Article

Identification of disguised extrapulmonary tuberculosis

Correspondence / American Journal of Emergency Medicine 38 (2020) 15151539 1517

[9] Sharpe JP, Magnotti LJ, Croce MA, Paulus EM, Schroeppel TJ, Fabian TC, et al. Crystal- loid administration during trauma resuscitation: does less really equal more? J Trauma Acute Care Surg 2014;77(6):828-32.

Identification of disguised extrapulmonary tuberculosis

One of the most important messages from the recent review is that Diagnostic difficulty can occur as a result of clinical presentations of extrapulmonary tuberculosis that overlap with other conditions [1]. Conditions which can overlap with extrapulmonary manifestations of tuberculosis include extrapulmonary manifestations of rheumatoid ar- thritis (RA), systemic lupus erythematosus (SLE), Immunoglobulin G4- Related Disease (IgG4-RD) and cryptococcal infection. In each of these disorders the extrapulmonary complications which occur may be indis- tinguishable from the extrapulmonary manifestations of tuberculosis.

RA-related pleural effusion vs tuberculous pleural effusion

This was the potential differential diagnosis in a 28-year-old woman who had long-standing RA in multiple joints. Laboratory tests showed increased serum titres of Rheumatoid factor (41 IU/mL) as well as anti- cyclic citrullinated peptide antibody (16.2 U/mL). She had achieved clin- ical remission after methotrexate and adalimumab.

Her subsequent clinical course was complicated by the development of fever, cough, and unilateral pleural effusion. A pleural biopsy specimen showed epitheloid cell granulomas with necrosis. Furthermore, auramine-stained organisms suggestive of M tuberculosis were identified in the biopsy specimen. She experienced symptomatic improvement, and some degree of resolution of the pleural effusion, after receiving antitu- berculous chemotherapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide [2].

RA-related pericardial effusion vs tuberculous pericarditis

This was the potential differential diagnosis in a 74-year-old man who developed a pericardial effusion after years of chronic RA. He was on treatment with methotrexate when he subsequently developed fever and progressive dyspnea. Further investigations revealed that he had a pericardial effusion with tamponade. His symptoms were relieved by aspiration of the pericardial effusion. Pericardial biopsy was also per- formed. Histological examination of the biopsy specimen showed a few poorly formed giant cell granulomas. He tested positive for M tuberculo- sis, both by mycoBacterial culture and by Polymerase chain reaction of the pericardial biopsy specimen. He responded well to an anti- tuberculous regime initially consisting of rifampicin, isoniazid, pyrazinamide and ethambutol [3].

Pleural effusion in systemic lupus erythematosus

When pleural effusion occurs in SLE, tuberculosis may, in a few in- stances, be the underlying cause. In one series, among 119 patients with 127 episodes of pleuritic/pleural effusion, 9% of cases had tubercu- losis as the underlying cause [4]. In another report a 17-year-old woman had a long history of arthritis attributable to SLE. Laboratory tests showed an antinuclear factor titre of 1/480, anti-DNA antibodies, and the presence of LE cells. Her clinical course was complicated by the sub- sequent development of fever, pleural effusion and pericardial effusion. Pleural biopsy revealed granulomatous pleurisy. Both the pleural effu- sion and the pericardial effusion resolved after a course of antitubercu- lous chemotherapy consisting of rifampicin, isoniazid, and pyrazinamide [5].

Coexistence of tuberculous pleurisy and Immunoglobulin G4- related pleuropulmonary disease

This was the clinical scenario in a patient with documented IgG4- related pneumonitis and IgG4-related pleural effusion. Histological ex- amination of a pleural biopsy specimen revealed presence of fibrosis and an abundance of IgG4-positive plasma cells. In addition, however, the specimen showed some epitheloid granulomas. M tuberculosis was subsequently cultured from the pleural effusion [6].

Pericardial effusion in SLE

According to one review symptomatic pericarditis “is estimated to occur in 25% of SLE patients at some point in the course of their dis- ease”[7]. Although pericardial effusion may be the initial manifestation of SLE in a patient who has SLE as the sole underlying cause of the effu- sion [8], clinicians should also be vigilant for the occurrence of tubercu- losis as the underlying cause of pericardial effusion in a patient with SLE [9]. In the latter case report the patient was a 48-year-old man who had a malar rash suggestive of SLE, and pericardial effusion with tamponade. Laboratory tests revealed an antinuclear factor titre of 1/640, in associa- tion with a speckled staining pattern. In addition, he tested positive for anti-Sjogren syndrome-related antigen. Pericardial aspiration was un- dertaken to relieve the tamponade. Further tests were performed, but M tuberculosis was not isolated from culture of the pericardial effusion. He was treated with high dose corticosteroids on the presumption that the pericardial effusion was solely attributable to SLE. Nevertheless, he remained symptomatic and febrile. Pericardial biopsy was then un- dertaken. This revealed caseating granulomas. Acid fast bacilli were cul- tured from the biopsy specimen. He responded well to quadruple antituberculous chemotherapy (individual drugs not specified) [9].

Disseminated tuberculosis in a patient with Cryptococcal meningitis

A 61-year-old patient who was seronegative for human immune de- ficiency virus (HIV) infection presented with headache, fever, and dry cough. Lumbar puncture yielded a cerebrospinal fluid (CSF) characterised by 20 white blood cells/ul with 80% neutrophils and 20% lymphocytes, and a CSF glucose concentration of 0.11 mmol/L (reference range 2.25-4.17 mmol/L). Yeasts were noted on CSF smear, and the qualitative cryptococcal antigen test was positive. thoracic computed tomography showed miliary shadowing in the lungs. A sample of bronchoalveolar la- vage fluid tested positive for M tuberculosis when evaluated by PCR. A smear of the bronchoalveolar lavage fluid also showed the presence of acid fast bacilli. The patient responded well to the combination of rifam- picin, isoniazid, ethambutol, pyrazinamide and fluconazole [10].

The above are examples of dual pathology characterised by coexistence of tuberculosis and a disorder that is capable of having extrapulmonary manifestations identical to those of M tuberculosis. In such patients strate- gies to identify tuberculosis include evaluation of biopsy tissue, not only by M tuberculosis culture [10], but also by PCR [3]. The advantage of PCR is that it can generate positive results within a few days.

In a patient with suspected disseminated tuberculosis the diagnosis can be expedited by PCR evaluation of a peripheral blood sample for ev- idence of M tuberculosis [1]. In addition, evaluation for M tuberculosis can be performed on the urine by PCR, and by measurement of the urinary concentration of lipoarabinomannan [12]. These two tests [11,12], which have their highest yield in HIV-positive subjects, could be use- fully included in the approach to suspected disseminated tuberculosis in the Emergency Department.

Finally, as shown in two of the reports [2,3], clinicians should be vig- ilant for the presence of a tuberculous aetiology when extrapulmonary complications of a non-tuberculous disorder occur in a patient who is on immunosuppressive therapy.

I have no funding and no conflict of interest.

1518 Correspondence / American Journal of Emergency Medicine 38 (2020) 1515-1539

Oscar M.P. Jolobe MRCP(UK) Medical Division Manchester Medical Society, Simon Building, Brunswick Street, Manchester M13 9PL, United Kingdom of Great Britain and Northern

Ireland E-mail address: [email protected].

8 January 2020

https://doi.org/10.1016/j.ajem.2020.01.039

References

Long B., Liang SY., Koyfman A., Gottlieb M. Tuberculosis: a focused review for the emergency medicine clinician. Am J Emerg Med 2020;38(5):1014-1022.
  • Nagafuchi Y, Shoda H, Fujio K, Ishii S, Sugiyama H, Yamamoto K. Tuberculous pleu-
  • risy diagnosed by medical thoracoscopy in an adalimumab-treated rheumatoid ar- thritis patient after treatment of latent tuberculosis infection. Mod Rheumtol 2013;23:1013-7.

    Wee W, Denton E, Daffy J. Tuberculous pericarditis leading to cardiac tamponade: importance of screening prior to immunosuppression. Respirology Case Rep 2015; 2:135-7.
  • Palavutitotai N, Buppajarntham T, Katchanart W. Etiologies and outcomes of pleural effusions in patients with systemic lupus erythematosus. J Clin Rheumatol 2014;20: 418-21.
  • Pereira JCB. Tuberculous serositis in patient with systemic lupus erythematosus-case
  • report and literature review. Rev Port Pneumol 2009;15:721-7.

    Suzuki N, Saeki T, Shimaoka Y, Kuriyama H, Nishibori T, Sato K. Two cases of IgG4- related disease with pleural effusion. Nihon Kokyuki Gakkai Zasshi 2011;49: 97-102 [Article in Japanese; abstract in English].
  • Tincani A, Rebaioli CB, Taglietti M, Shoenfeld Y. Heart involvement in systemic lupus erythematosus, anti-phospholipid syndrome and neonatal lupus. Rheumatology 2006;45:iv8-iv13.
  • Bezwada P, Quadri A, Shaikh A, Ayala-Rodriguez C, Green S. Myopericarditis and pericardial effusion as the initial presentation of systemic lupus erythematosus. Case Rep Med 2017. https://doi.org/10.1155/2017/6912020 Volume. Article ID 6912020.
  • Christia P, Miles J, Katsa I, Maraboto C, Faillace R. Case of tuberculous pericarditis mimicking lupus carditis. Am J Med 2017;130:e475-7.
  • Musabande M, Mukabatsinda C, Riviello E, Ogbuagu O. Concurrent cryptococcal
  • meningitis and disseminated tuberculosis occurring in an immunocompetent male. BMC Case Rep 2015. https://doi.org/10.1136/bcr-2015-213380.

    Folgueira L, Dekgado R, Palenque E, Aguado JM, Noriega A. Rapid diagnosis of myco- bacterium tuberculosis by PCR. J Clin Microbiol 1996;34:512-5.
  • Kerkhoff AD, barr DA, Schutz C, Burton R, Lawn SD, Meintjies G. Disseminated tuber-
  • culosis among hospitalized HIV patients in South Africa: a common condition that can be diagnosed by urine-based assays. Sci Rep 2017. https://doi.org/10.1038/ s41598-017-09895-7.

    The authors respond: Diagnosis of Extrapulmonary Tuberculosis and Avoiding Anchoring Bias

    We thank Dr. Jolobe for his insightful comments regarding our re- view “Tuberculosis: a focused review for the emergency medicine clinician” [1,2]. Dr. Jolobe highlighted several conditions that pres- ent similarly to tuberculosis (TB), including pleural effusion in a pa- tient with previously diagnosed rheumatoid arthritis and systemic lupus erythematosus, pericardial effusion in a patient with previ- ously diagnosed rheumatoid arthritis and systemic lupus erythema- tosus, immunoglobulin G4-related pleuropulmonary disease and tuberculous pleurisy, and disseminated tuberculosis in a patient with cryptococcal meningitis [1].

    Dr. Jolobe recommended primarily using polymerase chain reaction for diagnosis of extrapulmonary tuberculosis, in conjunction with biopsy of the affected tissue and culture for mycobacteria [1]. PCR, in- cluding nucleic acid amplification testing (NAAT), can provide a more rapid diagnosis when compared with cultures and may detect as few as 10 mycobacteria [2-4]. The Xpert MTB/RIF assay is a commercial cartridge-based NAAT with specificities above 95% for the detection of Mycobacterium tuberculosis in cerebrospinal fluid, pleural fluid, and urine when compared to culture [5,6]. However, the sensitivity for the Xpert MTB/RIF was only 50.9% using pleural fluid, 71.1% using

    cerebrospinal fluid, 82.7% using urine, and 97.2% for bone tissue or joint fluid when compared to culture based on a 2018 Cochrane review [6]. Thus, we believe that this assay should not be relied upon solely to exclude the diagnosis of extrapulmonary TB [4]. Instead, PCR should be used in conjunction with clinical evaluation and other testing such as imaging and culture for Mycobacterium tuberculosis.

    Finally, the scenarios described by Dr. Jolobe included patients with immunocompromised states that may increase the risk for many other conditions in addition to tuberculosis, including bacte- rial infections, acute coronary syndrome, pulmonary embolism, cardiac tamponade, vasculopathy, pulmonary hypertension, and pleural disease [1,7,8]. It is therefore imperative to maintain a broad differential and avoid diagnostic momentum and anchoring bias when evaluating Immunocompromised patients presenting to the emergency department with cough, fever, weight loss, night sweats, or chest pain.

    Declaration of competing interest

    None.

    Acknowledgements

    MG, BL, SYL, and AK conceived the idea for this manuscript and con- tributed substantially to the writing and editing of the review. This man- uscript did not utilize any grants, and it has not been presented in abstract form. This clinical review has not been published, it is not under consider- ation for publication elsewhere, its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electron- ically without the written consent of the copyright-holder. This review does not reflect the views or opinions of the U.S. government, Department of Defense, U.S. Army, U.S. Air Force, Brooke Army Medical Center, or SAUSHEC EM Residency Program.

    Brit Long Brooke Army Medical Center, Department of Emergency Medicine, 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United States Corresponding author at: 3841 Roger Brooke Dr, Fort Sam Houston, TX

    78234, United States.

    E-mail address: [email protected].

    Stephen Y. Liang Divisions of Emergency Medicine and Infectious Diseases, Washington University School of Medicine, Saint Louis, MO, USA

    E-mail address: [email protected].

    Alex Koyfman The University of Texas Southwestern Medical Center, Department of Emergency Medicine, 5323 Harry Hines Boulevard, Dallas, TX 75390,

    United States

    Michael Gottlieb

    Department of Emergency Medicine, Rush University Medical Center,

    Chicago, IL, United States

    13 January 2020

    https://doi.org/10.1016/j.ajem.2020.01.030

    References

    1. Jolobe OMP. Identification of disguised extrapulmonary tuberculosis. Am J Emerg Med 2020;38(7):1517-8.

    Leave a Reply

    Your email address will not be published. Required fields are marked *