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Salivary gland virus disease
SALIVARY
GLAND VIRUS DISEASE
An Introduction Seymow
IIofnzan,
ZJ. 8. S. Smutoga
of This Disease to the Dental Profession Caphirin (DC)
U8N
(CVA-60)
T
I-IF: PKKPOSE of this report is to bring to the attention of the dental profession a rare and fatal disease emanating from the salivary glands which occurs primarily in premature and newborn infants. Until recently, salivary gland virus disease could be diagnosed only by postmortem micropathologic study. Newer but inadequate methods now depend on exfoliative cytology, which will be discussed later. As knowledge of this disease increases, it appears that its frequency increases. Huebner, in a personal communication quoted by Nelson and W;r‘att,l has been able to isolate the virus from the urine of 30 per cent of a series of apparently healthy newborn infants. Disseminated salivary gland virus disease (cptomegalic inclusion disease) is a usually fatal viral infection transmitted in utero. It may localize in the salivary glands, in which case it apparently is nonpathogenic, or it may disseminate to one or more of the vital organs, resulting in the death of the inI’ant. It is t,hought that the Grus lies dormant within the salivary glands of adults without clinical manifestation and that it is transmitted across the placental membranes to the fetus. The prevailing theory concerning this apparent adult inlmunity is that susceptibility may be greatest during fetal and early neonatal life and that beyond these periods there is an increase in natural resistance to the virus by a high antibody titer build-up.? The disease derives its name from the fact that the inclusions are most commonly found in ductal and acinar epithelium of the salivary glands. Antcmortem diagnoses pose a difficult problem, for there arc no effective diagnostic criteria at present. Since the major pathologic conditions develop in utero, evidencc of serious illness is not disco\-cred until after the infant is born. Confirmalion of this disease is based upon the presence of pathognomonic giant cells. These cells cont,ain a large intranuclear inclusion body whid~ almost completely fills the nuclear space. A narrow, pale halo separates it from the nuclear membrane. Within the cytoplasm may be found coarse. granular inclusions (Figs. 1 and 2). Recent Stud& in rleci rot1 mic+rosirop)- it~di(~att~that I hese bodies arc viral -The not to be Service at This Department
uyiniuus 01’ asaertiuus ~:untained herein are thr private ones of the author and arc construed as official OL’ reflecting the views of the Navy Department or the Naval large. investigation was conducted while the author was a graduate student in the of Stomatology. Boston University School OP Mcdicinc. 249
ts ymptomatology in tlic infected ~~cwhorii int’ant depends upon which organs are most severely attacked by the virus. Th sali\-al? glands, panewas, livw, kidneys, lungs, and brain arch most ~‘roqut~ntl~~ involved, and thcl lesions produced may be symptomatically eonsist,cnt with destructive infections involving any of these organs. Dea.th may result i’twn licfipatic, renal, or lmlmor~ai~y insufficiency with scvcrc lrenmrrhage, nw1cr:111~, within t~vo to cigh t. weeks aft,er 1)irt.h. The most effective method of ante-mortem diagnosis of salivary gland virus disease known to date is based on exfoliative cytology. If the virus infectioil is in the kidneys, it may bc possible to recox-cr the c)?.omegalic cells from urirtcl residue; if it is in tho stomach. the cells may bc rcwvwed via gastric aspir+ iions; and if it is in the lungs, bronchial aspirations ma!- yield these cytomegalic cells.’ However. these arc, at best,, chanw findings. hJore atrcluatc. but still dependent upon chanw organ infection, is the? cultivation of the virus from the afore-mentioned samples. Weller and associates5 have successfully grown the virus from urine specimens of infected infants, and Smith” has
\‘olume 15 \lmhrtr 2
SALIVARY
GLAND
VlRUS
DISEASE
251
Culturing t.lu: virus grown them from salivary glands recovered at. autopsy. is a long and difficult procedure, however, and very few laboratories are equipped or have the personnel trained to perform this service. Crammer7 has recently reported that cytomegalic cells have been recovered from salivary
Fig. 2.--EsfrJliate~l
cyton,egalic
cell in lun,en of bronchiole.
secretions as well as from urinary sediment and bronchial secretions. If this is true, it is not unfeasible that these cells may be isolated from the areas of Stensen’s and Wharton’s ducts in asymptomatic adults by means of the Papanicolaou smear technique, thereby revealing in advance a potential source of future fetal infection. Such an investigation is now being conducted. TP the results are posit.ivr, dentistry in the near future may play a major part. in tht: prenatal diagnosis of salivary gland virus discaso by routine oral Papanicolmu smears. The generous cooperation and advice of Dr. R. I’. Sherwin, Associate Pathologist at Massachusetts Memorial Hospital, is gratefully acknowledged. The generous cooperation of I’. A. Vamey, DTl, who spent many evenings typing this paper, is also greatly appreciated.
252
IIOFE’MA;“\:
I. Nelson, J. S., and Wyatt, J. I?.: Salivary Gland Virus Disease, Meditzilu, 38: ZY:j, 195!1. Spontaneous Salivary Gland Virus it1 (‘l~irrrpanzws~ 2. Fogel, F. S., and Pinkerton, A.: A. M. A. Arch. Path. 60: 281-285. 1955. 3. Medeeris. D. N. : Cvtomegalic Inclusion; 1)isease. Pediatrics 19: 407. I9.17. 4. Iduse, s.‘A., and Smith, g Cr.: Electron 9licr&opy of Salivary Giaud Viruses, .~QI. .l. Path. 32: 642, 1956 (Abstrart!. 1 solativn 0 f .rIltr;L-~de:~I~ 5. Weller. T. H.. Maeaulev, J. C., Craig. J. M., and Wirth, P.: inclusio;l Produc&g Ag&ts Fyom Inf&nts With illnesses Resembling Cytomogalic~ Inclusion Disease, Proc. Sot. Exper. Biol. & Med. 84: 4, 1957. Propagation in Tissue Culture of a Cytopathopenic Virus From I-[umatl 0. Smith, H. G.: Salivary Gland Virus Disease, Yroe. Sot. Exper. Hiol. 9r Med. 92: 424, 1956. L. R.: Cytomegalic Disease of the Nose, I,aryngoscope 70: X7-45. 19C,O. 7. Cramnwl
GLAND VIRUS DISEASE
An Introduction Seymow
IIofnzan,
ZJ. 8. S. Smutoga
of This Disease to the Dental Profession Caphirin (DC)
U8N
(CVA-60)
T
I-IF: PKKPOSE of this report is to bring to the attention of the dental profession a rare and fatal disease emanating from the salivary glands which occurs primarily in premature and newborn infants. Until recently, salivary gland virus disease could be diagnosed only by postmortem micropathologic study. Newer but inadequate methods now depend on exfoliative cytology, which will be discussed later. As knowledge of this disease increases, it appears that its frequency increases. Huebner, in a personal communication quoted by Nelson and W;r‘att,l has been able to isolate the virus from the urine of 30 per cent of a series of apparently healthy newborn infants. Disseminated salivary gland virus disease (cptomegalic inclusion disease) is a usually fatal viral infection transmitted in utero. It may localize in the salivary glands, in which case it apparently is nonpathogenic, or it may disseminate to one or more of the vital organs, resulting in the death of the inI’ant. It is t,hought that the Grus lies dormant within the salivary glands of adults without clinical manifestation and that it is transmitted across the placental membranes to the fetus. The prevailing theory concerning this apparent adult inlmunity is that susceptibility may be greatest during fetal and early neonatal life and that beyond these periods there is an increase in natural resistance to the virus by a high antibody titer build-up.? The disease derives its name from the fact that the inclusions are most commonly found in ductal and acinar epithelium of the salivary glands. Antcmortem diagnoses pose a difficult problem, for there arc no effective diagnostic criteria at present. Since the major pathologic conditions develop in utero, evidencc of serious illness is not disco\-cred until after the infant is born. Confirmalion of this disease is based upon the presence of pathognomonic giant cells. These cells cont,ain a large intranuclear inclusion body whid~ almost completely fills the nuclear space. A narrow, pale halo separates it from the nuclear membrane. Within the cytoplasm may be found coarse. granular inclusions (Figs. 1 and 2). Recent Stud& in rleci rot1 mic+rosirop)- it~di(~att~that I hese bodies arc viral -The not to be Service at This Department
uyiniuus 01’ asaertiuus ~:untained herein are thr private ones of the author and arc construed as official OL’ reflecting the views of the Navy Department or the Naval large. investigation was conducted while the author was a graduate student in the of Stomatology. Boston University School OP Mcdicinc. 249
ts ymptomatology in tlic infected ~~cwhorii int’ant depends upon which organs are most severely attacked by the virus. Th sali\-al? glands, panewas, livw, kidneys, lungs, and brain arch most ~‘roqut~ntl~~ involved, and thcl lesions produced may be symptomatically eonsist,cnt with destructive infections involving any of these organs. Dea.th may result i’twn licfipatic, renal, or lmlmor~ai~y insufficiency with scvcrc lrenmrrhage, nw1cr:111~, within t~vo to cigh t. weeks aft,er 1)irt.h. The most effective method of ante-mortem diagnosis of salivary gland virus disease known to date is based on exfoliative cytology. If the virus infectioil is in the kidneys, it may bc possible to recox-cr the c)?.omegalic cells from urirtcl residue; if it is in tho stomach. the cells may bc rcwvwed via gastric aspir+ iions; and if it is in the lungs, bronchial aspirations ma!- yield these cytomegalic cells.’ However. these arc, at best,, chanw findings. hJore atrcluatc. but still dependent upon chanw organ infection, is the? cultivation of the virus from the afore-mentioned samples. Weller and associates5 have successfully grown the virus from urine specimens of infected infants, and Smith” has
\‘olume 15 \lmhrtr 2
SALIVARY
GLAND
VlRUS
DISEASE
251
Culturing t.lu: virus grown them from salivary glands recovered at. autopsy. is a long and difficult procedure, however, and very few laboratories are equipped or have the personnel trained to perform this service. Crammer7 has recently reported that cytomegalic cells have been recovered from salivary
Fig. 2.--EsfrJliate~l
cyton,egalic
cell in lun,en of bronchiole.
secretions as well as from urinary sediment and bronchial secretions. If this is true, it is not unfeasible that these cells may be isolated from the areas of Stensen’s and Wharton’s ducts in asymptomatic adults by means of the Papanicolaou smear technique, thereby revealing in advance a potential source of future fetal infection. Such an investigation is now being conducted. TP the results are posit.ivr, dentistry in the near future may play a major part. in tht: prenatal diagnosis of salivary gland virus discaso by routine oral Papanicolmu smears. The generous cooperation and advice of Dr. R. I’. Sherwin, Associate Pathologist at Massachusetts Memorial Hospital, is gratefully acknowledged. The generous cooperation of I’. A. Vamey, DTl, who spent many evenings typing this paper, is also greatly appreciated.
252
IIOFE’MA;“\:
I. Nelson, J. S., and Wyatt, J. I?.: Salivary Gland Virus Disease, Meditzilu, 38: ZY:j, 195!1. Spontaneous Salivary Gland Virus it1 (‘l~irrrpanzws~ 2. Fogel, F. S., and Pinkerton, A.: A. M. A. Arch. Path. 60: 281-285. 1955. 3. Medeeris. D. N. : Cvtomegalic Inclusion; 1)isease. Pediatrics 19: 407. I9.17. 4. Iduse, s.‘A., and Smith, g Cr.: Electron 9licr&opy of Salivary Giaud Viruses, .~QI. .l. Path. 32: 642, 1956 (Abstrart!. 1 solativn 0 f .rIltr;L-~de:~I~ 5. Weller. T. H.. Maeaulev, J. C., Craig. J. M., and Wirth, P.: inclusio;l Produc&g Ag&ts Fyom Inf&nts With illnesses Resembling Cytomogalic~ Inclusion Disease, Proc. Sot. Exper. Biol. & Med. 84: 4, 1957. Propagation in Tissue Culture of a Cytopathopenic Virus From I-[umatl 0. Smith, H. G.: Salivary Gland Virus Disease, Yroe. Sot. Exper. Hiol. 9r Med. 92: 424, 1956. L. R.: Cytomegalic Disease of the Nose, I,aryngoscope 70: X7-45. 19C,O. 7. Cramnwl