Recommendations for the treatment of Sjögren's syndrome^☆

ABSTRACT

The recommendations proposed by the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology for the treatment of Sjögren's syndrome were based on a systematic review of literature in Medline (PubMed) and the Cochrane databases until October 2014 and on expert opinion in the absence of studies on the subject. 131 articles classified according to Oxford & Grade were included. These recommendations were developed in order to guide the management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in this country.

Keywords:
Sjögren's syndrome; Treatment; Recommendations; Guidelines; Systematic review

RESUMO

As recomendações propostas pela Comissão de Síndrome de Sjögren da Sociedade Brasileira de Reumatologia para tratamento da síndrome de Sjögren foram baseadas em uma revisão sistemática da literatura nas bases de dados Medline (PubMed) e Cochrane até outubro de 2014 e opinião de especialistas na ausência de artigos sobre o assunto. Foram incluídos 131 artigos classificados de acordo com Oxford & Grade. Essas recomendações foram elaboradas com o objetivo de orientar o manejo adequado e facilitar o acesso aos tratamentos para aqueles pacientes com adequada indicação de recebê-los, considerando o contexto socioeconômico brasileiro e os medicamentos disponíveis no país.

Palavras-chave
Síndrome de Sjögren; Tratamento; Recomendações; Diretrizes; Revisão sistemática

Introduction

Sjögren's syndrome (SS) is a relatively common autoimmune rheumatic disease, which is most common in women in the fifth decade of life.¹ According to a Brazilian population study, the prevalence of primary SS is 0.17%.² SS can occur in association with other autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in variable rates, up to 22.2% in patients with RA.^3,4

SS is a slowly progressive chronic disease, characterized by a lymphocytic infiltrate that affects the epithelium of exocrine (mainly salivary and tear) glands, leading to a decreased production of tears and saliva. This is a systemic disease with high risk of transformation to lymphoma that primarily affects the joints, lungs, central nervous system (CNS), peripheral nervous system (PNS) and kidneys in approximately 50% of patients.⁵

More recent studies have shown that there are subgroups of patients with different clinical manifestations, histological patterns (presence of germinative centers), cytokine profile and prognosis.^6,7 In the near future, better genetic^8-10 and phenotypic characterization will be able to determine different treatment patterns. But nowadays it is possible to define treatment strategies based on symptoms (symptomatic treatment), and on the type and severity of systemic manifestations. These guidelines recommend the use of EULAR Sjögren's Syndrome Disease Activity (ESSDAI), a tool validated both internationally¹¹ and in Brazil,¹² as criteria for disease activity and response to treatment.

These recommendations were developed in order to guide the management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in the country. Due to the length of this review, specific topics such as management during pregnancy and treatment of lymphoma associated with SS were not addressed. The recommendations were based on studies on primary Sjögren's syndrome. Considering the lack of studies in patients with association with other autoimmune diseases, these recommendations can be extrapolated to secondary Sjögren's syndrome.

Materials and methods

Articles were reviewed in MEDLINE (PubMed) and the Cochrane databases until December 2013. The manual update was held in October 2014. The search strategy was based on structured questions according to PICO (i.e. “Patient”, “Intervention”, “Controls” and “Outcome”) format. These descriptors were used for cross-searching in accordance with the theme proposed in each of PICO questions. For all PICOs, the filter “random” was used, limiting the search to controlled studies. Studies published from January to October 2014 and some case series on extraglandular manifestations were manually included. After analyzing titles and abstracts, 131 articles related to questions that generated the evidence that provided the basis for these guidelines were selected (Fig. 1). The studies were classified according to Oxford & GRADE in degrees of recommendation and strength of evidence as follows:

• A: Experimental or observational studies of better consistency.

• B: Experimental or observational studies of lower consistency.

• C: Case reports (non-controlled studies).

  D: Opinion devoid of a critical evaluation, based on consensus, physiological studies, or animal models.

Fig. 1
Flow diagram of the selection of evidence for Sjögren's syndrome treatment.

Some recommendations were based solely on the opinion of experts from the Sjögren's Syndrome Scientific Committee of the Brazilian Society of Rheumatology (BSR), in the absence of studies on subjects. These recommendations were also graded as a D level and are not preceded by the reference.

PICOs were structured by a multidisciplinary team that was comprised of nine rheumatologists, members of the Sjögren's Syndrome Scientific Committee of BSR, with eight professionals from different areas (dentists, ophthalmologists, pathologists and physiotherapists); all were members of the Expanded Study Group on Sjögren's Syndrome (Grupo Ampliado de Estudos em Síndrome de Sjögren - GAESS - Brazil). The recommendations were formulated mainly based on evidence and reviewed by all participants at two meetings and several rounds of communication via the Internet, from April 2013 until October 2014.

Recommendations

Based on those 14 PICOs used in this survey, we organized didactically 16 questions with 44 recommendations, divided into three major topics and summarized in Figs. 2^-5:

• Part 1. General and patient education recommendations.

• Part 2. Symptomatic management of dryness.

• Part 3. Systemic treatment for glandular and systemic manifestations.

Fig. 2
Flowchart for the symptomatic treatment of dryness of SS.

Fig. 3
Flowchart for the treatment of musculoskeletal symptoms. NSAIDs, non-steroidal anti-inflammatory drugs; GC, glucocorticoids.

Fig. 4
Flowchart for the treatment of neurological systemic manifestations. PN, peripheral polyneuropathy; CNS, central nervous system; MS, multiple sclerosis; GC, glucocorticoids; MP, methylprednisolone; CYC, cyclophosphamide.

Fig. 5
Flowchart for the treatment of systemic kidney, lung and vasculitis manifestations. GN, glomerulonephritis; TIN, tubulointerstitial nephritis; GC, glucocorticoids; MP, methylprednisolone; CYC, cyclophosphamide.

Part 1. General and patient education recommendations

Q1. What are the general recommendations based on expert opinion?

• 1.

  The management of SS must be performed by a multidisciplinary team including at least a rheumatologist, a dentist and an ophthalmologist. The rheumatologist is the reference specialist in the management of SS (D).

• 2.

  Patients with early diagnosis and improved glandular reserve show a better response to treatment (D).

• 3.

  It is recommended that treatment strategies of systemic manifestations are stratified according to disease severity, based not only on clinical impression of the specialist, but also with the use of ESSDAI. Systemic treatment should be instituted in the face of a moderate ESSDAI (≥5). A response to treatment was considered where a decrease of ESSDAI ≥3 points was detected (D).

• 4.

  Patients with SS should avoid the use of caffeinated drinks, alcohol and tobacco (D).

• 5.

  It is recommended that patients receive general education for hygiene and measures to prevent dehydration and irritation of mucous membranes (Table 1) (D).

Table 1
Patient education: measures for hygiene and hydration of mucous membranes.

SS patients should be encouraged to drink fluids frequently, preferably water.

SS patients should be informed that tobacco, caffeine and various medications such as diuretics, beta blockers, antidepressants and anxiolytics, are known causes of dryness and can worsen the glandular symptoms.

To prevent tear evaporation, the patient must avoid dry environments, air conditioning, wind, and also activities that decrease eye blinking, such as using the computer or reading for a long period of time.

Patients with symptomatic dry eye should use environment humidifiers, and glasses with side shields during exposure to wind or when practicing outdoor sports.

Preventive measures for oral health aim to control biofilm, caries, loss of teeth and oral candidiasis. For this purpose, it is important to maintain a good oral hygiene, keeping intraoral pH (basic) with the use of buffers and restricting consumption of sugar.

Careful oral hygiene includes the same recommendations for the general population, with special attention to prosthesis hygiene and choosing less abrasive products, avoiding products that increase dryness of the mucosa, for example, toothpastes containing sodium lauryl sulfate and the use of alcohol-containing mouth rinse.

Removable total dental prosthesis users should daily cleaned their dentures using a dental brush with stiff bristles with toothpaste, switching to a soft bristles brush for oral mucosa cleaning. Once a week, the prosthesis must be immersed in an aqueous solution containing 1% sodium hypochlorite solution during 30 min; then the prosthesis should be rinsed in running water. One can obtain this concentration of sodium hypochlorite by diluting a tablespoon of chlorine bleach in a glass containing 300 mL of filtered water.

Q2. Exercise is effective in treating patients with SS?

• 6.

  Women with SS have a lower physical ability,¹³ and the practice of aerobic exercise at moderate to high intensity leads to the improvement of aerobic capacity, fatigue, perceived exertion and depression.¹⁴ (B)

Q3. What are the effectiveness and safety of vaccines in patients with SS?

• 7.

  It is recommended that general guidelines for vaccination in patients with autoimmune diseases are followed¹⁵ (C), and the vaccination status of the patient must be checked at the patient baseline assessment. It is also recommended to administer vaccines in stable periods of the disease; live attenuated vaccines should be avoided. Immunization against influenza^16,17 (A) and Pneumococcus are indicated,¹⁸ (A) with application of other vaccines according to the immunization schedule (D).

Q4. SS patients should receive supplementation with vitamin D?

• 8.

  Vitamin D deficiency should be investigated and, if necessary, its supplementation should be instituted^16-23 (C).

Part 2. Symptomatic management of dryness

Q5. What is the topical treatment for dry mouth?

• 9.

  Saliva substitutes improve comfort^24-31 (C) and ideally should contain fluoride, bactericides and buffered solutions that help to combat biofilm, the formation of caries and candidiasis³² (D).

• 10.

  Mechanical and/or chemical gustatory stimulating agents, for instance, hard candies and sugar-free chewing gum,³² (D) may be helpful. Solutions or mouthwashes containing malic acid, fluoride and xylitol have similar efficacy to traditional stimulating agents containing citric acid, but with the advantage of maintaining a less acid pH.³³ (B)

Q6. What is the topical treatment for dry eye?

• 11.

  The frequent use of lubricant eyedrops containing glucans or carboxymethylcellulose improves comfort and functional tests^34-40 (A). These eyedrops should be preservative-free, hypotonic, higher colloidal osmolality products.^37,41 (A) Gel formulations are of longer duration and generate greater relief, but may cause temporary blurred vision.

• 12.

  Topical cyclosporin 0.05% bid for 6-12 weeks is effective for symptomatic and functional improvement of dry eye^42-56 (A). The occurrence of eye irritation is common; thus, this drug is recommended at the lowest effective concentration (0.05%)⁵⁵ (A).

• 13.

  Topical glucocorticoids can be used for the most symptomatic cases^57,58 (A) for a limited period, because of the risk subcapsular cataract, glaucoma and infection³⁴ (D). Non-steroidal anti-inflammatory drugs (NSAIDs) must not be routinely used, due to the high risk of corneal perforation^59,60 (D).

• 14.

  Lacrimal puncta occlusion improves symptoms and outcomes of ocular tear tests. This strategy is superior to lubricant eyedrops, and is indicated in severe cases refractory to topical treatment with eyedrops^61-65 (A).

Q7. What are the effectiveness and safety of muscarinic agonists and mucolytics in systemic symptomatic treatment of dryness?

• 15.

  Muscarinic agonists such as pilocarpine (5 mg bid, qid) and cevimeline (30 mg, tid), are more beneficial in the symptomatic treatment of dry mouth^66-69 (A), but they may also be useful in treating moderate to severe⁴¹ (D) dry eye^66,67,69-73 (A).

• 16.

  It is recommended that the dose and the range of pilocarpine be adjusted as tolerated^66,67 (A).

• 17.

  Although not available in Brazil, cevimeline is the safest muscarinic agonist, with lower rates of side effects and of treatment discontinuation, thanks to a more selective action on M3 receptors^74,75 (C).

• 18.

  The most frequent side effect of muscarinic agonists is sweating^69,72,74 (A). One should be aware of the contraindications for the use of muscarinic agonists, especially pilocarpine, in asthma and cardiac disease patients⁴¹ (D).

• 19.

  The mucolytic agent N-acetylcysteine, at a dose of 200 mg tid, may be an option for muscarinic agonists in patients with intolerance, and also in patients with dryness in other places, such as the skin, vagina and airways⁷⁶ (A).

Q8. What are the effectiveness and safety of supplementation with fatty acids in patients with SS?

• 20.

  Supplementation of fatty acids (omega-3) can be used, since this is a low-risk intervention and promotes the improvement of symptoms and of functional dry eye tests, although the results have been controversial in different studies^77-82 (A).

Part 3. Systemic treatment for glandular and systemic manifestations

Q9. What are the effectiveness and safety of hydroxychloroquine and immunosuppressants in the treatment of patients with SS?

• 21.

  There is no evidence of significant improvement in glandular symptoms with the use of hydroxychloroquine in SS. However, there is improvement of laboratory and inflammatory parameters^83-90 (A).

• 22.

  There is no evidence for the use of systemic immunosuppressants in treating symptoms of dryness. While some open and controlled studies have shown improvement in laboratory and inflammatory parameters, a high frequency of adverse events precluded their use for dry syndrome^91-98 (B).

• 23.

  The choice of immunosuppressive drug treatment for systemic manifestations will depend on the affected organ and severity⁶⁰ (D).

Q10. What are the effectiveness and safety of biologic therapies in the treatment of patients with SS?

• 24.

  Anti-TNF therapy is not indicated for the treatment of glandular or systemic manifestations of SS^99-102 (A).

• 25.

  Rituximab is effective in improving many manifestations in SS, as glandular involvement (A), fatigue (A), disease activity (C), immunological parameters (A), glandular lymphocytic infiltration, systemic manifestations, and quality of life^103-105 (C).

• 26.

  Rituximab is not indicated as sole treatment of the symptoms of dryness. This drug is a therapeutic option for systemic manifestations that failed conventional treatment^103-106 (C). By clinical criteria, in selected cases, rituximab can be considered for serious and specific glandular manifestations, such as refractory parotiditis⁶² (D).

• 27.

  Abatacept^106-109 (C) and belimumab¹¹⁰ (C) are promising drugs to improve disease activity, immunological profile and quality of life. These drugs can be considered in the treatment of SS in refractory cases and with high systemic disease activity.

Q11. What is the treatment of articular manifestations, myositis and fatigue in patients with SS?

• 28.

  Initial treatment of arthritis resulting from SS can be carried out with hydroxychloroquine, with or without low doses of glucocorticoids or NSAIDs for symptomatic relief⁸³ (C). In case of treatment failure with hydroxychloroquine, this drug can be replaced or associated with methotrexate^60,96 (D). In those rare refractory cases under an optimal methotrexate dosage, the use of rituximab is recommended¹⁰⁶ (C).

• 29.

  Myositis characterized by weakness, elevated creatine kinase (CK) and electroneuromyographic changes should initially be treated with prednisone. In those rare refractory cases, methotrexate is recommended (D).

• 30.

  Noninflammatory pattern arthralgia with diffuse pain in the absence of myositis should be treated as a painful amplification syndrome, with analgesia and exercise, with attention to the potential risk of worsening of dryness, caused by a pharmacological adverse effect (D).

• 31.

  The treatment of fatigue includes the prescription of aerobic exercise of moderate to high intensity ¹⁴ (B), and a proper management of the underlying disease. Different classes of drugs have been tested and have not proved to be effective or safer, because they have unacceptable rates of adverse events, such as dehydroepiandrosterone (DHEA)¹¹¹ (A), fatty acids⁸² (A), hydroxychloroquine^89,90 (A), azathioprine⁹⁴ (A), leflunomide⁹⁷ (A), mycophenolate⁹⁸(A) and anti-TNF agents¹⁰² (A). At the discretion of the clinician, rituximab^103-105,112 (A) may be a therapeutic option, considering the evidence of inflammation and the impact on functional capacity and quality of life.

Q12. What is the treatment of neurological manifestations in the peripheral nervous system in patients with SS?

• 32.

  For the treatment of PNS involvement, the combination of high-dose glucocorticoids (with subsequent tapering) and an immunosuppressant (azathioprine, cyclophosphamide, mycophenolate) is recommended^60,113,114 (C).

• 33.

  Patients with mononeuritis multiplex should start a scheme of intravenous methylprednisolone and cyclophosphamide¹¹³ (C).

• 34.

  Patients with ataxic polyneuropathy and sensory ganglioneuronopathy have poorer responses to all treatments¹¹³ (C). Therefore, for these patients, the association of IVIG to the therapeutic regimen with glucocorticoids and immunosuppressive drugs is recommended, in an attempt to achieve a better clinical response¹¹⁵ (C).

• 35.

  When no clinical improvement is observed in the initial treatment, rituximab is recommended¹¹⁶ (C). Patients with vasculitis and cryoglobulinemia have better responses to rituximab¹¹⁶ (C).

• 36.

  IVIG is a therapeutic option for all types of PNS involvement, when previous schemes failed^115,117,118 (C).

• 37.

  Plasmapheresis should be reserved for severe cases refractory to all previous measures, since no studies were published justifying its routine use¹¹⁹ (C).

Q13. What is the treatment of neurological manifestations in the central nervous system in patients with SS?

• 38.

  For the treatment of CNS involvement, a combination of glucocorticoids and cyclophosphamide at high doses is recommended^113,120-124 (C). In the face of no clinical improvement, rituximab is recommended^60,125 (C).

• 39.

  Subacute febrile aseptic meningitis can be treated initially solely with glucocorticoids, depending on the clinical condition¹²² (C).

Q14. What is the treatment of pulmonary (parenchymal and lower airways) manifestations in patients with SS?

• 40.

  In the presence of symptomatic interstitial pulmonary disorder, treatment with glucocorticoids plus an immunosuppressive agent (azathioprine or cyclophosphamide) is recommended^126-129 (C). Mycophenolate mofetil is an option in refractory cases or in those patients with contraindication to other immunosuppressive agents¹³⁰ (C). Rituximab may be considered in refractory cases of interstitial pneumonia, and overtreatment of fibrotic changes related to the sequel should be avoided¹⁰⁶ (C).

• 41.

  Bronchiolitis respiratory tract manifestations may be mild, justifying only the use of inhaled and/or systemic corticosteroid therapy¹³¹ (C). Immunosuppressive drugs should be according to specialist opinion⁶⁰ (D).

Q15. What is the treatment of glomerular and tubulointerstitial renal manifestations in patients with SS?

• 42.

  Considering clinician opinion high-dose glucocorticoids might be indicated, with or without association with other immunosuppressive agents^132-137 (C).

• 43.

  In GNs, intravenous methylprednisolone in association with cyclophosphamide is recommended^132,133 (C). Azathioprine and cyclosporine may be options in mild to moderate cases¹³² (C). Rituximab should be considered in refractory cases^106,132,137 (C).

Q16. What are the effectiveness and safety of drug therapy in the treatment of vasculitis in patients with SS?

• 44.

  The recommended treatment for vasculitis, regardless of the organ involved, is immunosuppression with high-dose intravenous methylprednisolone for three days, in combination with immunosuppressants (azathioprine, mycophenolate mofetil, or cyclophosphamide); cyclophosphamide has been the most commonly used immunosuppressant^138-141 (C). Treatment of cutaneous vasculitis may be initially carried out with an oral glucocorticoid (0.5-1 mg/kg/day) or with intravenous methylprednisolone (depending on the severity of the condition) plus an immunosuppressant. Cases refractory to initial treatment can be treated with rituximab^142,143 (C).

• Funding
  Brazilian Society of Rheumatology.
• ☆
  Study conducted at Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology.

Acknowledgements

The authors acknowledge Walber Vieira Pinto (President of SBR in the biennium 2012-2014) and César Emile Baaklini (President of SBR in the biennium 2014-2016), for supporting the development of these guidelines.

Referências

• ¹
  Garcia-Carrasco M, Ramos-Casals M, Rosas J, Pallares L, Calvo-Alen J, Cervera R, et al. Primary Sjogren's syndrome: clinical and immunologic disease patterns in a cohort of 400 patients. Medicine. 2002;81:270-80.
• ²
  Valim V, Zandonade E, Pereira AM, de Brito Filho OH, Serrano EV, Musso C, et al. Primary Sjogren's syndrome prevalence in a major metropolitan area in Brazil. Revista Brasileira de Reumatologia. 2013;53:24-34.
• ³
  Haga HJ, Naderi Y, Moreno AM, Peen E. A study of the prevalence of sicca symptoms and secondary Sjogren's syndrome in patients with rheumatoid arthritis, and its association to disease activity and treatment profile. International Journal of Rheumatic Diseases. 2012;15:284-8.
• ⁴
  Kosrirukvongs P, Ngowyutagon P, Pusuwan P, Koolvisoot A, Nilganuwong S. Prevalence of dry eye syndrome and Sjogren's syndrome in patients with rheumatoid arthritis. Journal of the Medical Association of Thailand=Chotmaihet thangphaet. 2012;95:S61-S9.
• ⁵
  Baldini C, Tavoni A, Merlini G, Sebastiani M, Bombardieri S. Primary Sjogren's syndrome: clinical and serological feature of a single centre. Reumatismo. 2005;57:256-61.
• ⁶
  Szodoray P, Alex P, Jonsson MV, Knowlton N, Dozmorov I, Nakken B, et al. Distinct profiles of Sjogren's syndrome patients with ectopic salivary gland germinal centers revealed by serum cytokines and BAFF. Clinical Immunology. 2005;117:168-76.
• ⁷
  Reksten TR, Jonsson MV, Szyszko EA, Brun JG, Jonsson R, Brokstad KA. Cytokine and autoantibody profiling related to histopathological features in primary Sjogren's syndrome. Rheumatology. 2009;48:1102-6.
• ⁸
  Reksten TR, Johnsen SJ, Jonsson MV, Omdal R, Brun JG, Theander E, et al. Genetic associations to germinal centre formation in primary Sjogren's syndrome. Annals of the rheumatic diseases. 2014;73:1253-8.
• ⁹
  Jonsson MV, Theander E, Jonsson R. Predictors for the development of non-Hodgkin lymphoma in primary Sjogren's syndrome. Presse Medicale. 2012;41 9 Pt 2:e511–6
• ¹⁰
  Theander E, Vasaitis L, Baecklund E, Nordmark G, Warfvinge G, Liedholm R, et al. Lymphoid organisation in labial salivary gland biopsies is a possible predictor for the development of malignant lymphoma in primary Sjogren's syndrome. Annals of the Rheumatic Diseases. 2011;70:1363-8.
• ¹¹
  Seror R, Bootsma H, Saraux A, Bowman SJ, Theander E, Brun JG, et al. Defining disease activity states and clinically meaningful improvement in primary Sjogren's syndrome with Eular Sjogren's Syndrome Disease Activity Index (Essdai) and patient-reported indexes (Esspri). Annals of the Rheumatic Diseases. 2014.
• ¹²
  Serrano EV, Valim V, Miyamoto ST, Giovelli RA, Paganotti MA, Cade NV. Transcultural adaptation of the Eular Sjogren's Syndrome Disease Activity Index (Essdai) into Brazilian Portuguese. Revista Brasileira de Reumatologia. 2013;53:483-93.
• ¹³
  Strombeck B, Ekdahl C, Manthorpe R, Jacobsson LT. Physical capacity in women with primary Sjogren's syndrome: a controlled study. Arthritis and Rheumatism. 2003;49:681-8.
• ¹⁴
  Strombeck BE, Theander E, Jacobsson LT. Effects of exercise on aerobic capacity and fatigue in women with primary Sjogren's syndrome. Rheumatology. 2007;46:868-71.
• ¹⁵
  van Assen S, Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Annals of the Rheumatic Diseases. 2011;70:414-22.
• ¹⁶
  Pasoto SG, Ribeiro AC, Viana VS, Leon EP, Bueno C, Neto ML, et al. Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on clinical manifestations and autoantibody profile in primary Sjogren's syndrome. Vaccine. 2013;31:1793-8.
• ¹⁷
  Milanovic M, Stojanovich L, Djokovic A, Kontic M, Gvozdenovic E. Influenza vaccination in autoimmune rheumatic disease patients. The Tohoku Journal of Experimental Medicine. 2013;229:29-34.
• ¹⁸
  Karsh J, Pavlidis N, Schiffman G, Moutsopoulos HM. Immunization of patients with Sjogren's syndrome with pneumococcal polysaccharide vaccine: a randomized trial. Arthritis and Rheumatism. 1980;23:1294-8.
• ¹⁹
  Muller K, Oxholm P, Sorensen OH, Thymann M, Hoier-Madsen M, Bendtzen K. Abnormal vitamin D3 metabolism in patients with primary Sjogren's syndrome. Annals of the Rheumatic Diseases. 1990;49:682-4.
• ²⁰
  Erten S, Sahin A, Altunoglu A, Gemcioglu E, Koca C. Comparison of plasma vitamin D levels in patients with Sjogren's syndrome and healthy subjects. International Journal of Rheumatic Diseases. 2014;18:70-5.
• ²¹
  Baldini C, Delle Sedie A, Luciano N, Pepe P, Ferro F, Talarico R, et al. Vitamin D in “early” primary Sjogren's syndrome: does it play a role in influencing disease phenotypes?. Rheumatology International. 2014;34:1159-64.
• ²²
  Liao CY, Wang CC, Chen IH, Shiang JC, Liu MY, Tsai MK. Hypokalemic paralysis as a presenting manifestation of primary Sjogren's syndrome accompanied by vitamin D deficiency. Internal Medicine. 2013;52:2351-53.
• ²³
  Agmon-Levin N, Kivity S, Tzioufas AG, Lopez Hoyos M, Rozman B, Efes I, et al. Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sjogren's syndrome. Journal of Autoimmunity. 2012;39:234-9.
• ²⁴
  Aliko A, Alushi A, Tafaj A, Isufi R. Evaluation of the clinical efficacy of Biotene Oral Balance in patients with secondary Sjogren's syndrome: a pilot study. Rheumatology International. 2012;32:2877-81.
• ²⁵
  Alpöz E, Guneri P, Onder G, Cankaya H, Kabasakal Y, Kose T. The efficacy of Xialine in patients with Sjogren's syndrome: a single-blind, cross-over study. Clinical Oral Investigations. 2008;12:165-72.
• ²⁶
  Frost PM, Shirlaw PJ, Challacombe SJ, Fernandes-Naglik L, Walter JD, Ide M. Impact of wearing an intra-oral lubricating device on oral health in dry mouth patients. Oral Diseases. 2006;12:57-62.
• ²⁷
  Alves MB, Motta AC, Messina WC, Migliari DA. Saliva substitute in xerostomic patients with primary Sjogren's syndrome: a single-blind trial. Quintessence International. 2004;35:392-6.
• ²⁸
  Johansson G, Andersson G, Edwardsson S, Bjorn AL, Manthorpe R, Attstrom R. Effects of mouthrinses with linseed extract Salinum without/with chlorhexidine on oral conditions in patients with Sjogren's syndrome. A double-blind crossover investigation. Gerodontology. 2001;18:87-94.
• ²⁹
  Rhodus NL, Bereuter J. Clinical evaluation of a commercially available oral moisturizer in relieving signs and symptoms of xerostomia in postirradiation head and neck cancer patients and patients with Sjogren's syndrome. The Journal of Otolaryngology. 2000;29:28-34.
• ³⁰
  van der Reijden WA, van der Kwaak H, Vissink A, Veerman EC, Amerongen AV. Treatment of xerostomia with polymer-based saliva substitutes in patients with Sjogren's syndrome. Arthritis and Rheumatism. 1996;39:57-63.
• ³¹
  Visch LL, Gravenmade EJ, Schaub RM, Van Putten WL, Vissink A. A double-blind crossover trial of CMC- and mucin-containing saliva substitutes. International Journal of Oral and Maxillofacial Surgery. 1986;15:395-400.
• ³²
  Furness S, Worthington HV, Bryan G, Birchenough S, McMillan R. Interventions for the management of dry mouth: topical therapies. The Cochrane Database of Systematic Reviews. 2011:CD340089.
• ³³
  da Silva Marques DN, da Mata AD, Patto JM, Barcelos FA, de Almeida Rato Amaral JP, de Oliveira MC, et al. Effects of gustatory stimulants of salivary secretion on salivary pH and flow in patients with Sjogren's syndrome: a randomized controlled trial. Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2011;40:785-92.
• ³⁴
  Aragona P, Rania L, Roszkowska AM, Spinella R, Postorino E, Puzzolo D, et al. Effects of amino acids enriched tears substitutes on the cornea of patients with dysfunctional tear syndrome. Acta Ophthalmologica. 2013;91:e437-44.
• ³⁵
  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. Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht von Graefes Archiv fur Klinische und Experimentelle Ophthalmologie. 2005;243:531-8.
• ³⁶
  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. 2002;16:601-7.
• ³⁷
  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 Sjogren's syndrome patients. The British Journal of Ophthalmology. 2002;86:879-84.
• ³⁸
  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. The British Journal of Ophthalmology. 2002;86:181-4.
• ³⁹
  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. The British Journal of Ophthalmology. 1999;83:1121-4.
• ⁴⁰
  Toda I, Shinozaki N, Tsubota K. Hydroxypropyl methylcellulose for the treatment of severe dry eye associated with Sjogren's syndrome. Cornea. 1996;15:120-8.
• ⁴¹
  Valim V, Trevisani VF, de Sousa JM, Vilela VS, Belfort R Jr. Current Approach to Dry Eye Disease. Clinical Reviews in Allergy & Immunology. 2014
• ⁴²
  Schultz C. Safety and efficacy of cyclosporine in the treatment of chronic dry eye. Ophthalmology and Eye Diseases. 2014;6:37-42.
• ⁴³
  Alves M, Fonseca EC, Alves MF, Malki LT, Arruda GV, Reinach PS, et al. Dry eye disease treatment: a systematic review of published trials and a critical appraisal of therapeutic strategies. The Ocular Surface. 2013;11:181-92.
• ⁴⁴
  Zhou XQ, Wei RL. Topical cyclosporine A in the treatment of dry eye: a systematic review and meta-analysis. Cornea. 2014;33:760-7.
• ⁴⁵
  Sall K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology. 2000;107:631-9.
• ⁴⁶
  Sall KN, Cohen SM, Christensen MT, Stein JM. An evaluation of the efficacy of a cyclosporine-based dry eye therapy when used with marketed artificial tears as supportive therapy in dry eye. Eye & Contact Lens. 2006;32:21-6.
• ⁴⁷
  Deveci H, Kobak S. The efficacy of topical 0.05% cyclosporine A in patients with dry eye disease associated with Sjogren's syndrome. International Ophthalmology. 2014;34:1043-8.
• ⁴⁸
  Demiryay E, Yaylali V, Cetin EN, Yildirim C. Effects of topical cyclosporine a plus artificial tears versus artificial tears treatment on conjunctival goblet cell density in dysfunctional tear syndrome. Eye & Contact Lens. 2011;37:312-5.
• ⁴⁹
  Su MY, Perry HD, Barsam A, Perry AR, Donnenfeld ED, Wittpenn JR, et al. The effect of decreasing the dosage of cyclosporine A 0.05% on dry eye disease after 1 year of twice-daily therapy. Cornea. 2011;30:1098-104.
• ⁵⁰
  Baiza-Duran L, Medrano-Palafox J, Hernandez-Quintela E, Lozano-Alcazar J. Alaniz-de la OJ. A comparative clinical trial of the efficacy of two different aqueous solutions of cyclosporine for the treatment of moderate-to-severe dry eye syndrome. The British Journal of Ophthalmology. 2010;94:1312-5.
• ⁵¹
  Kim EC, Choi JS, Joo CK. A comparison of vitamin a and cyclosporine a 0.05% eye drops for treatment of dry eye syndrome. American Journal of Ophthalmology. 2009;147:e3, 206-13.
• ⁵²
  Roberts CW, Carniglia PE, Brazzo BG. Comparison of topical cyclosporine, punctal occlusion, and a combination for the treatment of dry eye. Cornea. 2007;26:805-9.
• ⁵³
  Barber LD, Pflugfelder SC, Tauber J, Foulks GN, Phase III. safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years. Ophthalmology. 2005;112:1790-4.
• ⁵⁴
  Kunert KS, Tisdale AS, Stern ME, Smith JA, Gipson IK. Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Archives of Ophthalmology. 2000;118:1489-96.
• ⁵⁵
  Stevenson D, Tauber J, Reis BL. Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-severe dry eye disease: a dose-ranging, randomized trial. The Cyclosporin A Phase 2 Study Group Ophthalmology. 2000;107:967-74.
• ⁵⁶
  Günduz K, Ozdemir O. Topical cyclosporin treatment of keratoconjunctivitis sicca in secondary Sjogren's syndrome. Acta Ophthalmol (Copenh). 1994;72:438-42.
• ⁵⁷
  Serra MSDLM, Simon Castellvi C, Kabbani O. Nonpreserved topical steroids and lacrimal punctal occlusion for severe keratoconjunctivitis sicca. Archivos de la Sociedad Española de Oftalmologia. 2000;75:751-6.
• ⁵⁸
  Aragona P, Spinella R, Rania L, Postorino E, Sommario MS, Roszkowska AM, et al. Safety and efficacy of 0.1% clobetasone butyrate eyedrops in the treatment of dry eye in Sjogren syndrome. European Journal of Ophthalmology. 2013;23:368-76.
• ⁵⁹
  Aragona P, Stilo A, Ferreri F, Mobrici M. Effects of the topical treatment with NSAIDs on corneal sensitivity and ocular surface of Sjogren's syndrome patients. Eye. 2005;19:535-9.
• ⁶⁰
  Ramos-Casals M, Brito-Zeron P, Siso-Almirall A, Bosch X, Tzioufas AG. Topical and systemic medications for the treatment of primary Sjogren's syndrome. Nature Reviews Rheumatology. 2012;8:399-411.
• ⁶¹
  Ervin AM, Wojciechowski R, Schein O. Punctal occlusion for dry eye syndrome. The Cochrane Database of Systematic Reviews. 2010:CD750067
• ⁶²
  Farrell J, Patel S, Grierson DG, Sturrock RD. A clinical procedure to predict the value of temporary occlusion therapy in keratoconjunctivitis sicca. Ophthalmic & Physiological Optics: the Journal of the British College of Ophthalmic Opticians. 2003;23:1-8.
• ⁶³
  Qiu W, Liu Z, Ao M, Li X, Wang W. Punctal plugs versus artificial tears for treating primary Sjogren's syndrome with keratoconjunctivitis sicca: a comparative observation of their effects on visual function. Rheumatology International. 2013;33:2543-8.
• ⁶⁴
  Holzchuh R, Villa Albers MB, Osaki TH, Igami TZ, Santo RM, Kara-Jose N, et al. Two-year outcome of partial lacrimal punctal occlusion in the management of dry eye related to Sjogren's syndrome. Current Eye Research. 2011;36:507-12.
• ⁶⁵
  Mansour K, Leonhardt CJ, Kalk WW, Bootsma H, Bruin KJ, Blanksma LJ, et al. Lacrimal punctum occlusion in the treatment of severe keratoconjunctivitis sicca caused by Sjogren's syndrome: a uniocular evaluation. Cornea. 2007;26:147-50.
• ⁶⁶
  Vivino FB, Al-Hashimi I, Khan Z, LeVeque FG, Salisbury PL 3rd, Tran-Johnson TK, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjogren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group. Archives of Internal Medicine. 1999;159:174-81.
• ⁶⁷
  Papas AS, Sherrer YS, Charney M, Golden HE, Medsger TA Jr, Walsh BT, et al. Successful treatment of dry mouth and dry eye symptoms in Sjogren's syndrome patients with oral pilocarpine: a randomized, placebo-controlled, dose-adjustment study. Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases. 2004;10:169-77.
• ⁶⁸
  Wu CH, Hsieh SC, Lee KL, Li KJ, Lu MC, Yu CL. Pilocarpine hydrochloride for the treatment of xerostomia in patients with Sjogren's syndrome in Taiwan – a double-blind, placebo-controlled trial. Journal of the Formosan Medical Association = Taiwan yi zhi. 2006;105:796-803.
• ⁶⁹
  Petrone D, Condemi JJ, Fife R, Gluck O, Cohen S, Dalgin P. A double-blind, randomized, placebo-controlled study of cevimeline in Sjogren's syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis and Rheumatism. 2002;46:748-54.
• ⁷⁰
  Tsifetaki N, Kitsos G, Paschides CA, Alamanos Y, Eftaxias V, Voulgari PV, et al. Oral pilocarpine for the treatment of ocular symptoms in patients with Sjogren's syndrome: a randomised 12 week controlled study. Annals of the Rheumatic Diseases. 2003;62:1204-7.
• ⁷¹
  Leung KC, McMillan AS, Wong MC, Leung WK, Mok MY, Lau CS. The efficacy of cevimeline hydrochloride in the treatment of xerostomia in Sjogren's syndrome in southern Chinese patients: a randomised double-blind, placebo-controlled crossover study. Clinical Rheumatology. 2008;27:429-36.
• ⁷²
  Fife RS, Chase WF, Dore RK, Wiesenhutter CW, Lockhart PB, Tindall E, et al. Cevimeline for the treatment of xerostomia in patients with Sjogren's syndrome: a randomized trial. Archives of Internal Medicine. 2002;162:1293-1300.
• ⁷³
  Ono M, Takamura E, Shinozaki K, Tsumura T, Hamano T, Yagi Y, et al. Therapeutic effect of cevimeline on dry eye in patients with Sjogren's syndrome: a randomized, double-blind clinical study. American Journal of Ophthalmology. 2004;138:6-17.
• ⁷⁴
  Noaiseh G, Baker JF, Vivino FB. Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjogren's syndrome. Clinical and Experimental Rheumatology. 2014;32:575-7.
• ⁷⁵
  Brimhall J, Jhaveri MA, Yepes JF. Efficacy of cevimeline vs. pilocarpine in the secretion of saliva: a pilot study. Special Care in Dentistry: Official Publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2013;33:123-7.
• ⁷⁶
  Walters MT, Rubin CE, Keightley SJ, Ward CD, Cawley MI. A double-blind, cross-over, study of oral N-acetylcysteine in Sjogren's syndrome. Scandinavian Journal of Rheumatology Supplement. 1986;61:253-8.
• ⁷⁷
  Manthorpe R, Hagen Petersen S, Prause JU. Primary Sjogren's syndrome treated with Efamol/Efavit. A double-blind cross-over investigation. Rheumatology International. 1984;4:165-7.
• ⁷⁸
  Oxholm P, Manthorpe R, Prause JU, Horrobin D. Patients with primary Sjogren's syndrome treated for two months with evening primrose oil. Scandinavian Journal of Rheumatology. 1986;15:103-8.
• ⁷⁹
  Aragona P, Bucolo C, Spinella R, Giuffrida S, Ferreri G. Systemic omega-6 essential fatty acid treatment and pge1 tear content in Sjogren's syndrome patients. Investigative Ophthalmology & Visual Science. 2005;46:4474-9.
• ⁸⁰
  Pinheiro MN Jr, dos Santos PM, dos Santos RC, Barros Jde N, Passos LF, Cardoso Neto J. Oral flaxseed oil (Linum usitatissimum) in the treatment for dry-eye Sjogren's syndrome patients. Arquivos Brasileiros de Oftalmologia. 2007;70:649-55.
• ⁸¹
  Singh M, Stark PC, Palmer CA, Gilbard JP, Papas AS. Effect of omega-3 and vitamin E supplementation on dry mouth in patients with Sjogren's syndrome. Special Care in Dentistry: Official Publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2010;30:225-9.
• ⁸²
  Theander E, Horrobin DF, Jacobsson LT, Manthorpe R. Gammalinolenic acid treatment of fatigue associated with primary Sjogren's syndrome. Scandinavian Journal of Rheumatology. 2002;31:72-9.
• ⁸³
  Tishler M, Yaron I, Shirazi I, Yaron M. Hydroxychloroquine treatment for primary Sjogren's syndrome: its effect on salivary and serum inflammatory markers. Annals of the Rheumatic Diseases. 1999;58:253-6.
• ⁸⁴
  Rihl M, Ulbricht K, Schmidt RE, Witte T. Treatment of sicca symptoms with hydroxychloroquine in patients with Sjogren's syndrome. Rheumatology. 2009;48:796-9.
• ⁸⁵
  Fox RI, Dixon R, Guarrasi V, Krubel S. Treatment of primary Sjogren's syndrome with hydroxychloroquine: a retrospective, open-label study. Lupus. 1996;5:S31-6.
• ⁸⁶
  Cankaya H, Alpoz E, Karabulut G, Guneri P, Boyacioglu H, Kabasakal Y. Effects of hydroxychloroquine on salivary flow rates and oral complaints of Sjogren's patients: a prospective sample study. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2010;110:62-7.
• ⁸⁷
  Yavuz S, Asfuroglu E, Bicakcigil M, Toker E. Hydroxychloroquine improves dry eye symptoms of patients with primary Sjogren's syndrome. Rheumatology International. 2011;31:1045-9.
• ⁸⁸
  Fox RI, Chan E, Benton L, Fong S, Friedlaender M, Howell FV. Treatment of primary Sjogren's syndrome with hydroxychloroquine. The American Journal of Medicine. 1988;85(4A):62-7.
• ⁸⁹
  Kruize AA, Hene RJ, Kallenberg CG, van Bijsterveld OP, van der Heide A, Kater L, et al. Hydroxychloroquine treatment for primary Sjogren's syndrome: a two year double blind crossover trial. Annals of the Rheumatic Diseases. 1993;52:360-4.
• ⁹⁰
  Gottenberg JE, Ravaud P, Puechal X, Le Guern V, Sibilia J, Goeb V, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjogren's syndrome: the JOQUER randomized clinical trial. Jama. 2014;312:249-58.
• ⁹¹
  Fox PC, Datiles M, Atkinson JC, Macynski AA, Scott J, Fletcher D, et al. Prednisone and piroxicam for treatment of primary Sjogren's syndrome. Clinical and Experimental Rheumatology. 1993;11:149-56.
• ⁹²
  Pijpe J, Kalk WW, Bootsma H, Spijkervet FK, Kallenberg CG, Vissink A. Progression of salivary gland dysfunction in patients with Sjogren's syndrome. Annals of the Rheumatic Diseases. 2007;66:107-12.
• ⁹³
  Miyawaki S, Nishiyama S, Matoba K. Efficacy of low-dose prednisolone maintenance for saliva production and serological abnormalities in patients with primary Sjogren's syndrome. Internal Medicine. 1999;38:938-43.
• ⁹⁴
  Price EJ, Rigby SP, Clancy U, Venables PJ. A double blind placebo controlled trial of azathioprine in the treatment of primary Sjogren's syndrome. The Journal of Rheumatology. 1998;25:896-9.
• ⁹⁵
  Drosos AA, Skopouli FN, Galanopoulou VK, Kitridou RC, Moutsopoulos HM. Cyclosporin a therapy in patients with primary Sjogren's syndrome: results at one year. Scandinavian Journal of Rheumatology Supplement. 1986;61:246-9.
• ⁹⁶
  Skopouli FN, Jagiello P, Tsifetaki N, Moutsopoulos HM. Methotrexate in primary Sjogren's syndrome. Clinical and Experimental Rheumatology. 1996;14:555-8.
• ⁹⁷
  van Woerkom JM, Kruize AA, Geenen R, van Roon EN, Goldschmeding R, Verstappen SM, et al. Safety and efficacy of leflunomide in primary Sjogren's syndrome: a phase II pilot study. Annals of the Rheumatic Diseases. 2007;66:1026-32.
• ⁹⁸
  Willeke P, Schluter B, Becker H, Schotte H, Domschke W, Gaubitz M. Mycophenolate sodium treatment in patients with primary Sjogren syndrome: a pilot trial. Arthritis Research & Therapy. 2007;9:R115.
• ⁹⁹
  Moutsopoulos NM, Katsifis GE, Angelov N, Leakan RA, Sankar V, Pillemer S, et al. Lack of efficacy of etanercept in Sjogren syndrome correlates with failed suppression of tumour necrosis factor alpha and systemic immune activation. Annals of the Rheumatic Diseases. 2008;67:1437-43.
• ¹⁰⁰
  Mavragani CP, Niewold TB, Moutsopoulos NM, Pillemer SR, Wahl SM, Crow MK. Augmented interferon-alpha pathway activation in patients with Sjogren's syndrome treated with etanercept. Arthritis and Rheumatism. 2007;56:3995-4004.
• ¹⁰¹
  Sankar V, Brennan MT, Kok MR, Leakan RA, Smith JA, Manny J, et al. Etanercept in Sjogren's syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial. Arthritis and Rheumatism. 2004;50:2240-5.
• ¹⁰²
  Mariette X, Ravaud P, Steinfeld S, Baron G, Goetz J, Hachulla E, et al. Inefficacy of infliximab in primary Sjogren's syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjogren's Syndrome (Tripss). Arthritis and Rheumatism. 2004;50:1270-6.
• ¹⁰³
  Dass S, Bowman SJ, Vital EM, Ikeda K, Pease CT, Hamburger J, et al. Reduction of fatigue in Sjogren's syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study. Annals of the Rheumatic Diseases. 2008;67:1541-4.
• ¹⁰⁴
  Meijer JM, Meiners PM, Vissink A, Spijkervet FK, Abdulahad W, Kamminga N, et al. Effectiveness of rituximab treatment in primary Sjogren's syndrome: a randomized, double-blind, placebo-controlled trial. Arthritis and Rheumatism. 2010;62:960-8.
• ¹⁰⁵
  Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, Berthelot JM, Perdriger A, Puechal X, et al. Treatment of primary Sjogren's syndrome with rituximab: a randomized trial. Annals of Internal Medicine. 2014;160:233-42.
• ¹⁰⁶
  Gottenberg JE, Cinquetti G, Larroche C, Combe B, Hachulla E, Meyer O, et al. Efficacy of rituximab in systemic manifestations of primary Sjogren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Annals of the Rheumatic Diseases. 2013;72:1026-31.
• ¹⁰⁷
  Adler S, Korner M, Forger F, Huscher D, Caversaccio MD, Villiger PM. Evaluation of histologic, serologic, and clinical changes in response to abatacept treatment of primary Sjogren's syndrome: a pilot study. Arthritis Care & Research. 2013;65:1862-8.
• ¹⁰⁸
  Meiners PM, Vissink A, Kroese FG, Spijkervet FK, Smitt-Kamminga NS, Abdulahad WH, et al. Abatacept treatment reduces disease activity in early primary Sjogren's syndrome (open-label proof of concept ASAP study). Annals of the Rheumatic Diseases. 2014;73:1393-6.
• ¹⁰⁹
  Tsuboi H, Matsumoto I, Hagiwara S, Hirota T, Takahashi H, Ebe H, et al. Efficacy and safety of abatacept for patients with Sjogren's syndrome associated with rheumatoid arthritis: Rheumatoid Arthritis with Orencia Trial toward Sjogren's syndrome Endocrinopathy (ROSE) trial-an open-label, one-year, prospective study-Interim analysis of 32 patients for 24 weeks. Modern Rheumatology/The Japan Rheumatism Association. 2014:1-7.
• ¹¹⁰
  Mariette X, Seror R, Quartuccio L, Baron G, Salvin S, Fabris M, et al. Efficacy and safety of belimumab in primary Sjogren's syndrome: results of the Beliss open-label phase II study. Annals of the Rheumatic Diseases. 2013.
• ¹¹¹
  Hartkamp A, Geenen R, Godaert GL, Bootsma H, Kruize AA, Bijlsma JW, et al. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren's syndrome: a randomised controlled trial. Annals of the Rheumatic Diseases. 2008;67:91-7.
• ¹¹²
  Carubbi F, Cipriani P, Marrelli A, Benedetto P, Ruscitti P, Berardicurti O, et al. Efficacy and safety of rituximab treatment in early primary Sjogren's syndrome: a prospective, multi-center, follow-up study. Arthritis Research & Therapy. 2013;15:R172.
• ¹¹³
  Delalande S, de Seze J, Fauchais AL, Hachulla E, Stojkovic T, Ferriby D, et al. Neurologic manifestations in primary Sjogren's syndrome: a study of 82 patients. Medicine. 2004;83:280-91.
• ¹¹⁴
  Danieli MG, Pettinari L, Morariu R, Monteforte F, Logullo F. Intravenous immunoglobulin and mycophenolate mofetil for long-standing sensory neuronopathy in Sjogren's syndrome. Case Reports in Immunology. 2012, 201863.
• ¹¹⁵
  Rist S, Sellam J, Hachulla E, Sordet C, Puechal X, Hatron PY, et al. Experience of intravenous immunoglobulin therapy in neuropathy associated with primary Sjogren's syndrome: a national multicentric retrospective study. Arthritis Care & Research. 2011;63:1339-44.
• ¹¹⁶
  Mekinian A, Ravaud P, Hatron PY, Larroche C, Leone J, Gombert B, et al. Efficacy of rituximab in primary Sjogren's syndrome with peripheral nervous system involvement: results from the AIR registry. Annals of the Rheumatic Diseases. 2012;71:84-7.
• ¹¹⁷
  Mori K, Iijima M, Koike H, Hattori N, Tanaka F, Watanabe H, et al. The wide spectrum of clinical manifestations in Sjogren's syndrome-associated neuropathy. Brain: a Journal of Neurology. 2005;128:518-34, 2.
• ¹¹⁸
  Morozumi S, Kawagashira Y, Iijima M, Koike H, Hattori N, Katsuno M, et al. Intravenous immunoglobulin treatment for painful sensory neuropathy associated with Sjogren's syndrome. Journal of the Neurological Sciences. 2009;279:57-61.
• ¹¹⁹
  Chen WH, Yeh JH, Chiu HC. Plasmapheresis in the treatment of ataxic sensory neuropathy associated with Sjogren's syndrome. European Neurology. 2001;45:270-4.
• ¹²⁰
  Tobon GJ, Pers JO, Devauchelle-Pensec V, Youinou P. Neurological disorders in primary Sjogren's syndrome. Autoimmune Diseases. 2012;2012:676459.
• ¹²¹
  Lafitte C, Amoura Z, Cacoub P, Pradat-Diehl P, Picq C, Salachas F, et al. Neurological complications of primary Sjogren's syndrome. Journal of Neurology. 2001;248:577-84.
• ¹²²
  Rossi R, Valeria Saddi M. Subacute aseptic meningitis as neurological manifestation of primary Sjogren's syndrome. Clinical Neurology and Neurosurgery. 2006;108:688-91.
• ¹²³
  Santosa A, Lim AY, Vasoo S, Lau TC, Teng GG. Neurosjogren: early therapy is associated with successful outcomes. Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases. 2012;18:389-92.
• ¹²⁴
  de Seze J, Delalande S, Fauchais AL, Hachulla E, Stojkovic T, Ferriby D, et al. Myelopathies secondary to Sjogren's syndrome: treatment with monthly intravenous cyclophosphamide associated with corticosteroids. The Journal of Rheumatology. 2006;33:709-11.
• ¹²⁵
  Mekinian A, Ravaud P, Larroche C, Hachulla E, Gombert B, Blanchard-Delaunay C, et al. Rituximab in central nervous system manifestations of patients with primary Sjogren's syndrome: results from the AIR registry. Clinical and Experimental Rheumatology. 2012;30:208-12.
• ¹²⁶
  Deheinzelin D, Capelozzi VL, Kairalla RA, Barbas Filho JV, Saldiva PH, de Carvalho CR. Interstitial lung disease in primary Sjogren's syndrome. Clinical-pathological evaluation and response to treatment. American Journal of Respiratory and Critical Care Medicine. 1996;154:794-9.
• ¹²⁷
  Parambil JG, Myers JL, Lindell RM, Matteson EL, Ryu JH. Interstitial lung disease in primary Sjogren's syndrome. Chest. 2006;130:1489-95.
• ¹²⁸
  Zhang L, Mo H, Zhu M, Wang L. Effect of cyclophosphamide on cytokines in patients with primary Sjogren's syndrome-associated interstitial lung disease in South China. Rheumatology International. 2013;33:1403-7.
• ¹²⁹
  Shi JH, Liu HR, Xu WB, Feng RE, Zhang ZH, Tian XL, et al. Pulmonary manifestations of Sjogren's syndrome. Respiration. International Review of Thoracic Diseases. 2009;78:377-86.
• ¹³⁰
  Fischer A, Brown KK, Du Bois RM, Frankel SK, Cosgrove GP, Fernandez-Perez ER, et al. Mycophenolate mofetil improves lung function in connective tissue disease-associated interstitial lung disease. The Journal of Rheumatology. 2013;40:640-6.
• ¹³¹
  Borie R, Schneider S, Debray MP, Adle-Biasssette H, Danel C, Bergeron A, et al. Severe chronic bronchiolitis as the presenting feature of primary Sjogren's syndrome. Respiratory Medicine. 2011;105:130-6.
• ¹³²
  Goules AV, Tatouli IP, Moutsopoulos HM, Tzioufas AG. Clinically significant renal involvement in primary Sjogren's syndrome: clinical presentation and outcome. Arthritis and Rheumatism. 2013;65:2945-53.
• ¹³³
  Kaufman I, Schwartz D, Caspi D, Paran D. Sjogren's syndrome – not just Sicca: renal involvement in Sjogren's syndrome. Scandinavian Journal of Rheumatology. 2008;37:213-8.
• ¹³⁴
  Ren H, Wang WM, Chen XN, Zhang W, Pan XX, Wang XL, et al. Renal involvement and followup of 130 patients with primary Sjogren's syndrome. The Journal of Rheumatology. 2008;35:278-84.
• ¹³⁵
  Yamamoto S, Okada Y, Mori H, Hirata S, Saito K, Inokuchi N, et al. Successful treatment of osteomalacia caused by renal tubular acidosis associated with Sjogren's syndrome. Modern Rheumatology/The Japan Rheumatism Association. 2013;23:401-5.
• ¹³⁶
  Yilmaz H, Kaya M, Ozbek MK, Safa Yildirim UUI. Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular acidosis. Rheumatology International. 2013;33:1879-82.
• ¹³⁷
  Maripuri S, Grande JP, Osborn TG, Fervenza FC, Matteson EL, Donadio JV, et al. Renal involvement in primary Sjogren's syndrome: a clinicopathologic study. Clinical Journal of the American Society of Nephrology: CJASN. 2009;4:1423-31.
• ¹³⁸
  Hasiloglu ZI, Albayram S, Tasmali K, Erer B, Selcuk H, Islak C. A case of primary Sjogren's syndrome presenting primarily with central nervous system vasculitic involvement. Rheumatology International. 2012;32:805-7.
• ¹³⁹
  Tsai TC, Chen CY, Lin WT, Lee WJ, Chen HC. Sjogren's syndrome complicated with IgA nephropathy and leukocytoclastic vasculitis. Renal Failure. 2008;30:755-8.
• ¹⁴⁰
  Cardoso R, Goncalo M, Tellechea O, Maia R, Borges C, Silva JA, et al. Livedoid vasculopathy and hypercoagulability in a patient with primary Sjogren's syndrome. International Journal of Dermatology. 2007;46:431-4.
• ¹⁴¹
  Golan TD, Keren D, Elias N, Naschitz JE, Toubi E, Misselevich I, et al. Severe reversible cardiomyopathy associated with systemic vasculitis in primary Sjogren's syndrome. Lupus. 1997;6:505-8.
• ¹⁴²
  Gottenberg JE, Guillevin L, Lambotte O, Combe B, Allanore Y, Cantagrel A, et al. Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Annals of the Rheumatic Diseases. 2005;64:913-20.
• ¹⁴³
  Ramos-Casals M, Garcia-Hernandez FJ, de Ramon E, Callejas JL, Martinez-Berriotxoa A, Pallares L, et al. Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. Clinical and Experimental Rheumatology. 2010;28:468-76.

Publication Dates

• Publication in this collection
  Sep-Oct 2015

History

• Received
  29 Mar 2015
• Received
  23 July 2015