major complication of the rheumatic diseases, is reported to occur in primary SS [48, 49]. The presence of PAH is associated with a poor prognosis in patients with SS. One report suggests that a subset of primary SS patients are at added risk in that the presence of RP, cutaneous vasculitis, and interstitial lung disease is more commonly seen when compared to patients with primary SS without PAH [49]. The presence of a positive anti-Ro/SSA, anti-RNP, rheumatoid factor or hypergammaglobulinemia in a patient with SS syndrome may also increase the risk for PAH [49]. When confronted with this subset of patients, it justifies a careful evaluation for underlying PAH with noninvasive screening by echocardiography and, if suspected, a right-heart catheterization to validate the diagnosis. Another report suggests that screening by echocardiography is warranted in primary SS patients when palpable purpura, antibody reactivity to Ro/SSA, and low C4 levels are present in that this subset of patients had increased risk for pericardial effusion and pulmonary hypertension [50]. There are now several therapeutic options for patients with PAH associated with a connective tissue disease that may improve outcome if not quality of life [51, 52].

The biological mechanism of what might link RP to primary SS is unknown. Very few studies have been done to investigate the causes of RP in primary SS and thus it is difficult to make any conclusions. Endothelium-dependent vasodilation using brachial artery responses measured by ultrasonography was reported to be impaired in patients with primary SS and RP when compared to healthy controls [53]. However, this study was small and remains unconfirmed. One theory is that interactions between blood vessels and activated lymphocytes might disturb endothelial function and cause abnormal vascular reactivity. Willeke et al. [26] reported that an increase in the number of interferon-gamma secreting peripheral blood mononuclear cells was seen in primary SS patients with RP compared to normal controls and to patients with primary SS without RP. The authors speculated there might be a pathological role of this subpopulation of interferon secreting T-lymphocyte that mediates vasospasm in these patients. The presence of RP has been associated with higher concentrations of circulating sL-selectin (CD62L) in the serum of patients with primary SS, suggesting that L-selectin is released from activated cells and may indicate a mechanism for vascular perturbation [54]. This study requires further confirmation but its results are consistent with a report that serum sL-selectin levels are elevated in patients with scleroderma [55].

15.1Evaluation of the Sjögren’s Syndrome and Raynaud’s Phenomenon

Most patients with primary SS will have relatively mild RP without digital ulceration or critical ischemia that threatens loss of the digit. The presence of severe RP and ischemic lesions should make the physician suspicious of a complicating secondary process or underlying associated rheumatic disease, especially scleroderma or lupus. Each patient should be fully evaluated for major or macrovascular disease that may be causing or aggravating the digital events. This begins with a good