Pulmonary hypertension (PH) is defined as mean pulmonary arterial pressure (mPAP) >20 mmHg instead of mPAP ≥25 mmHg [1]. Pulmonary alveolar microlithiasis (PAM) is a rare disease characterised by the widespread intra-alveolar accumulation of microliths and rarely causespulmonary hypertension(PH). It is caused by mutation of the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells which is located on chromosome 4p15.2 [2]. It presents early till 5^th decadeand very rarely in 6th decade. Majority of patients have family history (1/3^rd) with no complaints at the time of diagnosis. Other Common Presentations include dyspnoea (24 percent), non-productive cough (14%), chest pain (6%), and asthenia (3%)[3]. The severity does not correlate with radiographic severity [4]. Here we present a rare case of PAM in elderly person in the 6th decade of life who was found to have Sand like calcification on chest X-ray during evaluation of his dyspnoea. 

Case Report 

A 59 years old male shopkeeper with Primary hypertension, Diabetes mellitus- II presented with progressive dyspnoea on exertion forsix months (mMRC grade I àmMRC grade III), dry cough for 01 month.He was asymptomatic for Paroxysmal Nocturnal Dyspnoea, Chest pain, Palpitations, Syncope, Pre- syncope, Pedal edema, Cyanosis, haemoptysis, fever, joint pains, skin rash, subcutaneous nodules, weight loss, chronic exposure to silica or Pets. On examination he was hemodynamically stable with tachypnea (respiratory rate of 28/min), Hypoxia (SpO2 88% on room air with further decline in SpO2 to 77% on 6 m walk test), bilateral grade III clubbing (Figure 1) raised JVP, apex beat localised to 5th ICS, 1 cm lateral to mid clavicular line, parasternal heave was present with palpable second heart sound. 

Figure 1: Sowing Grade 3 Clubbing in both Upper and Lower Limbs

Chest examination revealed bilateral crackles till mid scapular region. There was hepatomegaly with firm consistency. On evaluation haematological, renal function test, renal function test including electrolytes,ECG were normal. ABG showed hypoxia (pH- 7.40, pO2-60, pCO2- 35, Lac- 0.5 and HCO3- 20.5). Chest X-ray showed sandpaper like calcification throughout the lung field (Figure 2) and HRCT chest revealed numerous sand-like calcifications scattered in bilateral lung fields with upper lobe preponderance. 

Figure 2: Multiple Small Sand-Like Calcifications in Bilateral Lung Fields (Sandstorm Appearance) Obscuring the Cardiac Silhouette and Diaphragm

Crazy Paving patterns of GGOs were noticed in both lung fields (Figure 3-4) Small subpleural para-septal areas of emphysemain bilateral lung fields suggestive of “Black Pleura sign” (Figure 4) with dilated Main pulmonary artery diameter of 40.5 mm. These findings were suggestive of pulmonary alveolar microlithiasis. On 2D Echoright atrium and right ventricle was dilated with mild tricuspid regurgitation and normal ejection fraction indicative of hypertensive heart disease and Pulmonary arterial hypertension. Lung function test revealed a mild restrictive pattern. He was managed as a case PAH due to PAM was managed with a short course of diuretics, Calcium channel blocker and other supportive measures after consultation. There was subjective improvement in the symptoms. He is being followed up for worsening of pulmonary function test. He is also planned to be registered for lung transplant which is the definite treatment of the definitive treatment for PAM is lung transplant.The other family members were counselled and screening. This case highlights the rare cause of pulmonary arterial hypertension as pulmonary alveolar microlithiasis.

Figure 3 and 4: HRCT Chest Showing Diffuse Sand-Like Calcifications with Upper-Lobe Predominance and Crazy-Paving Pattern

Table 1: Detailed Evaluation of the Patient

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterised by the widespread intra-alveolar accumulation of minute calculi called microliths. It is also one of the rare causes of pulmonary hypertension(PH) due to mutation of the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells on chromosome 4p15.2[2]. Incidence is reported only in the case series with a slight male predominance (50.2%) as compared to female (41.2%) with similar results from the other part of the country. The age of Presentation is generally under the age of 50 years[5]. Our patient had unusual presentation of PAM in elderly in 6^th decade. Also, the Majority of patients are asymptomatic at the time of diagnosis [4].  Dyspnoeais the commonest symptom of presentation in our case as well as others too [3]. Generally, the diagnosis is confirmed on ​​HRCT which reveals micronodular calcifications primarily located along Broncho vascular bundles, and subpleural and peri lobular regions [6], Diffuse ground glass opacities are often present [6], Calcific thickening of the interlobular septa may be seen, as well as subpleural cystic changes [7] which is consistent with our case. Hence bronchoscopy was not done. It has been well established that bronchoscopy is usually not needed for diagnosis, bronchoalveolar lavage (BAL) and transbronchial biopsy can be useful if the diagnosis is uncertain and in cases with Lamellar microliths which have been identified in lavage fluid and on transbronchial biopsy [3]. The differentials considered in this case was diffuse pulmonary ossification, Metastatic pulmonary calcification, Sarcoidosis, tuberculosis and Silicosis which was ruled out using suitable test (Table 1). However, in our case the patient could not afford the test hence genetic testing was not done. The screening X-rays of the family members were done which were normal. This disease is autosomal recessive in inheritance so the family members were counselled about the consequences of the disease and to avoid the consanguineous marriages. There is no established therapy for PAM[2]. Lung transplantation has been successful in the treatment of PAM and recurrence of PAM in the transplanted lungs has not been reported with follow up out to 15 years [8]. Few investigational therapieslike bisphosphonates, Etidronate and Sodium thiosulphate have shown benefit in case reports[8-9]. PAM is generally slow, and it often takes decades before patients develop symptoms or reduced pulmonary function and fatal outcome [4]. Due to no definite treatment available and lack of Lung transplant our patient is under close follow up with 03 monthly Pulmonary function test. 

The present case is a very rare hereditary cause of Dyspnoea with pulmonary arterial hypertension i.e. Pulmonary alveolar microlithiasis presenting late in the 6th decade of life being managed conservatively and under close follow up and he is planned for investigational therapy if worsening.

1. Sumimoto, K et al. “Optimal cut-off of tricuspid regurgitation velocity according to the new definition of pulmonary hypertension—its use in predicting pulmonary hypertension.” Circulation Reports, vol. 2, no. 10, 2020.

2. Castellana, G et al. “Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide.” European Respiratory Review, vol. 24, no. 138, 2015, pp. 607–620.

3. Mariotta, S et al. “Pulmonary alveolar microlithiasis: review of Italian reports.” European Journal of Epidemiology, vol. 13, 1997.

4. Escribano, P et al. “Characterisation of pulmonary arterial hypertension patients initiating a new pulmonary arterial hypertension specific therapy in the context of age: insights from EXPOSURE.” The Journal of Heart and Lung Transplantation, vol. 40, no. 4, 2021, pp. S109.

5. Delic, J.A. et al. “Pulmonary alveolar microlithiasis.” Radiographics, vol. 36, no. 5, 2016, pp. 1334–1338.

6. Khaladkar, S.M. et al. “Pulmonary alveolar microlithiasis—clinico-radiological dissociation: a case report with radiological review.” Journal of Radiology Case Reports, vol. 10, 2016.

7. Crespo, M. “Lung transplantation for pulmonary alveolar microlithiasis.” The Journal of Thoracic and Cardiovascular Surgery, 2010.

8. Cakir, E et al. “Response to disodium etidronate treatment in three siblings with pulmonary alveolar microlithiasis.” Respiration, vol. 89, 2015.