Aspects of xerostomia prevalence and treatment among rheumatic inpatients

failed to prove statistical significance of older age in prevalence of sicca symptoms. Treatment administered to rheumatic patients for xerostomia in the HKUM is neither sufficient nor adequate.

Research is conducted worldwide on the correlation of rheumatic diseases with xerostomia and patients' quality of life (37)(38)(39)(40)(41). It has been established that one of the most common factors causing xerostomia are rheumatic diseases, especially the socalled secondary Sjögren's syndrome (sSS) (1,2,4,7,9,25,29,(32)(33)(34)(35)(36)42). Secondary Sjögren's syndrome is diagnosed when autoimmune changes in exocrine glands appear, following other rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and scleroderma. Salivary gland dysfunction appears due to progressing lymphocytic infiltration in salivary acini, which in turn leads to inflammatory reaction causing acinar atrophy and proliferation of connective tissue. Sometimes such pathological changes originate in the minor salivary glands and may result in early symptoms of xerostomia, which are less intense than those in cases when the major salivary glands are affected. Sjögren's syndrome tends to afflict persons at the ages of 40 to 50 years, with the ratio of women to men commonly ranging from 5:1 to 17:1. Quite often secondary Sjögren's syndrome is misdiagnosed (1,2,7,9,25,29,(34)(35)(36)42), and this leads to inadequate treatment and impairment of patient's quality of life.
In the course of the present study, no sources were found indicating any recent research in Lithuania on prevalence of xerostomia and its correlation with other factors among patients with rheumatic diseases. The aim of the present study was to fill this gap, as well as to review current modalities of treatment administered for xerostomia in our country (and in Hospital of Kaunas University of Medicine (HKUM) in particular). Furthermore, it was a matter of great importance for us to present xerostomia as an existing problem, which has either been mostly ignored or has not received adequate solutions yet.
The aim of the present study was to analyze the prevalence of xerostomia and its correlation with age, sex, and xerophthalmia, as well as to evaluate modalities of treatment administered for xerostomia to inpatients with rheumatic diseases during the period of 1998 to 2004 in the Department of Rheumatology of the HKUM.

Materials and methods
Inpatients' archival case records from the Department of Rheumatology of the HKUM (for the years 1998 to 2004) were selected for thorough analysis. This selection was based on four main diseases -rheumatoid arthritis (AR), systemic lupus erythematosus (LES), scleroderma (SC), and systemic sclerosis (SS) -which in comparison to other rheumatic diseases were known to be most conducive to xerostomia, i.e. secondary Sjögren's syndrome (1,2,4,7,9,25,29,32,35,36,42). The numbers of inquiries per disease were as follows: AR -207, LES -165, SC -109, SS -2 (too small for further statistical analysis). The total initial number of inquiries was 516; all selected in chronological sequence. It should be noted that the number of inquiries was an important statistical parameter for our study, in the course of which all the HKUM case-records of rheumatologic inpatients for the period of 1998-2004 with LES, SC, SS and for the period of 2003-2004 with AR were analyzed. We found that 25 patients were using xerogenic medications (tranquillizers, sedatives, etc.) and discovered 8 cases of seropositive or reactive arthritisall of which were excluded from further analysis (33 cases in total). The analyzed population consisted of 12.6% of men and 87.4% of women (1:7 ratio). Their mean age was 51.9±0.7 years; for men it was 54.3±1.8 years (n=61) and for women -51.5±0.7 years (n=422) (P<0.05) (t test, t=0.168). Table 1 shows the categorization of the analyzed population according to disease and sex.
It demonstrates that the mean age of patients with Mean age in patients with LES is lower than that in other disease groups (c²=6420.4; df=3, P<0.001).
LES is lower than that of patients with other selected diseases (AR, SC, and SS) (P<0.001; df=3).
For the purpose of our analysis, the patients were divided into three groups according to their age: group 1 -up to 45 years, group 2 -45 to 60 years, group 3more than 60 years (Fig. 1).
The fields in our questionnaire were name and surname, sex, case record number, age, disease, xerostomia (administered treatment), xerophthalmia (administered treatment). A patient was considered xerostomia-positive when oral dryness, dry tongue, salivary deficiency, and xerostomia were indicated in his/her case record. A patient was considered xerophthalmiapositive when ocular dryness, keratoconjunctivitis sicca, lacrimal deficiency, and xerophthalmia were indicated in his/her case record. The present study was approved by the Ethics Committee for Biomedical Research at Kaunas University of Medicine.
Statistical analysis. The obtained data were analyzed and compared using the SPSS software, version 10.0 for Windows. Student's t test coefficient between variable parameters such as mean values of age in different groups was calculated. c² correlation coefficient between age groups, sex, xerostomia, and xerophthalmia was also calculated. All the data were expressed as a mean±standard deviation (SD). Values of P<0.05 were considered significant, P<0.01 -very significant.

Results
All of the selected cases were included in further analysis. A more exact breakdown of the analyzed population into categories by age and disease is presented in Table 1.
Xerostomia was recorded in 14.5% (n=67) of all patients. Our evaluation of its prevalence revealed a 1:3 men-to-women ratio (M:W = 1:3). The mean age of xerostomia-positive patients was 55.9±1.4 years, while that of xerostomia-negative patients was 51.2±0.7 years (P=0.013, df=48). Table 2 shows the prevalence of xerostomia in respect to the variables of disease and sex. In order to determine sex-related differences in the prevalence of xerostomia among patients in each disease group, a men-to-women ratio was calculated for the prevalence of xerostomia (expressed in percentage). It is remarkable that there were significant sex-related variations in the prevalence of xerostomia between different disease groups. The highest prevalence of xerostomia was found in the group of patients with SC. However, there were no xerostomia-positive cases among men with SC at all.
Our study also revealed that xerostomia was treated only in 17.7% (n=12) of all xerostomia-positive cases. Treatment for xerostomia was administered to 12.5% of AR patients (n=3), and it was as follows: bearberry tea (1 case), sour diet (2 cases). Less than Medicina (Kaunas) 2008; 44 (12) one-third of LES patients (26.7%, n=4) received only sour diet (in all cases), and 16.1% of SC patients (n=5) were treated with pilocarpine (1 case), fuchsine (safranin-O) and vitamin B for cracks at the corners of the lips (1 case), artificial saliva (1 case), and sour diet (2 cases). Xerophthalmia was diagnosed in 13.7% of all patients examined (n=66). There were 4.9% (n=2) of the xerophthalmia-positive cases among men, and 14.1% (n=24) of cases among women, which shows 2.5 times higher prevalence of xerophthalmia among women. The majority (85.7%) of all xerostomiapositive patients were also xerophthalmia-positive (P<0.01, c²=360.225, df=1). Table 3 shows prevalence of xerophthalmia in respect to differences in disease and sex.
The highest prevalence of xerophthalmia was found in the group of patients with SC. In patients with other diseases, a similar distribution of xerophthalmia was observed even within different age groups. Fig. 3 shows the prevalence of xerophthalmia caused by different diseases in relation to respective age groups.
It should be noted that there was a marked sexrelated difference in the prevalence of xerophthalmia among AR and LES patients -there were significantly more xerophthalmia-positive women than men in these two groups. Moreover, there were no xerophthalmia-positive men with SC at all. Fig. 3 shows that the older the analyzed age group was, the higher was the prevalence of xerostomia and xerophthalmia, but the difference was too small to be statistically significant.
Our study showed that xerophthalmia was treated in 84.8% (n=56) of xerophthalmia-positive cases. In the AR group, 84.6% (n=22) of patients received treatment: artificial tears and eye drops (15 cases), and only eye drops (7 cases). In the LES group, 93.3% (n=14) of patients received treatment: artificial tears  Fig. 2 for graphical expression of distribution of xerostomia according to age and disease. See Fig. 3 for graphical expression of distribution of xerophthalmia according to age and disease. and eye drops (10 cases), and only eye drops (4 cases).
In the SC group, 80.0% (n=20) of patients received treatment with artificial tears and eye drops (15 cases) or only eye drops (5 cases). Our study has shown that frequency and quality of treatment administered for xerostomia were markedly different from those of treatment administered for xerophthalmia.

Discussion
For the purposes of our study, we divided all rheumatic patients into separate disease groups. Then we investigated correlations of those diseases with age and sex pertaining to emergence of xerostomic symptoms. Our results proved to be either identical or very similar to those found in relevant medical publications (1,2,4,7,9,25,29,32,35,36,42). In addition, new data on current prevalence of xerostomia in Lithuania and on specifics of its treatment were obtained.
Most of the patients in our study were women (see Table 1). We calculated ratios of sex distribution in separate disease groups. In SC group, the ratio of women to men was the highest -11:1, and in AR group -the lowest, 4.5:1 (Tables 2 and 3).
We divided our patients into three age groups: group 1 -up to 45 years, group 2 -45 to 60 years, and group 3 -more than 60 years. We found that younger patients were mostly in LES group (Fig. 1). In other disease groups, the distribution of patients by age was almost equal, and all these diseases were more prevalent in older patients.
Our study has confirmed that symptoms of xerostomia and xerophthalmia are quite often diagnosed in rheumatic patients. We have established a distinct correlation of higher prevalence of xerostomia with a respective rheumatic disease and female sex. We could not find any significant difference in the prevalence of sicca symptoms between younger and older age groups. Xerostomia is more frequently diagnosed in women than men. In most cases, xerostomia becomes apparent in older age concomitantly with rheumatologic diseases and is often accompanied by xerophthalmia. This allows us to draw the conclusion that female sex and xerophthalmia could serve as reliable indicators of possible xerostomia in rheumatic patients.
The prevalence of xerostomia varies in different rheumatic disease groups investigated by us.
However, while most published studies reported that the prevalence of xerostomia in these disease groups was 15% for AR, 30% for LES, 32% for SC (2,25,41,43,44); our findings are as follows: AR -11.6%, LES -9.1%, SC -28.4%. The comparison of the above results demonstrates a significant discrepancy in the LES group, which is rather difficult to explain. Perhaps, it is due to the fact that the population of our patients in LES group was considerably younger than that of other disease groups. It is quite possible that in the case of equal age distribution, the results would become similar (15)(16)(17)39).
We could not establish a significant reliable direct dependence of sicca symptoms on age ( Fig. 2 and Table 3). The prevalence of sicca symptoms increases with age, but it is too low to be relevant. Still there is a distinct increase in the prevalence of sicca symptoms after the age of 45. The question could be raised here, what are the main factors influencing sicca symptoms: the age of the patient or the duration of a rheumatic disease? However, this is beyond the scope of the present study.
Likewise, a higher prevalence of sicca symptoms was found in women. Men afflicted with rheumatic diseases only seldom displayed these symptoms (Tables 2 and 3). It is evident that the level of sex hormones and age are factors that exert a considerable influence on the exocrine glands and can evoke the sensation of dryness by affecting patients' psychological state. Age per se has no influence on the functioning of major salivary glands, and ageing alone does not cause their dysfunction (14,15,43,45,46). However, comorbid diseases and intake of medications should be pointed out as the main factors, which arise with advanced age and increase the risk of developing sicca symptoms. Aging may also lead to aggravated forms of general diseases, especially of those pertaining to the immune system (e.g. rheumatic diseases) (43,44). It is hard to identify precisely a single or main etiological factor causing xerostomia; therefore, this kind of research is liable to various conjectures and errors.
Xerostomia was treated only in 12 cases (17.7%) out of the total (n=70) of the examined population complaining of oral dryness. In comparison, xerophthalmia was treated in 56 (84.8%) of all (n=66) diagnosed cases.
Only in 2 cases out of the 12, in which patients were treated for xerostomia, the administered treatment was almost correct from the odontological point of view: artificial saliva and pilocarpine were prescribed. In all other cases, the treatment was sour diet (8 cases), bearberry (Arctostaphylos uva-ursi) tea (1 case), vitamin B plus fuchsine for lubrication of the corners of the lips (1 case). This clearly demonstrates that the majority of the treatment tactics were both insufficient and inadequate for fully restoring the quality of patients' lives. The treatment with vitamin B and fuchsine (safranin-O) can be evaluated only as prophylaxis against possible appearance of candidiasis at the corners of the lips, but not as a valid solution for the problems arising in the oral cavity. To the best of our knowledge, bearberry tea is a folk remedy against urinary tract infections, which due to its antibacterial and sympathomimetic qualities can have a positive effect on the oral cavity and the salivary glands in case of xerostomia as well. Unfortunately, when used for periods longer than three weeks, it produces acute symptoms of intoxication (47). We have not been able to find any articles quoted in foreign databases on the use of bearberries for treating xerostomia.
Our study has revealed that in Lithuania only a small percentage of xerostomia-positive patients receive treatment, and in most cases this treatment is completely inadequate (1-3, 22, 26, 27, 42).
Our findings show that symptoms of ocular and oral sicca were closely related. The majority (85.7%) of xerostomic patients were also xerophthalmia positive (P<0.01). This points to the characteristic feature of rheumatic patients -generalized exocrinopathy (43,48).
One of the shortcomings of our study was that no clinical tests were performed to examine the functioning of the salivary and lacrimal glands. Likewise, the patients were never directly, individually, and purposefully questioned about their sicca symptoms, their need for treatment, or efficiency of the treatments administered to them. In our opinion, such purposeful questioning would only determine more exactly the influence of sex and age on xerostomia and would reveal even a higher prevalence of sicca symptoms in rheumatic patients (15)(16)(17)(21)(22)(23)(24)(25).
However, we consider the initial patients' complaints and competence of the rheumatologists who had compiled the anamneses as valid enough for us to conclude that the results of our study are essentially correct. We believe that the data collected in the course of three years on all the hospitalized rheumatic patients with the referenced diseases are quite comprehensive and indicative of the actual xerostomiarelated problems, which afflict patients with oral sicca symptoms caused by other diseases as well.
Summarizing, with some displayed characteristics of rheumatologic inpatients, we maintain that women suffering from rheumatic diseases in advanced age should be warned about high probability of developing symptoms of oral and ocular dryness with all the ensuing complications. Treatment of oral and ocular dryness in rheumatic patients has not received adequate and sufficient attention yet (33). Further studies should focus in detail on prevalence and treatment of xerostomia, as well as on level of discomfort experienced by patients with other diseases, which are conducive to oral dryness. We believe that the problem of xerostomia is rather new in Lithuania, since we have failed to find any records of clinical studies on it conducted in our country.

Conclusions
1. The prevalence of xerostomia is several times higher in women than men.
2. Xerostomia is significantly related to xerophthalmia in patients with rheumatic disorders.
3. Treatment of xerostomia, unlike that of xerophthalmia, is both insufficient and inadequate.