Sjögren syndrome Flashcards
Sjögren syndrome- Signs and symptoms?
The hallmark symptom of SS is dry mouth and keratoconjunctivitis sicca (dry eyes).[8] Vaginal dryness and dry skin and dry nose may also occur.[8] Other organs of the body may also be affected including kidneys, blood vessels, lungs, liver, pancreas, and brain.[8]
Sjögren syndrome-
Skin dryness in some people with SS may be the result of lymphocytic infiltration into skin glands. The symptoms may develop insidiously, with the diagnosis often not considered for several years, because the complaints of sicca may be otherwise attributed to medications, a dry environment, aging, or may be regarded as not of severity warranting the level of investigation necessary to establish the presence of the specific underlying autoimmune disorder.[9]
SS can damage vital organs of the body with symptoms that may plateau or worsen, or 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 can treat problems symptomatically. Others are forced to cope with blurred vision, constant eye discomfort, recurrent mouth infections, swollen parotid glands, dysphonia (vocal disorders including hoarseness), and difficulty in swallowing and eating. Debilitating fatigue and joint pain can seriously impair quality of life. Some patients can develop renal (kidney) involvement (autoimmune tubulointerstitial nephritis) leading to proteinuria (excess protein in urine), urinary concentrating defect, and distal renal tubular acidosis.
Associated conditions
SS is associated with a number of other medical conditions, many of which are autoimmune or rheumatic disorders, such as celiac disease,[10][11] fibromyalgia, SLE (lupus), autoimmune thyroiditis, multiple sclerosis and spondyloarthropathy,[12] and several malignancies, principally non-Hodgkin lymphoma.[12][13]
Sjögren syndrome - Cause
Genetic factors
The observation of high rates of autoimmune disorders in families of SS is linked with a genetic predisposition to the syndrome.[15] Studies on the polymorphisms of human leukocyte antigen (HLA)-DR and HLA-DQ gene regions in SS patients show differential susceptibility to the syndrome due to different types of the resulting autoantibody production.[15]
Hormonal factors
Since SS is associated with a high prevalence in women, sex hormones, especially estrogen, are believed to affect humoral and cell-mediated immune responses affecting susceptibility to the syndrome.[15] Androgens are generally considered to prevent autoimmunity.[16] Studies on mice models suggest estrogen deficiency stimulates presentation of autoantigens, inducing SS-like symptoms.[15]
Microchimerism factors
Microchimerism of fetal cells (offspring lymphoid cells in maternal circulation) may generate autoimmunity in women who have been previously pregnant.[16][17] Generation of an autoimmune potential via microchimerism may lead to a switch from a silent form of autoimmunity with age-dependent decrease in self-tolerance.[16]
Environmental factors
Viral proteins, engulfed molecules, or degraded self-structures may initiate autoimmunity by molecular mimicry and increase the chances of SS development.[16] Epstein-Barr virus, hepatitis C, and human T-cell leukemia virus-1 are among the most studied infectious agents in SS.[16] Damaged self-structures targeted for apoptosis may be mistakenly exposed to the immune system, triggering autoimmunity in exocrine glands, which are often prone to autoimmune responses.[16
Sjögren syndrome- pathopshysiology?
Hormonal factors
Sex hormones seem to influence humoral and cell-mediated immune response, with estrogen being considered one of the biggest factors responsible for sex-immunologic dimorphism.[32] Estrogen deficiency appears to play a role in development of SS.[33] It has been hypothesized that androgen administration to the ocular surface may serve as an effective therapy for dry eyes.[34]
Inflammation
Epithelial cells in SS lesions are active participants in the induction and perpetuation of the inflammatory process. Environmental and hormonal factors, in concert with an appropriate genetic background, are believed to trigger SS, which dysregulates epithelial cells and allows aberrant homing and activation of dendritic cells (DCs), T cells, and B cells
Environmental factors, such as glandular viral infection, could prompt epithelial cells to activate the HLA-independent innate immune system through toll-like receptors.[27] Although a number of infectious, exogenous agents have been implicated in the pathogenesis of SS, such as Epstein-Barr virus (EBV), human T-lymphotropic virus 1, and hepatitis C virus, their association with SS appears weak
Sjögren syndrome- Diagnosis
SS is usually classified as either ‘primary’ or ‘secondary’. Primary Sjögren syndrome occurs by itself and secondary Sjögren syndrome occurs when another connective tissue disease is present.
Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as antinuclear antibody (ANA) and rheumatoid factor (because SS frequently occurs secondary to rheumatoid arthritis), which are associated with autoimmune diseases
The rose bengal test uses a stain that measures state and function of the lacrimal glands. This test involves placing the non-toxic dye rose bengal on the eyes. The dye’s distinctive colour helps in determining the state and functioning of tear film and the rate of tear evaporation. Any distinctive colour change can indicate SS, but confirming the condition requires many related diagnostic tools.[35]
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 5 mm (0.20 in) of liquid is usually indicative of SS. This measurement analysis varies among people depending on other eye-related conditions and medications in use when the test is taken.[35] A slit-lamp examination can reveal dryness on the surface of the eye.
Symptoms of dry mouth and dryness in the oral cavity are caused by the reduced production of saliva from the salivary glands (parotid gland, submandibular gland, and sublingual gland). To check the status of salivary glands and the production of saliva, a salivary flow-rate test is performed, in which the person is asked to spit as much as they can into a cup, and the resulting saliva sample is collected and weighed. This test’s results can determine whether the salivary glands are functioning adequately. Not enough saliva produced could mean the person has SS.[35] An alternative test is non-stimulated whole saliva flow collection, in which the person spits into a test tube every minute for 15 minutes. A resultant collection of less than 1.5 ml (0.053 imp fl oz; 0.051 US fl oz) is considered a positive result
A lip/salivary gland biopsy takes a tissue sample that can reveal lymphocytes clustered around salivary glands, and damage to these glands due to inflammation. This test involves removing a sample of tissue from a person’s inner lip/salivary gland and examining it under a microscope. In addition, a sialogram, a special X-ray test, is performed to see if any blockage is present in the salivary gland ducts (i.e. parotid duct) and the amount of saliva that flows into the mouth.[35]
Also, a radiological procedure is available as a reliable and accurate test for SS. 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. 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, and autoantibodies against Ro (SSA) and/or La (SSB) antigens.
SS can be excluded from people with past head and neck radiation therapy, acquired immunodeficiency syndrome (AIDS), pre-existing lymphoma, sarcoidosis, graft-versus-host disease, and use of anticholinergic drugs.
Sjögren syndrome- Prevention?
There is no prevention mechanism for SS due to its complexity as an autoimmune disorder. However, lifestyle changes can reduce the risk factors of getting SS or reduce the severity of the condition with patients who have already been diagnosed. Diet is strongly associated with inflammation that is mostly seen in many autoimmune related diseases including SS. An experimental study concludes that SS patients show high sensitivity to gluten that directly relates to inflammation.[37] Moderate exercise is also helpful in SS patients, mainly reducing the effect of lung inflammation.[38]
Sjögren syndrome- Treatment
Eye care
Moisture replacement therapies such as artificial tears may ease the symptoms of dry eyes. Some patients with more severe problems use goggles to increase local humidity or have punctal plugs 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. Salagen, a manufactured 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.
Vaginal dryness
In women with SS, vaginal dryness, vulvodynia and dyspareunia (painful sexual intercourse) are often reported; personal lubricants are recommended to help lessen irritation or pain that may result from dryness in the vaginal and vulva areas.[35]
Musculoskeletal
Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed, and sometimes IVIG (intravenous immunoglobulin). Also, disease-modifying antirheumatic drugs (DMARDs) such as methotrexate may be helpful. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate. However, these prescribed drugs have a range of side effects such as nausea, loss of appetite, dizziness, hair loss, stomach aches/cramps, headache, liver toxicity, and increased risk of infections. Also, people who take drugs to suppress the immune system are more likely to develop cancer later.[35]
Systemic
For systemic symptoms, including fatigue, joint pain, myositis and neuropathy, biologic immunosuppressant drugs such as rituximab and belimumab that work via B-cell pathology are often used and have less toxic profiles than traditional immunosuppressive regimens.
Dental care
Preventive dental 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 cavities.[39] 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 for all xerostomia patients—such as those undergoing head and neck radiation therapy, which often damages the salivary glands, which are more susceptible to radiation than other body tissues.
Sjögren syndrome- Epidemiology?
SS is the second most common rheumatic autoimmune disorder, behind rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).[48][49] There are no geographical differences in the rates of SS.[50] SS has been reported in all areas of the world, although regional rates have not been well studied.[50][51] Depending on the criteria for determining prevalence, studies estimate the prevalence of SS at 500,000 to 2 million people in the United States. Moreover, other broader studies of prevalence of SS range widely with some reports of up to a prevalence of 3% of the population.[48] A few studies that have been conducted on the incidence of SS report that the incidence of the syndrome varies between 3 and 6 per 100,000 per year.[48][52]
Nine out of ten SS patients are women.[14][51] In addition to prevalence in women, having a first-degree relative with an autoimmune disease and previous pregnancies have been identified as epidemiological risk factors.[53] Differences in prevalence due to race and ethnicity are unknown.
Although SS occurs in all age groups, the average age of onset is between ages 40 and 60, although experts note that up to half of all cases may be left undiagnosed or unreported.[14][48][54][55] The prevalence of SS generally increases with age.[48]
SS is reported in 30-50% of people with rheumatoid arthritis and 10-25% with systemic lupus erythematosus.[14
