230
Brief clinical and laboratory observations
The Journal of Pediatrics August 1975
The results suggeqt that culture of the blood is a valuable diagnostic technique in children u n d e r 2 years of age in whom the initial clinical diagnosis is p n e u m o n i a or U R I / F U O a n d who have rectal temperatures of 38.9 ~ C (102 ~ F) or higher and white blood cell counts of 15,000/ m m 3 or higher. The results indicate that bacteremia is infrequent in child~ren~ in whom the diagnosis is otitis media and; pharyngkis and in children with white blood cell counts Under~ 15,000/mm ~ or rectal temperatures under 38.9 ~ C (10/2~ F). Since the inciflence of bacteremia is significant in the young child with p n e u m o n i a or U R I / F U O who also has an elevated white blood cell count and elevated rectal temperature, the data are persuasive that such children must be carefully observed and managed. N o n e of the
children with bacteremia in the present study progressed to severe life-threatening disease. Some of the untreated children with pneumococcemia appeared to recover spontaneously and had negative cultures of blood when reexamined within 48 hours. Nevertheless, the children who are initially bacteremic may progress to meningitis or other serious complications ~ and therefore require cautious management.
Congenital bronchiectasis due to deficiency of bronchial cartilage ( I4'Tlliams- Campbell syndrome)
or after measles or p n e u m o n i a . Death m a y occur before the age of 5 years; those surviving suffer from frequent respiratory tract ~infections and have limited physical activity, but there is a tendency for some i m p r o v e m e n t over the years. Because there has been only one previously published autopsy, the following case is reported.
A case report Ruth E. Mitchell, M.D., D.C.H.,* and R. Graham Bury, M.R.A.C.P., D.C.H., Hobart, Tasmania
IN BOTH LOBAR and generalized bronchiectasis in children, cases have been reported in which the primary cause is a congenital deficiency of the bronchial cartilaginous plates. The generalized condition appears to be rare. Initially five cases were reported by Williams and Campbell in 1960,1 including one autopsy study which showed bronchiectasis distal to the first division of the segmental bronchi associated with deficiency in these bronchial cartilage plates. A n additional 15 cases were added by 1972, and the condition was n a m e d the Williams-Campbell syndrome. 2-' These studies showed that the children have characteristic clinical features. Typically there is persistent cough, wheezing, and emphysema which develops in early infancy after a mild respiratory infection
From the Departments of Pathology and ChiM Health, Medical School, University of Tasmania. *Reprint address: Departmentof Pathology, Universityof Tasmania, Hobart, Tasmania.
REFERENCES 1. McGowan JE Jr, Bratton L, Klein JO, and Finland M: Bacteremia in a "walk-in" pediatric clinic, N Engl J Med 288:1309, 1973. 2. Myers MG, Wright PF, Smith AL, and Smith DH: Complications of occult pneumococcal bacteremia in children, J PEDIATR84:656, 1974.
CASE R E P O R T Clinical features. Patient D. W. had his first attack of bronchitis with wheezing at the age of 11 months. He had not had measles or any other significant illness before this time. Three similar but short-lived attacks occurred over the next year, but from the age of 21/2 onward an expiratory wheeze was present continuously. The lungs became overdistended and despite fluctuation in intensity, there was a continual deterioration in exercise tolerance. Treatment for bronchial asthma was ineffective. Central cyanosis with clinical signs of pulmonary hypertension was first detected at the age of 389 years. Apart from expiratory rhonchi a soft inspiratory wheeze was often heard and moist r~les were only rarely present. On only two occasions was there clinical and radiologic evidence to suggest pneumonia. The blood count and serum immunoglobulins were normal, the eosinophil count was normal in the peripheral blood, and the concentration of sweat sodium was 35 mEq/l, The roentgenograms of the chest showed severe hyperinflation of the lungs with progressive cardiac enlargement in the last few months; the electrocardiogram showed evidence of right ventricular strain. At bronchoscopy, done for bronchial lavage, the lower lobe bronchi were seen to collapse during expiration, and pulmonary artery pressure obtained during cardiac catherization shortly before death was 80/40 mm Hg. There was progressive worsening of dyspnea and cyanosis, and he died at the age of 4 years, 1 month. Pathologic features.* Abnormalities were confined to the cardiovascular and respiratory systems. The heart was enlarged (weight, 170 gm compared to the *These studies were made in collaborationwith Dr. John Nesbit.
Volume 87 Number 2
Fig. 1. The lungs have been sliced and are viewed from the posterior aspect. There is generalized bronchiectasis. The right middle and upper lobe have been dissected to display the dilated bronchi and the sudden tapering which occur 1 cm from the pleural surface. The arrow indicates the right upper apical segmental bronchus at the point where the cartilage plates became small and no longer form complete rings. Distal to this bronchiectasis is apparent and only occasional nodules of cartilage are present. normal of 70 gm), mainly due to hypertrophy and dilatation of the right side. The lungs were emphysematous and together weighed 400 gm. These were fixed by endotracheal perfusion. After slicing, one half was retained for microdissection. Several of the segmental bronchi Were dissected, cleared, stained with toluidine blue, dehydrated, and mounted in araldite between glass for microscopic examination. 5 The trachea and extrapulmonary bronchi appeared normal. The pulmonary artery and its major branches were slightly dilated, and branches passing to the lower lobes contained some antemortem thrombi. The lungs contained numerous nodular congested areas, especially in the lower lobes in association with the pulmonary arterial thrombi. Both lungs showed generalized cylindrical bronchiectasis involving all divisions o f the segmental bronchi. Microdissection of the right middle and upper lobes showed that bronchiectasis was present distal to the first division of the segmental bronchus and extended to within 1 cm of the pleural surface. Here the bronchus suddenly tapered and gave off a few fine branches with a narrow lumen (Fig. 1). Similar fine lateral branches were shown by dissection to arise more proximally from the dilated bronchi. Sometimes an axial bronchus could be recognized, but often the bronchus divided dichotomously giving two equally dilated branches. The bronchiectatic walls were thin and extremely compliant.
Brief clinical and laboratory observations
23 1
Fig. 2. Two bronchi are shown. Near the point of branching a small nodule of cartilage is present (top, left). An obliterated bronchiole at the lower edge is represented by a layer of smooth muscle inside which is some loose connective tissue. (Hemotoxylin and eosin; x 50).
Although normal amounts of cartilage were present in the lobar and main segmental bronchi, it suddenly became reduced to small plates where bronchiectasis was observed. Microscopic features. By serial sections using many blocks it was possible to trace several segmental bronchi to their fifth division. Distal to the main segmental bronchi the lumen was greatly enlarged and the wall very thin. The epithelium was intact and normal and the lamina propria was congested and contained collections of chronic inflammatory cells; mucosal glands were infrequent. The smooth muscle layer and elastic networks superficial and deep to it appeared normal, although greatly attenuated because o f the bronchiectasis. Small plates of histologically normal cartilage were present at many of the sites where branching occurred (Fig. 2). They became smaller and increasingly infrequent as the bronchus divided and were not seen after the fourth division of the segmental bronchus. Bronchial mounts also showed this distribution; when compared with similarly mounted normal bronchi the deficiency of cartilage and associated compliancy were readily apparent. There were few recognizable bronchioles. Dilated thin-walled passages lined by a single layer of columnar epithelium were surrounded by a narrow band of smooth muscle, and a few elastic and collagen fibers were presumed to be distal bronchi. Loose fibrous scars in the respiratory tissue were not uncommon, and serial sections
232
Brief clinical and laboratory observations
Fig. 3. Distensive panlobular emphysema in one of the most affected regions of the lung. (Hemotoxylin and eosin; X 150.) through these areas usually showed strands of smooth muscle or traces of a bronchiolar lumen. Obliterative bronchiolitis was therefore a significant feature in this case. There was generalized distensive emphysema, focally much worse in some areas, of a panlobular type. The extraordinary degree of distension of the respiratory tissue is shown in Fig. 3. Compared with the lungs of six children of a comparable age dying of conditions not involving the lung, the cartilage appeared to be the only deficient tissue; others were essentially normal, although distorted by the bronchiectasis and emphysema. DISCUSSION A comparison of these autopsy findings with the only other recorded case I shows a remarkable similarity; in each death occurred at a similar age with right ventricular failure, pulmonary congestion, emPhysema, and similar bronchial wall abnormalities. Identical bronchial appearances may be found in lobes resected for progressive congenital lobar emphysema. CampbelP described 12
Commentary T H E C L I N I C A L AND P A T H O L O G I C
F E A T U R E S in t h e
patient described by Mitchell and Bury are the same as
The Journal of Pediatrics August 1975
cases, eight of which he studied by microdissection. In these cases the deficiency of bronchial cartilage also did not involve the main segmental bronchi, but beyond this point there was a great diminution of the amount of cartilage present, that allowed dilatation of the otherwise normal wall. The compliant bronchial wall allows collapse during expiration with distal air trapping. The frequency of a localized deficiency of bronchial cartilage in childhood emphysema is uncertain. It was present in Campbell's 12 cases, but in only three of 36 cases reported by Leape and Longino.6. The amount of inflammation present, indicated by mucosal damage and metaplasia and by bronchiolitis obliterans, is variable from case to case and must play an important part in the clinical outcome. In this case obliterative bronchiolitis was present, but the bronchi, with their thin compliant bronchial wails and uniform, widespread deficiency of cartilage, did not appear to be damaged by inflammation. These observations support the view that there is a condition of congenital deficiency of bronchial cartilages which allows bronchiectasis to develop in segmental bronchi distal to the first division, and that such changes are primary and not due to infection. Although the generalized condition is rare it has distinctive features which should enable a clinical diagnosis to be made. More cases may well be recognized in the future. *Using different techniques and no mierodissection.
REFERENCES
1. Williams H, and Campbell P: Generalized bronchiectasis associated with deficiency of cartilage in the bronchial tree, Arch Dis Child 35:182, 1960. 2. Dietzsch HJ, and Wunderlich P: Das Williams-Campbell Syndrom-eine Sonderform generalisverter angeborener Bronchiektasen, Z Erkr Atmungsorgane 130:387, 1969. 3. Petr~inyi G: Uber die bedeutung des Williams-Campbell Syndroms in der differentialdiagnose der chronischen Bronchopneumopathien im Kindersalter, Prax Pneumol 20:721, 1966. 4. Williams HF, Landau LI, and Phelan PD: Generalized bronchiectasis due to extensive deficiency of bronchial cartilage, Arch Dis Child 47:432, 1972. 5. Campbell PE: Congenital lobar emphysema: Etiological studies, Aust Paediatr J 5:226, 1969. 6. Leape LL, and Longino LA: Infantile lobar emphysema, Pediatrics 34:246, 1964.
those Dr. Williams and I described in 1960. A deficiency of bronchial cartilage in all these cases now seems beyond question; less certain is the cause of the cartilaginous defect. Is this truly a developmental anomaly or is the cartilage destroyed by inflammation that occurs postna-
Brief clinical and laboratory observations
The Journal of Pediatrics August 1975
The results suggeqt that culture of the blood is a valuable diagnostic technique in children u n d e r 2 years of age in whom the initial clinical diagnosis is p n e u m o n i a or U R I / F U O a n d who have rectal temperatures of 38.9 ~ C (102 ~ F) or higher and white blood cell counts of 15,000/ m m 3 or higher. The results indicate that bacteremia is infrequent in child~ren~ in whom the diagnosis is otitis media and; pharyngkis and in children with white blood cell counts Under~ 15,000/mm ~ or rectal temperatures under 38.9 ~ C (10/2~ F). Since the inciflence of bacteremia is significant in the young child with p n e u m o n i a or U R I / F U O who also has an elevated white blood cell count and elevated rectal temperature, the data are persuasive that such children must be carefully observed and managed. N o n e of the
children with bacteremia in the present study progressed to severe life-threatening disease. Some of the untreated children with pneumococcemia appeared to recover spontaneously and had negative cultures of blood when reexamined within 48 hours. Nevertheless, the children who are initially bacteremic may progress to meningitis or other serious complications ~ and therefore require cautious management.
Congenital bronchiectasis due to deficiency of bronchial cartilage ( I4'Tlliams- Campbell syndrome)
or after measles or p n e u m o n i a . Death m a y occur before the age of 5 years; those surviving suffer from frequent respiratory tract ~infections and have limited physical activity, but there is a tendency for some i m p r o v e m e n t over the years. Because there has been only one previously published autopsy, the following case is reported.
A case report Ruth E. Mitchell, M.D., D.C.H.,* and R. Graham Bury, M.R.A.C.P., D.C.H., Hobart, Tasmania
IN BOTH LOBAR and generalized bronchiectasis in children, cases have been reported in which the primary cause is a congenital deficiency of the bronchial cartilaginous plates. The generalized condition appears to be rare. Initially five cases were reported by Williams and Campbell in 1960,1 including one autopsy study which showed bronchiectasis distal to the first division of the segmental bronchi associated with deficiency in these bronchial cartilage plates. A n additional 15 cases were added by 1972, and the condition was n a m e d the Williams-Campbell syndrome. 2-' These studies showed that the children have characteristic clinical features. Typically there is persistent cough, wheezing, and emphysema which develops in early infancy after a mild respiratory infection
From the Departments of Pathology and ChiM Health, Medical School, University of Tasmania. *Reprint address: Departmentof Pathology, Universityof Tasmania, Hobart, Tasmania.
REFERENCES 1. McGowan JE Jr, Bratton L, Klein JO, and Finland M: Bacteremia in a "walk-in" pediatric clinic, N Engl J Med 288:1309, 1973. 2. Myers MG, Wright PF, Smith AL, and Smith DH: Complications of occult pneumococcal bacteremia in children, J PEDIATR84:656, 1974.
CASE R E P O R T Clinical features. Patient D. W. had his first attack of bronchitis with wheezing at the age of 11 months. He had not had measles or any other significant illness before this time. Three similar but short-lived attacks occurred over the next year, but from the age of 21/2 onward an expiratory wheeze was present continuously. The lungs became overdistended and despite fluctuation in intensity, there was a continual deterioration in exercise tolerance. Treatment for bronchial asthma was ineffective. Central cyanosis with clinical signs of pulmonary hypertension was first detected at the age of 389 years. Apart from expiratory rhonchi a soft inspiratory wheeze was often heard and moist r~les were only rarely present. On only two occasions was there clinical and radiologic evidence to suggest pneumonia. The blood count and serum immunoglobulins were normal, the eosinophil count was normal in the peripheral blood, and the concentration of sweat sodium was 35 mEq/l, The roentgenograms of the chest showed severe hyperinflation of the lungs with progressive cardiac enlargement in the last few months; the electrocardiogram showed evidence of right ventricular strain. At bronchoscopy, done for bronchial lavage, the lower lobe bronchi were seen to collapse during expiration, and pulmonary artery pressure obtained during cardiac catherization shortly before death was 80/40 mm Hg. There was progressive worsening of dyspnea and cyanosis, and he died at the age of 4 years, 1 month. Pathologic features.* Abnormalities were confined to the cardiovascular and respiratory systems. The heart was enlarged (weight, 170 gm compared to the *These studies were made in collaborationwith Dr. John Nesbit.
Volume 87 Number 2
Fig. 1. The lungs have been sliced and are viewed from the posterior aspect. There is generalized bronchiectasis. The right middle and upper lobe have been dissected to display the dilated bronchi and the sudden tapering which occur 1 cm from the pleural surface. The arrow indicates the right upper apical segmental bronchus at the point where the cartilage plates became small and no longer form complete rings. Distal to this bronchiectasis is apparent and only occasional nodules of cartilage are present. normal of 70 gm), mainly due to hypertrophy and dilatation of the right side. The lungs were emphysematous and together weighed 400 gm. These were fixed by endotracheal perfusion. After slicing, one half was retained for microdissection. Several of the segmental bronchi Were dissected, cleared, stained with toluidine blue, dehydrated, and mounted in araldite between glass for microscopic examination. 5 The trachea and extrapulmonary bronchi appeared normal. The pulmonary artery and its major branches were slightly dilated, and branches passing to the lower lobes contained some antemortem thrombi. The lungs contained numerous nodular congested areas, especially in the lower lobes in association with the pulmonary arterial thrombi. Both lungs showed generalized cylindrical bronchiectasis involving all divisions o f the segmental bronchi. Microdissection of the right middle and upper lobes showed that bronchiectasis was present distal to the first division of the segmental bronchus and extended to within 1 cm of the pleural surface. Here the bronchus suddenly tapered and gave off a few fine branches with a narrow lumen (Fig. 1). Similar fine lateral branches were shown by dissection to arise more proximally from the dilated bronchi. Sometimes an axial bronchus could be recognized, but often the bronchus divided dichotomously giving two equally dilated branches. The bronchiectatic walls were thin and extremely compliant.
Brief clinical and laboratory observations
23 1
Fig. 2. Two bronchi are shown. Near the point of branching a small nodule of cartilage is present (top, left). An obliterated bronchiole at the lower edge is represented by a layer of smooth muscle inside which is some loose connective tissue. (Hemotoxylin and eosin; x 50).
Although normal amounts of cartilage were present in the lobar and main segmental bronchi, it suddenly became reduced to small plates where bronchiectasis was observed. Microscopic features. By serial sections using many blocks it was possible to trace several segmental bronchi to their fifth division. Distal to the main segmental bronchi the lumen was greatly enlarged and the wall very thin. The epithelium was intact and normal and the lamina propria was congested and contained collections of chronic inflammatory cells; mucosal glands were infrequent. The smooth muscle layer and elastic networks superficial and deep to it appeared normal, although greatly attenuated because o f the bronchiectasis. Small plates of histologically normal cartilage were present at many of the sites where branching occurred (Fig. 2). They became smaller and increasingly infrequent as the bronchus divided and were not seen after the fourth division of the segmental bronchus. Bronchial mounts also showed this distribution; when compared with similarly mounted normal bronchi the deficiency of cartilage and associated compliancy were readily apparent. There were few recognizable bronchioles. Dilated thin-walled passages lined by a single layer of columnar epithelium were surrounded by a narrow band of smooth muscle, and a few elastic and collagen fibers were presumed to be distal bronchi. Loose fibrous scars in the respiratory tissue were not uncommon, and serial sections
232
Brief clinical and laboratory observations
Fig. 3. Distensive panlobular emphysema in one of the most affected regions of the lung. (Hemotoxylin and eosin; X 150.) through these areas usually showed strands of smooth muscle or traces of a bronchiolar lumen. Obliterative bronchiolitis was therefore a significant feature in this case. There was generalized distensive emphysema, focally much worse in some areas, of a panlobular type. The extraordinary degree of distension of the respiratory tissue is shown in Fig. 3. Compared with the lungs of six children of a comparable age dying of conditions not involving the lung, the cartilage appeared to be the only deficient tissue; others were essentially normal, although distorted by the bronchiectasis and emphysema. DISCUSSION A comparison of these autopsy findings with the only other recorded case I shows a remarkable similarity; in each death occurred at a similar age with right ventricular failure, pulmonary congestion, emPhysema, and similar bronchial wall abnormalities. Identical bronchial appearances may be found in lobes resected for progressive congenital lobar emphysema. CampbelP described 12
Commentary T H E C L I N I C A L AND P A T H O L O G I C
F E A T U R E S in t h e
patient described by Mitchell and Bury are the same as
The Journal of Pediatrics August 1975
cases, eight of which he studied by microdissection. In these cases the deficiency of bronchial cartilage also did not involve the main segmental bronchi, but beyond this point there was a great diminution of the amount of cartilage present, that allowed dilatation of the otherwise normal wall. The compliant bronchial wall allows collapse during expiration with distal air trapping. The frequency of a localized deficiency of bronchial cartilage in childhood emphysema is uncertain. It was present in Campbell's 12 cases, but in only three of 36 cases reported by Leape and Longino.6. The amount of inflammation present, indicated by mucosal damage and metaplasia and by bronchiolitis obliterans, is variable from case to case and must play an important part in the clinical outcome. In this case obliterative bronchiolitis was present, but the bronchi, with their thin compliant bronchial wails and uniform, widespread deficiency of cartilage, did not appear to be damaged by inflammation. These observations support the view that there is a condition of congenital deficiency of bronchial cartilages which allows bronchiectasis to develop in segmental bronchi distal to the first division, and that such changes are primary and not due to infection. Although the generalized condition is rare it has distinctive features which should enable a clinical diagnosis to be made. More cases may well be recognized in the future. *Using different techniques and no mierodissection.
REFERENCES
1. Williams H, and Campbell P: Generalized bronchiectasis associated with deficiency of cartilage in the bronchial tree, Arch Dis Child 35:182, 1960. 2. Dietzsch HJ, and Wunderlich P: Das Williams-Campbell Syndrom-eine Sonderform generalisverter angeborener Bronchiektasen, Z Erkr Atmungsorgane 130:387, 1969. 3. Petr~inyi G: Uber die bedeutung des Williams-Campbell Syndroms in der differentialdiagnose der chronischen Bronchopneumopathien im Kindersalter, Prax Pneumol 20:721, 1966. 4. Williams HF, Landau LI, and Phelan PD: Generalized bronchiectasis due to extensive deficiency of bronchial cartilage, Arch Dis Child 47:432, 1972. 5. Campbell PE: Congenital lobar emphysema: Etiological studies, Aust Paediatr J 5:226, 1969. 6. Leape LL, and Longino LA: Infantile lobar emphysema, Pediatrics 34:246, 1964.
those Dr. Williams and I described in 1960. A deficiency of bronchial cartilage in all these cases now seems beyond question; less certain is the cause of the cartilaginous defect. Is this truly a developmental anomaly or is the cartilage destroyed by inflammation that occurs postna-
