18.1Introduction

Primary SjšgrenÕs syndrome (SS) usually has a benign course centered on sicca features and general musculoskeletal features that are managed symptomatically [1]. However, a subset of SS patients develops more severe extraglandular disease that warrants close monitoring and aggressive treatment [2, 3]. Although the extraglandular manifestations often show a similarity to systemic lupus erythematosus (SLE), there are important differences between the types of clinical presentations that may be present in the SS and SLE patient [4]. Both SS and SLE patients exhibit constitutional symptoms (fatigue, arthralgia, myalgia, low-grade temperatures, lymphadenopathy) that are treated in a similar manner using NSAIDs and hydroxychloroquine [5]. SS patients develop skin rashes including leukocytoclastic vasculitis, RaynaudÕs phenomenon, and hematologic complications, which also receive treatment regimens similar to SLE.

However, it is important to distinguish between the SS and SLE because there are important differences in the treatment of each set of patients [2, 5]. In particular, the issue of lymphoproliferation (including increased risk of lymphoma) and a higher prevalence of lymphocytic inÞltrative disease (interstitial nephritis, autoimmune hepatitis, and interstitial pneumonitis) occur in the SS patient as well as a different type of particular skin rashes (hyperglobulinemic purpura and anetoderma) and the risk of lymphoma. Also, the types and incidence and type of neuropathies (peripheral and central), including

demyelinating disorders, may differ in the SS and SLE patient. Further, the SS patient may exhibit overlap with other autoimmune disorders including rheumatoid arthritis (RA), scleroderma, polymyositis, polyarteritis nodosa-like vasculitis, and primary biliary cirrhosis, which will require particular therapies.

This chapter will emphasize the Òday-to-dayÓ approach that we pursue at our clinic for treatment of common questions in SS patients. A summary of extraglandular manifestations discussed in this chapter is presented in Table 18.1. This chapter will supplement the other contributions in this book on ÒTraditional Oral Therapies of SS,Ó ÒBiologic Therapies Including CD20, CD20 and BAFF,Ó and novel ÒEmerging Therapies: Tyrosine Kinase and Jak Kinases, Gene Therapy and microRNA targets.Ó Also, the speciÞc treatment of neuropathies, Þbromyalgia, and ENT manifestations is covered in more detail in additional chapters of this book.

Due to increasing specialization and subspecialization of medicine, SS patients are increasingly turning to the rheumatologist to co-ordinate and manage a vast array of intricate medical issues. Indeed, rheumatologists are Þnding themselves not only playing the central ÒquarterbackÓ in the treatment of the SS patient, but also increasingly becoming some patientsÕ primary care provider, treating an array of problems associated with very complicated patients.

Further, other specialists (including emergency room physicians or orthopedic surgeons) are unclear what extraglandular manifestations may be the result of SS, as they try to sort through the patientÕs complaint of chest pain or

Kidney glomerulonephritis including

Amyloid, cryoglobulinemia, immune complex (including unrecognized SLE)

Interstitial nephritis, renal tubular acidosis with periodic paralysis (low K), metabolic acidosis, renal stones (nephrocalcinosis), glomerulonephritis, renal calculus Obstructive nephropathy

Cyclophosphamide Azathioprine Mycophenolic acid

Oral potassium and sodium carbonate (3Ð12 g/day) Rituximab

Bladder

Interstitial cystitis

Cystitis due to prior therapy (i.e., cyclophosphamide) Polyuria due to polydipsia

Pentosan polysulfate sodium

Recognition of anti-cholinergics exacerbating sicca symptoms