Sjogren's Syndrome

Novel Insights in Pathogenic, Clinical and Therapeutic Aspects

Alessia Alunno, Elena Bartoloni, Roberto Gerli

• Publisher: Academic Press
• Year: 2016
• Print ISBN: 9780128036044
• eBook ISBN: 9780128036327
• Topic: Medicine
• Subtopic: Diseases & Allergies

Sjogren's Syndrome: Novel Insights in Pathogenic, Clinical and Therapeutic Aspects provides the reader with an overview of current knowledge about Sjogren's Syndrome. The book summarizes the huge amount of literature concerning related advances in genetic background, pathogenesis, clinical picture, and therapeutic approaches. It integrates basic immunology concepts, clinical aspects, and pharmacological issues.Scientific progress has allowed us to unmask novel pathogenic mechanisms, to perform genome wide studies, and to identify clinical and serological features associated with different disease subsets and, eventually, different disease prognoses. In addition, the increasing knowledge about SS pathogenesis provides the rationale to employ targeted therapies in SS as has already occurred in rheumatoid arthritis and systemic lupus erythematosus.- Discusses heterogeneity of topics and audience, from basic immunology to clinical aspects and therapeutics- Provides novel lines of investigation and supports the management of patients requiring novel therapeutic approaches- Presents a deeper knowledge on SS clinical management as well as on immunological aspects possibly leading to new lines of investigation- Offers a bridge between the clinician and the scientist, and vice versa- Provides the reader with most recent and relevant updates due to the novelty of topics

Chapter 1

Introduction

History of Sjögren’s Syndrome

C. Baldini, and S. Bombardieri University of Pisa, Pisa, Italy

Abstract

Sjögren's syndrome (SS) is a complex disorder characterized by both organ-specific and systemic manifestations, potentially expanding to lymphoproliferative complications. In addition to presenting as primary or secondary disease, SS can occur in association with organ-specific autoimmune diseases, as well as in overlapping complex entities with the major connective tissue diseases. Over the years, SS has been described first as an organ-specific disorder involving salivary and lachrymal glands, and then as a systemic autoimmune disease displaying significant extraglandular manifestations. In this chapter we review the crucial steps in the history of SS.

Keywords

History; Lachrymal glands; Mikulicz syndrome; Salivary glands; Sjögren's syndrome

1. Introduction

Sjögren’s syndrome (SS) is a complex disorder characterized by both organ-specific and systemic manifestations, potentially expanding to lymphoproliferative complications.¹ In addition to occurring as a primary or secondary disease, SS can occur in association with organ-specific autoimmune diseases, as well as in overlapping complex entities with the major connective tissue diseases.^2,3

SS is named after the Swedish ophthalmologist Henrik Sjögren, who presented his doctoral thesis in 1933.⁴ However, the historical traces of SS can be found in a number of case reports published during the 19th century before Henrik Sjögren. Over the years, SS has been described first as an organ-specific disorder involving salivary and lachrymal glands, and then as a systemic autoimmune disease displaying significant extraglandular manifestations.^5–7

Norman Talal has suggested that the history of SS can be subdivided into three phases⁸: firstly, the initial definition of SS through a series of reports documenting its glandular manifestations; secondly, beginning in the 1950s, the second definition of SS as an autoimmune disorder potentially involving different organs and systems; and thirdly, since the 1980s, the era of molecular biology.

1.1. The History of Sjögren’s Syndrome Before Henrik Sjögren

In the late 1890s through the early 1900s, many cases were published describing the presence of simultaneous ocular and oral dryness, sometimes with coexistent chronic rheumatism or gout. These cases can be considered as “antecedents” to the actual SS. The most relevant reports published in the 50 years before Henrik Sjögren’s doctoral thesis are described below according to their temporal appearance in the literature.

The entity “keratitis filamentosa” (filamentous keratitis) was first reported in 1882 by the ophthalmologist Thomas Leber who, in his lecture “About the Origin of the Retinal Detachment,” described three patients with a dry inflammation of the cornea and conjunctiva with filamentous formations. Leber thought that they were associated to a viral infection of the cornea and did not associate this entity with the dryness of the ocular surface; however, his observation played an important role in the future concepts of SS.⁹

A few years later, at the beginning of 1888, Hutchison (1828–1913) published the case of a 60-year-old woman with a severe oral dryness, severe dysphagia, and arrested salivary secretion of the glands. Hutchison hypothesized that her condition could have been the result of a chronic nervous state.^10,11 On March 9 of the same year in London, Dr. WB Hadden (1856–93) presented to the Clinical Society his own case of dry mouth. He used the neologism of xerostomia to describe the case of a 65-year-old woman with dry mouth, “nearly unable to swallow” … “her tongue was red, absolutely dry and cracked in all directions like a “crocodile’s skin” … “No tears appeared when she tried to cry.” The xerostomia improved if treated with pilocarpine (Jaborandi). According to Sir William Osler, in his famous text book The Principles and Practice of Medicine (1982), Hutchison was the first to have coined the term xerostomia, while Hadden was the first to have associated the condition to the “involvement of some center which controls the secretions of the salivary and buccal glands.”¹²

In 1892 the Polish surgeon Dr. Johann Mikulicz-Radecki (1850–1905) reported to the Society for Scientific Medicine in Koenigsberg the case of a 42-year-old farmer with painless symmetrical enlargement of the lachrymal and salivary glands. There was no evidence of diminution in either lachrymal or salivary secretions. He died 14 months later. The histological examination of the submandibular glands showed extensive acinar atrophy and intense round cell infiltration, which today are known to be suggestive of salivary glands with mucosa-associated lymphoid tissue lymphoma.¹³ Bilateral swelling of the lachrymal and salivary glands without other disease was called Mikulicz disease after him; when this condition was found in association with other diseases including tuberculosis, sarcoidosis, lymphoma, it was termed Mikulicz syndrome.¹⁴ Later, Morgan and Castleman concluded, on the basis of pathological descriptions, that Mikulicz disease and SS were the same entity.¹⁵

In 1925 the dermatologist Henri Gougerot (1881–1955) described three separate cases of progressive and chronic dryness of mouth caused by atrophy of the salivary glands. Dryness of the eyes, nose, larynx, and vagina was variably involved, suggesting that a direct assault to the glands or the alteration of the sympathetic innervations of the glands may have been involved.¹⁶

In 1928–29 Houwer presented four patients without tear secretion. He wrote that keratitis filamentosa was bilateral and chronic; half of the patients had keratitis filamentosa in combination with arthritis. Houwer admitted that he did not know if an innervational, toxic, or trophic cause was present, including urates. None of his patients had keratomalacia or avitaminosis A.¹⁷

Some clinicians over time have thought that Mikulicz, Gougerot, and Houwer had published basic concepts of what later became known as SS, and that their names should be proposed as eponyms to complement the term of SS (ie, Sjögren-Mikulicz syndrome, Gougerot-Sjögren disease, or Gougerot-Houwer-Sjögren syndrome).

Among the other authors cited subsequently by Henrik Sjögren himself as having reported cases of dry eyes and dry mouth in the decades between 1889 and 1930, the following should be mentioned: Fischer, Wagenmann, Umber, Fuchs, Deutschmann, Kreiker, Schöninger, Stock, Clegg, Scheerer, Albrich, Isakowitz, Engelking, Avizonis, Betsch, Knapp, Vogt, Pillat, Duke-Elder, Hauer, and Wissmann.^5,7

None of these authors, however, had highlighted the systemic “nature” of the disease before Henrik Sjögren.

1.2. The History of Sjögren’s Syndrome: Henrik Sjögren

Henrik Sjögren (1899–1986) was born in Köping, a small city in central Sweden on lake Malaren. His father, Conrad Johansson, was a businessman while his mother, Emelie, worked in a bank. In 1923, for practical reasons the family legally changed its name to the mother’s maiden name, Sjögren (Sjö = lake and gre = branch of tree). Henrik studied medicine in the Karolinska Institute, and in 1927 received his medical degree as a “physician.” During his medical studies, he became engaged to Maria Hellgren, the daughter of a well-known oculist. After graduating, he continued working at the eye clinic of Serafimer Hospital at the Karolinska Institute. In 1929 the Royal Medical Board of Sweden sent him to Jönköping to examine a group of Swedish immigrants from the Ukraine, many of whom had trachoma and tear deficiency. Following their cases, Henrik Sjögren became interested in surfocular dryness.^5,7,8,10

In 1930, Henrik Sjögren observed a middle-aged woman with lachrymal, salivary, and sweat hyposecretion and “rheumatismus chronicus.” He introduced the neologism keratoconjunctivitis sicca (KCS) to describe her ocular manifestations, which were assessed with rose bengal and methylene blue. This...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• List of Contributors
• Preface
• Chapter 1. Introduction: History of Sjögren’s Syndrome
• Chapter 2. Clinical Features
• Chapter 3. Management of Sjögren’s Syndrome
• Chapter 4. Classification Criteria for Sjögren’s Syndrome
• Chapter 5. Imaging Procedures Useful for the Diagnosis of Sjögren’s Syndrome: Abnormalities of the Major Salivary Glands
• Chapter 6. Sjögren’s Syndrome–Associated Lymphoma
• Chapter 7. Spontaneous and Inducible Animal Models of Sjögren’s Syndrome
• Chapter 8. Genetics, Genomics, Gene Expression Profiling, and Epigenetics in Sjögren’s Syndrome
• Chapter 9. Autoantigens and Autoantibodies in the Pathogenesis of Sjögren’s Syndrome
• Chapter 10. Sjögren’s Syndrome and Environmental Factors
• Chapter 11. Histology of Sjögren’s Syndrome
• Chapter 12. Glandular Epithelium: Innocent Bystander or Leading Actor?
• Chapter 13. T Cells in the Pathogenesis of Sjögren’s Syndrome: More Than Just Th1 and Th2
• Chapter 14. B Lymphocytes in Primary Sjögren’s Syndrome
• Chapter 15. Cytokines, Chemokines, and the Innate Immune System in Sjögren’s Syndrome
• Chapter 16. Autoantibodies and Autoantigens in Sjögren’s Syndrome
• Chapter 17. Outcome Measures in Sjögren’s Syndrome and Perspectives in Clinical Trial Design
• Chapter 18. Novel Therapeutic Strategies in Sjögren’s Syndrome: B-Cell Targeting
• Chapter 19. Novel Therapeutic Strategies in Sjögren’s Syndrome: T-Cell Targeting
• Chapter 20. New Biological Avenues for Sjögren’s Syndrome
• Index