Jump to content

Sjögren's disease

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by 24.99.85.70 (talk) at 03:15, 1 September 2011 (→People with Sjögren's Syndrome). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Sjögren's disease
SpecialtyImmunology, rheumatology Edit this on Wikidata

Sjögren's syndrome (/[invalid input: 'icon']ˈʃoʊɡr[invalid input: 'ɨ']nz/ SHOH-grinz), also known as "Mikulicz disease" and "Sicca syndrome",[1] is a systemic autoimmune disease 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.[citation needed] 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.[citation needed]

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 disorder such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, primary biliary cirrhosis etc. (secondary Sjögren's syndrome).[citation needed]

An autoantigen is alpha-Fodrin.[4]

It should not be confused with the Sjögren–Larsson syndrome, also denoted T. Sjögren syndrome in early studies.

Signs and symptoms

The hallmark symptom of the disorder is a generalized dryness, typically involving 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, peripheral nervous system (distal axonal sensorimotor neuropathy) and brain.

Sjögren's syndrome is associated with increased levels of IL-1RA in CSF, an interleukin 1 antagonist, suggesting that there was first increased activity in the interleukin 1 system, then an auto-regulatory up-regulation of IL-RA in attempts to reduce the successful binding of Interleukin 1 to its receptors. It is likely that Interleukin 1 is the marker for fatigue, however IL-1RA increases are observed in the CSF and is associated with increased fatigue through cytokine induced sickness behavior.[5] Patients with secondary Sjögren's syndrome also often exhibit signs and symptoms of their primary rheumatic disorders, such as SLE, Rheumatoid Arthritis or Systemic Sclerosis.

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.[6] [7]

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. An alternative test is nonstimulated whole saliva flow collection, in which the patient spits into a test tube every minute for 15 minutes. A resultant collection of less than 1.5 mL is considered a positive result.[8] It takes longer time to perform than a Schirmer test, but does not require specific equipment.

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 correlation. The other advantage of ultrasound is that complications of the disease such as extra-nodal lymphomas can often be detected 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.

The Revised Classification Criteria for Sjögren's Syndrome[9] requires the presence of signs, symptoms, and lab findings.

Patient-reported symptoms must include both ocular symptoms, such as daily, persistent, troublesome dry eyes for more than 3 months, and oral symptoms, such as needing to drink water to swallow food.

Objective evidence of eye involvement relies on Schirmer's test and the Rose bengal score (or similar). Histopathology studies should show focal lymphocytic sialadenitis. Objective evidence of salivary gland involvement is tested through ultrasound examinations, the level of unstimulated whole salivary flow, a parotid sialography, or salivary scintigraphy. Autoantibodies against Ro (SSA) and/or La (SSB) antigens are also expected.

SS can be excluded from people with past head and neck radiation therapy, hepatitis C infection, Acquired immunodeficiency syndrome (AIDS), pre-existing lymphoma, sarcoidosis, graft-versus-host disease, and use of anticholinergic drugs (since a time shorter than 4-fold life of the drug).

Pathogenesis

Cell mediated auto-immunity causes the apoptosis of the ductal and acinar epithelial cells which is responsible for the glandular tissue damage.[10]

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. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate.[11]

Dry eyes

Punctal plugs[12]

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 Sjögren'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 optometrist or ophthalmologist's office. Generally, collagen plugs are inserted first. These plugs will dissolve within a few days, so it gives the patient a chance to see if there is any improvement in comfort. Generally, the improvement is immediate. If you wish to proceed with permanent plugs you may, although these too can be removed if necessary.

Dental care

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 cavities must also be treated, as cavities 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 cavities in almost every tooth. In severe cases, the only viable treatment may be to extract all of the patient's teeth and treat with prosthetics such as dentures and/or implants.

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.[13] About 5% of patients with Sjögren's syndrome will develop some form of lymphoid malignancy.[14] Patients with severe cases are much more likely to develop lymphomas than patients with mild or moderate cases.[15] The most common lymphomas are salivary extranodal marginal zone B cell lymphomas (MALT lymphomas in the salivary glands)[13] and diffuse large B-cell lymphoma.[15]

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.[16]

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

Multiple monoclonal antibodies were under investigation in 2007.[17] The most promising seemed to be the anti-CD20 rituximab and the anti-CD22 epratuzumab whilst the anti-TNF-α and IFN-α drugs seemed less effective.

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. The Primary Sjögren's Syndrome Registry in the UK is a tissue biobank of samples taken for research supported by the Medical Research Council. The Registry supports clinical trials and genetic studies of Sjögren's Syndrome and is open to patients wishing to participate in research studies and researchers studying the disease.

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.[18][19]

People with Sjögren's Syndrome

Notable individuals who have been identified as having Sjögren's syndrome includes two-time U.S. Open champion Venus Williams. See external link below for more information.

See also

References

Notes
  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. ^ Harboe E, Tjensvoll AB, Vefring HK, Gøransson LG, Kvaløy JT, Omdal R. (2009). Fatigue in primary Sjögren's syndrome—a link to sickness behaviour in animals? Brain Behav Immun.23(8):1104–8. doi:10.1016/j.bbi.2009.06.151 PMID 19560535
  6. ^ 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)
  7. ^ V Goëb; et al. (2007). "Clinical significance of autoantibodies recognizing Sjögren's syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sjögren's syndrome". doi:10.1111/j.1365-2249.2007.03337.x. {{cite web}}: Explicit use of et al. in: |author= (help)
  8. ^ [1] Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19323359, please use {{cite journal}} with |pmid=19323359 instead.
  9. ^ 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)
  10. ^ "Sjogren's syndrome: apoptosis by anti-SSA and anti-SSB antibodies" (PDF). 2006.
  11. ^ "SJÖGREN'S SYNDROME: A GUIDE FOR THE PATIENT". Retrieved 2010-04-27. {{cite web}}: Cite has empty unknown parameter: |1= (help)
  12. ^ Dr. J. Parks, Ancaster ON Canada
  13. ^ 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.
  14. ^ 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.
  15. ^ 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)
  16. ^ 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)
  17. ^ 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)
  18. ^ 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. PMID 16339583. {{cite journal}}: URL–wikilink conflict (help)CS1 maint: multiple names: authors list (link)
  19. ^ 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)


Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Sjögren%27s_disease&oldid=447781762"