Ann Rheum Dis 1999;58:465–473 465 REVIEW Ann Rheum Dis: first published as 10.1136/ard.58.8.465 on 1 August 1999. Downloaded from Treatment of oral dryness related complaints (xerostomia) in Sjögren’s syndrome Willy A van der Reijden, Arjan Vissink, Enno C I Veerman, Arie V Nieuw Amerongen Primary Sjögren’s syndrome (SS) is a systemic This review describes the current treatments autoimmune disorder characterised by a with regard to xerostomia focused on patients chronic, progressive loss of salivary and lac- with SS. Because the treatment of the cause of rimal function resulting in symptoms of oral oral dryness in Sjögren patients is possible so and ocular dryness. The involvement of far, treatment is focused on stimulation of the exocrine glands is the result of a focal, periduc- residual capacity of the salivary glands and/or tal mononuclear cell infiltrate and the subse- substitution of saliva with mouth rinses or quent loss of secretory epithelial cells.1 As a saliva substitutes if stimulation of residual consequence, major changes occur in both the secretory capacity produces a too small eVect. salivary flow rate and salivary composition.2–9 In addition, these patients need special care for In the case of secondary SS a second preservation of their dentition and protection autoimmune disease is involved, mostly rheu- of their susceptible oral mucosa. With the matoid arthritis. exception of systemic treatments, there are The role of saliva in maintaining oral health clinically no diVerences in the treatment and even quality of life is obvious in people who approach of the oral complaints in patients are lacking suYcient saliva.10–12 The eVects of with primary and secondary SS as the choice of the reduced salivary flow rate (xerostomia) and treatment is generally related to the level of the changed salivary composition in SS are appar- residual salivary secretion. ent (table 1): there are problems in eating, speaking, and swallowing12–15 and frequently 16 Systemic treatment disturbances in taste perception. In addition, http://ard.bmj.com/ Systemic treatment of SS is generally based on reduced clearance of food, changes in micro- treatments applied in related autoimmune dis- bial ecology and a reduced buVer capacity have eases such as rheumatoid arthritis (RA) and their eVects on oral health: an increased systemic lupus erythematosus (SLE). In pa- susceptibility to dental caries and oral infec- tients with secondary SS, such an approach is tions are important clinical manifestations of obvious because of the treatment of the under- Section Oral the oral component of SS.17 18 When the lying autoimmune disease. In primary Sjögren Biochemistry, systemic disease advances, salivary secretion patients the use of anti-rheumatics (for exam- on September 28, 2021 by guest. Protected copyright. Department of Oral declines further.7 Biology, Academic ple, non-steroidal anti-inflammatory drugs, A reduction of the salivary flow rate below Centre for Dentistry NSAIDs) is to suppress inflammation. physiological values can be induced by several Amsterdam (ACTA), Both prednisone and piroxicam, as examples other causes as well.19 Dry mouth symptoms Amsterdam, the of steroid and NSAIDs, did not significantly Netherlands are known as a side eVect of more than 400 improve the functional or histological param- W A van der Reijden drugs.20 21 In most of these cases the level of eters of the salivary and lacrimal glands in SS.27 ECIVeerman reduction of the salivary flow is slight and can A V Nieuw Amerongen Therefore, the use of NSAIDs in SS is only be compensated for by mechanical or gustatory indicated for the treatment of arthralgia and stimulation. Other common causes of pro- Department of Oral myalgia and for arthritis.28 Besides analgesics, longed hyposalivation include other autoim- and Maxillofacial other anti-rheumatics that may be useful are Surgery, University mune disorders such as systemic lupus (hydroxy)chloroquine and methotrexate (table Hospital Groningen, erythematosus,22 23 uncontrolled diabetes 2). Administration of hydroxychloroquine re- Groningen, the mellitus24 25 and salivary gland injury as a result Netherlands sulted in a significant decrease of immunoglobu- of radiotherapy in the head and neck region.26 A Vissink lin serum concentrations.37 38 In two small Table 1 Consequences of xerostomia prospective trials the observed subjective im- Correspondence to: provement was not convincing,37 38 while in a DrWAvanderReijden, Dryness of the mouth* Burning sensation Section Clinical Oral Thirst sensation Mucus accumulation larger retrospective trial by the same authors Microbiology, Department of DiYculties in oral functioning Changes in soft tissues about 55 per cent of the patients noted improve- Oral Biology, Academic DiYculties in wearing dentures Shift in oral microbial flora ment in ocular symptoms (pain and dryness).39 Centre for Dentistry Nocturnal oral discomfort Xerostomia induced caries Amsterdam, Van der Fatigue Taste disturbances The same trial showed improvement of corneal Boechorststraat 7, 1081 BT integrity and lacrimal gland function in 50 per Amsterdam, the Netherlands. *A good correlation between subjective oral dryness and meas- cent of the patients, improvement of subjective ured salivary flow rates is observed in about 70% of the Accepted for publication patients.12 The other patients complain about oral dryness not- oral symptoms (pain and dryness) in about 60 16 April 1999 withstanding a normal salivary flow or the opposite. per cent of the patients and a significantly 466 van der Reijden, Vissink, Veerman, et al Table 2 Major therapeutic agents tried for Sjögren’s syndrome Drug Trial design Patients* Results Reference Ann Rheum Dis: first published as 10.1136/ard.58.8.465 on 1 August 1999. Downloaded from Cyclosporin (systemic) open (continuation of double blind trial) 9 primary SS subjective xerostomia improvement in 88% (p<0.01), mean 29 worsening immunopathology minor salivary glands of 1.2 at a labial biopsy score from 0–4), no eVect on salivary and lacrimal gland function Cyclophosphamide case report 1 primary SS, good response on myositis symptoms; from extensive 30 (intravenous) later development muscle fibre necrosis to type II muscle fibre atrophy. of polymyositis Azathioprine double blind, randomised, placebo controlled 13 primary SS no clinical or biochemical changes, six withdrew because of 31 side eVects Prednisone double blind, randomised, placebo controlled 8 primary SS no objective improvement on salivary gland function; 27 subjective improvement on xerostomia and xerophthalmia Piroxicam double blind, randomised, placebo controlled 8 primary SS no changes 27 á Interferon 2 + open study v hydroxychloroquine 10 primary SS improvement in salivary and lacrimal function, no changes 32 prednisone minipulse in immunopathology; in three patients transient alopecia as side eVect single blinded v sucralfate 28 primary SS + improvement in salivary gland function in 50% of the 33 2 secondary SS patients; in nine patients decrease of lymphocytic infiltration in salivary glands Methotrexate open 17 primary SS at 0.2 mg/kg/week: improvement of subjective oral and 34 ocular symptoms, decrease of parotid gland enlargement frequency, dry cough and purpura; no increase of salivary and lacrimal gland function Sulfasalazine open 10 primary SS improvement in two patients in arthralgia and fatigue; in 35 two patients no improvement; six patients dropped out by severe side eVects. D-penicillamine open 4 primary SS subjective improvement in saliva (4 patients) and tear 36 secretion (2 patients); side eVects in two patients: pruritic rash and oral ulcers, respectively. Hydroxychloroquine open 3 primary SS subjective improvement in saliva, tear and vaginal secretion; 37 rose bengal staining became negative in 2 patients open, controlled 10 primary SS decreased serum immunoglobulin levels; decreased 37 rheumatoid factor levels double blinded placebo controlled crossover 19 primary SS decreased serum immunoglobulin levels; no clinical 38 beneficial eVects on salivary and lacrimal gland function open, retrospective 50 primary SS decreased IgG levels; slight improvement of oral and ocular 39 symptoms and of arthralgia/myalgia á Hydroxychloroquine + open v interferon 2 10 primary SS no changes in serum immunoglobulin and rheumatoid factor 32 prednisone (mini-pulse levels; no changes in salivary or lacrimal gland function and daily 5 mg) *Only medicated patients are listed, SS = Sjögren’s syndrome. increased salivary flow rate in 82 per cent of the guishing characteristics between patients who patients.39 Whether the eYcacy of hydroxychlo- withdrew the study and patients who com- roquine is related to the duration of administra- pleted it. Therapeutic benefit of azathioprine tion needs further study, but administration of on symptoms, signs, serological and histologi- http://ard.bmj.com/ hydroxychloroquine for less than one year prob- cal parameters was not observed. This in com- ably will result in less beneficial results.38 39 bination with the high incidence of adverse Moreover, the response to hydroxychloroquine reactions makes azathioprine not indicated in of a population of patients with SS may be influ- the treatment of SS. enced by the diagnostic criteria that has been Another T cell intervening treatment is the used to select the patients for the study.39 The use of low dose cyclosporin A. This agent acts “San Diego criteria” for diagnosing SS are by interleukin 2 inhibition and will lead to sup- on September 28, 2021 by guest. Protected copyright. mainly focused on the autoimmune parameters, pression of T cell proliferation. In an open trial which increase the chance of response to an subjective xerostomia symptoms improved in immunomodulating drug when compared with 88% (p<0.01) of the patients.29 However, a patient selection on the “European criteria”, mean worsening immunopathology of the which depend strongly on clinical dryness minor salivary glands of 1.2 (at a labial biopsy symptoms.40 41 With respect to side eVects such score from 0–4) was observed (p<0.01) and as retinopathy, a known adverse reaction of high there was no eVect on salivary and lacrimal dose antimalarial use, hydroxychloroquine can gland function.