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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 1  |  Page : 21-24

Lymphocytic interstitial pneumonia in an infant with diffuse cystic pulmonary tuberculosis


1 Department of Pediatrics, Christian Institute of Health Sciences and Research Hospital, Dimapur, Nagaland, India
2 Department of Pathology, Christian Institute of Health Sciences and Research Hospital, Dimapur, Nagaland, India
3 Department of Radiodiagnosis, Christian Institute of Health Sciences and Research Hospital, Dimapur, Nagaland, India

Date of Submission06-Oct-2021
Date of Decision12-Jan-2022
Date of Acceptance23-Jan-2022
Date of Web Publication25-Feb-2022

Correspondence Address:
Dr. Wonashi R Tsanglao
Paediatric Intensive Care Unit, Christian Institute of Health Sciences and Research Hospital, Dimapur, Nagaland
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ipcares.ipcares_304_21

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  Abstract 

Background: Lymphocytic interstitial pneumonia (LIP) is a rare disorder causing diffuse involvement of the lung parenchyma, including cystic changes. It is generally associated with autoimmune diseases in adults and human immunodeficiency virus infection in children. Concurrent LIP with pulmonary tuberculosis (TB) is rare and has not been reported in the pediatric population. Clinical Description: An 8-month-old infant who was recently diagnosed with miliary pulmonary TB and on antitubercular treatment presented with fast breathing for 2 days. Salient examination findings were tachypnea, with oxygen saturation of 84% in room air. High-resolution computed tomography of the chest showed diffuse involvement of both lungs with bilateral cystic changes. Histopathological examination of a lung biopsy specimen was consistent with LIP. Management: First-line antitubercular therapy was continued as per the national guideline, and methylprednisolone pulse was administered for 3 days followed by maintenance prednisolone for 8 weeks. The child responded well clinically and was kept under close follow-up. Radiological improvement became apparent at 15-month follow-up. Conclusion: Presence of diffuse cystic lung disease in pulmonary TB should raise suspicion for LIP. Lung biopsy is diagnostic and should be considered in such cases.

Keywords: Diffuse cystic lung disease, lymphocytic interstitial pneumonia, pulmonary tuberculosis


How to cite this article:
Tsanglao WR, Miachieo N, Ao MK, Aier T, Kikon S. Lymphocytic interstitial pneumonia in an infant with diffuse cystic pulmonary tuberculosis. Indian Pediatr Case Rep 2022;2:21-4

How to cite this URL:
Tsanglao WR, Miachieo N, Ao MK, Aier T, Kikon S. Lymphocytic interstitial pneumonia in an infant with diffuse cystic pulmonary tuberculosis. Indian Pediatr Case Rep [serial online] 2022 [cited 2022 May 27];2:21-4. Available from: http://www.ipcares.org/text.asp?2022/2/1/21/338486

Lymphocytic interstitial pneumonia (LIP) is a benign lymphoproliferative disorder limited to lungs. It is characterized by inflammatory reaction of the bronchus-associated lymphoid tissue, leading to cellular infiltration of pulmonary interstitium by reactive lymphocytes, plasma cells, and histiocytes.[1] Although the exact pathogenesis is unknown, LIP is considered to be a pathological, nonspecific immunologic response to different stimuli. [Table 1] depicts the various immunodeficiency, autoimmune, and infectious diseases that are associated with it.[1] The common infectious causes of LIP are human immunodeficiency virus (HIV) and Epstein–Barr virus.[1],[2],[3] Although Mycobacterium tuberculosis is also listed as a cause, an exhaustive literature search could not identify any reports in children.
Table 1: Diseases associated with lymphocytic interstitial pneumonia

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Here, we describe an 8-month-old infant on antitubercular therapy (ATT) for a recently diagnosed miliary pulmonary tuberculosis (TB), who presented with an acute respiratory illness, displayed diffuse cystic lung disease on imaging, and histopathological evidence of LIP.


  Clinical Description Top


An 8-month-old male child was brought to the emergency room with a history of fast breathing for 2 days. The onset was sudden, with no preceding fever, runny nose, cough, noisy breathing, loose stools, vomiting, or abdominal distension. He had a significant history of being admitted in our hospital with acute respiratory failure 6 weeks earlier (at the age of 6.5 months), severe enough to have required volume-controlled, synchronized intermittent mechanical ventilation for 7 days. The etiological diagnosis established at that admission was pulmonary TB. This had been based on bilateral miliary shadows on a chest radiograph [Figure 1]a and detection of acid-fast bacilli (AFB) on gastric aspirate (1+) that was rifampicin sensitive on GenXpert. The cerebrospinal fluid examination was normal. His weight was 6.7 kg (3rd to 15th centile for age), length 68 cm (50th to 85th centile), weight for length less than 3rd centile, and head circumference 44 cm (50th to 85th centile). He was started on four-drug ATT along with prednisolone. He was uneventfully extubated, weaned off oxygen, and discharged on day 16 of hospitalization to be followed up every 2 weeks in the outpatient department. The child remained well and compliant to treatment. History before the first hospitalization was unremarkable. The child was immunized and his developmental milestones were appropriate for age. He was on home-based complementary food following exclusive breastfeeding till 6 months of age. His parents had no past or current evidence of TB and were HIV negative.
Figure 1: (a) Initial chest X-ray (first admission) showing bilateral miliary infiltrates, and right upper lobar consolidation. (b) Chest X-ray (current admission) showing persistence of radiological findings

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At admission, he was alert with a respiratory rate of 70 per minute, subcostal recessions, heart rate of 156 per minute, blood pressure of 85/46 mmHg (50th to 90th centile), and temperature of 99°F. The oxygen saturation was 84% in room air that improved to 100% with supplemental oxygen at 2 L/min. His weight was 7.1 kg (3rd centile), length 70 cm (15th to 50th centile), weight for length less than 3rd centile, and head circumference 45 cm (50th to 85th centile). There was no clubbing, cyanosis, lymphadenopathy, or pallor on general examination. On respiratory examination, chest movement was symmetrical with no deformity; air entry was equal on both sides; and breath sounds were vesicular with no added sounds. Cardiovascular, abdominal, and central nervous system examinations were unremarkable. Based on past and present clinical presentation, a provisional diagnosis of recurrent pneumonia with failure to thrive was made and investigations were planned accordingly.


  Management and Outcome Top


His total white cell count was elevated (19.470/mm3) with 58% neutrophils and 37% lymphocytes. The erythrocyte sedimentation rate was 8 mm in the 1st h. Chest X-ray showed persistence of bilateral infiltrates compared to the previous one [Figure 1]a and [Figure 1]b. Gastric aspirates for AFB were negative. Arterial blood gas analysis, serum electrolytes, serum lipase, and kidney and liver function tests were normal. High-resolution computed tomography (HRCT) of the chest showed extensive centrilobular nodules with tree-in- bud pattern in both lungs, multiple areas of patchy consolidation, ground-glass opacities, cavities in the right upper lobe, enlarged mediastinal lymph nodes, and well-defined cysts in the anterior and apicoposterior segments of the left upper lobe, posterior and lateral segment of the left lower lobe, and posterior segment of the right upper lobe, with few of them showing continuation with subsegmental bronchi [Figure 2]. There was no evidence of pulmonary hypertension on echocardiography. Genetic screen for cystic fibrosis done in view of recurrent pneumonia and the evidence of diffuse lung disease on HRCT was negative.
Figure 2: (a) High-resolution computed tomography chest showing well defined cysts in the anterior segment of left upper lobe and posterior segment of right upper lobe (yellow arrows), with areas of consolidation (red arrow). (b) Extensive, diffusely scattered centrilobular nodules with multiple patchy consolidation and ground glass opacities (green arrows)

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[Figure 3] depicts the clinical course of the illness. The persistence of tachypnea, chest retractions, and oxygen requirement in the setting of a probable diffuse lung disease prompted us to perform an ultrasound-guided lung biopsy on the 17th day of hospitalization. The histopathological report revealed dense and diffuse infiltrates in the pulmonary interstitium, comprising lymphocytes and mononuclear cells, septal thickening, and gross architectural destruction suggestive of LIP. In addition, there was presence of caseating granulomas, Langerhans giant cell, and intra-alveolar macrophages [Figure 4]. Ziehl–Neelsen stain for AFB, and wet mount and Giemsa stain for Pneumocystis carinii were negative. Normal immunoglobulin (Ig) levels (IgG 680 mg/dl, IgM 96 mg/dl, and IgA 80 mg/dl) and CD4 count (918 cells/mm3) ruled out immunodeficiency.
Figure 3: Clinical timeline of the patient from admission (day 1) to discharge (day 42)

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Figure 4: Lung histopathology: (a) interstitial thickening with dense mononuclear interstitial infiltrate (white arrow) and gross architectural destruction (yellow arrow). (b) Dense interstitial lymphocytic infiltrates (yellow arrow), with intra-alveolar macrophage (black arrow) and epitheloid granuloma (white arrow)

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On the 22nd day, he was started on methylprednisolone (30 mg/kg/dose once a day) for 3 days, followed by oral prednisolone (1 mg/kg/day). Following this, there was a dramatic response in his respiratory status with tachypnea and chest retractions normalizing within 3 days. The child became oxygen independent by the 35th day of admission and was discharged on the 42nd day. [Figure 3] depicts the timeline of clinical events. Prednisolone was continued for a total of 8 weeks, followed by gradual tapering. ATT was stopped on completion of 6 months in view of clinical improvement and negative mycobacterial culture. At the 15-month follow-up visit, he was asymptomatic and his growth curves (weight and weight for length) demonstrated an upward trajectory. Although the chest X-ray still showed right-sided opacities, there was clearing of the cyst on the right upper and mid-zone.


  Discussion Top


LIP is considered to be in the spectrum of benign lymphoproliferative disorders of the lung. This includes conditions such as Castleman disease, angioimmunoblastic lymphadenopathy, follicular bronchiolitis (FB), infectious mononucleosis, lymphomatoid granulomatosis, posttransplant lymphoproliferative disorder, nodular lymphoid hyperplasia, and immunoglobulin Ig4-related disease. Clinically, LIP is characterized by cough, tachypnea, wheezing, and exercise intolerance in older children. Examination generally reveals tachypnea, retractions, and bilateral crackles. In severe cases, failure to thrive, digital clubbing, and cyanosis may be seen.[4]

The finding of LIP in this patient was intriguing. Cystic lung disease is a rare presentation of pulmonary TB,[5] and only one case has been reported in infancy by Jana et al.[6] The exact pathogenesis of cyst formation in pulmonary TB is unclear. The proposed mechanisms of cyst formation include check-valve obstruction due to inflammation and luminal narrowing of the bronchioles, peribronchiolar fibrosis, and excavation of the necrotic material by draining bronchi.[5],[7] LIP is a known cause of cystic lung disease, wherein cyst formation is postulated to result from compression of the bronchioles by lymphocytic infiltration, leading to bronchiolar stenosis and subsequent poststenotic bronchiolar ectasia.[1],[8] We were unable to identify any case report of children in which there was concurrent LIP and cystic pulmonary TB. LIP has been described in a 54-year-old adult with pulmonary TB but sans the cystic changes.[9]

HRCT in LIP usually shows ground-glass opacities, centrilobular nodules, septal thickening, and cystic changes, as seen in our case.[1] In a series of HRCT findings in 22 patients (age range 24–83 years) with biopsy-proven LIP, ground-glass opacities and poorly defined diffuse centrilobular nodules were seen in all (100%); subpleural nodules in 19 cases (86%); septal thickening in 18 cases (81%); cystic changes and mediastinal lymphadenopathy in 15 cases (68%).[10] Histologically, LIP is characterized by diffuse and dense infiltrates of immature and mature lymphocytes, plasma cells, and histiocytes predominantly in the pulmonary interstitium.[1] Secondary findings include presence of proteinaceous fluid, mononuclear inflammatory cells, foamy macrophages, or giant cells within the alveolar spaces. The histopathological differential diagnosis of LIP includes P. carinii pneumonia in immunocompromised patients and hypersensitivity pneumonitis. In the latter, cystic changes are rarely seen on radiography, and the lymphocytic infiltrate is patchy and less dense.

Currently, there are no established guidelines for treatment of LIP.[1],[2],[3] Steroids are generally used as first line, with clinical and/or radiologic response reported in 50%–60% of cases.[1],[3] Prednisolone (0.75–1.0 mg/kg/day) for 8–12 weeks or until stabilization, followed by slow taper to 0.25 mg/kg/day for another 6–12 weeks, has been recommended.[1] A case series of children with LIP and FB has also reported good response with pulse methylprednisolone and oral prednisolone.[4] Use of second-line agents, such as cyclophosphamide, hydroxychloroquine, azathioprine, and rituximab, has been described, though the level of evidence is anecdotal.[2],[3],[4] The prognosis of LIP is unknown. An adult case series reports several outcomes; spontaneous resolution, resolution posttreatment, respiratory failure, progression to lymphoma, and a 5-year mortality rate of 33%–50%.[1],[2] Data pertaining to outcomes in children with LIP after prolonged steroids are limited, though high morbidity and mortality have been reported.[4]



Declaration of patient consent

The authors certify that they have obtained the appropriate consent from the parents. In the form, the patient's parents have given his consent for the images and other clinical information to be reported in the journal. The patient's parents understand that the name and initials will not be published, and due efforts have been made to conceal the same, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Swigris JJ, Berry GJ, Raffin TA, et al. Lymphoid interstitial pneumonia: A narrative review. Chest 2002;122:2150-64.  Back to cited text no. 1
    
2.
Cha SI, Fessler MB, Cool CD, et al. Lymphoid interstitial pneumonia: Clinical features, associations and prognosis. Eur Respir J 2006;28:364-9.  Back to cited text no. 2
    
3.
Panchabhai TS, Farver C, Highland KB. Lymphocytic interstitial pneumonia. Clin Chest Med 2016;37:463-74.  Back to cited text no. 3
    
4.
Prenzel F, Harfst J, Schwerk N, et al. Lymphocytic interstitial pneumonia and follicular bronchiolitis in children: A registry-based case series. Pediatr Pulmonol 2020;55:909-17.  Back to cited text no. 4
    
5.
Perim J, Pimenta ES, Marchiori E. Cystic tuberculosis: A very unusual aspect of a common disease. Pulmonology 2020;26:400-3.  Back to cited text no. 5
    
6.
Jana M, Bansal S, Bhalla AS, et al. Cystic lung disease in tuberculosis. Indian J Pediatr 2021;88:734-5.  Back to cited text no. 6
    
7.
Ko KS, Lee KS, Kim Y, et al. Reversible cystic disease associated with pulmonary tuberculosis: Radiologic findings. Radiology 1997;204:165-9.  Back to cited text no. 7
    
8.
Ichikawa Y, Kinoshita M, Koga T, et al. Lung cyst formation in lymphocytic interstitial pneumonia: CT features. J Comput Assist Tomogr 1994;18:745-8.  Back to cited text no. 8
    
9.
Maurer JR, Choi HS. Lymphocytic interstitial pneumonitis manifesting concurrently with active tuberculosis. Arch Intern Med 1984;144:1855-7.  Back to cited text no. 9
    
10.
Johkoh T, Müller NL, Pickford HA, et al. Lymphocytic interstitial pneumonia: Thin-section CT findings in 22 patients. Radiology 1999;212:567-72.  Back to cited text no. 10
    


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