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Microlithiasis alveolaris pulmonum
Tubercle, Lond., (1960), 41, 276
276
CASE
REPORT
Microlithiasis Alveolaris Pulmonum By M. H. WATERS from Spynie Hospital, Elgin, Scotland
This very rare disease was first described by Harbitz who published an account of it in 1918. The second case was not reported until 1932. Sosman and others (1957) in an extremely detailed and comprehensive paper described 23 cases seen by them. They stated that they knew of two others not reported. Also described are 22 other cases previously published, of which the authors regarded 20 as being in all probability genuine cases of microlithiasis alveolaris pulmonum and two ofcloubtful authenticity. Of the 24 cases seen by these authors, four were confirmed at necropsy and five by lung biopsy. The remainder were diagnosed by radiographic appearances only. 28 of the 45 cases described by Sosman and his colleagues had no real symptoms and 28 were picked up by routine radiographic examination for the armed forces, pre-employment examination, chest survey programme or as relatives of other cases. Further cases have been described by Manz (1954), Mikhailov (1954), Gilsanz, Palacios and Barrera (1956), Biressi and Casassa (1956), Finkbiner, Decker and Cooper (1957), Foote (1957), Greenberg (1957), Chinachoti and Tangchai (1957), Thomson (1959) and Abdel-Hakim and others (1959); making a total of 58 cases so far reported. Prior to the publication of this paper only five cases are known to have occurred in this country, two of them being brothers. This paper describes two further cases occurring in sisters. 1 Mrs. W. McG., age 31 was first seen on Bth June, 1958. She stated that four weeks previously she had developed a dry cough, which was worse at night. Seven days later she commenced to produce sputum. She also complained of anorexia, lassitude, increasing dyspnoea on exertion, some sweating at night and pain behind the sternum on coughing. She had pneumonia in infancy and again when 13 years of age. She was a healthy looking woman weighing 7 st. 12 Ibs. Fine crepitations were present over the bases of the lungs, especially on the right side. Radiographically there was miliary type of shadowing of all lung fields, most dense at the bases (Fig. 1). Multiple puncture tuberculin test was positive and ESR estimation was 20 mm. in one hour (Westergren). Sputum was negative [01' tubercle bacilli on animal inoculation. It was at first considered that the patient had miliary tuberculosis of the lungs, although she seemed too well. She was admitted to hospital and commenced treatment with 1 g. streptoduocin and 200 mgs, isoniazid daily. On the seventh day she developed an erythematous rash on the trunk and hcr temperature-s-previously normal-rose to 99.8°; so the treatment was changed to PAS and isoniazid. Ten days later the patient took her own discharge, but the same chemotherapy was continued at home. She was seen at the local chest clinic on 25th July. On this occasion she still looked well and her weight hacl increased to 8 st. 2 lbs, Her E.S.R. remained elevated at 22 mm. in one hour (Westergren). She stated that she felt better and had neither cough nor dyspnoea. Crepitations were still detected over the lungs and the x-ray appearances were unaltered. She was with some difficulty persuaded to return to hospital for further investigation on 30th July. The diagnosis of malignant metastases was now considered but no primary growth was found and she also seemed too well to justify this diagnosis. Although the lesions were much too dense and there was no other evidence to support the diagnosis, sarcoidosis was considered to be a faint possibility and she was given 20 mg. prednisolone daily in addition to her chemotherapy, along with 30 units A.C.T.H. gel intramuscularly on two successive days every two weeks. She was discharged from hospital on 11 th August, again at her own request, and against advice and continued her treatment unaltered until December when over three weeks the prednisolone was gradually reduced in dosage and she ceased taking the PAS and isoniazid of her own accord. CASE
MICROLITHIASIS ALVEOLARIS PULMONUM
277
She was examined as an out-patient at monthly in tervals following discharge from hospital a nd appeared to keep quite well, apart from occasional dyspnoea and nocturnal cough which developed 5 months after leaving hospital. Crepitations still persisted over the lung bases and the x-ray appearances remained subs tantially un altered . Sinc e no accurate d iagnosis had so far been made the chest x-rays were sent to Dr. Peter Kerley for his opinion. He thought that the appea ra nces were typical of microlithiasis alveolaris pulmonum and suggested examination of other members of the family as far as possible. One sister, Mrs.]. H . G .
Fro. I. - Case I. Chest radiograph at the start of the illness. (Case 2), was then found also to have microlithiasis alveolaris pulmonum. Neither of the patients had any children. Two married sisters with their fam ilies of two and three chi ldre n were x-rayed and the appearances were normal. Two au nts and three uncles whose ages were 74, 70, BO, 6B and 59 respectively, wer e traced and found to be wel l. They declined examination and it seemed unlikely that they were suffering from microlithiasis alveolaris pulrnonum, T he mother of Mrs. W. MeG. and Mrs.]. H. G. died in her thirties and th e cau se of death was st ated as pulmonary tuberculosis, but it may well have been microlit hiasis alveolari s pu lrnonurn. The fa ther died of diab etes at the age of 50.
278
TUBERCLE
On 31st March, 1959, Mrs. W'. MeG. developed a febrile illness which was diagnosed by her family doctor as 'flu'. She then had a productive cough, increased dyspnoea and pain across the chest. She was admitted to hospital on 5th April at 12.05 a.m, and was obviously extremely ill. Her temperature was subnormal (96.4°), pulse rate 168 and respiration 'H. She complained of frontal headache. She slept for short periods, became unconscious at 6.15 a.m, and died at 7.30 a.m, Unfortunately permission to perform a necropsy was not obtained. CASE
2
Mrs. J. H. G. age 36, (a sister of Case I), was examined on 30th January, 1958 and found to have microlithiasis alveolaris pulmonum. At that time she had a cold with a productive cough and dyspnoea on exertion. Her general condition was good, but there was some cyanosis of the face and hands ancl
FIG. 2. - Case 2. Chest radiograph one month before death. the finger nails were clubbed. Her weight was 8 st. 131bs., pulse rate was 104 and the blood pressure 154/100. Fine crepitations were detected oyer the bases of the lungs. Radiographically there was miliary shadowing in both lungs coalescing over the lower two thirds of the lung fields to form dense shadows. Multiple puncture tuberculin test was positive. Blood examination revealed: erythrocytes-5,600,OOOI cmm, haemoglobin-113%, colour index-l.O, leucocytes-10,400/cmm with polymorphs 75%, lymphocytes 21 %, monocytes 1 %, eosinophilis I % and basophils 2 %. Admission to hospital for further investigation was strongly advised but firmly declined by the patient, who insisted that she was keeping well. She was therefore visited at home on three further occasions
MICROLITHIASIS ALVEOLARIS PULMONUM
279
and consented to have her chest x-rayed after each examination. When examined on 21st November, oedema of the legs (which did not improve when she was given an oral diuretic) was noticed. On 16th January, 1959, triple rhythm and a systolic mitral murmur were also detected; the x-ray showed small apical pneumothoraces (Fig. 2). Otherwise her chest condition seemed to be no worse though she was losing weight. On the 18th February, at 5.00 p.m., however, she was admitted to hospital with severe cyanosis, moderate dyspnoea, anasarca and retention of urine and slight fever. She died on the following day.
FIG. 3. - Case 2. Macroscopic appearances of cut section of lung.
Post-mortem Report The lungs weighed 3,050 g., the right lung 1,750 g., the left lung 1,300 g. (Normal female values 566 g. and 538 g., total 1,104 g.). There was much pleural thickening and fibrous adhesions were seen on both lung surfaces, especially the right. The lungs felt immensely heavy and solid and 'stood' on their bases without falling over. On section they were uniformly gritty and the cut surfaces felt like coarse sandpaper to the finger rubbed gently over the lung tissue (Fig. 3). With the naked eye, but better with a hand lens, small gritty concretions were seen throughout the lung substance apparently lying in expanded alveoli.
280
TUBERCLE
These concretions could be scraped out by the knife edge. The apex of the right lung showed a large emphysematous area and similar small foci were noted elsewhere. The bronchial tree was slightly more prominent than usual as a result of peribronchial fibrosis. The hilar and mediastinal lymph nodes were slightly enlarged. The heart weighed 300 gm, and showed prominent right ventricular myocardial hypertrophy but no other feature. The spleen and kidneys showed no unusual changes.
Histological appearances Sections showed the striking and classical features of microlithiasis alveolaris pulmonum, calcified spherules being present in most of the air sacs in any field studied. These spherules occasionally showed a laminated appearance but the larger ones were of irregular shape. Alveolar destruction had occurred focally, allowing the formation of quite large concretions. Interstitial fibrosis and round cell infiltration were noted where spherules were most frequent and alveolar destruction most pronounced. Peribronchial fibrosis was the only other feature of note. The hilar lymph nodes showed reactive hyperplasia and mild anthracosis. Calcific material was not evident.
Comment Unfortunately neither of these patients would agree to further investigations such as pulmonary function tests and laboratory examination of blood and urine specimens. However, up to the present time such investigations have proved singularly unhelpful in eliciting the cause of the disease. A full description of the pathological findings has been given by Kent, Gilbert and Meyer (1955) and Sosman and others (1957). The only frequent symptoms of this complaint are cough, dyspnoea and pain across the front of the chest and these are common to many other diseases of the lungs. One interesting finding radiographically (apparently so far not reported) was observed in the two cases described, both of which showed at some stage small pneumothoraces at the apices (see Fig. 2). Presumably emphysematous areas developed at the apices, subsequently ruptured and the resultant collapse was limited by adhesion between the pleurae. At necropsy in Case 2 the right lung was densely adherent to the parietal pleural and the left pleural cavity contained fluid. No cause for the formation of the pulmonary concretions has been proved so far and the disease remains a medical mystery. I wish to thank Mr. P. L. Brunnen for his most helpful advice on preparing this paper, and Dr. A. . Logie Stalker for his report on the autopsy findings.
Summary Two cases of microlithiasis alveolaris pulmonum occurring in sisters are described. The diagnosis was confirmed in one case by necropsy. References Abdel-Hakim, M., EI-MaIlah, S., Hashem, M., and Abdel-Halim, S. (1959). Thorax, 14, 263. Biressi, P. C., and Casassa, P. M. (1956). Minerva metl., Torino, 47, (2),930. Ohinachoti, N., and Tangchai, P., (1957). Dis Chest, 32, 687. Finkbiner, R. B., Decker,]. P., and Oooper, D. A., (1957). Amer. Rev. Tuberc., 75,122. Foote, E. L., (1957). J. Maine med. Ass., 48, 230. Gilsanz, V., Palacios, J. M., and Alonso Barrera, J. M., (1956). Rev. clin. esp., 61, 392. Greenberg, M.J., (1957). Thorax, 12, 171. Harbitz, F., (1918). Arch. intern. Med., 21, 139. Kent, G., Gilbert, E. S., and Meyer H. H., (1955). Arch. Path., 60, 556. Manz, A., (1954). Beitr. Klin. Tuberk., 111, 598. Mikhailov, V., (1954). Klin. med., Mask., 32, No.3, p. 31. Sosman, M. C., Dodd, G. D., Jones, W. D., and Pillmore, G. D., (1957), Amer. J. Roentgenol., 77, 947. Thomson, W. B., (1959). Thorax, 14, 76.
276
CASE
REPORT
Microlithiasis Alveolaris Pulmonum By M. H. WATERS from Spynie Hospital, Elgin, Scotland
This very rare disease was first described by Harbitz who published an account of it in 1918. The second case was not reported until 1932. Sosman and others (1957) in an extremely detailed and comprehensive paper described 23 cases seen by them. They stated that they knew of two others not reported. Also described are 22 other cases previously published, of which the authors regarded 20 as being in all probability genuine cases of microlithiasis alveolaris pulmonum and two ofcloubtful authenticity. Of the 24 cases seen by these authors, four were confirmed at necropsy and five by lung biopsy. The remainder were diagnosed by radiographic appearances only. 28 of the 45 cases described by Sosman and his colleagues had no real symptoms and 28 were picked up by routine radiographic examination for the armed forces, pre-employment examination, chest survey programme or as relatives of other cases. Further cases have been described by Manz (1954), Mikhailov (1954), Gilsanz, Palacios and Barrera (1956), Biressi and Casassa (1956), Finkbiner, Decker and Cooper (1957), Foote (1957), Greenberg (1957), Chinachoti and Tangchai (1957), Thomson (1959) and Abdel-Hakim and others (1959); making a total of 58 cases so far reported. Prior to the publication of this paper only five cases are known to have occurred in this country, two of them being brothers. This paper describes two further cases occurring in sisters. 1 Mrs. W. McG., age 31 was first seen on Bth June, 1958. She stated that four weeks previously she had developed a dry cough, which was worse at night. Seven days later she commenced to produce sputum. She also complained of anorexia, lassitude, increasing dyspnoea on exertion, some sweating at night and pain behind the sternum on coughing. She had pneumonia in infancy and again when 13 years of age. She was a healthy looking woman weighing 7 st. 12 Ibs. Fine crepitations were present over the bases of the lungs, especially on the right side. Radiographically there was miliary type of shadowing of all lung fields, most dense at the bases (Fig. 1). Multiple puncture tuberculin test was positive and ESR estimation was 20 mm. in one hour (Westergren). Sputum was negative [01' tubercle bacilli on animal inoculation. It was at first considered that the patient had miliary tuberculosis of the lungs, although she seemed too well. She was admitted to hospital and commenced treatment with 1 g. streptoduocin and 200 mgs, isoniazid daily. On the seventh day she developed an erythematous rash on the trunk and hcr temperature-s-previously normal-rose to 99.8°; so the treatment was changed to PAS and isoniazid. Ten days later the patient took her own discharge, but the same chemotherapy was continued at home. She was seen at the local chest clinic on 25th July. On this occasion she still looked well and her weight hacl increased to 8 st. 2 lbs, Her E.S.R. remained elevated at 22 mm. in one hour (Westergren). She stated that she felt better and had neither cough nor dyspnoea. Crepitations were still detected over the lungs and the x-ray appearances were unaltered. She was with some difficulty persuaded to return to hospital for further investigation on 30th July. The diagnosis of malignant metastases was now considered but no primary growth was found and she also seemed too well to justify this diagnosis. Although the lesions were much too dense and there was no other evidence to support the diagnosis, sarcoidosis was considered to be a faint possibility and she was given 20 mg. prednisolone daily in addition to her chemotherapy, along with 30 units A.C.T.H. gel intramuscularly on two successive days every two weeks. She was discharged from hospital on 11 th August, again at her own request, and against advice and continued her treatment unaltered until December when over three weeks the prednisolone was gradually reduced in dosage and she ceased taking the PAS and isoniazid of her own accord. CASE
MICROLITHIASIS ALVEOLARIS PULMONUM
277
She was examined as an out-patient at monthly in tervals following discharge from hospital a nd appeared to keep quite well, apart from occasional dyspnoea and nocturnal cough which developed 5 months after leaving hospital. Crepitations still persisted over the lung bases and the x-ray appearances remained subs tantially un altered . Sinc e no accurate d iagnosis had so far been made the chest x-rays were sent to Dr. Peter Kerley for his opinion. He thought that the appea ra nces were typical of microlithiasis alveolaris pulmonum and suggested examination of other members of the family as far as possible. One sister, Mrs.]. H . G .
Fro. I. - Case I. Chest radiograph at the start of the illness. (Case 2), was then found also to have microlithiasis alveolaris pulmonum. Neither of the patients had any children. Two married sisters with their fam ilies of two and three chi ldre n were x-rayed and the appearances were normal. Two au nts and three uncles whose ages were 74, 70, BO, 6B and 59 respectively, wer e traced and found to be wel l. They declined examination and it seemed unlikely that they were suffering from microlithiasis alveolaris pulrnonum, T he mother of Mrs. W. MeG. and Mrs.]. H. G. died in her thirties and th e cau se of death was st ated as pulmonary tuberculosis, but it may well have been microlit hiasis alveolari s pu lrnonurn. The fa ther died of diab etes at the age of 50.
278
TUBERCLE
On 31st March, 1959, Mrs. W'. MeG. developed a febrile illness which was diagnosed by her family doctor as 'flu'. She then had a productive cough, increased dyspnoea and pain across the chest. She was admitted to hospital on 5th April at 12.05 a.m, and was obviously extremely ill. Her temperature was subnormal (96.4°), pulse rate 168 and respiration 'H. She complained of frontal headache. She slept for short periods, became unconscious at 6.15 a.m, and died at 7.30 a.m, Unfortunately permission to perform a necropsy was not obtained. CASE
2
Mrs. J. H. G. age 36, (a sister of Case I), was examined on 30th January, 1958 and found to have microlithiasis alveolaris pulmonum. At that time she had a cold with a productive cough and dyspnoea on exertion. Her general condition was good, but there was some cyanosis of the face and hands ancl
FIG. 2. - Case 2. Chest radiograph one month before death. the finger nails were clubbed. Her weight was 8 st. 131bs., pulse rate was 104 and the blood pressure 154/100. Fine crepitations were detected oyer the bases of the lungs. Radiographically there was miliary shadowing in both lungs coalescing over the lower two thirds of the lung fields to form dense shadows. Multiple puncture tuberculin test was positive. Blood examination revealed: erythrocytes-5,600,OOOI cmm, haemoglobin-113%, colour index-l.O, leucocytes-10,400/cmm with polymorphs 75%, lymphocytes 21 %, monocytes 1 %, eosinophilis I % and basophils 2 %. Admission to hospital for further investigation was strongly advised but firmly declined by the patient, who insisted that she was keeping well. She was therefore visited at home on three further occasions
MICROLITHIASIS ALVEOLARIS PULMONUM
279
and consented to have her chest x-rayed after each examination. When examined on 21st November, oedema of the legs (which did not improve when she was given an oral diuretic) was noticed. On 16th January, 1959, triple rhythm and a systolic mitral murmur were also detected; the x-ray showed small apical pneumothoraces (Fig. 2). Otherwise her chest condition seemed to be no worse though she was losing weight. On the 18th February, at 5.00 p.m., however, she was admitted to hospital with severe cyanosis, moderate dyspnoea, anasarca and retention of urine and slight fever. She died on the following day.
FIG. 3. - Case 2. Macroscopic appearances of cut section of lung.
Post-mortem Report The lungs weighed 3,050 g., the right lung 1,750 g., the left lung 1,300 g. (Normal female values 566 g. and 538 g., total 1,104 g.). There was much pleural thickening and fibrous adhesions were seen on both lung surfaces, especially the right. The lungs felt immensely heavy and solid and 'stood' on their bases without falling over. On section they were uniformly gritty and the cut surfaces felt like coarse sandpaper to the finger rubbed gently over the lung tissue (Fig. 3). With the naked eye, but better with a hand lens, small gritty concretions were seen throughout the lung substance apparently lying in expanded alveoli.
280
TUBERCLE
These concretions could be scraped out by the knife edge. The apex of the right lung showed a large emphysematous area and similar small foci were noted elsewhere. The bronchial tree was slightly more prominent than usual as a result of peribronchial fibrosis. The hilar and mediastinal lymph nodes were slightly enlarged. The heart weighed 300 gm, and showed prominent right ventricular myocardial hypertrophy but no other feature. The spleen and kidneys showed no unusual changes.
Histological appearances Sections showed the striking and classical features of microlithiasis alveolaris pulmonum, calcified spherules being present in most of the air sacs in any field studied. These spherules occasionally showed a laminated appearance but the larger ones were of irregular shape. Alveolar destruction had occurred focally, allowing the formation of quite large concretions. Interstitial fibrosis and round cell infiltration were noted where spherules were most frequent and alveolar destruction most pronounced. Peribronchial fibrosis was the only other feature of note. The hilar lymph nodes showed reactive hyperplasia and mild anthracosis. Calcific material was not evident.
Comment Unfortunately neither of these patients would agree to further investigations such as pulmonary function tests and laboratory examination of blood and urine specimens. However, up to the present time such investigations have proved singularly unhelpful in eliciting the cause of the disease. A full description of the pathological findings has been given by Kent, Gilbert and Meyer (1955) and Sosman and others (1957). The only frequent symptoms of this complaint are cough, dyspnoea and pain across the front of the chest and these are common to many other diseases of the lungs. One interesting finding radiographically (apparently so far not reported) was observed in the two cases described, both of which showed at some stage small pneumothoraces at the apices (see Fig. 2). Presumably emphysematous areas developed at the apices, subsequently ruptured and the resultant collapse was limited by adhesion between the pleurae. At necropsy in Case 2 the right lung was densely adherent to the parietal pleural and the left pleural cavity contained fluid. No cause for the formation of the pulmonary concretions has been proved so far and the disease remains a medical mystery. I wish to thank Mr. P. L. Brunnen for his most helpful advice on preparing this paper, and Dr. A. . Logie Stalker for his report on the autopsy findings.
Summary Two cases of microlithiasis alveolaris pulmonum occurring in sisters are described. The diagnosis was confirmed in one case by necropsy. References Abdel-Hakim, M., EI-MaIlah, S., Hashem, M., and Abdel-Halim, S. (1959). Thorax, 14, 263. Biressi, P. C., and Casassa, P. M. (1956). Minerva metl., Torino, 47, (2),930. Ohinachoti, N., and Tangchai, P., (1957). Dis Chest, 32, 687. Finkbiner, R. B., Decker,]. P., and Oooper, D. A., (1957). Amer. Rev. Tuberc., 75,122. Foote, E. L., (1957). J. Maine med. Ass., 48, 230. Gilsanz, V., Palacios, J. M., and Alonso Barrera, J. M., (1956). Rev. clin. esp., 61, 392. Greenberg, M.J., (1957). Thorax, 12, 171. Harbitz, F., (1918). Arch. intern. Med., 21, 139. Kent, G., Gilbert, E. S., and Meyer H. H., (1955). Arch. Path., 60, 556. Manz, A., (1954). Beitr. Klin. Tuberk., 111, 598. Mikhailov, V., (1954). Klin. med., Mask., 32, No.3, p. 31. Sosman, M. C., Dodd, G. D., Jones, W. D., and Pillmore, G. D., (1957), Amer. J. Roentgenol., 77, 947. Thomson, W. B., (1959). Thorax, 14, 76.