Women represent close to 90% of all patients, so relatively few patients are men [9]. This gender aspect remains unexplained. A recent overview of the published studies did not Þnd any consistent differences between female and male SS. Individual studies showed statistically highly signiÞcant differences in some characteristics, but other studies could show differences quite in the opposite direction [10]. This is probably due to selection bias. This similarity of SS in women and men is consistent with the current praxis to use the same set of diagnostic criteria for both women and men.

SS typically starts at 40Ð50 years. Patients with atypical presentation, such as a 9-year-old boy presenting with SS-like condition, should be carefully analyzed for a Òpseudo-SS,Ó some but not all of which are mentioned in the current EuropeanÐAmerican criteria. If such a patient Þnally is shown to suffer from pSS, he probably has some very important individual factor(s) predisposing him to this disease, because it precipitates it against the odds and in spite of barriers, which normally prevent its development in such a setting. The story could be unraveled from both of these two ends, the typical or the atypical. However, as it is easier to deÞne the typical than atypical, the starting point of the present chapter is the typical patient with SS. Some reasons, which might explain the targeting of the exocrine glands of middle aged women for SS, are discussed below.

11.2Acinar Cell

Primary secrete of exocrine glands is produced by acinar cells. SS is characterized by, diminished secretion of in particular resting tear and salivary ßuid, secretory cell failure. If causes and mechanisms are looked for SS, the secretory acinar cell should be in focus.

Acinar cells function in part spontaneously to provide resting (non-stimulated) basal secretion, which does not vary much over time. However, this does not necessarily mean fully resting, but only refers to lack of any major stimulus (see

below for more). In contrast, secretion triggered by a stimulus leads to stimulated secretion over and above secretion provided by the resting ßow. The effector arm of this reßex arch is formed by the sympathetic and parasympathetic nerve Þbers.

From the point of view of the sympathetic nervous system the exocrine gland function can be divided into two distinct phases. During the resting phase, arteriolar blood ßows via metarterioles directly to post-capillary venules, bypassing the peri-acinar capillary network. This together with some spontaneous background activity typical for the autonomic nervous system might explain the continuous and relatively stable (non-regulated) ßow of resting saliva. This two-phase organization can possibly also be based on parallel organization of the acinar and intralobular capillary networks [11].

During the stimulation phase sympathetic nerve endings release norepinephrine (noradrenaline), which relaxes the precapillary sphincters and redirects arteriolar blood ßow to peri-acinar capillary network. The increased hydrostatic capillary pressure causes formation of transudate ßuid. This transudate forms bulk of the watery ßow drawn into the acinar lumen as a result of osmosis generated by the action of the parasympathetic nervous system (see below). Acinar cells do not have the capacity to store much ßuid although they contain some mucins. Instead, they produce it from plasma. It was earlier thought that sympathetic stimulation diminishes salivary ßow, but this conclusion was based on an artifact observed in early salivary gland studies in which supra-physiological concentrations of epinephrine were used. Concentrations used were so high that they caused a general vasoconstriction of arterioles and prevented almost totally ßow of blood through (met)arterioles and capillaries and, thus, also the subsequent formation of watery saliva.

Activity of the sympathetic nervous system needs to occur in a topologically and timely coordinated fashion together with the acetylcholinemediated (Fig. 11.1) parasympathetic stimulation of the acinar cells (Fig. 11.2). Therefore, logically also from the point of view of the