Pulmonary alveolar microlithiasis

BY. J. Dis. Chest (1978) 72, 151

PULMONARY

ALVEOLAR G. S. THIND

Department

of

MICROLITHIASIS

AND J. L. BHATIA

Tuberculosis and Chest Diseases, Medical Amritsar, India

College Hospital,

Summary Three cases of pulmonary alveolar microlithiasis stage of this condition. Two were siblings.

are reported

at the symptom-free

Pulmonary alveolar microlithiasis is rare and less than 100 cases have been reported in the world literature. Although the radiological picture is diagnostic, many cases are mistaken for other disorders with a miliary radiological pattern, particularly when there are a few symptoms and clinical signs. We have found six patients with this disease in a short period. Three of these have been reported previously (Bhatia & Thind 1976). We report here three more cases, two of whom are siblings. Case Reports Case 1 A man aged 18 years, came to the Tuberculosis and Chest Diseases Hospital, Amritsar, on 10 May 1975 complaining of slight haemoptysis three days previously. He had no other complaint. A chest radiograph revealed bilateral diffuse sand-like opacities, more marked in the middle and lower zones. The heart shadow was normal. No abnormality was detected on physical examination. He was admitted with the diagnosis of pulmonary alveolar microlithiasis for further investigation. The Mantoux test with l/1000 O.T. was negative. Repeated sputum examination was negative for acid-fast bacilli, using both the smear and concentration method was negative. Sputum and laryngeal swab cultures did not yield tubercle bacilli. The skin bleeding time was 3 minutes and clotting time 34 minutes. All members of his family had normal chest radiographs. Ventilatory function tests showed a forced expiratory volume in one second (FEVr) of 3 litres (predicted 4.3 litres) and a vital capacity (VC) of 3.5 litres (predicted 5.2 litres). The FEVr/VC ratio was 86 “/ . Eleven days after admission to hospital he underwent a right thoracotomy and biopsy of the right lower lobe. The texture of the right lung was gritty. Microscopy showed the typical appearance of pulmonary alveolar microlithiasis (Fig. 1). About 2530% of the alveoli contained microliths. The alveolar walls were normal and there was no evidence of fibrosis. Under high magnification (Fig. 2) the microliths show concentric laminations. Case 2 A boy aged 14 years was referred on 22 February 1975 when abnormalities on his chest radiograph had failed to clear following 18 months’ antituberculous chemotherapy. Corticosteroids had also been administered during the first six weeks of antituberculous treatment. This boy, although without symptoms, had been thought to have miliary tuberculosis in August 1974 when a chest radiograph, performed before submucosal resection of the nasal septum, 16

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G. S. Thind and J. L. Bhatia

Fig. 1. Microscopical and normal alveolar

Fig. 2. Highly

section of the lung biopsy (Case 1) showing walls

magnified

view of a microlith

showing

typical intera alveolar microliths

typical

concentric

laminations

showed widespread fine, nodular pulmonary infiltrate. The Mantoux test was negative and sputum examinations showed no acid-fast bacilli. All members of his family underwent chest radiographs and one elder sister was found to have a similar radiographic picture, also at first diagnosed as miliary tuberculosis. In February 1975 fine inspiratory crepitations were heard at the base of the right lung. A review of his chest radiographs from August 1974 to February 1975 showed no change in the fine nodular opacities. A typical chest radiograph showed bilateral fine nodulations of calcific density, most marked in the lower and mid-zones, with relative sparing of the apices. There was some confluence of the opacities on the right, obscuring the outline of the right hemidiaphragm. The appearances were considered characteristic of pulmonary alveolar microlithiasis. His Mantoux test was positive in 1975, but repeated sputum examination was negative for tubercle bacilli. Ventilatory function tests were not obtained.

Pulmonary Alveolar Microlithiasis

153

Case 3 A woman aged 24 years was an elder sister of Case 2. As described above, she was at first considered to have miliary tuberculosis on the basis of a radiographic appearance of widespread pulmonary mottling. She was symptom-free when she was given antituberculous chemotherapy and corticosteroids for two months, after which the corticosteroids were stopped and antituberculous therapy alone continued for a further 18 months. In February 1975 physical examination revealed no abnormality. The Mantoux test was positive but repeated sputum examination was negative for tubercle bacilli. Ventilatory function tests were not obtained. The radiographic appearances were typical of pulmonary alveolar microlithiasis. Shortly after seeing us in 1975, this patient and her brother (Case 2) were lost to follow-up. In all the above three cases the haemoglobin, total and differential white cell counts and blood films, the skin bleeding time and clotting time were normal. Examinations of urine and stools were normal. Serum urea and electrolytes, serum albumin and globulin, serum calcium and phosphorus, alkaline phosphatase and liver function tests were all normal. LE cell preparations were negative.

DISCUSSION Most patients with pulmonary alveolar microlithiasis remain symptom-free for many years despite extensive radiological changes. There is some evidence to suggest that the disease begins in early life. We have previously reported mild changes in the lungs of a four-year-old child (Bhatia & Thind 1976). Nevertheless, there are at least two cases on record in which previous chest radiographs were normal (Krokowski & Michel 1966; Rotem et al. 1963), suggesting that in some cases the disease is acquired later in life. The absence of symptoms in the presence of extensive radiological changes for many years is well documented (Sosman et al. 1957; Mandi et al. 1968; Frazer & Pare 1970). Well advanced cases may start with exertional dyspnoea which gradually increases in severity. Later on cyanosis, polycythaemia and slight cough with mucoid expectoration develop; occasionally clubbing of the fingers and in some rare cases haemoptysis may be noted. Respiratory insufficiency ultimately leads to death from heart failure. In most cases the disease is progressive, but it may become arrested, and the clinical state and radiological appearances remain unchanged for months or years (Oka et al. 1966; Frazer & Pare 1970). The progressive nature of pulmonary alveolar microlithiasis has been noted by various authors (Sosman et al. 1957; Al-Damlugi et al. 1973; Tharairajasingam et al. 1975 ; Bhatia & Thind 1976). No progression was apparent in Cases 2 and 3 over 18 months and both remained symptom-free. The characteristic picture of pulmonary alveolar microlithiasis on the chest radiograph is of bilateral sand-like micronodules of calcific density, usually most marked in the middle and lower zones, with relative sparing of the apices. Few other conditions show such a striking disparity between the extensive radiographic appearances and minimal symptoms. Lung biopsy is usually unnecessary to confirm the diagnosis. Despite the relative ease with which this condition can be diagnosed, many cases are not recognized for many years and perhaps not until after death. Many are mistaken for miliary tuberculosis, silicosis, berylliosis, sarcoidosis, lipoidal emboli, haemosiderosis, fungal infections and carcinomatosis. In more than half of the reported cases the initial diagnosis was miliary tuberculosis. The familial occurrence of pulmonary alveolar microlithiasis was first reported by Mikhailov (1954) and emphasized by Sosman et al. (1957). In over half the reported

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cases, a familial incidence has been demonstrated, almost invariably amongst siblings, and only in two instances in a parent and child (Drinkovic et al. 1961). The possibility of congenital error of metabolism at the level of the alveolar surface membrane has been suggested (Caffery & Altman 1965; Sosman et al. 1957). No treatment has been shown to improve the condition. Amongst agents which have been shown to be of no therapeutic benefit are corticosteroids and chelating agents such as sodium versenate. ACKNOWLEDGEMENTS

We are grateful to Dr G. S. Bhatia and Dr B. M. Kalan for their assistance at various stages in investigations of these cases, and to Mrs J. Kearney for secretarial help. REFERENCES S. F., AL-OMARI, M. M. & AL-FAKHRI, S. (1973) Pulmonary alveolar microlithiasis in two siblings in Iraq. Br. J. Dis. Chest 67, 246. BHATIA, J. L. & THIND, G. S. (1976) Pulmonary alveolar microlithiasis. Ind. J. Tuberc. 23, 110. CAFFERY, P. R. & ALTMAN, R. S. (196.5) Pulmonary alveolar microlithiasis occurring in premature twins. Pediatrics, Springfield 66, 758. DRINKOVIC, I., STROHAL, K. & SABLTICA, B. (1962) Pulmonary alveolar microlithiasis. Fortsch. Rontgenstr. 97, 180. FRASER, R. G. & PARE, P. J. A. (1970) Diagnosis of Diseases of the Chest, Vol. II, pp. 1131-4. Philadelphia: Saunders. ~~OKOWSKI, E. & MICHEL, H. (1966) The roentgenogram in the course of microlithiasis alveolaris pulmonum. Fortschr. Rontgemtr. 105, 201. MANDI, L., SINAY, A., KELEMEN, J. T., SZABO, A. & DAYKA, A. (1968) Alveolar microlithiasis. Prax. Pneumol. 22, 230. MIKHAILOV, V. (1954) Pulmolithiasis endalveolaris et interstitialis difusa. f&z. Med. (Moskow) 32, 31. OKA, S., SHIRAISHI, K., OGATA, K., GOTO, Y., YASUDA, T. & HANAGIHARA, H. (1966) Pulmonary alveolar microlithiasis. Report of three cases. Am. Rev. resp. Dis. 93, 612. ROTEM, Y., SOLOMON, M. & HERTZFRANKLENHUIS, M. (1963) Pulmonary alveolar microlithiasis. Ann. paediat. Suppl. 201, 4. SOSMAN, M. D., DODD, G. D., JONES, W. D. & PILLMORE, G. J. (1957) The familial occurrence of pulmonary alveolar microlithiasis. Am. J. Roentgenol. 77, 947. THARAIRAJASINGAM, S., DHARMASENA, B. D. & KASTHURIRATNA, T. (1975) Pulmonary alveolar microlithiasis. Amt. Radiol. 19, 17.5.

AL-DAMLUJI,