Sjögren’s disease: When the dysregulated immune system attacks healthy tissues and organs

Sjögren’s disease is a rheumatic condition. The deregulated immune system attacks healthy tissues and organs, particularly the salivary and lacrimal glands. In the field of rare diseases, it is estimated that between 5,000 and 6,000 people in Portugal suffer from the illness, which was identified in the first half of the 20th century. Causes, symptoms, and treatment set the tone for an interview with rheumatologist Vasco C. Romão.

in – 21 April, 2024

Unexplained and incapacitating fatigue, joint pain and dry mouth, eyes, skin and vagina are among the ‘palpable’ symptoms of Sjögren’s disease, a rare condition characterised by deregulation of the immune system, which attacks healthy tissues and organs. A disease that “can appear at any age and in both sexes but affects nine times more women than men and appears more frequently after the age of 45”, emphasises Vasco C. Romão, Visiting Assistant Professor at the University of Lisboa. In Portugal, despite the lack of concrete data on the number of citizens affected by this disease, it is estimated that it could be between 5,000 and 6,000.

Although there is no cure for Sjögren’s disease, various treatments can help to control the symptoms, aided by drugs. Rheumatology is the speciality of medicine dedicated to the study of this type of systemic rheumatological disease, which involves several organs and systems. “All people suspected of having Sjögren’s disease should be referred by their GP to a rheumatology hospital consultation”, warns Vasco C. Romão, coordinator of the Sjögren’s Syndrome Consultation at ULS Santa Maria and also a researcher.

Understanding the diseases also implies knowing a little about their history. Henrik Sjögren, a Swedish ophthalmologist, identified patients with this disease in the 1930s. In what context was this discovery made?

Henrik Sjögren was a Swedish ophthalmologist (1899-1996) who was sent in 1929 by the Swedish College of Medicine to Jönköping, a town 300 Km from Stockholm, to examine a group of immigrants of Swedish descent, from Ukraine. This population had a high prevalence of trachoma, a chronic eye infection [conjunctivitis] caused by the ‘notorious’ Chlamydia trachomatis, which caused dry eyes by destroying mucus-producing cells. A year later, in 1930, as an ophthalmology intern in Stockholm, he observed a lady with decreased tear, saliva and sweat production, associated with a history of ‘chronic rheumatism’. Two other similar cases were added to this, and they were the first three patients described with dry eyes in the context of the condition now known as Sjögren’s disease – or syndrome, a name that was to be abandoned. In 1933, he published his doctoral thesis, which included nineteen patients with this pathology, ten of whom showed signs of inflammation and deformation of the joints.

How does Sjögren’s Disease manifest itself?

Sjögren’s disease – or syndrome, the name being abandoned – is a rheumatic disease in which the dysregulated immune system attacks healthy tissues and organs, particularly the salivary and lacrimal glands. The chronic inflammatory process destroys the tissues and leads to symptoms such as dry mouth and dry eyes.  The lack of saliva and tears can lead to dental problems (cavities) with difficulty chewing or swallowing, or a feeling of sand in the eyes and sores on the front of the eye (cornea). There is also inflammation in the rest of the body which leads to other frequent symptoms such as intense, unexplained tiredness and pain in the muscles and joints. There may also be episodes of ‘mumps’ in adulthood and in up to 30-40% of cases it affects other organs, causing symptoms such as fever, night sweats, weight loss, swelling of the joints or lymph nodes, red or purple patches on the skin, anaemia, a decrease in platelets and white blood cells. In rarer cases, it can also affect the lungs, kidneys, thyroid, liver, pancreas, nerves or brain (very rare).

Is there more than one type of Sjögren’s disease?

In fact, there is only one Sjögren’s disease. The term secondary Sjögren’s disease, historically used and being progressively abandoned, refers to cases in which there is another autoimmune rheumatological disease (rheumatoid arthritis, lupus, systemic sclerosis, among others) and, at the same time, complaints of dry eye and dry mouth, or other suggestive symptoms. Nowadays we know that Sjögren’s disease can exist simultaneously with other diseases and is not ‘secondary’ to them, but rather an individualised and specific disease.

Is the cause of this autoimmune disease known? Does genetic predisposition or environmental issues play a role?

As with most immune-mediated rheumatological diseases, there is no single cause – or one that is not yet known. There is usually a general genetic predisposition to this type of disease, such as an aunt, grandmother or cousin with lupus or rheumatoid arthritis, which forms a ‘breeding ground’ in which certain environmental stimuli such as tobacco, infections, stress, diet, among others, can lead to the development of the disease. Some viral infections, such as mononucleosis, have been associated with an increased risk of developing Sjögren’s disease, but so far it has not been possible to define a clear cause-effect relationship.

Are some population groups more affected?

Sjögren’s disease can appear at any age and in both sexes, but it affects nine times more women than men and appears more frequently after the age of 45. Post-menopausal women are therefore the group most affected. Generally, younger people (20-30 years old) don’t have as many symptoms of dry eyes and mouth, although they do or may have other typical symptoms, and the diagnosis is only made later.

How is the diagnosis made?

The diagnosis is made based on symptoms, clinical observation and the results of analyses and other complementary tests. Assessment by a Rheumatologist, Ophthalmologist and Stomatologist/Dentist is essential and should be carried out whenever possible at an early stage. The clinical examination assesses the existence and severity of dry mouth and eyes, swelling of the salivary glands, lymph nodes or joints, spots on the skin and other changes. The function of the salivary glands can be measured by the amount of saliva produced in each period or by scintigraphy of the salivary glands. The lack of tears and the search for ulcers (sores) on the cornea can be carried out in an ophthalmology consultation. The most important analyses include antinuclear antibodies (ANA), anti-SSA/anti-SSB and rheumatoid factor. Lip salivary gland biopsy, a simple procedure in which some of the small salivary glands in the mucous membrane of the mouth are removed, identifies a specific inflammation. The diagnosis is always clinical and made based on the rheumatologist’s opinion, considering his observation and the results of the tests. No single test can make the diagnosis.

Is there a cure for this disease or just treatment to relieve the symptoms?

Although there is no cure for Sjögren’s disease, various treatments can help control the symptoms. In addition, some immunomodulatory or immunosuppressive drugs can help modify the progression of the disease. Finally, there are several clinical trials underway at advanced stages that may lead to drugs approved specifically for this disease in the future.

How is the treatment done?

Given the involvement of the mouth and eyes, good oral and ocular health care is essential, with frequent assessment by a stomatologist/dentist and an ophthalmologist. The use of tears and artificial saliva are important to relieve the symptoms of dryness. In severe cases, oral or ocular gels, topical ocular cyclosporine, which controls inflammation of the lacrimal glands, or closure of the tear duct can be used. Pilocarpine increases saliva production and is indicated for the treatment of more severe symptoms. In addition, joint and muscle pain can be treated with anti-inflammatories or, when there is arthritis (joint inflammation), low-dose corticosteroids or immunomodulatory drugs such as hydroxychloroquine, methotrexate or leflunomide. Fatigue can improve with some of these drugs and with physical exercise. Treatment of other more serious manifestations depends on the organs affected and usually requires higher doses of corticosteroids or immunosuppressive drugs.

Can you give us an estimate of the number of Portuguese with this disease?

There is no concrete data in Portugal. It was thought to be one of the most common inflammatory rheumatic diseases, but recent European studies estimate that it affects less than 0.1 per cent of the general population (0.03 to 0.05 per cent). This would mean that up to 5,000 to 6,000 Portuguese may have Sjögren’s disease. The PORTRESS study, based on the National Register of Rheumatic Patients [], is the first to assess the characteristics of more than 1,300 people with this disease in Portugal.

In Portugal, do people with this disease find a response from the health system, particularly in terms of consultation and follow-up?

All people with suspected Sjögren’s disease should be referred by their general practitioner to a Rheumatology hospital consultation. Although there are still some gaps in some areas and hospitals in the country, where unfortunately there is no Rheumatology speciality, the National Health Service (SNS) in general, and rheumatologists in particular, have the capacity to respond to the diagnosis, follow-up, and treatment of people with this disease. Rheumatology is the speciality of medicine dedicated to the study of this type of systemic rheumatological disease – i.e. involving several organs and systems – and has an extensive and demanding training curriculum (internship) in the diagnosis, treatment, and monitoring of all rheumatic diseases, including Sjögren’s Disease. Collaboration with other specialities, especially in this case Ophthalmology and Stomatology, is essential for the proper care of these patients. In addition, depending on the type of involvement of other organs, assessment and guidance by other medical specialities may be necessary, namely Pulmonology, Neurology, Gastroenterology, Haematology, Gynaecology-Obstetrics, among others. It is therefore very important to monitor these patients in centres with experience and access to specialised care. At the Hospital de Santa Maria (ULS Santa Maria), there has been a Sjögren’s Syndrome Multidisciplinary Consultation since 2016, where patients with suspected Sjögren’s Syndrome are assessed on the same day by specialists from Rheumatology, Stomatology and Ophthalmology. Once the diagnosis has been confirmed or excluded, follow-up and treatment of the various symptoms and the disease is scheduled. More than 900 multidisciplinary consultations have been held to date, in a model that was recently successfully replicated at the Egas Moniz Hospital, ULS Lisboa Ocidental.

Is research being carried out in our country into this rare disease?

Yes. At ULS Santa Maria there is a Sjögren’s Disease Consultation, where patients with this pathology are monitored and, whenever applicable, proposed to take part in studies. We also have a Sjögren’s Disease Collection of biological samples (blood, saliva, salivary glands) in the Biobank of the Faculty of Medicine of the University of Lisbon (Faculdade de Medicina da Universidade de Lisboa). At the Rheumatology Department of the ULS Santa Maria there are several ongoing studies looking at different areas of the disease, from its mechanisms and causes to treatments and clinical trials with innovative drugs. These studies have been published in various scientific journals and presented at national and international congresses, including the International Symposium on Sjögren’s Disease, taking place in April in the Netherlands. In addition, other rheumatology services in the National Health Service (SNS) and the social and private sector, such as the Portuguese Institute of Rheumatology, also have ongoing studies with large numbers of patients.

Finally, is it possible to maintain a good quality of life with Sjögren’s Disease?

Although Sjögren’s Disease was once considered to be a disease that did not significantly affect the lives of those affected, it is now known that it causes a significant reduction in quality of life. The impact of Sjögren’s disease is felt on many levels, from unexplained and disabling fatigue to joint pain and dry mouth, eyes, skin, and vagina. Various dimensions of social, personal, professional, and relational life are affected and seriously compromised. Even so, there has been progress in knowledge about this pathology and the approach at different levels, pharmacological and non-pharmacological, is currently key to improving the quality of life of those affected. The near future promises to bring good news, with more alternatives for the appropriate treatment of patients affected by this serious and complex condition.

About Vasco C. Romão

Vasco C. Romão, MD, PhD, is a rheumatologist at the Rheumatology Service of ULS Santa Maria where he is the coordinator of the Sjögren’s Syndrome Consultation. From 2017 to 2023 he was the Sjögren’s Syndrome Coordinator for the ERN-ReCONNET European Reference Network. He is also a researcher at the Rheumatology Research Unit of the Institute of Molecular Medicine (Instituto de Medicina Molecular) and an Invited Assistant Professor at the Faculty of Medicine of the University of Lisbon (Faculdade de Medicina da Universidade de Lisboa). His research focuses on the clinical and pathogenic aspects of Sjögren’s disease, as well as the pathobiology of the synovial membrane and rheumatoid arthritis. He is the author of more than 70 publications and 200 scientific communications.