Abstract
Tuberculosis, a global public health concern, is emerging as an important complication in children with nephrotic syndrome. We report a case of an adolescent with nephrotic syndrome who developed fatal miliary tuberculosis after initiation of steroid therapy, presenting as a bronchoesophageal fistula. The case highlights the importance of maintaining a high index of suspicion prior to starting immunosuppressive therapy in pediatric patients of nephrotic syndrome.
Keywords: Complications, Miliary tuberculosis, Tracheoesophageal fistula, Bronchoesophageal fistula, Nephrotic syndrome
Introduction
Tuberculosis, a global public health concern, is an important preventable cause of death in both children and adults. In particular, tuberculosis is emerging as an important infectious complication of pediatric nephrotic syndrome [1, 2].
Tuberculous involvement of the esophagus is very rare (0.3%) [3]. The spread of disease from the tracheobronchial tree to the esophagus can present as a tracheoesophageal or bronchoesophageal fistula (BEF). Here we report a case of a boy with nephrotic syndrome presenting with a tuberculous BEF, highlighting the importance of screening for tuberculosis in children diagnosed with nephrotic syndrome prior to starting steroid treatment.
Case Report
A 13-year-old boy, a case of steroid-responsive nephrotic syndrome on treatment for a year, had complaints of difficulty swallowing liquids, associated with coughing, for ten days, along with fever with evening peaks of temperature and loss of appetite for the last 1 month. There was no family history of, or history of contact with, tuberculosis. His oral cavity and oropharyngeal examination were unremarkable. Indirect laryngoscopy revealed pooling of saliva in both pyriform sinuses. His systemic examination and laboratory test results revealed nothing abnormal. The esophagus appeared normal on esophagogastroduodenoscopy. A contrast barium swallow revealed a slightly dilated esophagus along its whole length with no segmental narrowing or dilatation, with contrast opacifying the left mainstream bronchi, suggestive of a BEF (Fig. 1). A high resolution computed tomography (CT) scan revealed bilateral centrilobular nodules, linear branching opacities and a small bilateral pleural effusion with no mediastinal lesion—all pointing towards an active infective pulmonary pathology (Fig. 2). Sputum examination revealed acid-fast bacilli (AFB), suggestive of pulmonary tuberculosis. A percutaneous gastrostomy was performed and the patient was kept nil per orally. He was started on a 4-drug directly observed anti-tuberculous regimen including isoniazid, rifampicin, pyrazinamide, and ethambutol. After 6 weeks, the initial sputum culture demonstrated growth of Mycobacterium tuberculosis, with no resistance to first-line drugs on drug susceptibility. The patient, however, expired at his residence two months into the intensive phase of treatment due to unrecognized complications.
Fig. 1.
Contrast barium swallow was ordered that revealed a slightly dilated esophagus along its whole length with no segmental narrowing or dilatation, with contrast opacifying the left mainstream bronchi, suggestive of a BEF
Fig. 2.
High resolution computed tomography scan of the chest, topogram (a) and axial (b) views, reveal bilateral centrilobular nodules, small linear branching opacities and minimal bilateral pleural effusion
Discussion
Tuberculosis is a global health problem, particularly in high burden areas like India, which is home to a quarter of the world’s incident cases of tuberculosis, with a prevalence of 2.8 million cases and 0.27 million tuberculosis related mortalities in 2012 [4]. Childhood tuberculosis represents a major unrecognized cause of disease and death during childhood in endemic countries, with immunocompromised children, in particular, at a higher risk for developing disseminated and severe forms of tuberculosis [5].
BEF in children may be congenital or acquired. Acquired BEF is an uncommon complication of trauma, ingestion of caustic materials, foreign body inhalation, and infections like pulmonary tuberculosis. While up to 19% of acquired non-malignant BEFs in adults are tuberculous, only a few cases have been reported in the pediatric age group, to the best of our knowledge [6–10].
Tuberculous BEF may arise due to erosion of tuberculous peribronchial lymph nodes into the esophagus and bronchi, or from direct extension of tuberculous ulceration or perforation of a tuberculous abscess. Less frequently, it may follow direct spread from affected thoracic vertebrae, or complicate endotracheobronchial tuberculosis [6].
Tuberculosis and its complications are more commonly seen in immunocompromised patients, patients receiving prolonged steroid therapy for nephrotic syndrome, renal transplant recipients, bone marrow transplant recipients, and rheumatoid arthritis patients taking infliximab [1].
Various authors have studied the relationship between tuberculosis and nephrotic syndrome [1, 2]. One such study reported that 9.3% patients of nephrotic syndrome developed tuberculosis after initiation of immunosuppressive therapy, pulmonary involvement being the commonest [1].
BEF being the only manifestation of miliary tuberculosis in our patient emphasizes the importance of having a high index of suspicion in immunosuppressed patients, allowing early diagnosis and management of such complications. History of fever, weight loss, dysphagia, and coughing while eating or drinking may indicate development of a tubercular fistula. The diagnosis can be aided by microbiological assessment of sputum for AFB. Radiological investigations including barium swallow and CT scans of the thorax may demonstrate a BEF and its associated pulmonary complications respectively. Endoscopic examination may aid in identifying the site of fistulae and allow biopsies to be taken. Histopathology usually reveals epithelioid granulomas with giant cells of Langhans type, and is especially useful in AFB negative cases.
Medical therapy with antitubercular drugs has become the mainstay of management of patients with tuberculous BEF. Surgery, once the treatment of choice, is now reserved for severe symptomatic perforations or failed medical therapy.
In conclusion, considering the high incidence and prevalence of tuberculosis in India, we suggest that all children being started on prolonged immunosuppressive therapy should be screened for tuberculosis and regularly followed up during treatment for any complication. Once diagnosed, anti-tubercular treatment should be started as soon as possible, along with supportive measures, to minimize the morbidity and mortality associated with the disease.
Compliance with Ethical Standards
Conflict of interest
The authors have no conflict of interest to disclose.
Ethical Approval
This study was in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments. For this type of study formal consent is not required.
Informed Consent
As the patient had expired, informed consent was taken from the patient’s parents for inclusion in the above case study.
References
- 1.Gulati S, Kher V, Gulati K, Arora P, Gujral R. Tuberculosis in childhood nephrotic syndrome in India. Pediatr Nephrol. 1997;11(6):695–698. doi: 10.1007/s004670050368. [DOI] [PubMed] [Google Scholar]
- 2.Kala U, Milner LS, Jacobs D, Thomson PD. Impact of tuberculosis in children with idiopathic nephrotic syndrome. Pediatr Nephrol. 1993;7(4):392–395. doi: 10.1007/BF00857548. [DOI] [PubMed] [Google Scholar]
- 3.Changal KH, Raina AH, Parra R, Khan MA. Esophageal tuberculosis; A rare cause of odynophagia: a case report. Egypt J Chest Dis Tuberc. 2013;62(2):349–351. doi: 10.1016/j.ejcdt.2013.06.005. [DOI] [Google Scholar]
- 4.TBC India. TB India 2014 Revised National Tuberculosis Control Programme Annual Status Report. TBC India. http://www.tbcindia.nic.in/pdfs/TB%20INDIA%202014.pdf. Published March 2014. Accessed 30 June 2015
- 5.Marais BJ. Childhood tuberculosis: epidemiology and natural history of disease. Indian J Pediatr. 2011;78:321–327. doi: 10.1007/s12098-010-0353-1. [DOI] [PubMed] [Google Scholar]
- 6.Gie RP, Kling S, Schaaf HS, Beyers N, Moore S, Schneider J. Tuberculous broncho-esophageal fistula in children: a description of two cases. Pediatr Pulmonol. 1998;25(4):285–288. doi: 10.1002/(SICI)1099-0496(199804)25:4<285::AID-PPUL9>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
- 7.Bhatia R, Mitra DK, Mukkerjee S, Berry M. Bronchoesophageal fistula of tuberculosis origin in a child. Pediatr Radiol. 1992;22(2):154. doi: 10.1007/BF02011325. [DOI] [PubMed] [Google Scholar]
- 8.Danino EA, Evans CJ, Thomas JH. Tuberculous bronchoesophageal fistula in a child. Thorax. 1995;10:351–353. doi: 10.1136/thx.10.4.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Lucaya J, Sole S, Badosa J, Manzanares R. Bronchial perforation and bronchoesophageal fistulas: tuberculous in origin. AJR Am J Roentgenol. 1980;135(3):525–528. doi: 10.2214/ajr.135.3.525. [DOI] [PubMed] [Google Scholar]
- 10.Erlank A, Goussard P, Andronikou S, Gie R, Sidler D, Ackermann C, et al. Oesophageal perforation as a complication of primary pulmonary tuberculous lymphadenopathy in children. Pediatr Radiol. 2007;37:636–639. doi: 10.1007/s00247-007-0482-5. [DOI] [PubMed] [Google Scholar]