Sjogren's Syndrome

A Clinical Handbook

Frederick B. Vivino

• Publisher: Elsevier
• Year: 2019
• ISBN:
  9780323675352
• Topic: Medicine
• Subtopic: Surgery & Surgical Medicine

Written by leaders in the field and edited by Dr. Frederick Vivino, this concise, practical resource provides best practices for the diagnosis and treatment of Sjogren's Syndrome. It offers a concise overview of this complex autoimmune disease, including information on specific clinical settings, childhood Sjogren's, extra-oral and extra-ocular manifestations, vaccine safety, complementary and alternative medicine, and much more.

• Provides concise, clinically focused content with an emphasis on diagnosis and treatment.
• Includes Sjogren's Syndrome Foundation Practice Guidelines and the most recent ACR-EULAR classification criteria.
• Consolidates today's available information and experience in this important area into one convenient resource.

Chapter 1

Sjögren's syndrome

Past, present, and future

Robert I. Fox, MD, PhD¹, and Carla M. Fox, RN^{2 1}Chief, Rheumatology Division, Scripps-XiMED Medical Center, La Jolla, CA, United States ²Scripps-XiMED Medical Center, Clinic Administrator, La Jolla, CA, United States

Abstract

The tantalizing task of writing a chapter entitled Sjögren's syndrome: past, present, and future as an introduction to this clinical handbook recounts a journey that is now over a century old with no end in sight, at least not in the foreseeable future. Sjӧgren's syndrome (SS) still remains one of the most challenging disorders to diagnose and manage. The transition from past to present is relatively easy, as there are many classic descriptions of SS from the 1950s, and these pioneering publications described the pathologic findings and clinical features that are virtually the same as we recognize today. This chapter will also highlight some of the diagnostic and therapeutic challenges that we presently face. Furthermore, we hope to point the directions that we must address in the future to identify the underlying cause(s) and therapies that fundamentally improve the SS patient's quality of life.

Keywords

Anti-SSA; Extraglandular manifestations; Henrik Sjögren; History; Lymphoproliferation; Neuroendocrine; Personalized medicine; Quality of life; Sjögren's syndrome

Perspective

Sjögren's syndrome (SS) is a chronic autoimmune, rheumatic disorder most commonly characterized by dryness of eyes and mouth due to lymphocytic infiltration of the lacrimal and salivary glandular tissues. The condition has “benign” features that include dryness as well as vague myalgias, fatigue, and cognitive changes. These features are still poorly understood and treated. The benign symptoms represent the impact of the inflammatory process on the immune, neural, hormonal, and vascular signals necessary for normal secretory function or cognitive processes. In addition, SS patients have specific extraglandular manifestations affecting the renal, pulmonary, neural (both central and peripheral), hematopoietic, lymphatic, cardiac, and gastrointestinal systems.¹ Although there are clear overlaps with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and scleroderma, there are also clear differences (serologic, clinical, pathogenic) that distinguish these disorders.

It is worth noting that in a multicenter study from excellent academic centers, the majority of patients with dry eyes due to SS were initially misclassified as having either SLE or RA based largely on the finding of a positive result in antinuclear antibody (ANA) or rheumatoid factor analysis.² This initial mislabeling of SS as another diagnosis deprives patients of adequate follow-up for their particular ocular and oral complications, as well as of the proper attention to the particular extraglandular manifestations that SS patients develop. It also hinders the enrollment in clinical trials of SS patients with significant extraglandular manifestations who may benefit from biological therapies but may still be sitting in pulmonary, renal, or hematology clinics undiagnosed or misdiagnosed.

Key points

1. • “Benign” features such as fatigue, myalgias, cognitive dysfunction, and dryness are poorly understood.
2. • A variety of extraglandular manifestations occur that overlap with SLE, RA, and scleroderma.

SS has a worldwide distribution, and interestingly, the genomic associations differ in distinct ethnic groups, even though the histologic features of the tissue biopsies and epitopes recognized by autoantibodies show great similarities.^3–5 Comparison of genetic and nongenetic factors in these different groups may help find the common pathways important in clinical symptoms.

There are also important geographic differences that are associated with differences in clinical manifestations among various SS populations. For example, studies have shown that pulmonary arterial hypertension (PAH) in Chinese and Korean cohorts is more prevalent in SS and SLE patients than in those with scleroderma. However, we have many Chinese and Korean SS patients in the United States, and our registries do not reflect this shift in PAH incidence.⁶ This type of comparison may lead the way to identify environmental factors that trigger PAH in people of different genetic backgrounds.

Key points

1. • SS is frequently misdiagnosed as SLE or RA.
2. • Genomic associations differ in different ethnic groups.
3. • Geographic differences are associated with differences in disease manifestations.

Brief review of the past—as “we only stand on the shoulders of past giants”

Early history

The traditional paragraph on the “history” of SS starts with Mikulicz, in 1892, describing a neck mass in a man with lymphocytic infiltrates and myoepithelial islands.⁷ The term Mikulicz syndrome was used to describe the affected patients until the 1920s when it was subsequently discarded, as it failed to distinguish SS from other lymphocytic infiltrative processes such as tuberculosis and lymphoma.⁸ Ironically, the recent recognition of the IgG4 syndrome (which occurs predominantly in men of this age and parallels Mikulicz's description) suggests that the original view of SS and Mikulicz syndrome as “identical disorders” was indeed incorrect.⁹

In retrospect, one of the earliest and most convincing descriptions of SS was given by a British physician, W. B. Hadden, who presented a case to his colleagues at the Clinical Society of London on March 9, 1888 (Fig. 1.1).¹⁰ Dr. Hadden described a 65-year-old woman who was admitted to the hospital with a 7-month history of progressive dry mouth associated with dysphagia and the need to constantly drink fluids. As Dr. Hadden related, 2 months earlier “she had the occasion to cry but no tears would come.” On examination, the patient was well appearing and her vital signs were normal. The only notable finding was the mouth; he recounted that “nearly all her teeth are wanting” and “the tongue was red, devoid of epithelium, and cracked in all directions like a crocodile's skin.”

Figure 1.1 Dr. Hadden's case of dry mouth.

The patient spent 2 weeks in the hospital for observation and other diagnostic measures of the day. Finally, at the conclusion of the observation period, the decision was made to treat her with a medicinal remedy (tincture of jaborandi) administered both orally and subcutaneously. The patient responded and continued this therapy as an outpatient. Interestingly, the active ingredient in tincture of jaborandi, pilocarpine, was FDA-approved in tablet form some 110 years later as the first prescription drug for SS known as Salagen^®.

In 1933, an ophthalmologist named HENRIK SJÖGREN (Fig. 1.2) described a constellation of ocular and oral dryness and arthritis in a large group of patients as part of his ophthalmology doctoral thesis in Scandinavia.¹¹ The present author had the honor to meet an elderly Dr. Sjögren in 1986 (at the time of the first International Symposium on Sjӧgren's Syndrome in Denmark)¹² shortly before his death at the age of 87 years from the complications of a stroke.

As an incentive to young researchers, it is important to note that Dr. Sjögren recounted how his thesis was given a poor grade and he was banished from academia to a remote region of Scandinavia to practice ophthalmology. He sustained himself during this “exile” and retained his “sanity” only by playing the piano until his early work was “rediscovered.” This rediscovery occurred after translation of his thesis into English 10 years later, followed by a series of articles in the 1950s, beginning with a widely read New England Journal Clinical Pathology Conference by Drs. Morgan and Bloch.¹³ Of importance, the basic clinical and pathologic features that we ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Contributors
• Preface
• Chapter 1. Sjögren's syndrome: Past, present, and future
• Chapter 2. Diagnosis and evaluation of Sjögren's syndrome
• Chapter 3. Oral manifestations and management in Sjögren's syndrome
• Chapter 4. Diagnosis and management of Sjögren's syndrome related dry eye
• Chapter 5. Approach to children with Sjögren’s syndrome
• Chapter 6. Extraglandular abnormalities in Sjögren's syndrome
• Chapter 7. Vasculitis in Sjögren's syndrome
• Chapter 8. Lymphoproliferative disease in Sjögren's syndrome
• Chapter 9. Sjögren's syndrome: Peripheral and autonomic nervous system involvement
• Chapter 10. Diagnosis and management of central nervous system Sjögren's syndrome
• Chapter 11. Treatment of Sjögren's syndrome internal organ manifestations and constitutional symptoms
• Chapter 12. Integrative rheumatology: Complementary and alternative medicine for the management of Sjögren's syndrome
• Chapter 13. Perioperative management of patients with Sjögren's syndrome
• Chapter 14. Utility and safety of vaccines in Sjögren's syndrome
• Chapter 15. The cost of Sjögren's syndrome and the value of patient resources and support in management
• Index