Table 35.5 Key recommendations for practice in primary care

Clinical recommendations

Sjogren’s syndrome (SjS) is a chronic autoimmune disorder affecting middle aged women characterized by dry eyes and dry mouth

Major clinical manifestations of Sjögren’s syndrome may be detected in primary health care Extraglandular disease can affects lung, liver, kidney (interstitial nephritis), skin vasculitis,

peripheral neuropathy, glomerulonephritis, and low C4 levels (immune complex disease) Complete blood cell count, erythrocyte sedimentation rate, liver function tests, proteinogram,

electrolytes and urinalysis, ANA and rheumatoid factor may be the first step for the immunological evaluation in primary health care

The presence of purpura, peripheral neuropathy, low complement levels, neutropenia and lymphopenia define a high-risk group for lymphoma development

Treatment recommendations

The muscarinic agonists pilocarpine and cevimeline can be used to relieve the symptoms of dry eyes and keratoconjunctivitis sicca

Muscarinic agonists improve subjective and objective signs and symptoms of xerostomia Management of extraglandular manifestations is mainly empirical: steroids and immunosup-

pressive agents are of some benefit; anti-B-cell therapy shows promising results

and dry eyes, salivary flow rates, and ocular tests [38–41]. Cevilimine also significantly reduces candidiasis, dental plaque, and gingival bleeding. In randomized, controlled trials, however, this medication is associated with sweating and nausea, rigors, and diarrhea in significant subsets of patients [38, 40, 41].

35.6.3Management of Extraglandular Features

Hydroxychloroquine may be used in patients with fatigue, arthralgias, and myalgias. NSAIDs can relieve the minor musculoskeletal symptoms of SjS as well as the painful parotid swelling that occurs in some patients. Glucocorticoids, immunosuppresive drugs, and biological agents are limited to patients with severe extraglandular manifestations.

35.7When to Refer to a Specialist

The goal of the evaluation for SjS in primary care is to know key recommendations (Table 35.5). This workup involves the coordination of various specialists in order to assess the different mucosal surfaces and internal organs involved. Primary SjS is a benign disease in the majority of cases but the prognosis depends on associated diseases and three potential complications of alarm for the family doctor:

(a)Eye pain due to corneal ulcer.

(b)Vasculitis.

(c)A change in lymphocyte proliferation the potential for the development of nonHodgkin’s lymphoma. Patients with SjS have a relative risk of lymphoma

Table 35.6 Information from your family doctor

Information is available from the AAFP online at http://familydoctor.org. and http://www.aafp. org/afp/2009/0315/p472.html

What is Sjögren syndrome?

Sjögren syndrome is a disease that causes a dry mouth and dry eyes. It is an autoimmune disease, which happens when your body’s immune system attacks your own cells. Most people with Sjögren syndrome have very mild symptoms, but it may affect other organs, such as the bowel, joints, kidneys, lungs, nervous system, and skin

Who gets it and why?

Sjögren syndrome is one of the most common autoimmune diseases. It usually affects women in their late 40s and early 50s. People with Sjögren syndrome may have other autoimmune diseases, such as rheumatoid arthritis or lupus. Doctors do not know what causes Sjögren syndrome

How do I know if I have Sjögren syndrome?

Most people with Sjögren syndrome have dry eyes and a dry mouth for months. Your eyes may feel gritty or itchy. Your mouth will be dry, and you may have trouble swallowing, eating dry foods, or even speaking. You should see your doctor if you think you might have Sjögren syndrome

How is it treated?

There are several artificial tear and saliva substitutes that may help your symptoms. Your doctor can prescribe other medicines that will help your body make more tears and saliva. Depending on your symptoms, you might also need medicines for your immune system

Is there a cure?

No, Sjögren syndrome is a lifelong disease

Where can I get more information?

Your doctor

The Sjögren’s Syndrome Foundation Web site: http://www.sjogrens.org/

elevated substantially over that of the general population, and clinically identifiable lymphomas occur in approximately 5% of patients. The predictors of lymphoma development in SjS are persistent enlargement of parotid glands, splenomegaly, lymphadenopathy, palpable purpura, leg ulcers, low levels of C4, mixed monoclonal cryoglobulinemia, and cross-reactive idiotypes of monoclonal rheumatoid factors [42]. When a lymphoproliferative process is suspected, the patient should be referred to a hematologist in order to confirm the diagnosis.

Three specialists, the ophthalmologist, gynecologist, and odontologist, should be routinely involved in the follow-up of the corresponding dryness (ocular, vaginal, and oral) and be available to consult on local complications. The main extraglandular involvements require cooperation with the corresponding specialist (nephrologist, neurologist, and hepatologist) [6].

Due to the heterogeneity and often non-specific nature of its clinical manifestations, SjS is probably the autoimmune disease most frequently undiagnosed. Primary care practitioners play an important role in identifying patients with possible SjS, by ordering specific tests to confirm the diagnosis, by making appropriate referrals, and by working with specialists to explain the disease and direct the patient to accurate information (Table 35.6) [43].

References

1.MavraganiCP,MoutsopoulosHM.ThegeoepidemiologyofSjögren’ssyndrome.Autoimmunity Reviews 2010;9:A305–A310.

2. Ramos-Casals M, Solans R, Rosas J, et al. Primary Sjögren syndrome in Spain. Clinical and immunologic expression in 1010 patients. Medicine. 2008;87:210–9.

3. Lawn JE, Rohde J, Rifkin S, et al. Alma-Ata 30 years on: revolutionary, relevant, and time to revitalise. Lancet. 2008;372(9642):917–27.

4. Sisó A, Aymamí A, Campoy A, et al. Síndrome de Sjögren primario: ?Una entidad infradiagnosticada por el Médico de Familia? 18º Congreso Nacional de la Sociedad Española de Medicina Familiar y Comunitaria. Zaragoza 1998. Aten Primaria. 1998;22 Suppl 1:390.

5. Allen J, Gay B, Crebolder H et al. The European definitions of general practice/family medicine. The key features of the discipline of general practice. EURACT 2005 (2005). Available in http://www.euract.org/index.php?folder_id=25 Accessed Date: [11-October-2010].

6. Kassan SjS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome. Arch Intern Med. 2004;164:1275–84.

7. Sorlí JV, Doménech IE, Zurián FJ, et al. Sjögren syndrome. Aten Primaria. 2009;41(7): 417–9.

8. Fox RI. Sjogren’s syndrome. Lancet. 2005;366:321–31.

9. Al-Hashimi I. The management of Sjogren’s syndrome in dental practice. J Am Dent Assoc. 2001;132:1409–17.

10. Caffery B, Simpson TL, Wang S, et al. Rose bengal staining of the temporal conjunctiva differentiates Sjögren’s syndrome from keratoconjunctivitis sicca. Invest Ophthalmol Vis Sci. 2010;51(5):2381–7.

11. García-Carrasco M, Ramos-Casals M, Rosas J, et al. Primary Sjögren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients. Medicine. 2002;81:270–80.

12. Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM. Clinical evolution, and morbidity and mortality of primary Sjogren’s syndrome. Semin Arthritis Rheum. 2000;29:296–304.

13. Fox PC, Bowman SJ, Segal B, et al. Oral involvement in primary Sjögren syndrome. J Am Dent Assoc. 2008;139:1592–601.

14. Belenguer R, Ramos-Casals M, Brito-Zeron P, et al. Influence of clinical and immunological parameters on the health-related quality of life of patients with primary Sjögren’s syndrome. Clin Exp Rheumatol. 2005;23:351–6.

15.Ostuni P, Botsios C, Sfriso P, et al. Prevalence and clinical features of fibromyalgia in systemic lupus erythematosus, systemic sclerosis, and Sjögren’s syndrome. Minerva Med. 2002;93:203–9.

16. Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classification of Sjogren’s syndrome. Results of a prospective concerted action supported by the European community. Arthritis Rheum. 1993;36:340–7.

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

18. Ramos-Casals M, Brito-Zerón P, Pérez-de-Lis M, et al. Sjögren syndrome or Sjögren disease? the histological and immunological bias caused by the 2002 criteria. Clin Rev Allergy Immunol. 2010;38(2–3):178–85.

19. Rosas J, Ramos-Casals M, Ena J, et al. Usefulness of basal and pilocarpine-stimulated salivary flow in primary Sjogren’s syndrome. Correlation with clinical, immunological and histological features. Rheumatology. 2002;41:670–5.

20. Theander E, Manthorpe R, Jacobsson LT. Mortality and causes of death in primary Sjögren’s syndrome: a prospective cohort study. Arthritis Rheum. 2004;50:1262–9.

21. Ioannidis JP, Vassiliou VA, Moutsopoulos HM. Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjogren’s syndrome. Arthritis Rheum. 2002;46:741–7.

22. Ramos-Casals M, Brito-Zeron P, Yague J, Akasbi M, Bautista R, Ruano M, et al. Hypocomplementaemia as an immunological marker of morbidity and mortality in patients with primary Sjogren’s syndrome. Rheumatology (Oxford). 2005;44:89–94.

23. Ramos-Casals M, Font J, Garcia-Carrasco M, et al. Primary Sjogren syndrome: hematologic patterns of disease expression. Medicine. 2002;81:281–92.

24. Brito-Zeron P, Ramos-Casals M, Nardi N, et al. Circulating monoclonal immunoglobulins in Sjogren syndrome: prevalence and clinical significance in 237 patients. Medicine. 2005;84: 90–7.

25. Pérez-de-Lis M, Akasbi M, Sisó A, et al. Cardiovascular risk factors in primary Sjögren’s syndrome: a case-control study in 624 patients. Lupus. 2010;19(8):941–8.

26. Kang JH, Lin HC. Comorbidities in patients with primary Sjögren’s Syndrome: a registrybased case-control study. J Rheumatol. 2010;37:1188–94.

27. Segal B, Bowman SJ, Fox PC, et al. Primary Sjögren’s Syndrome: health experiences and predictors of health quality among patients in the United States. Health Qual Life Outcomes. 2009;7:46.

28. Meijer JM, Meiners PM, Huddleston Slater JJ, et al. Health-related quality of life, employment and disability in patients with Sjogren’s syndrome. Rheumatology. 2009;48(9): 1077–82.

29. Aragona P, Di Stefano G, Ferreri F, Spinella R, Stilo A. Sodium hyaluronate eye drops of different osmolarity for the treatment of dry eye in Sjögren’s syndrome patients. Br J Ophthalmol. 2002;86(8):879–84.

30. Aragona P, Papa V, Micali A, Santocono M, Milazzo G. Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye. Br J Ophthalmol. 2002;86(2):181–4.

31. Brignole F, Pisella PJ, Dupas B, Baeyens V, Baudouin C. Efficacy and safety of 0.18% sodium hyaluronate in patients with moderate dry eye syndrome and superficial keratitis. Graefes Arch Clin Exp Ophthalmol. 2005;243(6):531–8.

32. Condon PI, McEwen CG, Wright M, Mackintosh G, Prescott RJ, McDonald C. Double blind, randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1% (w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome. Br J Ophthalmol. 1999;83(10):1121–4.

33. McDonald CC, Kaye SB, Figueiredo FC, Macintosh G, Lockett C. A randomised, crossover, multicentre study to compare the performance of 0.1% (w/v) sodium hyaluronate with 1.4% (w/v) polyvinyl alcohol in the alleviation of symptoms associated with dry eye syndrome. Eye (Lond). 2002;16(5):601–7.

34. Toda I, Shinozaki N, Tsubota K. Hydroxypropyl methylcellulose for the treatment of severe dry eye associated with Sjögren’s syndrome. Cornea. 1996;15(2):120–8.

35. Papas AS, Sherrer YS, Charney M, et al. Successful treatment of dry mouth and dry eye symptoms in Sjögren’s syndrome patients with oral pilocarpine: a randomized, placebo-controlled, dose-adjustment study. J Clin Rheumatol. 2004;10(4):169–77.

36. Vivino FB, Al-Hashimi I, Khan Z, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-con- trolled, fixed-dose, multicenter trial. P92-01 Study Group. Arch Intern Med. 1999;159(2): 174–81.

37. Wu CH, Hsieh SC, Lee KL, Li KJ, Lu MC, Yu CL. Pilocarpine hydrochloride for the treatment of xerostomia in patients with Sjögren’s syndrome in Taiwan – a double-blind, placebo-con- trolled trial. J Formos Med Assoc. 2006;105(10):796–803.

38. Fife RS, Chase WF, Dore RK, et al. Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome: a randomized trial. Arch Intern Med. 2002;162(11):1293–300.

39. Leung KC, McMillan AS, Wong MC, Leung WK, Mok MY, Lau CS. The efficacy of cevimeline hydrochloride in the treatment of xerostomia in Sjögren’s syndrome in southern Chinese patients: a randomised double-blind, placebo-controlled crossover study. Clin Rheumatol. 2008;27(4):429–36.

40. Ono M, Takamura E, Shinozaki K, et al. Therapeutic effect of cevimeline on dry eye in patients with Sjögren’s syndrome: a randomized, double-blind clinical study. Am J Ophthalmol. 2004;138(1):6–17.

41. Petrone D, Condemi JJ, Fife R, Gluck O, Cohen S, Dalgin P. A double-blind, randomized, placebo-controlled study of cevimeline in Sjögren’s syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis Rheum. 2002;46(3):748–54.

42. Voulgarelis M, Moutsopoulos HM. Malignant lymphoma in primary Sjögren’s syndrome. Isr Med Assoc J. 2001;3:761–6.

43. Kruszka P, O’Brian RJ. Diagnosis and management of Sjögren syndrome. Am Fam Physician. 2009;79(6):465–70.

Part IV

Therapeutic Aspects