KL Yam, Ch Lau, CK Li

Abstract

A nine year old Chinese girl presented with recurrent parotitis. Immunological and radiological investigations confirmed primary Sjogren syndrome. This condition is less common in children than in adults. However physicians should be alerted to this diagnosis in children with recurrent parotitis because of the possible implication: the need of long term follow up for emergence of autoimmune and lymphoproliferative diseases. Symptomatic treatment for the disability should be offered.

Introduction

Inflammation of the salivary glands may be acute, chronic or recurrent. Mumps is the commonest cause of acute parotitis in children, and it usually confers life-long immunity. Other infective organisms causing ascending infections include Staphylococcal aureus and Streptococcal species. Chronic parotitis due to ductal obstruction by a stone or tumour is rare in children. Though recurrent parotitis is uncommon, it is a well recognized condition in childhood.¹ It is characterised by repeated attacks of fever and painful swellings of the parotid glands, sometimes accompanied by muco-purulent discharge from the Stensen's ducts. lt may be unilateral or bilateral. The majority of cases are idiopathic. However there are also cases caused by Sjogren syndrome, which can either be primary,^2-8 or secondary to autoimmune diseases.^4,6,7,9 Our report is a case of primary Sjogren syndrome in a nine year old Chinese girl presented with recurrent parotitis.

Case Report

The patient first presented at the age of nine years because of acute parotitis. She had sudden onset of fever and a painful, red, hot left parotid swelling. Past health revealed that the child had numerous similar episodes. The first episode of parotitis occurred at the age of two and she was diagnosed as having mumps. Subsequently she had ten episodes of parotid swelling involving usually the left gland, but occasionally the right. Each episode typically began with fever followed by a painful, red, hot parotid swelling. The symptoms usually subsided following treatment with antibiotics prescribed by general practitioners.

In recent two years, the girl experienced dryness of the mouth. She did not prefer or avoid sour food. There was no dryness or gritty sensation of the eyes, persistent cough or hoarseness of voice. There was no unexplained fever, joint pain, skin rash, photosensitivity, loss of appetite or loss of weight. Family history revealed that her mother had non-insulin dependent diabetes mellitus and her paternal grandmother had systemic lupus erythematosus.

Physical examination revealed that she was febrile and her left parotid gland was inflammed with pus draining from the left Stensen's duct. Her dental hygiene was satisfactory. Ophthalmological examination and Schirmir's test were normal: right eye 19 mm, left eye 25 mm. There were only shotty cervical and submandibular lymph nodes. Examination of the respiratory, cardiovascular and central nervous systems and the abdomen was normal. Her growth percentiles were normal.

Investigation results were as follow: Haemoglobin 12.7 g/dl, white blood cells 14 x 10⁹/L (neutrophil 69%, lymphocyte 25%, monocyte 6%), platelet 231 x 10⁹/L. Erythrocyte sedimentation rate was 57mm/hr. C-reactive protein was 50.8 mg/L.(normal <8) Serum amylase was 640 U/L.(normal 45-116 U/L) These returned to normal after the child received antibiotic treatment. Serological test was negative for mumps and cytomegalovirus. Monospot test for heterophil antibody was negative. Pus swab from Stensen's duct grew commensals only. Renal function test and liver function test were normal. Thyroid function test was normal. Arterial blood gas showed no acidosis and urinalysis was normal.

Immunological studies revealed that antinuclear antibody was 1:2560 (speckled pattern). Anti-ds DNA was positive during parotitis but became negative after the attack. Rheumatoid factor (latex agglutination) was positive. Anti-thyroglobulin antibody titre <100, anti-microsomal antibody titre <100. Anti-ENA showed Ro+, La+, Sm-, RNP-, Jol-, Sd 70-. Tests for anti-salivary duct antibody and anti-tissue antibody were not available in our locality. C3 was 121 mg/dl (normal: 60-130 mg/dl) and C4 18 mg/dl (normal <100 mg/dl). Immunoglobulin pattern showed IgG 1944 mg/dl (age corrected normal: 724-1380 mg/dl), IgA 278 mg/dl (normal: 68-229mg/dl), 1gM 142 mg/dl (normal: 88-275 mg/dl), IgE 33 IU/ml (normal <100IU/ml). Protein electrophoresis showed a normal pattern without any paraproteinaemia.

Ultrasound examination of both parotid glands (Fig. 1) showed multiple punctate echogenic densities and small hypoechoic areas scattering throughout both glands, compatible with bilateral sialectactic changes. There was no abscess or mass lesion. No opaque stones were seen on plain radiograph. Sialogram of the left parotid duct (Fig. 2) showed irregular, beaded appearance of the main parotid duct and multiple punctate contrast collections within the parotid parenchyma: compatible with chronic non-obstructive sialectasis. Magnetic resonance imaging (Fig. 3) also showed sialectasis in both parotid glands. Chest radiograph and ultrasound examination of abdomen were normal. Lip biopsy was suggested but refused by parents.

Fig. 1 Ultrasound of the left parotid gland showing multiple echogenic densities and hypoechoic areas.

Fig. 2 Sialogram of the left parotid gland showing irregular beaded appearance of the parotid ducts and multiple punctate contrast collections.

Fig. 3 Magnetic resonance imaging of the parotid glands showing sialectasis.

The child responded to antibiotic treatment and her parotitis subsided quickly.

Discussion

Sjogren syndrome is a symptom complex of unknown aetiology, usually occurring in middle age or elderly women, marked by keratoconjunctivitis sicca, xerostomia and enlargement of the parotid glands. It may be primary, or secondary to autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus.

There are no universally accepted criteria for the diagnosis of Sjogren syndrome at present.⁶ Immunological, radiological and histological investigations are supportive. Most patients with Sjogren syndrome have high titre of autoantibodies such as anti-nuclear antibodies, most commonly directed to the antigens Ro and La. A speckled or nucleolar pattern of immunofluorescence is frequently found. More than 95% of patients with Sjogren syndrome have anti-Ro and more than 85% have it in association with anti-La antibodies.¹⁰ Our child has high titre of antinuclear antibodies with speckled pattern and positive anti-Ro and anti-La antibodies.

Besides anti-nuclear antibodies and anti-ENA(anti-Ro and anti-La), other autoantibodies such as rheumatoid factor, anti-salivary duct antibody or other organ-specific autoantibodies are frequently found. These organ-specific autoantibodies are not matched by organ-specific diseases.^11,12 Moreover polyclonal hypergammaglobulinemia is almost uniformly present.¹⁰ These suggest that activation of B-cells in Sjogren syndrome is polyclonal in nature. This is reflected in our child's grossly elevated IgG and absence of paraproteinemia on protein electrophoresis.

Other common laboratory abnormalities include anaemia, leucopenia, elevated ESR, hypothyroidism and renal tubular acidosis. Our child does not have any of the above features.

Patients with Sjogren syndrome usually have non-obstructive punctate, globular or cavitary sialectasia on sialogram; bilateral and multiple scattered cysts on ultrasound scan;¹³ area of low intensity between nodular parenchyma of high signal intensity on T₂WI images on magnetic resonance imaging.¹⁴ Their chest radiograph may be normal or show the following pattern: reticulonodular pattern, patchy consolidation and atelectasis, pneumonitis or pleural effusion. Although our child had a normal chest radiograph, her sialogram, ultrasound scan and magnetic resonance imaging were typical of the disease.

As the minor salivary glands in lower lip reflect the same histology as the major salivary glands or the parotid glands, lip biopsy is traditionally used for histopathological examination. The salivary glands in Sjogren syndrome typically show proliferation of ductal lining cells to form epimyoepithelial islands.¹⁰ However there are recent report suggesting that the classical histopathological criteria do not seem sufficiently specific, with only half of the patients having the characteristic findings.¹⁵ Hence, although the procedure was refused by the parents, in view of the fact that other investigations show characteristic findings of Sjogren syndrome, we feel that the lip biopsy may not be necessary to establish the diagnosis.

Epidemiological studies show that Sjogren syndrome is one of the commonly diagnosed connective tissue diseases in adults. However, it is rare in children. Literature review showed that few cases of primary Sjogren syndrome in childhood have been reported.^3-8 The number of reports has increased in recent years (Table). This may be related to the increased availability of immunological, radiological or pathological investigations and the recognition that keratoconjunctivitis sicca or xerostomia may develop two to four years after the onset of recurrent parotitis.^3,5 As in our case, the child also developed xerostomia several years after the onset of parotitis.

The relationship of Sjogren syndrome and idiopathic recurrent parotitis is not clear. Previous reports of idiopathic recurrent parotitis in children are mainly based on clinical features alone.¹ Whether they suffer from primary Sjogren syndrome or whether they indeed represent a separate group is not certain. It has been suggested that there were two subgroups: those with onset of parotid swellings below five years old and those at or above five years old. The latter group would deserve screening for underlying systemic immune disorders.² However, a recent report showed a child with primary Sjogren syndrome diagnosed at the age of nine year old, although the onset of her symptom dated back to the age of three month.³ Likewise in our patient, her symptoms dated back to infancy. It is not possible to ascertain whether these two patients had positive immunological markers if they were investigated at younger age, or whether these markers developed later in the course of the disease.

The distinction between the two groups has prognostic significance: idiopathic recurrent parotitis is of benign nature and will undergo spontaneous remission by adolescent and adulthood, whereas Sjogren syndrome in adult is associated with the development of connective tissue diseases and Iymphoproliferative diseases. Hence, there is a need for long term follow up to test for immunological markers, and if necessary, to proceed to radiological and histological investigations in children with recurrent parotitis.

Besides looking out for the possible development of autoimmune diseases and lymphoproliferative diseases, physicians caring for children with Sjogren syndrome should be alerted to the clinical silent renal tubular acidosis and hypothyroidism,^10,11 which are often associated with the syndrome.

Symptomatic treatment should be offered for the disability. Xerophthalmia may be alleviated by artificial tears, lubricating eye ointment, oral bronihexine or surgical obliteration of the nasolacrimal duct to reduce drainage. Nasal spray of normal saline may be used for the dryness of the nasal mucosa. For xerostomia, frequent sips of water or sour lemon drops are helpful. Oral fluoride, attention to dental care and prompt treatment of eye or oral infection are important.^4,7,11,16

In conclusion, children with recurrent parotitis may suffer from primary Sjogren syndrome. Our patient represents a rarely recognised disease in the Chinese population. This is also the first reported case in Hong Kong. Due to the small number of cases diagnosed and the lack of long term follow up reports, it is not certain whether these children will be at risk of developing autoimmune diseases or lymphoma as in adult patients.^3,4,7 These patients should be followed up until further study showed that childhood primary Sjogren syndrome have a different prognosis from the adult cases.

References

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