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LUPUS FROM B.C.G.
1174
postnatally; and their presence in these cases represents some delay in the normal maturation ’process of the liver-which is scarcely surprising when that organis grossly abnormal in other respects. Dible and his colleagues justifiably conclude that the pathological findings only
in these infants development and
were
were
in
attributable to their stage of no way incompatible with viral
hepatitis. The relationship
of this neonatal hepatitis, apparently contracted in utero, to juvenile cirrhosis is next considered by Dible and his associates. In 2 infants who developed jaundice within a few days of birth and died after three and seven weeks, necropsy showed distinct diffuse hepatic fibrosis such as occasionally follows infective hepatitis in adults. In the absence of any other aetiological factor Dible et al. conclude that these 2 cases may represent the sequelae to the acute type of disease seen in the 4 previous cases. It seems unlikely that the virus of ordinary infective hepatitis is responsible for in-utero infection, for there is no evidence that infective hepatitis in the mother is transmitted to the fcetus. On the other hand, Stokes et a1.2 have reported the case of a woman, subsequently shown to be a carrier of an icterogenic virus, whose infant developed jaundice at four months and died with hepatic cirrhosis at eighteen months. In view of the frequency of icterogenic virus in blood-plasma, the rarity of in-utero infection implies either a considerable resistance to transplacental transmission of the virus or a simultaneous transmission of antibodies. Possibly neither type of infective-hepatitis virus is responsible, but some other agent such as herpes virus.3 Virological studies in further cases should answer this very important question. VASCULAR INJURIES IN WAR IT has long been known that primary ligation of majoi peripheral arteries gives poor results. In the 1939-4f war the results were possibly worse than those previousl3 reported,4 and DeBakey and Simeonefound that o: 2471 patients with arterial wounds only 135 had beer treated by primary repair and reconstitution of th{ " damaged artery. Since division of critical arterie: and (axillary, brachial, femoral, popliteal) so often lead, to loss of limb or life, it is understandable- that a mor( active policy of arterial repair was initiated by th( American medical services in the Korean conflict. Som{ "
encouraging preliminary reports are now appearing. The interval between wounding and arrival at th{ surgical centre is vitally important ; and in Korea evacuation by helicopter reduced the average interval below the critical level of ten hours. Zipermannotes a definite correlation between lack of vascular-surgical experience and amputation-rate ; this was so evident that a special centre for the teaching and practice oj vascular surgery was established in Korea. Ziperman reviews 218 peripheral vascular injuries, of which 162 involved " critical " arteries. In 132 cases the arterial wounds were repaired by end-to-end anastomosis, arteriorrhaphy, and vein grafting. The outstanding feature is the proportion of extremities lost-20% in the whole Korean series, compared with 40% in a 1939-45 series.5 Results were especially impressive in partial arterial tears which after debridement can be repaired by evertion sutures. Longitudinal closure of a defect may be followed by such narrowing of the lumen that thrombosis ensues.7 Moore et al.8emphasise that damage of the intima always much exceeds that of the adventitia, and conclude that resection of the entire length of the injured vessel followed 2.
Stokes, J. jun., Wolman,
I.
J., Blanchard, M. C., Farquhar, J. D. Amer. J. Dis. Child. 1951, 82, 213. 3. France, N. E., Wilmers, M. J. Lancet, 1953, i, 1181. 4. Brown, J. J. M. Brit. J. Surg. war suppl. no. 2, 1948, p. 354. 5. DeBakey, M. E., Simeone, F. A. Ann. Surg. 1946, 123, 534. 6. Ziperman, H. H. Ibid, 1954, 139, 1. 7. Maybury, B. C. Brit. med. Bull. 1944, 2, 142. 8. Moore, H. G. jun., Nyhus, L. M., Kanar, E. A., Harkins, H. N. Surg. Gynec. Obstet. 1954, 98, 129.
by end-to-end anastomosis gives the most satisfactory results with the least disturbance of blood-flow. Where the severed ends of the artery cannot be safely approximated a free vein graft seems to be the best method ; the place of preserved arterial grafts has not been fully determined. The use of’Vitallium tubes and other prostheses has apparently been abandoned. Ziperman strongly advises against ligation of the concomitant undamaged vein-a point which most surgeons would endorse. LUPUS FROM B.C.G. Lupus vulgaris usually starts with the implantation of tubercle bacilli from an external source. In children it may develop from a primary tuberculous sore. In adults, who have probably already done battle with the tubercle bacillus in the lungs or bowel, bacilli implanted in the skin more commonly give rise to a different kind of lesion-verrucous skin tuberculosis. This suggests to Dowling and Wetherley-Mein1 that the type of immunity derived from primary infection of the skin differs from The bacillus that derived from extracutaneous foci. recovered from the lesion of lupus is of low virulence, and such strains are rarely found in tuberculosis in other systems,2 so it seems probable that the organism is attenuated in the skin itself ; once lupus is initiated, the attenuated strain is of sufficient virulence to maintain the characteristically chronic process. Jensen3 predicted the production of lupus vulgaris by the intentional inoculation of artificially attenuated tubercle bacilli-i.e., B.C.G. Lomholt 4 first reported such a case. Ustvedt5 thought that the lupus must have arisen through superinfection, but Tolderlund6 considered that the bacillus recovered from this case was indistinguishable from B.C.G. 2 further cases of lupus following B.C.G. vaccination were reported 78 but without9 bacteriological proof of the causal organism. Marcussen has now described 3 cases, in 2 of which there was good clinical and bacteriological evidence that the lupus was In all 3 cases the lesion not due to superinfection. spread from the site of B.C.G. vaccination, and in 1 it had persisted for three years. All 3 patients were 2 had no known before vaccination. tuberculin-negative tuberculous contact, and a tubercle bacillus recovered from their lesions proved identical with B.C.G. in cultural behaviour and pathogenicity. In B.c.G.-vaccinated patients who subsequently develop tuberculosis of organs other than the skin, it is usual to find tubercle bacilli of high virulence ; and such cases are attributed to fresh infection. The close similaritv of the bacillus of lupus to B.C.G. makes this attribution less convincing in cases of skin tubercle. If, however, the laboratory criteria for their separation are valid, B.C.G. vaccination can probably give rise to progressive infection of the skin for at least several years. It has long been known that B.C.G. can survive in the tissues for up to eighteen months, and a case of tuberculous lymphadenitis attributed to B.C.G. was diagnosed three years after vaccination. Marcussen raises the question of variation in the potency of the vaccine. If this were a material factor, one might have expected many more cases of lupus. Also, the accidental injection of enormous doses of B.C.G. has not provoked long-standing local infection. Variation in the host’s response is a more probable explanation of these rare cases. It may be significant that one of Marcussen’s cases was inoculated four times before 1. Dowling, G. B., Wetherley-Mein, G. In Modern Trends in Dermatology. Edited by R. M. B. MacKenna. London, 1954. 2. Griffith, A. S. Lancet, 1916, i, 721. 3. Jensen, K. A. Cited by Marcussen (footnote 9). 4. Lomholt, S. Acta tuberc scand. 1946, 20, 136. 5. Ustvedt, H. J. In Modern Practice in Tuberculosis. Edited by T. Holmes Sellors and J. L. Livingstone, London, 1952. 6. Tolderlund, K. Cited by Marcussen (footnote 9). 7. Kalkoff, K. W. Hautarzt, 1950, 1, 366. 8. Gilje, O. Acta derm.-venereol., Stockh. 1952, 32, 51. 9. Marcussen, P. V. Brit. J. Derm. 1954, 66, 121.
1175 skin positivity was obtained. Marcussen points out that these exceptional cases, which readily respond to treatment, do not affect the value of B.C.G. as a
lasting
prophylactic
measure.
PULMONARY TUBEROUS SCLEROSIS PATIENTS with tuberous sclerosis
usually come under because of mental defect or epileptic fits resulting from cerebral damage. These symptoms generally appear in infancy, and the diagnosis can be made with confidence if the characteristic skin lesionsadenoma sebaceum or peau chagrinée-are present. Subungual fibromas are also peculiar to tuberous sclerosisand may be accompanied by brittleness and longitudinal ridging of the nails. Sometimes retinal tumours (phakomas) may be observed,2 and tumours These features of the kidneys are not uncommon.3 are well recognised, and the hereditary nature of the disease was established by Kirpicznik4 as long ago as 1910. Much less is known about the pulmonary manifestations. Berg and Vejlens5 first described these in 1939 ; but only a few examples have since come to light, and it was not until 1949 that a case in this country was first reported.6 Dawsonhas now added 4 cases to the 9 previously recorded. The presenting symptom of pulmonary tuberous sclerosis is usually breathlessness due to pulmonary medical
care
insufficiency or to spontaneous pneumothorax-a common complication. Ha’moptysis may occur, but cough and sputum are usually absent since infection of the lungs is only an occasional terminal event. Respiratory symptoms do not usually appear until the third decade, but they may be the cause of the patient seeking medical advice. In tuberous sclerosis sex-distribution is equal, but the pulmonary form affects women more commonly than men. Unless spontaneous pneumothorax is present, physical examination of the chest is not informative. dubbing of the fingers has not been observed-a negative finding that may be of some diagnostic help. The typical radiographic appearance is of a network of lines throughout both lung fields, giving a miliary, reticular, or honeycomb effect. Death, from pulmonary insufficiency,
spontaneous pneumothorax,
or
congestive heart-failure,
average about five years after the onset of symptoms. Typically, the lungs are riddled with cysts varying in size from a pinhead to a pea, and those under the pleura produce small elevations of lying its surface. Vejlensfound no special relationship between the cysts and the bronchial tree, although some communicated with the finer bronchi. The cysts are set in a firm matrix of new tissue which more or less replaces the normal lung and is composed of smoothThe muscle fibres, fibrous tissue, and blood-vessels. smooth-muscle fibres are usually the predominant element a feature of so few other conditions that their - an<1 presence strongly suggests the diagnosis. The vascularity of the new tissue may help to account for the large amount of iron pigment commonly found in the lungs, and for the small haemoptyses which sometimes occur. The stimulus causing the normal lung elements to hypertrophy in this way is unknown. Confronted with a clinical and radiographic picture which suggests pulmonary tuberous sclerosis, the clinician will seek confirmation of the diagnosis in other systems. Curiously, gross mental defect and epileptic fits are seldom associated with lung involvement ; Dawson, for example, discovered only 1 instance of the pulmonary form in 64 fully investigated cases with
ensues on an
just
1.
2. 3. 4. 5.
6. 7. 8.
Kothe, R. Arch. Derm. Syph., Wien. 1904, 68, 33, 359. van der Hoeve, J. v. Graefes Arch. Ophthal. 1921, 105, 880. Bielschowsky, M., Gallus. J. Psychol. Neurol., Lpz. 1913, 20 ; Ergänz. i, 1. Kirpicznik, J. Virchows Arch. 1910, 202, 358. Berg. G., Vejlens, G. Acta pœdiat., Stockh. 1939, 26, 16. Oswald, N., Parkinson, T. Quart. J. Med. 1949, 18, 1. Dawson, J. Ibid, 1954, 23, 113. Vejlens, G. Acta path. microbiol. scand. 1941, 18, 317.
mental symptoms. The presence of adenoma sebaceum, peau chagrinie, subungual fibromas, or retinal phakomas may give a clue to the diagnosis ; and physical examination or excretion urography may disclose irregularities in the shape of the kidneys suggesting renal tumours. Rhabdomyomas of the heart are sometimes associated with tuberous sclerosis.9 Radiography of the skull may reveal thickening of the bones or areas of increased density,lO and calcification of patches of sclerosis " in the brain may show as " cotton balls." 11 Nodular periosteal thickening and cyst-like spaces may be seen in radiographs of the limb bones.12 Rarely only the respiratory system may be obviously affected ; Licht 13 and Borberg 14 have each reported 1 such case, and Dawsonconsiders that 6 reported cases of diffuse cystic lung disease may also have been of this nature. Here a family history of tuberous sclerosis, the clinical features, and possibly lung biopsy may aid differentiation from other conditions with a similar radiographic picture, such as inhalation fibrosis, miliary tuberculosis,
sarcoidosis, lymphangitis carcinomatosa, scleroderma, cystic bronchiectasis, bronchiolectasis, chronic bronchiolitis, diffuse pulmonary fibrosis of unknown origin, and the group of diseases described by Thannhauser 15 the " generalised eosinophilic granulomas." A further possible diagnostic difficulty has been uncovered by Dawson,who has shown that abnormalities in the chest radiograph may be localised as well as generalised. In one of his cases with various stigmata of tuberous sclerosis chest films showed only a lobulated opacity which was found from a biopsy specimen to be a mucin-secreting adenoma ; as there were numerous tumours elsewhere in the body the lung lesion was regarded, like these, as an expression of the underlying disease. The first radiographs of another case showed only infiltration in the left upper lobe, although the as
typical generalised pattern appeared in subsequent films ; and Dawson points out that Paliard et al.16 previously reported a case in which radiography showed opacities confined to the upper lobes. More information about pulmonary tuberous sclerosis would be welcome, and the interest aroused by Dawson’s paper may result in the recognition of more examples of the condition. PENICILLIN IN DIPHTHERIA DIPHTHERTA has become uncommon in this country and in the U.S.A., so experience of treatment with penicillin is very limited. It has been used only in combination with antitoxin, and this combination has been found to have little if any advantage over antitoxin alone in saving life and reducing complications.17-2o Cruickshank et al.21 found that a dosage of 40,000 units of penicillin four-hourly, combined with antitoxin, shortened the duration of carriage of Corynebacterium diphtheriae in acute faucial diphtheria, but they did not comment on the influence of penicillin on the clinical course of the disease. There are likely to be few opportunities in this country of confirming or refuting the finding, by Calvet and Herrera,22 that penicillin alone in large dosage (500,000 units six-hourly) is superior to antitoxin alone in the treatment of faucial and laryngeal 9. Farber, S. Amer. J. Path. 1931, 7, 105. 10. Dalsgaard-Nielsen, T. Nord. med. Tidskr. 1935, 10, 1541. 11. Marcus, H. Svenska LäkSällsk. Förh. 1924, 358. 12. Gottlieb, J. S., Lavine, G. R. Arch. Neurol. Psychiat., Chicago, 1935, 33, 379. 13. Licht, E. de F. Acta radiol., Stockh. 1942, 23, 151. 14. Borberg, A. Clinical and Genetic Investigations into Tuberous Sclerosis and Recklinghausen’s Neurofibromatosis. Copenhagen, 1951. 15. Thannhauser, S. J. Lipidoses. New York. 1950. 16. Paliard, Plauchu, Galy, and Papillon. Poumon, 1946, 2, 205. 17. Dodds, R. J. Brit. med. J. 1946, ii, 8. 18. Karelitz, S., Wassermann, L. R., Moloshok, R. J. Pediat. 1947, 30, 18. 19. Weinstein, L. Amer. J. med. Sci. 1947, 213, 318. 20. Bruyn, H. B.,Brainerd. H., Leppla, B. W. Ibid, 1950, 219, 408. 21. Lancet, 1948, ii, 517. 22. Calvet J. R., Herrera, R. G. Bol. Coll. mád. Habana, 1953, 4, 501.
postnatally; and their presence in these cases represents some delay in the normal maturation ’process of the liver-which is scarcely surprising when that organis grossly abnormal in other respects. Dible and his colleagues justifiably conclude that the pathological findings only
in these infants development and
were
were
in
attributable to their stage of no way incompatible with viral
hepatitis. The relationship
of this neonatal hepatitis, apparently contracted in utero, to juvenile cirrhosis is next considered by Dible and his associates. In 2 infants who developed jaundice within a few days of birth and died after three and seven weeks, necropsy showed distinct diffuse hepatic fibrosis such as occasionally follows infective hepatitis in adults. In the absence of any other aetiological factor Dible et al. conclude that these 2 cases may represent the sequelae to the acute type of disease seen in the 4 previous cases. It seems unlikely that the virus of ordinary infective hepatitis is responsible for in-utero infection, for there is no evidence that infective hepatitis in the mother is transmitted to the fcetus. On the other hand, Stokes et a1.2 have reported the case of a woman, subsequently shown to be a carrier of an icterogenic virus, whose infant developed jaundice at four months and died with hepatic cirrhosis at eighteen months. In view of the frequency of icterogenic virus in blood-plasma, the rarity of in-utero infection implies either a considerable resistance to transplacental transmission of the virus or a simultaneous transmission of antibodies. Possibly neither type of infective-hepatitis virus is responsible, but some other agent such as herpes virus.3 Virological studies in further cases should answer this very important question. VASCULAR INJURIES IN WAR IT has long been known that primary ligation of majoi peripheral arteries gives poor results. In the 1939-4f war the results were possibly worse than those previousl3 reported,4 and DeBakey and Simeonefound that o: 2471 patients with arterial wounds only 135 had beer treated by primary repair and reconstitution of th{ " damaged artery. Since division of critical arterie: and (axillary, brachial, femoral, popliteal) so often lead, to loss of limb or life, it is understandable- that a mor( active policy of arterial repair was initiated by th( American medical services in the Korean conflict. Som{ "
encouraging preliminary reports are now appearing. The interval between wounding and arrival at th{ surgical centre is vitally important ; and in Korea evacuation by helicopter reduced the average interval below the critical level of ten hours. Zipermannotes a definite correlation between lack of vascular-surgical experience and amputation-rate ; this was so evident that a special centre for the teaching and practice oj vascular surgery was established in Korea. Ziperman reviews 218 peripheral vascular injuries, of which 162 involved " critical " arteries. In 132 cases the arterial wounds were repaired by end-to-end anastomosis, arteriorrhaphy, and vein grafting. The outstanding feature is the proportion of extremities lost-20% in the whole Korean series, compared with 40% in a 1939-45 series.5 Results were especially impressive in partial arterial tears which after debridement can be repaired by evertion sutures. Longitudinal closure of a defect may be followed by such narrowing of the lumen that thrombosis ensues.7 Moore et al.8emphasise that damage of the intima always much exceeds that of the adventitia, and conclude that resection of the entire length of the injured vessel followed 2.
Stokes, J. jun., Wolman,
I.
J., Blanchard, M. C., Farquhar, J. D. Amer. J. Dis. Child. 1951, 82, 213. 3. France, N. E., Wilmers, M. J. Lancet, 1953, i, 1181. 4. Brown, J. J. M. Brit. J. Surg. war suppl. no. 2, 1948, p. 354. 5. DeBakey, M. E., Simeone, F. A. Ann. Surg. 1946, 123, 534. 6. Ziperman, H. H. Ibid, 1954, 139, 1. 7. Maybury, B. C. Brit. med. Bull. 1944, 2, 142. 8. Moore, H. G. jun., Nyhus, L. M., Kanar, E. A., Harkins, H. N. Surg. Gynec. Obstet. 1954, 98, 129.
by end-to-end anastomosis gives the most satisfactory results with the least disturbance of blood-flow. Where the severed ends of the artery cannot be safely approximated a free vein graft seems to be the best method ; the place of preserved arterial grafts has not been fully determined. The use of’Vitallium tubes and other prostheses has apparently been abandoned. Ziperman strongly advises against ligation of the concomitant undamaged vein-a point which most surgeons would endorse. LUPUS FROM B.C.G. Lupus vulgaris usually starts with the implantation of tubercle bacilli from an external source. In children it may develop from a primary tuberculous sore. In adults, who have probably already done battle with the tubercle bacillus in the lungs or bowel, bacilli implanted in the skin more commonly give rise to a different kind of lesion-verrucous skin tuberculosis. This suggests to Dowling and Wetherley-Mein1 that the type of immunity derived from primary infection of the skin differs from The bacillus that derived from extracutaneous foci. recovered from the lesion of lupus is of low virulence, and such strains are rarely found in tuberculosis in other systems,2 so it seems probable that the organism is attenuated in the skin itself ; once lupus is initiated, the attenuated strain is of sufficient virulence to maintain the characteristically chronic process. Jensen3 predicted the production of lupus vulgaris by the intentional inoculation of artificially attenuated tubercle bacilli-i.e., B.C.G. Lomholt 4 first reported such a case. Ustvedt5 thought that the lupus must have arisen through superinfection, but Tolderlund6 considered that the bacillus recovered from this case was indistinguishable from B.C.G. 2 further cases of lupus following B.C.G. vaccination were reported 78 but without9 bacteriological proof of the causal organism. Marcussen has now described 3 cases, in 2 of which there was good clinical and bacteriological evidence that the lupus was In all 3 cases the lesion not due to superinfection. spread from the site of B.C.G. vaccination, and in 1 it had persisted for three years. All 3 patients were 2 had no known before vaccination. tuberculin-negative tuberculous contact, and a tubercle bacillus recovered from their lesions proved identical with B.C.G. in cultural behaviour and pathogenicity. In B.c.G.-vaccinated patients who subsequently develop tuberculosis of organs other than the skin, it is usual to find tubercle bacilli of high virulence ; and such cases are attributed to fresh infection. The close similaritv of the bacillus of lupus to B.C.G. makes this attribution less convincing in cases of skin tubercle. If, however, the laboratory criteria for their separation are valid, B.C.G. vaccination can probably give rise to progressive infection of the skin for at least several years. It has long been known that B.C.G. can survive in the tissues for up to eighteen months, and a case of tuberculous lymphadenitis attributed to B.C.G. was diagnosed three years after vaccination. Marcussen raises the question of variation in the potency of the vaccine. If this were a material factor, one might have expected many more cases of lupus. Also, the accidental injection of enormous doses of B.C.G. has not provoked long-standing local infection. Variation in the host’s response is a more probable explanation of these rare cases. It may be significant that one of Marcussen’s cases was inoculated four times before 1. Dowling, G. B., Wetherley-Mein, G. In Modern Trends in Dermatology. Edited by R. M. B. MacKenna. London, 1954. 2. Griffith, A. S. Lancet, 1916, i, 721. 3. Jensen, K. A. Cited by Marcussen (footnote 9). 4. Lomholt, S. Acta tuberc scand. 1946, 20, 136. 5. Ustvedt, H. J. In Modern Practice in Tuberculosis. Edited by T. Holmes Sellors and J. L. Livingstone, London, 1952. 6. Tolderlund, K. Cited by Marcussen (footnote 9). 7. Kalkoff, K. W. Hautarzt, 1950, 1, 366. 8. Gilje, O. Acta derm.-venereol., Stockh. 1952, 32, 51. 9. Marcussen, P. V. Brit. J. Derm. 1954, 66, 121.
1175 skin positivity was obtained. Marcussen points out that these exceptional cases, which readily respond to treatment, do not affect the value of B.C.G. as a
lasting
prophylactic
measure.
PULMONARY TUBEROUS SCLEROSIS PATIENTS with tuberous sclerosis
usually come under because of mental defect or epileptic fits resulting from cerebral damage. These symptoms generally appear in infancy, and the diagnosis can be made with confidence if the characteristic skin lesionsadenoma sebaceum or peau chagrinée-are present. Subungual fibromas are also peculiar to tuberous sclerosisand may be accompanied by brittleness and longitudinal ridging of the nails. Sometimes retinal tumours (phakomas) may be observed,2 and tumours These features of the kidneys are not uncommon.3 are well recognised, and the hereditary nature of the disease was established by Kirpicznik4 as long ago as 1910. Much less is known about the pulmonary manifestations. Berg and Vejlens5 first described these in 1939 ; but only a few examples have since come to light, and it was not until 1949 that a case in this country was first reported.6 Dawsonhas now added 4 cases to the 9 previously recorded. The presenting symptom of pulmonary tuberous sclerosis is usually breathlessness due to pulmonary medical
care
insufficiency or to spontaneous pneumothorax-a common complication. Ha’moptysis may occur, but cough and sputum are usually absent since infection of the lungs is only an occasional terminal event. Respiratory symptoms do not usually appear until the third decade, but they may be the cause of the patient seeking medical advice. In tuberous sclerosis sex-distribution is equal, but the pulmonary form affects women more commonly than men. Unless spontaneous pneumothorax is present, physical examination of the chest is not informative. dubbing of the fingers has not been observed-a negative finding that may be of some diagnostic help. The typical radiographic appearance is of a network of lines throughout both lung fields, giving a miliary, reticular, or honeycomb effect. Death, from pulmonary insufficiency,
spontaneous pneumothorax,
or
congestive heart-failure,
average about five years after the onset of symptoms. Typically, the lungs are riddled with cysts varying in size from a pinhead to a pea, and those under the pleura produce small elevations of lying its surface. Vejlensfound no special relationship between the cysts and the bronchial tree, although some communicated with the finer bronchi. The cysts are set in a firm matrix of new tissue which more or less replaces the normal lung and is composed of smoothThe muscle fibres, fibrous tissue, and blood-vessels. smooth-muscle fibres are usually the predominant element a feature of so few other conditions that their - an<1 presence strongly suggests the diagnosis. The vascularity of the new tissue may help to account for the large amount of iron pigment commonly found in the lungs, and for the small haemoptyses which sometimes occur. The stimulus causing the normal lung elements to hypertrophy in this way is unknown. Confronted with a clinical and radiographic picture which suggests pulmonary tuberous sclerosis, the clinician will seek confirmation of the diagnosis in other systems. Curiously, gross mental defect and epileptic fits are seldom associated with lung involvement ; Dawson, for example, discovered only 1 instance of the pulmonary form in 64 fully investigated cases with
ensues on an
just
1.
2. 3. 4. 5.
6. 7. 8.
Kothe, R. Arch. Derm. Syph., Wien. 1904, 68, 33, 359. van der Hoeve, J. v. Graefes Arch. Ophthal. 1921, 105, 880. Bielschowsky, M., Gallus. J. Psychol. Neurol., Lpz. 1913, 20 ; Ergänz. i, 1. Kirpicznik, J. Virchows Arch. 1910, 202, 358. Berg. G., Vejlens, G. Acta pœdiat., Stockh. 1939, 26, 16. Oswald, N., Parkinson, T. Quart. J. Med. 1949, 18, 1. Dawson, J. Ibid, 1954, 23, 113. Vejlens, G. Acta path. microbiol. scand. 1941, 18, 317.
mental symptoms. The presence of adenoma sebaceum, peau chagrinie, subungual fibromas, or retinal phakomas may give a clue to the diagnosis ; and physical examination or excretion urography may disclose irregularities in the shape of the kidneys suggesting renal tumours. Rhabdomyomas of the heart are sometimes associated with tuberous sclerosis.9 Radiography of the skull may reveal thickening of the bones or areas of increased density,lO and calcification of patches of sclerosis " in the brain may show as " cotton balls." 11 Nodular periosteal thickening and cyst-like spaces may be seen in radiographs of the limb bones.12 Rarely only the respiratory system may be obviously affected ; Licht 13 and Borberg 14 have each reported 1 such case, and Dawsonconsiders that 6 reported cases of diffuse cystic lung disease may also have been of this nature. Here a family history of tuberous sclerosis, the clinical features, and possibly lung biopsy may aid differentiation from other conditions with a similar radiographic picture, such as inhalation fibrosis, miliary tuberculosis,
sarcoidosis, lymphangitis carcinomatosa, scleroderma, cystic bronchiectasis, bronchiolectasis, chronic bronchiolitis, diffuse pulmonary fibrosis of unknown origin, and the group of diseases described by Thannhauser 15 the " generalised eosinophilic granulomas." A further possible diagnostic difficulty has been uncovered by Dawson,who has shown that abnormalities in the chest radiograph may be localised as well as generalised. In one of his cases with various stigmata of tuberous sclerosis chest films showed only a lobulated opacity which was found from a biopsy specimen to be a mucin-secreting adenoma ; as there were numerous tumours elsewhere in the body the lung lesion was regarded, like these, as an expression of the underlying disease. The first radiographs of another case showed only infiltration in the left upper lobe, although the as
typical generalised pattern appeared in subsequent films ; and Dawson points out that Paliard et al.16 previously reported a case in which radiography showed opacities confined to the upper lobes. More information about pulmonary tuberous sclerosis would be welcome, and the interest aroused by Dawson’s paper may result in the recognition of more examples of the condition. PENICILLIN IN DIPHTHERIA DIPHTHERTA has become uncommon in this country and in the U.S.A., so experience of treatment with penicillin is very limited. It has been used only in combination with antitoxin, and this combination has been found to have little if any advantage over antitoxin alone in saving life and reducing complications.17-2o Cruickshank et al.21 found that a dosage of 40,000 units of penicillin four-hourly, combined with antitoxin, shortened the duration of carriage of Corynebacterium diphtheriae in acute faucial diphtheria, but they did not comment on the influence of penicillin on the clinical course of the disease. There are likely to be few opportunities in this country of confirming or refuting the finding, by Calvet and Herrera,22 that penicillin alone in large dosage (500,000 units six-hourly) is superior to antitoxin alone in the treatment of faucial and laryngeal 9. Farber, S. Amer. J. Path. 1931, 7, 105. 10. Dalsgaard-Nielsen, T. Nord. med. Tidskr. 1935, 10, 1541. 11. Marcus, H. Svenska LäkSällsk. Förh. 1924, 358. 12. Gottlieb, J. S., Lavine, G. R. Arch. Neurol. Psychiat., Chicago, 1935, 33, 379. 13. Licht, E. de F. Acta radiol., Stockh. 1942, 23, 151. 14. Borberg, A. Clinical and Genetic Investigations into Tuberous Sclerosis and Recklinghausen’s Neurofibromatosis. Copenhagen, 1951. 15. Thannhauser, S. J. Lipidoses. New York. 1950. 16. Paliard, Plauchu, Galy, and Papillon. Poumon, 1946, 2, 205. 17. Dodds, R. J. Brit. med. J. 1946, ii, 8. 18. Karelitz, S., Wassermann, L. R., Moloshok, R. J. Pediat. 1947, 30, 18. 19. Weinstein, L. Amer. J. med. Sci. 1947, 213, 318. 20. Bruyn, H. B.,Brainerd. H., Leppla, B. W. Ibid, 1950, 219, 408. 21. Lancet, 1948, ii, 517. 22. Calvet J. R., Herrera, R. G. Bol. Coll. mád. Habana, 1953, 4, 501.