18.14.10 Pulmonary alveolar microlithiasis 4265 S.

18.14.10 Pulmonary alveolar microlithiasis 4265 S.J. Bourke

18.14.10  Pulmonary alveolar microlithiasis 4265 Prevention and management Prevention of lipoid pneumonia is focused on minimizing any tendency to aspiration associated with impaired swallowing, and in persuading the user of vegetable and mineral oils to adopt alternative habits. Stopping further exposure to exogenous lipids is also important in the treatment of the disease. Corticosteroids have been used where there is associated inflammation, but their effectiveness is doubtful. In acute massive lipoid pneumonia treatment is largely supportive. Therapeutic bronchoalveolar lavage has occasionally been used in an attempt to remove lipid from the alveoli. Endogenous lipoid pneumonia Lipoid pneumonia is a feature of obstructive pneumonitis, particu- larly where there is occlusion of a bronchus by a carcinoma, but also in diseases characterized by bronchiolitis or chronic interstitial in- flammation. In this situation the lipid is endogenous, consisting of cholesterol released from decaying cells and surfactant, which are taken up by macrophages. Macroscopically the area of lung shows consolidation with a characteristic yellow discolouration as a ‘chol- esterol pneumonia’ or ‘golden pneumonia’. Histologically there is an abundance of lipid-​laden macrophages with cholesterol crystals on polarized light microscopy. Excess lipid in the lungs is also a feature of Niemann–​Pick lipid-​storage disease and fat embolism to the lungs from frac- tured bones. Therefore, although lipid-​laden macrophages in bronchoalveolar lavage fluid are a characteristic feature of ex- ogenous lipoid pneumonia, endogenous causes also need to be considered. FURTHER READING Ameille J, et al. (1995). Respiratory symptoms, ventilatory impairment and bronchial reactivity in oil mist-​exposed automobile workers. Am J Indust Med, 27, 247–​56. Balakrishnan S (1973). Lipoid pneumonia in infants and children in South India. Brit Med J, 4, 329–​31. Betancourt SL, et al. (2010). Lipoid pneumonia: spectrum of clinical and radiologic manifestations. Am J Roentgol, 194, 103–​9. Borrie J, Gwynne JF (1973). Paraffinoma of lung: lipoid pneumonia. Thorax, 28, 214–​21. Brander PE, et al. (1992). Fire-​eater’s lung. Eur Respir J, 5, 112–​14. Brown AC, et al. (1994). Exogenous lipoid pneumonia due to nasal application of petroleum jelly. Chest, 105, 969–​70. Chang HY, et al. (1993). Successful treatment of diffuse lipoid pneu- monitis with whole lung lavage. Thorax, 48, 947–​8. Corwin RW, Irwin RS (1985). The lipid-​laden alveolar macrophage as a marker of aspiration in parenchymal lung disease. Am Rev Respir Dis, 132, 576–​81. Gondouin A, et  al. (1996). Exogenous lipid pneumonia:  a retro- spective multicentre study of 44 cases in France. Eur Respir J, 9, 1463–​9. Hadda V, Khilnani GC (2010). Lipoid pneumonia:  an overview. Expert Rev Respir Med, 4, 799–​807. Kiselina AM, et al. (2011). Analysis of fatty acids in ghee and olive oil and their probable causal effect in lipoid pneumonia. J Med Biochem, 30, 141–​7. Kitchen JM, et al. (2008). Perils of fire eating. Thorax, 63, 401. Lee JS, et al. (1999). Exogenous lipoid pneumonia: high-​resolution CT findings. Eur Radiol, 9, 287–​91. Miller GJ, et  al. (1971). The lipoid pneumonia of blackfat tobacco smokers in Guyana. Q J Med, 40, 457–​70. Oldenburger D, et  al. (1972). Inhalation lipoid pneumonia from burning fats. JAMA, 222, 1288–​9. Segev D, et  al. (1999). Kerosene-​induced severe acute respiratory failure in near drowning: reports on four cases and review of the literature. Crit Care Med, 27, 1437–​40. Venkatnarayan K, et  al. (2014). Diesel siphoner’s lung:  exogenous lipoid pneumonia following hydrocarbon aspiration. Lung India, 31, 63–​6. 18.14.10  Pulmonary alveolar microlithiasis S. J. Bourke ESSENTIALS Pulmonary alveolar microlithiasis is characterized by the depos- ition of calcium phosphate in the alveolar air spaces as a result of mutations of the SLC34A2 gene. The patient is often symptom-​ free when the diagnosis is made after a chest radiograph is taken incidentally and reveals calcified micronodules, but typically the disease progresses to respiratory failure over about 10–​20 years. Etidronate has led to improvement in some cases that have been detected early. Lung transplantation is the main option in ad- vanced disease. Fig. 18.14.9.1  Section of lung showing exogenous lipoid pneumonia due to aspirated paraffin. There is interstitial fibrosis containing oil vacuoles which are enclosed within multinucleated giant cells (haematoxylin and eosin stain, medium magnification). By courtesy of Dr T. Ashcroft.

section 18  Respiratory disorders 4266 Introduction Pulmonary alveolar microlithiasis is a rare lung disease in which calcium phosphate is deposited within the alveolar spaces forming microliths, as a result of mutations of the SLC34A2 gene. The diffuse microliths give a characteristic appearance of calcified micronodules on a chest radiograph, sometimes described as ‘sandstorm lung’. About 1200 patients with pulmonary alveolar microlithiasis have been reported in the medical literature since its initial description in 1918. The disease occurs worldwide, but predominantly in Turkey, Japan, India, America, and the Middle East, and about 25% of re- ported cases have been of Turkish descent. Pathogenesis The disease is an autosomal recessive condition caused by muta- tions of the solute carrier family 34, member 2 gene, SLC34A2, on the short arm of chromosome 4. Several different mutations have been described, including frameshifts, chain terminations, and amino acid substitutions. The gene has 13 exons and encodes a 690-​amino acid protein, the sodium-​phosphate cotransporter, which is primarily expressed in the apical membrane of alveolar type II cells. The recycling of surfactant releases phosphate into the alveoli, and SLC34A2 gene mutations result in impaired clear- ance of phosphate by the sodium-​phosphate transporter. The ac- cumulated phosphate binds calcium, forming calcium-​phosphate microliths, which are typically about 1 mm in diameter. Initially they are predominantly located in the lower lobes, but progress to involve all areas of the lungs and extend to fill the entire alveolar space, leading to damage to the alveolar membrane and fibrosis, with impairment of gas exchange. The diffuse micronodular calcification of pulmonary alveolar microlithiasis is very different from dystrophic or metastatic lung calcification seen in other circumstances. Dystrophic lung calcifi- cation consists of calcium deposition in tissue damaged by infec- tions such as tuberculosis, histoplasmosis, or varicella pneumonia, or diseases such as chronic sarcoidosis, silicosis, or longstanding mitral stenosis. Metastatic lung calcification refers to the phenom- enon where there is calcium deposition in the interstitium of normal lungs as a result of hypercalcaemia, primary or secondary hyper- parathyroidism, vitamin D intoxication, diffuse myelomatosis, or chronic renal failure. In pulmonary alveolar microlithiasis there is no abnormality of calcium metabolism and serum calcium and phosphate levels are normal. In most cases of pulmonary alveolar microlithiasis the lungs are the only organs affected, but the gene is expressed to a lesser extent in other tissues, and calcium deposits have been occasionally found in the kidneys, seminal vesicles, urethra, gallbladder, heart valves, and arteries. Clinical features and diagnosis The diagnosis is often made before symptoms have developed when a chest radiograph is performed for other reasons, and shows a dramatic typical ‘sandstorm’ pattern of diffuse bilateral calcified micronodules (Fig. 18.14.10.1). The dramatic radiographic appear- ances are typically out of proportion to the absence of symptoms or signs at this stage. However, the disease gradually progresses over several decades, with symptoms typically arising at about the age of 30–​40 years. Breathlessness and a dry cough are the dominant symptoms. Haemoptysis and chest pain occur occasionally. As the disease progresses lung function tests show a restriction of lung vol- umes with impaired gas diffusion. In advanced stage disease respira- tory failure develops with hypoxaemia and hypercapnia, pulmonary hypertension, and right ventricular failure. Crackles, clubbing, and signs of respiratory failure are late features. In some cases, subpleural cysts give rise to recurrent pneumothoraces, and pleural adhesions may become prominent. The diagnosis can usually be made from the characteristic radiographic appearances of profuse, small, calcified nodules (Fig. 18.14.10.1). Initially the calcified micronodules are predom- inantly situated in the mid and lower zones, but gradually these progress to all areas. The pattern is different from other causes of calcification such as chronic sarcoidosis, healed calcified varicella pneumonia, pneumoconiosis, histoplasmosis, and miliary tuber- culosis, or chronic renal failure. Computed tomography demonstrates the numerous sand-​like calcifications and sometimes also shows subpleural cysts and fi- brosis. Lung biopsy is rarely necessary for diagnosis, but typically shows numerous intra-​alveolar rounded calcified microliths. DNA sequencing of the SLC34A2 gene can be undertaken, and other family members can be tested for the disease. Serum levels of calcium and phosphate are usually normal, but elevated serum concentrations of surfactant protein SP-​A and SP-​D Fig. 18.14.10.1  A chest radiograph showing the typical ‘sandstorm’ appearances of pulmonary alveolar microlithiasis with micronodular calcific densities throughout the lungs. http://​www.ispub.com/​ostia/​index.php?xmlFilePath=journals/​ijpm/​vol9n1/​pam.xml