Masqueraders of pneumonia in A case series

Authors: Hardeep Kaur, Vivek Bhat, Bal Mukund, Gaurav Mahajan

Abstract

Pneumonia remains the top most killer of under-five Indian children. Pneumonia in children is usually caused by viral or bacterial infections. However, there are some unusual causes of pneumonia that merit consideration when pneumonia is recurrent or persistent.

INTRODUCTION

Recurrent pneumonia is defined by 2 episodes of pneumonia in a year or more than 3 episodes during life time. Persistent pneumonia is defined by the persistence of symptoms and signs with radiographic abnormalities for >1 month even after effective antibiotic therapy. A few unusual causes of pneumonia in children are airway malformation, congenital lung malformation, aspiration syndromes, hypersensitivity pneumonitis, and primary immunodeficiencies. We present a case based discussion of various causes of recurrent and persistent pneumonia in children.

CASE 1

Three years old female symptomatic for the last 2 years with recurrent episodes of pneumonia. Her antenatal and perinatal period was uneventful. There was no history of recurrent abortions in the mother, sibling deaths, unusual presentations such as non-healing ulcers, skin lesions, recurrent diarrhea, oily stool, recurrent ear discharge, recurrent rhinitis, food allergy, exposure to pigeons, vomiting post feeds or forced feeding in past. Child started eating home cooked food including wheat, rice, and lentils at 9 months of age. She had failure to thrive post-weaning. The mother recalled an increase in her respiratory distress post lentil consumption occasionally. She had a history of multiple hospitalizations as pneumonia, which responded partially to IV antibiotics without complete remission ever. Her CXR was s/o perihilar dense bilateral consolidation with characteristic sparing of lower lobes. CECT chest was s/o peritracheal [Figure 1a], peri-bronchial consolidations in upper and middle lobes bilaterally with sparing of the lower lobe with interstitial thickening [Figure 1b]. Multiplanar reformat images in the axial section were suggestive of perihilar dense consolidation with peripheral sparing [Figure 1c]. Her radionuclide milk scan was positive for gastroesophageal reflux grade 2. In view of characteristic features of hypersensitivity pneumonitis with upper and middle lobe involvement, her IgG levels for suspected lentil hypersensitivity were sent which were high with a level of 76 mgA/L as against a cut-off of <10 mgA/L. Her serum IgE for lentil level was 0.87 kUA/L against a normal cut-off <0.35 kUA/L. Child was diagnosed as a case of lentil hypersensitivity and was treated with oral steroids along with the complete omission of lentils from her diet and anti-GER medication. She was started on alternative sources of protein such as eggs. She became asymptomatic after 15 days.

CASE 2

Five months, well thriving male was admitted with complaints of fever, cough, and fast breathing of 5 days duration. He was initially managed on supportive care with heated humidified high-flow nasal cannula oxygen as a suspected case of Acute Bronchiolitis. He continued to deteriorate despite supportive care. His hemogram was suggestive of mild anemia with an elevated TLC count of 22,300/mm^3^ and platelet count of 6.3 lakh/mm^3^. Sepsis biomarkers, such as Procalcitonin and C-reactive peptide, were negative for bacterial infection. The blood smear did not show any toxic changes or left shift or neutrophilia. CXR was suggestive of bilateral non-homogenous reticulonodular opacities. His systemic examination was unremarkable. His ABG report suggested hypoxemia with - Ph 7.436, PCO2- 41.0, PO2- 54.5, BE -3.1, HCO3- 20.9 meq/L. He was started on IV antibiotics and put on non-invasive ventilation support. However, he continued to worsen clinically. His CECT chest was suggestive of diffuse lung injury with ground glass attenuation in central and peripheral aspects [Figure 2a] with interstitial thickening [Figure 2b] and left lower lobe consolidation with a single cavitatory lesion in the posterior basal segment of left lower lobe [Figure 2c]. In view of this, neonatal interstitial lung disease like surfactant protein deficiency was considered. The patient was unfit for bronchoalveolar lavage. Next-generation sequencing was sent to rule out congenital causes of infantile interstitial lung disease. He was started on IV methylprednisolone pulse @ 10 mg/kg/d in view of moderate to severe interstitial lung disease. However, on day two of pulse steroid therapy, he started having massive pulmonary bleed and succumbed to his illness. Histopathology of the lung specimen was suggestive of minimal features of pneumonitis with the presence of proteinaceous material in the alveoli which showed weak positive staining with Periodic acid shiff which supported the diagnosis of pulmonary alveolar proteinosis. Next-generation sequencing report was suggestive of the presence of X-linked combined immune deficiency with a mutation in exon 2 at gene locus IL2RG with c.157 deletion. The final diagnosis was infantile interstitial lung disease with pulmonary hemorrhage with X-linked combined immunodeficiency due to IL2RG gene mutation.

CASE 3

Seven years male, vegan, presented with clinical features of persistent pneumonia. He was well nourished and built without any h/o recurrent cough, fever, diarrhea, weight loss, hemoptysis, skin rash, joint pain, exposure to pets/birds, or contact with a case of tuberculosis. He had one episode of undocumented pneumonia at 5 years followed by a second episode at the age of 10 years. Clinically, he had respiratory distress with reduced air entry in the right infra-axillary area. He was hemodynamically stable with normal room air saturations. The child was given IV antibiotics and supportive therapy. However, he continued to deteriorate despite therapy. His CXR was suggestive of consolidation right middle lobe and lower lobe with an air-fluid level. His CECT chest was done which suggested the presence of a large cystic lesion in the right lower lobe posterior basal segment with the presence of air-fluid level [Figure 3a], Bronchiectatic changes adjacent to a cystic lesion in the right lower lobe [Figure 3b] with dense consolidation medial basal segment of right lower lobe [Figure 3c]. Differential diagnoses considered were infected hydatid cyst right lung or congenital cystic pulmonary adenomatoid malformation (CPAM). His Serum IgG for hydatid cyst was sent which was negative. In view of no response to medical management, he underwent a right lower lobe lobectomy. Histopathology of the lung specimen was suggestive of multiple cysts lined by ciliated epithelium with underlying alveolar spaces with sold-appearing areas, foamy intra-alveolar macrophages, lobar pneumonia in resolution phase with peripheral foci of necrosis with dense neutrophilic infiltrates without any atypical or malignant cells. The child recovered completely after the lobectomy. Screening to rule out other associated anomalies was done. The final discharge diagnosis was congenital CPAM type 3.

DISCUSSION

Hypersensitivity pneumonitis also known as extrinsic allergic alveolitis is often associated with exposure to aeroallergens such as pigeon droppings, dog or cat’s dander in children. Lentil hypersensitivity is relatively less commonly diagnosed as a cause of hypersensitivity pneumonitis mainly due to a lack of awareness about this entity as well as the non-availability of standard cut-off levels for IgG lentil Ag. Recently, a study published by AIIMS New Delhi had given cut-off levels of 10 mgA/L to label as hypersensitivity to lentil Ag.[1]

Hypersensitivity pneumonitis is an immune-mediated inflammatory disorder with a suggested prevalence of around 4/1,000,000 children.[2] Clinical features are non-specific and may mimic viral or bacterial pneumonia. BAL fluid in hypersensitivity pneumonitis generally suggests lymphocyte predominance.[3] The most common clinical features are cough, fever, and respiratory distress[4] CECT chest may suggest the presence of nodules, centrilobular consolidation, ground glassing, and bronchiectasis in chronic exposure.[15] There is usually a history of force-feeding daal (Lentils) as part of a weaning diet. Treatment with steroids and abstinence from lentils have a dramatic response.[4]

Interstitial lung diseases (ILD) are the rarer causes of persistent hypoxemia and respiratory distress in infants.[6] Most of the ILDs are congenital in origin which tend to present in early neonatal periods.[7] Of the congenital causes of ILDs, mutation in surfactant protein deficiency disorders and pulmonary alveolar proteinosis are lethal in nature.[7] Milder variants usually manifest when there is some superadded bacterial or viral infection. Usually, any infant with prolonged oxygen dependency, clubbing, diffuse lung involvement, or crazy paving appearance should be evaluated for possible interstitial lung disease.[8] Our patient had one of the rarer forms of X-linked combined immune deficiency with mutation in exon 2 at gene locus IL2RG with c.157 deletions. This could be a novel cause of infantile ILD presenting as pulmonary alveolar proteinosis.

Congenital lung malformation are rare congenital lung disorders with an expected incidence of 0.94 per 10,000 live births.[9] A study conducted by Gulla et al.[10] suggested that lung hypoplasia is the commonest congenital lung malformation in India. Usually, congenital lung malformations present with features of recurrent pneumonia, failure to thrive, or hemoptysis.[11] They may remain asymptomatic in early childhood and may get unmasked only when they get infected and present as pneumonia. Early diagnosis may help prevent pneumonectomy or lobectomy and reduce overall lung damage. Moreover, certain types of CPAM such as type 4 CPAM have pre-malignant potential and hence required to be removed even in asymptomatic patients.

CONCLUSION

In order to avoid mis-diagnosis, there is a heightened need to create awareness about rarer causes of pneumonia in children such as lentil hypersensitivity, congenital lung malformations, and interstitial lung disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.