functions and functional differences [10]. In addition, saliva contains secretory immunoglobulin A (sIgA), which can neutralize viruses and bacterial and enzyme toxins [6].

The oral cavity naturally harbors more than 500 different microbial species [11]. Among these, oral Streptococci, Actinomyces [12, 13], and Candida species [14] are the most frequent. Containing approximately 99.5% water and 0.5% organic and inorganic components such as electrolytes and proteins, saliva has the ability to modulate the oral microßora by favoring the attachment and proliferation of certain microorganisms and promoting the clearance of others [3]. Quantitative and qualitative changes of saliva can, thus, result in dental caries and erosion [15] and candidiasis [16].

Following intake of food containing fermentable carbohydrates such as sugar and starch, the pH in dental bioÞlm will drop and remain lowered until the carbohydrates are cleared from the mouth and the bacterial acid is buffered. The amount of acid produced by the bacteria and the saliva buffering capacity counteracting the decrease in pH determine the total decrease in pH. Demineralization of tooth enamel, the initial step in the caries process, occur when pH goes below a critical value; the pH at which saliva and bioÞlm cease to be saturated with respect to enamel mineral. Hence, it is crucial to reduce the amount of time that the pH stays below this value [4].

Saliva is buffered by three main systems, namely, the phosphate, the carbonate/ bicarbonate, and the protein buffer system, reviewed in Refs. [1, 4]. Within the physiological pH range, hydrogen and dihydrogen phosphate are the dominant forms of phosphate. Unstimulated saliva mainly contains dihydrogen phosphate, whereas stimulated saliva contains mainly hydrogen phosphate. The total saliva phosphate concentration decreases with increasing ßow rate. Consequently, the contribution of phosphate to the overall buffer capacity is reduced from 50% in resting saliva to approximately 10% in (highly) stimulated saliva [4].

The saliva bicarbonate concentrations vary from less than 1 mmol/L in resting saliva and

up to 60 mmol/L in highly stimulated saliva [3]. Due to these variations, the contribution from the bicarbonate buffer system to the overall buffer capacity varies from a little less than half in resting saliva to more than 90% in stimulated saliva (at high ßow rates). Hydration of carbon dioxide to carbonic acid is mediated by the enzyme carbonic anhydrase, which is present in the salivary glands as well as in saliva [4].

Last, several of the proteins in saliva can act as buffers. When the pH exceeds a proteinÕs isoelectric point, the protein can release protons and accept protons when pH declines the isoelectric point. With their isoelectric point around pHs 5 and 9, many salivary proteins exhibit good buffering properties at alkaline, and especially at acidic pH values. The buffering effect of proteins is less than bicarbonate and phosphate in human saliva, but has its own niche in integuments on mucosa and teeth and become the predominant buffering substances at these sites. By increasing the viscosity of saliva when pH becomes acidic, some salivary proteins also contribute physically by forming a diffusion barrier that protects the teeth against acid load [4]. Buffering capacity of stimulated saliva is easily measured by use of commercially available test strips (Dentobuff R strip, Orion Diagnostica Oy, P.O. Box 83, FI-02101 Espoo, Finland).

14.1.2 Assessment of Oral Dryness

14.1.2.1Subjective Symptoms—Xerostomia

Oral dryness creates an environment prone to development of disease in the oral cavity and associated tissues. In addition to protection against caries and other disease states in the oral cavity, such as bacterial and fungal infections, saliva is important for digestion, reviewed in Ref. [17].

The Þrst step in assessing xerostomia and salivary gland hypofunction in the evaluation of SS must include a thorough interview of the patient, with the purpose of ruling out possible inßuence by medication, other chronic disease, and previous radiation therapy to the head and neck

region. Of importance in the revised AmericanÐ European criteria for SS [18] patient classiÞcation are also questions regarding symptoms of oral dryness, such as (1) daily feeling of dry mouth for at least 3 months, (2) recurrent feeling of swollen salivary glands as an adult, and (3) drinking liquids to help to wash down dry foods. In addition, the physician can ask whether the patient has less saliva than usual, if the dryness is more pronounced at night or day, and how much water he/she drinks during 1 day.

Dry mouth can inßuence patientsÕ health, well-being, and overall quality of life [19], with impact on speech, changes in taste sensation, and swallowing difÞculties. PatientsÕ complaints may include burning sensation of the oral mucosa and tongue and impaired taste [20], dry lips, oral soreness, ulcers, difÞculties in speaking, chewing dry foods, and difÞculties in wearing removable dentures, reviewed in Ref. [21], summarized in Table 14.1. A recent study has also shown the economic impact of primary SjšgrenÕs syndrome, manifested through increased oral health care costs. With careful management and use of appropriate preventive measures, many of the negative health consequences can be minimized [22].

When the mouth is examined, the oral mucosa and tongue may be dry and sticky and the intraoral examination mirror may stick to the buccal mucosa or tongue. An increase in facial mimics is often observed. In women, the Òlipstick sign,Ó where lipstick adheres to the front teeth, may be a useful indicator of xerostomia [23]. The cracker/wafer test has also been validated to identify individuals with xerostomia [24]. Lips may be cracked, peeling, and atrophic [25]. Clinical

Table 14.1 Approximate frequency of oropharyngeal clinical manifestations in patients with SjšgrenÕs syndrome. Adapted and modiÞed from Rhodus [21]

symptoms of dry mouth may include sensitive and depapillated tongue (Fig. 14.1a), explosive development of dental caries [25] at atypical sites (cervical, buccal, and incisal) (Fig. 14.1b), and fungal/yeast infections (candidiasis) of the mouth and pharynx [16]. In addition, pronounced tooth wear/dental erosion (Fig. 14.1c) may occur [26].

The main reason for complaints and symptoms of oral dryness/xerostomia is a deÞciency in the continuous secretion of mucin-rich resting saliva. Previous reports indicate that the submandibular and sublingual salivary glands are most severely affected in SS [27]. As a result, the lubricating saliva from these glands is the Þrst that is lost, while the watery, protein-rich parotid saliva remains seemingly at Þrst, unaffected. Although xerostomia most often is associated with low saliva ßow rates, xerostomia may exist without the patient fulÞlling criteria for the diagnosis of hyposalivation, and hyposalivation may be symptom less [20]. Most likely, the sensation of oral dryness is due to localized oral dryness, notably in the palate where the salivary Þlm is the thinnest, and not a complete absence of oral ßuids [28]. Consequently, total salivary secretion can therefore be within normal values, while unstimulated, resting saliva is affected, giving a low secretion rate.

14.1.2.2Objective Measurements of Hyposalivation

Sialometry

Measuring of unstimulated and stimulated whole saliva are two simple screening tests for the salivary gland involvement in SS and should ideally be a routine part of any oral examination. Subjective reports of xerostomia are not sufÞcient when diagnosing SS [29, 30]. However, it is debated how objective and reliable the unstimulated salivary secretion measurements are and how the unstimulated secretion from the parotid gland compares to the submandibular and sublingual glands [27, 31, 32]. In any case, to obtain reproducible, valid, and comparable results, the test should be standardized to routinely be carried out in the morning or midmorning after the patient has been fasting overnight. In addition, cleaning of teeth, mouth rinsing, chewing gum,

Fig. 14.1 Female patient with primary SjšgrenÕs syndrome. (a) Sensitive, depapillated tongue with fungal/yeast infection (candidiasis). Note also dry, atrophic lower lip. (b) Extensive dental caries experience as indicated by Þllings at atypical sites and abundant prosthetic

restorations; buccal Þllings in the upper jaw and a nineunit bridge in the lower jaw. Recurrent cervical/root caries in the lower front indicate currently active caries disease. (c) Pronounced tooth wear/dental erosion on palatal and occlusal surfaces of the teeth

or smoking of tobacco should be avoided at least 2 h before the test is performed.

Tools required for measuring unstimulated and stimulated saliva are a timer and a 5 or 10-mL cylinder graded by 0.1 mL or, alternatively, a precision electronic weight balance with at least two digits and a plastic cup can be used to estimate the volume of saliva secreted. For stimulated saliva, 1 g parafÞn may serve as an inert chewing material for masticatory stimulation of saliva secretion [4].

Unstimulated saliva is usually collected over 15 min and stimulated saliva collected over 5 min. Before collection of saliva starts, the patient should be seated in a chair and should relax for 10Ð15 min. The surrounding environment should be calm and relaxing.

Unstimulated saliva is collected without any masticatory or gustatory stimulus and is basically

passive drooling of the saliva into the cylinder/cup. The patient should be seated in a relaxed position with elbows resting on the knees and the head tilted forward between the arms. Saliva is allowed to passively drain from the lower lip into a cylinder or pre-weighed container. Any movement in the tongue, cheeks, jaws, or lips should be avoided as this may stimulate secretion. Following an initial swallowing action, collection starts. After 15 min of drooling, the patient must empty all residual saliva into the collection device [4].

Stimulated saliva should be collected after the measurement of unstimulated salivary ßow. It includes the same steps, except the application of an inert chewing stimulus and a shorter collection time of 5 min. Every time the mouth Þlls up with saliva, the patient is instructed to spit into the cylinder or pre-weighed container.