A 5-year-old girl presented with an acute onset fever, for about 4 days. She was seen initially in her local emergency room and a chest X-ray was done to rule out pneumonia. This showed a marked, diffuse reticulonodular pattern of parenchymal opacity bilaterally (Figure 1), incongruous with her clinical appearance. In reviewing the history, she was well until about 4 days before her presentation with a dry cough, night sweats, and daily fevers. During this time, she had no other significant respiratory symptoms, including no chest pain, no shortness of breath, no tachypnoea, and no haemoptysis.
Her medical history included a possible episode of pneumonia at one year of age, diagnosed and treated as an outpatient. A chest X-ray done at this time showed the beginning of a reticulonodular pattern that was considered to be due to infection and not followed up, as she recovered and remained clinically well thereafter. She had no hospital admissions or surgical procedures done. She received all of her immunizations. She had received salbutamol and fluticasone inhalers for an episode of wheezing at 3 years of age but had not used these thereafter. She had no atopic features. She was born premature, at 32 weeks, and required NICU admission for 2 weeks to establish feeding; there were no reported respiratory issues during the admission. She has a twin sister who has had no medical concerns. The family history was noncontributory but the parents were of Middle-Eastern descent and consanguineous, being first cousins. The patient had not travelled outside of the country and there was no obvious tuberculosis contact.
She had normal vital signs and normal oxygen saturations in room air (heart rate 100/min, respiratory rate 22/min, saturation 97%, temperature 36.1 degrees Celsius, and blood pressure 90/51 mmHg). Her height and weight were on the 3rd percentile. She had mildly increased work of breathing but was otherwise comfortable at rest. Her chest had bibasal inspiratory crepitations, bronchial breath sounds in the midzones bilaterally, and clear upper zones. Her cardiovascular, gastrointestinal, and head/neck examination was normal.
Her nasopharyngeal swab was found to be positive for influenza A. Her complete blood count was unremarkable with a white cell count of 7.2 x 109/L, haemoglobin of 123 g/L, and platelets of 223 x 109/L. Her inflammatory markers were done, with a C-reactive protein of 15.9 mg/L and an erythrocyte sedimentation rate of 41 mm/hr. Immunoglobulins were sent showing a normal IgG of 10.5 g/L, normal IgM of 1.9 g/L, and slightly elevated IgA of 2.4 g/L. She had normal electrolytes, including normal serum calcium and magnesium. Her liver enzymes were also normal.
A wide differential that included rheumatological, infectious, oncological, respiratory, and immunological causes was considered and so multiple investigations were then arranged. She had gastric aspirates and a tuberculin skin test to rule out tuberculosis, all of which were normal. Autoantibodies were sent and she was found to be mildly antinuclear antibody (ANA) positive (titres of 1 : 160) but her other autoantibodies were negative. She had adenine deaminase (ADA) levels and lymphocyte immunophenotyping done to rule out immune deficiency, which were normal. She had a normal sweat chloride. Bronchoscopy with bronchoalveolar lavage (BAL) was done: there was no bacterial or fungal growth on culture and the fluid was normal in appearance; BAL cell count showed WBC 127 x 106/L (3% neutrophils, 2% lymphocytes, and 95% macrophages) and RBC 303 x 106/L.
In regard to other imaging, she had a normal abdominal and thyroid ultrasound. Her chest CT showed diffuse interstitial lung disease, essentially characterized by interstitial lobular septal thickening (Figures 2(a), 2(b), and 2(c)). This raised possible diagnoses of pulmonary alveolar microlithiasis, dendritic pulmonary ossification (DPO), and pulmonary alveolar proteinosis (PAP).
As the imaging was not definitive, a lung biopsy was done; tissue was obtained from the lingula, which was sent for microbiology and pathology. The microbiology was negative. Pathology demonstrated presence of calcium concretions within the alveolar spaces, with blue discoloration at the edges and an eosinophilic centre on hematoxylin and eosin (H&E) stain; some structures had a concentric lamellar arrangement on trichrome staining (Figures 3(a) and 3(b)). These findings were consistent with the diagnosis of pulmonary alveolar microlithiasis, with an incidental influenza infection explaining her acute symptoms.
The patient was then discharged home after recovery from the biopsy. Genetic testing showed homozygous pathogenic mutations in the SLC34A2 gene (NM_006424.2:c.226C>T [p.Gln76*] in exon 03). Her sister was then brought for chest X-ray and CT, which showed similar findings, and was also positive on genetic testing.