10.1Introduction

Musculoskeletal manifestations such as myalgias, arthralgias, an intermittent non-erosive mild polyarthritis affecting mainly small joints, are common in patients with primary Sjögren’s syndrome. Myositis may also occur but much less frequently. The most important features of these manifestations are described in this chapter.

10.2Arthralgias and Arthritis

Articular involvement is the most common extra-glandular manifestation of primary Sjögren’s syndrome as noted by a number of different authors [1–5]. Arthralgias, with or without evidence of arthritis, may occur in 40–75% of patients and in about one third of them, they occur at presentation [1, 4–6]. Arthralgias, morning stiffness, and intermittent arthritis are frequent but chronic polyarthritis is not; when it occurs it is often non-erosive. It should be noted, however, that arthritis has not been universally reported in patients with primary Sjögren’s syndrome; for example, Kruize et al. from the Netherlands followed 31 patients for 10–12 years and failed to observe arthritis in any of them [7]. This contrasts with another longitudinal study conducted in Finland in which arthritis developed in 24% of 110 patients diagnosed between 1977 and 1992 and reexamined between 1994 and 1997 [1]. Finally, it seems that arthritis occurs with comparable frequency in patients with earlyvs. late-onset disease (12.5% vs. 9.8, respectively), as noted by Haga et al. from Denmark [8] and confirmed by Ramos-Casals et al. from Spain [9]; however, this is not always the case as articular involvement was reported in nearly 30% vs. 46% (not statistically significant) of primary Sjögren’s syndrome patients older comparable to younger than 70 years of age [10].

10.3Arthritis: Patterns of Expression

The arthropathy of primary Sjögren’s syndrome is usually symmetric and intermittent, affecting shoulders, wrists, hands, knees, ankles, and feet; it is typically nonerosive and non-deforming. The patterns of arthritis in these patients and its associated immunological and clinical features have been recently described by Haga et al. [6]. These authors studied 102 patients and followed them for about 5 years; arthralgias occurred in nearly 75% of these patients whereas arthritis was demonstrated in about 18% of them. The most commonly affected joints were shoulders, wrists, MCP joints, ankles, and MTP joints. Symmetrical bilateral arthritis was most commonly observed in ankles, wrists, shoulders, and MTP joints and less so in the MCP joints. Five patients had longstanding persistent arthritis, and one developed seronegative rheumatoid arthritis (RA). The presence of arthralgias/arthritis was not correlated with any clinical or immunological feature, and

erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values were normal. This study demonstrated that the arthritis of primary Sjögren’s syndrome is usually mild, self-limited, involving joints of various sizes, and not associated with other clinical and immunological features. A typical pattern is unior bilateral arthritis of the ankles, which in fact has been felt to be characteristic in patients with primary Sjögren’s syndrome, [6] but other joints may also be affected. Involvement of the cricoarytenoid joints has been reported infrequently [11, 12].

Rheumatoid factor (IgM-RF) is reported in a variable proportion of patients with primary Sjogren’s syndrome (32–74%) [1, 4–6, 13]. In the study by Garcia Carrasco et al., for example, IgM-RF was present in 38% of patients; these IgM-RF positive patients had articular involvement more often than the seronegative ones (45% vs. 33%, p = 0.017) [13]. Anti-cyclic citrullinated peptide (CCP) antibodies are much less common in patients with primary Sjogren’s syndrome (4–10%) [6, 14, 15] but when present synovitis is much more likely to be present as well [15].

10.4Differential Diagnosis: RA, SLE, and Other Arthropathies

Mild synovitis affecting mainly the small joints of the hands and feet is common in patients with primary Sjögren’s syndrome, but also in those with RA and SLE. The presence of IgM-RF may not be helpful in distinguishing RA from primary Sjögren’s syndrome since it is positive in both [16–18]; however, the presence of anti-CCP antibodies may favor the diagnosis of RA over primary Sjögren’s syndrome [14, 19]. In fact anti-CCP antibody positivity has been reported only in a minority of patients with primary Sjögren’s syndrome [20–22], who according to Atzeni et al. may later develop RA [15].

Joint involvement in SLE varies, ranging from non-erosive arthropathy (it is the most frequent form), erosive symmetrical polyarthritis with deformities similar to RA and mild deforming arthropathy (characterized as Jaccoud’s); severe functional disability may occur. In general, arthritis is less frequent in patients with primary Sjögren’s syndrome than in those with SLE [22]. Furthermore, the arthritis pattern of these patients is not directly comparable to those with SLE. In SLE, arthritis usually starts in the small hand joints (MCPs and PIPs) in a symmetrical fashion, and may be indistinguishable from early RA. The main distinguishing feature between the arthritis of primary Sjögren’s syndrome and SLE is the high frequency of ankle arthritis and the lack of deformities in the first [6].

Sarcoidosis should also be considered in the differential diagnosis because of the presence of sicca symptoms and even a positive biopsy of the minor salivary glands in these patients. The presence of hilar adenopathy and erythema nodosum in conjunction with arthritis usually involving the knees and ankles in conjunction with granulomas in the minor labial salivary gland biopsy as well as absence of reactivity to Ro/SSA and La/SSB favors the diagnosis of sarcoidosis [23]. Chronic arthritis in sarcoidosis is usually non-deforming and non-erosive involving the ankle, knees, and hand joints but a Jaccoud’s type arthritis has also been described. Finally, ankle

Both of these viruses have been associated with the pathogenesis of primary Sjögren’s syndrome, although the evidence for this is circumstantial.

In conclusion, arthritis in primary Sjögren’s syndrome is less common than in RA and in SLE, and is usually mild, resolving, and not associated to other clinical and immunological features. The arthritis pattern is more like the pattern found in retrovirus infections than in other inflammatory rheumatic diseases.

Figure 10.1 depicts such algorithm.

10.5Myalgias and Myositis: Diagnosis, Classification, and Role of Muscular Biopsy

Fatigue and myalgias are common in patients with primary Sjögren’s syndrome, although the underlying mechanisms are mainly unknown. A mild inflammatory myopathy of insidious onset and characterized by proximal muscle weakness has been described. Myalgias have been reported in 33% of patients with primary Sjögren’s syndrome [25] whereas fibromyalgia (FM), characterized by widespread chronic muscle pain, stiffness, and fatigue, has been reported in 47–55% of these patients [26, 27]. An inflammatory cell infiltrate on muscle biopsy has been described in some patients without any muscle symptoms.

Subclinical myositis, with histopathological signs of myositis, is very common and has been reported in 72% of patients with primary Sjögren’s syndrome [28] whereas clinically significant signs of polymyositis (PM) have been reported in 2.5–10% of these patients [29]. Inclusion body myositis (IBM)-like features have also been reported [30–32]. Most of the histopathological data in primary Sjögren’s syndrome derive from reports of single patients or smaller series of cases [33–36]. Perivascular inflammation and interstitial myositis without involvement of muscle fibers have been described [33] but this picture is relatively common in several other rheumatological diseases and its clinical significance is uncertain [34, 37, 38].

More recently, Lindvall et al. [28] investigated all patients with primary Sjögren’s syndrome registered at their rheumatology unit. The aim of the study was to relate light microscope and immunomorphological muscle biopsy findings to clinical symptoms, especially regarding pain in relation to inflammatory myopathy. They reported that histopathological signs of myositis, with or without degeneration, were present in 72% of muscle biopsies and the inflammation was always localized perivascularly; however, muscle symptoms were not related to histological signs of muscle inflammation. The criteria for FM were fulfilled by 27% of patients, whereas 17% had experienced muscle pain with no FM. The remaining 56% had not experienced muscle pain. None of the patients had clinical symptoms of IBM; however, 28% showed rimmed vacuoles in association with muscle fiber degeneration, and inflammation as well. The authors concluded that IBM-like findings may represent vacuolar myopathic degeneration due to previous subclinical muscle inflammation rather than a specific clinical entity.

To determine whether treatment of subclinical myositis can prevent the development of manifest degenerative changes, treatment trials are required. The presence of