Mycobacterium tuberculosis (MTB) infection is the ninth leading cause of death worldwide, with many individuals with undiagnosed active or latent disease. The presence of parenchymal lung disease, such as interstitial lung disease (ILD), has been suggested to increase the risk of pulmonary tuberculosis (TB). In the clinical setting of ILD, the diagnosis of an underlying MTB infection may be challenging due to the interstitial process and underlying fibrosis, which may mask the infection. An atypical presentation and misleading radiological patterns may delay the diagnosis of the underlying MTB infection. Herein, we describe a unique case of ILD complicated by active MTB infection in an 84-year-old male, which presented as a diagnostic and clinical challenge. Eventually, due to hypoxia and respiratory failure, the patient expired

Cheema, Muhammad Azaz I.

Iftikhar, Asma

Sahni, Sonu

Wong, Christian

English

The Touro College and University System

Touro Scholar Touro College of Osteopathic Medicine (New York) Publications and Research Touro College of Osteopathic Medicine (New York) 2018 Mycobacterium tuberculosis Infection in the Setting of Interstitial Lung Disease: Coincidence or Bad Luck? Christian Wong Touro College of Osteopathic Medicine Sonu Sahni Touro College of Osteopathic Medicine (New York), sonu.sahni@touro.edu Muhammad Azaz I. Cheema Asma Iftikhar Follow this and additional works at: https://touroscholar.touro.edu/tcomny_pubs  Part of the Infectious Disease Commons, Internal Medicine Commons, and the Pulmonology Commons Recommended Citation Wong, C., Sahni, S., Cheema, M. A. I., & Iftikhar, A. (2018). Mycobacterium tuberculosis infection in the setting of interstitial lung disease: Coincidence or bad luck? Cureus, 10(10) doi:10.7759/cureus.3391 This Article is brought to you for free and open access by the Touro College of Osteopathic Medicine (New York) at Touro Scholar. It has been accepted for inclusion in Touro College of Osteopathic Medicine (New York) Publications and Research by an authorized administrator of Touro Scholar. For more information, please contact Timothy J Valente timothy.valente@touro.edu. Received 09/04/2018 Review began  09/24/2018 Review ended  09/26/2018 Published 10/01/2018© Copyright 2018Wong et al. This is an open accessarticle distributed under the terms ofthe Creative Commons AttributionLicense CC-BY 3.0., which permitsunrestricted use, distribution, andreproduction in any medium,provided the original author andsource are credited.Mycobacterium tuberculosis Infection inthe Setting of Interstitial Lung Disease:Coincidence or Bad Luck?Christian Wong  , Sonu Sahni  , Muhammad Azaz I. Cheema  , Asma Iftikhar 1. Department of Primary Care, Touro College of Osteopathic Medicine, New York, USA 2. Department ofInternal Medicine, Brookdale University Hospital Medical Center, New York, USA 3. Department ofPulmonary and Critical Care Medicine, New York Presbyterian Hospital Queens, Roslyn, USA 4.Department of Pulmonary and Critical Care Medicine, New York Presbyterian Hospital Queens, NewYork, USA Corresponding author: Sonu Sahni, sonu.sahni@touro.edu Disclosures can be found in Additional Information at the end of the articleAbstractMycobacterium tuberculosis (MTB) infection is the ninth leading cause of death worldwide,with many individuals with undiagnosed active or latent disease. The presence of parenchymallung disease, such as interstitial lung disease (ILD), has been suggested to increase the risk ofpulmonary tuberculosis (TB). In the clinical setting of ILD, the diagnosis of an underlying MTBinfection may be challenging due to the interstitial process and underlying fibrosis, which maymask the infection. An atypical presentation and misleading radiological patterns may delay thediagnosis of the underlying MTB infection. Herein, we describe a unique case of ILDcomplicated by active MTB infection in an 84-year-old male, which presented as a diagnosticand clinical challenge. Eventually, due to hypoxia and respiratory failure, the patient expired.Categories: Internal Medicine, Infectious Disease, PulmonologyKeywords: interstitial lung disease, mycobacterium, tuberculosis, infectious disease, pulmonarydiseases, radiologyIntroductionMycobacterium tuberculosis (MTB) infection is the ninth leading cause of death worldwide andthe leading cause from a single infectious agent, ranking above human immunodeficiency virusinfection/acquired immune deficiency syndrome (HIV/AIDS) [1]. With approximately one-thirdof the world’s population having been exposed to MTB, there exist many individuals withundiagnosed active or latent disease [1]. Susceptibility to infection may be due to a compromiseof the immune system, the use of immune-modulating drugs, or an underlying disease such asbronchogenic cancer [2]. It has also been described in the literature that the presence ofparenchymal lung disease, such as idiopathic pulmonary fibrosis (IPF), a type of interstitiallung disease (ILD), increases the risk of pulmonary tuberculosis (TB) [3].ILD is an umbrella term for a group of disorders that present with a similar constellation ofsigns and symptoms, including progressively worsening dyspnea on exertion, dry cough, andbibasilar inspiratory crackles on auscultation. Aside from IPF, other causes of ILD includeoccupational work exposures, fungal etiology, or atypical bacterial pneumonia. In the clinicalsetting of ILD, the diagnosis of an underlying MTB infection may be challenging due to theinterstitial process and underlying fibrosis, which may mask the infection. Herein, we describea unique case of ILD complicated by an active MTB infection in an 84-year-old male, which1 2 3 4 Open Access CaseReport  DOI: 10.7759/cureus.3391How to cite this articleWong C, Sahni S, Cheema M I, et al. (October 01, 2018) Mycobacterium tuberculosis Infection in theSetting of Interstitial Lung Disease: Coincidence or Bad Luck?. Cureus 10(10): e3391. DOI10.7759/cureus.3391presented as a diagnostic and clinical challenge.Case PresentationAn 84-year-old, Ecuadorian, non-smoker, Spanish-speaking male with a past medical history ofdementia, hypertension, and hyperparathyroidism presented with cough productive ofpurulent sputum associated with persistent shortness of breath and non-exertional retrosternalchest pain for the past five days. The patient denied any fever, chills, or night sweats. Uponfurther questioning, the patient revealed that he was an ex-farm worker who worked in sugarcane fields where he was exposed to smoke daily for approximately 30-35 years. As per a familymember, there has been no recent weight loss or hemoptysis noted. Prior to presentation, thepatient was evaluated by his primary care physician and was prescribed a course ofazithromycin without relief of his symptoms. Chest radiography revealed possible left lowerlobe pneumonia and the patient was referred for admission to the hospital for theadministration of intravenous antibiotics.On presentation at the hospital, initial vital signs were a blood pressure of 141/79 mmHg, aheart rate of 112 beats per minute, an oxygen saturation of 96% on room air, a respiratory rateof 14 breaths per minute, and a temperature of 37.6 degrees Celsius. On physical examination,the patient seemed to be fatigued with the presence of bibasilar rhonchi on auscultation. Therest of the physical exam was unremarkable. Initial lab results are shown in Table 1.2018 Wong et al. Cureus 10(10): e3391. DOI 10.7759/cureus.3391 2 of 8Investigation Results (normal values)Total Bilirubin 2 (0.0-1.2mg/dl)Direct Bilirubin 1.8 (0.0-0.3mg/dl)Alkaline Phosphatase 230 (40-130U/L)Albumin 2.2 (3.5-5.2 g/dl)Aspartate Amino Transferase/Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT) 25 (5-41U/L)Alanine Aminotransferase/ Serum Glutamate-Pyruvate Transaminase (ALT/SGPT) 17 (5-40U/L)Sodium Level 141 (136-145mmol/l)Potassium Level 4.5 (3.5-5.1mmol/l)Carbon Dioxide Level 19 (22-29mmol/l)Chloride Level 106 (98-107mmol/l)Blood Urea Nitrogen 42 (8-23mg/dl)Creatinine 1.1 (0.70-1.20mg/dl)Calcium Level 10.1 (8.6-10.4mg/dl)Random Glucose 127 (74-99mg/dl)Total Creatine Kinase 14 (20-200U/L)Troponin I <0.017 (0.010-0.030ng/ml)White Blood Count 24.5 (4.80-10.80K/uL)Hematocrit 34.1 (40-50%)Hemoglobin 10.5 (13.3-17.7g/dl)Platelet Count 74 (150-400K/uL)Mean Corpuscular Volume 92.4 (80-100fl)Prothrombin Time International Ratio 1.17 (0.87-1.13)Activated Partial Thromboplastin time 26.6 (25-35 second)Prothrombin Time 13.4 (10-13 second)TABLE 1: Laboratory resultsThe patient was admitted and intravenous ceftriaxone and azithromycin were initiated, with aworking diagnosis of community-acquired pneumonia. Approximately 36 hours intohospitalization, the patient became dyspneic and acutely hypoxic with oxygen saturationdropping to 80% on room air and the patient was started on high flow oxygen via nasal cannula2018 Wong et al. Cureus 10(10): e3391. DOI 10.7759/cureus.3391 3 of 8(HFNC). A repeat chest x-ray showed multi-lobular pneumonia (Figure 1). Subsequentcomputed tomography (CT) of the chest showed diffuse bilateral scattered patchy and nodularopacities, with underlying scarring and fibrosis consistent with interstitial lung disease (Figure2), according to radio-clinical criteria.FIGURE 1: Chest radiography showing increased reticularmarkings and areas of consolidation suggestive of multilobularpneumonia2018 Wong et al. Cureus 10(10): e3391. DOI 10.7759/cureus.3391 4 of 8FIGURE 2: Computed tomography of the chest showing diffusebilateral scattered patchy and nodular opacities throughout thelungs, possibly representative of multifocal pneumoniathroughout the lungsArrows point to consolidation with a pneumonia-like patternDespite high flow oxygen, the patient’s condition continued to decline, becoming morehypoxic. HFNC was changed to bi-level positive airway pressure, as the patient remainedhypoxic on HFNC. Additional testing, such as respiratory viral panel, mycoplasma,streptococcus pneumonia, and HIV were all negative. Gram staining of the sputum culture wasalso found to be negative. Bronchoscopy was declined by family members due to the invasivenature of the procedure. Eventually, the sputum culture for acid-fast bacilli (AFB) returned tobe positive. The patient was expectantly started on rifampin, isoniazid, pyrazinamide, andethambutol (RIPE) therapy.Despite targeted therapy, the patient further deteriorated, requiring intubation and wastransferred to the intensive care unit due to hypoxic respiratory failure. The patient was startedand maintained on RIPE therapy due to the AFB positive sputum culture. The patient continuedto remain hypoxic despite the RIPE therapy and expired six weeks after admission. It wasthought that the combination of interstitial process combined with the overlappingmycobacterial infection caused the demise of this patient.DiscussionWe highlight a case of an 84-year-old male with underlying interstitial lung disease, which wasfurther complicated by an active MTB infection. The diagnosis and management of activetuberculosis infections in patients with an underlying interstitial process may provechallenging, which demonstrates the uniqueness of this case. Very limited data are available2018 Wong et al. Cureus 10(10): e3391. DOI 10.7759/cureus.3391 5 of 8exploring the relationship of MTB in ILD patients. In a study by Chung MJ et al., 143consecutive patients with IPF were analyzed and it was found that the incidence of tuberculosisin patients with IPF was more than five times higher than that of the general population [3]. Inaddition, the most common CT findings in the study were subpleural nodules, lobar andsegmental consolidations that are atypical manifestations for MTB, as they mimic lung canceror bacterial pneumonia [3]. In our case, CT was described as diffuse, bilateral, scattered, patchy,and nodular opacities with confluence in the left apex measuring approximately 3.7 cm,possibly representing multifocal pneumonia. Due to such a pattern on radiologicalexams, wide-spectrum antimicrobial therapy was warranted. Further complicating our case wasthe absence of the typical presentation of an active MTB infection.In an earlier study examining the relationship of chronic ILD and tuberculosis, Shachor et al.retrospectively reviewed 162 cases from 1970 to 1984 and found that 5%-6.2 % patients withchronic ILD have a positive culture for MTB, which was found to be approximately 4.5 times theincidence in the general population [4]. This indicates that the MTB incidence is higher in theILD patients. From the literature, it seems apparent that the incidence of MTB in the ILDpopulation is more than what is normally seen in the general population. However, not muchdata is available for other mycobacterial infections, which may also demonstrate a deleteriouseffect in the setting of ILD. In a 2012 study by Park et al. of 795 IPF patients, pulmonaryinfections with Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterium (NTM)were found in 35 (4.4%) and 16 patients (2.0%), respectively, which was higher than the generalpopulation. In addition, as expected, TB was more common in patients who were treated withimmunosuppressants and among the 51 IPF patients who had mycobacterial infections,nine (18%) died during follow-up, three due to the progression of pulmonary tuberculosis [5].Our patient proved to be a clinical challenge due to radiological findings that were consistentwith changes seen in pneumonia. However, with a history of being an Ecuadorian farm workerwho presented with pleuritic chest pain, hypoxia, and shortness of breath, ILD secondary tooccupational hazards was also part of the differential. Appropriate measures were taken inorder to treat the ILD without any improvement in the clinical picture. During the rapiddeterioration of our patient, the eventual culture of the sputum was found to be positive forMTB. Despite the initiation of RIPE therapy alongside treatment measures for the ILD, thepatient expired. The decision to culture the sputum was a fortuitous one, as the patient did notpresent with the traditional features of tuberculosis such as a cough, fever, chills, night sweats,weight loss, or hemoptysis. In fact, it has been observed that up to a third of MTB patientspresent with atypical symptoms (lack of greater than weeks of cough or fever) [6]. A furtherexacerbation of the situation could be attributed to the fact that older patients (>65 yearsold), as well as those who do not present without respiratory symptoms, are misdiagnosed morefrequently, delaying the correct diagnosis of pulmonary tuberculosis [7]. The progression of ILDis acknowledged to be heterogeneous, with some patients remaining stable for prolongedperiods, others showing more rapid steady progression, and still others succumbing to acuteexacerbation [8]. It is quite possible that an acute exacerbation of the ILD was the onus for thereactivation of his latent tuberculosis or vice versa. The specific interaction between ILD andtuberculosis is still unknown, however, it has been suggested that a diffusely damaged lungparenchyma increases the susceptibility to dormant tuberculosis [4]. It is generally understoodthat interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha are the main players inpreventing the reactivation of tuberculosis. However, a study in Japan showed that levels ofTNF-alpha and IFN-gamma were significantly higher in ILD patients versus non-ILD patients[9]. It is plausible that the acute and chronic exacerbations of parenchymal damage of the lungssecondary to the ILD somehow inhibit the sustainment of granulomas via a non-cytokinepathway, thus allowing the mycobacterium to reactivate and spread. This phenomenon mayhave contributed to the rapid decline of our patient and his ultimate demise.ILD with concomitant tuberculosis is a relatively rare occurrence, which may be challenging to2018 Wong et al. Cureus 10(10): e3391. DOI 10.7759/cureus.3391 6 of 8diagnose. The symptoms of the ILD can often mask an underlying pulmonary infection and canresult in a misdiagnosis of the patient. Due to the rarity of having these two illnesses at thesame time, there are no established management protocols or algorithms. Current guidelinesrecommend the initial test in all cases of suspected ILD to include a urine dipstick, fulldifferential blood cell count, serum urea, electrolytes and creatinine, and liver function tests.Other tests, such as tuberculin tests, are largely dependent upon clinical context [10]. However,a high clinical suspicion and, arguably, cases such as ours will demonstrate the importance ofruling out an MTB infection as a standard for all ILD patients, especially in the indigenouspopulation.ConclusionsHerein we presented an interesting case of ILD with concomitant tuberculosis, a rarephenomenon which may present as a clinical challenge. As evidence suggests there is anincreased presence of tuberculosis in the setting of ILD. A diagnostic approach inclusive ofruling out mycobacterium infection should be adopted. Clinicians involved in the managementof ILD should take consideration of possible concomitant infection.Additional InformationDisclosuresHuman subjects: Consent was obtained by all participants in this study. Conflicts of interest:In compliance with the ICMJE uniform disclosure form, all authors declare the following:Payment/services info: All authors have declared that no financial support was received fromany organization for the submitted work. Financial relationships: All authors have declaredthat they have no financial relationships at present or within the previous three years with anyorganizations that might have an interest in the submitted work. Other relationships: Allauthors have declared that there are no other relationships or activities that could appear tohave influenced the submitted work.References1. World Health Organization: Global Tuberculosis Report 2017. World Health Organization,Geneva; 2017.2. 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Mycobacterium tuberculosis Infection in the Setting of Interstitial Lung Disease: Coincidence or Bad Luck?

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Mycobacterium tuberculosis Infection in the Setting of Interstitial Lung Disease: Coincidence or Bad Luck?

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