Pulmonary alveolar microlithiasis

Pulmonary Alveolar Microlithiasis is a rare depositional disease of the lung

1. Pulmonary Alveolar Microlithiasis By Dr.S.Sesha Sai Dept o f Pulmonary Medicine SMC, VJA.

2. Rare autosomal recessive disorder. Depositional disorder of the lung. Intra-alveolar accumulation of spherical calcified concretions ( calciferites , calcospherites , or microliths ), without any calcium metabolism disorder 1 . Presentation - any age, usually occur in third or fourth decade. Pulmonary Alveolar Microlithiasis

3. Incidental Diagnosis. Marcello Malpighi – described in 1868. Harbitz – histopathology in 1918. Harbitz Syndrome. 2 Named “ Microlithiasis Alveolaris Pulmonum ” by Puhr 3 in 1933. More than 1000 cases have been reported in the world literature. 4 Introduction

4. Aetiology remains unclear Mutations of the  SLC34A2  gene considered to be the cause SLC34A2  expressed in alveolar type II cells and codes for Na-Pi IIb sodium-dependent phosphate transporter. 6,7 This protein transports the phosphorus ion from the alveolar space into the alveolar type II cells. Etiology and Genetics

5. As alveolar type II cells are unable to clean up the phosphorus ion from the alveolar space resulting in its accumulation and forming microliths rich in calcium phosphate. No sex predilection . 5 NPT2b also expressed in gut, breast, liver, testes, prostate, kidney, ovaries, pancreas. Parental consanguinity will be present in several cases. Etiology and Genetics

6. Pathology 9

7.  Mostly diagnosed incidentally during radiography of the chest for other reasons. Many patients have no clinical symptoms. Dyspnoea, nonproductive cough, chest pain and asthenia. Hemoptysis and pneumothorax are also reported. Clinical Features

8. Pulmonary fibrosis, respiratory failure and cor pulmonale . Blood levels of calcium - normal Smoking and infection may accelerate disease progression.

9. The diagnosis can be made with confidence from the classic radiographic pattern and the striking radiological and clinical dissociation. Isotopic bone imaging tracer studies can trace the pulmonary uptake of  99m   Tc diphosphonate .  Investigations

10. Open lung biopsy, needle biopsy, transbronchial biopsy and bronchoalveolar biopsy under CT scan guidance. Lung biopsy - most definitive procedure for confirmation of PAM. 18-FDG PET in pulmonary alveolar microlithiasis - inflammatory pathology.

11. Routine blood biochemistry including serum calcium concentration, hepatic, renal and functions are usually normal. Identification of the SLC34A2 gene mutation.  Serum concentrations of the surfactant proteins A and D are elevated - markers to monitor the activity and progression of the disease. Spirometry shows restrictive pattern.

12. Extrapulmonary

13. Lymphocytic interstitial pneumonitis Pericardiac cyst Non-Hodgkin lymphoma Antiphospholipid syndrome Discoid lupus, rheumatoid arthritis, psoriasis, osteopetrosis , Sjogren syndrome Hypertrophic pulmonary osteoarthropathy , and pectus excavatum , diaphyseal aclasis and autosomal recessive Waardenburg-anophthalmia syndrome. Milk alkali Syndrome 15 Associations 17,19

14. No definite treatment is available. Home oxygen therapy Disodium etidronate - inhibits the micro crystal growth of hydroxy -apatite - dose of 10 mg / kg per day orally - 1 year - considerable regression of the calcific densities 21 . This therapy remains controversial given the limited number of reports in the literature . Treatment 16-21

15. The therapeutic bronchoalveolar lavage (BAL) is not helpful in PAM unlike PAP. Corticosteroids are generally considered to be ineffective. Lung transplantation remains the only possible treatment for end-stage disease. The longest survival for PAM treated by transplantation is 15 years without recurrence . Bilateral lung replacement is preferred. To date, no recurrence after transplantation has been reported, confirming that PAM is caused by a local alteration in the alveolar metabolism.

16. Some authors have reported survival of 20 yrs Few cases with a follow-up period of 40 yrs after the diagnosis have been reported However, most cases only have up to 10 yrs of follow-up time after the initial diagnosis Most of the patients of PAM die of progressive respiratory insufficiency. Prognosis 18

17. Ferreira Francisco FA, Pereira e Silva JL, Hochhegger B, Zanetti G, Marchiori E. Pulmonary alveolar microlithiasis . State-of- theart review. Respir Med . 2013;107:1–9. Harbitz F. Extensive calcification of the lungs as a distinct disease. Arch Intern Med 1918;21(1):139–46 Puhr L. Mikrolithiasis alveolaris pulmonum . Virchows Arch Pathol Anat 1933;290(1):156–60. Castellana G, Carone D, Castellana M. Microlithiasis of seminal vesicles and severe oligoasthenospermia in pulmonary alveolar microlithiasis (PAM): report of an unusual sporadic case. Int J Fertil Steril 2015; 9(1):137–40. Mariotta  S, Ricci A,  Papale  M, et al Pulmonary alveolar microlithiasis : report on 576 cases published in the literature.  Sarcoidosis Vasc Diffuse Lung Dis  2004; 21: 173–181 orut  A,  Senyigit  A,  Ugur  SA, et al Mutations in  SLC34A2  cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis . Am J Hum Genet 2006; 79: 650–656 Huqun , Izumi S, Miyazawa H, et al Mutations in the  SLC34A2  gene are associated with pulmonary alveolar microlithiasis . Am J Respir Crit Care Med 2007; 175: 263–268. Murer  H, Forster I,  Biber  J The sodium phosphate cotransporter family SLC34.  Pflugers Arch 2004; 447:763–767 References

18. Sumikawa H, Johkoh T, Tomiyama N, Hamada S, Koyama M, Tsubamoto M,  et al . Pulmonary alveolar microlithiasis : CT and pathologic findings in 10 patients. Monaldi Arch Chest Dis 2005;63:59-64 Pracyk JB, Simonson SG, Young SL, Ghio AJ, Roggli VL, Piantadosi CA. Composition of lung lavage in pulmonary alveolar microlithiasis . Respiration 1996;63:254-60 Siddiqui NA, Fuhrman CR. Best cases from the AFIP: pulmonary alveolar microlithiasis . Radiographics 2011;31(2):585–90. Felson B. Thoracic calcifications. Dis Chest 1969; 56(4):330–43 Malhotra B, Sabharwal R, Singh M, et al. Pulmonary alveolar microlithiasis with calcified pleural plaques. Lung India 2010;27(4):250–2. Pant K, Shah A, Mathur RK, et al. Pulmonary alveolar microlithiasis with pleural calcification and nephrolithiasis . Chest 1990;98(1):245–6 Portnoy LM, Amadeo B, Hennigar GR. Pulmonary alveolar microlithiasis . An unusual case (associated with milk-alkali syndrome). Am J Clin Pathol 1964;41: 194–201. References

19. Giuseppe Castellana, Giorgio Castellana, Mattia Gentile, Roberto Castellana, Onofrio Resta European Respiratory Review 2015 24: 607-620 Kashyap S, Mohapatra PR. Pulmonary alveolar microlithiasis . Lung India 2013;30:143-7 Åsa Lina M. Jönsson , Ulf Simonsen , Ole Hilberg , Elisabeth Bendstrup European Respiratory Review 2012 21: 249-256; Atsushi Saito, MD, PhD a,bFrancis X. McCormack, MD. Researchgate . June 2016 Samano MN, Waisberg DR, Canzian M, et al. Lung transplantation for pulmonary alveolar microlithiasis : a case report. Clinics (Sao Paulo) 2010; 65: 233–236 Ozcelik U, Yalcin E, Ariyurek M, et al. Long-term results of disodium etidronate treatment in pulmonary alveolar microlithiasis . Pediatr Pulmonol 2010; 45(5):514–7 References