Pulmonary alveolar microlithiasis (PAM) is a rare diffuse lung disease characterized by extensive deposition of calcium phosphate microcrystals in the alveoli. The familial incidence of this disease is as high as 38% - 61%, and the disease has been confirmed to be an autosomal recessive genetic disease.
Etiology
This disease is associated with SLC34A2 gene mutation and is autosomal recessive. This disease has obvious familial aggregation and is mostly limited to sibs. SCL34A2 is a gene encoding sodium phosphate cotransporter, and is mainly involved in the metabolism of inorganic phosphorus. It is expressed in various tissues of the human body, predominantly lung tissue, particularly in alveolar type II cells. Alveolar type II cells produce alveolar surfactants, and phospholipids are an important component. Old surfactants are taken by alveolar type II cells, and are degraded by alveolar macrophages after recirculation. Degraded phospholipids release phosphates, which should have been cleared in the alveolar cavities. SCL34A2 dysfunction can reduce phosphate clearance and lead to the formation of microliths in the alveoli. In sporadic cases, it has been found that environmental and dietary factors may be associated with the disease.
Pathology
The disease mainly invades the lungs, causing induration and increased weight. In light microscopy, countless concentric calcified corpuscles with a diameter of 0.01 - 3 mm are present in the alveolar cavities, and can occupy 25% - 80% of the alveolar space. Macrophages can sometimes be seen around the stones, but there is no inflammatory reaction. In the early stage, the alveolar wall structure is normal. In the late stage, interstitial fibrosis and giant cell formation cause the alveolar wall to thicken, resulting in bullae and occasionally pneumothorax.
Clinical manifestations
Most patients with PAM are asymptomatic for years or decades. Most patients seek medical attention after typical imaging changes are found during physical examinations. Most patients begin to experience recurrent cough or progressively exacerbated dyspnea at the age of 30 - 40. Clinical symptoms may be separated from imaging examinations. The disease progresses slowly, with no symptoms in the early stage, and with complications such as pulmonary interstitial fibrosis, emphysema, spontaneous pneumothorax, pulmonary hypertension, and cor pulmonale in the late stage. Most patients die of respiratory failure 10 - 15 years after diagnosis.
Auxiliary examination
Typical chest x-ray shows diffuse, granular, nodular opacities in both lungs, with a diameter of about 1 mm, mainly in the middle and lower lung fields, with hazy heart margin and diaphragmatic surface, with typical sandstorm sign. CT shows diffuse, evenly sized, hyperdense, miliary nodules, with characteristic calcification, mainly in the lower lungs. The mediastinal window may show typical black pleura sign and flame sign. High-resolution CT can show the morphology, density, and distribution of small nodules with a diameter of less than 1 mm, which is very valuable for the diagnosis of this disease.
Diagnosis
The presence of flame sign or black pleura sign in CT can be used to diagnose this disease.
Treatment
Symptomatic supportive treatment is often used clinically. Systemic application of glucocorticoids and bronchoalveolar lavage have been proven to be ineffective. Oxygen therapy is very necessary for patients with respiratory failure, which can improve hypoxia symptoms and increase exercise tolerance. Previous studies have shown that etidronate disodium can inhibit the formation of calcium phosphate crystals and dissolve the formed calcified plaques, and has a certain effect in some PAM patients. Lung transplantation is the only effective treatment for end-stage PAM.