INFECTIONS AND SALIVARY GLAND DISEASE IN PEDIATRIC AGE:

HOW TO MANAGE

Susanna EspositoPediatric 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: TransmissionThe 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

mese15th 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 infectionsCytomegalovirus – causes cytomegalic inclusion disease, in newborns, children and adults and has multiple systemic manifestationsParainfluenza 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 orifice3. Fever, chills and leukocytosis4. 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

tuberculosisAnaerobic

streptococciActinomyces

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 testsOral hygienePus aspirated through catheter or collected aseptically on a cotton-wool swab by milking the ductEncourage 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 obstruction2. Cellulitis of the face and neck3. Osteomyelitis of adjacent facial bones4. 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

ActinomycosisCaused by Actinomyces israelii.

Types:1. Primary endogenous, ascending infection via salivary ducts. Infection penetrates from mouth into gland and affects it entirely2. 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

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