279

Introduction

Sjögren syndrome (SS; Gougerot – Sjögren syndrome) is an autoimmune disorder in which immunocytes dam-age the salivary and lacrimal glands, and other exocrine glands. Dry mouth and dry eyes are seen with lymphoid infiltrates in these and other exocrine glands, and serum autoantibodies ( Fig. 37.1 ).

SS has two main forms ( Table 37.1 ):

• Primary Sjögren syndrome (SS-1), in which dry eyes and dry mouth are seen, in the absence of a connective tissue disease. This is uncommon and sometimes termed ‘sicca syndrome’, but the latter term is also used non-specifi cally for dry mouth and eyes.

• Secondary Sjögren syndrome (SS-2), which comprises dry eyes and dry mouth together with a connective tissue disease, is more common. The connective tissue associa-tion is usually with (in descending order of frequency):

• rheumatoid arthritis (RA) • systemic lupus erythematosus • polymyositis • scleroderma.

Incidence

SS itself is uncommon, although the very rarity may lead to underdiagnosis.

Age SS can affect any age, but the onset is most common in middle-age or older.

Key points • Sjögren syndrome (SS) is the association of dry

mouth and dry eyes. • SS is an autoimmune disorder. • 90% of SS patients are female. • Dry eyes and mouth alone are termed sicca

syndrome or primary SS. • Dry eyes and mouth with a connective tissue

disease are termed secondary SS. • Dry mouth predisposes to difficulties speaking and

swallowing. • Complications may include caries, candidiasis and

sialadenitis – and lymphoma. • Diagnosis is confirmed by detection of serum

autoantibodies SS-A and SS-B, and other investigations. Diagnosis can be aided by a salivary gland biopsy.

• Management is with sialogogues and salivary substitutes and preventive dentistry.

37 Sjögren syndrome

PrimarySjögren’s

SecondarySjögren’s

Autoimmune disorderse.g. connective tissue

disease

Dry mouthDry eyes

Fig. 37.1 Sjögren syndrome

Feature SS-1 SS-2

Connective tissue disease – +

Oral involvement More severe Less common

Ocular involvement More common Less common

Recurrent sialadenitis More common Less common

Lymphoma More common Less common

Main serum autoantibody SS-B SS-A

Table 37.1 Sjögren syndrome: comparison of subtypes

Common and important oral conditions3

280

Sex The majority of patients affected by SS are women.

Geographic There is no known geographic incidence to SS.

Predisposing factors

See Figure 37.2 .

• Sjögren syndrome may have a genetic basis: there is association especially to HLA class II antigens HLADRB1*15-DRB1*0301 and TAP1-0101 TAP2-0101. SS is sometimes found in other family members and it is also found more commonly in families that have members with other autoimmune disorders.

• A Sjögren-like syndrome can be produced by viruses [Epstein – Barr virus, hepatitis C virus, HIV, human T lymphotropic virus 1 (HTLV-1)].

• A Sjögren-like syndrome can be produced by graft-versus-host-disease (see Ch. 40).

Aetiology and pathogenesis

• The antigen in SS is unknown, but viruses may be im-plicated.

• The autoimmune response usually mainly affects exocrine glands, particularly the salivary, lacrimal, and vaginal.

• The lungs, brain, nerves, joints, kidneys, thyroid and liver can also be affected in SS.

• Autoantibodies found in SS are commonly against: • IgM (rheumatoid factor – an IgG antibody against

IgM) • ribonucleoproteins, especially Sjögren syndrome-A

(SS-A or Ro), and SS -B (La) • others antigens such as:

– alpha-fodrin – alpha-amylase – muscarinic M3 receptor – carbonic anhydrase – actin – salivary duct. However, in sicca syndrome (where

oral symptoms are typically more severe) these are less frequently found than in secondary SS, suggesting they may be causally unrelated to the duct damage.

Fragmentation of autoantigens such as La (SS-B) or alpha-fodrin during apoptosis (cell death) causes the redistribution of these autoantigens, leading to the production of the autoantibodies in SS ( Fig. 37.3 ).

• SS appears to be the result of lymphocyte-mediated destruction of exocrine glandular acini, which starts with periductal infi ltration initially mainly by B but later mainly by T lymphocytes ( Fig. 37.4 ). The distribution of the membrane pore channel (water channel) protein aquaporin-5 is abnormal in SS, perhaps as a result of paracrine effect of TNF-alpha, and the neurogenic regulation of the salivary gland also becomes impaired ( Fig. 37.5 ). One theory is that Sjögren syndrome is caused by a defi ciency of suppressor T lymphocytes and subsequent overac-tivity of B lymphocytes, with release of interleukin-10 (IL-10) and the production of autoantibodies. Anti-muscarinic 3 receptor antibody plays an im-portant role in cholinergic hyper-responsiveness in SS. CD40/CD40L (CD40 ligand) and Bcl-2 family proteins, in tandem with B cell-activating factor (BAFF), protect infiltrating lymphocytes from ap-optosis.

• Although the gland acini atrophy, the duct epithelium tends to persist and proliferates – sometimes to the extent that the duct lumens may become obliterated, producing islets of epithelium known as ‘epimyoepi-thelial islands’. The fully developed lesion of SS in major glands thus appears as a dense mass of lym-phocytes interspersed by islands of epithelium, a pat-tern termed the ‘benign lymphoepithelial lesion’ (BLL). Occasionally, BLL exist in the absence of sero-logical and other features of SS.

• B-cell overproduction may eventually lead to lym-phoma ( Fig. 37.6 ).

Clinical features

Sjögren syndrome has a clinical spectrum that extends from an organ-specific autoimmune process to a systemic disorder. The early manifestations may be non-specific, such as fatigue, arthralgia, and Raynaud’s phenomenon, and it can be 8 – 10 years from the initial symptoms to full-blown SS. Since the signs and symptoms can be so subtle

VirusesConnective

tissue diseases

Sjögren’s syndrome

Liverdisease

Graft versushost disease

Fig. 37.2 Sjögren syndrome: possible aetiological factors

Sjögren syndrome 3

281

and non-specific, a thorough history and careful physical examination are mandatory.

SS presents mainly with ( Box 37.1 ):

• eye complaints, including sensations of grittiness, soreness, itching, dryness, blurred vision or light in-tolerance. The eyes may be red with infection of the conjunctivae and soft crusts at the angles (keratocon-junctivitis sicca). The lacrimal glands may swell

• oral complaints (often the presenting feature), includ-ing:

• xerostomia: often the most frequent and obvious clinical component, although not all patients com-plain of dry mouth ( Fig. 37.7 )

• soreness or burning sensation • diffi culty eating dry foods, such as biscuits (the

cracker sign) • diffi culties in controlling dentures

• diffi culties in speech: there may be a clicking quality of the speech as the tongue tends to stick to the palate

• diffi culties in swallowing • complications such as unpleasant taste or loss of

sense of taste; oral malodour; caries; candidiasis; sialadenitis.

Oral and salivary gland examinations are important. The mouth may appear dry, and on examination there may be:

• tendency of the mucosa to stick to a dental mirror • food residues ( Fig. 37.8 ) • lack of salivary pooling • frothiness of saliva and absence of frank salivation

from major gland duct orifi ces • a characteristic tongue appearance; lobulated, usually

red, surface with partial or complete depapillation • in advanced cases – obviously dry and glazed oral

mucosae.

Oral complications • Unpleasant taste, loss of sense of taste or malodour. • Candidiasis is common and may cause soreness and

redness of the oral mucosa or angular cheilitis. • Dental caries tends to be severe, affect smooth sur-

faces and is diffi cult to control. • Ascending (suppurative) sialadenitis is a hazard. • Salivary gland enlargement is not uncommon in

Sjögren syndrome. It is: • usually caused by the SS infl ammatory process • intermittently caused by bacterial ascending infec-

tion (acute sialadenitis; Fig. 37.9 )

Glandular cell activationSS-A expression

CD4 T cellinfiltration

Impairedsecretion

B cellactivation

HORMONESOestrogens

SICCAsyndrome

Extraglandularfeatures

Lymphoma

MetalloproteinasesToll receptors Autoantibodies

Granzyme AFas/Fas Perforin

VIRUSHLA

IL-1 IFN

IL-2

Fig. 37.3 Sjögren syndrome: pathogenesis

Fig. 37.4 Sjögren syndrome: histopathology showing dense lymphocytic periductal infi ltrate (focal sialadenitis)

Common and important oral conditions3

282

• occasionally massive and associated with enlarge-ment of the regional lymph nodes, a condition called ‘pseudolymphoma’

• rarely due to lymphoma. • Mikulicz’s disease (MD) is the term given to persistent

salivary and lacrimal gland enlargement associated with raised serum immunoglobulin G4 (IgG4) and promi-nent infi ltration of IgG4-expressing plasmacytes in the lacrimal and salivary glands. It is characterized by few autoimmune reactions and good responsiveness to corticosteroids; complications include autoimmune pancreatitis, retroperitoneal fi brosis, tubulointerstitial nephritis, autoimmune hypophysitis and Riedel’s thyroiditis.

➤ Box 37.1

Sjögren syndrome main features

Oral signs and symptoms • Dry mouth • Cracker sign • Burning • Salivary swelling and sialadenitis • Caries • Candidiasis • Abnormal taste • Malodour

Ocular signs and symptoms • Foreign body sensation • Inability to tear • Light intolerance

Others • Fatigue • Fever • Kidney, muscle, nerve, liver, joint, thyroid involvement • Connective tissue disease

HLA-DR +

Lymphoma

Na

Igs

Fas +

CD4 Th1:IFN IL-2 Th2:IL-4-6 and 10

H2O

T

B B

Fig. 37.6 Sjögren syndrome showing evolution to lymphoma

Initial lesion

NaMucin

H2O

T

T

Mucin

Later lesion

NaH2O

T

TB

HLA-DR +

Na

La

M3 receptor Fas +

CD4 Th1:IFN IL-2 Th2:IL-4-6 and 10

Carbonic anhydrase

H2O

T

T

Fig. 37.5 Sjögren syndrome showing evolution of salivary lesion

Sjögren syndrome 3

283

Extraoral complications • Connective tissue disease in SS usually precedes the

onset of dry eyes and dry mouth, and, therefore, pa-tients presenting with dry eyes and dry mouth alone probably have primary SS, unless a connective tissue disease manifests within about 1 year. The connective tissue disease in secondary SS is typically longstand-ing and should be clinically obvious; rheumatoid ar-thritis is the most common.

• Extraglandular complaints of SS can include ( Fig. 37.10 ):

• Raynaud phenomenon • arthralgia • myalgia • fatigue • skin ulceration or rash • dyspnoea • dry vagina • bruising, bleeding and purpura • numbness and other neurological features. • Associations of SS can include: • autoimmune (Hashimoto’s) thyroiditis • gastro-oesophageal refl ux disease (GORD) • primary biliary cirrhosis • malignant or pseudomalignant lymphoprolifera-

tion. Mostly in primary SS, these are B-cell lympho-mas, which result from B-cell lymphoproliferation in mucosal-associated lymphoid tissue (MALT lym-phoma) and which may develop into monoclonal gammopathies (such as Waldenstrom’s macroglob-ulinaemia). Pseudolymphoma or frank lymphoma should be suspected when there is persistent sali-vary gland enlargement, lymphadenopathy or lung nodules. Mixed monoclonal cryoglobulins may be found, and when these contain rheumatoid factor cross-reactive for V kappa IIIb related or VH1-re-lated idiotypes, they may be markers for lym-phoma.

Fig. 37.7 Sjögren syndrome showing dry mouth

Fig. 37.8 Sjögren syndrome showing food residues in vestibule

Fig. 37.9 Sjögren syndrome showing salivary swelling

Common and important oral conditions3

284

• In pregnancy in SS, the autoantibodies may move transplacentally and cause fetus/infant heart block.

Diagnosis

A subjective feeling of dry mouth (xerostomia) is com-mon, although reduced salivary flow (hyposalivation) is not always confirmed by objective studies (see Ch. 8). Indeed, of older people 16 – 25% complain of xerosto-mia – usually caused by drugs. If SS is suspected; how-ever, specialist referral is warranted since investigations may be needed, and the differential diagnosis may include:

• viral infections: • hepatitis C virus • HIV • HTLV-1 • EBV • sarcoidosis • glandular deposits in: • haemochromatosis • lipoproteinaemias • amyloidosis • lymphomas.

The diagnosis of SS is mainly on the history, clinical examination and investigation, including:

• ocular symptoms • oral symptoms

• ocular signs • autoantibodies • salivary gland involvement • histopathology.

The American – European diagnostic criteria (revised) for Sjögren syndrome are shown in Box 37.2 .

Eye examination Examination of the eyes by a specialist is most important ( t0020 Table 37.2 ).

Autoantibodies and other blood tests Autoantibody assays can be extremely helpful in diag-nosis, and are readily available, inexpensive and fairly non-invasive. SS-A (Ro) and SS-B (La) antibodies are found especially in primary SS, may have diagnostic value in patients with unexplained parotid swelling and may antedate clinical evidence of Sjögren syndrome by months or years.

Blood tests may be indicated to:

• examine for SS-A and SS-B • assess erythrocyte sedimentation rate (ESR) or plasma

viscosity • exclude anaemia • examine IgA immune complexes • exclude similar syndromes seen in infection with hep-

atitis C virus, EBV, HTLV-1 or HIV.

Salivary gland examination Salivary gland examination, functional studies and bi-opsy may be indicated ( Box 37.2 , Table 37.2 , a0010 Algorithms 37.1 and a0020 37.2 ).

Salivary flow measurements (sialometry) These are relatively simple and non-invasive, but are non-specific, and not especially sensitive. Objective evi-dence of diminished salivary flow in Sjögren syndrome includes a:

• decreased resting secretion rate of whole saliva <1.5ml in 15 minutes: this is more closely associated with symptoms of xerostomia than are stimulated flow rates. The test should be standardized by being carried out: after overnight fasting; first thing in morning; no food or drink for at least 1 hour be-fore the test; no smoking for at least 1 hour before

Autoimmune

MediatorVascular

Inflam-matory

GastrointestinalLung Pancreas Kidney

Hepatobiliary

Exocrine

Non-exocrine

Pseudo-lymphoma

Lymphoma

Thyroiditis

Fever FatigueHaematologicRaynaud

MuscleJointSkinNeurologic

Xerophthalmia

Xerostomia

Surface

Internalorgan

B cellinfiltrate

Fig. 37.10 Sjögren syndrome – extraglandular complications

Sjögren syndrome 3

285

the test; and with the patient being asked to dribble all their saliva into a measuring container for 15 minutes

• decreased stimulated fl ow rates: usually regarding fl ows of <0.5ml per gland in 5 minutes to 5ml per gland in 10 minutes as abnormal. Use various means of stimulation, such as 10% citric acid dropped on-to the tongue, and collect parotid saliva using a Carlsson – Crittenden cup placed over Stensen’s papilla.

Salivary gland biopsy Biopsy of salivary glands can be useful in the diagnosis of Sjögren syndrome. Biopsy of major glands involves a skin incision and slight possibilities of facial nerve in-jury, scarring and salivary fistula. Therefore, minor sali-vary glands are usually biopsied.

Minor glands in the palate and lower lip are acces-sible, but the latter site is preferred both from the as-pects of patient comfort and access for the operator, and also because the extent and pattern of histopatho-logical changes on labial salivary gland (LSG) biopsy correlate with those in parotid and submandibular glands.

The LSG biopsy technique involves: local analgesia; simple linear incision in the lower labial mucosa just to one side of the midline; at least five lobules of LSG are blunt dissected out and removed; and one or two sutures may be are placed to ensure haemostasis. There are few adverse effects except occasional minor hypo-aesthesia.

Focal sialadenitis is the characteristic histopatho-logical feature. LSG histology, if used with a focus score (FS), provides a reproducible and objective eval-uation of severity of inflammation. Other features such as fibrosis or fatty atrophy, duct dilatation and hyper-plasia, however, are non-specific. A focus is defined as an aggregate containing 50 or more mononuclear cells: the FS is the number of such aggregates in each 4mm 2 area. The mononuclear cells are predominantly T-helper inducer cells. The FS is reliable only where gland lobes with acinar atrophy and interstitial fibrosis are excluded, and where an adequately large specimen is examined. The threshold FS generally used for diagno-sis of SS is one focus per 4mm 2 , though others use slightly higher thresholds. Focal sialadenitis in an ade-quate LSG biopsy (at least 4 – 5 lobules) appears to be the most disease-specific and sensitive diagnostic method.

➤ Box 37.2

Sjögren syndrome American – European diagnostic criteria*

SS is diagnosed if 4 of these 6 criteria are positive (especially if histopathology and serology are positive) or if there are ocular symptoms or oral symptoms, plus any 2 of the other 4 criteria:

Ocular symptoms At least one of these:

• daily persistent troublesome dry eyes for >3 months • recurrent sensation of sand or gravel • need to use teardrops >3 times daily

Oral symptoms At least one of these:

• daily feeling of dry mouth >3 months • recurrent or persistently swollen salivary glands as

adult • frequently drink liquids to aid swallowing dry foods

Ocular signs At least one of these:

• Schirmer <5mm in 5 minutes • Rose – Bengal score >4

Histopathology Focus score >1 on LSG†

Salivary gland involvement At least one of these abnormal:

• scintigraphy – reduced concentration/uptake/excretion • sialography – diffuse sialectasis • unstimulated whole salivary fl ow <1.5ml in

15 min

Serum autoantibodies At least one of these:

• SS-A (Ro) • SS-B (La)

*Focus = cluster of 50 or more lymphocytes in a labial salivary gland (LSG) †Focus score = average number of foci in a 4 mm 2 area

See Vitali et al (2002) for detail

Table 37.2 Salivary investigations in Sjögren syndrome

Investigation Typical findings Comments

Sialometry Reduced Non-specific, but readily available

Salivary gland biopsy

Focal lymphocytic infiltrate Acinar atrophy Fibrosis

More specific

Sialography Sialectasis Non-specific, but often available

Scintigraphy Reduced radionuclide uptake

Non-specific, but expensive

Common and important oral conditions3

286

Sialography Sialography has the following characteristics:

• shows sialectasis (this is the most typical fi nding, it is most sensitive using oil-based contrast media and is seen particularly in parotid glands and may correlate with histological scores and scintigraphy)

• specifi city is low • time-consuming • may be painful • may produce hazards, such as granulomatous reac-

tions or infection.

Salivary scintiscanning Salivary scanning (scintigraphy) has the following char-acteristics:

• Shows diminished radionuclide uptake and sponta-neous secretion, or secretion following citric acid or pilocarpine stimulation

• Is relatively non-invasive • Examines both parotid and submandibular glands si-

multaneously

• Changes correlate with sialographic, fl ow rate and LSG histological changes, but are non-specifi c

• Quantitative registration of uptake and secretion phases with correction for vascular background might improve the diagnostic and monitoring value of sali-vary scintigraphy.

Ultrasonography This is proving to be a useful method for evaluating salivary gland involvement in Sjögren syndrome and may replace other diagnostic techniques, such as sialog-raphy or salivary scintigraphy.

Magnetic resonance imaging This can be helpful in showing soft tissue changes.

Sialochemistry • Analysis of saliva composition (sialochemistry) for

the diagnosis and monitoring of salivary disease has had some enthusiastic proponents, but has been of no

Reduced salivary flowand/or dry eyes, and

positive Schirmer test

Connective tissuedisease

Dry mouth

ANA or Scl 70positive?

Yes No

American–Europeancriteria positive?

SS-A or SS-Bpositive?

No

Labial gland biopsypositive for SS?

No

Sicca syndromeSarcoidosis, others

Yes

Primary Sjögrensyndrome

Yes

Secondary Sjögrensyndrome

Yes

Algorithm 37.1 Dry mouth diagnosis

Sjögren syndrome 3

287

practical value. It could prove to be of value in moni-toring the disease process in view of the non- invasive nature. The diagnostically and prognostically most promising recent sialochemical fi ndings have been of raised levels of:

• lactoferrin • beta 2 -microglobulin • interleukin-6 • lysozyme • sodium, chloride, albumin, lactoferrin, IgA and

IgG (however, these are non-specifi c and rarely correlate with salivary fl ow or histological changes).

Management

• Sjögren syndrome remains an incurable condition, since no therapeutic modality has been identifi ed that reliably modifi es the course of the disease. Recently

there have been attempts to control the underlying autoimmune pathogenic mechanisms of lymphoid infi ltration and cytokine release.

• Patient information is an important aspect in management.

• Any connective tissue or other disorders should be treated by a physician.

• Patients with severe extraglandular manifestations are usually treated by a physician with systemic corti-costeroids and other immunosuppressive drugs.

• The patient should be followed up regularly, particu-larly because of the possible complication of lym-phoma, which may manifest with:

• fi rm tender persistent salivary swelling • lymphadenopathy • nodular lung lesions • cough • dyspnoea • hepatosplenomegaly. • Other aspects of care include the following: • The use of a humidifi er in the bedroom.

Sjögren syndrome

Improved adequately?

Chewing gum

Persist in dietarycontrol and oral

hygiene

No

Diabetic sweets

YesImproved adequately?

No

Salivary substitute

Improved adequately?

No

Pilocarpineor cevimeline

Algorithm 37.2 Sjögren syndrome management

Common and important oral conditions3

288

• For dry eyes, methylcellulose eye drops or, rarely, ligation or cautery of the nasolacrimal duct.

• For dry mouth it can be helpful for the patient to: sip water or other fl uids throughout the day; pro-tect the lips with lip salve; take small bites of food; eat slowly; eat soft, creamy foods (casseroles, soups) or cool foods with a high liquid content (melon, ice cream); and to moisten foods with wa-ter, gravies, sauces, extra oil, dressings, sour cream, mayonnaise or yoghurt.

• It is wise for the patient to avoid: mouth-breathing; any drugs that may produce xerostomia (e.g. tricyclic antidepressants); alcohol (including in mouthwashes); smoking; caffeine (coffee, some soft drinks); dry foods, such as biscuits (or moisten in liquid fi rst); spicy foods; and oral healthcare products containing sodium lau-ryl sulphate, which may irritate the mucosa.

• Salivation may be stimulated by using: chewing gums (containing xylitol or sorbitol, not sucrose); diabetic sweets; cholinergic drugs, such as pilo-carpine or cevimeline that stimulate salivation (sial-ogogues) – which should be used by the specialist as discussed in Chapter 7; and transglossal electri-cal stimulation.

• Salivary substitutes may help symptomatically. Various apart from water are available, including: methylcellulose; Saliva Orthana and Oralbalance are particularly useful since they contain fl uoride (see Ch. 5) and mucin. However, there may be religious or cultural objections to use of mucin by some Muslims, Hindus, Jews and Rastafarians:

products containing carboxymethylcellulose (e.g. Glandosane or Luborant) may then be preferred.

• Complications should be avoided or managed by: • avoiding sugary foods • keeping the mouth clean • using fl uorides • using mouthwashes of chlorhexidine. • Dental caries is best controlled by dietary control of

sucrose intake, and the daily use of fl uorides as tooth-pastes, mouthwashes and gels (1% sodium fl uoride gels or 0.4% stannous fl uoride gels).

• Candidiasis may cause soreness or burning and, thus, should be treated with antifungals until there is nei-ther erythema nor symptoms. Topical antifungals in liquid form, such as nystatin or amphotericin suspen-sion, are the most effective and acceptable. Other preparations such as miconazole or fl uconazole are also effective. Dentures should be left out of the mouth at night and stored in sodium hypochlorite solution, chlorhexidine or benzalkonium chloride to disinfect. An antifungal, such as miconazole gel or amphoter-icin, or nystatin ointment, should be spread on the denture before reinsertion

• Bacterial sialadenitis needs treating with a penicilli-nase-resistant antibiotic, such as fl ucloxacillin.

• Lymphomas; an oncological opinion is indicated; chemotherapy may be required.

Websites Arthritis Link: http://www.arthritislink.com/arthhlinks.htm Sjögren’s Syndrome Foundation: http://www.sjogrens.org British Sjögren’s Syndrome Association: http://www.bssa.uk.net

Further reading Bialek E . J . , Jakubowski W . , Zajkowski P . , Szopinski K . T . , Osmolski A . 2006

US of the major salivary glands: anatomy and spatial relationships, pathologic conditions, and pitfalls . Radiographics 26 ( 3 ) : 745 – 7 63

Chikui T . , Okamura K . , Tokumori K . et al 2006 Quantitative analyses of sonographic images of the parotid gland in patients with Sjögren’s syndrome . Ultrasound Med Biol 32 ( 5 ) : 617 – 6 22

Jonsson R . , Haga H . -J . , Gordon T . P . 2000 Current concepts on diagnosis, autoantibodies and therapy in Sjögren’s syndrome . Scand J Rheumatol 29 : 341 – 34 8

Mahoney E . J . , Spiegel J . H . 2003 Sjögren’s disease . Otolaryngol Clin North Am 36 ( 4 ) : 733 – 7 45

Manoussakis M . N . , Moutsopoulos H . M . 2000 Sjögren’s syndrome: autoimmune epithelitis . Baillière’s Best Pract Res Clin Rheumatol 14 : 73 – 95

Mavragani C . P . , Moutsopoulos N . M . , Moutsopoulos H . M . 2006 The management of Sjögren’s syndrome . Nat Clin Pract Rheumatol 2 ( 5 ) : 252 – 2 61

Moutsopoulos N . M . , Moutsopoulos H . M . 2001 Therapy of Sjögren’s syndrome . Springer Semin Immunopathol 23 : 131 – 1 45

Nakamura H . , Kawakami A . , Eguchi K . 2006 Mechanisms of autoantibody production and the relationship between autoantibodies and the clinical manifestations in Sjögren’s syndrome . Transl Res 148 ( 6 ) : 281 – 28 8

Patient information sheet

SJÖGREN SYNDROMEPlease read this information sheet. If you have any questions, particularly about the treatment or potential side-effects, please ask your doctor.

• This is an uncommon condition.• The cause is unknown but it is immunological and

possibly viral.• It is not known to be infectious.• It is not usually inherited.• Dry mouth is common.• Other mouth problems may include soreness, tooth

decay and salivary swelling.• Dry eyes are commonly found.• Joint and other problems may be associated.• Rarely, a very few patients may, after years, develop

a tumour. You should get yourself checked regularly.• X-rays, blood tests and biopsy may well be required.• Symptoms can usually be controlled but not cured

with simple drugs.• Useful website: http://www.sjsworld.org.• Advice is available from: British Sjögren’s Syndrome

Association, PO Box 10867, Birmingham, B16 0ZW (http://www.bssa.uk.net)

Sjögren syndrome 3

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Ohara T . , Itoh Y . , Itoh K . 2000 Reevaluation of laboratory parameters in relation to histological fi ndings in primary and secondary Sjögren’s syndrome . Intern Med 39 : 457 – 4 63

Ramos-Casals M . , Loustaud-Ratti V . , De Vita S . et al and the SS-HCV study group 2005 Sjögren syndrome associated with hepatitis C virus: a multicenter analysis of 137 cases . Medicine (Balt) 84 ( 2 ) : 81 – 8 9

Rehman H . U . 2003 Sjögren’s syndrome . Yonsei Med J 44 ( 6 ) : 947 – 9 54 Reyes S . L . I . , Leon B . F . , Rozas V . M . F . , Gonzalez J . P . , Naves P . R . 2006 BAFF: A

regulatory cytokine of B lymphocytes involved in autoimmunity and lymphoid cancer . Rev Med Chil 134 ( 9 ) : 1175 – 11 84 . Epub 2006 Dec 12

Salaffi F . , Argalia G . , Carotti M . et al 2000 Salivary gland ultrasonography in the evaluation of primary Sjögren’s syndrome. Comparison with minor salivary gland biopsy . J Rheumatol 27 : 1229 – 12 36

Shimizu M . , Okamura K . , Yoshiura K . , Ohyama Y . , Nakamura S . , Kinukawa N . 2006 Sonographic diagnostic criteria for screening Sjögren’s syndrome . Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102 ( 1 ) : 85 – 93 . Epub 2006 Apr 17

Skopouli F . N . , Dafni U . , Loannidis J . P . et al 2000 Clinical evolution, and morbidity and mortality of primary Sjögren’s syndrome . Semin Arth Rheum 29 : 296 – 304

Stea E . A . , Routsias J . G . , Samiotaki M . et al 2007 Analysis of parotid glands of primary Sjögren’s syndrome patients using proteomic technology reveals altered autoantigen composition and novel antigenic targets . Clin Exp Immunol 147 ( 1 ) : 81 – 8 9

Vitali C . , Bombardieri S . , Jonsson R . et al 2002 Classifi cation criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American – European Consensus Group . Ann Rheum Dis 61 : 554 – 55 8

Yamamoto M . , Takahashi H . , Ohara M . et al 2006 A new conceptualization for Mikulicz’s disease as an IgG4-related plasmacytic disease . Mod Rheumatol 16 ( 6 ) : 335 – 3 40 . Epub 2006 Dec 20