Acta Otorrinolaringológica Gallega

Caso Clínico

Parotidite recorrente juvenil e a utilidade da sialoendoscopia: apresentação de uma série de casos e revisão da literatura

Juvenile recurrent parotitis and sialoendoscopy utility: case series and literature review

Isabel Esteves Costa, Daniel Miranda, Ana Sousa Menezes, Berta Madureira Rodrigues,
Miguel Quintas-Neves.

Hospital de Braga, Portugal

Correspondencia:

Isabel Esteves Costa.

Hospital de Braga

Correo electrónico:

isabelcostaorl@gmail.com

Fecha de envío: 09/7/2019

Fecha de aceptación: 15/1/2020

ISSN:
2340-3438

Edita:
Sociedad Gallega de Otorrinolaringología

Periodicidad:
continuada.

Web:
www.sgorl.org/ACTA

Correo electrónico:
actaorlgallega@gmail.com

Abstract

Background: Juvenile recurrent parotitis (JRP) is the second most frequent cause of repeated inflammatory episodes of the parotid gland (after mumps) that occurs in childhood. It is associated with non-obstructive and non-suppurative idiopathic dilatation of glandular ducts and affects mainly males. Nowadays, treatment of JRP attacks is mainly symptomatic and conservative. The main objective of the current article is to present two cases of JRP and to overview the existing literature about diagnostic and therapeutic utility of sialendoscopy in children suffering of this disease.

Case summary: The authors present two clinical cases of first-onset JRP in a four and six-year-old female. One of them showed bilateral involvement and imaging confirmed the presence of multiple parotid microcysts without signs of lithiasic formations. In both cases, all acute crises were successfully treated symptomatically. In addition to recurrent episodes of parotitis, there were no other positive criteria for Sjogren’s syndrome, systemic lupus erythematosus or rheumatoid arthritis in any of our cases and none of them were positive for autoantibodies.

Discussion: JRP is a self-limited condition that should prompt investigation for underlying diseases, such as Sjogren’s syndrome and other autoimmune pediatric disorders (mainly if there is bilateral involvement). Here we present two cases of JRP that lasted until pre-adolescence.

Keywords

Juvenile recurrent parotitis; sialectasis; paediatric; sialendoscopy; childhood

Resumo

Introdução: A parotidite recorrente juvenil (PRJ) constitui a segunda causa mais frequente de episódios inflamatórios recorrentes da glândula parotídea (seguindo-se à parotidite vírica, também conhecida como papeira) durante a infância. Está associada à dilatação não-obstrutiva e não-supurativa idiopática dos ductos parotídeos e afecta sobretudo o sexo masculino. Actualmente, o tratamento preconizado passa por medidas sintomáticas e conservadoras. O principal objectivo deste estudo consiste na apresentação de dois casos clínicos de PRJ com revisão da literatura actual acerca da utilidade diagnóstica e terapêutica da sialendoscopia nas crianças esta patologia.

Descrição do caso clínico: Os autores apresentam dois casos clínicos de adolescentes do sexo feminino com o diagnóstico de PRJ com início aos 4 e 6 anos de idade. Um dos casos revelou a presença de envolvimento bilateral, sendo que o estudo imagiológico confirmou a presença de múltiplos micro-quistos parotídeos, sem sinais de sialolítiase. Em ambos os casos, todos os episódios agudos foram eficazmente tratados de forma sintomática e conservadora. Para além dos episódios de parotidite recorrente, não se verificou a presença de nenhum outro critério positivo para síndrome de Sjogren, Lúpus Eritematoso Sistémico ou Artrite Reumatóide em nenhum dos casos apresentados.

Discussão: A parotidite recorrente juvenil é uma condição auto-limitada que deve levar à investigação de outras patologias subjacentes, sobretudo no caso de envolvimento bilateral. Os autores apresentam dois casos de PRJ com duração até à pré-adolescência.

Palavras-chave

Parotidite recorrente juvenil; parotidite aguda recorrente; pediatria; sialendoscopia; infância

Introduction

Juvenile recurrent parotitis (JRP) is the second most frequent cause of repeated inflammatory episodes of the parotid gland (after mumps) that occurs in childhood. It is usually idiopathic, unilateral and associated with non-obstructive and non-suppurative dilatation of glandular ducts (sialectasis), followed by fever and general malaise1-3. Its etiology is unknown but theories suggest that these ductal abnormalities cause reduction of salivary flow and predispose to recurrent inflammation of parotid gland. Other studies suggest an association between this condition and upper airway infections, allergy, immunodeficiency or autoimmune and congenital diseases1-4. The age of onset is known to vary from 2 to 16 years and several studies report male preference5. Age of onset of symptoms also helps in differential diagnosis between JRP and a chronic inflammatory disease, particularly in cases of bilateral involvement. The number and frequency of attacks are variable and have a negative impact on school activity and quality of life of these children. Diagnosis is essentially clinical and confirmed by imaging. Due to its accessibility and the fact that it is non-invasive, ultra-sonography (US) remains the gold-standard diagnostic method and usually shows hypoechoic areas that correspond to sialectasis and intraparotid lymph nodes1,4-6.

Historically, treatment has varied between conservative measures and surgical procedures. Nowadays, treatment of JRP attacks is mainly symptomatic and conservative (analgesics, antipyretics, sialogogues, warm massages of the parotid gland, hydration, mouth rinses or antibiotics for more severe or persistent suppurative episodes)1,7. Nonetheless, none of these measures proved to be useful in preventing JRP. There is now increasing evidence that sialendoscopy, a minimal invasive endoscopic technique, can have an important role in diagnosis, treatment and prevention of JRP attacks. Although, as far as we know, there is limited literature about pediatric sialendoscopy efficacy8-12.JRP has a tendency to spontaneous remission at puberty, thus presenting a very favorable prognosis1,4,7.

The main objective of the current article is to present two cases of JRP and to overview the existing literature about diagnostic and therapeutic utility of sialendoscopy in children suffering of this disease (which however is not available in our center).

Clinical case

Case 1

A 12 year-old female, with no relevant past medical history, presented to an otolaryngology office with a history of recurrent unilateral episodes of parotitis since 6 years old. She also complaint of sporadic joint pain, mainly at the end of the day and after exercise but had no other symptoms like dry mouth, dry eyes, salivary colic or purpura/rash.

The patient underwent two parotid US in the acute phase (at 1st and 3rd year after onset of symptoms) that showed diffuse increase and heterogeneity of right parotid gland with scattered multiple hypoechoic areas, without signs of sialolithiasis or ductal obstruction. She also underwent an head MRI in the 5th year of the disease, in a non-acute phase (figure 1), that showed small multiple cystic formations on the right parotid gland, involving both superficial and deep lobes, coexisting with some solid formations, suggesting a salt and pepper appearance. These findings were suggestive of juvenile form of Sjogren’s disease. She was also evaluated by Pediatrics, and Sjogren’s disease and rheumatoid arthritis (RA) diagnosis were not confirmed.

Case 2

A 6-year-old girl with a history of obesity, adenoidectomy and myringotomy with tympanostomy tubes at 4 years old, transitory selective IgA deficiency and isolated left body hemi-hypertrophy presented to an otolaryngology office with complaints of recurrent episodes of bilateral parotitis since 4 years-old (with a frequency of >5 episodes per year and 15-16 episodes so far). There were no symptoms of dry mouth, dry eyes, salivary colic or purpura/rash. Physical examination (in non-acute phase) showed malar erythema and swelling with no parotid tumefactions and no drainage through Stensen’s ducts.

In this case, multiple parotid US during acute-phases showed heterogeneity and enlargement of the right parotid gland, coexisting with multiple hypoechoic areas (figure 2). Head MRI (non-acute phase) showed mild bilateral parotid parenchymal heterogeneity and the presence of multiple parotid microcysts (predominantly on the right side); there were no visible signs of ductal obstruction or lithiasic formations (figure 3). She was followed by Genetics for Beckwith-Wiedemann syndrome’s screening which was negative.

Note that both patients had been immunized by mumps vaccine as part of Measles, Mumps, and Rubella (MMR) vaccine.

The laboratory tests results (in non-acute phase) are listed in table 1.

	Case 1	Case 2	Reference values
Serologies*	Neg	Neg	-
ANA test	R (>1/640 - speckled pattern)	NR	-
Imunologies (mg/dL) IgG IgA IgM IgE C3 C4	934 116 149 411 Normal (113) Normal (19)	N/A 26 N/A N/A Normal (136) Normal (35)	27-195 35-239 <190,9 90-180 10-40
Anti-Ro (SS-A)	Neg	N/A	-
Anti-La (SS-B)	Neg	N/A	-
Rheumatoid factor (IU/mL)	< 10	< 10	<15
C reactive protein (mg/dL)	<2,90	6,6	<3,0
Sedimentation velocity	11	N/A	1-20
TSH Free T4	2,6 0,93	4,360 1,22	0.358-3.74 0,76-1,46
Allergology study	N/A	Neg	-
*Serological study included Anti Human Immunodeficiency Virus (HIV) I and II ANA: anti-nuclear antibody; > Neg: negative NR: non-reactive N/A: not available TSH: thyroid-stimulating hormone

In addition to recurrent episodes of parotitis, there were no other positive criteria for Sjogren’s syndrome, SLE or RA in any of our cases and none of them were positive for autoantibodies.

In our cases, all acute crises were successfully treated symptomatically, mainly with nonsteroidal anti-inflammatory drugs and local measures.

In case 1, the child progressed with a total of seven crises and had been asymptomatic for 3 years. The last episode occurred at 9 years old. In case 2, there was a resolution of IgA deficiency over a year of follow-up. None of them required hospital admission in any of their attacks.

Discussion

These two interesting cases corroborate that JRP is a self-limiting condition, occurring at any age during childhood. Although the frequency of acute episodes is known to be higher in first school year, Ericson et al. showed that age of onset can vary between 3 and 16 years13. Currently, its etiology remains uncertain and genetic, infectious and immune-mediated causes have all been proposed9. In a subset of patients, it is believed that genetic factors may be involved in the manifestation of juvenile parotitis14. Families with two sibs affected or with members of more than one generation affected have been reported in literature. Some reports show that transmission patterns in some families are consistent with autosomal dominant inheritance with incomplete penetrance. Some genes which may be responsible for JRP in these families have been studied. Genes coding for salivary enzyme genes, structural elements of the pancreatic duct system, or genes involved in immune response may be candidates15. Mutations in a gene encoding for a trypsin inhibitor (SPINK1 gene) have also been reported which show that proteolytic imbalance may play a role in the development of symptoms. Some authors propose an autoimmune origin; however, the self limiting nature of this disease and the absence of detectable autoantibodies makes this unlikely.16 By causing dehydration in child with sialectasis, it is known that upper respiratory tract infections may also have a role in JRP.17

Ascending infections from the oral cavity have been considered the primary event in JRP. Maynard (1965) proposed that recurrent episodes of parotid swelling was the final result of a sequence of events that include a low grade inflammation of the gland in the first place, possibly caused by a low salivary flow rate due to dehydration. This leads to distortion and metaplasia of the ducts, which in turn causes excessive mucus secretion. All these changes can finally predispose to recurrent parotid inflammations.17

Symptoms usually diminish or vanish completely after puberty, which was confirmed with our cases. So far, there is no explanation for that, but most authors defend that gland tissue regeneration and return to normal function is a preponderant mechanism for spontaneous resolution of symptoms18. Parotid infections at a young age affects the immune system, and some theories argue that this disease may represent immaturity of the immunologic response. No evidence suggests that allergy is a cause.

In the present study, we found only female patients, which does not correspond to the trend of most studies that have demonstrated male preponderance. However, females are predominantly affected when the disease begins later, after puberty9,19. This disease is usually manifested by painful swelling associated with local pain and fever. Manifestations normally lasts from some days to a couple of weeks and usually solve spontaneously, with or without treatment4,19.

The role of antibiotics in treatment of JRP is controversial and restricted to suppurative events. Until now, no medication is available to prevent recurrences5,7,9.

About 80-90% of B lymphocytes in the parotid gland produce IgA. IgA deficiency is related with a deficit of B lymphocytes and is the most common immune defect; also, IgA is the major immunoglobulin secreted into the mucosal surfaces. Deficiency of this immunoglobulin can lead to an inability to clear inflammatory stimuli and a lack of local immunity. Because of that, selective IgA deficiency has been associated with various inflammatory disorders. Some authors also support that IgA deficiency can be associated with JRP, as there are reports of patients with JRP and isolated immunoglobulin A deficiency20. This fact is in agreement with our sample, since one child (case 2) revealed transitory IgA deficiency, which resolved after one year of follow-up. Further investigations are needed to determine the possible role of IgA deficiency in recurrent parotitis. Also, there is no evidence to support that IgA levels can correlate with evolution and prognosis of JRP. The authors recommend testing immunoglobulins levels for all cases of JRP21-23.

Several imaging modalities are available for JRP diagnosis. Sialography and US remain the most frequently used ones. Sialography consists of an opacification of the salivary ducts using a retrograde intra-cannular injection of a radiopaque contrast agent. It is very useful for clear detection of ductal anomalies such as sialoliths and strictures, by showing multiple small radiopaque areas within the gland24,25. Although, it has the disadvantage of needing to cannulate the salivary duct and exposing the patient to a significant amount of radiation25. On the other hand, Mayumi et al., Rubaltelli et al. and Nozaki et al. showed that US is able to detect heterogeneity in the structure of the gland, hypoechoic areas, corresponding to sialectasia, and intraparotid lymph nodes in the vast majority of cases25-27. Besides, US also allows the detection of other situations, such as masses and lymphadenopathy.  However, none of these ultrasonographic findings were proved to be specific to JRP. Furthermore, US is not able to detect salivary duct stenosis (in these cases, US may only show an unspecific heterogeneity on the gland architecture)26-28. To note that approximately 20–40% of the salivary lithiasis is not opaque on plain films, but most of these are visible on ultrasound. Beyond that, a normal US or sialography does not exclude the condition of JRP. Digital sialography is contraindicated during episodes of acute inflammation.and and some authors consider that this procedure is best avoided in self-limiting pediatric cases. Other modalities are also currently used, such as Computed Tomography (CT), Sialo-CT and MRI but they add no further information and are not usually needed in the majority of cases. MR sialography is a revolutionary technique that allows the visualization of the ducts without any dye injection and, therefore, without pain and radiation. Its main disadvantage is the time required for reconstruction26-28. In children with classic clinical findings, US alone is diagnostic and MR sialography is not usually required. Although they cannot substitute US, MR and MR sialography can accurately detect sialectasis and signal intensity changes according to the inflammatory phase of the gland disease (acute vs. chronic). Besides, MR sialography can be very useful in atypical and unilateral cases27,28. Summarizing, sialography evaluates mainly the ductal anomalies, US shows the parenchymal changes and MR/MR sialography evaluates the entire process. Given that, the authors propose performing parotid US for diagnosis in typical and acute cases, reserving MR or MR sialography for the subsequent study of cases with atypical presentation and evolution.

In recent years, there are many authors emphasizing the role of sialendoscopy in diagnosis, treatment and prevention of JRP attacks. First introduced in the 1990s by Katz and Gundlach29, sialendoscopy is becoming a promising conservative approach to salivary gland diseases, since it is associated with high success rates and low morbidity. The underlying technique consists on irrigation and washing of the affected ductal system and dilatation of all the ductal strictures under direct vision. Besides, it comes with the possibility of insert some surgical instruments for dilatation procedures and allows for delivery of therapeutic medications, such as steroids, which increases the efficacy and reduces the systemic side effects of the steroid treatment24,29-32. Sialendoscopy has higher sensitivity than US in JRP diagnosis since most patients with sialendoscopic diagnosis of duct stenosis have no duct dilatation on US analysis. Shacham et al. presented their experience with 70 children and showed that there was no recurrence for 93% (n=65) of the patients treated with sialendoscopy during a follow-up of 6 to 36 months23. For all these reasons, sialendoscopy is now recognized as a safe technique in children with JRP. Some authors advocate that diagnostic sialendoscopy must be also considered as the first step in complementary examination in children with salivary gland obstructive disease. However, sialendoscopy should not be performed during acute inflammation of salivary glands as it may increase the pain and swelling. Inflammation also leads to a decreased cannulation rate and poor visibility of salivary ducts which may result in complications such as duct perforation and stenosis30-32. The authors consider that, over time and whenever available, sialendoscopy should be considered as a first line therapeutic option especially in relapsing and refractory cases.

The level of suspicion for auto-imune diseases must be higher when bilateral involvement is present. In case 1 (unilateral case) we found a reactive ANA (anti-nuclear antibody) test, with a speckled pattern. The ANA test may be positive in several autoimmune disorders, like in systemic lupus erythematosus (SLE), but other types of disorders and even heathy people may also be positive for ANA. Different cellular fluorescent patterns have been associated with different autoimmune disorders, although some overlap can exist. Speckled pattern can be associated with SLE, Sjögren syndrome, scleroderma, polymyositis or rheumatoid arthritis (RA)33-36

The current article aimed to exemplify two cases of JRP with an excellent evolution and to clarify some diagnostic and therapeutic dillemas, mainly about sialendoscopy and its promising utility in the near future.

Acknowledgments

Neuroradiology department of Hospital de Braga

Funding Source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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FIGURES:

Figure 1. Case 1 - Head MRI. (A) Axial Short tau inversion recovery (STIR) sequence demonstrates multiple cystic formations on the right parotid gland, involving both superficial and deep lobes. Most of these formations do not show restricted diffusion on Diffusion-weighted imaging (DWI) (B) and apparent diffusion coefficient (ADC) map (C); enlarged retropharyngeal lymph nodes of inflammatory etiology, predominantly on the right side, are also seen.

Figure 2. Case 2 - Parotid ultrasonography demonstrates parenchymal heterogeneity characterized by several infracentimetric hypoechoic areas (A). Multiple enlarged cervical lymph nodes are also evident, presenting with an oval shape appearance and presence of fatty hilum – findings that are suggestive of inflammatory etiology (B).

Figure 3. Case 2 - Head MRI. (A) Coronal Short tau inversion recovery (STIR) sequence demonstrates multiple microcysts on the right parotid gland. Several enlarged lymph nodes of inflammatory etiology are also shown, namely on the retropharyngeal and parotid spaces (A), as well as on cervical posterior (B) space. (C, D) On Diffusion- weighted imaging (DWI) the enlarged lymph nodes show restricted diffusion.