Pulmonary alveolar microlithiasis: no longer in the stone age

Abstract

Pulmonary alveolar microlithiasis (PAM) is a rare parenchymal lung disease caused by variants in the SCL34A2 gene and characterised by the accumulation of intra-alveolar microliths. PAM has been reported in fewer than 1100 cases throughout the world. It is an autosomal recessive hereditary disease and often associated with consanguinity. Progress with respect to the genetic background and pathophysiology has resulted in an increased understanding of the disease in recent years. Until now, 30 genetic different SLC34A2 variants have been reported, which all are considered significant for disease development. There is no sex difference and the majority of cases are diagnosed at the age of 30–40 years. Many patients are asymptomatic and the diagnosis is made at random. When symptomatic, dyspnoea, cough, chest pain and fatigue are common complaints. The diagnosis of PAM can confidently be based on typical radiographic findings and genetic testing proving rare biallelic SCL34A2 gene variants. Bronchoalveolar lavage and histopathology may show microliths. There is no disease-specific treatment and management is supportive. Lung transplantation should be considered in advanced cases.

Pulmonary Alveolar Microlithiasis: A Unique Case of Familial PAM Complicated by Transplant Rejection

“…Imaging studies frequently reveal fine, sand-like micronodular interstitial hyperdensities with basilar predominance [ 1 ]. A four-tier grading system for radiologic severity has recently been proposed [ 16 ]. The degree of clinicopathologic dissociation is often significant in PAM, with extensive radiologic progression and minimal associated clinical symptoms [ 16 ].…”

“…A four-tier grading system for radiologic severity has recently been proposed [ 16 ]. The degree of clinicopathologic dissociation is often significant in PAM, with extensive radiologic progression and minimal associated clinical symptoms [ 16 ]. It is essential to differentiate PAM from other diseases with similar radiographic appearances, including miliary tuberculosis, fungal infection, pneumonia, sarcoidosis, amyloidosis, pulmonary alveolar proteinosis, pulmonary hemosiderosis, metastatic calcification, and pneumoconiosis [ 7 , 16 ].…”

“…Pulmonary function testing can aid in the diagnosis, though PFTs are often normal early in the disease. In advanced disease, testing typically shows a restrictive pattern with reduced DLCO [ 16 ]. Routine blood tests have no value in PAM diagnosis and generally are normal [ 1 , 16 ].…”

“…In advanced disease, testing typically shows a restrictive pattern with reduced DLCO [ 16 ]. Routine blood tests have no value in PAM diagnosis and generally are normal [ 1 , 16 ]. PAM's definitive diagnosis lies on typical radiographic findings plus genetic testing or, in the absence of testing, radiography with tissue diagnosis [ 16 ].…”

“…Routine blood tests have no value in PAM diagnosis and generally are normal [ 1 , 16 ]. PAM's definitive diagnosis lies on typical radiographic findings plus genetic testing or, in the absence of testing, radiography with tissue diagnosis [ 16 ]. Bronchoalveolar lavage can help recover microliths but is otherwise unremarkable and not used for diagnosis [ 12 ].…”