324 Short reportsDiscussion

In the original article by Dubowitz et al. (1970)and in the subsequent studies there were few infantsofvery lowweight or gestational age: there were only3 infants at 32 weeks, one at 31, and 2 at 28 weeks.The line for the lower gestations is an extrapolationof the correlation found nearer term. Singer et al.(1973) added a further 16 scores below 32 weeks.It is therefore gratifying to have found a satisfactorycorrelation between the scored and calculated agesin the present study. The correlation couldprobably be improved if detailed antenatal findingswere also used to calculate the duration of gestation.But it is in communities where such antenatal careis minimal that the highest incidence of very pre-mature deliveries occurs. Mothers from lesssophisticated backgrounds are, however, surprising-ly accurate with their dates.

SummaryThe accuracy of gestational age assessment

(Dubowitz et al., 1970) was tested for infantsweighing 1500 g or less. There was good correla-tion with known dates. This system is applicable toand accurate for infants delivered very prematurely.

We thank Dr. J. G. Burger of Groote Schuur Hospitalfor permission to publish; the Medical Research Councilof South Africa for financial support; and Miss C. Vaderfor statistical analysis.

REFERENCES

Amiel-Tison, C. (1968). Neurological evaluation of the maturityof newborn infants. Archives of Disease in Childhood, 43, 89.

Brueton, M. J., Palit, A., and Prosser, R. (1973). Gestational ageassessment in Nigerian newbom infants. Archives of Disease inChildhood, 48, 318.

Dubowitz, L. M. S., Dubowitz, V., and Goldberg, C. (1970).Clinical assessment of gestational age in the newbom infant.Journal of Pediatrics, 77, 1.

Farr, V., Mitchell, R. G., Neligan, G. A., and Parkin, J. M. (1966).The definition of some external characteristics used in theassessment of gestional age in the newborn infant. Develop-mental Medicine and Child Neurology, 8, 507.

Jaroszewicz, A. M., and Boyd, I. H. (1973). Clinical assessment ofgestional age in the newborn. South African Medical Journal,47, 2123.

Lubchenco, L. O., Hansman, C., Dressler, M., and Boyd, E. (1963).Intrauterine growth as estimated from liveborn birth-weightdata at 24 to 42 weeks of gestation. Pediatrics. 32, 793.

Singer, B., Blake, L., and Wolfsdorf, J. (1973). Estimation ofgestational age of African newborn infants by a scoring system.South African Medical Journal, 47, 2074.

A. F. MAIAN* and S. C. HIGGSDepartment of Paediatrics and Child Health,University of Cape Town, Observatory, SouthAfrica 7900.

*Correspondence to Dr. A. P. Malan.

Desquamative fibrosing alveolitisunresponsive to steroid or

cytotoxic therapyFibrosing alveolitis is not uncommon in adults

but is rare in infancy, though cases have beenreported with predominantly a fibrosing pattern(Hilton and Rendle-Short, 1961) and with a des-quamative pattern (Liebow 1972; Howatt et al.,1973). We describe a further case diagnosed byneedle lung biopsy which showed a number ofimportant differences from the usual adult pattern.

Case reportThe patient was a male infant delivered by forceps

at 39 weeks' gestation, weighing 3 * 6 kg, to a 40-year-oldmother whose pregnancy had been complicated by mildhypertension for which she received diazepam andnitrazepam. 2 previous children, aged 10 and 14 years,and both parents were healthy. Though his immediateneonatal progress was uncomplicated and he was dis-charged home on the 5th day, he was readmitted to theChurchill Hospital aged 2 months because of persistenttachypnoea and failure to thrive. He had an occasionaldry cough and was very irritable. There were no ab-normal physical signs apart from his obvious growthfailure. At this stage a number of investigations werecarried out which failed to reveal any cause forhis problems. Cystic fibrosis and immunodeficiencydisorders were excluded and no pathogens were isolated.He was treated with high calorie feeds but did not gainweight.Over the next 2 months the infant became obviously

cyanosed at rest and pink when given °2. Despitepersistent tachypnoea there were still no abnormal signsin his chest and chest x-rays were thought to be normal.Arterial blood gases showed hypoxia breathing air with aPo2 of27 torr, Pco2 of 35 torr, andpH 7 - 3. When given90%O2 the Po2 rose to 287 torr, suggesting severeventilation-perfusion imbalance and excluding atelacta-sis or cardiac causes of right to left shunting. He wastransferred to Brompton Hospital for further investiga-tion. His chest was now clinically hyperinflated andthis was confirmed by x-rays. Lung mechanics werestudied in the whole body infant plethysmograph(Dr. M. Radford). Thoracic gas volume was 240 ml(expected 135 ml) confirming the hyperinflation, andairways resistance was 16 cm H2O/l per s (expected: 12to 14 cm H20/l per s).A needle aspiration biopsy of the left lung was carried

out under radiological control (Dr. I. Kerr). This wasreported (Dr. K. W. Hinson) as showing thickening ofalveolar walls with mononuclear cell infiltrations.Other large mononuclear cells lined the alveolar spacesand were present free in the lumen. There was noapparent increase in fibrous tissue. Examination forPnewnoqystis carinit was negative, as was screening for arange of autoantibodies. Because of the histological

Short reports

FIG. 1.-Whole lung sections from each lung to show the diffuse nature of the disease process. (H. and E. normal size.)

FIG. 2.-Thickening of walls, a cuboidal or low columnar lining to air spaces containing many desquamated cells.(H. and E. x 66.)

326 Short reportspicture treatment was begun with prednisolone whichwas increased to a maximum of 20 mg/day with noimprovement. He developed signs of heart failure andwas digitalized. At the age of 7 months treatment wasbegun with azothioprine up to a dose of 25 mg/day butthis made no difference to his clinical condition, bloodgases, or lung mechanics. His chest remained clear toauscultation and he did not develop clubbing but slowlydeteriorated and died at the age of 9 months.

Necropsy. This revealed a thin infant weighing5 * 23 kg. There was pronounced right ventricularhypertrophy and dilatation. The lungs were enlargedand showed a diffuse, fine cystic pattern with clearlobular demarcation. The bronchial tree was normal.Histologically there were diffuse changes throughoutboth lungs (Fig. 1) which were essentially the same asthose seen earlier in the needle biopsy. Apart from themononuclear inflammatory cell infiltration of alveolarwalls and desquamation of cells into the lumen (Fig. 2),there was also some eosinophilic, PAS-positive materialpresent, sometimes spilling into the bronchioles. Thismaterial was apparently derived from breakdown of thedesquamated large mononuclear cells; it did not reactfor fibrin and no iron was present. Both the mono-nuclear cells and the derived material reacted positivelywith Alcian Blue and Sudan Black, suggesting the pre-sence of acid mucopolysaccharides and lipids-possiblyphospholipid. A prominent feature was smooth musclehyperplasia around bronchiolar walls and particularly atthe necks of alveolar ducts. Further smooth musclehyperplasia was identified around arterioles indicatingpulmonary hypertension. The rest of the necropsyfindings were unremarkable.

DiscussionThis infant suffered a severe progressive pul-

monary disease which did not respond to steroidsor immunosuppressive agents. The histologicalappearance of the lungs, with preservation of thearchitecture, minimal fibrosis, and infiltration, andan extensive alveolar exudate composed of cellsof PAS-positive cytoplasm, is that characterized byLeibow, Steer, and Billingsley, (1965) as des-quamative interstitial pneumonia. Though Leibow(1972) makes a clear distinction between desquama-tive interstitial pneumonitis and fibrosing alveolitisboth in adults and children, other authorities(Scadding and Hinson, 1967; Brown and Turner-Warwick, 1971; Patchefsky, Fraimow, and Hoch,1973) believe that the two conditions are at differentends of the spectrum of diffuse fibrosing alveolitis.Although the infant received oxygen for the last

6 months of life, pulmonary disease developedbefore oxygen therapy was started and pulmonaryhistology at biopsy and at necropsy showed changesquite distinct from those attributed to pulmonaryoxygen toxicity.

In adults this is one of the group of restrictivelung diseases characterized by breathlessness,hypoxia, fine basal crepitations, clubbing, mottlingon the chest x-ray, and small stiff lungs. In adultswith desquamative type of histology the response tosteroid therapy or immunosuppressive agents isusually good (Brown and Turner-Warwick, 1971).Infants usually have a rapidly progressive diseasewith tachypnoea, hypoxia reversed by oxygen, andhyperinflation of the lungs, though the present caseis the only one known to us in which this wasconfirmed physiologically in life. The disease israre, only 8 cases have been described in infants;the prognosis is poor. Cases with a fibrosinghistology described by Feinerman and Harris (1957),Mann (1959), and Hilton and Rendle-Short (1961)have all died, though 2 of the cases in infancy re-viewed by Leibow (1972) with the desquamativehistology did respond as expected (Brown andTurner-Warwick, 1971) to steroids. Our case andthe one described by Howatt et al. (1973) did not.The case described here is the only one in infancyin which both steroids and immunosuppressiveagents have been tried and proved unhelpful.

SummaryA case of desquamative fibrosing alveolitis

beginning in early infancy is described. Thedisease was characterized by tachypnoea, hypoxiarelieved by O°, absence of signs in the chest orclubbing, and radiological and physiological evi-dence of hyperinflation. The diagnosis was madeby needle biopsy of the lung. Treatment withsteroids and immunosuppression was withouteffect and the infant died at 9 months. The diseasehas a high mortality in infancy, only 2 out of 9reported cases having survived. The differencefrom the usual course in adults and older childrenis noted.We thank Professor J. P. M. Tizard for allowing us to

report a case admitted under his care, and for his helpin the preparation of the manuscript.

REFERENCES

Brown, C. H., and Turner-Warwick, M. (1971). The treatment ofcryptogenic fibrosing alveolitis with immunosuppressant drugs.Quarterly Journal of Medicine, 40, 289.

Feinerman, B., and Harris, L. E. (1957). Unusual interstitialpneumonitis. Proceedings of the Staff Meetings of the MayoClinic, 32, 637.

Hilton, H. B., and Rendle-Short, J. (1961). Diffuse progressiveinterstitial fibrosis of the lungs in childhood. (Hamman-Richsyndrome). Archives of Disease in Childhood, 36, 102.

Howatt, W. F., Heidelberger, K. P., LeGlovan, D. P., and Schnitzer,B. (1973). Desquamative interstitial pneumonia. AmericanJournal of Diseases of Children, 126, 346.

Liebow, A. A. (1972). Desquamative interstitial pneumonia.Pulmonary Disorders, Vol. I, Disorders of the Respiratory Tractin Children, p. 325. Ed. by E. L. Kendig. Saunders, Philadel-phia.

Short reports 327Liebow, A. A., Steer, A., and Billingsley, J. G. (1965). Desquama-

tive interstitial pneumonia. American Journal of Medicine, 39,369.

Mann, T. P. (1959). Diffuse progressive interstitial fibrosis oflungs in infancy. Proceedings of the Royal Society of Medicine,52, 638.

Patchefsky, A. S., Fraimow, W., and Hocb, W. S. (1973). Des-quamative interstitial pneumonia. Pathological findings andfollow-up in thirteen patients. Archives of Internal Medicine,132, 222.

Scadding, J. G., and Hinson, K. P. W. (1967). Diffuse fibrosingalveolitis (diffuse interstitial fibrosis of the lungs). Thorax, 22,291.

S. E. BARNES,* S. GODFREY4t G. H. MILLWARD-SADLER, and N. R. C. ROBERTON*Departments of Paediatrics and Pathology of TheUnited Oxford Hospitals, and the Brompton Hospital,London.

*Correspondence to Dr. S. B. Barnes,9John Radcliffe Hospital,Headington, Oxford OX3 9DU.

tPresent address: Department of Paediatrics and NeonatalMedicine, Hammersmith Hospital, London W12.

*Present address: Department of Paediatrics, Addenbrooke'sHospital, Cambridge.

The following articles will appear in future issues of this journal:

Enteropathogenic Esch. coli gastroenteritis in premature children and infants treated with fosfomycin.F. Baquero, T. Cafiedo, A. Rodriguez, and E. Jaso.Malabsorption syndrome with cow's milk intolerance: clinical findings and course in 54 cases. P. Kuitunen,J. K. Visakorpi, E. Savilahti, and P. Pelkonen.Small intestinal biopsy in cow's milk protein allergy in infancy. J. L. Fontaine and J. Navarro.Annotation: Cow's milk protein intolerance: transient food intolerance of infancy. J. Walker-Smith.Immediate metabolic response to a low dose of insulin in children presenting with diabetes. J. D. Baum,P. Jenkins. and A. Aynsley-Green.Isosorbide in treatment of infantile hydrocephalus. J. Lorber.Cytomegalovirus-mononucleosis in a newbom infant. M. Umetsu, Y. Chiba, K. Horino, S. Chiba, and T. Nakao.Thymic dysplasia, persistence of measles virus, and unexpected infant death. P. F. Roberts.