|Year : 2022 | Volume
| Issue : 4 | Page : 258-260
A Child with Recurrent Respiratory Infections: When Right is Not Always Right!
Anvesh Reddy1, Chirag Thakur1, Anmol Bhatia2, Joseph L Mathew1
1 Department of Pediatrics, Pediatric Pulmonology Unit, PGIMER, Chandigarh, India
2 Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh, India
|Date of Submission||20-Oct-2022|
|Date of Decision||28-Oct-2022|
|Date of Acceptance||29-Oct-2022|
|Date of Web Publication||29-Nov-2022|
Prof. Joseph L Mathew
Department of Pediatrics, PGIMER, Chandigarh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Reddy A, Thakur C, Bhatia A, Mathew JL. A Child with Recurrent Respiratory Infections: When Right is Not Always Right!. Indian Pediatr Case Rep 2022;2:258-60
|How to cite this URL:|
Reddy A, Thakur C, Bhatia A, Mathew JL. A Child with Recurrent Respiratory Infections: When Right is Not Always Right!. Indian Pediatr Case Rep [serial online] 2022 [cited 2023 Jan 30];2:258-60. Available from: http://www.ipcares.org/text.asp?2022/2/4/258/362249
| Clinical Description|| |
A 12-year-old girl presented with a history of recurrent episodes of fever, dry cough, and nasal discharge, starting from early infancy. Each episode lasted for 3–5 days and responded to a combination of antibiotics, cough syrups, and bronchodilators, prescribed by local practitioners. The cough gradually increased in severity and became productive by 8 years of age. Subsequently, the child also started experiencing recurrent episodes of a feeling of tightness in the chest, wheezing, and difficulty in breathing, which were triggered by upper respiratory tract infections. These episodes occurred 3–4 times a year. There was no exacerbation with physical exertion, cold air, exposure to dust or smoke, or seasonal variation. She was treated with short courses of bronchodilators and oral steroids on some occasions.
During her most recent episode, she was hospitalized elsewhere for 7 days. There, she was presumed to have an acute episode of bronchial asthma, complicated by pneumonia, hence was prescribed inhaled corticosteroids, intravenous (IV) antibiotics, and supplemental oxygen. A chest radiograph was done at that hospital [Figure 1]a. She was referred to our institution due to the persistence of symptoms despite these interventions, and to ascertain the diagnosis.
|Figure 1: (a) Chest X-ray (with incorrect marker) suggesting left-sided heart and cardiac apex (red arrow), suspicion of bronchiectasis (yellow arrows), and a calcified axillary lymph node on the right side (black arrow). (b) Chest X-ray showed dextrocardia with right-sided cardiac apex (pink arrow), bilateral bronchiectasis (yellow arrows), and a calcified axillary lymph node on the left side (black arrow).|
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The child was second in birth order, born at term by vaginal delivery (at home). There was no history of parental consanguinity. Her older and younger siblings (aged 16 and 9 years, respectively) were healthy. There was no history of tuberculosis or similar illness in any family member. The child had attained age-appropriate developmental milestones and was studying in class six. Her vaccination was up to date.
What additional history can help to determine the diagnosis?
The clinical phenotype suggested recurrent respiratory tract infections that were initially mild but progressively increased in severity. There was no history of delayed passage of meconium at birth, prolonged neonatal jaundice, the passage of greasy or bulky stools, recurrent episodes of ear discharge, recurrent diarrhea or skin pustules, lymph node enlargement, episodes of syncope or chest pain, or bluish discoloration of nails or lips. There was no history of witnessed or suspected foreign body aspiration, recurrent feed aspiration, choking episodes while eating or drinking, or history of blood transfusion. There was also no history of close contact with tuberculosis. These points in history ruled out cystic fibrosis, primary/secondary immune deficiency, congenital cardiac disease, aspiration syndromes, and a forgotten airway foreign body.
At presentation, the pulse rate was 89/min, respiratory rate 26/min, blood pressure 112/65 mmHg (all within the normal range), temperature 99°F, and oxygen saturation 97% in room air. The weight was 29 kg (−1.6 z-score), height was 137 cm (−1.7 z-score), and body mass index was 15.45 (−0.98 z-score). There was mild pallor, but no clubbing, lymphadenopathy, elevated jugular venous pressure, icterus, or signs of nutritional deficiency. The tonsils were not enlarged. Tenderness was evident over both maxillary sinuses, but not the frontal or ethmoidal sinuses. The nose and ear examinations were normal. A Bacille Calmette–Guérin scar was noted.
The respiratory system examination showed a centrally positioned trachea, symmetric chest wall shape and movements, equal breath sounds, and bilateral, diffuse, end-expiratory wheeze. There were no crackles. The heart sounds were normal but more prominent on the right side of the chest. There was no murmur. On abdominal percussion, liver dullness appeared to be present on the left side. Neurological system examination was normal.
What diagnoses would you consider at this stage and why?
The child had recurrent respiratory infections from early infancy, progressing to develop the aforementioned manifestations, indicative of chronic suppurative lung disease (CSLD) by the age of 8 years. She also appeared to have had recurrent sinusitis, although there was no otitis media. Therefore, the differential diagnoses could be primary ciliary dyskinesia (PCD), or congenital airway malformations. Other clinical possibilities had already been excluded by elicitation of a detailed history. The presence of wheezing against the background of CSLD was attributed to secondary allergic bronchopulmonary aspergillosis (ABPA), complicating the primary diagnosis.
What are the salient features in the chest X-ray?
The initial chest X-ray that had been done outside [Figure 1]a had poor penetration, evidenced by the absence of discernible intervertebral spaces. The lung parenchyma appeared normal, although careful examination raised the suspicion of dilated bronchi. There was a single calcified right axillary lymph node. As the quality of this X-ray was not optimal, we repeated one in our institution [Figure 1]b. This showed dextrocardia with the cardiac apex oriented toward the right side, and multiple dilated bronchi suggesting bronchiectasis. The calcified lymph node was also evident but on the left side. We concluded that the marker on the first chest X-ray had been placed incorrectly; whereby dextrocardia was missed altogether. Further, the poor exposure resulted in difficulty to appreciate bronchiectasis.
What should be the next steps of evaluation?
Formal otorhinolaryngological examination confirmed frontal sinusitis, bilateral intact tympanic membranes, and no middle-ear effusion. An X-ray of the paranasal sinuses showed bilateral opacified maxillary sinuses but unremarkable bilateral ethmoidal, frontal, and sphenoid sinuses. Pure-tone audiometry and impedance tympanogram confirmed normal hearing.
The presence of dextrocardia prompted us to perform ultrasonography of the abdomen which showed the liver on the left side and the spleen on the right side, confirming abdominal situs inversus. There was also a right-sided aortic arch.
We investigated for secondary infections. Sputum examination did not show any bacteria on Gram staining. However, the culture yielded Pseudomonas aeruginosa. Sputum smear microscopy showed pseudohyphae but no fungi on culture.
To confirm bronchiectasis radiologically while avoiding the excessive radiation of a computed tomography scan, chest magnetic resonance imaging was performed [Figure 2]. This confirmed the right-sided aortic arch, dextrocardia, and situs inversus. There was bilateral central bronchiectasis with otherwise unremarkable lung parenchyma. Thus, the clinical diagnosis considered was CSLD with sinusitis, due to a possible PCD with situs inversus, most likely Kartagener's syndrome. Wheezing was attributed to secondary ABPA.
|Figure 2: Axial T2-weighted MRI (a and b) lung section showing mild bilateral central bronchiectasis (white arrow), right-sided aortic arch (yellow arrow). Coronal T2-weighted MRI (c and d) lung cuts showing dextrocardia (blue arrow), liver on the left side (orange arrow), spleen (red arrow), and stomach (green arrow) on the left side.|
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What to do next to confirm the diagnosis?
To confirm PCD, nasal mucosal scrapings from the right inferior turbinate were sent for ultrastructural examination of cilia by transmission electron microscopy (TEM). However, the quantity of samples sent was reported as inadequate. Hence, a flexible fiberoptic bronchoscopy-guided tracheal/bronchial mucosal biopsy sample for TEM examination was planned during the follow-up.
Investigations for ABPA showed serum total immunoglobulin E (IgE) elevated to 1171 IU/ml, (normal <100 IU/ml), however, Aspergillus specific IgE was 0.10 kUA/l (laboratory normal <0.35 kUA/l), and Aspergillus specific IgG was 1.08 U/ml (laboratory normal <8.0 U/ml). The absolute eosinophil count was also normal –68 cells/μL (0.5%), hence, ABPA could not be confirmed. Skin prick test for Aspergillus antigen was unavailable in our institution.
| Management|| |
The child received IV antibiotics for 7 days as per the sputum culture sensitivity pattern. Her family was taught gentle chest physiotherapy and airway toileting. As ABPA had been suspected, she was administered oral corticosteroids, which were given for only 5 days as it was not confirmed. She also received inhaled bronchodilator for 5 days. The otorhinolaryngologist prescribed nasal corticosteroids for 3 months, for chronic sinusitis. The child improved with these medications.
| Discussion|| |
PCD is a rare, but clinically and genetically, nonhomogeneous group of disorders of ciliary motility. It is inherited in an autosomal recessive manner. Its estimated prevalence is about one in 10,000–40,000 in Norwegian and Japanese population surveys of situs inversus and bronchiectasis.
Cilia are present at the apical surface of the epithelial cells of the upper and lower respiratory tracts, female reproductive tract, spermatozoa, and ependymal lining of brain ventricles. Abnormal ciliary function in the respiratory tracts impedes clearance of airway secretions, resulting in increased susceptibility to recurrent bacterial infection, ultimately leading to the development of bronchiectasis. During embryogenesis, motile cilia play a pivotal role in determining organ laterality, hence, laterality defects are observed in half the cases of PCD. Kartagener's syndrome is a variant of PCD, with the classic triad of sinusitis, bronchiectasis, and situs inversus.
Clinical symptoms and signs of PCD include respiratory distress at birth in term neonates, early and recurrent rhinitis, persistent serous otitis media, chronic wet cough, and sometimes hydrocephalus. The diagnosis of PCD is often delayed due to a low index of suspicion. However, it is one of the rare causes of chronic lung disease, presenting with respiratory distress starting from birth.
A diagnostic predictive score, the PCD rule (abbreviated as PICADR) is helpful in suspecting PCD and considering further evaluation to confirm the diagnosis of PCD. It is a simple, seven-point questionnaire, to be applied to children with chronic respiratory symptoms, originating in early infancy/childhood. Four points are scored for the presence of situs abnormality, two points each for being born at tern, experiencing respiratory symptoms from the neonatal period, admission to a neonatal unit, and the presence of a congenital heart defect. One point each is scored for the presence of persistent perenniel rhinitis and the presence of chronic ear symptoms. Thus, out of a total possible score of 14, the index child scored 10. A score >5 has sensitivity and specificity of 0.90 and 0.75, respectively.
Currently, nasal nitric oxide measurement is the preferred screening test for suspected PCD. Assessing ciliary beat pattern and ciliary beat function using high-speed video microscopy is also helpful, although it cannot differentiate genetic PCD from secondary ciliary dyskinesia caused by bacterial or viral infections. However, these facilities are unavailable in our institution. In India, they are available at AIIMS, New Delhi, although other institutions (including ours) are attempting to establish similar services. TEM ciliary ultrastructural examination was earlier considered the gold standard test. The classic defects are the absence of outer dynein arms, combined absence of outer and inner dynein arms, and microtubular disarrangement with the absence of inner dynein arms. However, it can be normal in about 20% of PCD cases. Genetic confirmation of PCD is still evolving. To date, mutations of only 60% of PCD cases have been identified. Immunofluorescence-linked antibodies to ciliary proteins can identify their absence or mislocalization and can be used to diagnose PCD. However, currently, there is no single gold standard investigation for diagnosing PCD.
PCD can result in long-term lung damage, but it has a relatively better prognosis than cystic fibrosis. In later life, male infertility may be observed. The outcome of PCD depends on genetic and phenotypic heterogeneity, associated comorbidities, and access to appropriate care. However, some children progress to severe bronchiectasis, end-stage lung disease, and premature death.
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.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]