Sjögren's syndrome M35.00

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Primary Sjögren's syndrome; Secondary Sjögren's Syndrome; Sicca Syndrome; Sjögren's syndrome

History
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Gougerot, 1925; Sjögren, 1933

Definition
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Rare autoimmunological disease characterized by increasing dryness of the mucous membranes (sicca syndrome: "dry eye, dry mouth") and characterized by chronic, progressive inflammation and insufficiency of exocrine glands. The syndrome can be subdivided as follows:

  • primary Sjögren's syndrome; cause unknown, not associated with collagenosis.
  • Secondary Sjögren's syndrome is associated with other diseases: rheumatoid arthritis (M06.99) and other collagenoses, hepatitis B (B16.9) and C (B17.1) and primary biliary cirrhosis (K74.3).

Classification
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Primary Sjögren's syndrome (in adults): association in 1/3 of cases with extraglandular symptoms such as arthralgia (rarely nondeforming, recurrent arthritis), vasculitis, polyneuropathy, rarely CNS symptoms (seizures, psychoses), interstitial nephritis, renal tubular acidosis, serositis, development of B-cell or pseudo-lymphoma. Usually detection of antinuclear antibodies, anti-SS-A and/or anti-SS-B and HLA-DR3. Primary Sjögren's syndrome (in children; rare): association with Hashimoto's thyroiditis, anti-SS-A and/or anti-SS-B antibodies, as well as recurrent anular erythema.

Secondary Sjögren's Syndrome: In the context of inflammatory or infectious diseases (rheumatoid arthritis, collagenosis, pulmonary fibrosis, primary biliary cirrhosis) with detectable antibodies against salivary gland ducts. There are frequent associations with chronic hepatitis C infection.

Etiopathogenesis
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Probably genetically determined autoimmune disease. Associations with increased expression of ICAM1 and HLA-DR antigen in conjunctival epithelia are described. Formation of circulating immune complexes leads to vasculitides. Furthermore, in larger collectives an association with chronic hepatitis C infection (13.4% of patients) can be detected. In this constellation, mixed cryoglobulinemia can be detected in large numbers.

Manifestation
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Especially 4th to 6th decade of life; women are affected 9 times more often than men.

Clinical features
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  • Slow start. Recurrent pressure-tolerating salivary gland swelling. Xerostomia associated with dysphagia. Dry, cornification-prone mucous membranes in the genital and anal tracts. Dryness of the eye (xerophthalmia) with keratoconjunctivitis sicca ( Schirmer test). Dry nasal mucosa, possibly with epistaxis, recurrent parotid swelling, sebostasis (sicca syndrome), keratitis filiformis sicca.
  • Systemic: Pancreatitis, primary biliary cirrhosis of the liver, interstitial nephropathy, (poly)myositis, chronic bronchitis may be associated. Also: Raynaud's syndrome (40%), arthritis (70%), lymphadenopathy (20%), esophagitis, tendency to allergies and gluten-sensitive sprue (10 times more frequent).
  • Dermatologically: hypohidrosis, reddened, scaly skin, partly anular, nodular, erythema exsudativum multiforme-like or pernio-like lesions. Brittle, thinning hair and nail growth disorders may occur. Less frequent are pellagroid changes, vitiligo or Raynaud's phenomenon.
  • Coincidence with primary chronic polyarthritis (rheumatoid arthritis), progressive systemic scleroderma, systemic lupus erythematosus or polyarteritis nodosa (about 50% of cases) may be present.
  • The primary Sjögren's syndrome in children must be considered a special form. Here, recurrent anular erythema of the face and trunk accompanied by intermittent fever and Hashimoto's thyroiditis is impressive. The sicca syndrome is initially absent.

Laboratory
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IgG, IgM increase

ANA positive (80% of cases)

RO antibody (SS-A) and LA antibody (SS-B) positive (85% and 35% respectively)

U1-RNP antibodies positive (30%).

Optionally detectable: antibodies against epithelial cells of the mucous glands; further: muscarinic antibodies (anti-M3), antibodies against cytoplasmic antigens; anti-alpha-fodrin antibodies.

Where appropriate, cryoglobulinemia; positive rheumatoid factor. Rare detection of thyroid gland antibodies.

Histology
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Chronic lymphocytic sialadenitis with fibrosis and consecutive obliteration of the glandular parenchyma. Objectification of sialadenitis by the so-called focus score: Number of lymphocytic foci (defined as infiltrate foci with >50 lymphocytes) are counted in 4 mm² of glandular tissue. The threshold value for a positive focus = 1). Atrophy of the glandular acini; remains of dilated excretory ducts remain.

Diagnosis
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  • Schirmer test (reduced tear secretion), Rose Bengal test (reduced staining), sialography, lip biopsy.
  • List of questions according to Vitali/classification criteria see tables 1 and 2.
  • For primary Sjögren's syndrome there is a > 90% diagnostic sensitivity and specificity if 4 of the 6 criteria are met, whereby the autoantibody detection is limited to anti-SS-A and -B.
  • For secondary Sjögren's syndrome there is > 90% diagnostic specificity compared to a collagenosis group without sicca syndrome if the 1st or 2nd criterion plus 2 of criteria 3, 4 and 5 are met (criterion 6 is obligatory positive).
  • Exclusion criteria: Pre-existing lymphoma, AIDS, sarcoidosis, graft-versus-host disease.

Differential diagnosis
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Mikulicz syndrome (no detection of SS-A or SS-B antibodies

Heerfordt's Syndrome.

Complication(s)
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Development of neonatal lupus erythematosus in newborns of mothers with SSA/Ro and SSB/La antibodies; vasculitis (in 10% of cases), malignant lymphomas (MALT-NHL in about 5% of cases also marginal zone lymphomas).

External therapy
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Symptomatic therapy of the individual symptoms.

  • Keratoconjunctivitis sicca or keratitis superficialis punctata: substitution of tear fluid with eye drops or gels, see Table 3. If necessary, use of bandage lenses (occlusion lenses) or tear duct plugs (punctum plugs).

Remember! Regular ophthalmological care to prevent complications such as corneal ulcers, bulb perforation, infections and shrinking of the conjunctiva!

  • Xerostomia: Artificial saliva preparations, e.g. Glandosane flavoured and neutral or R236, citric acid glycerol 0.5/1 or 2% (NRF 7.4.), R066 if necessary apply or spray several times a day onto the mucous membrane of the mouth and throat. Mouthwashes with glycerine water and chewing gum are also recommended.
  • Lubricatio deficiens: The dryness of the genital mucous membranes occurring in the context of Sjögren's syndrome can cause problems, especially during sexual intercourse. For local therapy, e.g. lubricants, emulsions or the vaginal gel pH 5 listed under NRF 25.3. are available, which are applied thinly to the vaginal entrance before intercourse. It should be noted, however, that the safety of condoms can be compromised.
  • Dry nasal mucous membranes: For symptomatic treatment of rhinitis sicca, various drops and ointments (e.g. R181, Nisita Nasal Ointment, Bepanthen), emulsions and oils (e.g. Coldastop) are available, which can be applied several times a day to the nasal entrance.

Progression/forecast
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The primary Sjögren's syndrome is characterized by a chronic, mostly benign course.

Increased mortality results from increased lymphoma incidence (5%) and organ involvement (4x increased mortality risk with lung involvement). The prognosis of secondary Sjögren's syndrome is defined by the prognosis of the underlying disease.

Tables
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Questionnaire for the detection of dry eyes and mouth in Sjögren's syndrome (according to Vitali)

American-European Consensus Group (AECG) criteria

  1. Eye symptoms (ocular symptoms)

    1. Have you been suffering for more than 3 months from daily, stressful dry eyes and mouth?

    2. Do you often feel a foreign body sensation (sand) in your eyes?

    3. Do you use tear substitutes more than 3 times a day?

  2. Mouth symptoms (oral symptoms)

    1. Have you been suffering from dry mouth for more than 3 months?

    2. As an adult, did you suffer from recurrent or permanent swelling of salivary glands?

    3. Are you forced to drink something to swallow dry food?

  3. Eye findings: Proven eye involvement, objectified by one of the two findings

    1. Schirmer test (<5mm in 5 min.)

    2. Bengalorosa scale (> 4 according to Bijsterfeld)

  4. Histopathology: focus search >1 in small saliva sample biopsy (focus defined as agglomeration of at least 50 mononuclear cells. Focus score defined as number of foci in 4qmm early tissue.

  5. Salivary gland manifestation: Proven involvement of the salivary glands by at least 1 of the following examinations.

    1. Scintigraphy of the salivary glands

    2. Sialography of the parotis

    3. unstimulated saliva flow (<1.5ml in 15 min.)

  6. autoantibodies

    1. Anti-SSA (Ro) and/or anti-SSB (La) - antibody positive.

A safe primary Sjögren's syndrome is assumed if at least 4 criteria, including at least 1 of criteria 4 and 6, are positive.

Safe secondary Sjögren³s syndrome requires the detection of criterion 1 or 2 and additionally 2 other positive criteria (only criteria 3,4,5)

Overview of the most important finished medicinal products suitable for substitution of lacrimal fluid

Substance

Concentration

Application form

Dosage

Preparation

Hydroxyethyl cellulose

2%

Drop

3-4 times 1 trip/day

Lacrigel eye drops

Hypromellose

0,3%

Drop

3-6 times 1 trip/day

Sicca-Stulln eye drops

Artelac eye drops

Sic-ophthal sine eye drops

Polyvinyl alcohol

1,4%

Drop

3-6 times 1 trip/day

Lacrimal OK Eye drops

Liquifilm N Eye drops

Carbomer / Mannitol

0,3% / 5%

Gel

4-6 times 1 trip/day

Thilo-Tears Gel

Polyacrylic acid / Sorbitol / Cetrimide

0,2% / 4% / 0,01%

Gel

4-8 times 1 trip/day

Vidisic Gel

Hypromellose / Glycerine / Polyvidon

0,2% / 1% / 2%

Drop

3-6 times 1 trip/day

Lacrisic eye drops

Hypromellose / Dextran

0,3% / 0,1%

Drop

3-6 times 1 trip/day

Isopto Naturale eye drops

Polyvinyl alcohol / Dexpanthenol

1,4% / 3%

Drop

3-6 times 1 trip/day

Siccaprotect eye drops

Literature
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  1. Brito-Zerón P et al (2015) How hepatitis C virus modifies the immunological profile of Sjögren syndrome: analysis of 783 patients. Arthritis Res Ther 17:250.
  2. Gorson KC et al (2003) Positive salivary gland biopsy, Sjogren syndrome, and neuropathy: clinical implications. Muscle Nerve 28: 553-560
  3. Gougerot H (1925) Insuffisance progressive et atrophie des glandes salivaires et muqueuses de la bouche, des conjonctives (et parfois de muqueuses, nasale, laryngée, vulvaire) "Serecheresse" de la bouche, des conjonctives, etc. Bull Soc franç Dermatol Syphiligr (Paris) 32: 376
  4. Hansen A et al (2003) New concepts in the pathogenesis of Sjogren's syndrome: many questions, fewer answers. Curr Opin Rheumatol 15: 563-570
  5. Kuhn A et al (2000) Annular erythema in Sjogren's syndrome. A variant of cutaneous lupus erythematosus? dermatologist 51: 270-275
  6. Miyagawa S et al (2004) Autoimmune thyroid disease in anti-Ro/SS-A-positive children with annular erythema: report of two cases. Br J Dermatol 150: 1005-1008
  7. Segerberg-Konttinen M et al (1986) Focus score in the diagnosis of Sjögren`s syndrome. Scand J Rheumatol Suppl 61: 47-51
  8. Sjögren HSC (1933) On the knowledge of keratoconjunctivitis sicca (keratitis filiformis with hypofunction of the lacrimal glands). Dissertation paper. Acta Ophthalmol (Copenhagen) supplement II: 1-151
  9. Ueki H et al (1991) Dermatological manifestations of Sjögren's syndrome. Dermatologist 42: 741-747
  10. Vitali C et al (2002) Classification criteria for Sjögren`s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61: 554-558

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Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

Authors

Last updated on: 29.10.2020