controversial. With regard to host factors, we can simply check the patient's medical records. It is also unlikely that, apart from HIV due to stigmatisation (although it's lessened in recent decades), the patient will oppose to any scrutiny towards so. Things get trickier when we deal with transmission factors, where immigration and travel history are fundamental. Some patients may want to hide their immigration history owing to their ambiguous immigration status. They may also want to avoid discrimination that accompanies disclosure. As medical professionals, it is very difficult to juggle the two effectively. On one hand, this piece of information is vital - any non-disclosure is sure to make the clinician drop TB off the list at an early stage unless there is any overt detail flagged during history-taking, especially in countries such as the UK where the prevalence is low. However, we also need to respect patient's privacy. Prising information in an intrusive manner may come across as rude, or even callous.
The importance of knowing a patient's immigration and travel history cannot be understated. A patient who has latent TB (post-exposure; lying dormant in the body, waiting for reactivation) is more likely to experience reactivation in 1-2 years after settling in the host country. Studies have shown that 5-72% of incoming immigrants have latent TB, contracted in their home countries. [8] The risk of contracting TB is also 12 times higher in low-income countries than high-income countries. [9] Travelling usually entails very low-risk of latent TB transmission - at approximately <1% travel year for most settings. [10] A review has appraised the risks of TB transmission in air-travel and outdoor settings. It states that transmission in these two contexts is very low, where outdoor transmission is comparable to the transmission rate of the general populations in host countries. [11] However, this is likely subjected to bias since not many patients can attribute their condition directly to air-travel or a particular setting during their travels. Travel transmission also depends on two crucial factors: (a) location, i.e. whether the country travelled is a high-burden TB country defined by the WHO, and (b) duration. It goes without saying that the longer the patient stays in a foreign country, especially a high-burden TB country, the greater the risk of transmission due to longer period of contact with the locals.
I've recently written a case report illustrating the phenomenon (I might publish it here later). The patient actively concealed the fact that he immigrated from Thailand twenty years ago and frequently travelled to the country, i.e. roughly 2-3 times a year. It was misdiagnosed as atypical pneumonia (since TB was never even contemplated as a possible differential diagnosis) and treated as such, until the patient developed seizures. A CT Scan was performed and to everyone's amazement, the patient had multiple space-occupying lesions that could be traced back to TB. It was then that the patient was put on Anti-TB medication. There must be a reason why the patient did not disclose such information. However, the root of the issue was the lack of proper communication. A deficit in the doctor-patient relationship could also be observed. The clinician should inspire more confidence in the patient to be able to obtain such key information in aid of making a correct diagnosis, thus initiating appropriate treatment regimens.
CT Scan: Tuberculoma (space-occupying lesion originating from TB) over the right frontal lobe, with hydrocephalus (extracted from Radiopaedia.org)
I've seen another case, this time at a TB Clinic in Hong Kong (I was on overseas attachment). Again, the patient's details are all obscured since consent cannot be obtained. I'll also adhere strictly to clinical facts to render the patient, as far as possible, unidentifiable. The patient, a middle-aged woman born and bred in Hong Kong, presented with a large, singular cervical (lower lateral neck) mass measured at roughly 10 cm x 12 cm. Its contours were regular. There were no overlying skin changes. It wasn't fixed to the underlying tissue. It was firm and not painful (non-tender). No other masses could be seen in the region. It wasn't translucent. Neck masses are always tricky. There are many possibilities but the list of differential diagnoses can be narrowed down if one is careful enough. In this case, judging by the history we've obtained from the patient, we thought it's more of a lymph node issue. The patient also presented with non-specific, constitutional symptoms, such as night sweats, low-grade fever, anorexia and malaise. All symptoms arose approximately a month ago. The patient, remarkably, presented with no respiratory symptoms, such as coughing and shortness of breath.
The routine tests were performed - blood tests and imaging. Ultrasound was done to guide needle aspiration - it is a technique whereby a needle is inserted into the mass. A sample is obtained and we can examine the cells within, which aids diagnosis-making immensely. The sample can also be used for multiple tests if required. At that stage, we're more worried about lymphoma and reactive lymphadenopathy (disease of the lymph node). Shortly after performing needle aspiration, we checked on the patient again to see if she was fine. At that point, the patient asked cautiously, 'What do you think it is?' I simply responded with, 'We're still waiting for the test results to come back. Until then, we don't want to worry you too much.' 'Well, there's this one thing I'm not sure if I should tell you...' And then the truth was out. It turned out that the patient had a home in Mainland China, which is one of the 30 high-burden TB countries on the WHO list. [12] She's got family living there and frequently visited. Owing to the geographical proximity between Hong Kong and Mainland China, she was able to stay in the latter for up to 4 months at a time. In addition to this, her house was situated in the outskirts of the city, close to the country's most famous rice paddies. Both the location and duration of the study were sufficiently alarming for us to undergo TB testing. When asked why the patient did not disclose this information at first, it was sobering- due to the long-standing political conflicts between Hong Kong and Mainland China, she was worried that she might be prejudiced in the clinical setting and branded a 'Mainlander' if she disclosed her travel and residence history.
Since the patient was born in Hong Kong, she would have received mandatory BCG vaccination upon birth. [13] However, patients can also contract TB after BCG vaccination, where the risk of contraction is only reduced by 50%. [14] Further tests were performed on the aspirate and the patient. A Chest X-Ray was also ordered. Surprisingly, it was normal. A test called PCR (Polymerase Chain Reaction) was done for quick testing of TB. It turned positive. Cytology was returned. It also showed findings typical of TB (presence of caseating necrosis and Langerhan giant cells). The patient was immediately put on anti-TB therapy and her condition dramatically improved. [15]
TB Lymphadenitis** - extracted from Wikipedia, not the real patient.
TB can manifest in a multiplicity of ways. There is no end to its many forms. There is a trove of case reports out there reporting the various, curiosity-invoking ways this 'Great Masquerader' adopts. Clinicians should be more wary to possibilities and courageous to ask patients facts material to clinical decision-making. Sometimes, there are reasons why patients do not disclose certain things. In such cases, communication skills are indispensable. A strong doctor-patient relationship is vital. We should be more compassionate to patients' needs and listen to their concerns, before we explain to them the significance of knowing the facts in question. This way, there is a higher chance of making a correct diagnosis. Patients are also benefited by the administration of appropriate treatment.
*The 30 high-burden TB countries altogether account for 87% of all new TB cases globally. India is the nation with the most new cases. Moreover, there is high correlation between TB and HIV since poverty and poor hygiene are risk factors for both conditions. For more details, refer to the website: https://www.who.int/news-room/fact-sheets/detail/tuberculosis.
**I think it's also better to clarify the two medical terms - lymphadenitis and lymphangitis. They refer to completely different things, although both involve inflammation. Lymphadenitis involves the lymph nodes, whereas lymphangitis, lymphatic ducts.
[1] Wolk B, Cao K. (2017) Tuberculosis - The Great Masquerader. American Journal of Respiratory Critical Care Medicine. 195:A5998.
[2] Lee J. (2015). Diagnosis and Treatment of Extrapulmonary Tuberculosis. Tuberculosis And Respiratory Diseases, 78(2), 47. https://doi.org/10.4046/trd.2015.78.2.47.
[3] Kulchavenya E. (2014). Extrapulmonary tuberculosis: are statistical reports accurate?. Therapeutic Advances In Infectious Disease, 2(2), 61-70. https://doi.org/10.1177/2049936114528173.
[4] García-Rodríguez J, Álvarez-Díaz H, Lorenzo-García M, Mariño-Callejo A, Fernández-Rial Á, Sesma-Sánchez P. (2011) Extrapulmonary tuberculosis: epidemiology and risk factors. Enferm Infecc Microbiol Clin29: 502–509.
[5] TB Risk Factors | Basic TB Facts. Centers for Disease Control and Prevention. (2020). Retrieved 13 November 2020, from https://www.cdc.gov/tb/topic/basics/risk.htm.
[6] Narayan D, Krishnan SN, Upender M, et al. (1994). Unusual inheritance of primary ciliary dyskinesia (Kartagener's syndrome). Journal of Medical Genetics 31:493-496.
[7] Patil N, Marco A, Montales M, Bhaskar N, Mittadodla P, & Mukasa L. (2015). Pulmonary tuberculosis in a patient with cystic fibrosis. North American Journal Of Medical Sciences, 7(5), 233. https://doi.org/10.4103/1947-2714.157494.
[8] Pareek M, Greenaway C, Noori T. et al. (2016). The impact of migration on tuberculosis epidemiology and control in high-income countries: a review. BMC Med14, 48. https://doi.org/10.1186/s12916-016-0595-5.
[9] Guthrie J, Ronald L, Cook V, Johnston J, & Gardy J. (2019). The problem with defining foreign birth as a risk factor in tuberculosis epidemiology studies. PLOS ONE, 14(4), e0216271. https://doi.org/10.1371/journal.pone.0216271.
[10] Denholm J, & Thevarajan I. (2016). Tuberculosis and the traveller: evaluating and reducing risk through travel consultation. Journal Of Travel Medicine, 23(3). https://doi.org/10.1093/jtm/taw008.
[11] Rieder H. (2001). Risk of Travel‐Associated Tuberculosis. Clinical Infectious Diseases, 33(8), 1393-1396. https://doi.org/10.1086/323127.
[12] Tuberculosis China. WHO. (2020). Retrieved 14 November 2020, from https://www.who.int/china/health-topics/tuberculosis#:~:text=Over%20the%20last%2030%20years,remains%20a%20public%20health%20concern.
[13] Lee S. (2008). The 60-year battle against tuberculosis in Hong Kong-a review of the past and a projection into the 21st century. Respirology, 13, S49-S55. https://doi.org/10.1111/j.1440-1843.2008.01334.x.
[14] Colditz G. (1994). Efficacy of BCG Vaccine in the Prevention of Tuberculosis. JAMA, 271(9), 698. https://doi.org/10.1001/jama.1994.03510330076038.
[15] Sellar R, Corbett E, D'Sa S, Linch D, & Ardeshna K. (2010). Treatment for lymph node tuberculosis. BMJ, 340(mar10 3), c63-c63. https://doi.org/10.1136/bmj.c63.
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