Sjögren's syndrome
Encyclopedia
Sjögren's syndrome also known as "Mikulicz
disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine gland
s that produce tears
and saliva
.
It is named after Swedish ophthalmologist
Henrik Sjögren
(1899–1986), who first described it.
Nine out of ten Sjögren's patients are women and the average age of onset is late 40s, although Sjögren's occurs in all age groups in both women and men. It is estimated to affect as many as 4 million people in the United States alone, making it the second most common autoimmune rheumatic disease.
Sjögren's syndrome can exist as a disorder in its own right (primary Sjögren's syndrome) or may develop years after the onset of an associated rheumatic disorder, such as rheumatoid arthritis
, systemic lupus erythematosus
, scleroderma
, primary biliary cirrhosis
etc. (secondary Sjögren's syndrome).
The disorder should not be confused with the Sjögren–Larsson syndrome, which was also denoted T. Sjögren syndrome in early studies.
, typically including xerostomia
(dry mouth) and xerophthalmia
(dry eyes), part of what are known as sicca symptoms. In addition, Sjögren's syndrome may cause skin
, nose
, and vaginal dryness, and may affect other organs of the body, including the kidney
s, blood vessel
s, lung
s, liver
, pancreas
, peripheral nervous system
(distal axonal sensorimotor neuropathy) and brain
.
Sjögren's syndrome is associated with increased levels in Cerebrospinal fluid
(CSF) of IL-1RA, an interleukin 1 antagonist. This suggests that the disease begins with increased activity in the interleukin 1 system, followed by an auto-regulatory up-regulation of IL-IRA to reduce the successful binding of interleukin 1 to its receptors. It is likely that interleukin 1 is the marker for fatigue, however, increased IL-1RA is observed in the CSF and is associated with increased fatigue through cytokine
induced sickness behavior
. On the other hand, Sjögren's syndrome is characterized by decreased levels of IL-1ra in saliva, which could be responsible for mouth inflammation and dryness. Patients with secondary Sjögren's syndrome also often exhibit signs and symptoms of their primary rheumatic disorders, such as SLE, Rheumatoid Arthritis or Systemic Sclerosis.
Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as anti-nuclear antibody
(ANA) and rheumatoid factor
(because SS frequently occurs secondary to rheumatoid arthritis), which are associated with autoimmune diseases. Typical Sjögren's syndrome ANA patterns are SSA/Ro
and SSB/La, of which SSB/La is far more specific; SSA/Ro is associated with numerous other autoimmune conditions but are often present in Sjögren's.
Schirmer's test
measures the production of tears: a strip of filter paper is held inside the lower eyelid for five minutes, and its wetness is then measured with a ruler. Producing less than five millimeters of liquid is usually indicative of Sjögren's syndrome. However, lacrimal function declines with age or may be impaired from other medical conditions. An alternative test is nonstimulated whole saliva flow collection, in which the patient spits into a test tube every minute for 15 minutes. A resultant collection of less than 1.5 mL is considered a positive result. It takes longer to perform than Schirmer's test, but does not require special equipment.
A slit-lamp examination
can reveal dryness on the surface of the eye. Salivary gland function can be tested by collecting saliva and determining the amount produced in a five minute period. A lip biopsy
can reveal lymphocyte
s clustered around salivary glands, and damage to these glands due to inflammation.
Ultrasound examination of the salivary glands is the simplest confirmatory test and has the added advantage of being non-invasive with no complications. The parenchyma of the gland demonstrates multiple, small-2-6 mm hypoechoic lesions which are representations of the lymphocytic infiltrates. Often sialectasis with calculi are demonstrated if the disease is advanced. The sonographic findings have excellent symptom correlation. The other advantage of ultrasound is that complications of the disease such as extra-nodal lymphomas can often be detected as larger 1–4 cm hypoechoic intra-parenchymal masses.
There is also a radiological
procedure which is a reliable and accurate test for Sjögren's syndrome. A contrast agent is injected into the parotid duct
, which opens from the cheek into the vestibule
of the mouth opposite the neck of the upper second molar tooth. Widespread puddling of the injected contrast scattered throughout the gland indicates Sjögren's syndrome.
The Revised Classification Criteria for Sjögren's Syndrome requires the presence of signs, symptoms, and lab findings.
Patient-reported symptoms must include both ocular symptoms, such as daily, persistent, troublesome dry eyes for more than three months, and oral symptoms, such as needing to drink water to swallow food.
Objective evidence of eye involvement relies on Schirmer's test and the Rose bengal score (or similar). Histopathology
studies should show focal lymphocytic sialadenitis. Objective evidence of salivary gland involvement is tested through ultrasound examinations, the level of unstimulated whole salivary flow, a parotid sialography, or salivary scintigraphy. Autoantibodies against Ro (SSA) and/or La (SSB) antigens are also expected.
SS can be excluded from people with past head and neck radiation therapy
, hepatitis C
infection, Acquired immunodeficiency syndrome
(AIDS), pre-existing lymphoma
, sarcoidosis
, graft-versus-host disease
, and use of anticholinergic
drugs (since a time shorter than four times the life of the drug).
of the ductal and acinar epithelial
cells which is responsible for the glandular tissue damage.
s may ease the symptoms of dry eyes. Some patients with more severe problems use goggles to increase local humidity or have punctal plug
s inserted to help retain tears on the ocular surface for a longer time. Additionally, cyclosporine (Restasis) is available by prescription to help treat chronic dry eye by suppressing the inflammation that disrupts tear secretion. Prescription drugs are also available that help to stimulate salivary flow, such as cevimeline (Evoxac) and pilocarpine
. Nonsteroidal anti-inflammatory drugs may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroid
s or immunosuppressive drugs may be prescribed. Also, disease-modifying antirheumatic drug
s (DMARDs) such as methotrexate
may be helpful. Hydroxychloroquine
(Plaquenil) is another option and is generally considered safer than methotrexate
. Salagen, a man-made form of pilocarpine, can be used to help produce tears as well as saliva in the mouth and intestines. It is derived from the Jaborandi plant.
In the advanced stage, despite the use of tear replacement drops, the eyes always feel burning,
scratchy, sore. The sufferer is always aware of some discomfort, the eyes feel worse in the morning and late evening. The use of tear replacement drops becomes tedious and ineffective. At this point it may be appropriate to consider punctal plugs.
Each eye has two sites at the inner corner of each eyelid where tears drain from the eye. The upper eyelid 'puncta' drains approximately 40% of the tears away and the lower puncta drains away the remaining 60% of the tears. If there is a problem with the quantity of tears, as there is in Sjögren's disease, plugging the lower puncta can result in the tears that the patient has remaining on the eye longer.
Punctal plugs can be inserted into the lower or upper tear drainage canals of the eyes. The procedure takes only a few minutes and is painless. It can be done in the optometrist or ophthalmologist's office. Generally, collagen plugs are inserted first. These plugs will dissolve within a few days, so it gives the patient a chance to see if there is any improvement in comfort. Generally, the improvement is immediate. The patient may proceed to use of permanent plugs, although these too can be removed if necessary.
treatment is also necessary (and often overlooked by the patient), as the lack of saliva associated with xerostomia creates an ideal environment for the proliferation of bacteria that cause dental caries
(cavities). Treatments include at-home topical fluoride application to strengthen tooth enamel and frequent teeth cleanings by a dental hygienist. Existing cavities must also be treated, as cavities that extend into the tooth can not be effectively treated through teeth cleaning alone, and are at a high risk of spreading into the pulp of the tooth, leading to the loss of vitality and need for extraction or root canal
therapy. This treatment regimen is the same as that used for all xerostomia patients, such as those undergoing head and neck radiation therapy which often damages the salivary glands, as they are more susceptible to radiation than other body tissues.
Unfortunately, many patients, not realizing the need for dental treatment, do not see a dentist until most of their teeth are beyond the point of restoration. It is not uncommon for a dentist to see a xerostomia patient with severe, untreatable cavities in almost every tooth. In severe cases, the only viable treatment may be to extract all of the patient's teeth and treat with prosthetics such as dentures or implants.
s, hoarseness, and difficulty in swallowing and eating. Debilitating fatigue
and joint pain can seriously impair quality of life. Some patients can develop renal involvement (autoimmune tubulointerstitial nephritis) leading to proteinuria
, urinary concentrating defect and distal renal tubular acidosis
.
Patients with Sjögren's syndrome have a higher rate of non-Hodgkin lymphoma
compared to both patients with other autoimmune diseases and healthy people. About 5% of patients with Sjögren's syndrome will develop some form of lymphoid malignancy. Patients with severe cases are much more likely to develop lymphomas than patients with mild or moderate cases. The most common lymphomas are salivary extranodal marginal zone B cell lymphomas (MALT lymphoma
s in the salivary glands) and diffuse large B-cell lymphoma.
with congenital heart block
requiring a pacemaker
.
On September 1, 2011, tennis player Venus Williams
announced that she had been diagnosed with Sjögren's syndrome, and that because of the disease, she was withdrawing from the 2011 US Open
.
were under investigation in 2007. The most promising seemed to be the anti-CD20
rituximab
and the anti-CD22
epratuzumab
; the anti-TNF-α and IFN-α drugs seemed less effective.
α-fodrin functions as an autoantigen in Sjögren's syndrome. Mucosal administration of α-fodrin has been shown to inhibit the progress of the disorder in mice.
Research on diseases such as Sjögren's syndrome focuses on increasing knowledge and understanding of the disorder, improving diagnostic techniques, and finding ways to treat, prevent, and cure the disorder. The Primary Sjögren's Syndrome Registry in the UK is a tissue biobank of samples taken for research supported by the Medical Research Council. The Registry supports clinical trials and genetic studies of Sjögren's Syndrome and is open to patients wishing to participate in research studies and researchers studying the disease.
An animal model of Sjögren's syndrome has been developed by immunizing mice with peptides from 60 kDa Ro-antigen. Days after immunization, salivary flow was decreased, and lymphocyte infiltrates as well as salivary dysfunction were observed which are highly reminiscent of human Sjögren's syndrome.
Jan Mikulicz-Radecki
Jan Mikulicz-Radecki was a Polish-Austrian surgeon. He was born May 16, 1850 in Czernowitz in the Austrian Empire and died June 4, 1905 in Breslau, German Empire .While his mother Freiin von Damnitz was Austrian, his parental ancestors of the Mikulicz...
disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine gland
Exocrine gland
Exocrine glands are a type of ductal glands that secrete their products into ducts that lead directly into the external environment...
s that produce tears
Tears
Tears are secretions that clean and lubricate the eyes. Lacrimation or lachrymation is the production or shedding of tears....
and saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
.
It is named after Swedish ophthalmologist
Ophthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...
Henrik Sjögren
Henrik Sjögren
Henrik Samuel Conrad Sjögren was a Swedish ophthalmologist best known for the eponymous condition Sjögren's syndrome. Sjögren is pronounced ; the syndrome is in English. Sjögren published a doctoral thesis in 1933 titled "On knowledge of keratoconjunctivitis) that eventually served as the basis...
(1899–1986), who first described it.
Nine out of ten Sjögren's patients are women and the average age of onset is late 40s, although Sjögren's occurs in all age groups in both women and men. It is estimated to affect as many as 4 million people in the United States alone, making it the second most common autoimmune rheumatic disease.
Sjögren's syndrome can exist as a disorder in its own right (primary Sjögren's syndrome) or may develop years after the onset of an associated rheumatic disorder, such as rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
, primary biliary cirrhosis
Primary biliary cirrhosis
Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...
etc. (secondary Sjögren's syndrome).
The disorder should not be confused with the Sjögren–Larsson syndrome, which was also denoted T. Sjögren syndrome in early studies.
Signs and symptoms
The hallmark symptom of Sjögren's syndrome is a generalized drynessDryness (medical)
Dryness is a medical condition in which there is local or more generalized decrease in normal lubrication of the skin or mucous membranes.Examples of local dryness include dry mouth, dry eyes, dry skin and vaginal dryness. These often have specific causes and treatments...
, typically including xerostomia
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
(dry mouth) and xerophthalmia
Xerophthalmia
Xerophthalmia is a medical condition in which the eye fails to produce tears. It may be caused by a deficiency in vitamin A and is sometimes used to describe that lack, although there may be other causes....
(dry eyes), part of what are known as sicca symptoms. In addition, Sjögren's syndrome may cause skin
Human skin
The human skin is the outer covering of the body. In humans, it is the largest organ of the integumentary system. The skin has multiple layers of ectodermal tissue and guards the underlying muscles, bones, ligaments and internal organs. Human skin is similar to that of most other mammals,...
, nose
Human nose
The visible part of the human nose is the protruding part of the face that bears the nostrils. The shape of the nose is determined by the ethmoid bone and the nasal septum, which consists mostly of cartilage and which separates the nostrils...
, and vaginal dryness, and may affect other organs of the body, including the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, lung
Human lung
The human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...
s, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
, peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
(distal axonal sensorimotor neuropathy) and brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
.
Sjögren's syndrome is associated with increased levels in Cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
(CSF) of IL-1RA, an interleukin 1 antagonist. This suggests that the disease begins with increased activity in the interleukin 1 system, followed by an auto-regulatory up-regulation of IL-IRA to reduce the successful binding of interleukin 1 to its receptors. It is likely that interleukin 1 is the marker for fatigue, however, increased IL-1RA is observed in the CSF and is associated with increased fatigue through cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
induced sickness behavior
Sickness behavior
thumb|350px|right|[[Michael Peter Ancher|Ancher, Michael]], "The Sick Girl", 1882, [[Statens Museum for Kunst]]Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection....
. On the other hand, Sjögren's syndrome is characterized by decreased levels of IL-1ra in saliva, which could be responsible for mouth inflammation and dryness. Patients with secondary Sjögren's syndrome also often exhibit signs and symptoms of their primary rheumatic disorders, such as SLE, Rheumatoid Arthritis or Systemic Sclerosis.
Diagnosis
Diagnosing Sjögren's syndrome is complicated by the range of symptoms a patient may manifest, and the similarity between symptoms of Sjögren's syndrome and those of other conditions. Nevertheless, the combination of several tests can lead to a diagnosis of Sjögren's syndrome.Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as anti-nuclear antibody
Anti-nuclear antibody
Anti-nuclear antibodies are autoantibodies directed against contents of the cell nucleus....
(ANA) and rheumatoid factor
Rheumatoid factor
Rheumatoid factor is an autoantibody most relevant in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG. RF and IgG join to form immune complexes that contribute to the disease process...
(because SS frequently occurs secondary to rheumatoid arthritis), which are associated with autoimmune diseases. Typical Sjögren's syndrome ANA patterns are SSA/Ro
Anti-SSA/Ro autoantibodies
Anti-SSA autoantibodies are anti-nuclear autoantibodies that are associated with among many autoimmune diseases, such as systemic lupus erythematosus , SS/SLE overlap syndrome, subacute cutaneous LE , neonatal lupus and primary biliary cirrhosis...
and SSB/La, of which SSB/La is far more specific; SSA/Ro is associated with numerous other autoimmune conditions but are often present in Sjögren's.
Schirmer's test
Schirmer's test
Schirmer's test determines whether the eye produces enough tears to keep it moist. This test is used when a person experiences very dry eyes or excessive watering of the eyes. It poses no risk to the subject. A negative test result is normal...
measures the production of tears: a strip of filter paper is held inside the lower eyelid for five minutes, and its wetness is then measured with a ruler. Producing less than five millimeters of liquid is usually indicative of Sjögren's syndrome. However, lacrimal function declines with age or may be impaired from other medical conditions. An alternative test is nonstimulated whole saliva flow collection, in which the patient spits into a test tube every minute for 15 minutes. A resultant collection of less than 1.5 mL is considered a positive result. It takes longer to perform than Schirmer's test, but does not require special equipment.
A slit-lamp examination
Slit lamp
The slit lamp is an instrument consisting of a high-intensity light source that can be focused to shine a thin sheet of light into the eye. It is used in conjunction with a biomicroscope...
can reveal dryness on the surface of the eye. Salivary gland function can be tested by collecting saliva and determining the amount produced in a five minute period. A lip biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
can reveal lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s clustered around salivary glands, and damage to these glands due to inflammation.
Ultrasound examination of the salivary glands is the simplest confirmatory test and has the added advantage of being non-invasive with no complications. The parenchyma of the gland demonstrates multiple, small-2-6 mm hypoechoic lesions which are representations of the lymphocytic infiltrates. Often sialectasis with calculi are demonstrated if the disease is advanced. The sonographic findings have excellent symptom correlation. The other advantage of ultrasound is that complications of the disease such as extra-nodal lymphomas can often be detected as larger 1–4 cm hypoechoic intra-parenchymal masses.
There is also a radiological
Radiology
Radiology is a medical specialty that employs the use of imaging to both diagnose and treat disease visualized within the human body. Radiologists use an array of imaging technologies to diagnose or treat diseases...
procedure which is a reliable and accurate test for Sjögren's syndrome. A contrast agent is injected into the parotid duct
Parotid duct
The parotid duct, also known as Stensen's duct, is the route that saliva takes from the parotid gland into the mouth.It passes through the buccal fat, buccopharyngeal fascia, and buccinator muscle then opens into the vestibule of the mouth next to the maxillary second molar tooth. The buccinator...
, which opens from the cheek into the vestibule
Vestibule of mouth
The vestibule of mouth is the anteriormost portion of the oral cavity. It is the space between the cheek/lips and the teeth....
of the mouth opposite the neck of the upper second molar tooth. Widespread puddling of the injected contrast scattered throughout the gland indicates Sjögren's syndrome.
The Revised Classification Criteria for Sjögren's Syndrome requires the presence of signs, symptoms, and lab findings.
Patient-reported symptoms must include both ocular symptoms, such as daily, persistent, troublesome dry eyes for more than three months, and oral symptoms, such as needing to drink water to swallow food.
Objective evidence of eye involvement relies on Schirmer's test and the Rose bengal score (or similar). Histopathology
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
studies should show focal lymphocytic sialadenitis. Objective evidence of salivary gland involvement is tested through ultrasound examinations, the level of unstimulated whole salivary flow, a parotid sialography, or salivary scintigraphy. Autoantibodies against Ro (SSA) and/or La (SSB) antigens are also expected.
SS can be excluded from people with past head and neck radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
, hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
infection, Acquired immunodeficiency syndrome
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
(AIDS), pre-existing lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
, sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
, graft-versus-host disease
Graft-versus-host disease
Graft-versus-host disease is a common complication after a stem cell transplant or bone marrow transplant from another person . Immune cells in the donated marrow or stem cells recognize the recipient as "foreign". The transplanted immune cells then attack the host's body cells...
, and use of anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
drugs (since a time shorter than four times the life of the drug).
Pathogenesis
Cell mediated auto-immunity causes the apoptosisApoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
of the ductal and acinar epithelial
cells which is responsible for the glandular tissue damage.
Treatment
There is neither a known cure for Sjögren's syndrome nor a specific treatment to permanently restore gland secretion. Instead, treatment is generally symptomatic and supportive. Moisture replacement therapies such as artificial tearArtificial tear
Artificial tears are lubricant eye drops used to treat the dryness and irritation associated with deficient tear production in keratoconjunctivitis sicca . They are also used to moisten contact lenses and in eye examinations....
s may ease the symptoms of dry eyes. Some patients with more severe problems use goggles to increase local humidity or have punctal plug
Punctal plug
A punctal plug is a small medical device that is inserted into the tear duct of an eye to block the duct. This prevents the drainage of liquid from the eye. They are used to treat dry eye....
s inserted to help retain tears on the ocular surface for a longer time. Additionally, cyclosporine (Restasis) is available by prescription to help treat chronic dry eye by suppressing the inflammation that disrupts tear secretion. Prescription drugs are also available that help to stimulate salivary flow, such as cevimeline (Evoxac) and pilocarpine
Pilocarpine
Pilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...
. Nonsteroidal anti-inflammatory drugs may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s or immunosuppressive drugs may be prescribed. Also, disease-modifying antirheumatic drug
Disease-modifying antirheumatic drug
Disease-modifying antirheumatic drugs is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression...
s (DMARDs) such as methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
may be helpful. Hydroxychloroquine
Hydroxychloroquine
Hydroxychloroquine is an antimalarial drug, sold under the trade names Plaquenil,Axemal, Dolquine, and Quensyl, also used to reduce inflammation in the treatment of rheumatoid arthritis and lupus...
(Plaquenil) is another option and is generally considered safer than methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
. Salagen, a man-made form of pilocarpine, can be used to help produce tears as well as saliva in the mouth and intestines. It is derived from the Jaborandi plant.
Dry eyes
Punctal plugsIn the advanced stage, despite the use of tear replacement drops, the eyes always feel burning,
scratchy, sore. The sufferer is always aware of some discomfort, the eyes feel worse in the morning and late evening. The use of tear replacement drops becomes tedious and ineffective. At this point it may be appropriate to consider punctal plugs.
Each eye has two sites at the inner corner of each eyelid where tears drain from the eye. The upper eyelid 'puncta' drains approximately 40% of the tears away and the lower puncta drains away the remaining 60% of the tears. If there is a problem with the quantity of tears, as there is in Sjögren's disease, plugging the lower puncta can result in the tears that the patient has remaining on the eye longer.
Punctal plugs can be inserted into the lower or upper tear drainage canals of the eyes. The procedure takes only a few minutes and is painless. It can be done in the optometrist or ophthalmologist's office. Generally, collagen plugs are inserted first. These plugs will dissolve within a few days, so it gives the patient a chance to see if there is any improvement in comfort. Generally, the improvement is immediate. The patient may proceed to use of permanent plugs, although these too can be removed if necessary.
Dental care
Preventive dentalDentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...
treatment is also necessary (and often overlooked by the patient), as the lack of saliva associated with xerostomia creates an ideal environment for the proliferation of bacteria that cause dental caries
Dental caries
Dental caries, also known as tooth decay or a cavity, is an irreversible infection usually bacterial in origin that causes demineralization of the hard tissues and destruction of the organic matter of the tooth, usually by production of acid by hydrolysis of the food debris accumulated on the...
(cavities). Treatments include at-home topical fluoride application to strengthen tooth enamel and frequent teeth cleanings by a dental hygienist. Existing cavities must also be treated, as cavities that extend into the tooth can not be effectively treated through teeth cleaning alone, and are at a high risk of spreading into the pulp of the tooth, leading to the loss of vitality and need for extraction or root canal
Root canal
A root canal is the space within the root of a tooth. It is part of a naturally occurring space within a tooth that consists of the pulp chamber , the main canal, and more intricate anatomical branches that may connect the root canals to each other or to the surface of the root.-Root canal anatomy:...
therapy. This treatment regimen is the same as that used for all xerostomia patients, such as those undergoing head and neck radiation therapy which often damages the salivary glands, as they are more susceptible to radiation than other body tissues.
Unfortunately, many patients, not realizing the need for dental treatment, do not see a dentist until most of their teeth are beyond the point of restoration. It is not uncommon for a dentist to see a xerostomia patient with severe, untreatable cavities in almost every tooth. In severe cases, the only viable treatment may be to extract all of the patient's teeth and treat with prosthetics such as dentures or implants.
Prognosis
Sjögren's can damage vital organs of the body with symptoms that may plateau or worsen, but the disease does not go into remission as with other autoimmune diseases. Some people may experience only the mild symptoms of dry eyes and mouth, while others have symptoms of severe disease. Many patients are able to treat problems symptomatically. Others are forced to cope with blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glandParotid gland
The paired parotid glands are the largest of the salivary glands. They are each found wrapped around the mandibular ramus, and secrete saliva through Stensen's ducts into the oral cavity, to facilitate mastication and swallowing and to begin the digestion of starches.-Location:The parotid glands...
s, hoarseness, and difficulty in swallowing and eating. Debilitating fatigue
Fatigue (physical)
Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
and joint pain can seriously impair quality of life. Some patients can develop renal involvement (autoimmune tubulointerstitial nephritis) leading to proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
, urinary concentrating defect and distal renal tubular acidosis
Renal tubular acidosis
Renal tubular acidosis is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. When blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid...
.
Patients with Sjögren's syndrome have a higher rate of non-Hodgkin lymphoma
Non-Hodgkin lymphoma
The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
compared to both patients with other autoimmune diseases and healthy people. About 5% of patients with Sjögren's syndrome will develop some form of lymphoid malignancy. Patients with severe cases are much more likely to develop lymphomas than patients with mild or moderate cases. The most common lymphomas are salivary extranodal marginal zone B cell lymphomas (MALT lymphoma
MALT lymphoma
MALT lymphoma is a form of lymphoma involving the mucosa-associated lymphoid tissue , frequently of the stomach, but virtually any mucosal site can be afflicted...
s in the salivary glands) and diffuse large B-cell lymphoma.
Complications
Among the complications discussed above, Sjögren's syndrome in women who become pregnant has been linked to increased incidence of neonatal lupus erythematosusNeonatal lupus erythematosus
Neonatal lupus erythematosus is the occurrence of SLE symptoms in an infant born from a mother with SLE, most commonly presenting with a rash resembling discoid lupus erythematosus, and sometimes with systemic abnormalities such as heart block or hepatosplenomegaly.The infants have no skin lesions...
with congenital heart block
Heart block
A heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....
requiring a pacemaker
Pacemaker
An artificial pacemaker is a medical device that uses electrical impulses to regulate the beating of the heart.Pacemaker may also refer to:-Medicine:...
.
Epidemiology
Sjögren's syndrome affects 1 million–4 million people in the United States. Most people are more than 40 years old at the time of diagnosis. Women are nine times more likely than men to have Sjögren's syndrome.On September 1, 2011, tennis player Venus Williams
Venus Williams
Venus Ebony Starr Williams is an American professional tennis player who is a former World No. 1 and is ranked World No. 101 as of 10 October 2011 in singles and World No. 20 in doubles as of 2011. She has been ranked World No. 1 in singles by the Women's Tennis Association on three separate...
announced that she had been diagnosed with Sjögren's syndrome, and that because of the disease, she was withdrawing from the 2011 US Open
2011 US Open (tennis)
The 2011 US Open was a tennis tournament played on the outdoor hard courts at the USTA Billie Jean King National Tennis Center in Flushing Meadows Park, of Queens, New York City, United States...
.
Research
Multiple monoclonal antibodiesMonoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
were under investigation in 2007. The most promising seemed to be the anti-CD20
CD20
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity....
rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
and the anti-CD22
CD22
CD22 or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells...
epratuzumab
Epratuzumab
Epratuzumab is a humanized monoclonal antibody. Potential uses may be found in oncology and in treatment of inflammatory autoimmune disorders, such as lupus...
; the anti-TNF-α and IFN-α drugs seemed less effective.
α-fodrin functions as an autoantigen in Sjögren's syndrome. Mucosal administration of α-fodrin has been shown to inhibit the progress of the disorder in mice.
Research on diseases such as Sjögren's syndrome focuses on increasing knowledge and understanding of the disorder, improving diagnostic techniques, and finding ways to treat, prevent, and cure the disorder. The Primary Sjögren's Syndrome Registry in the UK is a tissue biobank of samples taken for research supported by the Medical Research Council. The Registry supports clinical trials and genetic studies of Sjögren's Syndrome and is open to patients wishing to participate in research studies and researchers studying the disease.
An animal model of Sjögren's syndrome has been developed by immunizing mice with peptides from 60 kDa Ro-antigen. Days after immunization, salivary flow was decreased, and lymphocyte infiltrates as well as salivary dysfunction were observed which are highly reminiscent of human Sjögren's syndrome.
See also
- Benign lymphoepithelial lesionBenign lymphoepithelial lesionBenign lymphoepithelial lesion is a type of benign enlargement of the parotid and/or lacrimal glands. This pathologic state is sometimes, but not always, associated with Sjögren's syndrome.-Eponym:...
- BioteneBioteneBiotene is a dental hygiene product manufactured by GlaxoSmithKline. It comes in a number of forms, including toothpaste, mouthwash and cream....
— a product range that offers comfort and helps strengthen saliva’s natural defences. - Keratoconjunctivitis siccaKeratoconjunctivitis siccaKeratoconjunctivitis sicca , also called keratitis sicca, xerophthalmia or dry eye syndrome is an eye disease caused by eye dryness, which, in turn, is caused by either decreased tear production or increased tear film evaporation. It is found in humans and some animals...
- ParotitisParotitisParotitis is an inflammation of one or both parotid glands, the major salivary glands located on either side of the face, in humans. The parotid gland is the salivary gland most commonly affected by inflammation.-Infectious parotitis:...
- XerostomiaXerostomiaXerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
External links
- The original text from this article was obtained from a public domainPublic domainWorks are in the public domain if the intellectual property rights have expired, if the intellectual property rights are forfeited, or if they are not covered by intellectual property rights at all...
resource at: www.ninds.nih.gov/health_and_medical/disorders/sjogrens_doc - Sjögren's Syndrome Foundation
- For those interested in research into Sjögren's Syndrome: Sjogren's Registry
- The NHS Choices website holds useful information on Sjogren's Syndrome