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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 1  |  Page : 74-79

Evaluation of Transbronchial Needle Aspiration Samples from Sarcoidosis Patients for the Presence of Mycobacterium


1 Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Submission12-Dec-2020
Date of Acceptance20-Feb-2021
Date of Web Publication13-Mar-2021

Correspondence Address:
Dr. Atefeh Abedini
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_213_20

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  Abstract 


Background: Tuberculosis (TB) and sarcoidosis are two chronic, systemic, and granulomatous diseases that have similar pulmonary and extrapulmonary manifestations. Given the similarities between the two diseases, it is suggested that the Mycobacterium genome may play a role in sarcoidosis. Identification of Mycobacterium species isolated from sarcoidosis patients optimizes the treatment process of patients. The present study investigates biopsy tissue samples from patients with sarcoidosis for the presence of Mycobacterium in the tissues. Methods: This descriptive cross-sectional study was performed on all sarcoidosis patients referred to Masih Daneshvari Hospital during 2017–2018 (401 patients). All patients who were outpatients or hospitalized in the bronchoscopy ward of Masih Daneshvari Hospital underwent transbronchial needle aspiration (TBNA). The cause of the TBNA procedure in patients was the presence of bilateral hilar lymphadenopathy in patients. Out of 401 patients with sarcoidosis, five patients showed positive smear or culture for Mycobacterium and were excluded from the study. Finally, 396 patients were included in the study. Results: The majority of participants in the present study were female (56.1%) with a mean age of 48.2 years and a mean ACE index of 73.4. Hypertension was found in16.2% of patients with sarcoidosis. 16.4% of patients had hyperlipidemia and 4.3% of patients had a history of ischemic heart disease. Redness of the eyes was seen in 13.1% of patients and 12.4% of the patients had diabetes. Also, 43.4% of the patients had skin lesions. Out of a total of 396 patients with sarcoidosis in the present study, 3.5% of the lymph and lung tissues of sarcoidosis patients (who were not infected with Mycobacterium tuberculosis by clinical signs and culture) contained amplifiable MTB DNA. Conclusion: In the present study and many previous related studies, the Mycobacterium genome has been observed in lymph node samples of mediastinal nodes and lung tissue of sarcoidosis patients. One of the strengths of the present study, which can make the results very reliable, is the high sample size in this study. It is suggested that similar studies with the use of control groups in large samples, investigate the presence of the Mycobacterium genome and its type in sarcoidosis patients.

Keywords: Genome, Mycobacterium tuberculosis, sarcoidosis, transbronchial needle aspiration


How to cite this article:
Kiani A, Rouzpeykar R, Idani E, Varahram M, Kazempour-Dizaji M, Taghavi K, Abedini A. Evaluation of Transbronchial Needle Aspiration Samples from Sarcoidosis Patients for the Presence of Mycobacterium. Biomed Biotechnol Res J 2021;5:74-9

How to cite this URL:
Kiani A, Rouzpeykar R, Idani E, Varahram M, Kazempour-Dizaji M, Taghavi K, Abedini A. Evaluation of Transbronchial Needle Aspiration Samples from Sarcoidosis Patients for the Presence of Mycobacterium. Biomed Biotechnol Res J [serial online] 2021 [cited 2021 Aug 5];5:74-9. Available from: https://www.bmbtrj.org/text.asp?2021/5/1/74/311097




  Introduction Top


Tuberculosis (TB) and sarcoidosis are two chronic, systemic, and granulomatous diseases that have similar pulmonary and extrapulmonary manifestations. TB caused by Mycobacterium TB (MTB) is a worldwide disease with an epidemic of approximately one in three people worldwide and two million deaths worldwide. TB remains one of the top ten epidemics by 2020. TB is a life-threatening infectious disease that expresses a wide range of clinical diseases, mostly caused by MTB. TB can affect all parts of the body, but the most common form of the disease is pulmonary TB.[1],[2]

Sarcoidosis is a granulomatous disease that often occurs between the second and fourth decades of life. This multisystem inflammatory disease is characterized by the accumulation of noncaseating granulomas in organs and varies in incidence around the world. In various studies, the prevalence of sarcoidosis has been reported from 0.03 to 640 per 100,000, which can be due to the lack of standard criteria for diagnosis, different methods of sample collection, lack of a specific or sensitive test for diagnosis, as well as the wide range of clinical manifestations.[3] The cause of the disease is unknown, but disorders of the immune system and genetic background are effective in the pathogenesis of the disease. Early reports of sarcoidosis, cite factors in rural areas such as wood-burning materials, plant pollen, and more recent studies have suggested that contact with inorganic particles, insecticides, and fungal and moldy environments are effective stimulants of the disease.[4] Job studies have shown a positive association with seafaring, metalworking, firefighting, and construction-related occupations.[5] Using polymerase chain reaction (PCR) techniques, DNA, and RNA of Mycobacteria and Propionibacterium were obtained from sarcoid tissues.[5] The onset of sarcoidosis appears to be the end result of an immune response to environmental stimuli. This raises the possibility that sarcoidosis may be an infectious agent induced by another infectious agent [Figure 1].
Figure 1: Causes developing the sarcoidosis

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Organ involvement in this disease is often asymptomatic and resolves on its own; however, it may lead to chronic fibrosis associated with dysfunction of the organs involved.[6] Due to the common involvement of the lungs and eyes and skin in sarcoidosis, the search for environmental factors has focused on antigens in the air. Sarcoidosis can involve the lungs, skin, eyes, and less commonly, lead to extrathoracic lymphadenopathy, liver, nervous system, and heart disease. Diagnosis of sarcoidosis requires the presence of a clinical picture corresponding to sarcoidosis with the presence of pathological information and often the diagnosis is not made with 100% confidence.[7],[8] The systemic manifestations of most patients with TB and sarcoidosis are very similar. Clinically, the characteristics of TB and sarcoidosis are often confused, and many cases of TB are initially treated as sarcoidosis and many cases of sarcoidosis are initially treated as TB.

In the Agarwal study, it was stated that due to the pathophysiological and clinical similarity between TB and sarcoidosis, these two diseases are thought to be two spectrums of a single disease. In addition to the pulmonary manifestations of TB and sarcoidosis, the extrapulmonary manifestations, which also include ocular involvement, are very similar and make it difficult to distinguish between the two diseases. The study also suggested that sarcoidosis was probably a syndrome with the Mycobacterium as an etiologic factor. Past studies have also shown that there is a molecular and immunological link between TB and sarcoidosis.[7] Several genes in the RD1 locus of the MTB genome have also been identified that are responsible for encoding several specific proteins, such as ESAT-6 and CFP-10. These proteins have also been shown to be found in sarcoidosis. Another Mycobacterium-specific protein is Mycobacterium catalase-peroxidase, which is found in 55% of sarcoidosis specimens sent to the laboratory. IgG antibodies against recombinant Mycobacterium peroxidase were detected in 48% of sarcoidosis patients with PPD-negative versus controls. These studies have shown that the immune response to sarcoidosis may be due to Mycobacterium virulence agents.[7]

In many cases, it is difficult to distinguish sarcoidosis from TB. Given the similarities between the two diseases, it is suggested that the Mycobacterium genome may play a role in sarcoidosis. The Mycobacterium genome is a genome found in the body of some people while they may not have any active or latent TB. Identification of Mycobacterium species isolated from sarcoidosis patients optimizes the treatment process of patients. The present study investigates lung biopsy tissue samples from patients with sarcoidosis for the presence of Mycobacterium, as well as determining the type of Mycobacterium in the tissues. The specific purpose of this study was to investigate the relationship between Mycobacterium and sarcoidosis.


  Methods Top


This descriptive cross-sectional study was performed on all sarcoidosis patients referred to the national sarcoidosis clinic at the Masih Daneshvari University Hospital in Iran, dedicated to patients with interstitial lung disease, during 2017–2018 (401 patients). The diagnosis was made by informing and attracting the cooperation of physicians all over the country, specialists, and subspecialties in the fields of internal medicine, lung, dermatology, and ophthalmology. All patients who were outpatients or hospitalized in the bronchoscopy ward of Masih Daneshvari Hospital underwent transbronchial needle aspiration (TBNA). The cause of the TBNA procedure in patients was the presence of bilateral hilar lymphadenopathy in patients. Here, the intervention specialist used a forceps probe to collect a sample from mediastinal or bilateral lymph nodes in the lungs which gives a direct vision. Patients' information including age, sex, initial disease chart, family history, clinical characteristics, imaging findings, patient tests, and sampling results were recorded in a questionnaire.[9]

Before the procedure, lymphadenopathy was confirmed by computed tomography (CT) scan of patients. Initial diagnosis of sarcoidosis by a pulmonologist based on the presence of consistent clinical signs and sampling of nonnecrotizing granuloma after rejection of other diagnoses (in chronic cases) or clinical picture consistent with Lofgren syndrome (bilateral hilar lymphadenopathy, erythema nodosum, and arthritis of the ankles) or clinical symptoms consistent with chronic sarcoidosis was performed. Patients with fungal infections or bacterial infections other than Mycobacterium were excluded from the study. Patients were followed up for at least 6 months and were excluded from the study if they were diagnosed with another disease.

Inclusion criteria were suffering from sarcoidosis, mediastinal lymphadenopathy accessible by endobronchial ultrasound, smear and culture of sputum negative for the presence of Mycobacterium, be literate, completing the moral consent form, no medication consumed by the patient at the time of the study, confirmation of CT scan of patients before lymphadenopathy procedure, the initial diagnosis of sarcoidosis by a pulmonologist based on the presence of clinical signs.

Exclusion criteria were patients with fungal infections or bacterial infections other than Mycobacterium patients with a different diagnosis and patients who refuse to continue research.

Patients' information including age, sex, initial disease record, family history, clinical characteristics, imaging findings, tests of patients, and sampling results, if any, as well as their symptoms and response to treatment was recorded in a questionnaire [Table 1],[Table 2],[Table 3]. Then, patients' information was analyzed in SPSS software (SPSS Statistics 27.0.1.0; USA). Also, the epidemiological characteristics of patients were obtained through standard questionnaires.
Table 1: Mean age distribution and angiotensin-converting enzyme in sarcoidosis patients

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Table 2: Frequency distribution of gender variables in patients with sarcoidosis

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Table 3: Frequency distribution of Mycobacterium genome based on polymerase chain reaction test in sarcoidosis patients

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Ethical considerations

In the present study, the individual freedom of volunteers or patients was observed. In the prepared consent, honesty was observed and it was signed by individuals. Acceptance of liability for social damages was included in the consent form. All information about the subjects was kept confidential and remained.

The TBNA procedure was performed on an outpatient basis with moderate sedation with midazolam and fentanyl and local anesthesia with lidocaine. All procedures were performed by the Forceps Olympus, Japan probe. The aspirated samples were poured into a container containing formalin and sent to the pathology laboratory. The final diagnosis was made by microscopic examination of TBNA specimens by a pathologist who was unaware of the characteristics of the sampled lymph nodes (blind) within 1 h. Finally, all adequate specimens were classified into two categories: sarcoidosis and nonsarcoidosis. The second container of sarcoidosis samples was transferred to the mycobacteriology laboratory in the shortest time.

Samples isolated from patients grown on Lunstein-Johnson culture medium were transferred to Middlebrook medium. After the bacteria had fully grown on this medium, the bacteria were placed at 80°C for 20 min to be killed. Out of 401 patients with sarcoidosis, five patients showed positive smear or culture for Mycobacterium and were excluded from the study. Finally, 396 patients were included in the study. In this study, the genetic fingerprinting method based on IS 6110 was used to identify different strains of Mycobacterium. DNA extraction was performed using DNA extraction kits. To identify and differentiate mycobacteria up to the species level, a gene fragment with a length of 439 bp in the position of 836-398 from the hsp65 sequence was amplified by two specific primers by PCR, and the PCR product was analyzed by two restriction enzymes (BstEII and HaeIII). By examining the patterns obtained from PCR digestion, the studied Mycobacterium species were separated from each other [Table 3].[2]


  Results Top


Out of 401 patients with sarcoidosis, five patients showed positive smear or culture for Mycobacterium and were excluded from the study. Finally, 396 patients were included in the study. The majority of participants in the present study were female (56.1%) with a mean age of 48.2 years and a mean ACE index of 73.4 [Table 2].

Redness of the eyes was seen in 13.1% of patients and 12.4% of the patients had type 2 diabetes. Also, 43.4% of the patients had skin lesions [Graph 1].



Hypertension was found in 16.2% of patients with sarcoidosis. 16.4% of patients had hyperlipidemia and 4.3% of patients had a history of ischemic heart disease. In the present study, 3.5% of the lymph and lung tissues of sarcoidosis patients (who were not infected with MTB by clinical signs and culture) contained amplifiable MTB DNA [Graph 2].




  Discussion Top


Although sarcoidosis has been identified as a granulomatous disease for more than a century, its cause is still unknown.[10] It has been reported that patients with TB were 8.09 times more likely to develop sarcoidosis than non-TB patients, while patients with sarcoidosis were 1.85 times more likely to develop TB compared to nonsarcoidosis individuals.[11] The aim of the current study was to investigate the presence of the TB genome in patients with sarcoidosis.

In a study by Ravan et al. On TB and sarcoidosis, it was shown that a multiobjective PCR specific for IS6110, MPB64, and B protein in MTB has a sensitivity of 77.77% and a specificity of 100% for the identification of MTB.[12] In Greece, Gazouli et al. reported that 71.7% of the lymph and lung tissues of sarcoidosis patients (who were not infected with MTB by clinical signs and culture) contained amplifiable MTB DNA.[13]

Gupta et al. have conducted extensive research on the molecular and cellular aspects of TB and sarcoidosis. Their analysis in a meta-analysis study showed that 30% of sarcoid samples had Mycobacterium nucleic acids and 48% of sarcoid samples had Mycobacterium DNA.[14] Thus, many studies have shown that MTB may be a common pathophysiological mechanism for both TB and sarcoidosis.[7] Drake et al. observed Mycobacterium DNA in 60% of sarcoidosis patients. Although the DNA sequences of the patients studied were more similar to MTB, similar sequences of other Mycobacterial species were also identified. They showed that the genome of MTB in TB patients and MTB in sarcoidosis patients were different.[5]

Dubaniewicz et al. have conducted extensive studies on both humoral and cellular immune responses of sarcoid patients in response to MTB antigen. Their results showed that stimulation of HSP antigen in MTB increased the levels of inflammatory cytokines, tumor necrosis factor-alpha, and interleukin (IL)-6 in the serum of patients with sarcoidosis and TB compared with healthy individuals. In addition, patients with sarcoidosis showed the lowest levels of IL-4 and the highest levels of IL-10 compared to patients with TB and the control group.[15] The close correlation of the immune response of patients with sarcoidosis and TB allows these two diseases to be of similar etiology. The results of Drake et al.'s research also showed that mycobacterial antigens may play a role in the pathogenicity of sarcoidosis by stimulating T-cell-specific antigen responses that are important in the formation of sarcoidosis granuloma.[5]

According to Branol et al., although Mycobacterium infection has long been a source of candidate antigens for sarcoidosis, there is recent strong evidence to support a causal relationship.[10] In susceptible hosts, sensitivity to appropriate microbial antigens (Mycobacterium, bacterial propionia, or others) may be sufficient to stimulate sarcoidosis. Evidence suggests that mycobacterial antigens are responsible for initiating or maintaining granuloma in some sarcoidosis patients.

Out of a total of 396 patients with sarcoidosis in the present study, 3.5% of the lymph and lung tissues of sarcoidosis patients (who were not infected with MTB by clinical signs and culture) contained amplifiable MTB DNA.

In the study of Eishi et al., the genome of MTB was not observed in any of the Japanese patients with sarcoidosis. However, in a small number of European patients with sarcoidosis (5 out of 65 samples, i.e., 7.6%), MTB genome was seen. They suggest that in samples with the MTB genome, mycobacteria may be involved in sarcoidosis, but it is probably the propionibacteria that cause inflammation. Because the total number of propionic bacterial genomes was much higher than the genome of mycobacteria. They suggest that the small amount of Mycobacterium genome found in patients without TB is due to Calmette–Guerin bacillus vaccination or latent infection.[16],[17]

Latent TB is a condition in which a person has MTB infection but does not currently have active TB and has no clinical or radiological findings. Kiani et al. stated in a study that there is a significant number of patients with latent TB in the population with sarcoidosis.[18]

In a case report, Motswaledi et al. identified mycobacteria in oral and skin lesions of sarcoidosis patients, which was histologically diagnosed with TB. However, the patient did not respond to anti-TB treatment but later responded favorably to systemic corticosteroids without causing the signs and symptoms of TB and thus left the final diagnosis of sarcoidosis. Finally, they state that although there is no evidence, it is likely that the Mycobacterium present in the patient's oral and cutaneous sarcoid lesions was involved in the pathogenesis of the disease.[19]

In a study, Masoud et al. examined the presence of Mycobacterium genome in lymph and lung samples from three groups of patients with sarcoidosis, MTB, and control. In this study, PCR DNA samples of MTB were not seen in any of the sarcoid patients.[20] In a study, Saboor et al. examined three groups of patients with sarcoidosis, TB, and controls to evaluate the presence of Mycobacterium DNA in lung tissue by PCR. In this study, MTB DNA was observed in half of sarcoid patients and non-TB Mycobacterium DNA was observed in more than 20% of sarcoidosis patients.[21]

The majority of participants in the present study were female (56.1%) with a mean age of 48.2 years and a mean ACE index of 73.4. It was previously reported that the age of onset of sarcoidosis in Iranian patients was higher than the global age range of sarcoidosis and the ratio of women to men was 2.4 times. Also, the average level of ACE was in the normal range.[3] Hypertension was found in 16.2% of patients with sarcoidosis. 16.4% of patients had hyperlipidemia and 4.3% of patients had a history of ischemic heart disease. Redness of the eyes was seen in 13.1% of patients and 12.4% of the patients had type 2 diabetes. Also, 43.4% of the patients had skin lesions.[18] In previous study Kiani et al. showed 56.8% of sarcoidosis patients were women, with a mean age of 49.39 ± 19.59 years, and 19.9% of patients with hypertension, 3.8% had hypertension. Also, 3.6% had a history of heart attack.[11] Additionally of Kiani et al., the mean age of patients with sarcoidosis was 50.20 ± 11.07, 26.7% of patients with sarcoidosis had hypertension, 20% had diabetes, 10% had ischemic heart disease, and 100% had skin appendages.[18] In the present study, 3.5% of the lymph and lung tissues of sarcoidosis patients (who were not infected with MTB by clinical signs and culture) contained amplifiable MTB DNA.

In the present study and many previous related studies, the Mycobacterium genome has been observed in lymph node samples of mediastinal nodes and lung tissue of sarcoidosis patients.[5],[13],[14],[16],[21] Also, in a number of studies, contrary to the results of the present study, other types of mycobacteria have been observed.[5],[14],[21] These contradictory results may suggest that although the MTB genome may play a role in sarcoidosis, it is not the only cause. There seems to be a link between the presence of the MTB genome and sarcoid infection. However, proving this and determining exactly how it relates requires further research. The study of the presence of the Mycobacterium genome in different countries will help to complete the results of these studies. The results of the present study indicate the potential role of mycobacterial infection in the pathogenesis of sarcoidosis. One of the strengths of the present study, which can make the results very reliable, is the high sample size in this study and also the evaluation of sarcoidosis patients in terms of not having TB or not being a carrier of Mycobacterium to enter the study. However, this study also had some limitations, including the fact that it was not possible to use control groups due to the extensive work. It is suggested that similar studies with other research methods, including the use of control groups in large samples, investigate the presence of the Mycobacterium genome and its type in sarcoidosis patients. It is also recommended that previous studies that have successfully detected Mycobacterium DNA by PCR be re-evaluated using quantitative PCR.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ramazanzadeh R, Shakib P, Rouhi S, Mohammadi B, Mohajeri P, Borji S. Molecular epidemiology of Mycobacterium tuberculosis isolates in Iran using spoligotyping. New Microbes New Infect 2020;38:100767.  Back to cited text no. 1
    
2.
Derakhshani Nezhad Z, Farnia P, Sheikholslami FM, Afraei Karahrudie M, Mozafari M, Seif S, et al. Prevalence of non-tuberculosis mycobacteria in patients referring to mycobacteriology research center of iran. Scientific Journal of Kurdistan University of Medical Sciences 2014;19.31-9.  Back to cited text no. 2
    
3.
World Health Organization. Global Tuberculosis Reportl: 2020. World Health Organization; 2011. Available from: https:https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf.2020.  Back to cited text no. 3
    
4.
Brett GZ. Epidemiological trends in tuberculosis and sarcoidosis in a district of London between 1958 and 1963. Tubercle 1965;46:413-6.  Back to cited text no. 4
    
5.
Drake WP, Dhason MS, Nadaf M, Shepherd BE, Vadivelu S, Hajizadeh R, et al. Cellular recognition of Mycobacterium tuberculosis ESAT-6 and KatG peptides in systemic sarcoidosis. Infect Immun 2007;75:527-30.  Back to cited text no. 5
    
6.
Mortaz E, Adcock IM, Barnes PJ. Sarcoidosis: Role of non-tuberculosis mycobacteria and Mycobacterium tuberculosis. Int J Mycobacteriol 2014;3:225-9.  Back to cited text no. 6
  [Full text]  
7.
Agrawal R, Gonzalez-Lopez JJ, Meier F, Gupta B, Pavesio CE. Ocular and systemic features of sarcoidosis and correlation with the International Workshop for Ocular Sarcoidosis diagnostic criteria. Sarcoidosis Vasc Diffuse Lung Dis 2015;32:237-45.  Back to cited text no. 7
    
8.
Cox CE, Davis-Allen A, Judson MA. Sarcoidosis. Med Clin North Am 2005;89:817-28.  Back to cited text no. 8
    
9.
Noordzij M, Dekker FW, Zoccali C, Jager KJ. Study designs in clinical research. Nephron Clin Pract 2009;113:c218-21.  Back to cited text no. 9
    
10.
Brownell I, Ramírez-Valle F, Sanchez M, Prystowsky S. Evidence for mycobacteria in sarcoidosis. Am J Respir Cell Mol Biol 2011;45:899-905.  Back to cited text no. 10
    
11.
Wang SH, Chung CH, Huang TW, Tsai WC, Peng CK, Huang KL, et al. Bidirectional association between tuberculosis and sarcoidosis. Respirology 2019;24:467-74.  Back to cited text no. 11
    
12.
Ravan P, Farnia P, Amirmozafari N, Taghavi K, Ahmadi M, Masjedi MR, et al. Molecular Epidemiology Analysis of TB in Five Regional States of Iran. Tanaffos 2013;12:26-30.  Back to cited text no. 12
    
13.
Gazouli M, Ikonomopoulos J, Trigidou R, Foteinou M, Kittas C, Gorgoulis V. Assessment of mycobacterial, propionibacterial, and human herpesvirus 8 DNA in tissues of greek patients with sarcoidosis. J Clin Microbiol 2002;40:3060-3.  Back to cited text no. 13
    
14.
Gupta D, Agarwal R, Aggarwal AN, Jindal SK. Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis. Eur Respir J 2007;30:508-16.  Back to cited text no. 14
    
15.
Dubaniewicz A, Kämpfer S, Singh M. Serum anti-mycobacterial heat shock proteins antibodies in sarcoidosis and tuberculosis. Tuberculosis (Edinb) 2006;86:60-7.  Back to cited text no. 15
    
16.
Eishi Y, Suga M, Ishige I, Kobayashi D, Yamada T, Takemura T, et al. Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clin Microbiol 2002;40:198-204.  Back to cited text no. 16
    
17.
Ishige I, Usui Y, Takemura T, Eishi Y. Quantitative PCR of mycobacterial and propionibacterial DNA in lymph nodes of Japanese patients with sarcoidosis. Lancet 1999;354:120-3.  Back to cited text no. 17
    
18.
Kiani A, Razavi F, Mortaz E, Emami H, Ghazali S, Anbardan AD, et al. The prevalence of latent tuberculosis infection among Iranian sarcoidosis patients. Biomed Biotechnol Res J 2018;2:247-53.  Back to cited text no. 18
  [Full text]  
19.
Motswaledi MH, Khammissa RA, Jadwat Y, Lemmer J, Feller L. Oral sarcoidosis: a case report and review of the literature. Aust Dent J 2014;59:389-94.  Back to cited text no. 19
    
20.
Masoud S, Mihan P, Hamed M, Mehdi M, Mohamad RM. The presence of mycobacterial antigens in sarcoidosis associated granulomas. Sarcoidosis Vasc Diffuse Lung Dis 2017;34:236-41.  Back to cited text no. 20
    
21.
Saboor SA, Johnson NM, McFadden J. Detection of mycobacterial DNA in sarcoidosis and tuberculosis with polymerase chain reaction. Lancet 1992;339:1012-5.  Back to cited text no. 21
    


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