Rheumatoid arthritis is an autoimmune disease that affects primarily the joints but also may involve extraarticular tissues such as the skin, blood vessels, lungs, and heart. Because the principal manifestations of the disease are in the joints, it is discussed in Chapter 21.
Sjögren syndrome is a chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of the lacrimal and salivary glands. It occurs as an isolated disorder (primary form), also known as the sicca syndrome, or more often in association with another autoimmune disease (secondary form). Rheumatoid arthritis is the most common associated disorder, while other patients have SLE, polymyositis, scleroderma, vasculitis, mixed connective tissue disease, or autoimmune thyroid disease.
The lacrimal and salivary glands characteristically show dense lymphocytic infiltration consisting mainly of activated CD4+ helper T cells and some B cells, including plasma cells. Serologic studies frequently reveal autoantibodies. Antibodies against two ribonucleoprotein antigens, SS-A (Ro) and SS-B (La) (see
Table 5.11 ), can be detected in as many as 90% of patients by sensitive techniques. High titers of antibodies to SS-A are associated with early disease onset, longer disease duration, and extraglandular manifestations, such as cutaneous vasculitis and nephritis. These autoantibodies also are present in a smaller percentage of patients with SLE and hence are not diagnostic of Sjögren syndrome. In addition, about 75% of patients have rheumatoid factor (an antibody reactive with self IgG), and 50% to 80% of patients have ANAs.
The pathogenesis of Sjögren syndrome remains obscure, but the pathology and serology, as well as an association, albeit weak, with HLA alleles, all point to activation of autoreactive T cells and B cells. The initiating trigger may be a viral infection of the salivary glands, which causes local cell death and release of tissue self antigens. In genetically susceptible individuals, CD4+ T cells and B cells specific for these self antigens may escape tolerance and participate in immune reactions that lead to tissue damage and, eventually, fibrosis. However, the role of particular cytokines or T cell subsets, and the nature of the autoantigens recognized by these lymphocytes, remain mysterious.
MORPHOLOGYLacrimalandsalivaryglandsarethemajortargetsofthedisease,butotherexocrineglands,includingthoseliningtherespiratoryandgastrointestinaltractsandthevagina,alsomaybeinvolved.Theearliesthistologicfindinginboththemajorandtheminorsalivaryglandsisperiductalandperivascularlymphocyticinfiltra tion.Eventuallythelymphocyticinfiltratebecomesextensive(Fig.
5.27 ),andinthelargersalivaryglands,lymphoidfollicleswithgerminalcentersmaybeseen.Theepithelialcellsliningtheductsmaybecomehyperplasticandobstructtheducts.Laterthereisatrophyoftheacini,fibrosis,andhyalinization;stilllaterinthecourse,theatrophicparenchymamaybereplacedwithfat.Insomecases,thelymphoidinfiltratemaybesointenseastogivetheappearanceofalymphoma.Indeed,thesepatientsareathighriskfordevelopmentofB-celllymphomasofthesalivaryglandandotherextranodalsites(Chapter12).Thehistologicfindingsarenotspecificordiagnosticandmaybemimickedbychronicsialdenitiscausedbyductalobstructionduetocalculi.