Pediatric Sjogren Syndrome 

Updated: Oct 15, 2018
Author: Marietta Morales De Guzman, MD; Chief Editor: Lawrence K Jung, MD 

Overview

Practice Essentials

Sjögren syndrome, which is rare in pediatric patients, is a slowly progressive inflammatory disorder that involves the exocrine glands.[1]  Mikulicz and others recognized the findings of keratoconjunctivitis and xerostomia as an entity in the late 1800s.[2]  In 1933, Sjögren recognized the association of this symptom complex with polyarthritis.

Subsequent studies showed that Sjögren syndrome may be a primary disorder or may be secondary to other autoimmune disorders, such as systemic lupus erythematosus (SLE),[3]  rheumatoid arthritis, scleroderma, and biliary cirrhosis. Extraglandular manifestations may mimic these other autoimmune disorders.[1]  The primary disorder is most common in women in the fourth and fifth decades of life. Sjögren syndrome may overlap with other pediatric autoimmune disorders and, less commonly, may present as a primary condition (see the images below). (See Etiology, Clinical, and Workup.)[4, 5]

Lower facial appearance of a 14-year-old adolescent girl with Sjögren syndrome. She exhibits both parotid and submandibular gland enlargement and chapped lips.

Lower facial appearance of a 14-year-old adolescen Lower facial appearance of a 14-year-old adolescent girl with Sjogren syndrome. She exhibits both parotid and submandibular gland enlargement and chapped lips.

Intraoral view of a 14-year-old adolescent girl with Sjögren syndrome. Hyposalivation results in erythema of the mucosa, gingivitis, decalcification or white spot lesions of the teeth at the cervical margin, and dental caries with extensive restorations of the posterior teeth.

Intraoral view of a 14-year-old adolescent girl wi Intraoral view of a 14-year-old adolescent girl with Sjogren syndrome. Hyposalivation results in erythema of the mucosa, gingivitis, decalcification or white spot lesions of the teeth at the cervical margin, and dental caries with extensive restorations of the posterior teeth.

Erythema of the labial mucosa with enlargement of the minor salivary glands and superficial mucoceles.

Erythema of the labial mucosa with enlargement of Erythema of the labial mucosa with enlargement of the minor salivary glands and superficial mucoceles.

The dorsal surface of the tongue demonstrates generalized atrophy of the filiform papillae, mild fissuring, and median rhomboid glossitis.

The dorsal surface of the tongue demonstrates gene The dorsal surface of the tongue demonstrates generalized atrophy of the filiform papillae, mild fissuring, and median rhomboid glossitis.

A 14-year-old adolescent girl with Sjögren syndrome with painful unilateral swelling of the knee and hyperpigmentation of the overlying skin.

A 14-year-old adolescent girl with Sjogren syndrom A 14-year-old adolescent girl with Sjogren syndrome with painful unilateral swelling of the knee and hyperpigmentation of the overlying skin.

The systemic and extraglandular features of Sjögren syndrome define the choice and extent of anti-inflammatory and immunomodulatory therapy, clinical course and disease outcome. (See Prognosis, Treatment and Medications.)

Overlapping symptoms consistent with SLE include neuropsychiatric manifestations, nephritis, and severe Raynaud phenomenon.[6]  Severe systemic manifestations may also develop without overt features of other autoimmune disorders.[3]

Patient education

As Sjögren syndrome is a chronic disease, participation in a local or national support group may be beneficial. The Sjögren's Syndrome Foundation is an example of an organization that helps individuals cope with this disease. Additional resources can be found at the Lupus Foundation of America and the Arthritis Foundation. For patient education information, see the Arthritis Center, as well as Sjögren’s Syndrome.

Background

 

 

 

Etiology

Multiple etiologic factors are likely involved in the pathogenesis of Sjögren syndrome.[1, 7] Lymphocytic infiltration in the glandular lobules is the characteristic abnormality in lacrimal or salivary gland biopsy findings. The disorder appears to be mediated by a complex cascade of immune events and is often characterized as an autoimmune exocrinopathy.[7, 8]

The predominant immune cells are activated memory CD4+ T cells that express alpha/beta T-cell receptors, suggesting a central role in the pathogenesis of this disorder.[7] Activated B cells are also found in the lesions, which may be responsible for the production of the autoantibodies to autoantigens Ro (SS-A) and La (SS-B). Anti-Ro (SS-A) is found in 40-45% of adult patients with Sjögren syndrome, and anti-La (SS-B) is found in 50% of these patients. The presence of anti-Ro (SS-A) and anti-La (SS-B) is associated with earlier onset, longer duration, and more extensive extraglandular manifestations of primary Sjögren syndrome.

Positivity in these antibodies appears to be higher in children, according to a systematic review of the literature (rheumatoid factor [RF], 66%; antinuclear antibody [ANA], 78%; SS-A, 74%; SS-B, 65%).[9, 10, 11] Because these autoantibodies are also observed in other autoimmune disorders, including SLE, further diagnostic tools must be used for a more definitive diagnosis. 

Researchers have found a high prevalence of anti-Muscarinic-3 acetylcholine receptor autoantibodies in Japanese children with primary Sjögren syndrome.[12] These antibodies are postulated to be involved in defective glandular function and as anti-SSA and anti-SSBA, could be potentially useful as a diagnostic marker for primary Sjögren in children and adolescent.   

Autoantibody production and evidence of a polyclonal gammopathy implicate B-cell dysfunction as a component of Sjögren syndrome pathogenesis. Increased levels of B-cell activating factor (BAFF) or B-lymphocyte stimulator (BLyS), which are essential for B-cell survival, can be found in patients with Sjögren syndrome. Thus, B-cell depletion therapies that include the anti-CD20 monoclonal antibody (rituximab) are being used in open-label studies.[13]

In situ evidence suggests that proinflammatory cytokines, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)–alpha are produced in the salivary glands. These cytokines are found in the infiltrating lymphocytes and the epithelial cells. This suggests that the infiltrating lymphocytes (ie, predominantly CD4+ T cells) play a role in the perpetuation of an aberrant immune response. Specific IL-10 haplotypes are associated with early onset and vasculitic features of disease. IL-21 levels was noted to correlate positively with serum IgG and IL-21 expression is increased as more lymphocytes infiltrated in LSG among patients with primary SS.[14, 15]  Additional cytokine and chemokine gene polymorphisms continue to be focus of several ongoing studies.

A higher incidence of Sjögren syndrome is found in family members of patients with the disease. The association of Sjögren syndrome with human leukocyte antigen (HLA)–B8, HLA-Dw3, HLA-DR3, and the DQA1*0501 allele supports the notion of genetic susceptibility.[16]

An active area of research involves genetic polymorphisms of cytokine genes, including IL10 and TNFA.[7] Associations with these polymorphisms might implicate inappropriate regulation of the immune response in Sjögren syndrome. Altered apoptotic mechanisms have also been implicated in the pathogenesis of Sjögren syndrome–related exocrinopathies. Exocrine gland tissue damage and chronic inflammation lead to fibrotic changes and impaired glandular function. The pathophysiology of extraglandular manifestations is thought to be due to similar immune mechanisms.

Epstein-Barr virus (EBV) replicates in the salivary glands during primary infection and remains latent in these organs. EBV deoxyribonucleic acid (DNA) is recovered from the salivary glands and saliva of patients with Sjögren syndrome. Its etiopathologic role cannot be proven. Human immunodeficiency virus (HIV), human T-cell leukemia-lymphoma virus type 1 (HTLV-1), and cytomegalovirus (CMV) are also being studied as possible inciting agents of the lymphoproliferation observed in the end organs.

Epidemiology

United States

Overall, Sjögren syndrome is the second most common autoimmune disorder in adults, after rheumatoid arthritis. In the United States, between 500,000 and 2 million adults have this disease.[2]

Primary disease is rare in childhood, as only 145 cases of primary disease have been described in the international pediatric literature.[9] Five percent of adult patients report onset of symptoms before age 12 years. Clinical manifestations and classification schema differ in pediatric patients; therefore, this disorder may be underreported. Features of Sjögren syndrome are well described in pediatric patients who have other autoimmune disorders and oftentimes it is defined as an overlapping syndrome.

International

Epidemiologic studies from different ethnic groups show prevalence rates similar to those in the United States.

Sex- and age-related demographics

The female-to-male ratio for Sjögren syndrome was 7:1 in one multicenter international pediatric cohort and 6:1 in a systematic review of the literature.[9, 10] In adults, the female-to-male ratio is approximately 9:1.[11]

In 2 studies, the mean age of diagnosis for primary juvenile Sjögren syndrome was 10 years.[9, 10] Although Sjögren syndrome has been recognized in patients of all ages, it primarily affects women in the fourth and fifth decades of life.

Prognosis

 

Patients with primary Sjögren syndrome usually have a good prognosis unless systemic and/or severe extraglandular manifestations develop. The prognosis of secondary Sjögren syndrome depends on the primary autoimmune disorder.

Although most adult patients have a mild and benign course, they often experience painful eye irritation, severe dental caries, and dyspareunia. Pediatric patients often do not have early sicca syndrome symptomatology but often have recurrent parotitis, which commonly is diagnosed as recurrent parotitis of childhood, another uncommon pediatric disorder with a bimodal age incidence of 2-5 and 10 years of age. Because of the insidious nature of these symptoms, patients often do not seek medical attention until more severe symptoms appear years later.

The time from disease onset until diagnosis is often 9 years in adults and perhaps as long as 3 years in pediatric patients. In a multicenter, retrospective review of 40 patients, few major complications were reported from time of onset (follow-up, 0-7.5 y).[10] According to another small report of pediatric patients with at least 3 years’ follow-up, minimal progression in disease status was reported.[17] Some pediatric patients may develop systemic features that involve the nervous system, kidney, and lungs.[10, 18, 19]

Lymphoproliferative disorders increase 40-fold in adult Sjögren syndrome. Although significant lymphoproliferation usually remains confined to the salivary and lacrimal glands, extraglandular lymphoproliferation (eg, lymphadenopathy, hepatosplenomegaly) sometimes resembles lymphoma (eg, pseudolymphoma) and may herald frank malignancies, including non-Hodgkin lymphoma, Waldenström macroglobulinemia, and B-cell lymphoma. Associations with lymphoproliferative diseases are not well described in pediatric populations.

 

Presentation

History

Clinical manifestations of pediatric Sjögren syndrome may vary more than those seen in adult patients.[17] The constellation of symptoms seen in children (eg, lower frequency of sicca syndrome, higher rates of parotid enlargement, higher prevalence of immunologic markers) may be similar to those found in young adult patients (ie, < 35 y).[20, 21]

Sicca syndrome

Symptoms of keratoconjunctivitis include dry eyes with reduced tear production, gritty or sandy sensation under the lids, red eyes, and photosensitivity. Keratoconjunctivitis is less prominent in primary juvenile Sjögren syndrome. Lacrimal gland enlargement appears to be a feature in primary and secondary pediatric Sjögren syndrome. The management of keratoconjunctivitis includes the use of artificial tears and conservation of natural tear flow.[9, 10, 22]

Symptoms of xerostomia include decreased saliva production and difficulties with chewing, swallowing, and even speech; abnormality in taste and smell; dental caries; mucosal burning sensation; sensitivity to spicy and acidic foods and beverages; increased risk for oral candidiasis; hoarseness of voice, and dysphonia (common in adults). Recurrent parotitis appears to be the most common oroglandular manifestation in pediatric populations.[9, 10]

Musculoskeletal symptoms

Symptoms include the following:

  • Arthralgia (often noninflammatory), morning stiffness, and nonerosive arthritis

  • Myalgia and muscle weakness

Cutaneous findings

Symptoms include the following:

  • Raynaud phenomenon

  • Nonthrombocytopenic purpura, especially of lower extremities

  • Nasal, vaginal, and cutaneous dryness

Gastrointestinal symptoms

Symptoms include the following:

  • Dysphagia, nausea, and epigastric and abdominal pain

  • Achalasia (in children)

  • Achlorhydria and chronic atrophic gastritis (adult patients)

  • Primary biliary cirrhosis

Pulmonary findings

Symptoms include the following:

  • Dyspnea due to mild interstitial disease

  • Dry cough

Renal symptoms

Symptoms include the following:

  • Interstitial nephritis

  • Renal tubular acidosis[23]

Additional findings

The following symptoms may also be seen in Sjögren syndrome:

  • Fatigue

  • Depression

  • Insomnia

  • Cognitive impairment

Physical Examination

The following may be noted on physical examination:

Parotid gland enlargement and recurrent parotitis (most prominent feature in pediatric populations)[9, 10, 22, 24]  

Upper lid prominence due to lacrimal gland enlargement

Corneal ulceration, vascularization, and uveitis

Vasculitic lesions - Purpura and erythema nodosum

Lymphadenopathy

Autoimmune thyroiditis

Nervous system manifestations - Peripheral sensorimotor neuropathy; central nervous system (CNS) disorders such as cognitive impairment, movement disorder, transverse myelopathy, encephalopathy, aseptic meningitis, dementia, optic neuropathy, and cranial neuropathies (in both adult and pediatric patients)

Musculoskeletal manifestations - Intermittent synovitis, chronic nonerosive oligoarticular or polyarthritis (Jaccoud arthropathy has been observed in adults), and myalgias

Oral cavity manifestations of Sjögren syndrome may include the following: 

See the list below:

  • Poor or absent pooling of saliva underneath the tongue.
  • Mild erythema and thinning of the mucosa

  • Dental caries

  • Traumatic erosions and ulcers, angular cheilitis, and chapped lips

  • Frothy, ropey, and thickened saliva

  • Erythema, fissuring, coating, and depapillation of the dorsal tongue

  • Halitosis

  • Gingivitis/periodontitis

  • Superficial mucoceles

 

DDx

Diagnostic Considerations

Conditions to consider in the differential diagnosis of Sjögren syndrome include the following:

 

Medications that cause sicca symptoms (anticholinergic agents)

Recurrent juvenile parotitis

Oropharyngeal candidiasis

Gingivitis/periodontitis

Retrograde bacterial sialadenitis

Halitosis

Superficial mucoceles

Compromised nutrition

Dryness of the nasal and vaginal mucosa and skin

Pregnancy complications due to autoantibodies

Mumps

Sarcoidosis

SLE 

Mixed connective tissue disease

Systemic sclerosis 

IgG 4 disease

Hepatitis C

Differentials

Anorexia Nervosa

Infections in the Immunocompromised Host

Lymphoproliferative Disorders

Pediatric Bulimia

Pediatric Graft Versus Host Disease

Pediatric HIV Infection

Pediatric Herpes Simplex Virus Infection

Pediatric Mononucleosis and Epstein-Barr Virus Infection

Vasculitis and Thrombophlebitis

Differential Diagnoses

 

Workup

Approach Considerations

Diagnosis of primary Sjögren syndrome is made in adults if the serology or histopathology is positive and if 4 of the American-European Consensus Group (AECG) criteria for adult patients are met[25] :

Mandatory criteria are as follows:

  • Characteristic histopathologic features on minor salivary gland biopsy findings: In minor salivary glands (obtained through normal-appearing mucosa) focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score of greater than 1, defined as a number of lymphocytic foci (that are adjacent to normal-appearing mucous acini and contain >50 lymphocytes) per 4 mm2 of glandular tissue OR

  • Serology: Anti-Ro (SS-A) or anti-La (SS-B)

AECG adult criteria are as follows (4 adult criteria needed):

  • At least 1 positive response to the ocular symptom questions (see Screening Questions, below)

  • At least 1 positive response to the oral symptom questions (see Screening Questions, below)

  • Ocular signs - Positive Schirmer tear test or Rose-Bengal stain findings

  • Salivary gland involvement revealed by at least 1 testing modality (salivary scintigraphy, parotid sialography, unstimulated salivary flow)

  • Exclusion criteria - Preexisting lymphoma, human immunodeficiency virus (HIV), hepatitis C, sarcoidosis, graft versus host disease (GVHD)

Criteria for pediatric patients have been proposed but not prospectively validated.[26] Only 76% sensitivity has been noted in studies of retrospective patients.[22] The clinical judgment of a pediatric rheumatologist is the criterion standard. However, the proposed pediatric criteria appear more sensitive than adult AECG criteria in classifying primary pediatric Sjögren syndrome. Diagnosis is based on the presence of 4 or more of the following proposed pediatric diagnostic criteria:

  • Exclusion of all other autoimmune diseases

  • Oral symptoms - Dry mouth, parotitis, and parotid gland enlargement

  • Ocular symptoms - Recurrent conjunctivitis and keratoconjunctivitis sicca

  • Other mucosal symptoms - Recurrent vaginitis or vulvovaginitis

  • Systemic symptoms - Fever of unknown origin, noninflammatory arthralgias, and hypokalemic paralysis

  • Presence of anti-Ro (SS-A), anti-La (SS-B), high titer ANA, or RF

  • Elevated serum amylase levels

  • Leukopenia and high erythrocyte sedimentation rate (ESR)

  • Polyclonal hyperimmunoglobulinemia

  • Renal tubular acidosis[23]

  • Histologic proof of lymphocytic infiltration of salivary gland or other organs

  • Objective documentation of ocular dryness - Schirmer tear test or Rose Bengal stain findings

  • Objective documentation of parotid gland enlargement - Sialography findings

On a complete blood count (CBC) with differential, mild anemia and leukopenia are often present in patients with Sjögren syndrome. Elevated erythrocyte sedimentation rate (ESR) is observed in 80-90% of patients, which may be related to hypergammaglobulinemia; however, C-reactive protein (CRP) levels are usually within the reference range. Hypergammaglobulinemia, up to several grams of immunoglobulin G (IgG), is observed in 70-80% of pediatric and adult patients.

Antibodies

ANA and rheumatoid factor RF levels are usually elevated in children. Anti-Ro (SS-A) and anti-La (SS-B) are also usually present in children.

Various autoantibodies may be found in patients with Sjögren syndrome; however, the clinical or diagnostic implication is often unclear. Autoantibodies include thyroglobulin, thyroid microsomal, mitochondrial, smooth muscle, parietal, peroxisomal, muscarinic receptors, and salivary duct (often present in adults with Sjögren syndrome) autoantibodies. Cryoglobulins and, occasionally, antiphospholipid antibodies are noted.[27]

Keratoconjunctivitis and Tear Production

In Rose Bengal staining, the dye stains damaged corneal epithelium and indicates keratoconjunctivitis. This is not often performed in children.

Schirmer tear test is used to evaluate tear production by lacrimal glands. A strip of filter paper is placed beneath the lower lid, and wetting of the paper is measured at 5 minutes. Less than 10 mm of film is abnormal, and less than 5 mm of wetting suggests decreased tear production and sicca syndrome. This test is performed more often in pediatric patients.

Saliva Production and Sialochemistry

Sialometry is the quantification of whole saliva or individual gland secretions at unstimulated (resting) or stimulated flow rates. These procedures are not commonly used in pediatric patients.

For salivary hypofunction, the flow rate for unstimulated whole saliva is less than 0.1 mL/min, whereas the rate for stimulated whole saliva is less than 0.5 mL/min. The collection period is a minimum of 5 minutes and often up to 15 minutes. When secretions from the parotid gland are evaluated, the modified Carlson-Crittenden collector is placed over the Stensen duct. Isolation of the salivary gland orifices in the floor of the mouth and gentle suction are used to collect submandibular and sublingual secretions together. Besides demonstrating salivary hypofunction, these methods can be used to evaluate the effectiveness of secretogogue therapy.

On sialochemistry, collected secretions can be chilled, frozen, and evaluated for electrolytes, immunoglobulins, and protein constituents. Although not diagnostic for Sjögren syndrome, a profile has been observed, including an increase in secretory levels of immunoglobulin A, lactoferrin, total protein, and sodium and chloride ions. In addition, decreased levels of lysozyme and potassium and phosphate ions are found. A change in the proteomic signature of a salivary peptide complex was noted in a boy who had clinical improvement of his Sjögren syndrome.[28] Although still considered experimental, these changes in salivary constituents are of unknown predictive value.

Sialography, Scintigraphy, and MRI

Sialography is a sensitive and specific radiographic technique for detecting sialectasis. However, sialography sensitivity has not been reported in the pediatric literature. These techniques are not commonly used at most pediatric centers; however, their use has been described by multiple investigators.[10, 29]

Technetium-99m (99m Tc) pertechnetate scintigraphy shows delayed uptake in Sjögren syndrome; often in correlation with pathologic changes.

Magnetic resonance imaging (MRI) visualizes the glandular parenchyma and aids in the evaluation of cystic or solid masses. In addition, the volumetric estimate of the gland size can be determined.

Salivary Gland Biopsy

The pathologic findings from biopsy are very useful in diagnosis and are often obtained in juvenile primary Sjögren syndrome workup. Because of its relative ease and lack of complications, labial minor salivary gland biopsy is preferred over parotid gland biopsy, which can result in facial nerve damage. However, minor salivary gland biopsy requires sufficient expertise to ensure adequacy of tissue collection.

In order to ensure that a representative sample has been obtained for histopathologic examination, harvesting 5-10 lobules of minor salivary glands is crucial. (See the image below.)

Biopsy of the minor salivary glands of the lower l Biopsy of the minor salivary glands of the lower lip may be useful in the diagnosis of Sjögren syndrome. A 1.5- to 2-cm incision of normal-appearing mucosa allows for the harvesting of 5 or more salivary gland lobules.

Histologic Findings

The characteristic histopathologic findings of the minor salivary glands include an inflammatory infiltrate adjacent to normal-appearing acinar structures. The inflammatory infiltrate consists of primarily lymphocytes and fewer plasma cells. Most of the infiltrating lymphocytes are activated CD4+ memory T lymphocytes. A focal periductal pattern is initially observed, with eventual confluence of the inflammatory infiltrate that replaces the acini. Periductal and perivascular hyaline deposits may be observed. (See the images below.)[7]

Low-power photomicrograph of a minor salivary glan Low-power photomicrograph of a minor salivary gland lobule showing multiple lymphocytic foci that are replacing the acinar structures (hematoxylin-eosin, 40 X).
Intermediate-power photomicrograph demonstrating a Intermediate-power photomicrograph demonstrating a chronic inflammatory aggregate of more than 50 lymphocytes and plasma cells with a periductal pattern. The inflammatory focus is adjacent to normal appearing acini (hematoxylin-eosin, 200 X).
High-power photomicrograph of the chronic inflamma High-power photomicrograph of the chronic inflammatory aggregate consists of lymphocytes and plasma cells around a ductal structure (hematoxylin-eosin, 400 X).

Unlike the parotid gland lesions, epimyoepithelial islands are rarely observed in the lymphocytic background. The finding of more than 1 focus of 50 or more inflammatory cells within a 4-mm2 area of glandular tissue supports the diagnosis of Sjögren syndrome. The greater the number of foci, the greater the correlation with a disease diagnosis. However, a negative biopsy finding cannot completely exclude a diagnosis of Sjögren syndrome. Biopsy findings may also be used to rule out granulomatous (sarcoid) or amyloid lesions.

When the major glands are enlarged, a benign lymphoepithelial lesion (BLEL) may develop. The characteristic features include a dense, lymphocytic infiltrate that is associated with the destruction of salivary gland acini, while the ductal epithelium persists. Hyperplasia of the ductal epithelium and myoepithelial cells forms epimyoepithelial islands within the lymphoid tissues. Formation of germinal centers may be observed. In adult patients, a determination of monoclonality of the lymphocytic infiltrate by immunohistochemical or gene rearrangement studies may be necessary in order to exclude a low-grade B-cell lymphoma.

Screening Questions

In the questionnaire of adult salivary hypofunction, positive responses to all 4 of the following questions indicate major salivary gland hypofunction[30] : (1) Do you sip liquids to aid in swallowing dry foods? (2) Does your mouth feel dry when eating a meal? (3) Do you have difficulties swallowing any foods? (4) Does the amount of saliva in your mouth seem to be too little?

Less than 50% of pediatric patients report ocular symptoms, whereas older patients with Sjögren syndrome more frequently report them. Ocular screening questions include the following: (1) Have you had persistent dry eyes daily for more than 3 months? (2) Do you have recurrent sensation of sand or gravel in your eyes? (3) Do you use tear substitutes more than 3 times daily?

Imaging Studies

A study by Cornec et al reported that the diagnostic performance of the American College of Rheumatology classification criteria for Sjögren's syndrome is notably improved by adding the salivary gland ultrasonography score. The study concluded that salivary gland ultrasonography should be included in future classification criteria for Sjögren's syndrome.[31, 32]

 

Treatment

Approach Considerations

Many of the symptoms associated with Sjögren syndrome can impair an individual's quality of life. In addition to sicca syndrome, concerns about facial appearance, depression, chronic fatigue, and joint pain must be addressed. Parotid enlargement and weight gain (if corticosteroids are used to manage the disease) may be problematic in adolescents. Artificial tears and conservation of natural tear flow are used in the management of keratoconjunctivitis.

Close attention must be paid to emotional and cognitive functioning of the adolescent coping with a chronic disease such as Sjögren syndrome.

Medical care for children with primary Sjögren syndrome is primarily based on strategies used for adults. No controlled studies in children with this disorder have been reported.

Discourage patients from smoking. Instruct patients to avoid windy and low-humidity environments. The family dwelling should be well humidified. Support normal school attendance and academic functioning in patients with juvenile Sjögren syndrome.[33]

Xerostomia

Means of addressing xerostomia include stimulation of salivary flow with sialagogues, such as pilocarpine (shown to be effective in increasing salivary flow in placebo-controlled, randomized adult trials) or cevimeline; mechanical stimulation of salivary flow with sugarless chewing gum or lozenges; and topical tissue hydration or lubrication with drinking water or artificial saliva. These measures are supportive and have only been well studied in adults, yet they may improve quality of life in patients of all ages.[34, 35]

Oral Hygiene

In Sjögren syndrome, calcium is leeched from teeth because of a reduction in saliva and as a result of the interaction between simple sugars and acidogenic bacteria. Therefore, good oral hygiene is necessary for caries control. Patients should avoid mouth rinses that contain alcohol, because they desiccate the mucosa.

Dental plaque reduction measures include twice-daily cleaning of the teeth with a toothbrush, using a fluoride-containing dentifrice, the daily use of dental floss, and increasing the number of professional cleanings to 3-4 times a year if carious lesions develop. Daily home use of topical fluorides, especially gel or toothpaste that contains 1.1% sodium fluoride or remineralizing gel with 0.05% sodium fluoride, sodium phosphate, and calcium carbonate, is recommended.[30]

If the patient has severe xerostomia, use custom fluoride trays or carriers to apply the topical fluorides. Use chlorhexidine gluconate oral rinse concurrently for 2-week periods when high numbers of Streptococcus mutans are found in the saliva (>1 X 106/mL saliva). Limit the intake of sugary food and beverages between meals. Use sweetener alternatives, if tolerated, such as aspartame, saccharin, sorbitol, and xylitol.

For the prevention of oral mucosal lesions such as chapped lips, use water- or lanolin-based lip moisturizers. Avoid lip products that are medicated with menthol or phenol, because they cause further drying. For traumatic erosions and ulcers, frequently hydrate and use artificial saliva or oral moisturizing agents, especially under removable oral prostheses.

For oropharyngeal candidiasis, recommend good oral hygiene, frequent oral hydration and lubrication, and nightly removal and cleaning of dental prostheses. The intermittent use of topical or systemic antifungal agents may be necessary to prevent recurrent infection. If topical antifungal agents are used, consultation with a compounding pharmacist is recommended in order to formulate sucrose-free suspensions or lozenges. (See the image below.)

The dorsal tongue demonstrates hyperplastic candid The dorsal tongue demonstrates hyperplastic candidiasis with focal erosions and a brown hairy tongue. Ulcerated fissures are observed on the corners of the mouth that represent angular cheilitis.

Extraglandular Manifestations

Extraglandular Manifestations

In adults, extraglandular or systemic manifestations often require immunolytic and immunomodulatory or disease-modifying antirheumatic drugs (DMARDs). No standardized immunosuppressive regimen has been established for childhood- or juvenile-onset patients. In one multicenter review, 55% of children received corticosteroids, 17.5% received nonsteroidal anti-inflammatory drugs (NSAIDS), and 12.5% received hydroxychloroquine.[10] Hydroxychloroquine was predominantly used for patients in a separate single-institution review.[17]

 

Consultations

The following consultations may be necessary:

  • Ophthalmologist - To diagnose keratitis and uveitis using slit-lamp examination and for supportive care for sicca syndrome and inflammatory changes

  • Dentist - To maintain salivary flow and to prevent caries and periodontal disease

  • Rheumatologist - For the diagnosis and long-term care of adult or pediatric disease; for the evaluation of extraglandular, systemic, or overlapping autoimmune disease symptoms; and for guidance in the use of immunosuppressive medications for extraglandular manifestations

  • Surgeon - For salivary gland biopsy

Diet

A nutritious well-balanced diet with the appropriate servings from the basic food groups is recommended. Patients should drink plenty of fluids with meals to aid in chewing, tasting, and swallowing. If tolerated, encourage the intake of dairy products, especially low-fat milk, yogurt, and cheese. Milk provides increased oral lubrication, while cheese has a beneficial anticaries effect.

Recommend that patients avoid dry, crunchy foods, because they are too difficult to swallow and may irritate the mucosa. Patients should also avoid spicy or acidic foods and beverages. In addition, avoiding simple carbohydrates, such as sucrose, and refined, highly processed foods, such as pastries and cookies, is important, to decrease the risk of dental caries. Alcoholic beverages and caffeinated drinks, such as coffee, tea, and cola, increase oral dryness.

If sweetener substitutes are used, monitor their intake, because some products may cause abdominal distress.

Recommend that patients eat foods at moderate temperatures. Foods can be liquefied or pureed if swallowing is a problem. If an increase in calories is needed because of an eating disorder, consider liquid nutritional supplements.

 

Medication

Medication Summary

Primary Sjögren syndrome usually follows a benign course in adult patients, and conservative management is indicated. Therapeutic approaches may include increasing lubrication with artificial tears, stimulating salivary flow with sugar-free gum or lozenges, and using vaginal lubricants. Saliva substitutes (eg, carboxymethylcellulose) are not usually effective. Cholinergic agonists have been shown to help increase salivary secretion and are approved by the US Food and Drug Administration (FDA) for this use. The treatment of secondary Sjögren syndrome is determined by the severity of the overlapping autoimmune disorder and may include the use of additional agents, such as methotrexate, azathioprine, cyclophosphamide, rituximab, mycophenolate, mofetil, and other biologic agents.

 

Cholinergic agonists

Class Summary

These agents stimulate salivary secretion.

Pilocarpine (Salagen)

Pilocarpine is a muscarinic M3 receptor agonist.

Cevimeline (Evoxac)

Cevimeline is a muscarinic M3 agonist. It has 40-fold less binding affinity to M2 receptors and therefore has the theoretical benefit of causing less stimulation of cardiac tissues. This agent has a longer duration of action than pilocarpine.

Immunosuppressive agents

Class Summary

These agents are used to treat extraglandular disease (ie, interstitial pneumonitis, glomerulonephritis, polyarthritis, vasculitis, pseudolymphoma, neurologic manifestations).

Prednisone

Prednisone is a corticosteroid with salt-retention properties used for its potent anti-inflammatory effects.

Nonsteroidal Anti-Inflammatory Drugs

Class Summary

The use of NSAIDs in Sjögren syndrome is similar to agents used for juvenile arthritis. These agents may be used to treat polyarthritis associated with Sjögren syndrome.

Ibuprofen (Motrin, Advil, Caldolor)

Ibuprofen is the drug of choice for patients with mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. It also has anti-inflammatory and antipyretic properties. Ibuprofen is available in 200-, 400-, 600-, and 800-mg doses.

Naproxen (Aleve, Naprosyn, Naprelan)

Naproxen is used for the relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which is responsible for prostaglandin synthesis.

Disease-Modifying Antirheumatic Drugs

Class Summary

These agents are used for polyarthritis not controlled with nonsteroidal anti-inflammatory drugs (NSAIDs). Methotrexate has been shown to be effective in managing polyarthritis. Other DMARDs, such as hydroxychloroquine, may be synergistic when coadministered with methotrexate.

Methotrexate (Trexall, Rheumatrex)

Methotrexate has an unknown mechanism of action in the treatment of inflammatory reactions (although it may involve adenosine receptors). The drug, which may affect immune function, ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust the dose gradually to attain a satisfactory response.

Antimalarial Agents

Class Summary

These agents may inhibit chemotaxis of eosinophils and the locomotion of neutrophils and may impair complement-dependent antigen-antibody reactions.

Hydroxychloroquine sulfate (Plaquenil)

The mechanism of action for this drug is unclear; in the treatment of inflammatory arthritis, the mechanism of action is unknown. Hydroxychloroquine sulfate may inhibit chemotaxis of eosinophils and the locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.