Pulmonary calcification in viral pneumonia · Pulmonary calcification in viral pneumonia E. L....
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J. clin. Path. (1969), 22, 361-366 Pulmonary calcification in viral pneumonia E. L. JONES AND A. H. CAMERON From the Departments of Pathology, University of Birmingham, and the Children's Hospital, Birmingham SYNOPSIS The finding of diffuse pulmonary calcification is reported in a 19-month-old female infant who died from an apparent viral pneumonia with systemic involvement due to varicella or herpes simplex infection. The observation is of interest because of the recently described occurrence of lung calcification following chickenpox in adults. Varicella pneumonia has recently become recognized as a cause of calcification in the lungs (Mackey and Cairney, 1960; Knyvett, 1966; British Medical Journal, 1968). Radiological investigation in the adult has shown that the calcification tends to occur three to five years after the primary pneumonia (Knyvett, 1966). The child reported in this paper developed striking pulmonary calcification during the active phase of a pneumonia which was part of a disseminated viral infection. CASE REPORT A 19-month-old child developed generalized oedema in September 1966. The nephrotic syndrome was diagnosed and she was treated with corticosteroids and on this she became oedema-free and was discharged. After a re- mission of seven weeks the oedema reappeared and she did not improve with a second course of corticosteroids. At this stage she was transferred to the Birmingham Children's Hospital. Examination showed gross oedema of the face, legs, and feet. An erythematous rash was noted on the chin, around the mouth, buttocks, and thighs. The blood pressure was 145/100 mm Hg. There was no evidence of heart failure and the lung fields were clear. INITIAL INVESTIGATIONS The levels of serum sodium were 139 m-equiv/l, potassium 3-2 m-equiv/l, chloride 95 m-equiv/l; blood urea 50 mg per 100 ml; urine protein 2-26 g in 24 hours; total serum proteins 3 9 g per 100 ml (albumin 0-8, globulin 3-1). Electrophoresis revealed an increased alpha2 globulin and decreased gamma globulin: haemoglobin 70 g/100 ml (48%), WBC 24,000 per cmm, ESR 45 mm in one hour. A swab from the rash on the buttock grew a very heavy mixed growth of Proteus, Escherichia coli, a few haemolytic streptococci, a heavy growth of coagulase-positive staphylococci, and a light growth of Candida. She was treated with prednisone, frusemide, spirolactone, penicil- Received for publication 7 October 1968. lin, and later cyclophosphamide. There was no improve- ment and three days after admission she had a generalized convulsion and became drowsy and confused; a generalized erythematous rash wasnoted and shegradually lapsed into coma. A few enlarged occipital lymph nodes were found, and as the child had recently been in contact with measles, a form of steroid-suppressed measles encephalitis was suspected. Complement-fixation tests against influenza A, B, C, parainfluenza 1, respiratory syncytial virus, adenovirus, Q fever, Mycoplasma pneumoniae, psittacosis-lymphogranuloma venereum, and measles were negative at 1/10. Complement-fixation tests against Varicella zoster virus or herpes simplex were not performed. LATER INVESTIGATIONS The blood urea was 77 mg per 100 ml; blood culture sterile; cerebrospinal fluid sterile, sugar 103 mg/100 ml, protein less than 15 mg per 100 ml. An EEG showed a grossly abnormal record with a general- ized bilateral distribution consistent with encephalitis. A chest radiograph showed 'extensive scattered opacities in both'lungs with aperibronchialdistributionconsistent with interstitial bronchopneumonia' (Fig. 1). There was no known history of a recent contact with either varicella or herpes simplex while the child was a patient in either hospital. One month before her admission at the first hospital she received a smallpox vaccination followed by a severe febrile reaction for three to four days when she was ill and irritable. The vaccination healed successfully and was not associated with a generalized vaccinia reaction. She continued to deteriorate, developed peripheral circulatory failure, and died 10 days after admission. NECROPSY The necropsy was performed 29 hours after death. The body was that of a well nourished female child (length 84 cm, head circumference 48 cm) showing oedema of the hands and lower limbs. There were extensive semi- confluent, vesicular, ulcerating lesions around the mouth, chin, perineum, and buttocks. The trachea and main bronchi were congested and 361 on February 14, 2020 by guest. Protected by copyright. http://jcp.bmj.com/ J Clin Pathol: first published as 10.1136/jcp.22.3.361 on 1 May 1969. Downloaded from
Transcript of Pulmonary calcification in viral pneumonia · Pulmonary calcification in viral pneumonia E. L....
J. clin. Path. (1969), 22, 361-366
Pulmonary calcification in viral pneumoniaE. L. JONES AND A. H. CAMERON
From the Departments ofPathology, University of Birmingham, and the Children's Hospital, Birmingham
SYNOPSIS The finding of diffuse pulmonary calcification is reported in a 19-month-old femaleinfant who died from an apparent viral pneumonia with systemic involvement due to varicella orherpes simplex infection. The observation is of interest because of the recently described occurrenceof lung calcification following chickenpox in adults.
Varicella pneumonia has recently become recognizedas a cause of calcification in the lungs (Mackey andCairney, 1960; Knyvett, 1966; British MedicalJournal, 1968). Radiological investigation in theadult has shown that the calcification tends tooccur three to five years after the primary pneumonia(Knyvett, 1966).The child reported in this paper developed striking
pulmonary calcification during the active phase ofa pneumonia which was part of a disseminated viralinfection.
CASE REPORT
A 19-month-old child developed generalized oedema inSeptember 1966. The nephrotic syndrome was diagnosedand she was treated with corticosteroids and on this shebecame oedema-free and was discharged. After a re-mission of seven weeks the oedema reappeared and shedid not improve with a second course of corticosteroids.At this stage she was transferred to the BirminghamChildren's Hospital. Examination showed gross oedemaof the face, legs, and feet. An erythematous rash wasnoted on the chin, around the mouth, buttocks, andthighs. The blood pressure was 145/100 mm Hg. Therewas no evidence of heart failure and the lung fields wereclear.
INITIAL INVESTIGATIONS The levels of serum sodiumwere 139 m-equiv/l, potassium 3-2 m-equiv/l, chloride95 m-equiv/l; blood urea 50 mg per 100 ml; urineprotein 2-26 g in 24 hours; total serum proteins 3 9 gper 100 ml (albumin 0-8, globulin 3-1). Electrophoresisrevealed an increased alpha2 globulin and decreasedgamma globulin: haemoglobin 70 g/100 ml (48%),WBC 24,000 per cmm, ESR 45 mm in one hour. A swabfrom the rash on the buttock grew a very heavy mixedgrowth of Proteus, Escherichia coli, a few haemolyticstreptococci, a heavy growth of coagulase-positivestaphylococci, and a light growth of Candida. She wastreated with prednisone, frusemide, spirolactone, penicil-Received for publication 7 October 1968.
lin, and later cyclophosphamide. There was no improve-ment and three days after admission she had a generalizedconvulsion and becamedrowsyandconfused; ageneralizederythematous rash wasnoted and shegradually lapsed intocoma. A few enlarged occipital lymph nodes were found,and as the child had recently been in contact withmeasles, a form of steroid-suppressed measles encephalitiswas suspected. Complement-fixation tests againstinfluenza A, B, C, parainfluenza 1, respiratory syncytialvirus, adenovirus, Q fever, Mycoplasma pneumoniae,psittacosis-lymphogranuloma venereum, and measleswere negative at 1/10. Complement-fixation tests againstVaricella zoster virus or herpes simplex were notperformed.
LATER INVESTIGATIONS The blood urea was 77 mg per100 ml; blood culture sterile; cerebrospinal fluid sterile,sugar 103 mg/100 ml, protein less than 15 mg per 100 ml.An EEG showed a grossly abnormal record with a general-ized bilateral distribution consistent with encephalitis. Achest radiograph showed 'extensive scattered opacities inboth'lungs with aperibronchialdistributionconsistent withinterstitial bronchopneumonia' (Fig. 1). There was noknown history of a recent contact with either varicella orherpes simplex while the child was a patient in eitherhospital. One month before her admission at the firsthospital she received a smallpox vaccination followed bya severe febrile reaction for three to four days when shewas ill and irritable. The vaccination healed successfullyand was not associated with a generalized vacciniareaction.She continued to deteriorate, developed peripheral
circulatory failure, and died 10 days after admission.
NECROPSY
The necropsy was performed 29 hours after death. Thebody was that of a well nourished female child (length84 cm, head circumference 48 cm) showing oedema ofthe hands and lower limbs. There were extensive semi-confluent, vesicular, ulcerating lesions around the mouth,chin, perineum, and buttocks.The trachea and main bronchi were congested and
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FIG. 1.
FIG. 3.
FIG. 1. Chest radiograph showing scattered opacitiesin both lung fields.
FIG. 2. Hyaline membranes lining alveoli. Haematoxylinand eosin. x 150.
FIG. 3. Cubical cell metaplasia ofalveolar septal cells withmultinucleate giant cells. Haematoxylin and eosin. x 150.
4 d....
;.... .s
FIG. 2.
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Pulmonary calcification in viral pneumonia 363
FIG. 4.
FIG. 6.
FIG. 4. Calcification of alveolar walls around vessels andbronchi. Von Kossa. x 35.
FIG. 5. Reticular calcification forming denser deposits.Von Kossa. x 150.
FIG. 6. Intraepidermal vesicle ofthe skin showing balloon-ing degeneration ofthe epidermis. Haematoxylin and eosin.x 150.
FIG. 5.
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contained tenacious mucoid secretion. The lungs wereoverweight (left 120 g, right 141 g), firm, and the basesshowed extensive diffuse nodular induration. The thymus(2-5 g) was markedly atrophied.The liver (479 g) was enlarged and pale. The cut
surface showed fatty change and congestion. The spleen(28 g) showed multiple small greyish white lesions 1 to2 mm in diameter. The adrenals were small and the cor-tices thin. The kidneys (left 79 g, right 77 g) weresymmetrically enlarged and ofapale, greyish-white colour.The capsules stripped easily to reveal smooth, swollen,oedematous surfaces with multiple small petechialhaemorrhages but no scarring or granularity. Cortico-medullary differentiation was maintained and the cortexwas pale in contrast to the darker medulla. The pelves,ureters, and bladder were normal. A recent adherentantemortem thrombus was found in the left renal veinextending from the hilum of the kidney into the inferiorvena cava. The right renal vein was normal. The cranialcavity was normal. There was no evidence of venoussinus thrombosis or meningitis. The brain (880 g) wasunderweight; it showed generalized oedema but no otherexternal feature of note. Examination after fixationshowed no unusual features.Postmortem bacteriological examination of the lung
yielded a heavy growth of Pseudomonas pyocyanea,moderate numbers of Klebsiella, and a small numberof Proteus mirabilis.Postmortem virological examination of the ileal
contents was negative. No other virological studies wereundertaken.
HISTOLOGY
The lungs showed areas of bronchopneumonia, pul-monary oedema, and congestion. Many alveoli werefilled with amorphous basophilic debris. In some areasthere was alveolar emphysema due to destruction ofalveolar walls by eosinophilic fibrinoid necrosis. Manyalveoli were lined by eosinophilic hyaline membranes(Fig. 2), and contained numerous swollen, lipid-containingmacrophages. Cubical cell metaplasia was frequent andmultinucleate giant cells were common (Fig. 3). The wallsof many peripheral alveoli bordering the interlobularsepta were impregnated by dark basophilic deposits ofcalcium (Fig. 4). In other areas the calcification wasmore extensive, forming a reticular pattern within thelobules and occasional denser masses of calcification(Fig. 5). Throughout the lung there was marked in-filtration with polymorphs and macrophages. A fewalveolar cells showed pale intranuclear inclusions.The skin showed intraepidermal vesicles formed by
extensive acantholysis and 'ballooning degeneration' ofthe epidermal cells (Fig. 6). The balloon cells wereswollen and had a homogeneous eosinophilic cytoplasm.Most of the nuclei had disappeared but some pyknoticforms remained. A few cells had eosinophilic intra-nuclear inclusions. The most superficial region of theepidermis and edge of the vesicle showed 'reticulardegeneration'. The upper dermis showed a mild mono-nuclear inflammatory cell infiltrate.The liver showed centrilobular fatty change and
FIG. 7. Well demarcated foci of necrosis in liver. Haema-toxylin and eosin. x 100.
well demarcated, punctate areas of necrosis up to 2 mmin diameter (Fig. 7). Their central portion consisted ofnecrotic debris and the periphery was congested. Nointranuclear inclusions were detected.The spleen (Fig. 8) and adrenals (Fig. 9) showed
similar small punctate areas of necrosis. A few intra-nuclear inclusions were identified in the cells of thezona fasciculata.The kidneys showed no abnormality of the glomeruli
apart from one with an intercapillary thrombus andlobular infarction. The tubules contained 'colloid' castsand the proximal tubular epithelium showed hydropicchange, and infiltration with lipid.The remaining organs were unremarkable.
DISCUSSION
Radiological evidence of pulmonary calcificationfollowing varicella pneumonia was first describedby Mackey and Cairney (1960), and the account byKnyvett (1966) has attracted further interest in thecondition. Darke and Middleton (1967) describedtwo patients with multiple calcified lesions who hadan attack ofchickenpox five and 23 years previously,respectively. A recent leading article (British MedicalJournal, 1968) further emphasizes the condition andmakes the point that some 16 to 33% of adults withchickenpox develop pneumonia with an estimated
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FIG. 8. Punctate area of necrosis in spleen. Haematoxylinand eosin. x 100.
mortality rate of 20% (Weinstein and Meade, 1956;Krugman, Goodrich, and Ward, 1957; Mermelsteinand Freireich, 1961). The histological featuresconsist of areas of fibrinoid necrosis, mononuclearinflammatory cell infiltration, giant cells, and intra-nuclear inclusion bodies in the cells of the alveolarsepta (Frank, 1950). There are also rare fatal casesof disseminated chickenpox in which focal areasof necrosis containing intranuclear inclusion bodiesare found in the adrenals, liver, spleen, and kidneyas well as in the lungs (Eisenbud, 1952).
In the paediatric age group chickenpox rarelycauses pneumonia but primary varicella pneumoniahas been reported as a necropsy finding in infantswith varicella neonatorum and congenital chicken-pox. Lucchesi, la Bocetta, and Peale (1947) describedtwo infants who developed the condition eight andnine days postnatally. A premature child (2,155 g)showed widely distributed varicella lesions in thelungs, liver, and gastrointestinal tract associatedwith the usual cutaneous changes. The lesionswere characterized by multiple areas of focalnecrosis and the presence of intranuclear in-clusions.
In the newborn and in young infants, the virus ofherpes simplex can cause a fatal viraemia withnumerous focal necroses in the visceral organs. This
FIG. 9. Adrenal cortex showing two discrete foci ofnecrosis. Haematoxylin and eosin. x 100.
was first recognized as a specific entity by Hass in1935. Eruption may occur anywhere on the skinbut is found most commonly about the face andgenitalia. In older infants herpetic stomatitis maygive rise to a specific herpetic hepatitis (Zuelzerand Stulberg, 1952). Macroscopically the lesions ofherpes simplex may be visible in the adrenal, liver,lung, and brain. Microscopically the lesions in allparts are essentially the same and consist of discreteareas of necrosis with or without surroundinginflammatory cell infiltration. Intranuclear eosino-philic homogeneous inclusions are present in theparenchymal cells in the edge of the lesions.
In our particular case specific viral studies werenot performed other than the routine culture of aloop of ileum at necropsy. However, the histologicalfindings were so strikingly similar to the describedlesions that we feel there is good presumptiveevidence for a systemic viral infection, either herpessimplex or varicella. The oral and genital dis-tribution of the vesicles in this case more closelyresembled herpes simplex infection.The findings of diffuse calcification in the lungs
following an apparent viral pneumonia is interestingbecause hitherto this occurrence has only beenreported in varicella infections and then some yearsafter the attack.
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To the best of our knowledge this is the first reportof histological calcification of the lung associatedwith a primary viral pneumonia.
The authors wish to thank Dr White for permission torecord clinical details of this case.
REFERENCES
British Medical Journal (1968). Leading article. 2, 68.Darke, C. S., and Middleton, R. S. W. (1967). Brit. J. Dis. Chest, 61,
198.
Eisenbud, M. (1952). Amer. J. Med., 12, 740.Frank, L. (1950). Arch. Path., 50, 450.Hass, G. M. (1935). Amer. J. Path., 11, 127.Knyvett, A. F. (1966). Quart. J. Med., 35, 313.Krugman, S., Goodrich, C. H., and Ward, R. (1957). New Engl. J.
Med., 257, 843.Lucchesi, P. F., LaBocetta, A. C., and Peale, A. R. (1947). Amer. J.
Dis. Child., 73, 44.Mackay, J. B., and Cairney, P. (1960). N.Z. med. J., 59, 453.Mermelstein, R. H., and Freireich, A. W. (1961). Ann. intern. Med.,
55, 456.Weinstein, L., and Meade, R. H. (1956). Arch. intern. Med., 98, 91.Zuelzer, W. W., and Stulberg, C. S. (1952). Amer. J. Dis. Child., 83,
421.
Reports and Bulletins prepared by the Association of Clinical BiochemistsThe following reports and bulletins are published by the Association of Clinical Biochemists. They may be obtainedfrom The Administrative Office, Association of Clinical Biochemists, 7 Warwick Court, Holborn, London, W.C.1.The prices include postage, but airmail will be charged extra. Overseas readers should remit by British Postal or MoneyOrder. If this is not possible, the equivalent of 10s. is the minimum amount that can be accepted.
SCIENTIFIC REPORTS
1 Colorimeters with Flow Through Cells. A criticalassessment of 4 instruments. 1965. P. M. G.BROUGHTON and C. RILEY. 13s. 6d.
2 Colorimeters. A critical assessment of 5 commercialinstruments. 1966. P. M. G. BROUGHTON, C. RILEY,J. G. H. COOK, P. G. SANDERS, and H. BRAUNSBERG. 15s.
3 Automatic Dispensing Pipettes. An assessment of 35commercial instruments. 1967. P. M. G. BROUGHTON,A. H. GOWENLOCK, G. M. WIDDOWSON, and K. A.AHLQUIST. 1Os.
TECHNICAL BULLETINS
9 Determination of Urea by AutoAnalyzer. November1966. RUTH M. HASLAM. 2s. 6d.
11 Determination of Serum Albumin by AutoAnalyzerusing Bromocresol Green. October 1967. B. E.NORTHAM and G. M. WIDDOWSON. 2s. 6d.
12 Control Solutions for Clinical Biochemistry. February1968. P. M. G. BROUGHTON. 2s. 6d.
13 An Assessment of the Technicon Type II SamplerUnit. March 1968. B. C. GRAY and G. K. MCGOWAN.ls.6d.
14 Atomic Absorption Spectroscopy. An Outline of itsPrinciples and a Guide to the Selection of Instru-ments. May 1968. J. B. DAWSON and P. M. G.BROUGHTON. 4s.
15 A Guide to Automatic Pipettes (2nd edition). June1968. P. M. G. BROUGHTON. 5s.
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