Introduction
Pulmonary alveolar microlithiasis is a rare pulmonary disease which is characterized by small calcified microliths within the alveolar spaces. It is an autosomal recessive disorder due to a mutation in the SLC34A2 gene that forms the pulmonary sodium-phosphorus cotransporter protein, specifically found in the type 2 pneumocytes or alveolar epithelial cells.
Type 2 pneumocytes secrete and recycle surfactant. Surfactant is the surface tension-reducing substance, thereby preventing the collapse of alveoli and increasing lung compliance. It is a mixture of lipids such as dipalmitoyl phosphatidylcholine, lecithin, and proteins. The SLC34A2 gene is responsible for the regulation of phosphate levels.
Mutation in the gene impairs the activity of the sodium phosphate cotransporter, resulting in the accumulation of phosphate within the alveoli. This accumulated phosphate forms tiny calcified microliths. It is usually an incidental finding and takes longer to diagnose as it is usually asymptomatic. It is mostly seen before 40 years.
Calcium phosphate deposits may be accumulated in various other organs such as the kidney, gallbladder, testes, and aorta. Deposits within the blood vessel may cause constriction of the vessels that can impede blood flow. The distribution of the microliths is usually bilateral, with a middle and lower portion predilection.
What Are the Signs and Symptoms of Pulmonary Alveolar Microlithiasis?
It is usually asymptomatic and only discovered incidentally on a chest radiograph.
The common signs and symptoms include
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Exertional dyspnea or difficulty in breathing.
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Persistent non-productive cough.
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Chest pain.
What Are the Diagnostic Tests to Be Carried Out?
The diagnostic tests that can be carried out are
Chest X-Ray: It shows infiltrates as fine sand-like calcifications, also called "sandstorm lungs," diffusely involving both the lungs, usually the middle and lower portions, often obliterating the mediastinal and diaphragmatic outlines. If the disease progresses further, the distribution of microliths is within the perilobular interstitium.
Chest Computed Tomography (CT) Scan: It shows symmetrical abnormalities in both lungs, usually marked calcifications. The characteristic findings are the calcified thickening of the interlobular septa, bronchovascular bundles, and pleura. The calcified interlobular septa are a pathognomonic feature. The calcifications are most prominent in the peripheral, mediastinal, and fissural subpleural regions.
Each lobe is surrounded by a fine, dense outline, giving an overall appearance of a stony lung. Ground glass opacities are also seen more commonly in children. The subpleural sparing of the calcifications usually occurs centrally within the secondary pulmonary lobules. It is also known as the black pleural sign.
Small subpleural cysts are also seen. Pleural calcifications give pencil-thin sharp, dense white lines along the coastal surfaces and the hemidiaphragm.
High-Resolution Computed Tomography (HRCT): It shows that the black pleural line on the chest radiograph is due to the thin-walled subpleural cyst of 5-10 mm in diameter. The radiographic feature of interlobular septal thickening, also referred as crazy paving, can be observed. Ground glass opacities may be due to an active inflammatory response to intra-alveolar microliths.
Paraseptal and subpleural emphysema may be present as regions of low attenuation adjacent to the pleural surface as small cysts. Parenchymal involvement may include characteristic features associated with interstitial lung disease like subpleural interstitial, and interlobular septal thickening, and few other features of pulmonary fibrosis, including subpleural reticular changes and traction bronchiectasis of the peripheral airways.
Progressive subpleural interstitial thickening may end up as pleural calcifications. The radiographic changes occur as a series of events starting from the calcific phase, which involves a small number of poorly calcified microliths and diffuse ground glass opacities.
In the next phase, the radiograph has a sandy appearance with scattered calcified micronodules of 2-4 mm diameter and preserved cardiac and diaphragmatic outlines. In the third phase, progressive opacification occurs with interstitial thickening and obscuration of cardiac and diaphragmatic outlines. In the last and the final phase, intense calcification of the interstitium with variable involvement of the interstitium with varied involvement of the pleural serosa produces a "white out" appearance of the lungs with apical sparing. This may progress to areas of dense opacifications or calcifications.
Pulmonary Function Test: There is a reduction in the pulmonary function involving forced expiratory volume in one sec per forced vital capacity ratio and diffusion capacity.
Positron Emission Tomography Scan: It shows a maximum standardized uptake value of 7.3 in areas without calcifications and decreased standardized uptake value of 2.6 in areas with dense calcifications. This pattern is highly suggestive of inflammation, especially in areas that are not yet calcified.
Bone Scintigraphy or Technetium 99m- Methylene Diphosphonate Bone Scan: It has a high affinity for calcification foci of soft tissue and can detect early pulmonary calcification. It shows diffuse radiotracer uptake. HRCT has made it necessary for the need for bone scintigraphy as a diagnostic modality in pulmonary alveolar microlithiasis.
Chest Ultrasonography: It may reveal pleural thickening, irregularities, and echogenic foci without acoustic shadowing in the subpleural area. The absence of acoustic shadowing, also known as the "comet tail" phenomenon, is because of a complex pleural interface with thickened pleura, subpleural microcyst, and thickened interstitium that may reduce the deep penetration of ultrasound waves.
Magnetic Resonance Imaging (MRI): It shows diffuse calcified micronodules, characterized by an increased signal intensity on T1-weighted images, particularly in the posterior lower zones.
Bronchoalveolar Lavage ( BAL): The presence of microliths in the bronchoalveolar fluid is also suggestive of pulmonary alveolar microlithiasis. The therapeutic bronchoalveolar lavage does not help dislodge the microliths, unlike pulmonary alveolar proteinosis.
Lung Biopsy: It provides the definitive diagnosis of pulmonary alveolar microlithiasis.
What Is the Management of Pulmonary Alveolar Microlithiasis?
There is no specific treatment modality for the disease. Bisphonates, an anti-osteoclastic agent, such as Etidronate, have been beneficial in treating pulmonary alveolar microlithiasis by inhibiting microliths formation. A lung transplant is the only and ultimate treatment for progressive disease.
Conclusion
Pulmonary alveolar microlithiasis is a rare pulmonary disease due to a mutation in the SLC34A2 gene in which the lung fills with bone-like alveolar calculi or microliths, resulting in slowly progressive respiratory failure. It is usually asymptomatic and only found as an incidental finding on a radiograph. There are no specific treatments for the disease, and lung transplantation is the only option for patients with progressive disease.
