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Sjögren syndrome

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Sjögren syndrome
SpecialtyImmunology, rheumatology Edit this on Wikidata

Sjögren's syndrome (Template:Pron-en) (also known as "Mikulicz disease," and "Sicca syndrome"[1]) is an autoimmune disorder in which immune cells attack and destroy the exocrine glands[2] that produce tears and saliva.

It is named after Swedish ophthalmologist Henrik Sjögren[3] (1899-1986), who first described it.

Nine out of ten Sjögren's patients are women and the average age of onset is late 40s, although Sjögren's occurs in all age groups in both women and men. It is estimated to strike as many as 4 million people in the United States alone making it the second most common autoimmune rheumatic disease. Sjögren's syndrome can exist as a disorder in its own right (Primary Sjögren's syndrome) or it may develop years after the onset of an associated rheumatic disorders such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, primary biliary cirrhosis etc. (Secondary Sjögren's syndrome).


An autoantigen is alpha-Fodrin.[4]

Signs and symptoms

The hallmark symptoms of the disorder are dry mouth and dry eyes (part of what are known as sicca symptoms). In addition, Sjögren's syndrome may cause skin, nose, and vaginal dryness, and may affect other organs of the body, including the kidneys, blood vessels, lungs, liver, pancreas, and brain.

Patients with secondary Sjögren's syndrome also have signs and symptoms of the associated rheumatic disorder.

Diagnosis

Diagnosing Sjögren’s syndrome is complicated by the range of symptoms a patient may manifest, and the similarity between symptoms from Sjögren's syndrome and those caused by other conditions. Nevertheless, the combination of several tests can lead to a diagnosis of Sjögren's syndrome.

Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as anti-nuclear antibody (ANA) and rheumatoid factor (because SS frequently occurs secondary to rheumatoid arthritis), which are associated with autoimmune diseases. Typical Sjögren's syndrome ANA patterns are SSA/Ro and SSB/La, of which SSB/La is far more specific; SSA/Ro is associated with numerous other autoimmune conditions but are often present in Sjögren's.[5]

The Schirmer test measures the production of tears: a strip of filter paper is held inside the lower eyelid for five minutes, and its wetness is then measured with a ruler. Producing less than five millimeters of liquid is usually indicative of Sjögren's syndrome. However, lacrimal function declines with age or may be impaired from other medical conditions. A slit-lamp examination is done to look for dryness on the surface of the eye. Salivary gland function can be tested by collecting saliva and determining the amount produced in a five minute period. A lip biopsy can reveal lymphocytes clustered around salivary glands, and damage to these glands due to inflammation.

Ultrasound examination of the salivary glands is the simplest confirmatory test and has the added advantage of being non-invasive with no complications.The parenchyma of the gland demonstrates multiple,small-2–6 mm hypoechoic lesions which are representations of the lymphocytic infiltrates. Often sialectasis with calculi are demonstrated if the disease is advanced.The sonographic findings have excellent symptom corelation.The other advantage of ultrasound is that complications of the disease such as extra-nodal lymphomas can often be dectected as larger 1–4 cm hypoechoic intra-parenchymal masses.

A radiological procedure can also be used as a reliable and accurate way of diagnosing Sjögren's syndrome. A contrast agent is injected into the parotid duct (of Stensen), which is a duct opening from the cheek into the vestibule of the mouth opposite the neck of the upper second molar tooth. Widespread puddling of the injected contrast scattered throughout the gland indicates Sjögren's syndrome.

Classification Criteria

Revised Classification Criteria for Sjögren's Syndrome[6]

1. Ocular symptoms: a positive response to at least one of the following questions:

1. Have you had daily, persistent, troublesome dry eyes for more than 3 months?
2. Do you have a recurrent sensation of sand or gravel in the eyes?
3. Do you use tear substitutes more than 3 times a day?

2. Oral symptoms: a positive response to at least one of the following questions:

1. Have you had a daily feeling of dry mouth for more than 3 months?
2. Have you had recurrently or persistently swollen salivary glands as an adult?
3. Do you frequently drink liquids to aid in swallowing dry food?

3. Ocular signs - that is, objective evidence of ocular involvement defined as a positive result for at least one of the following two tests:

1. Schirmer's test, performed without anaesthesia (≦5 mm in 5 minutes)
2. Rose bengal score or other ocular dye score (≧4 according to van Bijsterveld's scoring system)

4. Histopathology: In minor salivary glands(obtained through normal-appearing mucosa) focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus score ≧1, defined as a number of lymphocytic foci (which are adjacent to normal-appearing mucous acini and contain more than 50 lymphocytes) per 4 mm2 of glandular tissue.

5. Salivary glandinvolvement: objective evidence of salivary gland involvement defined by a positive result for at least one of the following diagnostic tests: 1.Ultrasound examination of the parotid and submandibular salivary glands is a very sensitive test with the salivary parenchyma demonstrating numerous, small 2–6 mm hypoechoic lesions representing periductal lymphocytic infiltrates.The appearances are almost pathgnomonic and Sjogren's is often incidentally diagnosed on head and neck ultrsound with good symptomatic correlation. 

2. Unstimulated whole salivary flow (≦ 1.5 mL in 15 minutes)
3. Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary,or destructive pattern), without evidence of obstruction in the major ducts.
4. Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed excretion of tracer

5. Autoantibodies: presence in the serum of the following autoantibodies:

1. antibodies to Ro (SSA) or La (SSB) antigens, or both

Revised rules for classification

For primary SS

In patients without any potentially associated disease, primary SS may be defined as follows:

a. The presence of any 4 of the 6 items is indicative of primary SS, as long as either item 4 (Histopathology) or 6 (Serology) is positive.
b. The presence of any 3 of the 4 objective criteria items (that is, items 3, 4, 5, 6)
c. The classification tree procedure represents a valid alternative method for classification, although it should be more properly used in clinical-epidemiological survey.

For secondary SS

In patients with a potentially associated disease (for instance, another autoimmune disorder[7]), the presence of item 1 or item 2 plus any two from among items 3, 4, and 5 may be considered as indicative of secondary SS.

Exclusive criteria

Past head and neck radiation therapy
Hepatitis C infection
Acquired immunodeficiency syndrome (AIDS)
Pre-existing lymphoma
Sarcoidosis
Graft-versus-host disease
Use of anticholinergic drugs (since a time shorter than 4-fold life of the drug)

Treatment

There is neither a known cure for Sjögren's syndrome nor a specific treatment to permanently restore gland secretion. Instead, treatment is generally symptomatic and supportive. Moisture replacement therapies such as artificial tears may ease the symptoms of dry eyes (some patients with more severe problems use goggles to increase local humidity or have punctal plugs inserted to help retain tears on the ocular surface for a longer time). Additionally, ciclosporin (Restasis) is available by prescription to help treat chronic dry eye by suppressing the inflammation that disrupts tear secretion. Prescription drugs are also available that help to stimulate salivary flow, such as cevimeline (Evoxac) and pilocarpine. Nonsteroidal anti-inflammatory drugs may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed. Also, disease-modifying antirheumatic drugs (DMARDs) such as methotrexate may be helpful.

Multiple monoclonal antibodies are currently under investigation.[8]

Punctal Plugs[9]

In the advanced stage, despite the use of tear replacement drops, the eyes always feel burning, scratchy, sore. The sufferer is always aware of some discomfort, the eyes feel worse in the morning and late evening. The use of tear replacements drops has become tedious and ineffective. At this point it may be appropriate to consider punctal plugs.

Each eye has two sites at the inner corner of each eyelid where tears drain from the eye. The upper eyelid 'puncta' drains approximately 40% of your tears away and the lower puncta drains away the remaining 60% of your tears. If there is a problem with the quantity of your tears, as there is in Sjogren's disease, plugging the lower puncta can result in the tears that you have remaining on the eye longer.

Punctal plugs can be inserted into the lower or upper tear drainage canals of the eyes. The procedure takes only a few minutes and is painless. It can be done in the office of your Optometrist or Ophthalmologist. Generally, collagen plugs are inserted first. These plugs will dissolve within a few days, so it gives you a chance to see if there is any improvement in your comfort. Generally, the improvement is immediate. If you wish to proceed with permanent plugs you may, although these too can be removed if necessary.


Preventive dental treatment is also necessary (and often overlooked by the patient), as the lack of saliva associated with xerostomia (dry mouth) creates an ideal environment for the proliferation of bacteria that cause dental caries (cavities). Treatments include at-home topical fluoride application to strengthen tooth enamel and frequent teeth cleanings by a dental hygienist. Existing caries must also be treated, as caries that extend into the tooth can not be effectively treated through teeth cleaning alone, and are at a high risk of spreading into the pulp of the tooth, leading to the loss of vitality and need for extraction or root canal therapy. This treatment regimen is the same as that used for all xerostomia patients, such as those undergoing head and neck radiation therapy which often damages the salivary glands, as they are more susceptible to radiation than other body tissues.

Unfortunately, many patients, not realizing the need for dental treatment, do not see a dentist until most of their teeth are beyond the point of restoration. It is not uncommon for a dentist to see a xerostomia patient with severe, untreatable caries in almost every tooth. In such cases, the only treatment is to extract all of the patient's teeth and fit the patient for dentures.

Prognosis

Sjögren's can damage vital organs of the body with symptoms that may plateau or worsen, but the disease does not go into remission as with other autoimmune diseases. Some people may experience only the mild symptoms of dry eyes and mouth, while others have symptoms of severe disease. Many patients are able to treat problems symptomatically. Others are forced to cope with blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, hoarseness, and difficulty in swallowing and eating. Debilitating fatigue and joint pain can seriously impair quality of life. Some patients can develop renal involvement (autoimmune tubulointerstitial nephritis) leading to proteinuria, urinary concentrating defect and distal renal tubular acidosis.

Patients with Sjögren's syndrome have a higher rate of non-Hodgkin lymphoma compared to both patients with other autoimmune diseases and healthy people.[10] About 5% of patients with Sjögren's syndrome will develop some form of lymphoid malignancy.[11] Patients with severe cases are much more likely to develop lymphomas than patients with mild or moderate cases.[12] The most common lymphomas are salivary extranodal marginal zone B cell lymphomas (MALT lymphomas in the salivary glands)[10] and diffuse large B-cell lymphoma.[12]

Complications

Among the complications discussed above, Sjögren's syndrome in women who become pregnant has been linked to increased incidence of neonatal lupus erythematosus with congenital heart block requiring a pacemaker.[13]

Epidemiology

Sjögren's syndrome affects 1-4 million people in the United States. Most people are more than 40 years old at the time of diagnosis. Women are 9 times more likely to have Sjögren's syndrome than men.

Research

The goals of research on diseases such as Sjögren's syndrome focus on increasing knowledge and understanding of the disorder, improving diagnostic techniques, and finding ways to treat, prevent, and cure the disorder.

An animal model of Sjögren's syndrome has been developed by immunizing mice with 60 kD Ro peptide. Days after immunization, salivary flow was decreased and lymphocyte infiltrates as well as salivary dysfunction was observed which are highly reminiscent of human Sjögren's syndrome.[14][15]

See also

References

  1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 602–3. ISBN 1-4160-2999-0.{{cite book}}: CS1 maint: multiple names: authors list (link)
  2. ^ Delaleu N, Immervoll H, Cornelius J, Jonsson R (2008). "Biomarker profiles in serum and saliva of experimental Sjögren's syndrome: associations with specific autoimmune manifestations". Arthritis Res. Ther. 10 (1): R22. doi:10.1186/ar2375. PMC 2374466. PMID 18289371.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  3. ^ Sjögren H. Zur Kenntnis der keratoconjunctivitis sicca. Doctoral thesis, 1933.
  4. ^ He J, Zhao J, Li Z (2008). "Mucosal administration of alpha-fodrin inhibits experimental Sjögren's syndrome autoimmunity". Arthritis Res. Ther. 10 (2): R44. doi:10.1186/ar2403. PMC 2453764. PMID 18419828.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  5. ^ Franceschini F, Cavazzana I (2005). "Anti-Ro/SSA and La/SSB antibodies". Autoimmunity. 38 (1): 55–63. doi:10.1080/08916930400022954. PMID 15804706. {{cite journal}}: Unknown parameter |month= ignored (help)
  6. ^ Vitali C, Bombardieri S, Jonsson R; et al. (2002). "Classification criteria for Sjögren's syndrome: a revised version of the [[Europe]]an criteria proposed by the [[American-European Consensus Group]]". Ann. Rheum. Dis. 61 (6): 554–8. doi:10.1136/ard.61.6.554. PMC 1754137. PMID 12006334. {{cite journal}}: Explicit use of et al. in: |author= (help); URL–wikilink conflict (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ [1]
  8. ^ Meijer JM, Pijpe J, Bootsma H, Vissink A, Kallenberg CG (2007). "The future of biologic agents in the treatment of Sjögren's syndrome". Clin Rev Allergy Immunol. 32 (3): 292–7. doi:10.1007/s12016-007-8005-6. PMC 2071970. PMID 17992596. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Dr. J. Parks, Ancaster ON Canada
  10. ^ a b Voulgarelis M, Skopouli FN (2007). "Clinical, immunologic, and molecular factors predicting lymphoma development in Sjogren's syndrome patients". Clin Rev Allergy Immunol. 32 (3): 265–74. doi:10.1007/s12016-007-8001-x. PMID 17992593.
  11. ^ Tzioufas AG, Voulgarelis M (2007). "Update on Sjögren's syndrome autoimmune epithelitis: from classification to increased neoplasias". Best Pract Res Clin Rheumatol. 21 (6): 989–1010. doi:10.1016/j.berh.2007.09.001. PMID 18068857.
  12. ^ a b Smedby KE, Baecklund E, Askling J (2006). "Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics". Cancer Epidemiol. Biomarkers Prev. 15 (11): 2069–77. doi:10.1158/1055-9965.EPI-06-0300. PMID 17119030.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ Manthorpe R, Svensson A, Wirestrand LE (2004). "Late neonatal lupus erythematosus onset in a child born of a mother with primary Sjögren's syndrome". Ann. Rheum. Dis. 63 (11): 1496–7. doi:10.1136/ard.2003.014944. PMC 1754813. PMID 15479901. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Scofield RH, Asfa S, Obeso D, Jonsson R, Kurien BT (2005). "Immunization with short peptides from the 60-kDa Ro antigen recapitulates the serological and pathological findings as well as the salivary gland dysfunction of Sjögren's syndrome". J Immunol. 175 (12): 8409–14. doi:10.1007/s12016-007-8001-x. PMID 16339583.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Kurien BT, Asfa S, Li C, Dorri Y, Jonsson R, Scofield RH (2005). "Induction of oral tolerance in experimental Sjögren's syndrome autoimmunity". Scand J Immunol. 61 (5): 418–25. doi:10.1111/j.1365-3083.2005.01593.x. PMID 15882433.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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