A 55 years old man with pulmonary alveolar microlithiasis

Abstract

Pulmonary alveolar microlithiasis (PAM) is a very rare diffuse chronic lung disease characterized by deposition of small spherules of calcium phosphate within the alveolar cavity. The disease is usually seen from birth up to 40 years of age and is usually diagnosed incidentally during radiography of the chest for other reasons. Most of patients are asymptomatic or having very mild symptoms and the majority of patients either have normal or restrictive pulmonary function test. Clinically, the course of the disease is different; it remains static in few patients or it may progress to pulmonary fibrosis, respiratory failure and cor pulmonale in others. In this case report, we present a 55-year-old man who presented with moderate shortness of breath which has progressed from mild symptoms with in the previous years. His chest high-resolution CT scan showed diffusely scattered, ill-defined little shadowy micronodules which involve the left lung; lingula and left lower lobe in particular. A lung biopsy confirmed the diagnosis of PAM. He was followed up for 1 year with treatment by steroid and alendronate, and no progression was noticed in fact improvement in pulmonary function test noticed. This is the first case report of PAM in Kurdistan.

INTRODUCTION

Pulmonary alveolar microlithiasis (PAM) is a very rare diffuse and chronic lung disease, characterized by the presence or deposition of small spherical calcium phosphate bodies containing concentric calcareous lamellas in pulmonary alveoli.[1,2,3,4] It was first named in 1933 by Puhr.[5] Although the etiology still remains not clear, PAM is considered to have an autosomal recessive pattern caused by mutations of the solute carrier family 34 (sodium phosphate), member 2 gene (the SLC34A2 gene), which encodes a sodium phosphate cotransporter.[6,7]

CASE REPORT

A 55-year-old man presented to our department with moderate to severe shortness of breath and dry cough that had worsened over the previous few years. Initially he became short of breath during moderate exertion and later he had shortness of breath even at rest. He denied having any history of recent respiratory tract infection and old chronic infections like tuberculosis. Furthermore, he had a slight cough with minimal sputum production. He has never smoked. He did not have history of any chronic drug use or any chronic medical problems apart from the shortness of the breath. He denied contact with any animal or bird.

Vitals were within normal range, he had coarse crackles mainly at the basal and middle zone of the left lung. The hemoglobin, total and differential white cell counts were within normal range. A full blood count revealed an elevated erythrocyte count of 6.05 × 10⁶ ml^-1 and Hematocrit 55%. Arterial blood gas analysis values in room air were: pH: 7.43, PaO₂: 51 mmHg, PaCO₂: 29 mmHg, HCO₃: 16 mmol l^-1 and O₂ saturation 87%. Pulmonary function tests revealed typical features of a restrictive defect with a reduced total lung capacity of 56% and vital capacity of 46%, and a forced expiratory volume in 1 s/forced vital capacity (FEV₁ /FVC):100. Echocardiography showed severe pulmonary hypertension, 82 mmHg, a dilated right heart and moderate tricuspid regurgitation. Liver and renal function tests were also within reference limits. Serum calcium and phosphate levels were normal. Moreover, skin tests for tuberculosis and studies for acid-fast bacilli were negative and also there was negative urinalysis. Additionally, the inflammatory markers like ESR, CRP and even Ferritin were within normal range. The plain chest X-ray films revealed a diffuse symmetric dense, micronodular (“sand-storm”) pattern mainly on the left side [Figure 1]. A high-resolution CT (HRCT) scan was obtained in the supine position at maximal inspiration at 10 mm intervals. All scans were photographed with window/level settings of 770/10, 1730/2810 and 1910/2500 Hounsfield Units. The examination showed diffuse symmetric lung abnormalities characterized by ground-glass attenuation and septal thickening with calcified nodules, resulting in a crazy-paving pattern. Subpleural calcification was also seen [Figure 2a and b]. Bronchoscopy and BAL were unremarkable. The patient had a transbronchial lung biopsy and histology revealed round, concentrically laminated microliths in the alveoli, which were periodic acid-Schiff (PAS) positive in keeping with the diagnosis of PAM. He was treated with Alendronate 70 mg once weekly, steroid initially as prednisolone 30 mg/day reduced over a month to 10 mg/day, with further reduction over coming months until we stopped it completely and the total duration for steroid use was 1 year, he is still on alendronate. Furthermore, with the current treatment his PFT (FEV₁ and VC) improved by 10% after a year of treatment.

Figure 1.

Illustrates the plain chest X-ray films which revealed a diffuse symmetric dense, micronodular (“sand-storm”) pattern mainly on the left side

Figure 2(a and b).

The HRCT scan of the chest showed diffuse symmetric lung abnormalities characterized by ground-glass attenuation and septal thickening with calcified nodules, resulting in a crazy-paving pattern. Subpleural calcification was also seen

DISCUSSION

The main feature of PAM is widespread laminated calcipherites in the alveolar spaces in the absence of any known disorder of calcium metabolism.[8,9] Patients may remain asymptomatic for many years and do usually become symptomatic between the third and fourth decades.[8,10,11] The clinical presentation usually illustrate a restrictive pattern of lung disease as seen in our patient.[8,10] In the early course of the disease pneumothorax may be observed. Adult patients commonly show progressive deterioration of the pulmonary function and death usually occurs in mid-life because of respiratory failure associated with cor pulmonale.[8,12] The chest radiograph usually shows small innumerable, widespread, and calcified nodules, which tend to be more at the base. HRCT scan has assisted in characterization of the imaging of the disease and can be beneficial in diagnosis. Ground-glass opacities due to volume averaging of tiny microliths are a common and major finding in the literature. Subpleural linear calcification and nodular fissural thickening are also usual findings.[9,10,13,14]

Although the imaging can help in diagnosing the disease but the lung biopsy is the best for definitive diagnosis.[14] Furthermore, Sahoo et al. recommend that (18) F-sodium fluoride PET/CT is a superior modality in characterization and assessment of the extent of disease in PAM compared to all other non-invasive imaging modalities thus (18) F-sodium fluoride PET/CT should be the investigation of choice in PAM.[15]

There is no known effective treatment for PAM, with the exception of lung transplantation.[16] To our knowledge, recurrence of the disease after lung transplantation has not been reported. Observational studies have found therapeutic BAL to be ineffective,[17,18,19] except for symptomatic improvement in one case, without improvement in conventional pulmonary radiography and HRCT.[20] Corticosteroids are generally considered to be ineffective. However, only a few authors have reported on the effect of corticosteroids.[7]