Rheumatoid arthritis dry mouth

Rheumatoid Arthritis and Sjögren’s Syndrome: Understanding the Link

Rheumatoid arthritis (RA) is frustrating enough on its own. But about 15 percent of people with RA develop a complication that affects the tear and saliva glands, causing dry mouth, dry eyes, dry skin, and additional symptoms that further aggravate their arthritis. It’s called Sjögren’s syndrome (SS).

Sjögren’s Syndrome Symptoms

Like rheumatoid arthritis, Sjögren’s syndrome is an autoimmune disorder: a condition that develops when your body is attacked by its own immune system. Complicating your care, Sjögren’s syndrome offers up its own list of symptoms, including a painful burning or gritty feeling in the eyes that can leave you prone to eye infections. You may also have a dry sensation in your mouth that increases the chances of dental decay or gum inflammation. In more extreme instances, Sjögren’s syndrome can affect other parts of the body, including your skin and internal organs like the lungs, liver, and kidneys.

Sjögren’s syndrome can occur by itself (primary Sjögren’s syndrome) or in conjunction with rheumatoid arthritis and other rheumatic conditions (secondary Sjögren’s syndrome), explains Philip L. Cohen, MD, chief of rheumatology at Temple University Hospital and professor of microbiology and immunology with the Lewis Katz School of Medicine at Temple University in Philadelphia. “Secondary SS usually occurs long after the diagnosis of RA and generally is less severe than primary SS.”

In order to prevent complications like eye damage or tooth loss, experts recommend that people with SS see both an ophthalmologist and a dentist regularly.

Living With Rheumatoid Arthritis and Sjögren’s Syndrome

Neen Monty of Queanbeyan, Australia, is no stranger to the demands of living with rheumatoid arthritis and Sjögren’s syndrome — the pain and swelling of joints, and the dry mouth and dry eyes. She was diagnosed with rheumatoid arthritis several years ago, but it wasn’t until later that her doctors suspected she was also dealing with Sjögren’s syndrome. Her struggles with her health inspired Monty to start a blog for others with arthritis called Arthritic Chick.

Monty admits that dealing with rheumatoid arthritis all on its own was very challenging and that coping with both rheumatoid arthritis and Sjögren’s syndrome can feel overwhelming at times.

“The No. 1 challenge of RA is the pain,” she says. “I have pain every day, though which joints are affected and how intense the pain is varies. It’s been that way for years now, so I’ve reached a certain level of acceptance. Sjögren’s seems minor compared to RA, but when my eyes flare up, I look like the elephant man! I can’t drive because I can’t see properly. My eyes are so painful and light-sensitive that I just have to sit in a darkened room for a few hours with my eyes closed.”

Monty has met the challenges of rheumatoid arthritis and Sjögren’s syndrome by being diligent about taking her prescribed medication. She also fights to keep a good attitude, no matter what symptoms she faces on a specific day. “For me, the most important thing is attitude,” Monty says. “I always try to stay positive. I try not to dwell on the pain, and I don’t talk about it much. I focus on what I can do rather than what I can no longer do. For example, I have always been a gym junkie. There are days when I can’t exercise, but most days I can do something — yoga, lift light weights, ride a recumbent bike, or just do some stretches. Even doing a little bit is better than nothing. Plus it gets me out of the house and gives me a goal.”

Monty also focuses on eating a healthy diet, which she believes further helps her in her fight against rheumatoid arthritis and Sjögren’s syndrome.

RA and Sjögren’s Syndrome: Treatment and Coping Tips

Nathan Wei, MD, director of the Arthritis Treatment Center in Frederick, Maryland, seconds Monty’s opinion that strict adherence to medication is the best course of action for both rheumatoid arthritis and Sjögren’s syndrome. The good news, according to Dr. Wei, is that treatment might not require you to do anything different.

“Both are systemic diseases, so biologic therapy for the RA will also treat the Sjögren’s,” he says. “Sjögren’s may require some local therapy for the dryness of the eyes and mouth.”

Sometimes doctors treating dry mouth will prescribe systemic drugs that increase secretions, such as Salagen (pilocarpine) or Evoxac (cevimeline). Eye physicians may also prescribe eye drops, such as Restasis (cyclosporine), for dry eye symptoms.

Remember, too, that some small steps may bring big relief. Avoid sweets but try sugarless gum or candy to counter mouth dryness, Wei suggests. Special toothpastes and ointments are often helpful, too. Also drink water frequently and try over-the-counter eye drops (artificial tears).

Characteristics of Sjögren’s syndrome in rheumatoid arthritis

Abstract

Objective. To compare features of SS in RA with primary SS and RA without SS.

Methods. Patients hospitalized between January 2007 and December 2010 were retrospectively studied. Seventy-four cases of overlap RA and SS (RA/SS) among 509 cases of RA were identified. Cases of SS (n = 187) detected during the same period acted as controls.

Results. Among those with RA/SS, there were 46 cases of RA-onset SS and 12 cases of SS-onset RA. Sixteen patients had simultaneous-onset RA and SS. Compared with RA without SS, RA/SS patients had more severe arthritis; a higher incidence of haematological abnormality, fever and rash; and a higher frequency of RF, ANAs and anti-SSA and anti-SSB antibodies (P < 0.05). Compared with primary SS, RA/SS patients were older, had more severe arthritis, anaemia and lung involvement; a lower incidence of fever, rash, leucopenia, thrombocytopenia and hyperthyroidism; and a higher frequency of RF, anti-keratin antibody, anti-perinuclear factor and anti-cyclic citrullinated antibodies (P < 0.05). Compared with RA and primary SS, RA/SS patients had higher disease activity scores of both RA and SS.

Conclusion. RA/SS patients have distinctive features, with more complications and systemic involvement. In addition, disease activity is higher in RA/SS.

Introduction

RA is a systemic autoimmune disease that causes joint damage as well as extra-articular complications. Sicca symptoms are common in patients with RA. SS is a chronic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. The features of SS are xerostomia and xerophthalmia, which are caused by impaired function of the salivary and lacrimal glands . Earlier studies classified SS as primary or secondary according to whether or not it coexisted with other CTDs. Secondary SS can be associated with diseases such as SLE and RA .

Previous studies have revealed profiles of the clinical manifestations of sicca symptoms that are distinct from those of primary SS (pSS). However, the percentage of RA patients who fulfil the SS classification criteria, and the prevalence of sicca symptoms in patients with RA, varies considerably among published studies . There is controversy about whether secondary SS is related to disease activity and disease duration in RA . In addition, the characteristics and pathogenesis of the SS in RA is unclear. Therefore research that focuses on the features of overlap RA and SS (RA/SS) is needed. In this study we systematically compared the clinical and serological characteristics of RA/SS with pSS and RA to establish features of RA in patients who are prone to developing the sicca syndrome. We also compared complications in different groups, such as the incidence of coronary heart disease, hypertension and diabetes mellitus, in an attempt to explore the clinical spectrum of RA/SS and to help physicians in the recognition of disease severity in patients with RA/SS.

Patients and methods

Patients

We retrospectively reviewed the medical records of 509 RA patients admitted between January 2007 and December 2010 to the Peking University People’s Hospital. All RA patients were evaluated for evidence of secondary SS according to the 2002 revised international classification criteria for SS . Seventy-four patients fulfilled the criteria for SS among 509 RA patients. Among the 74 patients who fulfilled the criteria for both RA and SS, there were 46 cases of RA-onset SS and 12 cases of SS-onset RA. Sixteen patients had simultaneous RA and SS. The control group consisted of 187 inpatients treated in the Peking University People’s Hospital who fulfilled the criteria for SS during the same period. For all patients, the onset and duration of either RA or SS were defined from the time when the diagnosis of RA or SS could be ascertained using established classification criteria. This study was approved by the Medical Ethics Committee of Peking University People’s Hospital. Patient consent was obtained according to the Declaration of Helsinki.

Clinical features and complications

The following features of disease were included in this study: arthritis, fever, rash, lymphadenopathy, RP, parotid gland enlargement, xerostomia, xerophthalmia, anaemia (Hb <12 g/dl), leucopenia (white blood cell count <4000/µl), thrombocytopenia (platelet count <100 000/µl), pulmonary involvement, renal involvement, hepatic involvement (autoimmune hepatitis, primary biliary cirrhosis), nervous system involvement, autoimmune thyroiditis, coronary heart disease, hypertension and diabetes mellitus.

Laboratory findings

All patients underwent extensive serological evaluations, including ANA, anti-SSA and anti-SSB antibodies, RF, anti-keratin antibody (AKA), anti-perinuclear factor (APF) and anti-CCP. Sera IgG, IgA and IgM were also measured.

Classification criteria

All patients were Chinese and fulfilled the ACR 1987 criteria for the diagnosis of RA and the 2002 revised international classification criteria for SS . The EULAR SS disease activity index (ESSDAI) and DAS28 scores were used as indices of disease activity.

Statistical analysis

Data analyses were performed using SPSS for Windows, version 16.0. Differences between groups were assessed using t-test and chi-square analyses for categorical variables. Logistic regression was used to adjust P-values by age, sex and duration of diseases. P < 0.05 were considered statistically significant.

Results

Among the 509 patients with RA, 74 (14.5%) fulfilled the criteria for both SS and RA. Forty-six patients (62.2%) had sicca symptoms after the diagnosis of RA (ranging from 6 months to 35 years). The diagnosis of SS preceded the diagnosis of RA by 9 months to 29 years in 12 patients (16.2%). Sixteen patients had RA and SS almost at the same time (Fig. 1).

Fig. 1

Onset of RA and SS in 74 patients with RA/SS.

Of these 74 patients, 46 (62.2%) had secondary SS after the diagnosis of RA. The diagnosis of RA preceded SS by 6 months to 35 years. In 12 patients (16.2%), the diagnosis of SS preceded RA by 9 months to 29 years. Sixteen patients (21.6%) had almost simultaneous RA and SS.

Fig. 1

Onset of RA and SS in 74 patients with RA/SS.

Of these 74 patients, 46 (62.2%) had secondary SS after the diagnosis of RA. The diagnosis of RA preceded SS by 6 months to 35 years. In 12 patients (16.2%), the diagnosis of SS preceded RA by 9 months to 29 years. Sixteen patients (21.6%) had almost simultaneous RA and SS.

Demographic data in RA/SS compared with pSS and RA

The demographic and general characteristics of the three groups (RA/SS, RA and pSS) are summarized in Table 1. The proportion of women in the RA/SS group was lower than in the pSS group (P = 0.041). Compared with patients with pSS and RA only, the duration of disease was longer in patients with RA/SS (P < 0.001).

Table 1

Comparison of features between groups

Mean (s.e.m.) for continuous variables or percentages for categorical variables. P < 0.05 are considered significant. P△ was adjusted by sex, age and duration of disease. aNumber varies due to missing data. NA: not applicable.

Table 1

Comparison of features between groups

Mean (s.e.m.) for continuous variables or percentages for categorical variables. P < 0.05 are considered significant. P△ was adjusted by sex, age and duration of disease. aNumber varies due to missing data. NA: not applicable.

Clinical manifestations and disease activity in RA/SS, RA and pSS

Comparison of laboratory findings between the groups

The laboratory findings of the three groups of patients are presented in Table 1. Compared with pSS patients, RA/SS patients had a higher frequency of RF, AKA, APF and anti-CCP. Statistical differences in RF-IgM, RF-IgA, ANA, anti-SSA, anti-SSB and IgG were observed between the RA/SS group and the RA group.

Comparisons of systemic involvement and clinical complications between the groups

As shown in Table 1, differences in the incidence of leucopenia, thrombocytopenia, anaemia, interstitial lung disease, autoimmune liver disease and hyperthyroidism between the RA/SS and pSS groups were statistically significant. RA/SS patients had a higher frequency of leucopenia, thrombocytopenia, anaemia, interstitial lung disease, autoimmune liver disease, renal involvement, nervous system involvement and coronary heart disease than RA patients.

Discussion

SS often coexists with other systemic autoimmune diseases, including RA and SLE. Since 1965, there have been several studies that have focused on RA associated with SS . Subsequent studies demonstrated significant differences in the clinical features of SS patients with and without RA . To our knowledge, this is the first study to describe the demographic, clinical, serological features, systemic involvement and complications of RA/SS, RA and SS patients systematically.

Studies have shown that the percentage of RA patients who fulfil the SS criteria ranges from 4% to 31% . In this study we demonstrated that 14.5% of the 509 RA patients fulfilled the SS criteria. During the study, all RA patients were asked about sicca symptoms identified with SS. One hundred and thirty-six of RA without SS patients have xerostomia syndrome and 98 have xerophthalmia. Overall, 159 of the patients who underwent SS-related examination had sicca symptoms. RA patients who have no complaint of sicca symptoms may not be included in the protocol of SS patients’ diagnosis. Hence, a portion of early SS patients might be missed. To reduce the rate of misdiagnosis, every RA patient was checked for ANA and anti-SSA/SSB antibodies, but some ANA-positive patients did not fulfil the SS criteria. Those patients may develop SS with disease duration and progression. Of these RA patients, only 16 underwent salivary gland biopsy because of lack of SS-related antibodies, but they had clear and definite sicca symptoms. All 16 patients were diagnosed as secondary SS. Others were not obliged to undergo the biopsies.

Drug therapy is very important for the progression of disease, so we analysed the treatment of these patients. Sixty per cent of RA patients lacked standard treatment for 1 month before being enrolled in the study, stopped taking medicine prescribed by doctors or used Chinese medicine irregularly. Forty per cent (n = 174) of the RA patients underwent standard treatment, such as MTX, SSZ, HCQ, LEF, prednisone or so on. Sixty-five per cent (n = 48) of the RA/SS patients lacked standard treatment, and 35% of the patients used MTX, SSZ, HCQ, LEF or prednisone regularly. There was no significant difference between these two groups. Ninety per cent (n = 163) of the SS patients lacked standard treatment. These drugs might influence the development of disease, but that cannot be calculated accurately.

Our data suggest that patients with RA/SS are older than patients with pSS. RA/SS patients had a longer duration of disease than those with RA only or pSS. Patients with RA/SS have a more severe form of arthritis. Sicca syndrome (xerostomia and xerophthalmia) appears to present a similar profile in patients with RA/SS and those with pSS. In addition, the statistically significant association of family history is of particular note. RA/SS patients had a more obvious family aggregation autoimmune disease tendency. As has been established, SS and RA are influenced by genetic factors. Previous studies have proved that pSS and secondary SS are associated with different genetic factors . This phenomenon deserves further study in patients with RA/SS, RA only and pSS.

Significant differences in RF, AKA, APF and anti-CCP between RA/SS and pSS patients are of note, suggesting that these parameters could be a useful tool in distinguishing pSS, RA and sSS. Primary SS patients and RA without SS patients can present with a variety of haematologic abnormalities, including anaemia, leucopenia and thrombocytopenia. Anaemia in RA patients is associated with DAS28 and RA patients with anaemia represent a greater cost burden to hospitals . The incidence of anaemia was higher in RA/SS patients than in RA and pSS patients. Therefore patients with RA/SS require more therapy during treatment and higher hospitalization costs. Through analysis we found that the incidence of haematological system abnormality is much higher in RA/SS patients than in those without. Previous research reported that the frequency of anaemia in pSS patients was 16% . In this study, the frequency of anaemia in pSS was 57.2%, which is higher than in previous studies and in RA patients. This may be associated with racial differences. Anaemia is defined as haemoglobin ≤11 g/dl in females and ≤12 g/dl in males in Chinese people. The deviation might come from the pilot samples. If the number of patients is large enough, the results will be more reliable. From previous reports, the incidence of anaemia in RA ranges from 33% to 60%, whereas in our study it is 21%. A study by Al-Ghamdia and Suzan showed that the prevalence of anaemia in RA is 61%, which might relate with disease duration and food imbalance. Da Mota et al. showed that anaemia in RA is related to disease activity and associated with inflammatory activity . From this study, the RA/SS patients had significantly longer disease duration and higher disease activity, which might be associated with the higher incidence of anaemia . Leucopenia and thrombocytopenia in RA without SS is often associated with drug toxicity. Leucopenia and thrombocytopenia are frequently seen in RA/SS and pSS, but seldom in RA only. The haematologic features of RA/SS have the similar characteristics in both RA and pSS patients.

Interstitial lung disease in patients with RA/SS is more common than in either pSS or RA. The incidence of autoimmune liver disease in RA/SS was higher than in RA, but lower than in pSS. The incidence of renal involvement in RA/SS is higher than in RA. Autoimmune thyroid diseases in pSS are very common. Perez et al. found that the percentage of thyroid dysfunction in SS patients was 45%. Autoimmune thyroiditis and autoimmune hyperthyroidism was 24 and 6%, respectively. The occurrence of clinically manifest hypothyroidism and subclinical hypothyroidism in RA patients was 6.8 and 2.5% in the Dutch population . In this study, hypothyroidism is more common than hyperthyroidism in patients of the three groups. Hyperthyroidism is more frequently seen in patients with RA/SS and RA without SS than in those with pSS. The features of systemic involvement may help to distinguish the three groups. More systemic involvement was found in RA/SS patients, which is an important observation for clinicians to be aware of.

Cardiovascular events in rheumatic diseases such as RA, SLE and SS have been previously reported . Patients with RA often experience cardiovascular events, which are potentiated by high disease activity . A 2-fold higher prevalence of diabetes mellitus has been demonstrated in patients with pSS . To our knowledge, no previous studies have identified the complications of coronary heart disease, hypertension and diabetes mellitus in well-defined RA/SS patients and compared them with those with RA without SS or with pSS. The incidence of coronary heart disease in RA/SS patients was higher than in patients with RA. RA/SS patients were at higher risk of cardiovascular events.

As to whether the sicca syndrome is associated with disease activity in RA, the answer varies between studies. Uhlig et al. concluded that high RA disease activity was a predictor of reduced saliva production. In the current study, we found that in patients with RA/SS, the scores of both DAS28 and ESSDAI were higher than other two groups, pointing to the greater disease activity in RA/SS patients. In this group, therefore, attention needs to focus on early intervention and treatment to prevent disease progression and complications.

Although the current study is a retrospective one, it suggests that patients with RA/SS have distinctive demographic, clinical and serological features. In addition, the profile of systemic involvement and complications appears to be different in those with RA/SS. Larger prospective studies are needed to confirm these preliminary results.

Acknowledgements

J.H. and Y.D. performed the study. Z.L. conceived the study and participated in the design. All authors read and approved the final manuscript.

Funding: This work was supported by the Beijing Natural Science Foundation (no. 7102155) and National Natural Science Foundation of China (nos 31070788 and 81128012).

Disclosure statement: The authors have declared no conflicts of interest.

1 Ramos-Casals M , Brito-Zeron P , Font J . The overlap of Sjogren’s syndrome with other systemic autoimmune diseases, Arthritis Rheum, 2007, vol. 36 (pg. 246-55) 2 Xu D , Tian X , Zhang W , Zhang X , Liu B , Zhang F . Sjogren’s syndrome-onset lupus patients have distinctive clinical manifestations and benign prognosis: a case-control study, Lupus, 2010, vol. 19 (pg. 197-200) 3 Moutsopoulos HM , Webber BL , Vlagopoulos TP , Chused TM , Decker JL . Differences in the clinical manifestations of sicca syndrome in the presence and absence of rheumatoid arthritis, Am J Med, 1979, vol. 66 (pg. 733-6) 4 Al-Ghamdia A , Suzan M . Extra-articular manifestations of rheumatoid arthritis: a hospital-based study, Ann Saudi Med, 2009, vol. 29 (pg. 189-93) 5 Da Mota LM , dos Santos Neto LL , Burlingame R , Ménard HA , Laurindo IM . Laboratory characteristics of a cohort of patients with early rheumatoid arthritis, Rev Bras Reumatol, 2010, vol. 50 (pg. 375-88) 6 Antero DC , Parra AG , Miyazaki FH , Gehlen M , Skare TL . Secondary Sjogren’s syndrome and disease activity of rheumatoid arthritis, Rev Assoc Med Bras, 2011, vol. 57 (pg. 319-22) 7 Vitali C , Bombardieri S , Jonsson R , et al. Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group, Ann Rheum Dis, 2002, vol. 61 (pg. 554-8) 8 Arnett FC , Edworthy SM , Bloch DA , et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis, Arthritis Rheum, 1988, vol. 31 (pg. 315-24) 9 Seror R , Ravaud P , Bowman SJ , et al. EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome, Ann Rheum Dis, 2010, vol. 69 (pg. 1103-9) 10 Prevoo MLL , van ‘t Hof MA , Kuper HH , et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis, Arthritis Rheum, 1995, vol. 38 (pg. 44-8) 11 Bloch KJ , Buchanan WW , Wohl MJ , Bunim JJ . Sjogren’s syndrome, a clinical, pathological, and serological study of sixty-two cases, Medicine, 1965, vol. 44 (pg. 187-231) 12 Hadj Kacem H , Kaddour N , Adyel FZ , Bahloul Z , Ayadi H . HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and CTLA-4 polymorphisms in Tunisian patients with rheumatoid arthritis and Sjögren’s syndrome, Rheumatology, 2001, vol. 40 (pg. 1370-4) 13 Escobar ME , Gerhardt C , Roesler E , et al. Anemia versus disease activity as cause of fatigue in rheumatoid arthritis, Acta Reumatol Port, 2010, vol. 35 (pg. 24-8) 14 Zlateva G , Diazaraque R , Viala-Danten M , Niculescu L . Burden of anemia in patients with osteoarthritis and rheumatoid arthritis in French secondary care, BMC Geriatr, 2010, vol. 10 pg. 59 15 Ramos-Casals M , Solans R , Rosas J , et al. Primary Sjogren syndrome in Spain: clinical and immunologic expression in 1010 patients, Medicine, 2008, vol. 87 (pg. 210-9) 16 Perez B , Kraus A , Lopez G , Cifuentes M , Alarcon-Segovia D . Autoimmune thyroid disease in primary Sjogren’s syndrome, Am J Med, 1995, vol. 99 (pg. 480-4) 17 Raterman HG , van HVP , Voskuyl AE , et al. Rheumatoid arthritis is associated with a high prevalence of hypothyroidism that amplifies its cardiovascular risk, Ann Rheum Dis, 2008, vol. 67 (pg. 229-32) 18 Innala L , Moller B , Ljung L , et al. Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: a five year prospective study, Arthritis Res Ther, 2011, vol. 13 pg. R131 19 Perez-De-Lis M , Akasbi M , Siso A , et al. Cardiovascular risk factors in primary Sjogren’s syndrome: a case-control study in 624 patients, Lupus, 2010, vol. 19 (pg. 941-8) 20 Uhlig T , Kvien TK , Jensen JL , Axell T . Sicca symptoms, saliva and tear production, and disease variables in 636 patients with rheumatoid arthritis, Ann Rheum Dis, 1999, vol. 58 (pg. 415-22)

Author notes

George Fragoulis1, James Reilly1, Shauna Kerr1, Iain. B. McInnes1 and Haralampos M. Moutsopoulos2, 1Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow, United Kingdom, 2Department of Pathophysiology, Medical School of Athens, Department of Pathophysiology, Athens, Greece

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: biopsies, rheumatoid arthritis (RA) and salivary gland, Sjogren’s syndrome

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Session Information

Date: Sunday, November 8, 2015

Session Title: Sjögren’s Syndrome Poster I: Clinical Insights into Sjögren’s Syndrome

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: The histopathological hallmark and a major diagnostic criterion of Sjögren’s syndrome (SS) is the presence of periductal lymphocytic infiltrates in the labial minor salivary glands (LMSG). SS can occur either as an entity alone (primary SS-pSS) or with rheumatoid arthritis (RA) and other autoimmune diseases. Sicca symptoms (primarily ocular) are observed in around 20-25% of RA patients. The present study examines the LMSG infiltrates in sicca-RA patients and compares their composition with this described in pSS.

Methods: 100 consecutive RA patients (2010 ACR criteria) answer a validated sicca symptoms questionnaire. Positive responders were evaluated for ocular and oral dryness including a LMSG biopsy. All samples in addition to haematoxylin and eosin were stained for the immunocyte populations in serial sections . Stained cells and total mononuclear cells (MNC) were counted in the entire section. Counts were expressed as cell incidence (percentage of cell type number/total infiltrating MNC number).

Results:

Conclusion:

The cell composition of the LMSG infiltrates of sicca-RA patients is different compared to that seen in biopsies of pSS patients. These differences, coupled with the known genetic and serologic dissimilarities may further attest for diverse pathophysiologic process operating in the genesis of these two entities.

  1. Characteristics of the minor salivary gland infiltrates in Sjögren’s syndrome. Christodoulou MI, Kapsogeorgou EK, Moutsopoulos HM. J Autoimmun. 2010 34(4):400-7

Table 1. a. ACR 2010 RA criteria, at the time of diagnosis.

Table 2. MSG biopsy lesion composition in RA patients with sicca compared to primary SS patients

Disclosure: G. Fragoulis, None; J. Reilly, None; S. Kerr, None; I. B. McInnes, None; H. M. Moutsopoulos, None.

To cite this abstract in AMA style:

Fragoulis G, Reilly J, Kerr S, McInnes IB, Moutsopoulos HM. Sicca Syndrome in Rheumatoid Arthritis: Is It a Real Sjögren’s? . Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/sicca-syndrome-in-rheumatoid-arthritis-is-it-a-real-sjgrens/. Accessed February 2, 2020. Favorite Save to PDF

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ACR Meeting Abstracts – https://acrabstracts.org/abstract/sicca-syndrome-in-rheumatoid-arthritis-is-it-a-real-sjgrens/

Sjögren’s syndrome

  • Learn about Sjogren’s syndrome and play an active role in your treatment. Not all information you read or hear about is trustworthy so always talk to your doctor or healthcare team about treatments you are thinking about trying. Reliable sources of further information are also listed in the section below. Self management courses aim to help you develop skills to be actively involved in your healthcare. Contact your local Arthritis Office for details of these courses.
  • Learn ways to manage symptoms. Most of the treatment for Sjögren’s syndrome is aimed at relieving symptoms of dry eyes and mouth and preventing and treating long-term complications such as infection and dental disease. Treatments may include:
    • regular use of artificial tears and lubricating ointments for the eyes to manage dryness
    • drinking water and/or using artificial saliva, mouth rinses or lozenges to relieve mouth dryness
    • moisturisers for the skin
    • avoidance of drying conditions, eg drafts from heaters and air conditioners, and exposure to dusty or windy weather, and use of a humidifier
    • medicines prescribed by your doctor (for example, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids or medicines that work on the immune system).
  • Live a healthy life. Stay physically active, eat a healthy diet, stop smoking and reduce stress to help your overall health and wellbeing.
  • Acknowledge your feelings and seek support. As there is no cure for Sjögren’s syndrome, it is natural to feel scared, frustrated, sad and sometimes angry. Be aware of these feelings and get help if they start affecting your daily life.
  • CONTACT YOUR LOCAL ARTHRITIS OFFICE FOR MORE INFORMATION AND SUPPORT SERVICES.

    Books:
    Rumpf, Teri et al 2003, The Sjogren’s syndrome survival guide, New Harbinger Publications, Oakland.Websites:
    Australian Rheumatology Association, Arthritis Research UK, American College of Rheumatology, Arthritis Foundation (US)

    IIMD, Resident Physician in the Ophtalmology Service at HUEC, Curitiba, PR
    IIIPhD in Surgery Principles and Physician at the Ophtalmology Residency Service at HUEC, Curitiba, PR
    IVPhD in Surgery Principles and Chief of the Rheumatology Service at HUEC, Curitiba, PR

    Correspondência para

    SUMMARY

    OBJECTIVE: To study the relationship of the presence of secondary SS with disease activity, duration in RA.
    METHODS: Eighty two patients with RA were submitted to Schirmer test, minor salivary gland biopsy, questionnaire on sicca symptoms, DAS-28 4v determination.
    RESULTS: In this population, 20 (24.3%) patients fulfilled the American-European classification criteria for secondary SS. No relation could be found between the presence of secondary SS and disease activity (p = 0.31) and RA duration (p = 0.95).
    CONCLUSION: Appearance of Secondary SS in RA patients is independent of RA duration or activity.

    Keywords: Arthritis, rheumatoid; dry eye syndromes; inflammation.

    RESUMO

    OBJETIVO: Estudar a associação entre presença de SS secundária e atividade e duração da artrite reumatoide.
    MÉTODOS: Oitenta e dois pacientes com artrite reumatoide foram submetidos ao teste de Schirmer, biópsia de glândula salivar menor, questionários acerca de sintomas de secura e determinação do DAS28 4v.
    RESULTADOS: Nesta população, 20 (24,3%) dos pacientes preenchiam os Critérios Americanos Europeus para classificação de SS Secundário. Nenhuma associação foi encontrada entre presençade SS secundário e atividade da doença (p = 0.31) e duração da doença (p = 0.95).
    CONCLUSÃO: O aparecimento de SS secundário em AR é independente da duração e atividade da AR.

    Unitermos: Artrite reumatoide; síndromes do olho seco; inflamação.

    Introduction

    Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory disease that affects lachrymal and salivary glands causing mucous dryness that affects mainly middle aged women1. SS can be a primary or a secondary disease when it is associated with other autoimmune disorders such as scleroderma and rheumatoid arthritis (RA)2. Superimposed SS in RA is an interesting finding. There is an important role of B cells and type I interferon in primary SS2,3 in contrast to the predominance of Th17 cytokines in RA4. As the physiopathology of these two diseases is distinct, it is possible to suggest that patients with RA and secondary SS have two different diseases or that RA secondary SS has a different physiopathology than the primary form. In this context we aimed to study if RA disease activity or severity have any association with occurrence of secondary Sjogren’s syndrome.

    Methods

    This study was approved by the Committee for Ethics in Research of our institution and all participants signed consent. To participate in the study patients had to present at least four criteria of the American College of Rheumatic Diseases for RA7. The included patients were selected from a single Rheumatology Clinic (Evangelic University Hospital) chosen according to appointment order and willingness to participate in the study. We excluded patients with ophthalmologic complications such as scleritis, episcleritis, scleromalacia, those with prior eye surgery and contact lenses users or those taking medications such as antidepressants, anticholinergics, antihistamine, diuretics, etc, those with hepatitis C or HIV infection or prior irradiation of the neck.

    All included patients had Schirmer test done according to standard recommendations and we considered a patient to be with definitive dry eye when values were equal or under 5 mm in at least one eye8. Biopsy of minor salivary gland was done in all included patients and sections were stained by hematoxylin-eosin and considered positive when a focus of 50 lymphocytes/4 mm2 was found9. Salivary gland biopsy was read by a blinded pathologist. Simultaneously with eye tests and minor salivary gland biopsy, patients had DAS-28 4v10,11 and also answered a questionnaire on sicca symptoms (oral and ocular). DAS 28 is a measurement of RA disease activity that takes into account number of swollen and tender joints, a measurement of general health by the patients and values of sedimentation rate. Patients with DAS28 values under 2.6 are considered under remission, with values between 2.6 and 3.1 as having mild disease activity; with values between 3.2 and 5.1 as having moderate activity and over 5.1 with high disease activity.

    Patient’s joint count was done by just one rheumatologist. Charts were reviewed for demographic data, HAQ12 and autoantibody profile (latex, anti CCP, anti Ro, Anti La).

    To consider a RA patient as having secondary SS it was necessary to fulfill the American European Criteria for secondary SS13,14.

    Data were grouped in contingency and frequency table. For association studies we used the chi-squared test for nominal data and unpaired t and Mann-Whitney tests for numeric data. The significance adopted was 5%.

    Results

    Studying DAS-28 according to the presence of secondary SS, we found a mean value of 2.81 ± 1.14 in those with SS and 3.35 ± 1.47 in those without it (p = 0.13). The mean value of DAS-28 in patients with Schirmer test under 5 mm was 3.1 ± 1.3 and in those with values higher than 5 mm it was 3.3 ± 1.4 (p = 0.50). Presence of Secondary SS according to DAS-28 is shown in Figure 1. Mean DAS-28 value in patients with subjective symptoms for dry eyes was 3.35 ± 1.58 and in those without it 3.04 ± 1.13 (p = 0.31).

    Table 1 shows data in RA patients with and without Secondary SS Syndrome.

    Discussion

    The presence of sicca symptoms was high in the studied population although only 24% of patients fulfilled criteria for secondary SS. The high prevalence of dry eyes in RA patients without fulfilling the diagnostic criteria for secondary SS has been noticed by Fujita et al.15 who found it in 90% of non-SS RA patients. In their study of 72 RA Japanese patients, just 10% of them had Secondary SS. The presence of secondary SS in RA has been found to be higher in other studies. Cimmino et al.5 found it in 17.5% of Italian RA patients and Martinez Castro et al.6, in 55% of Spanish RA population. This high variability may be due to the genetic background of the studied population and methods chosen to evaluate glandular dysfunction.

    Secondary SS is usually included as an extra-articular manifestation of rheumatoid arthritis16. According to Fox et al.17, SS associated with RA occurs in a different genetic background than the primary disease (HLA DR4) and this author suggests that SS associated with RA has a different pathogenetic process than that associated with lupus and with scleroderma. As we found in the present work, this later author noticed that ocular symptoms of dryness are more common than oral ones in RA patients.

    Our results also show that neither secondary SS occurrence nor eye sicca subjective and objective findings have any relation to disease duration. A study done in Spain found that patients with RA duration up to 10 years had a prevalence of secondary SS of 17% and after 30 years it was as high as 25%18. This relationship with disease duration was not confirmed by Uhlig et al.19 but was present in a Study done in the United Kingdom20.

    The association between secondary SS and disease activity was also studied by Fujita et al.15 who found that RA activity had no significant correlation with the presence of dry eye, however it had some relationship in those patients that fulfilled the diagnosis of secondary SS. Although we did not graduate severity of sicca findings, we could not find a higher RA activity measured by DAS-28 in patients with secondary SS when compared to those without it in the present study. No relationship could also be established with functional index. Wolfe et al.21, although they did not study Secondary SS, found that sicca symptoms are more common in patients with RA with increased HAQ scores, pain and global severity as well as total joint replacement and work disability.

    According to the present findings rheumatologists and ophthalmologists should be aware of high indices of sicca symptoms in RA and seek for secondary SS independently of the activity or duration of rheumatoid arthritis.

    2. Fox RI, Liu AY. Sjogren’s syndrome in dermatology. Clin Dermatol. 2006;24:393-413.

    3. Dorner T. Crossroads of B cell activation in autoimmunity: rationale of targeting B cells. J Rheumatol Suppl. 2006;77:3-11.

    5. Cimmino MA, Salvarani C, Macchioni P, Montecucco C, Fossaluzza V, Mascia MT. Extra-articular manifestations in 587 Italian patients with rheumatoid arthritis. Rheumatol Int. 2000;19:213-7.

    6. Martinéz-Castro E, Olivé Marqués A, Bonet Llorach M, Carbonell Abeló J, Cobo Valeri E, Juncà Valdor S. Rheumatoid arthritis and SS: special reference to the course time of rheumatoid arthritis. Med Clin (Barc). 1990;94:655-9.

    7. Arnett FC, Edworthy SM, Bloch DA, Mc Shane DJ, Fries JF, Cooper NS et al. The American Rheumatology Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-24

    8. Afonso AA,Monroy D, Stern ME, Feuer WJ, Tseng SC, Pflugfelder SC et al. Correlation of tear fluorescein clearance and Schirmer test scores with ocular irritation symptoms. Ophtalmology 1999;106:803-10.

    9. Daniels TE, Whitcher JP. Association of patterns of labial salivary gland inflammation with kerotoconjuctivitis sicca. Analysis of 618 patients with suspected Sjögren’s syndrome. Arthritis Rheum. 1994;37:869-77.

    11. Fransen J, van Riel PLCM. DAS remission cut points. Clin Exp Rheumatol. 2006; 24(Suppl 43):S29-S32.

    13. Vitali C, Bomardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carson SE 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.

    15. Fujita N, Igarashi T,Kurai T, Sakane N, Yoshino S, Takahasi H. Correlation between dry eye and rheumatoid arthritis activity. Ophthalmology 2005;140:808-13.

    16. Theander E, Jacobsson LTH. Relationship of Sjogren’s syndrome to other connective tissue and autoimmune disorders. Rheum Dis Clin Noth Am. 2008;34:935-47.

    17. Fox R. Sjögren’s syndrome. Lancet 2005;366:321-30.

    18. Carmona L, Gozalez-Alvaro I, Balsa A, Angel Belmonte M, Tena X, Sanmarti R. Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates of disease severity. Ann Rheum Dis. 2003;62:897-900.

    19. Uhlig T, Kvien TK, Jensen JL, Axéll T. Sicca symptons, saliva and tear production and disease variables in 636 patients with rheumatoid arthritis. Ann Rheum Dis. 1999;58:415-22.

    20. Young A, Koduri G. Extra-articular manifestations and complications of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2007; 21:909-27.

    21. Wolfe F, Michaud K. Prevalence, risk and risk factors for oral and ocular dryness with particular emphasis on rheumatoid arthritis. J Rheumatol. 2008;35:1023-30.

    Correspondência para:
    Thelma L Skare
    Rua João Alencar Guimarães,796 Curitiba – PR
    CEP: 80310420

    Submitted on: 01/17/2011
    Approved on: 03/16/2011
    Conflict of interest: None.

    Study conducted at Serviços de Reumatologia e de Oftalmologia do Hospital Universitário Evangélico de Curitiba, Curitiba, PR

    5 Ways Rheumatoid Arthritis Affects Your Skin

    By

    Paige Greenfield

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    When you have rheumatoid arthritis (RA), you know it causes inflammation and pain in your joints. However, you may be surprised to notice that RA can affect other parts of your body, such as your skin. In some instances, the skin symptoms are due to RA itself. In others, drugs you take to control RA may lead to skin issues. Here are five RA-related issues that may appear.

    1. Raynaud’s Phenomenon

    In Raynaud’s phenomenon, the blood vessels that send blood to your fingers and toes constrict. This can occur because of cold temperatures or stress. Symptoms related to Raynaud’s that can affect your skin include:

    • Fingers and/or toes turning white or blue

    • Feelings of coldness, pain, and numbness

    • Throbbing, tingling, or warmth when the blood returns

    • Slow-healing sores, called ulcers, on your fingertips

    Be sure to dress appropriately in cold weather. Though it sounds extreme, you also may want to consider wearing gloves when shopping in the refrigerator and freezer aisles of the grocery store.

    2. Rheumatoid Nodules

    About 50% of people with RA also get rheumatoid nodules. These are lumps of tissue that develop under the skin. They often form over bony areas like your fingers or elbows. Sometimes, nodules go away without treatment. A class of drugs called disease-modifying antirheumatic drugs (DMARDs) used to treat RA can help nodules disappear as well.

    3. Bruising

    Corticosteroid medications help control inflammation caused by RA. These drugs can also cause thinning of the skin and make you more vulnerable to bruising.

    4. Red Dots

    RA can sometimes cause a condition called vasculitis, or inflammation of blood vessels that feed the skin. A telltale sign of vasculitis is red dots (medical term “petechiae”). In extreme cases, you could see ulcers on the legs, under the fingernails, or in nail beds. If you notice any of these symptoms, tell your doctor right away. You may need immediate treatment.

    5. Sun Sensitivity

    One of the medications to treat RA, methotrexate, a DMARD, can increase your sensitivity to the sun. Some people who take nonsteroidal anti-inflammatory drugs (NSAIDs) may also be more sensitive to sunlight. Be sure to practice sun safety, which includes wearing sunblock with SPF 30 or above that also protects against UVA and UVB light. Reapply every 90 minutes.

    Key Takeaways

    • RA can affect your skin, either because of the disease itself or because of medications you take to treat it.

    • In Raynaud’s phenomenon, the blood vessels that send blood to your fingers and toes constrict as a result of cold temperatures or stress.

    • About 50% of people with RA get rheumatoid nodules, lumps of tissue that develop under the skin.

    • RA can sometimes cause vasculitis, or inflammation of blood vessels that feed the skin. A telltale sign is red dots.

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