==== Front Ann Saudi MedAnn Saudi MedAnnals of Saudi Medicine0256-49470975-4466King Faisal Specialist Hospital and Research Centre 1829965710.5144/0256-4947.2008.304asm-4-303aWhat's Your Diagnosis?Diagnosis: Pulmonary alveolar microlithiasis after exposure to mustard gas Rajabi Mohammad A. From the Department of Surgery, Isfahan University of Medical Science, Isfahan, IranCorrespondence and reprints: Mohammad Ali Rajabi, MD, Associate Professor of Surgery, Isfahan University of Medical Science Sofe St. Al Zahra Hospital, PO Box 901 Isfahan, Iran, T: +983-11-668-7611, F: +983-11-668 7611, rajabi@med.mui.ac.irJul-Aug 2008 28 4 1 2 01 1 2008 Copyright © 2008, Annals of Saudi Medicine2008This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. ==== Body Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology and pathogenesis. 2,3 This disorder is characterized by intra-alveolar development and deposition of microliths or calcispherytes containing calcium phosphate.2,3 The age range of patients is from newborn to 80 years. The mean age at presentation is in the third to fourth decade with no sexual predominance, but in approximately half the reported cases a familial pattern has been found. Most of the patients have few or no symptoms despite the gross radiographic changes. The dissociation between the definite x-ray pattern of the lungs and the relatively poor clinical symptoms is the most common characteristic of this disease. However, a certain degree of dyspnea with productive cough may occur together with a sporadic hemoptysis, thoracic pain and sometimes spontaneous pneumothorax.4,5 The lungs are hardened with associated deterioration of pulmonary hypertension and thus cor pulmonale occurs.6 Pulmonary fibrosis is also observed in association with PAM.7,8 In such cases, as in our patient, a posteroanterior chest x-ray shows a dissemination of radio-opaque nodules of almost equal sizes and the lungs appear to be sprinkled with sand. Very fine sand-like micronodulations with calcified densities were observed throughout both lungs fields (Figure 1). Histological examination demonstrated onion-skin-like microliths occupying the alveoli. Amorphous eosinophilic material filled the alveoli (Figure 2). Some authors suggested that PAM may be a peculiar exudative response to a variety of insults, which include pneumonia and rheumatic fever.9–11 Our report describes PAM after exposure to mustard gas. In other cases of microlithiasis sandstorm-associated, the exact cause has not been proved; only in 50% of cases has a genetic or familial factor been reported, but other causes have not been confirmed. In all cases, either acquired or genetic, it can be assumed that there is a disorder in the bronchial cilia or alveolar endothelium. Therefore, it can be concluded that acquired causes can induce enzymatic disorders similar to those in genetic defects.4 Although the clinical features of this disease have been well described, the mechanism which may induce microliths to form is unknown. Inhalation of specific powders was thought to be involved in the origin of microliths as some patients lived in the same rural district and worked on the same farmlands. In addition, the pattern of serial scans clearly indicated that the lung mucociliary function was impaired in patients with microlithiasis. This may suggest that slowing of the clearance may represent a pathogenetic factor capable of favoring the formation of alveolar microliths. In patients who smoke “snuff “ (a particular mixture of tobacco and oriental gum) this hypothesis is favored. Finally, cases of PAM secondary to lung cancer, tubercular remains and pleural mesothelioma have also been reported.4 The etiology of pulmonary alveolar microlithiasis has remained obscure;1–15 however, familial occurrence is a notable feature and has been observed in more than half of reported cases.15 However, our patient did not have a familial history of PAM or any other pulmonary disorders. His previous lab tests and chest roentgenograms showed a normal pulmonary condition before the exposure to mustard gas. His symptoms and roentgenographic changes appeared after the exposure to mustard gas. The pattern observed in his chest x-ray consisted of disseminated uniform fine radio-opaque nodules. Our initial diagnosis was miliary tuberculosis as the radiologic pattern is somewhat similar.11–14 However, as the patient did not have other features of tuberculosis, the diagnosis of microlithiasis was suggested and then confirmed by lung biopsy. The diagnosis of microlithiasis can be confirmed by bronchoalveolar lavage (BAL) or lung biopsy.13,14 It is notable that a miliary pattern on chest roentgenograms may be seen in disseminated tuberculosis, fungal infection, neoplastic processes, sarcoidosis, pneumoconiosis, hemosiderosis, amyloidosis and metastatic pulmonary calcification associated with chronic renal failure and hemodialysis.3,14 These diseases, however, are usually associated with severe respiratory symptoms, whereas the peculiar feature of PAM is its asymptomatic nature and the paucity of physical signs, which are difficult to correlate with the gross roentgenographic abnormality.15,16 For treatment of pulmonary microlithiasis, the use of diphosphonate to reduce calcium phosphate precipitation in pulmonary alveolus is suggested.1–17 This treatment would have induced only a trivial improvement in the x-ray pattern without any improvement in the evaluative course of the disease.3–16 The use of steroids is ineffective and the use of therapeutic bronchoalveolar lavage fluid (BAL) is controversial.1–19 There are reports of lung transplantation for end-stage lung diseases.13, 19 Figure 1 Chest x-ray showing bilateral apical bullae, diseeminated sand-like discrete radio-opaque micronodules predominantly in the lower zones. Lungs appear to be sprinkled with sand. Figure 2 Photomicrograph showing laminated appearance of a microlith (hematoxylineosin, ×40). ==== Refs REFERENCES 1 Gocmen A Toppare MF Kiper N Treatment of pulmonary alveolar microlithiasis with a diphosphonate Respiration 1992 59 250 254 1485012 2 Castellana G Lamorgese V Pulmonary alveolar microlithiasis Respiration 2003 70 549 555 14665786 3 Mariotta S Ricci A Papale M Pulmonary alveolar microlithiasis: report on 576 cases published in the literature Sarcoidosis Vasc Diffuse Lung Dis 2004 21 173 181 15554073 4 Lauta MV Pulmonary alveolar microlithiasis: an overview of clinical and pathological features together with possible therapies Respir med 2003 97 1081 1085 14561014 5 Shishido S Toritani T Nakano H A case of alveolar microlithiasis which developed spontaneous pneumothorax due to progression of emphysematous bullae during 34 years after established diagnosis Nihon Kyobu Shikkan Gakkai Zasshi 1993 31 881 885 8366628 6 Synetos A Dilaveris P Gialafos E severe pulmonary hypertension due to pulmonary alveolar microlithiasis Int J Cardiol 2006 26 396 397 7 Corut A Senyigit A Ugur SA Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis Am J Hum Genet 2006 79 650 656 16960801 8 Castellana G Gentile M Castellana R Pulmonary alveolar microlithiasis: clinical features, evolution of the phenotype, and review of the literature Am J Medical Genetics 2002 111 220 224 9 Sampsonas F Karkoulias K Kaparianos T Tsiamita M Pulmonary Alveolar Microlithiasis in a Patient with Rheumatic Valvular Heart Disease Am J Med Scien 2007 334 128 130 10 Brandenburg VM Schubert H images in clinical medicine: pulmonary alveolar microlithiasis N Engl J Med 2003 348 1555 1558 12700375 11 Haruko M Isao Y Miyuki K A case of pulmonary alveolar microlithiasis with a high concentration of pulmonary surfactant apoproteins A and D in serum Respiration Research 2000 19 176 180 12 Þenyiðit A Yaramis A Gurkan F Pulmonary alveolar microlithiasis: a rare familial inheritance with report of six cases in a family. 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