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INFECTIONS AND SALIVARY GLAND
DISEASE IN PEDIATRIC AGE:
HOW TO MANAGE
Susanna Esposito
Pediatric Highly Intensive Care Unit
Fondazione IRCCS Ca’ Granda Ospedale
Maggiore Policlinico, University of Milan
Milan, Italy
Xerostomia
Infective Agent: Bacteria,
Viruses, Fungi
Dehydration
post-surgical states
Sjogren syndrome
Drugs e.g.
Antihistamines
Irradiation
Sialolithiasis,
Congenital and
iatrogenic
glandular
defects,
strictures
salivary gland infections
Factors important in pathogenesis of
salivary gland infections
Toddler with mumps parotitis
Mumps: Viral etiology
 Caused by mumps virus.
 Family: paramyxoviridae.
 Genus: parainfluenza virus.
 Pleomorphic, enveloped with helical nucleocapsid.
 The viral genome is ss-RNA, with negative polarity.
 The viral envelope is covered with two glycoprotein spikes,
the HN which posses both hemagglutinine and
neuraminidase activities , and the fusion glycoprotein.
Mumps: Transmission
The mumps virus replicates in the upper respiratory
tract and is spread through direct contact with
respiratory secretions or saliva or through fomites.
The infectious period or time that an infected person
can transmit mumps to a non-infected person is from 3
days before symptoms appear to about 9 days after
the symptoms appear.
The incubation time, which is the period from when a
person is exposed to virus to the onset of any
symptoms, can vary from 16 to 18 days (range 12-25
days).
Mumps Clinical features
 Mumps is a highly infectious child-hood disease.
 IP, about three weeks.
 Mumps starts with moderate fever, malaise, pain on
chewing or swallowing, particularly acidic liquids.
 Followed by inflammation of the salivary glands,
particularly the parotid glands.
 The swelling appears in front of the ear.
Mumps treatment
• There is no specific antiviral therapy;
treatment is entirely supportive
• Antipyretics (acetaminophen or ibuprofen)
are indicated for fever
• Bed rest should be guided by the
patient's needs, but no evidence indicates
that it prevents complications
• The diet should be adjusted to the
patient's ability to chew
MENINGOENCEPHALOMYELITIS - I
• The most frequent complication in childhood
• Clinical manifestations occur in more than 10% of patients
• The incidence of mumps meningoencephalitis is approximately 250/
100,000 cases
• The mortality rate is about 2%
• May be either:
I. Primary infection of neurons:
parotitis frequently appears at the same
time or following the onset of encephalitis
II. Postinfectious encephalitis with demyelination:
encephalitis follows parotitis by an
average of10 days.
MENINGOENCEPHALOMYELITIS - II
• Mumps meningoencephalitis is clinically
indistinguishable from meningoencephalitis of
other origins
• The cerebrospinal fluid may show a lymphocytic
pleocytosis of less than 500 cells/ mm3,
although occasionally the count may exceed
2,000 cells/mm3
ORCHITIS AND EPIDIDYMITIS
• These complications rarely occur in prepubescent
boys but are common (14-35%) in adolescents
and adults
• The testis is most often infected with or without
epididymitis; epididymitis may also occur alone
• Bilateral orchitis occurs in approximately 30% of
patients. Rarely, there is a hydrocele
• The orchitis usually follows parotitis within 8 days
• Orchitis may also occur without evidence of
salivary gland infection
OOPHORITIS
Pelvic pain and tenderness are noted in about 7% of
postpubertal female patients. There is no evidence
of impairment of fertility
PANCREATITIS
• Mild or subclinical pancreatic involvement is common,
but severe pancreatitis is rare
• It may be unassociated with salivary gland
manifestations and may be misdiagnosed as
gastroenteritis
• Epigastric pain and tenderness, which are suggestive,
may be accompanied by fever, chills, vomiting, and
prostration
• An elevated serum amylase value is characteristically
present in patients with mumps, with or without
clinical manifestations of pancreatitis
MYOCARDITIS
• Serious cardiac manifestations are extremely
rare
• Mild infection of the myocardium may be more
common than is recognized.
• Electrocardiographic tracings revealed changes,
mostly depression of the ST segment, in 13% of
adults in one series
• Such involvement may explain the precordial pain,
bradycardia, and fatigue sometimes noted among
adolescents and adults with mumps
ARTHRITIS
• Migratory polyarthralgia and even arthritis
are occasionally seen in adults with mumps
but are rare in children
• The knees, ankles, shoulders, and wrists
are most commonly affected
• The symptoms last from a few days to 3
mo, with a median duration of 2 wk
THYROIDITIS
• It is uncommon in children
• A diffuse, tender swelling of the thyroid
may occur about 1 wk after the onset of
parotitis
• Antithyroid antibodies subsequently develop
OCULAR COMPLICATIONS
• Dacryoadenitis may occur with painful
swelling, usually bilateral, of the lacrimal
glands
• Optic neuritis (papillitis) may occur
• Symptoms vary from loss of vision to mild blurring,
with recovery in 10-20 days
Treatment of complications
• Orchitis should be treated with local support and
bed rest
• Mumps arthritis may respond to a 2-wk course of a
nonsteroidal anti-inflammatory agent or
corticosteroids
• Salicylates do not appear to be effective
MUMPS VACCINE
• Vaccine virus strains:
– worldwide the Jeryl Lynn strain (or RIT 4385 derived from
Jeryl Lynn strain) is the most widely used vaccine strain
– the formerly widely used Urabe strain has been withdrawn
from many countries following data concerning vaccine-
associated meningitis
– other vaccine strains have been developed, e.g., in Russia
(Leningrad-3), Croatia (L-Zagreb), Switzerland (Rubini),
Japan (e.g., Torii)
• Most vaccines produced in chick embryo fibroblast cell
cultures
NATIONAL VACCINATION SCHEDULE (VNP 2012-
2015)
# MMR2: second dose or catch-up
Ministry of Health, Directorate General of Heath Prevention
Vaccine birth
3rd
mese
5th
mese
6th
mese
11th
mese
13th
mese
15th
mese
5-6 y
11-18
y
>65 y Every
10
years
DTPa DTPa DTPa DTPa DTPa dTpa dT
IPV IPV IPV IPV IPV
HBV HBV HBV HBV HBV
Hib Hib Hib Hib
MMR MMR MMR# MMR#
PCV PCV PCV PCV
Men C Men C Men C
HPV HPV
Influenza Flu
Varicella Var
From van Loon et al. MMWR 1995; 44(SS3): 1-14
Mumps vaccination coverage and the vaccine
strains used
(From Eriksen J et al., Epidemiol Infect 2013)
Mumps epidemic: UK 2004-2005
(From Savage E et al., MMWR 2006; 55: 173-175)
Factors that could influence mumps outbreaks
(From Eriksen J et al., Epidemiol Infect 2013)
From Hukic M et al., Euro Surveill 2014
From Hukic M et al., Euro Surveill 2014
From Hukic M et al., Euro Surveill 2014
MUMPS: DIFFERENTIAL DIAGNOSIS
The differential diagnosis of parotitis is broad and
includes:
• bacterial (suppurative) parotitis
• parotid duct stone
• drug reactions
• recurrent parotitis of childhood
• Other viruses, such as influenza, coxsackievirus A,
echovirus, and parainfluenza viruses 1 and 3, can
cause parotitis and are usually responsible for
“recurrent mumps”
• parotid tumor
• Sjögren syndrome
Other viral infections
Cytomegalovirus – causes cytomegalic inclusion disease, in
newborns, children and adults and has multiple systemic
manifestations
Parainfluenza types 2 and 3, echo and coxsackie viruses
– non-specific suppurative sialadenitis
Bacterial infections of salivary glands:
Acute suppurative parotitis (bacterial sialadenitis):
• Seen mostly in adults with salivary gland abnormalities
and other predisposing factors
•A retrograde infection via salivary duct may occur if the
flow of saliva is reduced or stopped
Predisposing factors:
 Drugs that reduce salivary flow such as diuretics.
 Salivary gland abnormalities such as calculus, mucus
plug or benign strictures
 Dehydration
 Sjogren's syndrome
Clinical features:
1. Unilateral or bilateral swelling of parotid glands.
Swelling may extend, involving pre- and postauricular
areas
2. Purulent salivary secretions at the duct orifice
3. Fever, chills and leukocytosis
4. Recurrent bouts of acute infection followed by
remission may lead to fibrosis
Common
isolates
Less isolates Rare
isolates
Alpha-
haemolytic
streptococci
Haemophilus
spp.
Neisseria
gonorrhoeae
Staphylococcus
aureus
Bacteroides
spp.
Mycobacterium
tuberculosis
Anaerobic
streptococci
Actinomyces
spp.
Eikenella spp. Treponema
pallidum
Bacteria commonly isolated from bacterial
parotitis
Treatment
Empirical parenteral antibiotic therapy with a penicillinase
resistant betalactam or, in case of risk of MRSA,
vancomycin
 Further therapy guided by culture and sensivity tests
Oral hygiene
Pus aspirated through catheter or collected aseptically on
a cotton-wool swab by milking the duct
Encourage the salivation by increased fluid intake and by
sialagogues e.g. lemon juice
In sever cases: surgical drainage of pus
If acute bacterial parotitis is untreated:
1. Extension of inflammation and oedema into the neck
leading to respiratory obstruction
2. Cellulitis of the face and neck
3. Osteomyelitis of adjacent facial bones
4. Septicaemia and death
Trough levels of vancomycin according to
dosage in children
(from Kim DI, et al. Korean J Pediatr 2010)
Vancomicina e tossicità renale
L’uso di dosi elevate di vancomicina, tali da
permettere il raggiungimento di livelli pre-dose
di 15-20 mg/L sembrano sicuri se
somministrati a soggetti senza rischio
aumentato di nefrotossicità e per un periodo
limitato (< 14 gg)
Nei casi dubbi o quando il monitoraggio non sia
possibile, considerare linezolid
Mycotic Infections in Immunicompromised
children
Actinomycosis
Caused by Actinomyces israelii.
Types:
1. Primary endogenous, ascending infection via salivary
ducts. Infection penetrates from mouth into gland and
affects it entirely
2. Secondary when transferred to gland from tissue
surrounding, non tender, non fluctuant indurated lesion
with formation of multiple fistulae with discharge of
sulphur granules
Juvenile recurrent parotitis (JRP) - I
• JRP is an inflammatoryrocess that results in recurrent,
painful swelling of the parotid gland
• The etiology is unknown: although autoimmune, ductal
obstruction, immune deficiency, and infectious causes have all
been proposed
• It is the second most common pediatric salivary gland
disorder after mumps
• While the most common age for it to appear is 3 to 6 years
old, it ranges from a couple of months of age to puberty, at
which time it usually self-resolves
• To diagnose JRP, a patient must have a clinical history
characterized by multiple episodes of same-sided swelling and
pain
• It also must be differentiated from sialolithiasis and other
causes of unilateral parotid swelling, which can occasionally
occur in pediatric patients (use imaging such as
ultrasonography)
• Treatment of JRP often begins with symptomatic
treatment, including antibiotics, analgesics, warm
compresses, and sialagogues
• Other treatments for recurrent inflammation have included
injection of the duct with a sclerosing agent, radiation,
ligature of the parotid duct, tympanic neurectomy, and
parotidectomy
• Many of those treatments, including radiation and
neurectomy, have fallen out of favor
Juvenile recurrent parotitis (JRP) - II
From: Treatment of Juvenile Recurrent Parotitis of Childhood: An Analysis of Effectiveness
JAMA Otolaryngol Head Neck Surg. 2015;141(2):126-129. doi:10.1001/jamaoto.2014.3036
Frequency of Parotitis Episodes Before and After Treatment With Ductal Corticosteroid Infusion
Figure Legend:
CONCLUSIONS
MMR vaccination coverage should be urgently
increased in Italy as well as in EU countries to
contain measles, mumps, rubella
Other causes of parotitis in childhood should
be followed by a pediatrician and an ENT
specialist
SEE YOU IN MILAN!

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Infections and salivary gland disease in pediatric age: how to manage - Slideset by Professor Susanna Esposito

  • 1. INFECTIONS AND SALIVARY GLAND DISEASE IN PEDIATRIC AGE: HOW TO MANAGE Susanna Esposito Pediatric Highly Intensive Care Unit Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan Milan, Italy
  • 2. Xerostomia Infective Agent: Bacteria, Viruses, Fungi Dehydration post-surgical states Sjogren syndrome Drugs e.g. Antihistamines Irradiation Sialolithiasis, Congenital and iatrogenic glandular defects, strictures salivary gland infections Factors important in pathogenesis of salivary gland infections
  • 3. Toddler with mumps parotitis
  • 4. Mumps: Viral etiology  Caused by mumps virus.  Family: paramyxoviridae.  Genus: parainfluenza virus.  Pleomorphic, enveloped with helical nucleocapsid.  The viral genome is ss-RNA, with negative polarity.  The viral envelope is covered with two glycoprotein spikes, the HN which posses both hemagglutinine and neuraminidase activities , and the fusion glycoprotein.
  • 5. Mumps: Transmission The mumps virus replicates in the upper respiratory tract and is spread through direct contact with respiratory secretions or saliva or through fomites. The infectious period or time that an infected person can transmit mumps to a non-infected person is from 3 days before symptoms appear to about 9 days after the symptoms appear. The incubation time, which is the period from when a person is exposed to virus to the onset of any symptoms, can vary from 16 to 18 days (range 12-25 days).
  • 6.
  • 7. Mumps Clinical features  Mumps is a highly infectious child-hood disease.  IP, about three weeks.  Mumps starts with moderate fever, malaise, pain on chewing or swallowing, particularly acidic liquids.  Followed by inflammation of the salivary glands, particularly the parotid glands.  The swelling appears in front of the ear.
  • 8. Mumps treatment • There is no specific antiviral therapy; treatment is entirely supportive • Antipyretics (acetaminophen or ibuprofen) are indicated for fever • Bed rest should be guided by the patient's needs, but no evidence indicates that it prevents complications • The diet should be adjusted to the patient's ability to chew
  • 9.
  • 10. MENINGOENCEPHALOMYELITIS - I • The most frequent complication in childhood • Clinical manifestations occur in more than 10% of patients • The incidence of mumps meningoencephalitis is approximately 250/ 100,000 cases • The mortality rate is about 2% • May be either: I. Primary infection of neurons: parotitis frequently appears at the same time or following the onset of encephalitis II. Postinfectious encephalitis with demyelination: encephalitis follows parotitis by an average of10 days.
  • 11. MENINGOENCEPHALOMYELITIS - II • Mumps meningoencephalitis is clinically indistinguishable from meningoencephalitis of other origins • The cerebrospinal fluid may show a lymphocytic pleocytosis of less than 500 cells/ mm3, although occasionally the count may exceed 2,000 cells/mm3
  • 12. ORCHITIS AND EPIDIDYMITIS • These complications rarely occur in prepubescent boys but are common (14-35%) in adolescents and adults • The testis is most often infected with or without epididymitis; epididymitis may also occur alone • Bilateral orchitis occurs in approximately 30% of patients. Rarely, there is a hydrocele • The orchitis usually follows parotitis within 8 days • Orchitis may also occur without evidence of salivary gland infection
  • 13. OOPHORITIS Pelvic pain and tenderness are noted in about 7% of postpubertal female patients. There is no evidence of impairment of fertility
  • 14. PANCREATITIS • Mild or subclinical pancreatic involvement is common, but severe pancreatitis is rare • It may be unassociated with salivary gland manifestations and may be misdiagnosed as gastroenteritis • Epigastric pain and tenderness, which are suggestive, may be accompanied by fever, chills, vomiting, and prostration • An elevated serum amylase value is characteristically present in patients with mumps, with or without clinical manifestations of pancreatitis
  • 15. MYOCARDITIS • Serious cardiac manifestations are extremely rare • Mild infection of the myocardium may be more common than is recognized. • Electrocardiographic tracings revealed changes, mostly depression of the ST segment, in 13% of adults in one series • Such involvement may explain the precordial pain, bradycardia, and fatigue sometimes noted among adolescents and adults with mumps
  • 16. ARTHRITIS • Migratory polyarthralgia and even arthritis are occasionally seen in adults with mumps but are rare in children • The knees, ankles, shoulders, and wrists are most commonly affected • The symptoms last from a few days to 3 mo, with a median duration of 2 wk
  • 17. THYROIDITIS • It is uncommon in children • A diffuse, tender swelling of the thyroid may occur about 1 wk after the onset of parotitis • Antithyroid antibodies subsequently develop
  • 18. OCULAR COMPLICATIONS • Dacryoadenitis may occur with painful swelling, usually bilateral, of the lacrimal glands • Optic neuritis (papillitis) may occur • Symptoms vary from loss of vision to mild blurring, with recovery in 10-20 days
  • 19. Treatment of complications • Orchitis should be treated with local support and bed rest • Mumps arthritis may respond to a 2-wk course of a nonsteroidal anti-inflammatory agent or corticosteroids • Salicylates do not appear to be effective
  • 20. MUMPS VACCINE • Vaccine virus strains: – worldwide the Jeryl Lynn strain (or RIT 4385 derived from Jeryl Lynn strain) is the most widely used vaccine strain – the formerly widely used Urabe strain has been withdrawn from many countries following data concerning vaccine- associated meningitis – other vaccine strains have been developed, e.g., in Russia (Leningrad-3), Croatia (L-Zagreb), Switzerland (Rubini), Japan (e.g., Torii) • Most vaccines produced in chick embryo fibroblast cell cultures
  • 21. NATIONAL VACCINATION SCHEDULE (VNP 2012- 2015) # MMR2: second dose or catch-up Ministry of Health, Directorate General of Heath Prevention Vaccine birth 3rd mese 5th mese 6th mese 11th mese 13th mese 15th mese 5-6 y 11-18 y >65 y Every 10 years DTPa DTPa DTPa DTPa DTPa dTpa dT IPV IPV IPV IPV IPV HBV HBV HBV HBV HBV Hib Hib Hib Hib MMR MMR MMR# MMR# PCV PCV PCV PCV Men C Men C Men C HPV HPV Influenza Flu Varicella Var
  • 22. From van Loon et al. MMWR 1995; 44(SS3): 1-14
  • 23. Mumps vaccination coverage and the vaccine strains used (From Eriksen J et al., Epidemiol Infect 2013)
  • 24. Mumps epidemic: UK 2004-2005 (From Savage E et al., MMWR 2006; 55: 173-175)
  • 25. Factors that could influence mumps outbreaks (From Eriksen J et al., Epidemiol Infect 2013)
  • 26. From Hukic M et al., Euro Surveill 2014
  • 27. From Hukic M et al., Euro Surveill 2014
  • 28. From Hukic M et al., Euro Surveill 2014
  • 29. MUMPS: DIFFERENTIAL DIAGNOSIS The differential diagnosis of parotitis is broad and includes: • bacterial (suppurative) parotitis • parotid duct stone • drug reactions • recurrent parotitis of childhood • Other viruses, such as influenza, coxsackievirus A, echovirus, and parainfluenza viruses 1 and 3, can cause parotitis and are usually responsible for “recurrent mumps” • parotid tumor • Sjögren syndrome
  • 30. Other viral infections Cytomegalovirus – causes cytomegalic inclusion disease, in newborns, children and adults and has multiple systemic manifestations Parainfluenza types 2 and 3, echo and coxsackie viruses – non-specific suppurative sialadenitis Bacterial infections of salivary glands: Acute suppurative parotitis (bacterial sialadenitis): • Seen mostly in adults with salivary gland abnormalities and other predisposing factors •A retrograde infection via salivary duct may occur if the flow of saliva is reduced or stopped
  • 31. Predisposing factors:  Drugs that reduce salivary flow such as diuretics.  Salivary gland abnormalities such as calculus, mucus plug or benign strictures  Dehydration  Sjogren's syndrome Clinical features: 1. Unilateral or bilateral swelling of parotid glands. Swelling may extend, involving pre- and postauricular areas 2. Purulent salivary secretions at the duct orifice 3. Fever, chills and leukocytosis 4. Recurrent bouts of acute infection followed by remission may lead to fibrosis
  • 33. Treatment Empirical parenteral antibiotic therapy with a penicillinase resistant betalactam or, in case of risk of MRSA, vancomycin  Further therapy guided by culture and sensivity tests Oral hygiene Pus aspirated through catheter or collected aseptically on a cotton-wool swab by milking the duct Encourage the salivation by increased fluid intake and by sialagogues e.g. lemon juice In sever cases: surgical drainage of pus If acute bacterial parotitis is untreated: 1. Extension of inflammation and oedema into the neck leading to respiratory obstruction 2. Cellulitis of the face and neck 3. Osteomyelitis of adjacent facial bones 4. Septicaemia and death
  • 34. Trough levels of vancomycin according to dosage in children (from Kim DI, et al. Korean J Pediatr 2010)
  • 35. Vancomicina e tossicità renale L’uso di dosi elevate di vancomicina, tali da permettere il raggiungimento di livelli pre-dose di 15-20 mg/L sembrano sicuri se somministrati a soggetti senza rischio aumentato di nefrotossicità e per un periodo limitato (< 14 gg) Nei casi dubbi o quando il monitoraggio non sia possibile, considerare linezolid
  • 36. Mycotic Infections in Immunicompromised children Actinomycosis Caused by Actinomyces israelii. Types: 1. Primary endogenous, ascending infection via salivary ducts. Infection penetrates from mouth into gland and affects it entirely 2. Secondary when transferred to gland from tissue surrounding, non tender, non fluctuant indurated lesion with formation of multiple fistulae with discharge of sulphur granules
  • 37. Juvenile recurrent parotitis (JRP) - I • JRP is an inflammatoryrocess that results in recurrent, painful swelling of the parotid gland • The etiology is unknown: although autoimmune, ductal obstruction, immune deficiency, and infectious causes have all been proposed • It is the second most common pediatric salivary gland disorder after mumps • While the most common age for it to appear is 3 to 6 years old, it ranges from a couple of months of age to puberty, at which time it usually self-resolves • To diagnose JRP, a patient must have a clinical history characterized by multiple episodes of same-sided swelling and pain • It also must be differentiated from sialolithiasis and other causes of unilateral parotid swelling, which can occasionally occur in pediatric patients (use imaging such as ultrasonography)
  • 38. • Treatment of JRP often begins with symptomatic treatment, including antibiotics, analgesics, warm compresses, and sialagogues • Other treatments for recurrent inflammation have included injection of the duct with a sclerosing agent, radiation, ligature of the parotid duct, tympanic neurectomy, and parotidectomy • Many of those treatments, including radiation and neurectomy, have fallen out of favor Juvenile recurrent parotitis (JRP) - II
  • 39. From: Treatment of Juvenile Recurrent Parotitis of Childhood: An Analysis of Effectiveness JAMA Otolaryngol Head Neck Surg. 2015;141(2):126-129. doi:10.1001/jamaoto.2014.3036 Frequency of Parotitis Episodes Before and After Treatment With Ductal Corticosteroid Infusion Figure Legend:
  • 40. CONCLUSIONS MMR vaccination coverage should be urgently increased in Italy as well as in EU countries to contain measles, mumps, rubella Other causes of parotitis in childhood should be followed by a pediatrician and an ENT specialist
  • 41. SEE YOU IN MILAN!