Pulmonary Alveolar microlithiasis

Authors: Sheeba Malik, vineela Hemraj, Bhavya Shivalingaiah, Merlyn Mony Vadakkan

DOI: 10.18231/j.ijirm.12789.1959320591

Keywords: PAM,Phosphate transport,alendronate

Abstract: Background: Pulmonary alveolar microlithiasis (PAM) is a rare pulmonary disease that is associated with the cumulation of hydroxyapatite microliths ( Calcium-phosphate concretions) within the lumen of the alveolar spaces. It’s a disease of heriditary origin, related to impairment of phosphate transport. The clinical course varies from being asymptomatic to respiratory insufficiency in patients. The incidence for India is 0.06 per million persons, making it extremely out of the common. There’s an absence of specific treatment options for PAM due to limited trials assesing efficacy of pharmacological therapies in it. Lung transplantation is the only proven resort for advanced PAM Case report : A 23 -year-old lactating mother with no underlying comorbidities presented to the out-patient department with complaints of intermittent chest pain with progressive dyspnoea on exertion since one month. On examination of the respiratory system, auscultation revealed vesicular breath sounds of decreased intensity with diffuse inspiratory fine crackles. Cardiac auscultation was unremarkable, without cyanosis or peripheral edema. She had no past history of pulmonary Tuberculosis of any other respiratory infections. Laboratory examinations revealed a negative result on sputum testing for acid-fast bacillus. Serum rapid testing for human immunodeficiency virus was negative. The chest radiograph revealed a diffuse opacity of high density with a symmetrical and bilateral micronodular pattern. A peripheral hyperlucency of both lung fields or a black pleural line was seen The finding was confirmed by an HRCT scan, which revealed diffuse calcification along the interlobar septa and subpleural regions in the lower pulmonary regions, with ground-glass attenuation and septal thickening in between resembling a ‘sandstorm apperance’. Multiple cysts along the subpleural line were identified as causing the black pleural line signs. The patient underwent a bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy. The branches of the bronchial tree were all patent . BAL showed alveolar macrophages with giant cells with no microliths. The histology findings revealed numerous calcified concretions and lamellar bodies on Haematoxylin and Eosin staining . BAL was showing alveolar macrophages with giant cells with no microliths. The electrocardiogram and echocardiography were unremarkable. Pulmonary function tests were not performed due to history of Lower segment caesaerean section (LSCS) 3 weeks back. Hematologic tests on blood cell counts and chemistry panels were unremarkable. 6 minute walk distance was 450 metres with no desaturation. A DNA sequencing analysis of whole coding regions of SLC34A2 was performed pro bono showing a genotype with a homozygous c.1402-1404delACC mutation in exon 12 of the SLC34A2 gene. It’s association with PAM is not well-established but given the structure of the mutation it was considered very likely that this mutation plays a role in the disease of the patient. The patient was started on Oral Alendronate (70 mg/week) with some dietary restrictions (low-phosphate diet). Followup was done after 6 months and the patient was doing symptomatically better but no improvement radiologically. Lung transplantation was advised along with family counselling. Discussion: The role of bisphosphonates in management of PAM is uncertain as usually steroids are used as an adjunct with them But, in this case monotherapy proved to be helpful for the patient as after two month follow-up, the patient was symptomatically better. Even so, lung transplantation being the only terminus. Conclusion : Pulmonary alveolar microlithiasis is a rare disease with no definitive treatment yet. Genetic counselling and affordable DNA analysis need to be principal , as finer awareness of aetiology and genotype–phenotype correlation may help to develop specific treatment consequentially.Need for trials assessing efficacy of different pharmacological therapies. References: 1. Patrick Kosciuk ,Cristopher Meyer, Kathryn A. Wikenheiser-Brokamp : Pulmonary Alveolar microlithiasis : European Respiratory Review 2020; 29(158): 200024; DOI: https://doi.org/10.1183/16000617.0024-2020 2. Åsa Lina M. Jönsson, Ulf Simonsen, Ole Hilberg : Pulmonary alveolar microlithiasis: two case reports and review of the literature : European Respiratory Review 2012; 21(125): 249-256; DOI: https://doi.org/10.1183/09059180.00009411