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 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 1  |  Page : 61-64

Recurrent pneumonia in a child: Knitting clinical and radiological features to clinch the diagnosis

1 Pediatric Pulmonology Unit, Advanced Pediatrics Centre, PGIMER, Chandigarh, India
2 Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh, India
3 Allergy and Immunology Unit, Department of Pediatrics, PGIMER, Chandigarh, India
4 Department of Pediatrics, Pediatric Emergency and Intensive Care Unit, PGIMER, Chandigarh, India

Date of Submission22-Jan-2022
Date of Decision23-Jan-2022
Date of Acceptance23-Jan-2022
Date of Web Publication25-Feb-2022

Correspondence Address:
Prof. Joseph L Mathew
Pediatric Pulmonology Unit, Advanced Pediatrics Centre, PGIMER, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_23_22

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Childhood pneumonia is a very common cause of morbidity and mortality in children, especially in developing countries. A small proportion of these are due to recurrent pneumonias. This is defined as the occurrence of more than one episode of pneumonia within a single year, or greater than 3 episodes within any duration; with radiographically documented clearing between episodes. A diligent, step-wise clinical approach and judicious laboratory investigations are required to establish clinical diagnosis. In this article, we describe the approach used to establish etiology in a case of recurrent pneumonia.

Keywords: Chest X-ray, chronic granulomatous disease, computed tomographic scan, recurrent pneumonia

How to cite this article:
Reddy A, Singh S, Mathew JL, Bhatia A, Rawat A, Jayashree M, Singh M. Recurrent pneumonia in a child: Knitting clinical and radiological features to clinch the diagnosis. Indian Pediatr Case Rep 2022;2:61-4

How to cite this URL:
Reddy A, Singh S, Mathew JL, Bhatia A, Rawat A, Jayashree M, Singh M. Recurrent pneumonia in a child: Knitting clinical and radiological features to clinch the diagnosis. Indian Pediatr Case Rep [serial online] 2022 [cited 2022 May 27];2:61-4. Available from: http://www.ipcares.org/text.asp?2022/2/1/61/338482

Childhood pneumonia is a very common cause of morbidity and mortality in children, especially in developing countries. A small proportion of these is due to recurrent pneumonia. This is defined as the occurrence of more than one episode of pneumonia within a single year or more than three episodes within any duration, with radiographically documented clearing between episodes. Diligent, step-wise clinical approaches and judicious laboratory investigations are required to establish clinical diagnosis. In this article, we describe the approach used to establish etiology in a case of recurrent pneumonia.

  Clinical Description Top

A 10-year-old girl presented with a history of recurrent episodes of fever, cough, and respiratory distress, since 6 years of age. The first episode lasted for 4 weeks, during which there was no loss of weight or diminished appetite. A chest X-ray showed heterogeneous opacities and areas of breakdown in the left upper zone [Figure 1]a. The treating physician presumed it to be tuberculosis (TB) and prescribed anti-TB therapy (ATT), without microbiological confirmation. She received standard regimen ATT for a total duration of 7.5 months. The parents reported strict compliance and there was resolution of cough and fever, and weight gain within 8 weeks.
Figure 1: Chest X-rays during the course of the illness. (a) X-ray during the first episode showed left upper lobe consolidation with breakdown areas (orange arrow). (b) X-ray during the second episode showed reticulonodular opacities (red arrows) in both lungs. (c) X-ray during a subsequent episode showed multiple reticulonodular opacities (red arrows) in both lungs. (d) X-ray during the current admission showed retrocardiac cosnolidation (gold arrow) with bilateral reticulonodular opacities (red arrows) with prominent pulmonary conus (white arrow)

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Eight months after completion of ATT, she again developed low-grade fever, dry cough, weight loss, and rapid breathing. Consultation was sought at a national-level institute designated for TB. The chest X-ray showed diffuse reticulonodular opacities [Figure 1]b. Gastric lavage samples were negative for Mycobacterium tuberculosis by GeneXpert. Nevertheless, she was diagnosed with pulmonary TB and prescribed ATT for 6 months again. Within 6 weeks, she became afebrile, the cough and respiratory distress ceased, and she started gaining weight.

However, within 3 months of completing ATT, the child developed multiple episodes of fever, cough, and respiratory distress every 3–4 months. Each episode was managed with oral antibiotics. During one of these episodes, the chest X-ray showed diffuse bilateral reticulonodular opacities [Figure 1]c. Although there was intermittent, transient relief with each course of antibiotics, she gradually developed worsening breathlessness. She was referred to our institution with a history of moderate-grade fever, cough with mucopurulent expectoration, and breathlessness at rest for 1 month.

What specific history should be asked in such a clinical setting and why?

[Table 1] depicts a broad (i.e., nonexhaustive) list of details to be elicited and the common causes of recurrent pneumonia that can be excluded.
Table 1: History that should be elicited in a child with recurrent pneumonia for determining etiology

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The child was second in birth order, born of a third-degree consanguineous union (parents were second cousins). Both her siblings, aged 13 and 9 years, were healthy. However, her mother had three spontaneous, first-trimester abortions after the third child's birth. There was no history of TB or any similar illness in any family member. Development had been normal, and she was currently in class IV. Vaccination was age-appropriate.

The heart rate was 132/minute, respiratory rate was 44/minute, blood pressure was 90/56 mmHg, and temperature was 99°F. She displayed intercostal and subcostal retractions, and oxygen saturation was 80% in room air. With administration of oxygen through nasal prongs, the saturation improved but did not normalize, and she was placed on continuous positive airway pressure (CPAP) support. The work of breathing remained high, necessitating noninvasive ventilation with synchronized intermittent mandatory ventilation-pressure control via nasal cannulae. Ceftazidime and cloxacillin were administered empirically to provide broad-spectrum antibiotic cover.

The weight was 18 kg (−3.57 Z score), height 115 cm (−3.12 Z score), and body mass index 13.61 (−1.54 Z score). There were pallor and grade 3 pandigital clubbing, but no icterus, lymphadenopathy, elevated jugular venous pressure, or signs of micronutrient or vitamin deficiencies were noted. The tonsils were not inflamed, and the aural examination was unremarkable. There were no signs of healed scars on the torso or limbs. The BCG scar was visible.

Chest examination revealed a centrally positioned trachea, appropriately located apex beat, diminished breath sounds over the left mammary area, coarse crackles, and occasional expiratory wheeze all over the chest. Cardiovascular examination revealed a nonpalpable, loud second heart sound with normal splitting. There was no evidence of right-sided heart failure. Abdominal and neurological system examinations were normal.

What are the salient features in serial chest X-rays?

All chest X-rays were reviewed. The X-ray done during the first episode [Figure 1]a showed a large area of consolidation with breakdown in the left upper lobe. This favored necrotizing pneumonia rather than pulmonary TB. The X-ray from the second episode [Figure 1]b showed bilateral reticulonodular opacities. This could be considered compatible with pulmonary TB radiologically. The third X-ray after two courses of ATT [Figure 1]c also displayed bilateral reticulonodular opacities, but with relative improvement. Radiologically, the persistence of opacities suggested progression to chronic lung disease. X-ray done in our institution, at admission, showed inhomogeneous air space opacities in both lungs with retrocardiac areas of consolidation and prominent pulmonary conus. The bony structures, thoracic soft tissues, cardiac shadow, and costophrenic angles appeared normal [Figure 1]d. There was no evidence of bronchiectasis in any of the X-rays.

What clinical diagnosis can be considered based on history, examination, and chest radiographs?

A syndromic diagnosis of recurrent pneumonia resulting in chronic suppurative lung disease (CSLD) with secondary pulmonary hypertension was considered. The underlying cause was thought to be the past pulmonary TB infection. The possibility of a concurrent secondary immunodeficiency (i.e., HIV infection) or hitherto unrecognized primary immunodeficiency was considered. Among the latter, chronic granulomatous disease (CGD) was considered most likely, based on the age at presentation, pattern of infections, and clinical findings. Disseminated BCG infection and Mendelian susceptibility to mycobacterial disease were considered remote possibilities. Other causes mentioned in [Table 1] were ruled out clinically as well as based on the chest X-rays.

What investigations should be planned?

Investigations were planned to identify: (1) the underlying cause of recurrent pneumonia; (2) the microbial etiology of the current episode; and (3) any complications of CSLD. The blood culture at admission was sterile. Sputum Gram stain did not identify any organisms, while its bacterial culture yielded only commensal organisms. Sputum fungal studies were also sent; though yeast species were identified on smear microscopy, it was considered insignificant, as the culture did not yield anything. Blood galactomannan assay (to identify invasive Aspergillus infection) was not elevated. Multiple gastric lavage specimens (as per our institutional protocol) were examined for acid-fast bacilli and GeneXpert, both of which were negative. Thus, an active infection was unlikely, but a past infection could not be ruled out. HIV serology was nonreactive. Screening nitro blue reduction test was positive, suggesting CGD. Dihydro rhodamine (DHR) assay showed reduced stimulation index of the patient's neutrophils compared to the control confirming CGD. A 2-D echocardiography showed mildly dilated main pulmonary artery (diameter 20 mm compared to the ascending aorta diameter of 17 mm), normal biventricular function, but no regurgitation across the tricuspid or pulmonary valves. Therefore, pulmonary arterial hypertension could not be confirmed on echocardiography.

Investigations for allergic bronchopulmonary aspergillosis were done, considering the presence of wheezing. The serum total IgE was elevated (2507 IU/ml, normal <100 IU/ml), as was Aspergillus-specific IgE (4.18 kUA/l, normal <0.35 kUA/l). This was consistent with fungal sensitization. A contrast-enhanced computed tomography (CT) of the chest was done [Figure 2] as per the guidelines of the European Respiratory Society to identify bronchiectatic changes.[1]
Figure 2: Selected axial contrast-enhanced computed tomography sections highlighting the important findings. (a) Lung window) showing bilateral variable sized acinar nodules (orange arrows). (b) Lung window showing extensive ground glass opacities with interstitial thickening (blue arrows) and an area of consolidation with breakdown in the left lower lobe (green arrow). (c) Mediastinal window showing dilated main pulmonary artery (red arrow) and enlarged bilateral hilar lymph nodes (yellow arrows)

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What does the computed tomographic scan show?

[Figure 2] shows multiple, variable-sized acinar nodules in both lungs (orange arrows) with bilateral diffuse confluent areas of ground-glass opacities with interstitial thickening (blue arrows) and fibrotic changes. There was a patch of consolidation in the left lower lobe showing breakdown and air bronchograms (green arrow). The mediastinal window sections showed dilatation of the main pulmonary artery (red arrow). There were multiple calcified and noncalcified conglomerate mediastinal and hilar lymph nodes without central necrosis (yellow arrows), the largest measuring 13 mm. Bronchiectasis was not noted. The radiological impression was active pulmonary infection, possibly fungal.

What would be the next modalities of investigation?

Since sputum examination was negative, but suspicion of fungal infection was apparent from the CT scan, flexible fiberoptic bronchoscopy was performed. It showed the presence of mucopurulent secretions in the airways. Analysis of bronchoalveolar lavage (BAL) fluid showed 1625 cells/mm3 (60% polymorphs, 25% monocytes, and 15% lymphocytes). BAL fluid Gram stain and bacterial culture were negative, AFB was not identified, and GeneXpert did not detect M. tuberculosis. Fungal elements were absent on BAL fluid smear, but galactomannan was elevated to 1.92 (laboratory cutoff 1.0), suggesting Aspergillus in the lung.

There was a dilemma regarding the decision to start antifungal therapy. The likelihood of fungal infection was strong: No bacteria had been identified; there was minimal improvement with the broad-spectrum antibiotics; CT scan findings were suggestive, and BAL galactomannan was elevated. On the other hand, blood galactomannan index was not elevated, sputum smear examination showed only yeast, and fungal hyphae were not detected on BAL examination. Taking everything into consideration, the treating team decided to start amphotericin on clinical grounds, to which she responded. The severity of cough reduced, sputum production ceased, and the respiratory status improved so that NIV support could be gradually omitted over the next 2 weeks.

  Discussion Top

CGD is a rare primary immunodeficiency disorder caused by an inherited defect of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. NADPH oxidase transfers electrons to molecular oxygen to generate superoxide anion (O2), which further dismutates to reactive oxygen species (ROS) including hydrogen peroxide, that is highly microbicidal. CGD is characterized by inadequate production of ROS due to mutations in genes encoding the NADPH oxidase complex. This results in decreased phagocytic capability to kill pathogens, particularly catalase-positive organisms, and recurrent pyogenic infections, such as pneumonia, abscesses, suppurative lymphadenitis, osteomyelitis, bacteremia, fungemia, and subcutaneous infections.[2] Staphylococcus aureus, Burkholderia cepacia, Serratia marcescens, Nocardia, and Aspergillus spp. are the usual responsible microorganisms.[3]

Fungal pneumonia in CGD is most commonly due to Aspergillus species affecting one or both lungs.[4] Radiographic manifestations include segmental or lobar consolidation (as seen in bacterial pneumonia), multiple subsegmental vaguely-defined opacities, and miliary nodules (akin to miliary TB).[5] Common CT scan findings include pulmonary nodules (often the initial radiologic manifestation of fungal infection), consolidation, pulmonary scarring, and bronchiectasis.[6],[7] Invasive pulmonary aspergillosis may present with a chronic nodular radiological picture (as in this case) or chronic progressive “microgranulomatous aspergillosis,” which is characterized by diffusely scattered, discrete, and confluent granulomas of the same age, in which the organisms are confined within the granulomas. Patients with CGD generally do not develop hyphal angioinvasion, the characteristic halo sign on CT scan, or cavities, unlike neutropenic patients in which Aspergillus causes angioinvasion and infarction.[8]

To conclude, a child with recurrent pneumonia and evidence of chronic nodular pneumonitis on chest X-ray should be investigated for CGD, even if the characteristic radiological patterns associated with Aspergillus infection are absent.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Chang AB, Fortescue R, Grimwood K, et al. European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis. Eur Respir J 2021;58:2002990.  Back to cited text no. 1
Martire B, Rondelli R, Soresina A, et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with Chronic Granulomatous Disease: An Italian multicenter study. Clin Immunol 2008;126:155-64.  Back to cited text no. 2
Segal BH, Leto TL, Gallin JI, et al. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore) 2000;79:170-200.  Back to cited text no. 3
Corrado ML, Cleri D, Fikrig SM, et al. Aspergillosis in chronic granulomatous disease: Therapeutic considerations. Am J Dis Child 1980;134:1092-4.  Back to cited text no. 4
Schoumacher RA, Tiller RE, Berkow RL. Invasive pulmonary aspergillosis in an infant: An unusual presentation of chronic granulomatous disease. Pediatr Infect Dis J 1987;6:215-7.  Back to cited text no. 5
Mahdaviani SA, Mehrian P, Najafi A, et al. Pulmonary computed tomography scan findings in chronic granulomatous disease. Allergol Immunopathol (Madr) 2014;42:444-8.  Back to cited text no. 6
Bondioni MP, Lougaris V, Di Gaetano G, et al. Early identification of lung fungal infections in chronic granulomatous disease (CGD) using multidetector computer tomography. J Clin Immunol 2017;37:36-41.  Back to cited text no. 7
Dennis CG, Greco WR, Brun Y, et al. Effect of amphotericin B and micafungin combination on survival, histopathology, and fungal burden in experimental aspergillosis in the p47phox-/- mouse model of chronic granulomatous disease. Antimicrob Agents Chemother 2006;50:422-7.  Back to cited text no. 8


  [Figure 1], [Figure 2]

  [Table 1]


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