Epidemiology

Sjögren syndrome typically manifests at 35-45 yr of age, with 90% of cases among women. It is uncommon in the pediatric age group. The mean age at diagnosis in children is 9-10 yr; 75% are girls. The disease can occur as an isolated disorder, referred to as primary Sjögren syndrome (sicca complex), or as a secondary form in association with other rheumatic disorders. Most commonly, it accompanies systemic lupus erythematosus, scleroderma, or mixed connective tissue disease and usually precedes the associated autoimmune disease by several years.

Etiology and Pathogenesis

The etiology of Sjögren syndrome is complex and includes genetic predisposition and possibly an infectious trigger. Lymphocytes and plasma cells infiltrate salivary glands, forming distinct periductal and periacinar foci that become confluent and may replace epithelial structure. This autoimmune exocrinopathy results in xerophthalmia (dry eyes, or keratoconjunctivitis sicca) and xerostomia (dry mouth). Several genes regulating apoptosis influence the chronicity of lymphocytic infiltration.

Clinical Manifestations

International classification criteria have been developed for the diagnosis of Sjögren syndrome in adult patients (Table 156-1), and diagnostic criteria in children have been proposed. Clinical manifestations are related to exocrine disease of the epithelial surfaces of the eyes, mouth, nose, larynx and trachea, vagina, and skin, leading to the common symptoms of photophobia, burning and itching eyes, blurred vision, painless unilateral or bilateral enlargement of the parotid glands, decreased sense of taste, dental caries, dysphagia, fissured tongue, and angular cheilitis. At the onset of the disease, recurrent parotid gland enlargement and parotitis are the most common manifestation in children, whereas sicca manifestations are most common in adults. Subjective symptoms of xerostomia complaints are relatively rare in juvenile cases and are seen in < 45% of patients overall, perhaps indicating that Sjögren syndrome is a slowly progressive disease. Serologic markers (antinuclear antibodies [ANA], and antibodies to Ro [SSA] and SSB [La]) and articular manifestations are significantly more frequent in adults. Frequencies of the finding of ANA and SSA and SSB antibodies in children are reported to be 78%, 75%, and 65%, respectively. Rheumatoid factor is detected in two thirds of pediatric patients with Sjögren syndrome. Additional clinical manifestations from a variety of organ involvement patterns include a decreased sense of smell, epistaxis, hoarseness, chronic otitis media, and internal organ exocrine disease involving the lungs, hepatobiliary system, pancreas, gastrointestinal tract, kidneys, musculoskeletal, hematologic, and central nervous system (CNS).

Non-exocrine disease manifestations of Sjögren syndrome may be related to inflammatory vascular disease (in skin, muscle and joints, serosal surfaces, and peripheral and central nervous systems), noninflammatory vascular disease (Raynaud phenomenon), mediator-induced disease (hematologic cytopenias, fatigue, and fever), and autoimmune endocrinopathy (thyroiditis).

Diagnosis

The diagnosis is based on clinical features supported by biopsy of the lip or glands demonstrating foci of lymphocytic infiltration, cryoglobulinemia, elevated erythrocyte sedimentation rate (ESR), hypergammaglobulinemia, positive rheumatoid factor, and detection of SSA and SSB antibodies. Anti-β-fodrin autoantibodies, directed against an apoptotic cleavage product of α-fodrin, are a useful diagnostic marker for juvenile Sjögren syndrome. The Schirmer test detects abnormal tear production (≤5 mm of wetting of filter paper strip in 5 min). Imaging studies, including MRI, technetium Tc 99m scintigraphy, and sialography, are useful in the diagnostic evaluation for Sjögren syndrome. Clinical presentation of recurrent parotitis and or recurrent parotid gland swelling in a child or adolescent is characteristic and should raise the suspicion for this disorder.

Differential Diagnosis

The differential diagnosis of Sjögren syndrome in children includes chronic recurrent parotitis, an inflammatory disease of unknown etiology that is characterized by intermittent unilateral/bilateral parotid swelling that is frequently associated with fever and may undergo remission with puberty. Unlike in Sjögren syndrome, there is a male predominance and lack of focal lymphocytic infiltrates on tissue biopsy in chronic recurrent parotitis. Other conditions in the differential diagnosis include infectious parotitis, polycystic parotid disease, tumors, and sarcoidosis. In these conditions, sicca complex, rash, arthralgia, and antinuclear antibodies are usually absent.

Treatment

Symptomatic treatment of Sjögren syndrome includes the use of artificial tears, oral lozenges, and fluids to limit the damaging effects of decreased secretions. Corticosteroids, nonsteroidal anti-inflammatory drugs, and hydroxychloroquine are among the more commonly used agents for treatment. Greater-potency immunosuppressive agents, such as cyclosporine and cyclophosphamide, are reserved for severe functional disorders and life-threatening complications.

Complications and Prognosis

The symptoms of Sjögren syndrome develop and progress slowly. Diminished salivary flow typically remains constant for years. Because monoclonal B-lymphocyte disease originates chiefly from lymphocytic foci within salivary glands or from parenchymal internal organs, there is increased risk for mucosa-associated lymphoid tissue (MALT) lymphoma. Maternal Sjögren syndrome can be an antecedent to the neonatal lupus syndrome (Chapter 152.1).