392

DR. LORBER: REFERENCES

Baggenstoss, A. H., Feldman, W. H., Hinshaw, H. C. (1947) Amer.Rev. Tuberc. 55, 54.

Brailey, M. E. (1943) Amer. J. publ. Hlth, 33, 343.Dubois, R., Linz, R., Leschanowski, H., Schlesser, R., Nattiez, R.

(1948) Acta clin. belg. 3, 1.Fanconi, G., Dolivo, G. (1948) in Fanconi and Löffler’s Strepto-

mycin und Tuberkulose. Basle ; p. 173.Flory, C. M., Correll, J. W., Kidd, J. G., Stevensón, L. D., Alvord,

L. C., McDermott. W., Muschenheim, C. (1948) Amer. Rev.Tuberc. 58, 4-21.

Lamy, M., Jammet, M. L., Aussannaire, M., Nézeloff, C., Guerod, L.(1948) Arch. franç. pédiat. 5, 299.

Levine, M. I. (1944) Amer. J. Dis. Child. 68, 385.Löffler, W., Piotti, A. (1948) in Fanconi and Löffler’s Streptomycin

und Tuberkulose. Basle; p. 55.McDermott, W., Muschenheim, C., Hadley, S. J., Bunn, P. A.,

Gorman, R. V. (1947) Ann. intern. Med. 27, 769.McEnery, E. T., Sweaney, H. C., Turner, G. C. (1949) Pediatrics,

4, 323.Medical Research Council (1948) Lancet, i, 582.Mitchell, G. F., Willis, H. S. (1944) Amer. Rev. Tuberc. 50, 316.Montgomery, G. L. (1948) Glasg. med. J. 29, 235.Morin, J. (1949) Acta tuberc. belg. 40, 48.Mouriquand, G., Boulez, N., Dechavanne, D., Fayard, C. (1948)

Rev. mens. pédiat. 376.Rubie, J., Mohun, A. F. (1949) Brit. med. J. i, 338.Sanford, H. N., O’Brien, D. E. (1947) J. Amer. med. Ass. 133, 691.Wallgren, A. (1941) Amer. J. Dis. Child. 61, 577.Wissler, H. (1948) in Fanconi and Löffler’s Streptomycin und

Tuberkulose. Basle; p. 171.Zollinger, H. U. (1948) Ibid, p. 336.

CYSTIC PULMONARY FIBROSIS IN

GENERALISED SCLERODERMAREPORT OF TWO CASES

R. E. CHURCH

M.A., M.B. Camb.REGISTRAR, SKIN DEPARTMENT

A. R. P. ELLISD.S.O., M.B. Camb.MEDICAL REGISTRAR

ADDENBROOKE’S HOSPITAL, CAMBRIDGE

With illustrations on plateTHE early symptoms of generalised scleroderma often

lead the patient to consult a dermatologist. However,the ramifications of the disease extend more deeply thanthe skin, since scleroderma is a disease of the connectivetissue as a whole. Recently attention has been focusedon the internal organs which may also be involvedin the sclerotic process (Beerman 1948). Affectionsof heart, oesophagus and alimentary tract, kidneys,pituitary, thyroid, adrenals, eyes, and larynx have allbeen described in scleroderma. Pulmonary changes arebecoming more widely recognised as they are sought,and it is to these that we are giving our particularattention.

In early descriptions of generalised scleroderma

dyspnoea and liability to pulmonary infection were

generally attributed to restriction of respiratory move-ments by sclerotic changes in the skin and muscles ofthe chest wall, but it seems likely that respiratorysymptoms may often have been due to undetectedfibrotic changes in the lungs themselves. In 1889 Finlaydescribed the case of a man, aged 36, with generalisedsclerosis of the skin, clawing of the hands, and pigmenta-tion. The patient was troubled with chronic cough anddyspncea. Examination showed impaired movement ofthe chest with signs of generalised bronchitis and ofconsolidation at the left base. Two years later Finlay(1891) recognised the association between sclerodermaand pulmonary fibrosis. Lewin and Heller (1895)reviewed a large number of published cases of sclero-derma, including that of Finlay. In 6 of these casesdyspnoea was conspicuous, and they associated it withsclerosis of the chest wall rather than of the lung.Thickening of the aryteno-epiglottic folds was suggestedas a contributory factor. Of their 28 autopsy cases,fibrosis of the lungs was present in at least 2, and emphy-sema, pleurisy, and tuberculosis were found in others.Matsui (1924) reported 6 cases of scleroderma with post-mortem findings. In 3 of these pulmonary fibrosis wasfound at autopsy though there had been no symptomsto suggest it during life.

Most of the previous reports on the lung changes inscleroderma have described generalised fibrosis of thelungs particularly affecting the lower lobes, with radio-logical appearances suggesting bronchiectasis. Linenthaland Talkov (1941) reported 3 cases of pulmonary fibrosisassociated with Raynaud’s phenomenon, a common

presenting feature of scleroderma. X-ray films of thechest in all 3 cases showed exaggerated lung markings,particularly affecting the lower zones, the apices beinglargely spared. Murphy et al. (1941) described the caseof a negress whose chest X-ray film showed a diffusenetwork of fibrosis throughout both lungs. Broncho-

graphy, as in most other reported cases, was normal.Weiss et al. (1943), in their description of 9 cases withheart involvement, found diffuse mottling opacity in thelungs of 6. The appearances suggested lipoid pneumoniaor bronchiectasis. Microscopic examination of the lungsfrom 2 of these cases showed extensive fibrosis and

thickening of the alveolar walls with coarse collagenousconnective tissue. Peribronchial and perivascular con-nective tissue was increased in amount, causing diminu-tion in the calibre of both bronchi and blood-vessels.Fox (1947) reported a case of scleroderma of acute onsetfollowing " influenza," in which chronic cough and

dyspncea developed and X-ray films showed diffuse

pulmonary fibrosis. Bourn (1947) remarked on thepresence of lung fibrosis in 2 of his 3 cases of acrosclerosiswith cesophageal lesions ; in 1 case the fibrosis affectedparticularly the right apex, whereas in the other it wasbasal.Four further cases of generalised scleroderma with

diffuse pulmonary fibrosis were recorded by Lloyd andTonkin (1948). The lung changes were predominantlybasal. Three of these cases presented with typicalRaynaud attacks. The case of Wigley et al. (1949) isof particular interest since dyspnoea and pulmonaryfibrosis preceded the appearance of skin changes by overtwo years. Other cases showing radiological evidence ofpulmonary sclerosis have been reported by Jackman(1943), Kanee (1944), Bevans (1945), Mathison andPalmer (1947), and East and Oram (1947).None of these writers mentions cystic changes in the

lung& in any of their cases. Dostrovsky (1947) howeverdescribes 3 cases of progressive scleroderma associatedwith fibrosis and cyst formation in the lungs, which hecalled pulmosclerosis cystica. The cases were under hisobservation for a long time. In the lung he found thatmuch of the lung tissue had been replaced by fibroustissue containing numerous cavities. In -all 3 cases therewas no clinical evidence of pulmonary fibrosis for aconsiderable period after the appearance of skin changes.

LEGENDS TO ILLUSTRATIONS ON PLATEDR. ROBERTS, DR. BLAIR

Fig. I-Case A, showing localised emphysema at right base due topartial obstruction of the right lower-lobe bronchus by a gland.The symptoms were continuous asthma.

Fig. 2-Case A, showing crowding of bronchi in right lower lobe.Fig. 3-Case A, lateral view of fig. 2.Fig. 4-Case A. Bronchogram five years later, showing normal broncht

in right lower lobe.Fig. 5-Case A, lateral view of fig. 4.Fig. 6-Case 11, showing collapse of right upper lobe.Fig. 7-Case II, when the lobe had re-expanded after bronchoscopy.Fig. 8-Case 11, bronchogram of right upper lobe showing absence ofbronchiectasis. -

Fig. 9-Case 8, showing collapse of left upper lobe.Fig. 10-Case 8, five months later, showing complete collapse of left

lung.Fig. II—Case 8, two years later. Oblique view. Bronchogram showingbronchiectasis of left upper lobe, but normal lower-lobe bronchi.

Fig. 12-Case 2, showing partial collapse of right upper lobe withpossible early bronchiectasis, due to blockage of bronchus.

Fig. 13-Case 2, end-result showing shrunken bronchiectatic right upperlobe.

Fig. 14-Case C (adult), showing cystic appearance of right upper lobe,with calcified gland at the root.

Fig. I5—Case C. Bronchogram showing cystic bronchiectasis of rightupper lobe, with calcified gland at the root.

Fig. 16-Case D (adult), showing disseminated calcified lesions in bothlungs with bronchial dilatation in the collapsed left lower lobe.

DR. ROBERTS, DR. BLAIR : BRONCHIECTASIS AND PRIMARY TUBERCULOSIS

DR. CHURCH. DR. ELLIS: PULMONARY FIBROSIS IN SCLERODERMA

SIR ADOLPHE ABRAHAMS : ARTERIAL CALCIFICATION

DR. J. LORBER : e STREPTOMYCIN IN TUBERCULOSIS

393

The histological changes in Dostrovsky’s cases are

discussed by Getzowa (1945), who suggests that the

primary morbid process takes place in the connectivetissue, the- blood-vessels and lung parenchyma beingsecondarily affected. The microscopic changes in the

lungs were found to be identical with those occurring inthe sclerosed skin. This is not in agreement with Baehrand Pollack (1947), who consider that the primary changesof scleroderma are vascular with endarteritis and fibrinoidnecrosis of the vessel walls and surrounding collagentissue. It may be concluded that fibrosis, which is thepredominant feature of scleroderma, particularly as itaffects the lungs, is secondary to these changes.

CASE-REPORTS

Case 1.-A married woman, aged 49, was well until fourteenyears ago when she was admitted to North CambridgeshireHospital with fever, weakness, and generalised pains in thelimbs and stiffness of the joints. This illness lasted for threemonths and was diagnosed as rheumatic fever. The painspersisted in the fingers, toes, knees, and spine. Raynaud’sphenomena are described as occurring in the fingers duringcold weather. Two years later the fingers began to contractinto a fixed position of flexion, and subsequently the patientnoticed difficulty in opening her eyes because the eyelids feltstiff. Intermittent dysphagia was first noticed at this time.Over a period of five years the patient lost 3 stone in weight.In 1942 she was admitted to Addenbrooke’s Hospital

diagnosed as sclerodactyly. Examination then showed amilder degree of her present condition, save that there wereno symptoms referable to the lungs and the X-ray filmsshowed only slight pleural thickening at the right base. Otherinvestigations at that time showed a basal metabolic rate(B.M.R.) of + 18%, negative Wassermann reaction, and anormal blood-count. Mantoux test (1 in 1000) was positive.

Six months ago she had an attack of laryngitis accompaniedby pleurisy. Since then she has had troublesome dyspnoea onexertion and cough with up to an ounce of sputum per day.The scleroderma continues to progress slowly and she hasnow lost 4 stone in weight since the onset of the disease.Family history : one sister suffers from stiffness of the

fingers attributed to rheumatoid arthritis.On examination, the patient is very emaciated with scanty

body hair. The skin of the face is pigmented, stretched, andtaut but not hard. The lips are thinned and contracted withradial furrowing. The nose is sharp and pinched with theskin drawn tightly over the cartilage. The fingers are fixedin a position of flexion of all the joints. There is slight clubbingof the nails and ulceration over some of the interphalangealjoints. The skin is shiny and pigmented over the fingers, hands,and in decreasing degree up the forearms. Hard pea-likesubcutaneous nodules are palpable round both elbow-joints.Flexion of the knee-joints is limited to 90°. The tongue issmooth and depapilated. The trachea is deviated to the left.There is poor but equal expansion of the chest and an impairedpercussion note over the left base where bronchial breathingis audible. There are rales and rhonchi over both lungs, mostmarked on the left side. No abnormalities were noted in othersystems.X-ray examination . of the hands and forearms shows

advanced rarification of the terminal phalanges, with calcar-eous deposits round the wrists and elbow-joints. X-ray filmsof the chest (fig. 1) show diffuse fibrosis, especially at the leftbase. A cyst is present at the left base and other fine cystic

outlines are visible throughout the left lung. A bronchogram

LEGENDS TO ILLUSTRATIONS ON PLATE

DR. CHURCH, DR. ELLIS

Fig. I-Case I on June 17, 1949 : diffuse fibrosis and cyst formation.Fig. 2-Case 2 on Dec. 9, 1946 : consolidation in right lower zone.(Film on April 21, 1947, showed further consolidation of right lung.)

Fig. 3-Case 2 on June 6, 1947 : cysts, particularly in right upper zone.SIR ADOLPIIE ABRAIIAMS

Fig. I-Calcified arteries of leg.Fig. 2-Calcified phalangeal artery of hallux.

DR. LORBER

Fig. I-Case 6 on admission : miliary, with opacity in left lung. (a)19 months later : opacity persists, with calcified mass in upper lobe.

Fig. 2-Case 14 on admission : miliary, with primary focus at righthilum. (a) After 6 months’ treatment : lesion larger (fatal case).

Fig. 3-Case 48 on admission : miliary, with primary lesion at righthilum. (o) After 10 months’ treatment : lesion much larger.

shows a mild degree of bronchiectasis, but the cysts were notentered by the iodised oil. A barium swallow showed no

abnormality of the oesophagus. -

No tubercle bacilli were found in the sputum. Electro-

cardiogram and urinary creatinine output were normal. Theurine contained no creatine. Red-cell count 3,740,000 perc.mm., Hb 10-4 g. per 100 ml., white cells normal.

Case 2.-A married woman, aged 47 years. In 1935, at theage of 33, she started to get typical Raynaud attacks, with" deadness " and pallor of the fingers. These attacks have

gradually become more severe. The feet, ears, nose, and

occasionally the tongue, are now similarly affected. At thesame time she noticed that her skin was becoming darker andshe began to suffer from epigastric pain and vomiting. Her

symptoms at that time suggested a peptic ulcer but a bariummeal in 1936 did not show an ulcer, though there was somedilatation of the stomach.

In 1937 she was admitted to Addenbrooke’s Hospital anddiagnosed as scleroderma with Raynaud’s phenomenon.Chemical investigations gave no support to the possibility ofher pigmentation being due to Addison’s disease. (Blood-pressure 115/75 mm. Hg.) She was treated with injections of’Padutin’ with slight improvement. However, she continuedto have attacks of abdominal pain and occasional episodes of.diarrhoea. The spleen was repeatedly palpable at this time.She lost weight.

In 1944 she began to have dysphagia. Her food seemed tostick substernally. A barium swallow showed a taperingconstriction at the lower end of the oesophagus, and follow-through showed considerable delay in the passage of bariumwith absence of the normal intestinal pattern and clumpingof the barium. For her dysphagia she subsequently used amercury bougie with considerable benefit.

In 1946 the vomiting became more severe and persistent.A gastroenterostomy was performed for pyloric stenosis. Shecontinued to vomit occasionally after the operation and soondeveloped a cough with mucopurulent sputum. There was onesmall haemoptysis and she became dyspnoeic on effort. Thiswas followed by a long illness with irregular fever and con-solidation of the right lung, beginning in the right lower lobe(fig. 1). The process gradually spread to involve part of theright upper lobe. Many samples of her sputum were negativefor tubercle bacilli. There was no leucocytosis but she had aconsiderable microcytic ansemia (Hb 8-2 g. per 100 ml.). Herweight had now fallen from 71/2 to 5 stone.No appreciable response followed a full course of chemo-

therapy (sulphadimidine 35 g. and penicillin 8 mega units),but her fever slowly settled and the opacity in her right chestgradually resolved to leave a cystic appearance particularlyaffecting the right upper zone (fig. 2). There was also someresidual fibrotic change in the left lung. The X-ray findingswere reported on by Dr.F. R. Berridge, radiologist to Adden-brooke’s Hospital, who correlated the lung changes with herscleroderma.

Since 1947 she has gradually improved and has gainedweight. She is still dyspnoeic on effort and has a troublesomecough with up to 1 oz. of sputum per day. Her anaemia hasimproved (Hb 11-0 g. per 100 ml.).On examination she now has the typical pinched immobile

facies of scleroderma with tightly stretched skin and fissuresradiating from the corners of her mouth. Small telangiectatic

spots are present on both cheeks and the lower lip. There isgeneralised pigmentation of the skin. The flexures, nipples,and her operation scar are not conspicuously pigmented butthere is one small patch of pigmentation inside the rightcheek. A few depigmented patches are present on the legs.The skin is dry and atrophic and there is induration of thesubcutaneous tissues, especially of the forearms. A typicalRaynaud’s attack was witnessed during recent examination.There is some limitation of movement in the joints of thefingers and wrists, but no obvious deformity of the hands.Small superficial ulcers are present on the fingers. The patientalso shows evidence (radiological only) of subcutaneouscalcinosis in the upper extremities. Cardiovascular examina-

tion, including E.C.G., shows no abnormality. Her blood-

pressure is now 130/80 mm. Hg. On routine examination theurine is also normal. Physical examination of the chest showsa pronounced dorsal kyphosis with poor but apparently equalexpansion. Percussion note is impaired over the right upperchest and there are poor breath sounds and occasional crepita-tions over the same area. There are no clinical signs of cavita-tion, which suggests that there is no free - communicationbetween the cysts and the corresponding bronchi.

I2