DEFINITION
Sjögren’s syndrome is a chronic inflammatory disorder of probable autoimmune nature characterized by infiltration of the exocrine glands, particularly the salivary and lacrimal glands, by lymphocytes and plasma cells.
The classic signs of the Sjögren’s syndrome, therefore, includes enlargement of the parotid glands with mucosal dryness manifest by DRY MOUTH(xerostomia) and DRY EYES (xerophthalmia).
This triad (dry mouth + dry eyes + lymphocytic infiltration) is also known as the sicca complex.
■ Patients with dry eyes are at increased risk for infections around the eye and may have damage to the cornea.
■ Dry mouth may cause an increase in dental decay, gingivitis (gum inflammation), and oral yeast infections (thrush) that may cause pain and burning. Some patients have episodes of painful swelling in the saliva glands around the face.
Complications in other parts of the body occur rarely in patients with Sjögren's syndrome. Pain and stiffness in the joints with mild swelling may occur in some patients, even in those without rheumatoid arthritis or lupus. Rashes on the arms and legs related to inflammation in small blood vessels (vascultis) and inflammation in the lungs, liver, and kidney may occur rarely and be difficult to diagnose. Neurological complications that cause symptoms such as numbness, tingling, and weakness have also been described in some patients.
PHYSIOPATHOLOGY
In this syndrome, the presence of lymphocytes and plasma cells infiltration in salivary and lacrimal glands cause an elevated secretion of cytokines with the formation of a chronic inflammatory state. So, lymphocytes and plasma cells destroy acinar cells in glands, through inflammation, and the conseguence is dryness. In this process of destruction may be involved NITRIC OXIDE produced by the inducible NOS isoform.
Sjögren’s syndrome exists in both a PRIMARY and SECONDARY form:
• Primary: occurs in absence of other autoimmune disorders.
• Secondary: occurs in people who do have another rheumatologic disease, most often systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis or polymyositis. In these case occurring with a well-defined connective tissue disease.
EPIDEMIOLOGY
The disease affects predominantly middle-aged women, in the peri- or post-menopausal period, in a female-to-male ratio of 9:1. However, it can be seen in both sexes and all ages. The prevalence is still unknown. Nevertheless, it is considered to be quite common since in addition to the primary syndrome, 30% of patients with rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis suffer secondary Sjögren’s syndrome. Besides, 2 to 5 % of people aged 60 and above have primary Sjögren’s syndrome.
CAUSES
The causes of Sjogren's syndrome are unknown. Contributing factors may include:
• Viral infections, for example the HCV virus or better EBV(parotite).doc
• Heredity
• Hormones
CLINICAL MANIFESTATIONS
The majority of the patients with Sjögren’s syndrome have symptoms related to diminished lacrimal and salivary gland functions.
1- The initial manifestations may be nonspecific and insidious, such as:
• Dry eyes and dry mouth
• Musculoskeletal (60%)
• Fatigue (60%)
• Arthralgias (60-70%)
• Myalgias (20-30%)
• Dry skin (40%)
• Vaginal dryness (40%)
2- The patients usually complain of dry eye symptoms, including burning, itching or foreign body (gritty, sandy) sensation and accumulation of thick, ropy secretions along the inner canthus of the eyes . With time conjunctival injection, reduced visual acuity and increased photosensitivity develop. These symptoms, which occur because of the decreased and altered tear production, result in the destruction of corneal and bulbar conjunctival epithelium defined as keratoconjunctivitis sicca.
3- Drying of the mouth, xerostomia, is frequent but variable in severity. Patients usually complain of difficulty in eating dry food (like trying to eat crackers without water), inability to speak continuously, oral soreness, changes in tasting and smelling and fissures of the tongue and lips (angular queilitis). An increase in dental caries is due to decreased saliva volume and the relative loss of its antibacterial factors. Physical examination shows a dry, erythematous, sticky oral mucosa.
4- Involvement of other exocrine glands occur less frequently. A decrease in the mucous gland secretions of the upper and lower respiratory tree results in dry nose, throat and trachea. Mucosal gland involvement of gastrointestinal tract can be associated with dysphagia, atrophic gastritis, esophageal mucosal atrophy, constipation and subclinical pancreatic insufficiency. Vulva and vaginal dryness can result in dyspareunia.
5- Extraglandular (systemic) features can complicate the course of the Sjögren’s syndrome and are seen in one third of the patients. In particular these manifestations are more common in patients with primary rather than secondary Sjögren’s syndrome. Such as:
• VASCULITIS (25%) affects small and medium sized vessels;
• POLYNEUROPATHIES (10-15%);
• RENAL INVOLVEMENT includes interstitial nephritis, clinically manifested as hypostenuria and renal tubular dysfunction with or without acidosis and Fanconi’s syndrome.
• NONEROSIVE ARTHRITIS is also common;
• DYSPNEA may be the presenting symptom of an underlying diffuse interstitial pneumonitis due to lymphocytic infiltration;
• CENTRAL NERVOUS SYSTEM INVOLVEMENT has been recognized only over the past decade and reported features include focal and diffuse defects, including multiple sclerosis, progressive dementia cognitive dysfunction and spinal cord involvement similar to transverse mielitis;
• The most common clinical features are nonthrombocytopenic purpura of the legs, skin ulceration, recurrent urticaria and mononeuritis multiplex;
• Raynaud’s phenomenon occurs in about 20% of the patients.
5- Malignant or pseudomalignant lymphoproliferation. As a result of the lymphocytic infiltration, 10% of patients may develop pseudolymphoma, a lymphoproliferative process, specially in primary Sjögren’s syndrome. Approximately 10% of these patients can develop non-Hodgkin lymphoma (1% of all patients with Sjögren syndrome). Most lymphomas derive from B cell lineage and may develop into monoclonal gammopathies (as Waldenstron’s macroglobulinemia).
Pseudolymphoma or frank lymphoma should always be suspected when persistent major salivary gland enlargement, lymphadenopathy or lung nodules are noted.
DIAGNOSIS
Diagnosis of Sjögren’s syndrome is based on the presence of two of the three following manifestations: keratoconjunctivitis sicca, xerostomia and an associated connective tissue or lymphoproliferative disorder.
Salivary or lacrimal gland enlargement may or may not be present.
Lab studies used to establish a diagnosis:
• Biopsies of saliva glands around the face or under the surface of the inner lip.
• Lacrimal proteins electrophoretic analysis
• Schirmer test is used for evaluation of tear secretion by the lacrimal glands. The test is performed with strips of filtered paper slipped beneath the inferior lid of an unanesthetized eye. After 5 minutes the wetting length of the paper is measured. Wetting of less than 5 mm is a strong indication for diminished secretion. Keratoconjunctivitis sicca, the sequelae of decreased tear production, is diagnosed with slit-lamp examination after using Rose Bengal staining of the corneal epithelium. Rose Bengal is a dye which stains the devitalized epithelium of both the cornea and conjunctiva.
Diagnosis depends also on a combination of other symptoms, physical findings, blood tests, and sometimes special studies.
Blood tests can determine the presence of:
• Erythrocyte sedimentation rate (ESR) is elevated in 80% of patients.
• Rheumatoid factor is present in 52% of cases of primary-type Sjögren syndrome and in 98% of secondary-type cases.
• Complete blood count (CBC)
• A mild normochromic normocytic anemia is present in 50% of patients.
• Leukopenia occurs in up to 42% of patients.
• Autoantibodies (immune system cells that help destroy foreign invaders);
• Anti-SS-A and anti-SS-B are present in most cases of primary-type Sjögren syndrome, while antisalivary duct antibodies are present in most cases of the secondary type.
• Antinuclear antibodies (ANA) of the speckled and homogeneous type are present in most cases of primary Sjögren syndrome.
• Creatinine clearance may be diminished in up to 50% of patients.
PROGNOSIS
The ophthalmologic and oral manifestations of Sjögren’s syndrome are generally not progressive. Patients with splenomegaly, bilateral parotid enlargement, and a history of radiation treatment are at especially high risk.
While Sjogren's syndrome is generally a benign condition, people with severe cases are at increased risk for developing lymphoma.
TREATMENTS
There is no cure for Sjogren's syndrome and no treatment that can restore the ability of the glands to produce moisture. The goal of treatment is to relieve symptoms.
Treatments include:
1- MEDICATION
• Artificial tears and vaginal lubricants can help relieve dryness. Restasis may be used to increase tear production.
• Dry mouth can be relieved by drinking water, chewing gum, or using saliva substitutes. Some patients benefit from using prescription medications that stimulate saliva flow, such as PILOCARPINE (Salagen) or CEVIMULINE (Evoxac).
• Steroids to relieve inflammation and swelling.
• Hydroxychloroquine (Plaquinel), an antimalarial drug used in lupus and rheumatoid arthritis, may be helpful in some patients with Sjögren's syndrome by reducing joint pain and rash experienced by some patients. Patients with rare but serious systemic symptoms, such as fever, rashes, abdominal pain, or lung or kidney problems, may require treatment with corticosteroids such as PREDNISONE (Deltasone and others) and/or immunosuppressive agents METHOTREXATE (Rheumatrex), AZATHIOPRINE (Imuran), MYCOPHENOLATE (Cellcept), CYCLOPHOSPHAMIDE (Cytoxan).
2- LIFESTYLE MEASURES
• Mild exercise can help relieve joint stiffness.
• Sipping liquids frequently and sucking on sugar-free candies can relieve dry mouth.
• Brushing, flossing, and seeing your dentist regularly can prevent cavities.
• Using nonscented moisturizers can help relieve dry skin.
