Sjögren's syndrome (SS) is defined by a triad of signs and symptoms:

  • xerophthalmia
  • xerostomia
  • nondeforming arthritis

It occurs in 0.5-2.0% of the population and is more common in women. Onset is usually in middle age. SS can occur in association with other connective tissue diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, or scleroderma. About 50% of cases occur in isolation and represent primary SS.15

In primary SS, exocrine glands are the most affected, with evidence of lymphocytic proliferation and fibrosis of lacrimal and salivary glands. The result is decreased tear and saliva production, causing ocular and oral signs and symptoms.

Extraglandular manifestations occur in one-fourth to one-third of patients. More than 80% of patients experience arthritis of the small joints. Lymphadenopathy, hepatosplenomegaly, and cutaneous vasculitis are also commonly present. Renal disease with an interstitial nephritis may occur in 40% of patients. The central or peripheral nervous system is affected in a minority of patients. Clinically significant pulmonary involvement with interstitial pneumonitis is relatively uncommon.

Pathophysiology

Primary SS is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and B-lymphocyte hyperactivity. Autoantibodies against non-organ-specific antigens are identifiable in the sera of these patients. More specifically, these autoantibodies are directed against rheumatoid factors and the extractable nuclear and cytoplasmic antigens (Ro/SSA and La/SSB).

The pathophysiology of the neurologic complications of SS is not known. It is presumed to be related to autoimmune-mediated vascular damage.18 Vasculitis is thought to be present, but other mechanisms, such as immune complex deposition and vasospasm, have not been excluded.

 

Neurologic manifestations

Primary SS has been reported to affect the peripheral nervous system (PNS) in up to 32% of patients17 and the CNS in up to 25%.16

PNS manifestations usually include a sensory or mixed sensorimotor polyneuropathy characterized by numbness, paraesthesias, and, rarely, pain. Distal weakness may occur and is usually mild.19 Carpal tunnel syndrome is well described with this disorder, and cranial neuropathies have been reported, especially of the trigeminal nerve.19

CNS symptoms tend to be quite variable and diffuse. SS can affect any part of the neuraxis. The manifestations are typically multifocal, recurrent, and progressive.20 Focal strokelike or brain stem deficits may be seen, as well as a more global encephalopathy.

The neurologic manifestations of SS have frequently led to its misdiagnosis as multiple sclerosis (MS).20 In a series of 20 patients ultimately diagnosed with SS, 13 had CNS symptoms identified before the correct diagnosis. Patients experienced such symptoms as spinal cord disease, cerebellar dysfunction, and optic neuropathy. Most experienced a relapsing-remitting course. Atypical for MS was the presence of peripheral neuropathy in more than 50% of patients.

Seizures occur in up to 1.5% of patients with SS and are usually partial, with or without secondary generalization. They are typically attributed to the vascular complications of the disease.21

Diagnosis

The diagnosis of SS is based on the presence of two of the three characteristic clinical manifestations: xerophthalmia, xerostomia, or nondeforming arthritis. Serologic evaluation for autoantibodies to Ro/SSA and La/SSB may help to confirm the diagnosis, but it is not necessary.

In SS patients with CNS disease, MRI will be abnormal in up to 80%. Findings include multiple subcortical white-matter and periventricular T2-weighted signal abnormalities. These can be difficult to distinguish from those seen in MS. Generalized cortical atrophy or discrete cerebral infarcts may also be seen. White-matter lesions may not resolve with treatment.

EEG is abnormal in more than 50% of patients.20 Findings include both epileptiform abnormalities and slowing. In two-thirds of patients, at least one or more abnormalities are seen in visual, auditory, or somatosensory evoked potentials.20

During active CNS disease in SS, spinal fluid may reveal a mild pleocytosis with reactive lymphoid cells. There is also evidence for increased intrathecal immunoglobulin G (IgG) synthesis. These findings may be indistinguishable from those in MS.20

Pathologic studies from SS patients with active CNS disease reveal several types of inflammation, including meningitis, small- to medium-vessel vasculitis, and mononuclear cell infiltration.20 Demyelination has not been described.

Treatment

Treatment is directed relieving symptoms by artificially replacing deficient body fluids. Artificial tears or other ocular lubrication is important to avoid corneal damage from dryness.

Glucocorticoids or other immunosuppressive agents may be used when the extraglandular involvement is severe, especially for clinically significant renal, pulmonary, or CNS involvement.

Seizures, when they occur, are treated with antiepileptic drugs and usually respond well. Treatment of the underlying inflammatory disorder is necessary for the long-term control of seizures.

Prognosis

There is no cure for SS and in many cases it is progressive. It is not known whether the use of immunosuppressive drugs alters the course of the disease.

Adapted from: Seiden L and Krumholz A. Inflammatory noninfectious disorders. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;135–154.
With permission from Elsevier (www.elsevier.com).

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Authored By: 
L Seiden
A Krumholz
Steven C. Schachter, MD
I<
Authored Date: 
03/2004
Reviewed By: 
Steven C. Schachter, MD
on: 
Wednesday, March 31, 2004