Numbness, tingling, and weakness also have been described in some patients. People with this disease have abnormal proteins in their blood. This suggests that the immune system, which normally functions to protect the body against cancers and infections, is reacting against its own tissue. Research suggests that genetic factors and possibly viral infections may predispose people to developing this condition.
Diagnosis depends on a combination of symptoms, physical examination, blood tests, and sometimes special studies. Dry eyes and mouth may be early signs of the condition but require further investigation, because these symptoms can be caused by many other conditions or medications. Special tests may assess any decrease in tear or saliva production.
Blood tests can determine the presence of antibodies immune system proteins that help destroy foreign invaders typical of the disease. Biopsies of saliva glands around the face or under the surface of the inner lip also may be used to make a diagnosis. Treatment is designed to lessen the most bothersome symptoms. Dry eyes usually respond to artificial tears applied regularly during the day or to gels applied at night. Other measures, such as plugging or blocking tear ducts, can be used in more severe cases.
Eye drops that reduce inflammation in the glands around the eyes, such as cyclosporine Restasis , may be used to increase tear production.
Drinking water, chewing gum, or using saliva substitutes may relieve dry mouth. Some patients benefit from using prescription medications that stimulate saliva flow, such as pilocarpine Salagen or cevimuline Evoxac. If patients develop yeast infections, anti-fungal therapies may be used.
Humidifiers and nasal saline irrigation may improve nasal dryness. Rheum Dis Clin North Am. Curr Opin Ophthalmol. Ocul Surf. Epub Jan Immunol Lett. Epub Jul Epub Feb Best Pract Res Clin Rheumatol.
Primary Sjogren syndrome. J Am Dent Assoc. Epub Jan 5. These findings suggest the intrinsically activated status of these cells and provide additional evidence that SGECs have a pivotal role in the induction and maintenance of lymphocytic infiltrates in SS patients. Patients spend several extra hours in bed trying to rest or sleep, but most report that they do not feel refreshed on awakening.
Joint disease in primary SS is typically an intermittent polyarticular arthropathy primarily affecting small joints, asymmetrically at times. Joint deformity and mild erosions occur uncommonly, and a nonerosive arthritis, resembling that of SLE, may occur transiently. Of these 9 cases, 8 involved the skin. In addition to the typical hypersensitivity-type rash, 3 of the SS patients with vasculitis had ulcerative lesions or violaceous discoloration of the digits.
Although common, pulmonary involvement is seldom clinically significant in patients with SS. Other potential pulmonary complications include lymphocytic alveolitis, lymphocytic interstitial pneumonitis and fibrosis, and pseudolymphoma. Patients with SS may have involvement of their entire gastrointestinal tract. Hepatitis C virus infection is not associated with typical primary SS, but a lymphocytic sialadenitis occurs with increased prevalence in patients with chronic hepatitis C infection.
The histopathologic appearance is similar to that of early stage 1 primary biliary cirrhosis. Patients with SS may have tubulointerstitial involvement of the kidneys affecting the tubules eg, distal renal tubular acidosis, impaired concentrating ability, hypercalcinuria, or proximal tubule defects. In SS patients who show evidence of glomerular lesions, hematuria, proteinuria, and renal insufficiency may be exhibited.
Some patients may progress to nephrotic syndrome. A number of patients may develop renal vasculitis with significant hypertension and renal insufficiency. One of the most common significant systemic manifestations of SS is neurologic disease, which can involve the cranial and peripheral nerves and, infrequently, the central nervous system. The neuropathy was associated with alterations of the endoneurial microvessels, but necrotizing vasculitis was not seen.
Hearing loss in these patients was correlated with the presence of anticardiolipin antibodies, suggesting an underlying autoimmune cause. An essential process in the transition from the autoimmune state to non-Hodgkin lymphoma is monoclonality, and monoclonal B-cell expansion occurs in some patients with SS, arising mainly from exocrine glands and less frequently from visceral organs or lymph nodes.
Patients with SS having risk factors for progression to lymphoma Table 1 should be closely monitored. Those with persistent gland enlargement, purpura, low levels of C4, and monoclonal cryoglobulinemia are at increased risk. Most lymphomas in patients with SS are of B-cell lineage and are of low- or intermediate-grade malignancy.
These lymphomas are usually localized in extranodal areas such as the salivary glands, gastrointestinal tract, thyroid gland, lung, kidney, or orbit. Localized, low-grade lymphoma affecting exocrine glands can be managed by watchful waiting; disseminated lymphoma may be treated with combination chemotherapy.
Many symptoms of SS are deceptively nonspecific, and the spectrum of clinical manifestations is very broad. Because SS is frequently seen in middle-aged women, symptoms of cutaneous, oral, and vaginal dryness may initially be attributed to menopause.
The early symptoms of dry eyes and mouth may be confused with atopic disease and anxiety, respectively. Additionally, xerostomia symptoms are common to many conditions and are, in part, subjective.
Signs suggestive of lymphoproliferation include significant enlargement of the salivary glands, lymphadenopathy, splenomegaly, and pulmonary infiltrates. Longitudinal monitoring of laboratory parameters in patients with SS may reveal findings associated with the development of lymphoma, such as the appearance of a monoclonal protein, new-onset leukopenia and anemia, and a loss of specific autoantibodies.
An analysis of symptoms in patients with SS and 44 control subjects found that Ocular Manifestations. Dry eye is the most prominent ocular manifestation of SS. Symptoms of dry eye may include sensations of itching, grittiness, or soreness, even though the eyes' appearance is normal. Ocular complaints may include photosensitivity, erythema, eye fatigue, decreased visual acuity, a discharge in the eyes, and the sensation of a film across the visual field.
Although diminished tear secretion is characteristic of SS, the actual tear flow rates are not well correlated with ocular discomfort. Because of decreased tear film and an abnormal mucus component, thick, rope-like secretions may accumulate along the inner canthus. Small superficial erosions of the corneal epithelium may result from desiccation; in severe cases, slitlamp examination may reveal filamentary keratitis, marked by mucus filaments that adhere to damaged areas of the corneal surface.
Conjunctivitis due to Staphylococcus aureus infection may also occur. Enlargement of the lacrimal glands is rare. Ocular complications may include corneal ulceration, vascularization, opacification, and, rarely, perforation. Oral Manifestations. Although the presenting symptoms of SS are frequently those of xerostomia, the patient may complain not of oral dryness, but of an unpleasant taste, difficulty eating dry food, such as crackers, soreness, or difficulties in controlling dentures.
In the early stages of SS, the mouth may appear moist, but as the disease progresses, the usual pooling of saliva in the floor of the mouth becomes absent and lines of contact between frothy saliva and the oral soft tissue are seen. In advanced disease, the oral mucosa appears dry and glazed and tends to form fine wrinkles. Extreme dryness of the mouth, causing the tongue to stick to the palate, may lead to a "clicking" quality in the speech of patients with SS.
Typically, the surface of the tongue becomes red and lobulated, with partial or complete depapillation. In patients with SS, chronic salivary gland inflammation leads to loss of function and decreased salivary flow rates, which are associated with an increased frequency of dental caries. Saliva contains lysozyme, lactoferrin, lactoperoxidase, and histidine-rich polypeptides, which inhibit bacteria and fungi.
This swallowing eliminates food debris, microorganisms, and loose cells from the mouth, providing a continuous "flushing" system that keeps the mouth clean and prevents colonization by bacteria.
In patients with SS and severe salivary hypofunction, the mean number and proportion of Streptococcus mutans and Lactobacillus organisms and the frequency of Candida organisms are reported to be increased. A recent trial compared the periodontal condition of 24 patients with SS, 27 patients with an autoimmune disease with SS, and 29 control subjects with subjective complaints of xerostomia only.
No significant difference in the periodontal condition of the 3 groups was found. Additional oral symptoms may include soreness, adherence of food to buccal surfaces, fissuring of the tongue, and dysphagia.
In addition to the appearance of dental caries, angular cheilitis associated with candidiasis may exist. In ambulatory patients, SS is the most common underlying cause of acute bacterial sialadenitis, usually staphylococcal or pneumococcal. Typically, affected patients have acute pain, trismus, and a tender swelling of the salivary gland. The regional lymph nodes may be enlarged and tender, and fever and malaise may exist in severe cases. Additional Xeroses. In female patients with SS, desiccation of the vagina and vulva may result in dyspareunia and pruritus.
Vaginal atrophy and reduced cervical mucus production correlated with age and menopause in this study, but not with any clinical or serologic manifestation of SS. In patients with SS, diminution or absence of glandular secretions of the respiratory tract can lead to dryness of the nose, throat, and trachea that results in persistent hoarseness and a chronic, nonproductive cough.
Involvement of the exocrine glands of the skin leads to skin dryness in patients with SS. The most frequent histologic finding is leukocytoclastic vasculitis, 22 characterized by necrotizing neutrophilic inflammation of small dermal blood vessels, usually resulting in palpable purpura, with slightly raised hemorrhagic skin lesions. Although often elusive, an early, accurate diagnosis of SS can help prevent or ensure timely treatment of many of the complications associated with the disease.
For example, early restoration of salivary function can relieve symptoms of dry mouth and may prevent or slow the progress of the oral complications of SS, including dental caries, oral candidiasis, and periodontal disease. Untreated severe dry eye can result in corneal perforation in the patient with SS, which may eventually lead to loss of the eye. Early diagnosis may contribute to prompt recognition and treatment of serious systemic complications of SS such as malignant lymphoma and interstitial lung disease.
Additionally, an extensive delay in diagnosis can affect the patient's psychological well-being because of the anxiety that accompanies an undiagnosed illness. An appropriate diagnosis of SS depends on recognition of its clinical manifestations, elimination of alternative differential diagnoses, and distinguishing primary from secondary SS. For example, recurrent parotid gland enlargement is more often found in patients with SS alone than in patients with RA plus SS. In addition, lymphadenopathy, purpura, Raynaud phenomenon, renal involvement, and myositis occur more often in patients with SS alone than in patients with RA plus SS.
Although minor salivary gland biopsy traditionally has been considered the "gold standard" for the diagnosis of SS, newer criteria permit classification of SS without necessarily performing this procedure. Of the 6 criteria given in Table 2 , 4 must be present to establish a diagnosis of SS, with 1 of the 4 being an objective measurement ie, by histopathologic examination or antibody screening.
As assessment of oral and ocular involvement is essential to the accurate diagnosis of SS. The Schirmer test for the eye quantitatively measures tear formation via placement of filter paper in the lower conjunctival sac. If less than 5 mm of paper is wetted after 5 minutes, the test result is positive.
Rose bengal scoring involves placement of 25 mL of rose bengal solution in the inferior fornix of each eye and having the patient blink twice. Slitlamp examination detects destroyed conjunctival epithelium caused by desiccation.
The rose bengal score—the sum of scores assigned to damage found in 3 regions of the eye—can define the presence of keratoconjunctivitis sicca. Sialometry measures unstimulated salivary flow into a calibrated tube for 15 minutes; normal flow is more than 1. While being simple and noninvasive, sialometry alone does not distinguish between causes of xerostomia.
Other tests used to evaluate salivary gland involvement include parotid sialography and salivary gland scintigraphy. Patients with SS show gross distortion of the normal pattern of parotid ductules on sialogram, with marked retention of contrast medium.
Scintigraphic findings in patients with SS include decreased uptake and release of technetium Tc 99m pertechnetate, with the extent of decrease paralleling the degree of xerostomia and salivary flow rate. Minor salivary gland biopsy remains a highly specific test for the salivary component of SS.
When performed properly, the patient experiences no more than temporary soreness, and healing without significant scarring is rapid. Focal lymphocytic sialadenitis, defined as multiple, dense aggregates of 50 or more lymphocytes 1 focus in perivascular or periductal areas in the majority of sampled glands, is a characteristic histopathologic feature of SS.
Patients with SS whose main complaint is persistent parotid gland swelling may have a parotid biopsy substituted for a salivary biopsy if lymphoma is suspected. The differential diagnosis of SS includes conditions and medications that can produce keratoconjunctivitis sicca, xerostomia, and parotid gland enlargement.
Xerostomia may be caused by amyloidosis, diabetes mellitus, sarcoidosis, SS, viral infections, trauma, or irradiation or may be psychogenic. Additionally, certain drugs may produce xerostomia, including antihypertensive, parasympatholytic, and psychotherapeutic agents. Dry eyes can be caused by amyloidosis, inflammation chronic blepharitis or conjunctivitis, pemphigoid, or Stevens-Johnson syndrome , SS, neurologic conditions that impair eyelid or lacrimal gland function, sarcoidosis, toxicity burns or drugs , and a variety of other conditions corneal anesthesia, blink abnormality, hypovitaminosis A, eyelid scarring, or trauma.
Bilateral parotid gland enlargement may be the result of endocrine disorders acromegaly or gonadal hypofunction , metabolic diseases chronic pancreatitis, diabetes mellitus, hepatic cirrhosis, or hyperlipoproteinemias , SS, or viral infections human immunodeficiency virus infection, hepatitis C, or mumps.
When keratoconjunctivitis sicca or xerostomia occurs in isolation, it is necessary to exclude potential causes, such as deficiency disorders or drugs, and medical conditions, such as infection, endocrinopathies, or degenerative diseases.
The differential diagnosis is especially important to therapy for systemic manifestations of SS. Differentiation of SS from RA, SLE, scleroderma, and other rheumatic disorders can be problematic, since all of these conditions can start with nonspecific manifestations such as arthralgias, myalgias, low-grade fever, and Raynaud phenomenon.
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